Applications of Uncrewed Aerial Vehicles (UAV) Technology to Support Integrated Coastal Zone Management and the UN Sustainable Development Goals at the Coast.

Data and information obtained from low-cost uncrewed aerial vehicles (UAVs), commonly referred to as 'drones', can be used to support integrated coastal zone management (ICZM) and sustainable development at the coast. Several recent studies in various disciplines, including ecology, engineering, and several branches of physical and human geography, describe the applications of UAV technology with practical coastal management potential, yet the extent to which such data can contribute to these activities remains underexplored. The main objective of this paper is to collate this knowledge to highlight the areas in which UAV technology can contribute to ICZM and can influence the achievement of the UN Sustainable Development Goals (SDGs) at the coast. We focus on applications with practical potential for coastal management activities and assess their accessibility in terms of cost, ease of use, and maturity. We identified ten (out of the 17) SDGs to which UAVs can contribute data and information. Examples of applications include surveillance of illegal fishing and aquaculture activities, seaweed resource assessments, cost-estimation of post-storm damages, and documentation of natural and cultural heritage sites under threat from, for example, erosion and sea-level rise. An awareness of how UAVs can contribute to ICZM, as well as the limitations of the technology, can help coastal practitioners to evaluate their options for future management activities. Supplementary Information: The online version contains supplementary material available at 10.1007/s12237-021-01001-5.

Extreme Obesity is Associated with Low Success Rate of Atrial Fibrillation Catheter Ablation.

BACKGROUND: Catheter ablation (CA) is an established treatment for patients with symptomatic atrial fibrillation (AF). The purpose of this study was to evaluate the safety and efficacy of single CA in AF patients with extreme obesity (body mass index [BMI] ≥ 40 kg/m2) and its long-term impact on body weight. METHODS: Patients with BMI ≥40 kg/m2 who underwent CA at the Ohio State University between 2012 and 2016 were included. The primary efficacy endpoint was no atrial arrhythmia lasting > 30 seconds without anti-arrhythmic drugs during 1-year follow-up after a single procedure. RESULTS: Out of 230 AF patients with BMI ≥ 40 kg/m2 undergoing CA, pulmonary vein isolation was achieved in 226 (98%) patients.Seventeen patients (7.4%) experienced acute major complications, including pericardial effusion, vascular complications and respiratory failure. Patient characteristics for 135 patients with complete 1-year follow-up were as follows: mean age 58.6 ± 9.6 years, mean BMI 44.5±4.7 kg/m2, female 63 (47%), non-paroxysmal AF 100 (74%), median CHA2DS2-VASc score 2 (IQR:1-3). In this cohort, the primary efficacy endpoint was achieved in 44 (33%) patients. Paroxysmal AF was associated with higher CA success compared to non-paroxysmal (51 vs. 26% [p < 0.01]).There was no significant weight change even in patients with successful AF CA. CONCLUSIONS: Extreme obesity is associated with low AF CA success, particularly in those with non-paroxysmal AF. Successful AF CA was not associated with long-term weight reduction. A better treatment strategy is needed in this population of AF and extreme obesity.

Expanded DNA and RNA Trinucleotide Repeats in Myotonic Dystrophy Type 1 Select Their Own Multitarget, Sequence-Selective Inhibitors.

There are few methods available for the rapid discovery of multitarget drugs. Herein, we describe the template-assisted, target-guided discovery of small molecules that recognize d(CTG) in the expanded d(CTG·CAG) sequence and its r(CUG) transcript that cause myotonic dystrophy type 1. A positive cross-selection was performed using a small library of 30 monomeric alkyne- and azide-containing ligands capable of producing >5000 possible di- and trimeric click products. The monomers were incubated with d(CTG)16 or r(CUG)16 under physiological conditions, and both sequences showed selectivity in the proximity-accelerated azide-alkyne [3+2] cycloaddition click reaction. The limited number of click products formed in both selections and the even smaller number of common products suggests that this method is a useful tool for the discovery of single-target and multitarget lead therapeutic agents.

Accuracy of contrast-enhanced computed tomography for thrombus detection prior to atrial fibrillation ablation and role of novel Left Atrial Appendage Enhancement Index in appendage flow assessment.

AIMS: To evaluate diagnostic accuracy of different protocols of contrast enhanced computed tomography venogram (CTV) for LAA thrombus detection in patients undergoing AF ablation and study the correlation of the novel LAA enhancement index (LAA-EI) to LAA flow velocity obtained using transesophageal echocardiography (TEE). METHODS: Study comprised of patients undergoing CTV and TEE on the same day from October 2016 to December 2017. Three CTV scanning protocols (described in results), were evaluated wherein ECG gating was used only for those with sinus rhythm on day of CTV. LAA-EI was calculated as Hounsfield Unit (HU) in the LAA divided by the HU unit in the center of the LA. The diagnostic accuracy for CTV was calculated in comparison to TEE. The LAA-EI was compared to LAA emptying velocities as obtained from TEE. RESULTS: 590 patients with 45.6% non-ECG-gated without delayed imaging, 26.9% non-ECG-gated with delayed imaging and 27.5% ECG-gated with delayed imaging, were included in the study. All three protocols had 100% negative predictive value with improvement in specificity from 61.8% to 98.1% upon adding delayed imaging. The LAA-EI correlated significantly with reduced LAA flow velocities (r = 0.45, p < .0001). The mean LAA emptying velocity in patients with LAA-EI of ≤ 0.6 was significantly lower than in those with LAA-EI of >0.6 (36.2 cm/s [95% CI: 32.6-39.7] vs, (58 cm/s [95% CI 55.3-60.8]), respectively (p < .0001). CONCLUSION: CTV with delayed imaging (with or without ECG gating) is highly specific in ruling out LAA thrombus. The novel LAA-EI can detect low LAA flow velocities.

Molecular basis for the distinct cellular functions of the Lsm1-7 and Lsm2-8 complexes.

Eukaryotes possess eight highly conserved Lsm (like Sm) proteins that assemble into circular, heteroheptameric complexes, bind RNA, and direct a diverse range of biological processes. Among the many essential functions of Lsm proteins, the cytoplasmic Lsm1-7 complex initiates mRNA decay, while the nuclear Lsm2-8 complex acts as a chaperone for U6 spliceosomal RNA. It has been unclear how these complexes perform their distinct functions while differing by only one out of seven subunits. Here, we elucidate the molecular basis for Lsm-RNA recognition and present four high-resolution structures of Lsm complexes bound to RNAs. The structures of Lsm2-8 bound to RNA identify the unique 2',3' cyclic phosphate end of U6 as a prime determinant of specificity. In contrast, the Lsm1-7 complex strongly discriminates against cyclic phosphates and tightly binds to oligouridylate tracts with terminal purines. Lsm5 uniquely recognizes purine bases, explaining its divergent sequence relative to other Lsm subunits. Lsm1-7 loads onto RNA from the 3' end and removal of the Lsm1 carboxy-terminal region allows Lsm1-7 to scan along RNA, suggesting a gated mechanism for accessing internal binding sites. These data reveal the molecular basis for RNA binding by Lsm proteins, a fundamental step in the formation of molecular assemblies that are central to eukaryotic mRNA metabolism.

Structural basis for the evolution of cyclic phosphodiesterase activity in the U6 snRNA exoribonuclease Usb1.

U6 snRNA undergoes post-transcriptional 3' end modification prior to incorporation into the active site of spliceosomes. The responsible exoribonuclease is Usb1, which removes nucleotides from the 3' end of U6 and, in humans, leaves a 2',3' cyclic phosphate that is recognized by the Lsm2-8 complex. Saccharomycescerevisiae Usb1 has additional 2',3' cyclic phosphodiesterase (CPDase) activity, which converts the cyclic phosphate into a 3' phosphate group. Here we investigate the molecular basis for the evolution of Usb1 CPDase activity. We examine the structure and function of Usb1 from Kluyveromyces marxianus, which shares 25 and 19% sequence identity to the S. cerevisiae and Homo sapiens orthologs of Usb1, respectively. We show that K. marxianus Usb1 enzyme has CPDase activity and determined its structure, free and bound to the substrate analog uridine 5'-monophosphate. We find that the origin of CPDase activity is related to a loop structure that is conserved in yeast and forms a distinct penultimate (n - 1) nucleotide binding site. These data provide structural and mechanistic insight into the evolutionary divergence of Usb1 catalysis.

Efficacy of inactivation of human enteroviruses by dual-wavelength germicidal ultraviolet (UV-C) light emitting diodes (LEDs).

The efficacy of germicidal ultraviolet (UV-C) light emitting diodes (LEDs) was evaluated for inactivating human enteroviruses included on the United States Environmental Protection Agency (EPA)'s Contaminant Candidate List (CCL). A UV-C LED device, emitting at peaks of 260 nm and 280 nm and the combination of 260∣280 nm together, was used to measure and compare potential synergistic effects of dual wavelengths for disinfecting viral organisms. The 260 nm LED proved to be the most effective at inactivating the CCL enteroviruses tested. To obtain 2-log10 inactivation credit for the 260 nm LED, the fluences (UV doses) required are approximately 8 mJ/cm2 for coxsackievirus A10 and poliovirus 1, 10 mJ/cm2 for enterovirus 70, and 13 mJ/cm2 for echovirus 30. No synergistic effect was detected when evaluating the log inactivation of enteroviruses irradiated by the dual-wavelength UV-C LEDs.

Cardiovascular and general health status of adults with Trisomy 21.

BACKGROUND: Patients with Trisomy 21 are now living well into adulthood. Little data exists to assist the cardiologist in the care of these patients. We sought to examine the cardiac and general health status of adults with Trisomy 21 undergoing cardiac evaluation. METHODS & RESULTS: A retrospective review of all affected adults >21years followed at 2 tertiary care institutions was performed. Of 193 patients identified, median age was 31 (range 21.1-60.5) years. Cardiac surgery was performed in childhood in 127 with 30 patients who did not undergo surgery developing Eisenmenger syndrome. The remaining 36 patients did not warrant early surgical intervention. Six patients were lost to follow-up. Significant cardiac residua were present in 117 (62%). Arrhythmias were present in 53 (28%) with 15 having atrial fibrillation (8%). Non-cardiac comorbidities were common and included sleep apnea, pulmonary hypertension, thyroid dysfunction, thromboses and recurrent infections. Hospitalization in adulthood occurred in 58 patients (51%); pneumonia and cardiac related surgeries being the most common reasons for hospitalization. Average age of death (n=23) was 39.8±8.5years. Transition of care to an adult provider was uncommon occurring in 54 (27%) patients. On multivariate analysis, presence of younger age and absence of pulmonary hypertension were the sole predictors of survival for the group as a whole, as well as those patients without Eisenmenger syndrome. CONCLUSIONS: Adults with Trisomy 21 have frequent cardiac and non-cardiac co-morbidities. Cardiologists caring for these patients should be familiar with the adult acquired medical problems these patients encounter.

Variability and degradation of homeostasis in self-sustained oscillators.

Homeostasis is known to be absolutely critical to the sustainability of living organisms. At the heart of homeostasis are various feedback loops, which can control and regulate a system to stay in a most favourable stable state upon the influence of various disturbance. While variability has emerged as a key factor in sustainability, too much variability could however be detrimental. It is thus absolutely crucial to understand the effect of fluctuation in different feedback loops. While modelling technique has achieved a great advancement to understand this issue, too a complicated model however often prevents us from disentangling different many processes. Here, we propose a novel model to gain a key insight into the effect of variability in feedback on self-sustained oscillation. Specifically, by taking into account variation in model parameters for self-excitation and nonlinear damping, corresponding to positive and negative feedback, respectively, we show how fluctuation in positive or negative feedback weakens the efficiency of feedback and affects self-sustained oscillations, possibly leading to a complete breakdown of self-regulation. While results are generic and could be applied to different self-regulating systems (e.g. self-regulation of neuron activity, normal cell growth, etc.), we present a specific application to heart dynamics. In particular, we show that fluctuation in positive feedback can lead to slow heart by either amplitude death or oscillation death pathway while fluctuation in negative feedback can lead to fast heart beat.

Applicability of UV resistant Bacillus pumilus endospores as a human adenovirus surrogate for evaluating the effectiveness of virus inactivation in low-pressure UV treatment systems.

Recent studies have demonstrated the potential to use Bacillus pumilus endospores as a surrogate for human adenovirus (HAdV) in UV disinfection studies. The use of endospores has been limited by observations of batch-to-batch variation in UV sensitivity. This study reports on a propagation method that utilizes a commercially available medium to produce UV tolerant B. pumilus endospores with a consistent UV sensitivity. It is further demonstrated that the endospores of B. pumilus strain (ATCC 27142), produced using this protocol (half strength Columbia broth, 5 days incubation, with 0.1mM MnSO4), display a UV dose-response that is similar to that of HAdV. Endospore stocks could be stored in ethanol for up to two months at 4 °C without a significant change in UV sensitivity. Synergistic endospore damage was observed by pre-heat treatment of water samples followed by UV irradiation. UV tolerant B. pumilus endospores are a potential surrogate of HAdV for UV treatment performance tests in water utilities which do not have in-house research virology laboratories.

Applicability of integrated cell culture quantitative PCR (ICC-qPCR) for the detection of infectious adenovirus type 2 in UV disinfection studies.

Practical difficulties of the traditional adenovirus infectivity assay such as intensive labor requirements and longer turnaround period limit the direct use of adenovirus as a testing microorganism for systematic, comprehensive disinfection studies. In this study, we attempted to validate the applicability of integrated cell culture quantitative PCR (ICC-qPCR) as an alternative to the traditional cell culture method with human adenovirus type 2 (HAdV2) in a low-pressure UV disinfection study and to further optimize the procedures of ICC-qPCR for 24-well plate format. The relatively high stability of the hexon gene of HAdV2 was observed after exposure to UV radiation, resulting in a maximum gene copy reduction of 0.5 log10 at 280 mJ cm(-2). Two-day post-inoculation incubation period and a maximum spiking level of 10(5) MPN mL(-1) were selected as optimum conditions of ICC-qPCR with the tested HAdV2. An approximate 1:1 correlation of virus quantities by the traditional and ICC-qPCR cell culture based methods suggested that ICC-qPCR is a satisfactory alternative for practical application in HAdV2 disinfection studies. ICC-qPCR results, coupled with a first-order kinetic model (i.e., the inactivation rate constant of 0.0232 cm(2) mJ(-1)), showed that an UV dose of 172 mJ cm(-2) achieved a 4-log inactivation credit for HAdV2. This estimate is comparable to other studies with HAdV2 and other adenovirus respiratory types. The newly optimized ICC-qPCR shows much promise for further study on its applicability of other slow replicating viruses in disinfection studies.

Determining UV inactivation of Toxoplasma gondii oocysts by using cell culture and a mouse bioassay.

The effect of UV exposure on Toxoplasma gondii oocysts has not been completely defined for use in water disinfection. This study evaluated UV-irradiated oocysts by three assays: a SCID mouse bioassay, an in vitro T. gondii oocyst plaque (TOP) assay, and a quantitative reverse transcriptase real-time PCR (RT-qPCR) assay. The results from the animal bioassay show that 1- and 3-log(10) inactivation is achieved with 4 mJ/cm(2) UV and 10 mJ/cm(2) low-pressure UV, respectively. TOP assay results, but not RT-qPCR results, correlate well with bioassay results. In conclusion, a 3-log(10) inactivation of T. gondii oocysts is achieved by 10-mJ/cm(2) low-pressure UV, and the in vitro TOP assay is a promising alternative to the mouse bioassay.

Aeromonas caviae strain induces Th1 cytokine response in mouse intestinal tract.

Aeromonas caviae has been associated with human gastrointestinal disease. Strains of this species typically lack virulence factors (VFs) such as enterotoxins and hemolysins that are produced by other human pathogens of the Aeromonas genus. Microarray profiling of murine small intestinal extracts, 24 h after oral infection with an A. caviae strain, provides evidence of a Th1 type immune response. A large number of gamma-interferon (gamma-IFN) induced genes are up-regulated as well as several tumor necrosis factor-alpha (TNF-alpha) transcripts. Aeromonas caviae has always been considered an opportunistic pathogen because it lacks obvious virulence factors. This current effort suggests that an A. caviae strain can colonize the murine intestinal tract and cause what has been described by others as a dysregulatory cytokine response. This response could explain why a number of diarrheal waterborne disease cases have been attributed to A. caviae even though it lacks obvious enteropathogenic properties.

Characterization of Aeromonas virulence using an immunocompromised mouse model.

An immunocompromised mouse model was used to characterize Aeromonas strains for their ability to cause opportunistic, extraintestinal infections. A total of 34 isolates of Aeromonas (A. hydrophila [n = 12]), A. veronii biotype sobria [n = 7], A. caviae [n = 4], A. enchelia [n = 4], A. allosaccharophila [n = 2], A. salmonicida (n = 4), and A. bestiarum [n = 1]) were introduced by intraperitoneal injection into immunocompetent or chemically compromised (using cyclophosphamide) mice. The ability of each isolate to persist in the liver and spleen tissue was monitored at 24 hours after exposure. A majority ofA. hydrophila and A veronii v. sobria strains, but none of the isolates of other Aeromonas species, were capable of persistent colonization (<300 cells/mg spleen and liver tissue at 24 hours). The presence or absence of several putative virulence factors (cytotoxicity to HEp-2, lipase activity, elastase activity, and hemolysis) were determined for each isolate using in vitro tests. There were no correlations between the presence or absence of biochemical test results for putative virulence factors and persistence of the isolate in spleen and liver tissue at 24 hours.

Identification by microarray of a common pattern of gene expression in intact intestine and cultured intestinal cells exposed to virulent Aeromonas hydrophila isolates.

The genus Aeromonas comprises known virulent and avirulent isolates and has been implicated in waterborne disease. A common infection model of human gastroenteritis associated with A. hydrophila uses neonatal mice. The goal of this research was to evaluate whether a murine small intestinal cell line could provide comparable results to the gene expression changes in the neonatal mouse model. Changes in mRNA expression in host cell cultures and intestinal tissues were measured after exposure to virulent Aeromonas hydrophila strains. A. hydrophila caused the up-regulation of more than 200 genes in neonates and over 50 genes in cell culture. Twenty-six genes were found to be in common between the two models, of which the majority are associated with the innate immune response.

Assessment of the effectiveness of low-pressure UV light for inactivation of Helicobacter pylori.

Three strains of Helicobacter pylori were exposed to UV light from a low-pressure source to determine log inactivation versus applied fluence. Results indicate that H. pylori is readily inactivated at UV fluences typically used in water treatment regimens. Greater than 4-log(10) inactivation was demonstrated on all three strains at fluences of less than 8 mJ cm(-2).

Comparison of UV inactivation of spores of three encephalitozoon species with that of spores of two DNA repair-deficient Bacillus subtilis biodosimetry strains.

When exposed to 254-nm UV, spores of Encephalitozoon intestinalis, Encephalitozoon cuniculi, and Encephalitozoon hellem exhibited 3.2-log reductions in viability at UV fluences of 60, 140, and 190 J/m(2), respectively, and demonstrated UV inactivation kinetics similar to those observed for endospores of DNA repair-defective mutant Bacillus subtilis strains used as biodosimetry surrogates. The results indicate that spores of Encephalitozoon spp. are readily inactivated at low UV fluences and that spores of UV-sensitive B. subtilis strains can be useful surrogates in evaluating UV reactor performance.