Foregut microbiome in development of esophageal adenocarcinoma

Esophageal adenocarcinoma (EA), the type of cancer linked to heartburn due to gastroesophageal reflux diseases (GERD), has increased six fold in the past 30 years. This cannot currently be explained by the usual environmental or by host genetic factors. EA is the end result of a sequence of GERD-related diseases, preceded by reflux esophagitis (RE) and Barrett’s esophagus (BE). Preliminary studies by Pei and colleagues at NYU on elderly male veterans identified two types of microbiotas in the esophagus. Patients who carry the type II microbiota are >15 fold likely to have esophagitis and BE than those harboring the type I microbiota. In a small scale study, we also found that 3 of 3 cases of EA harbored the type II biota. The findings have opened a new approach to understanding the recent surge in the incidence of EA. 

Our long-term goal is to identify the cause of GERD sequence. The hypothesis to be tested is that changes in the foregut microbiome are associated with EA and its precursors, RE and BE in GERD sequence. We will conduct a case control study to demonstrate the microbiome disease association in every stage of GERD sequence, as well as analyze the trend in changes in the microbiome along disease progression toward EA, by two specific aims. Aim 1 is to conduct a comprehensive population survey of the foregut microbiome and demonstrate its association with GERD sequence. Furthermore, spatial relationship between the esophageal microbiota and upstream (mouth) and downstream (stomach) foregut microbiotas as well as temporal stability of the microbiome-disease association will also be examined. Aim 2 is to define the distal esophageal metagenome and demonstrate its association with GERD sequence. Detailed analyses will include pathway-disease and gene-disease associations. Archaea, fungi and viruses, if identified, also will be correlated with the diseases. A significant association between the foregut microbiome and GERD sequence, if demonstrated, will be the first step for eventually testing whether an abnormal microbiome is required for the development of the sequence of phenotypic changes toward EA. If EA and its precursors represent a microecological disease, treating the cause of GERD might become possible, for example, by normalizing the microbiota through use of antibiotics, probiotics, or prebiotics. Causative therapy of GERD could prevent its progression and reverse the current trend of increasing incidence of EA

Scientific Assessment for Urban Air Mobility (UAM)

Better connecting the international research community and the International Civil Aviation Organization (ICAO) enables effective assessments of novel aviation innovations. The International Forum for Aviation Research (IFAR) created a group on Urban Air Mobility (UAM) to explore the broad array of aspects relevant to the ICAO mandate. The assessment began with a study of the current industry landscape, including an overview of existing market studies, proposed aircraft designs and concepts, and potential paths of industry evolution. The Industry Assessment is summarized into key takeaways highlighting the need for international assessments on economic and societal factors associated with UAM, common understanding of the extent to which the nascent industry can leverage current infrastructure and regulatory structures, and harmonization of industrywide terminology. The subsequent Scientific Assessment, developed through cooperative efforts between international domain experts, captures 17 focus areas relevant to UAM. All focus areas present opportunities for further research. Key takeaways include: the need for further study of the impact of autonomous systems (AS) on the industry; infrastructure requirements (including vertiports and weather sensing) to support the industry; and data requirements (including domains such as cybersecurity, emissions, and safety) to ensure safe, scalable operations. Finally, a brief overview of the current standards landscape as relevant to the Scientific Assessment is presented, which displays the benefits of applying digital systems engineering techniques to map current research efforts to ongoing standards activities

Urban Air Mobility Research at the DLR German Aerospace Center - Getting the HorizonUAM Project Started

Efficiency, safety, feasibility, sustainability and affordability are among the key characteristics of future urban mobility. The project “HorizonUAM - Urban Air Mobility Research at the German Aerospace Center (DLR)” provides first answers to this vision by pooling existing competencies of individual institutes within DLR. HorizonUAM combines research about urban air mobility (UAM) vehicles, the corresponding infrastructure, the operation of UAM services, as well as public acceptance and market development of future urban air transportation. Competencies and current research topics including propulsion technologies, flight system technologies, communication and navigation go along in conjunction with the findings of modern flight guidance and airport technology techniques. The project analyses possible UAM market scenarios up to the year 2050 and assesses economic aspects such as the degree of vehicle utilization or cost-benefit potential via an overall system model. Furthermore, the system design for future air taxis is carried out on the basis of vehicle family concepts, onboard systems, aspects of safety and security as well as the certification of autonomy functions. The analysis of flight guidance concepts and the sequencing of air taxis at vertidromes is another central part of the project. Selected concepts for flight guidance, communication and navigation technology will also be demonstrated with drones in a scaled urban scenario. This paper gives an overview of the topics covered in the HorizonUAM project, running from mid-2020 to mid-2023, as well as an early progress report

Cavity-enhanced field-resolved spectroscopy

Femtosecond enhancement cavities1 are key to applications including high-sensitivity linear2–4 and nonlinear5,6 gas spectroscopy, as well as efficient nonlinear optical frequency conversion7–10. Yet, to date, the broadest simultaneously enhanced bandwidths amount to <20% of the central optical frequency8,9,11–15. Here, we present an ultrabroadband femtosecond enhancement cavity comprising gold-coated mirrors and a wedged-diamond-plate input coupler, with an average finesse of 55 for optical frequencies below 40 THz and exceeding 40 in the 120–300 THz range. Resonant enhancement of a 50-MHz-repetition-rate offset-free frequency comb spanning 22–40 THz results in a waveform-stable ultrashort circulating pulse with a spectrum supporting a Fourier limit of 1.6 cycles, enabling time-domain electric-field-resolved spectroscopy of molecular samples with temporally separated excitation and molecular response16. The contrast between the two is improved by taking advantage of destructive interference at the input coupler. At an effective interaction length with a gas of up to 81 m, this concept promises parts-per-trillion-level ultrabroadband electric-field-resolved linear and nonlinear spectroscopy of impulsively excited molecular vibrations

Cavity-Enhanced Few-Cycle Mid-IR Pulses for Field-Resolved Spectroscopy

Up to tenfold power enhancement of waveform-stable few-cycle pulses is demonstrated in a minimally-dispersive resonator (22-37 THz). This enables spectroscopy of molecular samples based on impulsive excitation and electro-optic sampling at 66 m interaction length

Individual- and Connectivity-Based Real-Time fMRI Neurofeedback to Modulate Emotion-Related Brain Responses in Patients with Depression: A Pilot Study

Introduction: Individual real-time functional magnetic resonance imaging neurofeedback (rtfMRI NF) might be a promising adjuvant in treating depressive symptoms. Further studies showed functional variations and connectivity-related changes in the dorsolateral prefrontal cortex (dlPFC) and the insular cortex. Objectives: The aim of this pilot study was to investigate whether individualized connectivity-based rtfMRI NF training can improve symptoms in depressed patients as an adjunct to a psychotherapeutic programme. The novel strategy chosen for this was to increase connectivity between individualized regions of interest, namely the insula and the dlPFC. Methods: Sixteen patients diagnosed with major depressive disorder (MDD, ICD-10) and 19 matched healthy controls (HC) participated in a rtfMRI NF training consisting of two sessions with three runs each, within an interval of one week. RtfMRI NF was applied during a sequence of negative emotional pictures to modulate the connectivity between the dlPFC and the insula. The MDD REAL group was divided into a Responder and a Non-Responder group. Patients with an increased connectivity during the second NF session or during both the first and the second NF session were identified as &ldquo;MDD REAL Responder&rdquo; (N = 6). Patients that did not show any increase in connectivity and/or a decreased connectivity were identified as &ldquo;MDD REAL Non-Responder&rdquo; (N = 7). Results: Before the rtfMRI sessions, patients with MDD showed higher neural activation levels in ventromedial PFC and the insula than HC; by contrast, HC revealed increased hemodynamic activity in visual processing areas (primary visual cortex and visual association cortex) compared to patients with MDD. The comparison of hemodynamic responses during the first compared to during the last NF session demonstrated significantly increased BOLD-activation in the medial orbitofrontal cortex (mOFC) in patients and HC, and additionally in the lateral OFC in patients with MDD. These findings were particularly due to the MDD Responder group, as the MDD Non-Responder group showed no increase in this region during the last NF run. There was a decrease of neural activation in emotional processing brain regions in both groups in the last NF run compared to the first: HC showed differences in the insula, parahippocampal gyrus, basal ganglia, and cingulate gyrus. Patients with MDD demonstrated deceased responses in the parahippocampal gyrus. There was no significant reduction of BDI scores after NF training in patients. Conclusions: Increased neural activation in the insula and vmPFC in MDD suggests an increased emotional reaction in patients with MDD. The activation of the mOFC could be associated with improved control-strategies and association-learning processes. The increased lOFC activation could indicate a stronger sensitivity to failed NF attempts in MDD. A stronger involvement of visual processing areas in HC may indicate better adaptation to negative emotional stimuli after repeated presentation. Overall, the rtfMRI NF had an impact on neurobiological mechanisms, but not on psychometric measures in patients with MDD