Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging.

A decline in capillary density and blood flow with age is a major cause of mortality and morbidity. Understanding why this occurs is key to future gains in human health. NAD precursors reverse aspects of aging, in part, by activating sirtuin deacylases (SIRT1-SIRT7) that mediate the benefits of exercise and dietary restriction (DR). We show that SIRT1 in endothelial cells is a key mediator of pro-angiogenic signals secreted from myocytes. Treatment of mice with the NAD+ booster nicotinamide mononucleotide (NMN) improves blood flow and increases endurance in elderly mice by promoting SIRT1-dependent increases in capillary density, an effect augmented by exercise or increasing the levels of hydrogen sulfide (H2S), a DR mimetic and regulator of endothelial NAD+ levels. These findings have implications for improving blood flow to organs and tissues, increasing human performance, and reestablishing a virtuous cycle of mobility in the elderly.

The establishment of resident memory B cells in the lung requires local antigen encounter.

Memory B cells are found in lymphoid and non-lymphoid tissues, suggesting that some may be tissue-resident cells. Here we show that pulmonary influenza infection elicited lung-resident memory B cells (BRM cells) that were phenotypically and functionally distinct from their systemic counterparts. BRM cells were established in the lung early after infection, in part because their placement required local antigen encounter. Lung BRM cells, but not systemic memory B cells, contributed to early plasmablast responses following challenge infection. Following secondary infection, antigen-specific BRM cells differentiated in situ, whereas antigen-non-specific BRM cells were maintained as memory cells. These data demonstrate that BRM cells are an important component of immunity to respiratory viruses such as influenza virus and suggest that vaccines designed to elicit BRM cells must deliver antigen to the lungs.

T-bet Transcription Factor Promotes Antibody-Secreting Cell Differentiation by Limiting the Inflammatory Effects of IFN-γ on B Cells.

Although viral infections elicit robust interferon-γ (IFN-γ) and long-lived antibody-secreting cell (ASC) responses, the roles for IFN-γ and IFN-γ-induced transcription factors (TFs) in ASC development are unclear. We showed that B cell intrinsic expression of IFN-γR and the IFN-γ-induced TF T-bet were required for T-helper 1 cell-induced differentiation of B cells into ASCs. IFN-γR signaling induced Blimp1 expression in B cells but also initiated an inflammatory gene program that, if not restrained, prevented ASC formation. T-bet did not affect Blimp1 upregulation in IFN-γ-activated B cells but instead regulated chromatin accessibility within the Ifng and Ifngr2 loci and repressed the IFN-γ-induced inflammatory gene program. Consistent with this, B cell intrinsic T-bet was required for formation of long-lived ASCs and secondary ASCs following viral, but not nematode, infection. Therefore, T-bet facilitates differentiation of IFN-γ-activated inflammatory effector B cells into ASCs in the setting of IFN-γ-, but not IL-4-, induced inflammatory responses.

Reprogramming to recover youthful epigenetic information and restore vision.

Ageing is a degenerative process that leads to tissue dysfunction and death. A proposed cause of ageing is the accumulation of epigenetic noise that disrupts gene expression patterns, leading to decreases in tissue function and regenerative capacity1-3. Changes to DNA methylation patterns over time form the basis of ageing clocks4, but whether older individuals retain the information needed to restore these patterns-and, if so, whether this could improve tissue function-is not known. Over time, the central nervous system (CNS) loses function and regenerative capacity5-7. Using the eye as a model CNS tissue, here we show that ectopic expression of Oct4 (also known as Pou5f1), Sox2 and Klf4 genes (OSK) in mouse retinal ganglion cells restores youthful DNA methylation patterns and transcriptomes, promotes axon regeneration after injury, and reverses vision loss in a mouse model of glaucoma and in aged mice. The beneficial effects of OSK-induced reprogramming in axon regeneration and vision require the DNA demethylases TET1 and TET2. These data indicate that mammalian tissues retain a record of youthful epigenetic information-encoded in part by DNA methylation-that can be accessed to improve tissue function and promote regeneration in vivo.

Isotopic and DNA analyses reveal multiscale PPNB mobility and migration across Southeastern Anatolia and the Southern Levant.

Growing reliance on animal and plant domestication in the Near East and beyond during the Pre-Pottery Neolithic B (PPNB) (the ninth to eighth millennium BC) has often been associated with a "revolutionary" social transformation from mobility toward more sedentary lifestyles. We are able to yield nuanced insights into the process of the Neolithization in the Near East based on a bioarchaeological approach integrating isotopic and archaeogenetic analyses on the bone remains recovered from Nevali Çori, a site occupied from the early PPNB in Turkey where some of the earliest evidence of animal and plant domestication emerged, and from Ba'ja, a typical late PPNB site in Jordan. In addition, we present the archaeological sequence of Nevali Çori together with newly generated radiocarbon dates. Our results are based on strontium (87Sr/86Sr), carbon, and oxygen (δ18O and δ13Ccarb) isotopic analyses conducted on 28 human and 29 animal individuals from the site of Nevali Çori. 87Sr/86Sr results indicate mobility and connection with the contemporaneous surrounding sites during the earlier PPNB prior to an apparent decline in this mobility at a time of growing reliance on domesticates. Genome-wide data from six human individuals from Nevali Çori and Ba'ja demonstrate a diverse gene pool at Nevali Çori that supports connectedness within the Fertile Crescent during the earlier phases of Neolithization and evidence of consanguineous union in the PPNB Ba'ja and the Iron Age Nevali Çori.

NAD+ in COVID-19 and viral infections.

NAD+, as an emerging regulator of immune responses during viral infections, may be a promising therapeutic target for coronavirus disease 2019 (COVID-19). In this Opinion, we suggest that interventions that boost NAD+ levels might promote antiviral defense and suppress uncontrolled inflammation. We discuss the association between low NAD+ concentrations and risk factors for poor COVID-19 outcomes, including aging and common comorbidities. Mechanistically, we outline how viral infections can further deplete NAD+ and its roles in antiviral defense and inflammation. We also describe how coronaviruses can subvert NAD+-mediated actions via genes that remove NAD+ modifications and activate the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome. Finally, we explore ongoing approaches to boost NAD+ concentrations in the clinic to putatively increase antiviral responses while curtailing hyperinflammation.

Structural modifications toward improved lead-203/lead-212 peptide-based image-guided alpha-particle radiopharmaceutical therapies for neuroendocrine tumors.

PURPOSE: The lead-203 (203Pb)/lead-212 (212Pb) elementally identical radionuclide pair has gained significant interest in the field of image-guided targeted alpha-particle therapy for cancer. Emerging evidence suggests that 212Pb-labeled peptide-based radiopharmaceuticals targeting somatostatin receptor subtype 2 (SSTR2) may provide improved effectiveness compared to beta-particle-based therapies for neuroendocrine tumors (NETs). This study aims to improve the performance of SSTR2-targeted radionuclide imaging and therapy through structural modifications to Tyr3-octreotide (TOC)-based radiopharmaceuticals. METHODS: New SSTR2-targeted peptides were designed and synthesized with the goal of optimizing the incorporation of Pb isotopes through the use of a modified cyclization technique; the introduction of a Pb-specific chelator (PSC); and the insertion of polyethylene glycol (PEG) linkers. The binding affinity of the peptides and the cellular uptake of 203Pb-labeled peptides were evaluated using pancreatic AR42J (SSTR2+) tumor cells and the biodistribution and imaging of the 203Pb-labeled peptides were assessed in an AR42J tumor xenograft mouse model. A lead peptide was identified (i.e., PSC-PEG2-TOC), which was then further evaluated for efficacy in 212Pb therapy studies. RESULTS: The lead radiopeptide drug conjugate (RPDC) - [203Pb]Pb-PSC-PEG2-TOC - significantly improved the tumor-targeting properties, including receptor binding and tumor accumulation and retention as compared to [203Pb]Pb-DOTA0-Tyr3-octreotide (DOTATOC). Additionally, the modified RPDC exhibited faster renal clearance than the DOTATOC counterpart. These advantageous characteristics of [212Pb]Pb-PSC-PEG2-TOC resulted in a dose-dependent therapeutic effect with minimal signs of toxicity in the AR42J xenograft model. Fractionated administrations of 3.7 MBq [212Pb]Pb-PSC-PEG2-TOC over three doses further improved anti-tumor effectiveness, resulting in 80% survival (70% complete response) over 120 days in the mouse model. CONCLUSION: Structural modifications to chelator and linker compositions improved tumor targeting and pharmacokinetics (PK) of 203/212Pb peptide-based radiopharmaceuticals for NET theranostics. These findings suggest that PSC-PEG2-TOC is a promising candidate for Pb-based targeted radionuclide therapy for NETs and other types of cancers that express SSTR2.

Pre-clinical evaluation of biomarkers for the early detection of nephrotoxicity following alpha-particle radioligand therapy.

PURPOSE: Cancer treatment with alpha-emitter-based radioligand therapies (α-RLTs) demonstrates promising tumor responses. Radiolabeled peptides are filtered through glomeruli, followed by potential reabsorption of a fraction by proximal tubules, which may cause acute kidney injury (AKI) and chronic kidney disease (CKD). Because tubular cells are considered the primary site of radiopeptides' renal reabsorption and potential injury, the current use of kidney biomarkers of glomerular functional loss limits the evaluation of possible nephrotoxicity and its early detection. This study aimed to investigate whether urinary secretion of tubular injury biomarkers could be used as an additional non-invasive sensitive diagnostic tool to identify unrecognizable tubular damage and risk of long-term α-RLT nephrotoxicity. METHODS: A bifunctional cyclic peptide, melanocortin 1 ligand (MC1L), labeled with [203Pb]Pb-MC1L, was used for [212Pb]Pb-MC1L biodistribution and absorbed dose measurements in CD-1 Elite mice. Mice were treated with [212Pb]Pb-MC1L in a dose-escalation study up to levels of radioactivity intended to induce kidney injury. The approach enabled prospective kidney functional and injury biomarker evaluation and late kidney histological analysis to validate these biomarkers. RESULTS: Biodistribution analysis identified [212Pb]Pb-MC1L reabsorption in kidneys with a dose deposition of 2.8, 8.9, and 20 Gy for 0.9, 3.0, and 6.7 MBq injected [212Pb]Pb-MC1L doses, respectively. As expected, mice receiving 6.7 MBq had significant weight loss and CKD evidence based on serum creatinine, cystatin C, and kidney histological alterations 28 weeks after treatment. A dose-dependent urinary neutrophil gelatinase-associated lipocalin (NGAL, tubular injury biomarker) urinary excretion the day after [212Pb]Pb-MC1L treatment highly correlated with the severity of late tubulointerstitial injury and histological findings. CONCLUSION: Urine NGAL secretion could be a potential early diagnostic tool to identify unrecognized tubular damage and predict long-term α-RLT-related nephrotoxicity.

Medication adherence to inflammatory bowel disease medications in Aotearoa New Zealand and correlation with health outcomes: A nationwide database analysis.

AIMS: Inflammatory bowel disease (IBD) management entails long-term medication therapy. Worse disease outcomes and reduced quality of life might arise from poor medication adherence (MA). This study is the first to investigate patients with IBD's adherence across Aotearoa New Zealand and its relationship with disease outcomes. METHODS: Dispensing claims data (Pharmaceutical Collection) were used to calculate (3- and 5-year) adherence, using daily polypharmacy possession ratio. Using hospitalization data (National Minimum Dataset), the relationship between adherence and the numbers of hospitalizations and corticosteroid dispensings was investigated. RESULTS: In total, 4654 patients (53% female; 55% Crohn's disease [CD], 45% ulcerative colitis [UC]; median age-at-first-dispensing, 43 years) and 3148 patients (54% female; 55% CD, 44% UC; median age-at-first-dispensing, 44 years) were in the 3- and 5-year cohorts, respectively. The 3- and 5-year cohorts had mean 4.6 and 4.2 IBD-related hospitalizations and 6.9 and 9.2 corticosteroid dispensings, respectively. Average adherence estimates were 77.4% (95% confidence interval: 76.9-78.0%) and 74.9% (95% confidence interval: 74.1-75.6%; 3 and 5 years), while 54% and 51% of patients, respectively, had good adherence (MA ≥ 80%). There was no correlation between adherence and the numbers of hospitalizations (Pearson's R = -.0007; P = .65 and R = -.04; P = .02 [3 and 5 years]) and corticosteroid dispensings (R = .08; P = <.0001 and R = .08; P = <.0001, respectively). CONCLUSION: MA of Aotearoa New Zealand patients with IBD is moderately high but just over half of patients meet the adherent threshold. There was no correlation between adherence and hospitalizations or corticosteroid dispensings; hence, research into longitudinal adherence patterns and associated factors is needed.

Transcutaneous Auricular Vagus Nerve Stimulation Normalizes Induced Gastric Myoelectrical Dysrhythmias in Controls Assessed by Body-Surface Gastric Mapping.

OBJECTIVES: Transcutaneous auricular vagus nerve stimulation (TaVNS) is a supplementary treatment for gastric symptoms resulting from dysrhythmias. The main objective of this study was to quantify the effects of 10, 40, and 80 Hz TaVNS and sham in healthy individuals in response to a 5-minute water-load (WL5) test. MATERIALS AND METHODS: Eighteen healthy volunteers aged between 21 and 55 years (body mass index: 27.1 ± 3.2) were recruited. Each subject fasted for up to eight hours and participated in four 95-minute sessions, which consisted of 30 fasted baseline, 30 minutes TaVNS, WL5, and 30 minutes post-WL5. Heart rate variability was assessed using sternal electrocardiogram. Body-surface gastric mapping and bloating (/10) were recorded. One-way ANOVA with post hoc Tukey test was performed to test the difference between TaVNS protocols in terms of frequency, amplitude, bloating scores, root mean square of the successive differences (RMSSD), and stress index (SI). RESULTS: On average, the subjects consumed 526 ± 160 mL of water, with volume ingested correlated to bloating (mean score 4.1 ± 1.8; r = 0.36, p = 0.029). In general, the reduction in frequency and rhythm stability during the post-WL5 period in sham was normalized by all three TaVNS protocols. Both 40- and 80-Hz protocols also caused increases in amplitude during the stim-only and/or post-WL5 periods. RMSSD increased during the 40-Hz protocol. SI increased during the 10-Hz protocol but decreased during the 40- and 80-Hz protocols. CONCLUSION: TaVNS proved effective in normalizing gastric dysrhythmias by WL5 in healthy subjects by altering both parasympathetic and sympathetic pathways.

Some differences between social work, spiritual care, and psychology: Content variance in end-of-life conversations.

OBJECTIVES: Within the multidisciplinary team, there can sometimes be lack of clarity as to the specific different contributions of each of the psycho-social-spiritual professionals: social workers, psychologist, and spiritual caregivers. This study examined the content of their end-of-life conversations with patients. METHODS: A total of 180 patients with terminal cancer received standard multidisciplinary care, including conversations with a social worker, psychologist, and spiritual caregiver. After each patient's death, these professionals reported using a structured tool which content areas had arisen in their conversations with that patient. RESULTS: Across all content areas, there were significant differences between social work and spiritual care. The difference between social work and psychology was slightly smaller but still quite large. Psychology and spiritual care were the most similar, though they still significantly differed in half the content areas. The differences persisted even among patients who spoke with more than 1 kind of professional. The 6 content areas examined proved to subdivide into 2 linked groups, where patients speaking about 1 were more likely to speak about the others. One group, "reflective" topics (inner and transpersonal resources, interpersonal relationships, one's past, and end of life), included all those topics which arose more often with spiritual caregivers or psychologists. The second group, "decision-making" topics (medical coping and life changes), was comprised of those topics which arose most commonly with social workers, bridging between the medical and personal aspects of care and helping patients navigate their new physical, psychological, and social worlds. SIGNIFICANCE OF RESULTS: These findings help shed light on the differences, in practice, between patients' conversations with social workers, psychologists, and spiritual caregivers and the roles these professionals are playing; can aid in formulating individualized care plans; and strengthen the working assumption that all 3 professions contribute in unique, complementary ways to improving patients' and families' well-being.

Associations Between Psycho-Social-Spiritual Interventions, Fewer Aggressive End-of-Life Measures, and Increased Time After Final Oncologic Treatment.

BACKGROUND: Little is known about the impact of spiritual caregivers, psychologists, and social workers on desired end-of-life (EoL) medical outcomes, such as reduced use of aggressive care in the final 2 weeks of life, having more time between the last active oncological treatment and death, and increased hospice use. PATIENTS AND METHODS: We conducted a prospective study of 180 patients with cancer and their families, their interactions with social work, psychology, and spiritual care, and the above three treatment outcomes. RESULTS: We found that having one or more spiritual care visits (adjusted odds ratio (AOR) = 2.02; P = .04), having more quality visits with the psychologist (P = .01), and speaking with someone about one's inner resources (AOR = 2.25; P = .03) all correlated with reduced EoL aggressive care. The key interventions correlating with increased time after final treatment were more visits with the spiritual caregiver or the social worker (AOR = 1.30; P < .001), and speaking about the medical treatment (AOR = 1.54; P < .001) and about interpersonal relationships (AOR = 2.28; P < .001). A subjectively good-quality connection with the spiritual caregiver correlated with increased hospice use (AOR = 10.00; P = .01). CONCLUSIONS: Patients with cancer who availed themselves of the spiritual care, psychology, and social work services, each profession in distinct ways, had significantly different outcomes in their EoL medical treatment, including undergoing fewer futile aggressive measures, having more time after their last active treatment, and using hospice services more. These outcomes directly bear on improved quality of life and reduced costs.

Carbon fluxes related to land use and land cover change in Baden-Württemberg.

Spatially explicit information on carbon fluxes related to land use and land cover change (LULCC) is of value for the implementation of local climate change mitigation strategies. However, estimates of these carbon fluxes are often aggregated to larger areas. We estimated committed gross carbon fluxes related to LULCC in Baden-Württemberg, Germany, using different emission factors. In doing so, we compared four different data sources regarding their suitability for estimating the fluxes: (a) a land cover dataset derived from OpenStreetMap (OSMlanduse); (b) OSMlanduse with removal of sliver polygons (OSMlanduse cleaned), (c) OSMlanduse enhanced with a remote sensing time series analysis (OSMlanduse+); (d) the LULCC product of Landschaftsveränderungsdienst (LaVerDi) from the German Federal Agency of Cartography and Geodesy. We produced a high range of carbon flux estimates, mostly caused by differences in the area of the LULCC detected by the different change methods. Except for the OSMlanduse change method, all LULCC methods achieved results that are comparable to other gross emission estimates. The carbon flux estimates of the most plausible change methods, OSMlanduse cleaned and OSMlanduse+, were 291,710 Mg C yr-1 and 93,591 Mg C yr-1, respectively. Uncertainties were mainly caused by incomplete spatial coverage of OSMlanduse, false positive LULCC due to changes and corrections made in OpenStreetMap during the study period, and a high number of sliver polygons in the OSMlanduse changes. Overall, the results showed that OSM can be successfully used to estimate LULCC carbon fluxes if data preprocessing is performed with the suggested methods.

Inhibition of the NAD salvage pathway in schistosomes impairs metabolism, reproduction, and parasite survival.

NAD, a key co-enzyme required for cell metabolism, is synthesized via two pathways in most organisms. Since schistosomes apparently lack enzymes required for de novo NAD biosynthesis, we evaluated whether these parasites, which infect >200 million people worldwide, maintain NAD homeostasis via the NAD salvage biosynthetic pathway. We found that intracellular NAD levels decline in schistosomes treated with drugs that block production of nicotinamide or nicotinamide mononucleotide-known NAD precursors in the non-deamidating salvage pathway. Moreover, in vitro inhibition of the NAD salvage pathway in schistosomes impaired egg production, disrupted the outer membranes of both immature and mature parasites and caused loss of mobility and death. Inhibiting the NAD salvage pathway in schistosome-infected mice significantly decreased NAD levels in adult parasites, which correlated with reduced egg production, fewer liver granulomas and parasite death. Thus, schistosomes, unlike their mammalian hosts, appear limited to one metabolic pathway to maintain NAD-dependent metabolic processes.

A Short Knowledge Assessment Tool Is Valid and Acceptable for Adults with Inflammatory Bowel Disease.

BACKGROUND: For people with inflammatory bowel disease, validated knowledge questionnaires are valuable to identify gaps in understanding and explore the impact on disease variables. AIMS: The aim of this study was to validate the short knowledge questionnaire Inflammatory Bowel Disease Knowledge Inventory Device 2, known as IBD-KID2, for use with adults with inflammatory bowel disease. METHODS: Concurrent validity of IBD-KID2 was assessed by comparing scores with those achieved on the Crohn's and Colitis Knowledge Score (CCKNOW). IBD-KID2 reliability was assessed with test-retest completion at two time points, generalizability assessed by comparing IBD-KID2 cohort scores at different recruitment centres, and acceptability assessed using participant survey. RESULTS: Seventy-five adults with inflammatory bowel disease completed the study. The mean percentage scores achieved on the IBD-KID2 and CCKNOW were 72.8% (SD 16.0) and 49.7% (SD 18.2), respectively. There was a significant correlation between IBD-KID2 and CCKNOW scores (R 0.573, P < 0.005), confirming concurrent validity. IBD-KID2 reliability was confirmed as no significant difference was seen between scores at test and retest (mean difference -0.2, P = 0.92). Generalizability was established as no significant score difference was seen between recruitment centres after controlling for population differences. The acceptability survey showed that 49 (69%) participants preferred IBD-KID2 to the CCKNOW, 60 (85%) found the IBD-KID2 easier to complete, and 38 (53%) considered the CCKNOW as most suitable for adults. CONCLUSIONS: IBD-KID2 is a valid, reliable, and generalizable tool for measuring knowledge in adults with inflammatory bowel disease with good acceptability. IBD-KID2 is easy and quick to complete, hence limiting respondent burden.

Boundary layer hydrodynamics of patchy biofilms.

Algal biofilms, ubiquitous in aquatic systems, reduce the performance of engineered systems and alter ecosystem processes. Biofilm morphology is dynamic throughout community development, with patchiness occurring due to periodic sloughing, but little is known about how community level physical structure affects hydrodynamics. This study uses high resolution particle image velocimetry (PIV) to examine spatially explicit turbulence over sparse, uniform and patchy biofilm at turbulent Reynolds numbers. All biofilms increase the near-bed turbulence production, Reynolds shear stress, and rotational flow compared to a smooth wall, and non-uniform biofilms have the greatest increase in these parameters, compared with a uniform or sparse biofilm. However, a higher drag coefficient over uniform biofilm compared with non-uniform biofilm indicates that percent coverage (the amount of area covered by the biofilm) is a useful predictor of a biofilm's relative effect on the total drag along surfaces, and in particular the effect on ship performance.

EEG monitoring during anesthesia in children aged 0 to 18 months: amplitude-integrated EEG and age effects.

BACKGROUND: The amplitude-integrated EEG (aEEG) is a widely used monitoring tool in neonatology / pediatric intensive care. It takes into account the amplitudes, but not the frequency composition, of the EEG. Advantages of the aEEG are clear criteria for interpretation and time compression. During the first year of life, the electroencephalogram (EEG) during sedation / anesthesia changes from a low-differentiated to a differentiated EEG; higher-frequency waves develop increasingly. There are few studies on the use of aEEG during pediatric anesthesia. A systematic evaluation of the aEEG in defined EEG stages during anesthesia / sedation is not yet available. Parameters of pediatric EEGs (power, median frequency, spectral edge frequency) recorded during anesthesia and of the corresponding aEEGs (upper and lower value of the aEEG trace) should be examined for age-related changes. Furthermore, it should be examined whether the aEEG can distinguish EEG stages of sedation / anesthesia in differentiated EEGs. METHODS: In a secondary analysis of a prospective observational study EEGs and aEEGs (1-channel recordings, electrode positions on forehead) of 50 children (age: 0-18 months) were evaluated. EEG stages: A (awake), Slow EEG, E2, F0, and F1 in low-differentiated EEGs and A (awake), B0-2, C0-2, D0-2, E0-2, F0-1 in differentiated EEGs. RESULTS: Median and spectral edge frequency increased significantly with age (p < 0.001 each). In low-differentiated EEGs, the power of the Slow EEG increased significantly with age (p < 0.001). In differentiated EEGs, the power increased significantly with age in each of the EEG stages B1 to E1 (p = 0.04, or less), and the upper and lower values of the aEEG trace increased with age (p < 0.001). A discriminant analysis using the upper and lower values of the aEEG showed that EEG epochs from the stages B1 to E1 were assigned to the original EEG stage in only 19.3% of the cases. When age was added as the third variable, the rate of correct reclassifications was 28.5%. CONCLUSIONS: The aEEG was not suitable for distinguishing EEG stages above the burst suppression range. For this purpose, the frequency composition of the EEG should be taken into account.

Multipath-Assisted Radio Sensing and State Detection for the Connected Aircraft Cabin.

Efficiency and reliable turnaround time are core features of modern aircraft transportation and key to its future sustainability. Given the connected aircraft cabin, the deployment of digitized and interconnected sensors, devices and passengers provides comprehensive state detection within the cabin. More specifically, passenger localization and occupancy detection can be monitored using location-aware communication systems, also known as wireless sensor networks. These multi-purpose communication systems serve a variety of capabilities, ranging from passenger convenience communication services, over crew member devices, to maintenance planning. In addition, radio-based sensing enables an efficient sensory basis for state monitoring; e.g., passive seat occupancy detection. Within the scope of the connected aircraft cabin, this article presents a multipath-assisted radio sensing (MARS) approach using the propagation information of transmitted signals, which are provided by the channel impulse response (CIR) of the wireless communication channel. By performing a geometrical mapping of the CIR, reflection sources are revealed, and the occupancy state can be derived. For this task, both probabilistic filtering and k-nearest neighbor classification are discussed. In order to evaluate the proposed methods, passenger occupancy detection and state detection for the future automation of passenger safety announcements and checks are addressed. Therefore, experimental measurements are performed using commercially available wideband communication devices, both in close to ideal conditions in an RF anechoic chamber and a cabin seat mockup. In both environments, a reliable radio sensing state detection was achieved. In conclusion, this paper provides a basis for the future integration of energy and spectrally efficient joint communication and sensing radio systems within the connected aircraft cabin.

Dosimetry of [212Pb]VMT01, a MC1R-Targeted Alpha Therapeutic Compound, and Effect of Free 208Tl on Tissue Absorbed Doses.

[212Pb]VMT01 is a melanocortin 1 receptor (MC1R) targeted theranostic ligand in clinical development for alpha particle therapy for melanoma. 212Pb has an elementally matched gamma-emitting isotope 203Pb; thus, [203Pb]VMT01 can be used as an imaging surrogate for [212Pb]VMT01. [212Pb]VMT01 human serum stability studies have demonstrated retention of the 212Bi daughter within the chelator following beta emission of parent 212Pb. However, the subsequent alpha emission from the decay of 212Bi into 208Tl results in the generation of free 208Tl. Due to the 10.64-hour half-life of 212Pb, accumulation of free 208Tl in the injectate will occur. The goal of this work is to estimate the human dosimetry for [212Pb]VMT01 and the impact of free 208Tl in the injectate on human tissue absorbed doses. Human [212Pb]VMT01 tissue absorbed doses were estimated from murine [203Pb]VMT01 biodistribution data, and human biodistribution values for 201Tl chloride (a cardiac imaging agent) from published data were used to estimate the dosimetry of free 208Tl. Results indicate that the dose-limiting tissues for [212Pb]VMT01 are the red marrow and the kidneys, with estimated absorbed doses of 1.06 and 8.27 mGyRBE = 5/MBq. The estimated percent increase in absorbed doses from free 208Tl in the injectate is 0.03% and 0.09% to the red marrow and the kidneys, respectively. Absorbed doses from free 208Tl result in a percent increase of no more than 1.2% over [212Pb]VMT01 in any organ or tissue. This latter finding indicates that free 208Tl in the [212Pb]VMT01 injectate will not substantially impact estimated tissue absorbed doses in humans.