Spatial scales of COVID-19 transmission in Mexico.

During outbreaks of emerging infectious diseases, internationally connected cities often experience large and early outbreaks, while rural regions follow after some delay. This hierarchical structure of disease spread is influenced primarily by the multiscale structure of human mobility. However, during the COVID-19 epidemic, public health responses typically did not take into consideration the explicit spatial structure of human mobility when designing nonpharmaceutical interventions (NPIs). NPIs were applied primarily at national or regional scales. Here, we use weekly anonymized and aggregated human mobility data and spatially highly resolved data on COVID-19 cases at the municipality level in Mexico to investigate how behavioral changes in response to the pandemic have altered the spatial scales of transmission and interventions during its first wave (March-June 2020). We find that the epidemic dynamics in Mexico were initially driven by exports of COVID-19 cases from Mexico State and Mexico City, where early outbreaks occurred. The mobility network shifted after the implementation of interventions in late March 2020, and the mobility network communities became more disjointed while epidemics in these communities became increasingly synchronized. Our results provide dynamic insights into how to use network science and epidemiological modeling to inform the spatial scale at which interventions are most impactful in mitigating the spread of COVID-19 and infectious diseases in general.

Dynamic clade transitions and the influence of vaccination on the spatiotemporal circulation of SARS-CoV-2 variants.

Since 2021, the emergence of variants of concern (VOC) has led Brazil to experience record numbers of in COVID-19 cases and deaths. The expanded spread of the SARS-CoV-2 combined with a low vaccination rate has contributed to the emergence of new mutations that may enhance viral fitness, leading to the persistence of the disease. Due to limitations in the real-time genomic monitoring of new variants in some Brazilian states, we aimed to investigate whether genomic surveillance, coupled with epidemiological data and SARS-CoV-2 variants spatiotemporal spread in a smaller region, can reflect the pandemic progression at a national level. Our findings revealed three SARS-CoV-2 variant replacements from 2021 to early 2022, corresponding to the introduction and increase in the frequency of Gamma, Delta, and Omicron variants, as indicated by peaks of the Effective Reproductive Number (Reff). These distinct clade replacements triggered two waves of COVID-19 cases, influenced by the increasing vaccine uptake over time. Our results indicated that the effectiveness of vaccination in preventing new cases during the Delta and Omicron circulations was six and eleven times higher, respectively, than during the period when Gamma was predominant, and it was highly efficient in reducing the number of deaths. Furthermore, we demonstrated that genomic monitoring at a local level can reflect the national trends in the spread and evolution of SARS-CoV-2.

Influence of Sonication on the Molecular Characteristics of Carbopol® and Its Rheological Behavior in Microgels.

In this work, the effect of sonication on the molecular characteristics of polyacrylic acid (Carbopol® Ultrez 10), as well as on its rheological behavior in aqueous dispersions and microgels, was analyzed for the first time by rheometry, weight-average molecular weight (Mw) measurements via static light scattering (SLS), Fourier transform infrared (FTIR) spectroscopy and confocal microscopy. For this, the precursor dispersion and the microgels containing 0.25 wt.% of Ultrez 10 were sonicated in a commercial ultrasound bath at constant power and at different times. The main rheological properties of the microgel, namely, shear modulus, yield stress and viscosity, all decreased with increasing sonication time, while the microgel's Herschel-Bulkley (H-B) behavior, without thixotropy, was preserved. Also, Mw of Ultrez 10 decreased up to almost one-third (109,212 g/mol) of its original value (300,860 g/mol) after 180 min of sonication. These results evidence a softening of the gel microstructure, which results from the reduction in the Mw of polyacrylic acid with sonication time. Separately, FTIR measurements show that sonication produces scission in the C-C links of the Carbopol® backbone, which results in chains with the same chemistry but lower molecular weight. Finally, confocal microscopy observations revealed a diminution of the size of the microsponge domains and more free solvent with sonication time, which is reflected in a less compact and softer microstructure. The present results indicate that both the microstructure and the rheological behavior of Carbopol® microgels, in particular, and complex fluids, in general, may be manipulated or tailored by systematic high-power ultrasonication.

Topology Testing and Demographic Modeling Illuminate a Novel Speciation Pathway in the Greater Caribbean Sea Following the Formation of the Isthmus of Panama.

Recent genomic analyses have highlighted the prevalence of speciation with gene flow in many taxa and have underscored the importance of accounting for these reticulate evolutionary processes when constructing species trees and generating parameter estimates. This is especially important for deepening our understanding of speciation in the sea where fast-moving ocean currents, expanses of deep water, and periodic episodes of sea level rise and fall act as soft and temporary allopatric barriers that facilitate both divergence and secondary contact. Under these conditions, gene flow is not expected to cease completely while contemporary distributions are expected to differ from historical ones. Here, we conduct range-wide sampling for Pederson's cleaner shrimp (Ancylomenes pedersoni), a species complex from the Greater Caribbean that contains three clearly delimited mitochondrial lineages with both allopatric and sympatric distributions. Using mtDNA barcodes and a genomic ddRADseq approach, we combine classic phylogenetic analyses with extensive topology testing and demographic modeling (10 site frequency replicates × 45 evolutionary models × 50 model simulations/replicate = 22,500 simulations) to test species boundaries and reconstruct the evolutionary history of what was expected to be a simple case study. Instead, our results indicate a history of allopatric divergence, secondary contact, introgression, and endemic hybrid speciation that we hypothesize was driven by the final closure of the Isthmus of Panama and the strengthening of the Gulf Stream Current ~3.5 Ma. The history of this species complex recovered by model-based methods that allow reticulation differs from that recovered by standard phylogenetic analyses and is unexpected given contemporary distributions. The geologically and biologically meaningful insights gained by our model selection analyses illuminate what is likely a novel pathway of species formation not previously documented that resulted from one of the most biogeographically significant events in Earth's history.

Dynamic clade transitions and the influence of vaccine rollout on the spatiotemporal circulation of SARS-CoV-2 variants in São Paulo, Brazil.

Since 2021, the emergence of variants of concern (VOC) has led Brazil to experience record numbers of in COVID-19 cases and deaths. The expanded spread of the SARS-CoV-2 combined with a low vaccination rate has contributed to the emergence of new mutations that may enhance viral fitness, leading to the persistence of the disease. Due to limitations in the real-time genomic monitoring of new variants in some Brazilian states, we aimed to investigate whether genomic surveillance, coupled with epidemiological data and SARS-CoV-2 variants spatiotemporal spread in a smaller region, can reflect the pandemic progression at a national level. Our findings revealed three SARS-CoV-2 variant replacements from 2021 to early 2022, corresponding to the introduction and increase in the frequency of Gamma, Delta, and Omicron variants, as indicated by peaks of the Effective Reproductive Number (Reff). These distinct clade replacements triggered two waves of COVID-19 cases, influenced by the increasing vaccine uptake over time. Our results indicated that the effectiveness of vaccination in preventing new cases during the Delta and Omicron circulations was six and eleven times higher, respectively, than during the period when Gamma was predominant, and it was highly efficient in reducing the number of deaths. Furthermore, we demonstrated that genomic monitoring at a local level can reflect the national trends in the spread and evolution of SARS-CoV-2.

Do carcass traits influence consumer perception of pork eating quality?

The objective of this study was to assess carcass traits' influence on pork eating quality as evaluated by consumers. A total of 1360 pork chops were used, with 824 from the sirloin end and 536 from the butt end of the loin (Longissimuss thoracis et lumborum), to produce 340 packages, each containing four pork chops. Untrained participants received one package of either sirloin or butt chops, being two pork chops from barrows and two from gilts. Participants answered a survey rating the tenderness, juiciness, flavour, and overall acceptability of each chop on an 8-point scale. Correlation analysis was conducted between carcass traits and pork eating quality attributes. For the descriptive analysis, classes (low, medium, and high) for carcass traits, Warner-Bratzler shear force (WBSF) and cooking loss were created based on our consumer responses dataset for palatability attributes. No significant correlations (P > 0.05) were observed between carcass traits and pork eating quality traits. Tenderness and overall acceptability were negatively correlated (P < 0.05) with cooking loss and WBSF. Loin intramuscular fat (IMF) content showed a weak negative correlation (P < 0.05) with WBSF and cooking loss. Consumers rated chops from the high and medium/high backfat thickness and loin IMF classes slightly higher for tenderness and juiciness, respectively. Additionally, chops from the low and/or medium WBSF and cooking loss classes received slightly higher scores for tenderness and juiciness than pork chops in the high classes. In conclusion, the study indicated that carcass traits had minimal impact on overall acceptability of pork by consumers.

Genetic Testing Guidelines Impact Care in Newborns with Congenital Heart Defects.

OBJECTIVE: To evaluate genetic evaluation practices in newborns with the most common birth defect, congenital heart defects (CHD), we determined the prevalence and the yield of genetic evaluation across time and across patient subtypes, before and after implementation of institutional genetic testing guidelines. STUDY DESIGN: This was a retrospective, cross-sectional study of 664 hospitalized newborns with CHD using multivariate analyses of genetic evaluation practices across time and patient subtypes. RESULTS: Genetic testing guidelines for hospitalized newborns with CHD were implemented in 2014, and subsequently genetic testing increased (40% in 2013 and 75% in 2018, OR 5.02, 95% CI 2.84-8.88, P < .001) as did medical geneticists' involvement (24% in 2013 and 64% in 2018, P < .001). In 2018, there was an increased use of chromosomal microarray (P < .001), gene panels (P = .016), and exome sequencing (P = .001). The testing yield was high (42%) and consistent across years and patient subtypes analyzed. Increased testing prevalence (P < .001) concomitant with consistent testing yield (P = .139) added an estimated 10 additional genetic diagnoses per year, reflecting a 29% increase. CONCLUSIONS: In patients with CHD, yield of genetic testing was high. After implementing guidelines, genetic testing increased significantly and shifted to newer sequence-based methods. Increased use of genetic testing identified more patients with clinically important results with potential to impact patient care.

Phosphate alternatives for meat processing and challenges for the industry: A critical review.

Meat and meat products provide high levels of nutrition and many health benefits to consumers, yet a controversy exists regarding the use of non-meat additives, such as the inorganic phosphates that are commonly used in meat processing, and particularly their relationship to cardiovascular health and kidney complications. Inorganic phosphates are salts of phosphoric acid (e.g., sodium phosphate, potassium phosphate, or calcium phosphate), whereas organic phosphates are ester compounds (e.g., the phospholipids found in cell membranes). In this sense, the meat industry remains active in its efforts to improve formulations for processed meat products with the use of natural ingredients. Despite efforts to improve formulations, many processed meat products still contain inorganic phosphates, which are used for their technological contributions to meat chemistry including improvements in water-holding capacity and protein solubilization. This review provides a thorough evaluation of phosphate substitutes in meat formulations and other processing technologies that can help eliminate phosphates from the formulations of processed meat products. In general, several ingredients have been evaluated as replacements for inorganic phosphates with varying degrees of success such as plant-based ingredients (e.g., starches, fibers, or seeds), fungi ingredients (e.g., mushrooms and mushroom extracts), algae ingredients, animal-based ingredients (e.g., meat/seafood, dairy, or egg materials), and inorganic compounds (i.e., minerals). Although these ingredients have shown some favorable effects in certain meat products, none have exactly matched the many functions of inorganic phosphates, so the support of extrinsic technologies, such as tumbling, ultrasound, high-pressure processing (HPP), and pulsed electric field (PEF), may be necessary to achieve similar physiochemical properties as conventional products. The meat industry should continue to investigate ways to scientifically innovate the formulations of, and the technologies used in, processed meat products while also listening to (and acting upon) the feedback from consumers.

High-frequency devices effect in vitro: promissing approach in the treatment of acne vulgaris?

Abstract Background: Acne vulgaris is an inflammatory skin disorder leading to an impairment of quality of life and is therefore not only a cosmetic issue. Its pathogenesis is multifactorial - of particular importance is the colonization with the bacterium Propionibacterium acnes. A wide range of different treatment options exists including topical and systemic treatments depending on severity. High Frequency (HF) therapy, historically developed in the 19th century, claims antimicrobial effects on acne skin, but solid data on its efficacy and mechanism of action is lacking. Objective: The main objective of this study was to determine the efficacy of HF therapy on skin flora and P. acnes in vitro using a commercial device as well as to review studies on the mechanism of action. Methods: The plasma source was investigated regarding electrical settings, heat, and ozone development. Bacterial skin flora, fungal isolates, and P. acnes were exposed to HF in vitro and compared to unexposed controls by evaluating the number of colonies on agar plates. To further analyze bacterial species from normal skin flora, 16S-sequencing was performed. Statistical analyses were carried out using row analysis and unpaired t-test. Results: HF treatment led to a significant reduction of almost every bacterial and fungal species investigated in this study. Moreover, the number of colonies forming units was significantly decreased in P. acnes after HF treatment compared to controls in vitro. Study limitations: The experiments were performed in vitro only. To assess clinical effects further in vivo experiments are necessary. Conclusions: The results collected in this study, although in vitro, provide a mechanistic basis for HF as a complementary treatment option for patients with acne. It might also have a beneficial effect on patients with superficial infectious skin of the skin.

High-frequency devices effect in vitro: promissing approach in the treatment of acne vulgaris?

BACKGROUND: Acne vulgaris is an inflammatory skin disorder leading to an impairment of quality of life and is therefore not only a cosmetic issue. Its pathogenesis is multifactorial - of particular importance is the colonization with the bacterium Propionibacterium acnes. A wide range of different treatment options exists including topical and systemic treatments depending on severity. High Frequency (HF) therapy, historically developed in the 19th century, claims antimicrobial effects on acne skin, but solid data on its efficacy and mechanism of action is lacking. OBJECTIVES: The main objective of this study was to determine the efficacy of HF therapy on skin flora and P. acnes in vitro using a commercial device as well as to review studies on the mechanism of action. METHODS: The plasma source was investigated regarding electrical settings, heat, and ozone development. Bacterial skin flora, fungal isolates, and P. acnes were exposed to HF in vitro and compared to unexposed controls by evaluating the number of colonies on agar plates. To further analyze bacterial species from normal skin flora, 16S-sequencing was performed. Statistical analyses were carried out using row analysis and unpaired t-test. RESULTS: HF treatment led to a significant reduction of almost every bacterial and fungal species investigated in this study. Moreover, the number of colonies forming units was significantly decreased in P. acnes after HF treatment compared to controls in vitro. STUDY LIMITATIONS: The experiments were performed in vitro only. To assess clinical effects further in vivo experiments are necessary. CONCLUSIONS: The results collected in this study, although in vitro, provide a mechanistic basis for HF as a complementary treatment option for patients with acne. It might also have a beneficial effect on patients with superficial infectious skin of the skin.

Decline in Functional Status While on the Waiting List Predicts Worse Survival After Lung Transplantation.

OBJECTIVES: To determine if decreases in the Karnofsky Performance Score (KPS) while on the waitlist predict decreased survival after lung transplantation (LTx). DESIGN: A retrospective evaluation of the United Network for Organ Sharing database. The KPS was evaluated at the time of listing for transplant and at the time of transplantation. Group I consisted of patients having a decrease in KPS during the time on the waiting list (from the time of listing to the time of transplant), and Group II consisted of patients whose KPS stayed the same or increased during the same period. The authors used propensity-score weighting for comparisons of these groups. SETTING: Retrospective observational database review. PARTICIPANTS: Adult patients undergoing lung transplantation. INTERVENTIONS: None. Patients were stratified according to a change in their KPS. MEASUREMENTS AND MAIN RESULTS: Patient and graft survival of patients with decreasing or not decreasing KPS were compared. Of the 27,558 subjects included in the analysis, 17,986 (65%) had worsening KPS, which was associated with worse graft (p = 0.0003) and patient (p = 0.0019) survival after LTx. Using multivariate regression, a decrease in KPS of ≥40 was associated with decreased survival, and an increase of ≥40 was associated with improved survival (HR = 1.245, 95% CI [1.181-1.312], p < 0.0001 and HR = 0.866, 95% CI [0.785, 0.955], respectively). Among patients with a KPS <40 at the time of transplant, those with a decrease in KPS of ≥40 had decreased graft and patient survival compared with those with a smaller decrease (p = 0.0002 and p = 0.0021, respectively). CONCLUSIONS: Deterioration of KPS on the waiting list for LTx is associated with significantly greater postoperative mortality in patients after LTx. These results should be taken into consideration when allocating organs. Strategies to increase or to prevent a decrease in KPS before LTx should be evaluated.

[Degenerative cervical myelopathy]. / Mielopatía cervical degenerativa: una patología cada vez más frecuente y que requiere diagnóstico y manejo precoz.

Degenerative cervical myelopathy (DCM) is the most common cause of spinal cord dysfunction in adults. Its prevalence is increasing as a result of population aging. The diagnosis of DCM is often delayed or overlooked, resulting in secondary neurologic morbidity. The natural course of DCM typically presents as a gradual neurological deterioration, with symptoms ranging from muscle weakness to complete paralysis, with variable degrees of sensory deficits and sphincter dysfunction. Magnetic resonance imaging (MRI) and electrophysiological studies allow the assessment of spinal cord function and its structural damage to determine treatment and clinical outcomes. All patients with signs and symptoms consistent with DCM should be referred to a spine surgeon for assessment and tailored treatment. Those patients with mild DCM can be managed non-operatively but require close monitoring and education about potentially alarming signs and symptoms. Surgery is not currently recommended for asymptomatic patients with evidence of spinal cord compression or cervical spinal stenosis on MRI, but they require a structured follow-up. Patients with moderate or severe DCM require surgical decompression to avoid further progression. The objective of this review is to raise awareness of degenerative cervical myelopathy and its increasing prevalence as well as to aid non-surgical healthcare workers for a timely diagnosis and management of this disabling condition.

Presenting signs and symptoms of artificial urinary sphincter cuff erosion

ABSTRACT Purpose To characterize the most common presentation and clinical risk factors for artificial urinary sphincter (AUS) cuff erosion to distinguish the relative frequency of symptoms that should trigger further evaluation in these patients. Materials and Methods We retrospectively reviewed our tertiary center database to identify men who presented with AUS cuff erosion between 2007 - 2020. A similar cohort of men who underwent AUS placement without erosion were randomly selected from the same database for symptom comparison. Risk factors for cuff erosion - pelvic radiation, androgen deprivation therapy (ADT), high-grade prostate cancer (Gleason score ≥ 8) - were recorded for each patient. Presenting signs and symptoms of cuff erosion were grouped into three categories: obstructive symptoms, worsening incontinence, and localized scrotal inflammation (SI). Results Of 893 men who underwent AUS placement during the study interval, 61 (6.8%) sustained cuff erosion. Most erosion patients (40/61, 66%) presented with scrotal inflammatory changes including tenderness, erythema, and swelling. Fewer men reported obstructive symptoms (26/61, 43%) and worsening incontinence (21/61, 34%). Men with SI or obstructive symptoms presented significantly earlier than those with worsening incontinence (SI 14 ± 18 vs. obstructive symptoms 15 ± 16 vs. incontinence 37 ± 48 months after AUS insertion, p<0.01). Relative to the non-erosion control group (n=61), men who suffered erosion had a higher prevalence of pelvic radiation (71 vs. 49%, p=0.02). Conclusion AUS cuff erosion most commonly presents as SI symptoms. Obstructive voiding symptoms and worsening incontinence are also common. Any of these symptoms should prompt further investigation of cuff erosion.

Microbial production of toluene in oxygen minimum zone waters in the Humboldt Current System off Chile.

Expansion of oxygen minimum zones in the world's oceans is likely to enhance the production of anaerobic metabolites by marine microorganisms. Here we show that toluene is present throughout the year in shelf waters of the upwelling ecosystem off Concepción (36° S), Chile, and it is a product of microbial anaerobic metabolism. The intra-annual variability in toluene concentrations is consistent with seasonal variability in the strengths of suboxic equatorial and oxygenated subantarctic water masses. Laboratory incubations of oxygen minimum zone water showed microbial production of toluene in the absence of O2. Toluene concentrations were elevated (up to 96 nM) in deeper O2-depleted waters and followed a seasonal pattern in oceanographic conditions. There is evidence to hypothesize that microbial production of toluene could be a homeostatic biochemical mechanism to thrive in the more acidic oxygen minimum zone waters. On the other hand, evidence indicates that microbial anaerobic degradation of toluene may be a source of NO2- by partial denitrification, as shown for aquifer sediments. Since toluene production was not detected in incubations under aerobic conditions, we hypothesize that oxygen minimum zone waters export toluene to surrounding oxygenated waters. Expansion of hypoxia in the ocean will certainly enhance the production and export of anaerobic metabolites by marine microorganisms.

Impact of SARS-CoV-2 Gamma lineage introduction and COVID-19 vaccination on the epidemiological landscape of a Brazilian city.

Background: The emergence of the Brazilian variant of concern, Gamma lineage (P.1), impacted the epidemiological profile of COVID-19 cases due to its higher transmissibility rate and immune evasion ability. Methods: We sequenced 305 SARS-CoV-2 whole-genomes and performed phylogenetic analyses to identify introduction events and the circulating lineages. Additionally, we use epidemiological data of COVID-19 cases, severe cases, and deaths to measure the impact of vaccination coverage and mortality risk. Results: Here we show that Gamma introduction in São José do Rio Preto, São Paulo, Brazil, was followed by the displacement of seven circulating SARS-CoV-2 variants and a rapid increase in prevalence two months after its first detection in January 2021. Moreover, Gamma variant is associated with increased mortality risk and severity of COVID-19 cases in younger age groups, which corresponds to the unvaccinated population at the time. Conclusions: Our findings highlight the beneficial effects of vaccination indicated by a pronounced reduction of severe cases and deaths in immunized individuals, reinforcing the need for rapid and massive vaccination.

Presenting signs and symptoms of artificial urinary sphincter cuff erosion.

PURPOSE: To characterize the most common presentation and clinical risk factors for artificial urinary sphincter (AUS) cuff erosion to distinguish the relative frequency of symptoms that should trigger further evaluation in these patients. MATERIALS AND METHODS: We retrospectively reviewed our tertiary center database to identify men who presented with AUS cuff erosion between 2007 - 2020. A similar cohort of men who underwent AUS placement without erosion were randomly selected from the same database for symptom comparison. Risk factors for cuff erosion - pelvic radiation, androgen deprivation therapy (ADT), high-grade prostate cancer (Gleason score ≥ 8) - were recorded for each patient. Presenting signs and symptoms of cuff erosion were grouped into three categories: obstructive symptoms, worsening incontinence, and localized scrotal inflammation (SI). RESULTS: Of 893 men who underwent AUS placement during the study interval, 61 (6.8%) sustained cuff erosion. Most erosion patients (40/61, 66%) presented with scrotal inflammatory changes including tenderness, erythema, and swelling. Fewer men reported obstructive symptoms (26/61, 43%) and worsening incontinence (21/61, 34%). Men with SI or obstructive symptoms presented significantly earlier than those with worsening incontinence (SI 14 ± 18 vs. obstructive symptoms 15 ± 16 vs. incontinence 37 ± 48 months after AUS insertion, p<0.01). Relative to the non-erosion control group (n=61), men who suffered erosion had a higher prevalence of pelvic radiation (71 vs. 49%, p=0.02). CONCLUSION: AUS cuff erosion most commonly presents as SI symptoms. Obstructive voiding symptoms and worsening incontinence are also common. Any of these symptoms should prompt further investigation of cuff erosion.

Price Transparency for Primary Hip & Knee Arthroplasty: An Overview of the Top 50 US News and World Report Orthopedic Hospitals.

BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) has mandated all hospitals to publish the charges of 300 common procedures to provide price transparency. The aims of our study are to evaluate 50 top orthopedic hospitals to determine compliance with this mandate and to assess the ease of finding cost information for arthroplasty procedures. METHODS: The websites of the top 50 US News and World Report (USNWR) orthopedic hospitals were searched to find publicly accessible procedural charges. Data included the number of clicks to locate pricing documents, number of files provided, and number of data rows pertaining to arthroplasty. Charge data was queried based on Diagnosis related group (DRG) codes (469, 470), Current Procedural Technology (CPT) codes (27130, 27477), and keyword searches ("arthroplasty", "total hip", and "total knee"). RESULTS: Forty-four (88%) of the top 50 USNWR Orthopedic institutions had publicly accessible files containing cost information. Thirty three of the 44 institutions provided results with DRG search while less than 10 institutions used CPT and keyword searches. There was an average of 226,190 (range 304-1,121,876) rows of data per file. Average charges varied depending on the use of DRG, CPT or keyword searches ($6,663-$117,072). CONCLUSION: The majority of compliant hospitals published large data files requiring the use of DRG codes to find cost information with extreme variation in resultant charges provided. These findings underscore the lack of direct patient benefit afforded by the current mandate, as pricing determinations require expert knowledge in medical coding and have a high variability in the reported charges.