Phylogenetic inference of inter-population transmission rates for infectious diseases.

Estimating transmission rates is a challenging yet essential aspect of comprehending and controlling the spread of infectious diseases. Various methods exist for estimating transmission rates, each with distinct assumptions, data needs, and constraints. This study introduces a novel phylogenetic approach called transRate, which integrates genetic information with traditional epidemiological approaches to estimate inter-population transmission rates. The phylogenetic method is statistically consistent as the sample size (i.e. the number of pathogen genomes) approaches infinity under the multi-population susceptible-infected-recovered model. Simulation analyses indicate that transRate can accurately estimate the transmission rate with a sample size of 200 ~ 400 pathogen genomes. Using transRate, we analyzed 40,028 high-quality sequences of SARS-CoV-2 in human hosts during the early pandemic. Our analysis uncovered significant transmission between populations even before widespread travel restrictions were implemented. The development of transRate provides valuable insights for scientists and public health officials to enhance their understanding of the pandemic's progression and aiding in preparedness for future viral outbreaks. As public databases for genomic sequences continue to expand, transRate is increasingly vital for tracking and mitigating the spread of infectious diseases.

Improvement in the 95-95-95 Targets Is Accompanied by a Reduction in Both the Human Immunodeficiency Virus Transmission Rate and Incidence in China.

BACKGROUND: In 2016, China has implemented the World Health Organization's "treat all" policy. We aimed to assess the impact of significant improvements in the 95-95-95 targets on population-level human immunodeficiency virus (HIV) transmission dynamics and incidence. METHODS: We focused on 3 steps of the HIV care continuum: diagnosed, on antiretroviral therapy, and achieving viral suppression. The molecular transmission clusters were inferred using HIV-TRACE. New HIV infections were estimated using the incidence method in the European Centre for Disease Prevention and Control HIV Modelling Tool. RESULTS: Between 2004 and 2023, the national HIV epidemiology database recorded 2.99 billion person-times of HIV tests and identified 1 976 878 new diagnoses. We noted a roughly "inverted-V" curve in the clustering frequency, with the peak recorded in 2014 (67.1% [95% confidence interval, 63.7%-70.5%]), concurrent with a significant improvement in the 95-95-95 targets from 10-13-<71 in 2005 to 84-93-97 in 2022. Furthermore, we observed a parabolic curve for a new infection with the vertex occurring in 2010. CONCLUSIONS: In general, it was suggested that the improvements in the 95-95-95 targets were accompanied by a reduction in both the population-level HIV transmission rate and incidence. Thus, China should allocate more effort to the first "95" target to achieve a balanced 95-95-95 target.

Film dressings from Thai mango seed kernel extracts versus nanocrystalline silver dressings in antibacterial properties.

Introduction: The extract from the Mango Seed Kernel (MSK) has been documented to exhibit antibacterial activity against Gram-positive and Gram-negative bacteria, including Staphylococcus aureus and Pseudomonas aeruginosa. This suggests that biomaterials containing MSK extract could be a viable alternative to conventional wound treatments, such as nanocrystalline silver dressings. Despite this potential, there is a notable gap in the literature regarding comparing the antibacterial effectiveness of MSK film dressings with nanocrystalline silver dressings. This study aimed to develop film dressings containing MSK extract and evaluate their antibacterial properties compared to nanocrystalline silver dressings. Additionally, the study aimed to assess other vital physical properties of these dressings critical for effective wound care. Materials and methods: We prepared MSK film dressings from two cultivars of mango from Thailand, 'Chokanan' and 'Namdokmai'. The inhibition-zone method was employed to determine the antibacterial property. The morphology and chemical characterization of the prepared MSK film dressings were examined with scanning electron microscopy (SEM) and Fourier-Transform Infrared Spectroscopy (FTIR), respectively. The absorption of pseudo-wound exudate and water vapor transmission rate (WVTR) of film dressings were evaluated. Results: The results showed that 40% of MSKC film dressing had the highest inhibition zone (20.00 ± 0.00 mm against S. aureus and 17.00 ± 1.00 mm against P. aeruginosa) and 20%, 30%, and 40% of MSKC and MSKN film dressings had inhibition zones similar to nanocrystalline silver dressing for both S. aureus and P. aeruginosa (p > 0.05). In addition, all concentrations of the MSK film dressings had low absorption capacity, and Chokanan MSK (MSKC) film dressings had a higher WVTR than Namdokmai MSK (MSKN) film dressings. Conclusion: 20%, 30%, and 40% of MSK film dressing is nearly as effective as nanocrystalline silver dressing. Therefore, it has the potential to be an alternative antibacterial dressing and is suitable for wounds with low exudate levels.

Residual transmission of HIV infection from mother to child in the Atlantic and littoral departments in Benin.

BACKGROUND: The implementation of the WHO's 2015 recommendations in Benin, requires an assessment of the progress made over time in preventing the transmission of the infection to exposed-infants, and the identification of its determinants. METHODS: This was a retrospective study of HIV-1 exposed-infants who underwent PCR between the 6th and 8th weeks of life. Early diagnostic tests were performed using the Abbott m2000 RealTime platform. Comparison of proportions tests (analysis of the significance of the difference in prevalence) with an error threshold of 5% were used to assess the determinants of the transmission. Statistical analysis was performed using R statistical software, version 4.1.3.0. RESULTS: A total of 5,312 infants benefited from early diagnosis by PCR between 2016 and 2021. Among them, 52% are males, tritherapy before pregnancy was the majority treatment used by mothers (30.6%) and monotherapy that of newborns (70%). Mixed breastfeeding is the feeding method with the highest prevalence. The overall transmission rate was 3.4% over the six years. The highest prevalence was achieved in 2018 (4.2%) and the lowest in 2021 (2.7%). The prevalence was lower when mothers were on tritherapy before pregnancy. The determinants of transmission were: mixed breastfeeding, lack of treatment in mothers (22.4%), lack of treatment in infants (19.7%), undefined treatments or absence of treatment in the mother-child pair. CONCLUSION: This study shows the contribution over time of the PMTCT program to reducing HIV transmission among exposed-infants and also underlines the need for proper conduct of treatment in any women of childbearing age.

High Moisture-Barrier Performance of Double-Layer Graphene Enabled by Conformal and Clean Transfer.

Graphene films that can theoretically block almost all molecules have emerged as promising candidate materials for moisture barrier films in the applications of organic photonic devices and gas storage. However, the current barrier performance of graphene films does not reach the ideal value. Here, we reveal that the interlayer distance of the large-area stacked multilayer graphene is the key factor that suppresses water permeation. We show that by minimizing the gap between the two monolayers, the water vapor transmission rate of double-layer graphene can be as low as 5 × 10-3 g/(m2 d) over an A4-sized region. The high barrier performance was achieved by the absence of interfacial contamination and conformal contact between graphene layers during layer-by-layer transfer. Our work reveals the moisture permeation mechanism through graphene layers, and with this approach, we can tailor the interlayer coupling of manually stacked two-dimensional materials for new physics and applications.

Real-World Adherence and Effectiveness of Remote Patient Monitoring Among Medicaid Patients With Diabetes: Retrospective Cohort Study.

BACKGROUND: The prevalence of diabetes in the United States is high and increasing, and it is also the most expensive chronic condition in the United States. Self-monitoring of blood glucose or continuous glucose monitoring are potential solutions, but there are barriers to their use. Remote patient monitoring (RPM) with appropriate support has the potential to provide solutions. OBJECTIVE: We aim to investigate the adherence of Medicaid patients with diabetes to daily RPM protocols, the relationship between adherence and changes in blood glucose levels, and the impact of daily testing time on blood glucose changes. METHODS: This retrospective cohort study analyzed real-world data from an RPM company that provides services to Texas Medicaid patients with diabetes. Overall, 180 days of blood glucose data from an RPM company were collected to assess transmission rates and blood glucose changes, after the first 30 days of data were excluded due to startup effects. Patients were separated into adherent and nonadherent cohorts, where adherent patients transmitted data on at least 120 of the 150 days. z tests and t tests were performed to compare transmission rates and blood glucose changes between 2 cohorts. In addition, we analyzed blood glucose changes based on their testing time-between 1 AM and 10 AM, 10 AM and 6 PM, and 6 PM and 1 AM. RESULTS: Mean patient age was 70.5 (SD 11.8) years, with 66.8% (n=255) of them being female, 91.9% (n=351) urban, and 89% (n=340) from south Texas (n=382). The adherent cohort (n=186, 48.7%) had a mean transmission rate of 82.8% before the adherence call and 91.1% after. The nonadherent cohort (n=196, 51.3%) had a mean transmission rate of 45.9% before and 60.2% after. The mean blood glucose levels of the adherent cohort decreased by an average of 9 mg/dL (P=.002) over 5 months. We also found that variability of blood glucose level of the adherent cohort improved 3 mg/dL (P=.03) over the 5-month period. Both cohorts had the majority of their transmissions between 1 AM and 10 AM, with 70.5% and 53.2% for the adherent and nonadherent cohorts, respectively. The adherent cohort had decreasing mean blood glucose levels over 5 months, with the largest decrease during the 6 PM to 1 AM time period (30.9 mg/dL). Variability of blood glucose improved only for those tested from 10 AM to 6 PM, with improvements of 6.9 mg/dL (P=.02). Those in the nonadherent cohort did not report significant changes. CONCLUSIONS: RPM can help manage diabetes in Medicaid clients by improving adherence rates and glycemic control. Adherence calls helped improve adherence rates, but some patients still faced challenges in transmitting blood glucose levels. Nonetheless, RPM has the potential to reduce the risk of adverse outcomes associated with diabetes.

Hydrophilic Modification of Polyester/Polyamide 6 Hollow Segmented Pie Microfiber Nonwovens by UV/TiO2/H2O2.

Polyester/polyamide 6 hollow segmented pie bicomponent spunbond hydro-entangled microfiber nonwovens (PET/PA6) with a microfilament structure have recently emerged in many markets around the world due to their green, high-strength, and lightweight properties. However, PET/PA6 is highly hydrophobic, which inhibits its large-scale application at present. In order to enhance the hydrophilic performance of PET/PA6, many methods have been applied, but the effects are not obvious. Ultraviolet (UV) irradiation treatment has proven to be an effective method to improve the hydrophilicity of fabrics. Herein, the aim of this paper was to investigate hydrophilic modification of PET/PA6 by UV/TiO2/H2O2. The effect of H2O2, nano-TiO2, and UV irradiation time on the morphology, elemental composition, hydrophilic properties, and mechanical properties of PET/PA6 were systematically investigated. The results showed that the modified microfibers were coated with a layer of granular material on the surface. It was found that the C 1s peak could be deconvoluted into six components (C-C-C, C-C-O, O-C=O, N-C=O, N-C-C, and C-C=O), and a suitable mechanism was proposed. Moreover, the water contact angle of PET/PA6 modified by 90 min irradiation with UV/TiO2/H2O2 decreased to zero in 0.015 s, leading to the water vapor transmission rate and the water absorption reaching 5567.49 g/(m2·24 h) and 438.81%, respectively. In addition, the modified PET/PA6 had an excellent liquid wicking height of 141.87 mm and liquid wicking rate of 28.37 mm/min.

Design of control strategies to help prevent the spread of COVID-19 pandemic.

This paper proposes control strategies to allocate COVID-19 patients to screening facilities, health facilities, and quarantine facilities for minimizing the spread of the virus by these patients. To calculate the transmission rate, we propose a function that accounts for contact rate, duration of the contact, age structure of the population, susceptibility to infection, and the number of transmission events per contact. Moreover, the COVID-19 cases are divided into different groups according to the severity of their disease and are allocated to appropriate health facilities that provide care tailored to their needs. The multi-stage fuzzy stochastic programming approach is applied to cope with uncertainty, in which the probability associated with nodes of the scenario tree is treated as fuzzy variables. To handle the probabilistic model, we use a more flexible measure, M e measure, which allows decision-makers to adopt varying attitudes by assigning the optimistic-pessimistic parameter. This measure does not force decision-makers to hold extreme views and obtain the interval solution that provides further information in the fuzzy environment. We apply the proposed model to the case of Tehran, Iran. The results of this study indicate that assigning patients to appropriate medical centers improves the performance of the healthcare system. The result analysis highlights the impact of the demographic differences on virus transmission, and the older population has a greater influence on virus transmission than other age groups. Besides, the results indicate that behavioral changes in the population and their vaccination play a key role in curbing COVID-19 transmission.

Measuring Basic Reproduction Number to Assess Effects of Nonpharmaceutical Interventions on Nosocomial SARS-CoV-2 Transmission.

Outbreaks of SARS-CoV-2 infection frequently occur in hospitals. Preventing nosocomial infection requires insight into hospital transmission. However, estimates of the basic reproduction number (R0) in care facilities are lacking. Analyzing a closely monitored SARS-CoV-2 outbreak in a hospital in early 2020, we estimated the patient-to-patient transmission rate and R0. We developed a model for SARS-CoV-2 nosocomial transmission that accounts for stochastic effects and undetected infections and fit it to patient test results. The model formalizes changes in testing capacity over time, and accounts for evolving PCR sensitivity at different stages of infection. R0 estimates varied considerably across wards, ranging from 3 to 15 in different wards. During the outbreak, the hospital introduced a contact precautions policy. Our results strongly support a reduction in the hospital-level R0 after this policy was implemented, from 8.7 to 1.3, corresponding to a policy efficacy of 85% and demonstrating the effectiveness of nonpharmaceutical interventions.

Emerging evidence on Omicron (B.1.1.529) SARS-CoV-2 variant.

COVID's Omicron variant has sparked a slew of concerns across the globe. This review aims to provide a brief overview of what we know about the Omicron variant right now. The new variant has been discovered in 149 countries across all six World Health Organization (WHO) regions since its discovery in South Africa on November 24, 2021 and became the dominant variant in the country in less than 3 weeks. The WHO has warned that the B.1.1.529 variant is spreading at an unprecedented rate, and has urged countries to prepare for the worst. Over the course of this time, researchers from Africa and around the world have uncovered a wealth of information about the virus's epidemiology and biological properties. Case numbers are increasing exponentially in hard-hit areas such as South Africa, United Kingdom, and USA (overtaking the delta variant), implying that the variant is highly transmissible. Initial research has provided some insights into the efficacy of vaccines against the Omicron variant and whether it produces major illness, however, much remains unknown, and additional work is needed to investigate what the initial reports represent in real-world situations.

Dynamics of SIR model with heterogeneous response to intervention policy.

In classical epidemic theory, behavior is assumed to be stationary. In recent years, epidemic models have been extended to include behaviors that transition in response to the current state of the epidemic. However, it is widely known that human behavior can exhibit strong history-dependence as a consequence of learned experiences. This history-dependence is similar to hysteresis phenomena that have been well-studied in control theory. To illustrate the importance of history-dependence for epidemic theory, we study dynamics of a variant of the SIRS model where individuals exhibit lazy-switch responses to prevalence dynamics, based on the Preisach hysteresis operator. The resulting model can possess a continuum of endemic equilibrium states characterized by different proportions of susceptible, infected and recovered populations. We consider how the limit point of the epidemic trajectory and the infection peak along this trajectory depend on the degree of heterogeneity of the response. Our approach supports the argument that public health responses during the emergence of a new disease can have fundamental long-term consequences for subsequent management efforts.

[Substance-related disorders and transition psychiatry]. / Substanzbezogene Störungen und Transitionspsychiatrie.

BACKGROUND: Addictive disorders are typically manifested during adolescence and have a high transmission rate into adulthood. When adulthood is reached the responsibility by the child and adolescent psychiatric care system ends and patients transition to adult psychiatry. A lack of supportive concepts and approaches to this transition can have detrimental effects on the long-term health of affected individuals. OBJECTIVE: Addiction treatment requirements of young adults transitioning between the systems of care are presented. Developmental psychopathological concepts are presented and treatment recommendations are provided. MATERIAL AND METHODS: The scientific literature on development-related approaches to addiction treatment was evaluated. Care conditions relevant to transitional psychiatry are discussed and a description of needs is carried out. RESULTS: Adolescents and young adults are very frequently affected by addictive disorders. The need for disorder-specific and age-specific transition-related concepts and services for these patients is high. During the transition from child and adolescent psychiatry to the psychiatric care system for adults, patients with substance-related disorders require treatment-related educational and age-appropriate psychosocial support services that address the high comorbidity and developmental delays. CONCLUSION: Age-specific and disorder-specific treatment services should be broadly expanded and the interfaces to youth welfare, addiction counseling and adult psychiatry should be better coordinated.

Intense and Mild First Epidemic Wave of Coronavirus Disease, The Gambia.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is evolving differently in Africa than in other regions. Africa has lower SARS-CoV-2 transmission rates and milder clinical manifestations. Detailed SARS-CoV-2 epidemiologic data are needed in Africa. We used publicly available data to calculate SARS-CoV-2 infections per 1,000 persons in The Gambia. We evaluated transmission rates among 1,366 employees of the Medical Research Council Unit The Gambia (MRCG), where systematic surveillance of symptomatic cases and contact tracing were implemented. By September 30, 2020, The Gambia had identified 3,579 SARS-CoV-2 cases, including 115 deaths; 67% of cases were identified in August. Among infections, MRCG staff accounted for 191 cases; all were asymptomatic or mild. The cumulative incidence rate among nonclinical MRCG staff was 124 infections/1,000 persons, which is >80-fold higher than estimates of diagnosed cases among the population. Systematic surveillance and seroepidemiologic surveys are needed to clarify the extent of SARS-CoV-2 transmission in Africa.

Mobility-Guided Estimation of COVID-19 Transmission Rates.

It is of critical importance to estimate changing disease-transmission rates and their dependence on population mobility. A common approach to this problem involves fitting daily transmission rates using a susceptible-exposed-infected-recovered-(SEIR) model (regularizing to avoid overfitting) and then computing the relationship between the estimated transmission rate and mobility. Unfortunately, there are often several very different transmission-rate trajectories that can fit the reported cases well, meaning that the choice of regularization determines the final solution (and thus the mobility-transmission rate relationship) selected by the SEIR model. Moreover, the classical approaches to regularization-penalizing the derivative of the transmission rate trajectory-do not correspond to realistic properties of pandemic spread. Consequently, models fitted using derivative-based regularization are often biased toward underestimating the current transmission rate and future deaths. In this work, we propose mobility-driven regularization of the SEIR transmission rate trajectory. This method rectifies the artificial regularization problem, produces more accurate and unbiased forecasts of future deaths, and estimates a highly interpretable relationship between mobility and the transmission rate. For this analysis, mobility data related to the coronavirus disease 2019 pandemic was collected by Safegraph (San Francisco, California) from major US cities between March and August 2020.

COVID-19 modelling by time-varying transmission rate associated with mobility trend of driving via Apple Maps.

Compartment-based infectious disease models that consider the transmission rate (or contact rate) as a constant during the course of an epidemic can be limiting regarding effective capture of the dynamics of infectious disease. This study proposed a novel approach based on a dynamic time-varying transmission rate with a control rate governing the speed of disease spread, which may be associated with the information related to infectious disease intervention. Integration of multiple sources of data with disease modelling has the potential to improve modelling performance. Taking the global mobility trend of vehicle driving available via Apple Maps as an example, this study explored different ways of processing the mobility trend data and investigated their relationship with the control rate. The proposed method was evaluated based on COVID-19 data from six European countries. The results suggest that the proposed model with dynamic transmission rate improved the performance of model fitting and forecasting during the early stage of the pandemic. Positive correlation has been found between the average daily change of mobility trend and control rate. The results encourage further development for incorporation of multiple resources into infectious disease modelling in the future.

COVID-19: Mechanistic model calibration subject to active and varying non-pharmaceutical interventions.

Mathematical models are useful in epidemiology to understand COVID-19 contagion dynamics. We aim to demonstrate the effectiveness of parameter regression methods to calibrate an established epidemiological model describing infection rates subject to active, varying non-pharmaceutical interventions (NPIs). We assess the potential of established chemical engineering modelling principles and practice applied to epidemiological systems. We exploit the sophisticated parameter regression functionality of a commercial chemical engineering simulator with piecewise continuous integration, event and discontinuity management. We develop a strategy for calibrating and validating a model. Our results using historic data from 4 countries provide insights into on-going disease suppression measures, while visualisation of reported data provides up-to-date condition monitoring of the pandemic status. The effective reproduction number response to NPIs is non-linear with variable response rate, magnitude and direction. Our purpose is developing a methodology without presenting a fully optimised model, or attempting to predict future course of the COVID-19 pandemic.

Signal Fluctuations and the Information Transmission Rates in Binary Communication Channels.

In the nervous system, information is conveyed by sequence of action potentials, called spikes-trains. As MacKay and McCulloch suggested, spike-trains can be represented as bits sequences coming from Information Sources (IS). Previously, we studied relations between spikes' Information Transmission Rates (ITR) and their correlations, and frequencies. Now, I concentrate on the problem of how spikes fluctuations affect ITR. The IS are typically modeled as stationary stochastic processes, which I consider here as two-state Markov processes. As a spike-trains' fluctuation measure, I assume the standard deviation σ, which measures the average fluctuation of spikes around the average spike frequency. I found that the character of ITR and signal fluctuations relation strongly depends on the parameter s being a sum of transitions probabilities from a no spike state to spike state. The estimate of the Information Transmission Rate was found by expressions depending on the values of signal fluctuations and parameter s. It turned out that for smaller s<1, the quotient ITRσ has a maximum and can tend to zero depending on transition probabilities, while for 1

Synthesis and characterization of nano starch-based composite films from kidney bean (Phaseolus vulgaris).

This study was aimed to synthesize and evaluate the nano starch-based composite films by the addition of nano starch in film formulation at 0.5, 1, 2, 5 and 10% level of total starch. The acid hydrolysis technique was used to reduce the size of starch granules of kidney bean starch. The physicochemical properties of both native and nano starch were determined. Nano starch showed a higher value for swelling power, solubility, water and oil absorption capacity when compared with native starch. The particle size of kidney bean nano starch was 257.7 nm at 100% intensity. The size of starch granule affects various properties of films. The thickness, solubility and burst strength of the composite films were increased significantly (p ≤ 0.05) with an increase in the concentration of nano starch in film formulation. While the moisture content and water vapour transmission rate (WVTR) were decreased significantly (p ≤ 0.05) with an increase in the concentration of nano starch in film formulation. The results suggested that kidney bean starch could be used for the development of packaging films. The utilization of nano starch in film formulations had an additional advantage in improving the film properties.

A Continuous Model of Three Scenarios of the Infection Process with Delayed Immune Response Factors.

The course of an infection was modeled as a controlled nonlinear process. Understanding the substantial differences observed in the trajectory of the disease caused by the new coronavirus SARS-CoV-2 is of critical importance at the moment. Numerous factors have been considered to explain the fact that symptoms vary highly among different people and the infection transmission rate varies among local populations. Virus replication within the host cell and the development of an immune response to virus antigens in the body are two interdependent processes, which have aftereffects and depend on the preexisting states of the cell and virus populations. Different scenarios with the same input parameters are necessary to consider for modeling the properties of the states. The efficiency of the immune response is the most important factor, including the time it takes to develop defense responses from three levels of the immune system, which is a complex system of the body. A computational description of infection scenarios was proposed on the basis of a delay differential equation with two values of the time lag. In the new model, transitions between phases of infectious disease depend on the initial virus dose and the delayed immune response to infection. A variation in the dose of the virus and response time can lead to a transition from an acute phase of the disease with overt symptoms to a chronic phase or fatal outcome. Asymptomatic transmission of viral infection was calculated and described in the model as a situation where the virus is rapidly and efficiently suppressed after a short replication phase, while still persisting in the body in minor amounts. An analysis of the model behavior is consistent with the theory that the initial number of virions can affect the quality of the immune response. The reasons that high individual differences are observed in the trajectory of COVID-19 disease and the formation of types of the immune response to coronavirus are still poorly understood. Known trajectories of hepatitis C virus (HCV) infection were used as a basis for model scenarios.

Dynamic quarantine: a comparative analysis of the Chilean public health response to COVID-19.

In this study, an analysis of the Chilean public health response to mitigate the spread of COVID-19 is presented. The analysis is based on the daily transmission rate (DTR). The Chilean response has been based on dynamic quarantines, which are established, lifted or prolonged based on the percentage of infected individuals in the fundamental administrative sections, called communes. This analysis is performed at a national level, at the level of the Metropolitan Region (MR) and at the commune level in the MR according to whether the commune did or did not enter quarantine between late March and mid-May of 2020. The analysis shows a certain degree of efficacy in controlling the pandemic using the dynamic quarantine strategy. However, it also shows that apparent control has only been partially achieved to date. With this policy, the control of the DTR partially falls to 4%, where it settles, and the MR is the primary vector of infection at the country level. For this reason, we can conclude that the MR has not managed to control the disease, with variable results within its own territory.