A useful formula for periodic Jacobi matrices on trees.

We introduce a function of the density of states for periodic Jacobi matrices on trees and prove a useful formula for it in terms of entries of the resolvent of the matrix and its "half-tree" restrictions. This formula is closely related to the one-dimensional Thouless formula and associates a natural phase with points in the bands. This allows streamlined proofs of the gap labeling and Aomoto index theorems. We give a complete proof of gap labeling and sketch the proof of the Aomoto index theorem. We also prove a version of this formula for the Anderson model on trees.

Pericyte dysfunction and loss of interpericyte tunneling nanotubes promote neurovascular deficits in glaucoma.

Reduced blood flow and impaired neurovascular coupling are recognized features of glaucoma, the leading cause of irreversible blindness worldwide, but the mechanisms underlying these defects are unknown. Retinal pericytes regulate microcirculatory blood flow and coordinate neurovascular coupling through interpericyte tunneling nanotubes (IP-TNTs). Using two-photon microscope live imaging of the mouse retina, we found reduced capillary diameter and impaired blood flow at pericyte locations in eyes with high intraocular pressure, the most important risk factor to develop glaucoma. We show that IP-TNTs are structurally and functionally damaged by ocular hypertension, a response that disrupted light-evoked neurovascular coupling. Pericyte-specific inhibition of excessive Ca2+ influx rescued hemodynamic responses, protected IP-TNTs and neurovascular coupling, and enhanced retinal neuronal function as well as survival in glaucomatous retinas. Our study identifies pericytes and IP-TNTs as potential therapeutic targets to counter ocular pressure-related microvascular deficits, and provides preclinical proof of concept that strategies aimed to restore intrapericyte calcium homeostasis rescue autoregulatory blood flow and prevent neuronal dysfunction.

Comprehensive comparative analysis of the periodontal pathogen Porphyromonas gingivalis: exploring the pan-genome, the reconstruction of the gene regulatory network and genome-scale metabolic network.

Porphyromonas gingivalis is a nonmotile, obligate anaerobic, Gram-negative bacterium known for its association with periodontal disease and its involvement in systemic diseases such as atherosclerosis, cardiovascular disease, colon cancer, and Alzheimer's disease. This bacterium produces several virulence factors, including capsules, fimbriae, lipopolysaccharides, proteolytic enzymes, and hemagglutinins. A comparative genomic analysis revealed the open pangenome of P. gingivalis and identified complete type IV secretion systems in strain KCOM2805 and almost complete type VI secretion systems in strains KCOM2798 and ATCC49417, which is a new discovery as previous studies did not find the proteins involved in secretion systems IV and VI. Conservation of some virulence factors between different strains was observed, regardless of their genetic diversity and origin. In addition, we performed for the first time a reconstruction analysis of the gene regulatory network, identifying transcription factors and proteins involved in the regulatory mechanisms of bacterial pathogenesis. In particular, QseB regulates the expression of hemagglutinin and arginine deaminase, while Rex may suppress the release of gingipain through interactions with PorV and the formatum/nitrate transporter. Our study highlights the central role of conserved virulence factors and regulatory pathways, particularly QseB and Rex, in P. gingivalis and provides insights into potential therapeutic targets.

Pilot testing of the International Council of Cardiovascular Prevention and Rehabilitation Registry.

The International Council of Cardiovascular Prevention and Rehabilitation developed an International Cardiac Rehabilitation (CR) Registry (ICRR) to support CR programs in low-resource settings to optimize care provision and patient outcomes. This study assessed implementation of the ICRR, site data steward experience with on-boarding and data entry, and patient acceptability. Multimethod observational pilot involves (I) analysis of ICRR data from three centers (Iran, Pakistan, and Qatar) from inception to May 2022, (II) focus group with on-boarded site data stewards (also from Mexico and India), and (III) semistructured interviews with participating patients. Five hundred sixty-seven patients were entered. Based on volumes at each program, 85.6% of patients were entered in ICRR. 99.3% patients approached consented to participate. The average time to enter data at pre- and follow-up assessments by source was 6.8-12.6 min. Of 22 variables preprogram, completion was 89.5%. Among patients with any follow-up data, of four program-reported variables, completion was 99.0% in program completers and 51.5% in none; of 10 patient-reported variables, completion was 97.0% in program completers and 84.8% in none. The proportion of patients with any follow-up data was 84.8% in program completers, with 43.6% of noncompleters having any data entered other than completion status. Twelve data stewards participated in the focus group. Main themes were valuable on-boarding process, data entry, process of engaging patients, and benefits of participation. Thirteen patients were interviewed. Themes were good understanding of the registry, positive experience providing data, and value of lay summary and eagerness for annual assessment. Feasibility and data quality of ICRR were demonstrated.

A Modulated Approach for Improving MFSK RADARS to Resolve Mutual Interference on Autonomous Vehicles (AVs).

This paper proposes a novel automotive radar waveform involving the theory behind M-ary frequency shift key (MFSK) radar systems. Along with the MFSK theory, coding schemes are studied to provide a solution to mutual interference. The proposed MFSK waveform consists of frequency increments throughout the range of 76 GHz to 81 GHz with a step value of 1 GHz. Instead of stepping with a fixed frequency, a triangular chirp sequence allows for static and moving objects to be detected. Therefore, automotive radars will improve Doppler estimation and simultaneous range of various targets. In this paper, a binary coding scheme and a combined transform coding scheme used for radar waveform correlation are evaluated in order to provide unique signals. AVs have to perform in an environment with a high number of signals being sent through the automotive radar frequency band. Efficient coding methods are required to increase the number of signals that are generated. An evaluation method and experimental data of modulated frequencies as well as a comparison with other frequency method systems are presented.

First detection of Leishmania DNA in Lutzomyia longipalpis sensu lato (Diptera: Phlebotominae) in southem Mexico.

Background & objectives: Lutzomyia longipalpis sensu lato is an important vector of Leishmania infantum, the causative agent of visceral leishmaniasis (VL) in Latin America. In Mexico, this species has been recorded in endemic areas of leishmaniasis transmission, but it has never been detected as infected with Leishmania sp. This study aimed to explore the presence of Leishmania DNA in Lutzomyia longipalpis s.l. from samples collected with a human baited trap from an endemic region of leishmaniasis in southeastern Mexico. Methods: This is a prospective study where a total of 45 specimens of Lu. longipalpis s.l. collected in two sites of Yucatan state with records of leishmaniasis were tested. The nuclear ribosomal Internal Transcribed Spacer was amplified for the detection of Leishmania DNA. Results: Two females were positive for Leishmania DNA. None of the specimens positive for parasite DNA were found fed or gravid. Our finding represents the first record of infection by Leishmania in Lu. longipalpis s.l. for the country. Interpretation & conclusion: More studies are necessary to understand the potential role of this vector species in the transmission cycle of the causative agent of leishmaniasis in the southeastern and other regions of Mexico.

Predicting Injury Risk Over Changes in Physical Activity in Children Using the Acute:Chronic Workload Ratio.

Limited research exists on the relationship between changes in physical activity levels and injury in children. In this study, we investigated the prognostic relationship between changes in activity, measured by the acute:chronic workload ratio (ACWR), and injury in children. We used data from the Childhood Health, Activity, and Motor Performance School Study Denmark (2008-2014), a prospective cohort study of 1,660 children aged 6-17 years. We modeled the relationship between the uncoupled 5-week ACWR and injury, defined as patient-reported musculoskeletal pain, using generalized additive mixed models. These methods accounted for repeated measures, and they improved model fit and precision compared with previous studies that used logistic models. The prognostic model predicted an injury risk of approximately 3% between decreases in activity level of up to 60% and increases of up to 30%. Predicted risk was lower when activity decreased by more than 60% (minimum of 0.5% with no recreational activity). Predicted risk was higher when activity increased by more than 30% (4.5% with a 3-fold increase in activity). Girls were at significantly higher risk of injury than boys. We observed similar patterns but lower absolute risks when we restricted the outcome to clinician-diagnosed injury. Predicted increases in injury risk with increasing activity were much lower than those of previous studies carried out in adults.

Operational tolerance is not always permanent: A 10-year prospective study in pediatric liver transplantation recipients.

Immunosuppression withdrawal can be safely performed in select liver transplantation recipients, but the long-term outcomes and sustainability of tolerance have not been well studied. We completed a 10-year prospective, observational study of 18 pediatric liver transplantation recipients with operational tolerance to (1) assess the sustainability of tolerance over time, (2) compare the clinical characteristics of patients who maintained versus lost tolerance, (3) characterize liver histopathology findings in surveillance liver biopsies; and (4) describe immunologic markers in patients with tolerance. Comparator patients from two clinical phenotype groups termed "stable" and "nontolerant" patients were used as controls. Of the 18 patients with operational tolerance, the majority of patients were males (n = 14, 78%) who were transplanted for cholestatic liver disease (n = 12, 67%). Median age at transplantation was 1.9 (range, 0.6-8) years. Median time after transplantation that immunosuppression had been discontinued was 13.1 (range, 2.9-22.1) years. As many as 11 (61%) maintained tolerance for a median of 10.4 (range, 1.9-22.1) years, whereas 7 (39%) lost tolerance after a median of 3.2 (range, 1.5-18.6) years. Populations of T regulatory cells (%CD4+ CD25hi CD127lo ) were significantly higher in patients with tolerance (p = 0.02). Our results emphasize that spontaneous operational tolerance is a dynamic and nonpermanent state. It is therefore essential for patients who are clinically stable off immunosuppression to undergo regular follow-up and laboratory monitoring, as well as surveillance biopsies to rule out subclinical rejection.

Extracting experimental parameter entities from scientific articles.

Systematic reviews are labor-intensive processes to combine all knowledge about a given topic into a coherent summary. Despite the high labor investment, they are necessary to create an exhaustive overview of current evidence relevant to a research question. In this work, we evaluate three state-of-the-art supervised multi-label sequence classification systems to automatically identify 24 different experimental design factors for the categories of Animal, Dose, Exposure, and Endpoint from journal articles describing the experiments related to toxicity and health effects of environmental agents. We then present an in depth analysis of the results evaluating the lexical diversity of the design parameters with respect to model performance, evaluating the impact of tokenization and non-contiguous mentions, and finally evaluating the dependencies between entities within the category entities. We demonstrate that in general, algorithms that use embedded representations of the sequences out-perform statistical algorithms, but that even these algorithms struggle with lexically diverse entities.

Prokaryotic population dynamics and interactions in an AnSBBR using tequila vinasses as substrate in co-digestion with acid hydrolysates of Agave tequilana var. azul bagasse for hydrogen production.

AIMS: The purpose of this study was to characterize the prokaryotic community and putative microbial interactions between H2 -producing bacteria (HPB) and non-HPB using two anaerobic sequencing batch biofilm reactors (AnSBBRs) fed with tequila vinasses in co-digestion with acid hydrolysates of Agave tequilana var. azul bagasse (ATAB). METHODS AND RESULTS: Two AnSBBRs were operated for H2 production to correlate changes in physicochemical and biological variables by principal component analysis (PCA). Results indicated that H2 yield was supported by Ethanoligenens harbinense and Clostridium tyrobutyricum through the PFOR pathway. However, only E. harbinense was able to compete for sugars against non-HPB. Competitive exclusion associated with competition for sugars, depletion of essential trace elements, bacteriocin production and resistance to inhibitory compounds could be carried out by non-HPB, increasing their relative abundances during the dark fermentation (DF) process. CONCLUSIONS: The global scenario obtained by PCA correlated the decrease in H2 production with the lactate:acetate molar ratio in the influent. At the beginning of co-digestion, this ratio had the minimum value considered for a net gain of ATP. This fact could cause the reduction of the relative abundance of C. tyrobutyricum. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study that demonstrated the feasibility of H2 production by Clostridiales from acid hydrolysates of ATAB in co-digestion with tequila vinasses.

New insights into microbial interactions and putative competitive mechanisms during the hydrogen production from tequila vinasses.

This study aimed to characterize the prokaryotic community and putative microbial interactions involved in hydrogen (H2) production during the dark fermentation (DF) process, applying principal components analysis (PCA) to correlate changes in operational, physicochemical, and biological variables. For this purpose, a continuous stirred-tank reactor-type digester fed with tequila vinasses was operated at 24, 18, and 12 h of hydraulic retention times (HRTs) to apply organic loading rates of 20, 36, and 54 g-COD L-1 d-1, corresponding to stages I, II, and III, respectively. Results indicated high population dynamics for Archaea during the DF process toward a decrease in total sequences from 6299 to 99. Concerning the Bacteria community, lactic acid bacteria (LAB) were dominant reaching a relative abundance of 57.67%, while dominant H2-producing bacteria (HPB) decreased from 25.76% to 21.06% during stage III. Putative competitive exclusion mechanisms such as competition for substrates, bacteriocins production, and micronutrient depletion carried out by Archaea and non-H2-producing bacteria (non-HPB), especially LAB, could negatively impact the dominance of HPB such as Ethanoligenens harbinense and Clostridium tyrobutyricum. As a consequence, low maximal volumetric H2 production rate (672 mL-H2 L-1 d-1) and yield (3.88 mol-H2 assimilated sugars-1) were obtained. The global scenario obtained by PCA correlations suggested that C. tyrobutyricum positively impacted H2 molar yield through butyrate fermentation using the butyryl-CoA:acetate CoA transferase pathway, while the most abundant HPB E. harbinense decreased its relative abundance at the shortest HRT toward the dominance of non-HPB. This study provides new insights into the microbial interactions and helps to better understand the DF performance for H2 production using tequila vinasses as substrate. KEY POINTS: • E. harbinense and C. tyrobutyricum were responsible for H2 production. • Clostridiales used acetate and butyrate fermentations for H2 production. • LAB won the competition for sugars against Clostridiales during DF. • Putative bacteriocins production and micronutrients depletion could favor LAB.

Mosquito species (Diptera: culicidae) collected after tropical storm cristobal in Merida, Yucatan, South-east Mexico.

After the tropical storm Cristobal, we performed special adult entomological collections in the peri-domicile of 35 houses from 25 neighborhoods of Mérida, Yucatan, Mexico in response to complaints from the community about an increased nuisance due to an abundance of mosquitoes. A total of 1,275 specimens from four genera and 13 species were collected: Aedes taeniorhynchus (92%), Culex quinquefasciatus (72%), Aedes aegypti (72%), Psorophora mexicana (36%), Psorophora cyanescens (32%), Aedes scapularis (24%), Culex nigripalpus (24%), Aedes albopictus (8%), Psorophora ferox (4%), Haemagogus equinus (4%), Aedes trivittatus (4%), Culex coronator (4%), Culex iolambdis (4%). From these collections, the increased mosquito nuisance was mainly the result of invasive species such as Aedes taeniorhynchus and Psorophora. City wide, vehicle mounted ULV spraying was performed by the MoH and the municipality of Merida to control adult mosquito populations. We report Culex iolambdis for the first time in Merida and Psorophora mexicana for the state of Yucatan.

Human MiniPromoters for ocular-rAAV expression in ON bipolar, cone, corneal, endothelial, Müller glial, and PAX6 cells.

Small and cell-type restricted promoters are important tools for basic and preclinical research, and clinical delivery of gene therapies. In clinical gene therapy, ophthalmic trials have been leading the field, with over 50% of ocular clinical trials using promoters that restrict expression based on cell type. Here, 19 human DNA MiniPromoters were bioinformatically designed for rAAV, tested by neonatal intravenous delivery in mouse, and successful MiniPromoters went on to be tested by intravitreal, subretinal, intrastromal, and/or intravenous delivery in adult mouse. We present promoter development as an overview for each cell type, but only show results in detail for the recommended MiniPromoters: Ple265 and Ple341 (PCP2) ON bipolar, Ple349 (PDE6H) cone, Ple253 (PITX3) corneal stroma, Ple32 (CLDN5) endothelial cells of the blood-retina barrier, Ple316 (NR2E1) Müller glia, and Ple331 (PAX6) PAX6 positive. Overall, we present a resource of new, redesigned, and improved MiniPromoters for ocular gene therapy that range in size from 784 to 2484 bp, and from weaker, equal, or stronger in strength relative to the ubiquitous control promoter smCBA. All MiniPromoters will be useful for therapies involving small regulatory RNA and DNA, and proteins ranging from 517 to 1084 amino acids, representing 62.9-90.2% of human proteins.

Management of Biliary Stricture in Pediatric Liver Transplantation Patients: Long-Term Outcomes.

Postoperative biliary complications have been reported to occur in 10% to 33% of pediatric liver transplantation (LT) recipients. Percutaneous intervention has become the primary treatment method for these complications; however, the efficacy and outcomes of these patients have not been well studied. Institutional pediatric LT from 1998 to 2019 were retrospectively reviewed to determine the patients referred for percutaneous treatment of post-LT biliary strictures. Clinical parameters, percutaneous transhepatic cholangiograms (PTCs), biliary catheter placement, cholangioplasty, and long-term outcomes were analyzed. Of the 396 consecutive pediatric LT recipients during our study period, 50 (12.6%) were diagnosed with biliary strictures on PTC. LT biliary reconstructions were Roux-en-Y hepaticojejunostomy in 28 patients (56%), choledochojejunostomy in 11 patients (22%), and choledochocholedochostomy in 11 patients (22%). Median age at LT was 23.2 months (interquartile range [IQR], 10.9-90.6), and 14 patients (28%) developed hepatic artery thrombosis. A total of 44 patients (88%) were treated with internal/external biliary catheters, of whom 38 (76%) underwent balloon cholangioplasty. By 12 months, 84% of patients had complete stricture resolution and catheter removal. Median total duration of catheter drainage was 152 days (IQR, 76-308). A total of 8 patients required additional surgery (biliary reconstruction or repeat LT [re-LT]) or died with a drainage catheter in place from complications unrelated to PTC intervention. Among the 6 patients (12%) treated with unilateral external biliary drainage catheters, 2 had catheters removed for inadequate drainage but then had spontaneous biliary obstruction resolution, 1 underwent duct reconstruction, and 3 required long-term catheterization. Biliary strictures following pediatric LT can be successfully treated with internal/external biliary drainage catheters and cholangioplasty if the stricture can be crossed. However, patients with isolated strictured ducts may require long-term external catheter drainage until re-LT or percutaneous obliteration of isolated ducts.

Synthetic Routes Towards the Synthesis of Geminal α-Difunctionalized Ketones.

The importance of gem-difunctionalized ketones is represented by their broad applications across chemical boundaries over recent years. The interesting reactivities that this class of compounds possess have made them ideal building blocks to access high-value organic molecules. Furthermore, the gem-difunctionalized ketone moiety has featured in numerous bioactive molecules. For these reasons, a plethora of routes to access such significant molecules have been developed by research groups worldwide - this account looks at delineating the synthesis of gem-difunctionalized ketones from carbonyl substrates, diazo compounds, sulfur ylides and alkynyl reactants.

Direct Synthesis of α-Fluoro-α-Triazol-1-yl Ketones from Sulfoxonium Ylides: A One-Pot Approach.

The work reported herein showcases a new route to access α-fluoro-α-triazol-1-yl ketones from sulfoxonium ylides via α-azido-α-fluoro ketone intermediates. In a one-pot, two-step sequence, the ketosulfoxonium reactant initially undergoes insertion of F+ and N3-, followed by a subsequent CuAAC reaction with arylacetylenes to install a 1,4-triazolo moiety. The approach allows for modification to both the sulfoxonium ylide and arylacetylene reactants. Fifteen examples have been reported, with yields ranging between 22% and 75%.

How well do self-interaction corrections repair the overestimation of static polarizabilities in density functional calculations?

We examine the effect of removing self-interaction error (SIE) on the calculation of molecular polarizabilities in the local spin density (LSDA) and generalized gradient approximations (GGA). To this end, we utilize a database of 132 molecules taken from a recent benchmark study [Hait and Head-Gordon, Phys. Chem. Chem. Phys., 2018, 20, 19800] to assess the influence of SIE on polarizabilities by comparing results with accurate reference data. Our results confirm that the general overestimation of molecular polarizabilities by these density functional approximations can be attributed to SIE. However, removing SIE using the Perdew-Zunger self-interaction-correction (PZ-SIC) method, implemented using the Fermi-Löwdin Orbital SIC approach, leads to an underestimation of molecular polarizabilities, showing that PZ-SIC overcorrects when combined with LSDA or GGA. Application of a recently proposed locally scaled SIC [Zope, et al., J. Chem. Phys., 2019, 151, 214108] is found to provide more accurate polarizabilities. We attribute this to the ability of the local scaling scheme to selectively correct for SIE in the regions of space where the correction is needed most.

Vitamin D supplementation: position Statement of the Iberoamerican Society of Osteoporosis and Mineral Metabolism (SIBOMM).

BACKGROUND: Vitamin D (VD) deficiency is a global pandemic that affects more than a third of the population worldwide. The population of Latin America and the Caribbean exceeds 620 million inhabitants with diverse ethnic origins and different latitudes and altitudes, which make comparisons and generalizations difficult. AIM AND METHOD: We sought to establish an expert consensus regarding the recommendations for VD supplementation in Latin America by means of the Delphi methodology. RESULTS: The prophylactic dosage of VD in the general population should be individualized according to age, race, body weight, sun exposure of an individual, altitude, and dietary and exercise habits, without ruling out existing chronic diseases. CONCLUSION: The importance of VD has been widely documented and its deficiency is a pandemic. Many individuals have difficulty meeting daily VD requirements through food and the sun. The population of Latin America and the Caribbean has diverse ethnics, cultures, in addition to living in different latitudes and altitudes. Therefore, it is important to make a position on VD supplementation, given the different characteristics, ages and serum levels of 25(OH)D.

An Overview of Autonomous Vehicles Sensors and Their Vulnerability to Weather Conditions.

Autonomous vehicles (AVs) rely on various types of sensor technologies to perceive the environment and to make logical decisions based on the gathered information similar to humans. Under ideal operating conditions, the perception systems (sensors onboard AVs) provide enough information to enable autonomous transportation and mobility. In practice, there are still several challenges that can impede the AV sensors' operability and, in turn, degrade their performance under more realistic conditions that actually occur in the physical world. This paper specifically addresses the effects of different weather conditions (precipitation, fog, lightning, etc.) on the perception systems of AVs. In this work, the most common types of AV sensors and communication modules are included, namely: RADAR, LiDAR, ultrasonic, camera, and global navigation satellite system (GNSS). A comprehensive overview of their physical fundamentals, electromagnetic spectrum, and principle of operation is used to quantify the effects of various weather conditions on the performance of the selected AV sensors. This quantification will lead to several advantages in the simulation world by creating more realistic scenarios and by properly fusing responses from AV sensors in any object identification model used in AVs in the physical world. Moreover, it will assist in selecting the appropriate fading or attenuation models to be used in any X-in-the-loop (XIL, e.g., hardware-in-the-loop, software-in-the-loop, etc.) type of experiments to test and validate the manner AVs perceive the surrounding environment under certain conditions.

Origin of High Activity and Durability of Twisty Nanowire Alloy Catalysts under Oxygen Reduction and Fuel Cell Operating Conditions.

The ability to control the surface composition and morphology of alloy catalysts is critical for achieving high activity and durability of catalysts for oxygen reduction reaction (ORR) and fuel cells. This report describes an efficient surfactant-free synthesis route for producing a twisty nanowire (TNW) shaped platinum-iron (PtFe) alloy catalyst (denoted as PtFe TNWs) with controllable bimetallic compositions. PtFe TNWs with an optimal initial composition of ∼24% Pt are shown to exhibit the highest mass activity (3.4 A/mgPt, ∼20 times higher than that of commercial Pt catalyst) and the highest durability (<2% loss of activity after 40 000 cycles and <30% loss after 120 000 cycles) among all PtFe-based nanocatalysts under ORR or fuel cell operating conditions reported so far. Using ex situ and in situ synchrotron X-ray diffraction coupled with atomic pair distribution function (PDF) analysis and 3D modeling, the PtFe TNWs are shown to exhibit mixed face-centered cubic (fcc)-body-centered cubic (bcc) alloy structure and a significant lattice strain. A striking finding is that the activity strongly depends on the composition of the as-synthesized catalysts and this dependence remains unchanged despite the evolution of the composition of the different catalysts and their lattice constants under ORR or fuel cell operating conditions. Notably, dealloying under fuel cell operating condition starts at phase-segregated domain sites leading to a final fcc alloy structure with subtle differences in surface morphology. Due to a subsequent realloying and the morphology of TNWs, the surface lattice strain observed with the as-synthesized catalysts is largely preserved. This strain and the particular facets exhibited by the TNWs are believed to be responsible for the observed activity and durability enhancements. These findings provide new insights into the correlation between the structure, activity, and durability of nanoalloy catalysts and are expected to energize the ongoing effort to develop highly active and durable low-Pt-content nanowire catalysts by controlling their alloy structure and morphology.