Purpose The aim of our study was to evaluate if therapeutic success in the first-line of anticancer treatments in patients with NSCLC may predict treatment success in the following lines. Methods We analyzed the data of patients with NSCLC stage III/IV from the TULUNG registry separately for chemotherapy, TKIs, ALK inhibitors, and immunotherapy in the first line during the years 2011–2019. „Succesful treatment “ was defined as PFS ≥ 6 months, a „good responder “ was a patient with ˃50% of „successful treatment “ lines. Treatment responses were analyzed separately for each drug group. Descriptive statistics, Fisher exact test, Pearson Chi-Squared test, log-rank test, and univariate/multivariate logistic regression models were used. Results The first-line TKI therapy was successful in 66.2%, while good responders accounted for 50.7% of the cohort and their rates were similar for all types of TKIs. First-line platinum-based chemotherapy was successful in 43.1% and 48.6% for combinations with pemetrexed and bevacizumab, respectively. Good responders accounted for 29.5% and 25.9%, respectively. In the group of ALK inhibitors, we observed treatment success in 52.3% of cases, while alectinib showed the highest effectiveness (up to 70%). Good responders constituted 50% of the group. In the first-line immunotherapy group, survival benefit was observed in 52.3%, and good responders constituted 52.3% of the cohort. Conclusion We concluded that the treatment success in first-line therapies in patients with NSCLC may predict survival benefits in the subsequent lines, particularly in EGFR- or ALK-positive disease and immunotherapy-treated patients.
The Multi-hollow Surface Dielectric Barrier Discharge (MSDBD) generated in ambient air at atmospheric pressure was used to treat maize, pea, wheat and parsley seeds. Plasma exposure was applied as a pre-treatment before the seeds coating with agrochemicals. The aim of this study was to decrease the dustiness of coated seeds using plasma pre-treatment. The optimization process of plasma treatment parameters for individual seed species consisted of choosing a suitable exposure time (20 s, 60 s) and airflow (10 L/min, 15 L/min). The plasma made the seeds' surface more hydrophilic; therefore, better agrochemicals adhesion was achieved on the seeds' surface. Wettability improvement was demonstrated via water uptake of seeds and apparent contact angle change. Ambient air plasma at a 15 L/min flow rate was measured using optical emission spectroscopy, and the values of vibrational (3000 K) and rotational (347 K) temperatures were obtained from spectra simulation. The surface temperature of the MSDBD ceramics plate was measured with a thermal camera for different gas flow rates and constant input power of 30 W because the temperature is crucial parameter for seed treatment. The surface morphology was not affected due to plasma treatment, even for a longer exposure time. A significant decrease in dustiness measured according to the Heubach method was achieved for pea (57.1%) and parsley (41.4%) seeds. A lower decrease in dustiness was registered in the case of wheat (14.6%) and maize (17%) seeds. The results showed that MSDBD plasma generated in the air at optimized conditions is able to decrease the coated seed dustiness regardless of seed type and size, while seeds germination and surface coverage percentage remained unchanged.
A large proportion of the world’s disease burden is attributable to mental illnesses. Although effective interventions are available, many patients still have limited access to evidence-based treatments. Aside from access, treatment gaps, including inappropriate medication selection and monitoring, are also routinely recognised. Mental health clinical pharmacists can help address these gaps and enable patients to receive optimised pharmaceutical care, particularly appropriate medication selection and monitoring. The European Society of Clinical Pharmacy (ESCP) Special Interest Group on Mental Health was established to improve standardised service provision in mental health settings across Europe. The Special Interest Group identified significant barriers (predominantly associated with reimbursement and position within the multidisciplinary team) to effective pharmaceutical care amongst those with mental illnesses. This commentary presents recommendations to address these gaps through improved mental health clinical pharmacy service provision.
Flash droughts, defined as events with unusually rapid onset and intensification, are emerging into the spotlight as dangerous subseasonal climatic phenomena capable of causing substantial socioenvironmental impacts. However, research on their spatiotemporal variability and major drivers in Central Europe has been limited thus far. This study used gridded soil moisture data from the SoilClim model for the region consisting of the Czech Republic, Slovakia and northern part of Austria in the 1961-2021 period. Established methods of flash drought detection were implemented and adapted to conduct their comprehensive spatiotemporal analysis. The gridded flash drought results were divided into four clusters using the Ward's hierarchical agglomerative method. Individual flash drought episodes were delimited for each cluster, divided into three phases (onset, course, end) and investigated separately in terms of drivers, represented by three meteorological variables (precipitation, actual evapotranspiration, maximum temperature) and atmospheric circulation types based on the objective classification (derived from flow strength, direction and vorticity). The frequency of flash droughts slightly decreased in the winter half-year and slightly increased in the summer half-year, with substantial amplification in the April-June season. The increase was slower than in the case of seasonal droughts, being driven by the longer-term accumulation of water deficit. Circulation drivers exhibited much stronger and more direct influence in the summer half-year, particularly causing the onset of flash drought episodes during the predominance of anticyclonic types and absence of cyclonic types, while the course of flash drought episodes was also connected to increased temperatures and often connected to warm airflow.
Kernel density estimations of circular data are an effective type of nonparametric estimation. The performance of these estimations depends significantly on a smoothing parameter referred to as bandwidth. Selecting suitable bandwidths for these types of estimation pose fundamental challenges, therefore fixed bandwidth selectors are often the initial choice. The study investigates common bandwidth selection methods and proposes novel methods which adopt the idea from the linear case. The attention is also paid to variable bandwidth selection. Using simulations which incorporate a range of circular distributions that exhibit multimodality, peakedness and skewness, the proposed methods were evaluated and then compared with other bandwidth selectors to determine their potential advantages. Two real datasets, one containing animal movements and the other wind direction data, were applied to illustrate the utility of the proposed methods.
In this paper, I discuss the dilemma of authenticity in ADHD subjectivity in the context of somatic, especially cerebral and neurochemical, personhood, which was stimulated by the rise of neuro-scientific knowledge, practices and technologies and their impact on culture and society. Through these processes, selfhood is continually identified with brainhood, in which mental processes are reduced to brain functions and neurochemistry. This has vast consequences on our understanding of human agency, morality and responsibility and opens existentialist questions about authenticity. In this sense, authenticity marks the effort to navigate the shifting relations of nature-culture and mind-brain and the uncertainty in conceptualisations of health, social functionality and normality. These dilemmas are practically significant in the case of subjectivities defined by psychiatric diagnosis in which the definition of authentic self impacts self-understanding and self-management of life strategies, such as treatment decisions.
Despite the high diversity of freshwater fishes in the Nearctic region, little is known about the composition of their parasite communities. We addressed the diversity of viviparous monogeneans of Gyrodactylus parasitizing highly diversified cypriniform fish inhabiting Nearctic watersheds. Nowadays, a thorough assessment of Gyrodactylus spp. diversity requires both morphological traits and genetic data. A combination of taxonomically important haptoral features and sequences of the ITS regions and 18S rDNA revealed 25 Gyrodactylus spp. parasitizing two catostomid and 15 leuciscid species sampled in six distinct localities in the United States and Canada. These include ten Gyrodactylus species recognized as new to science and described herein (G. ellae n. sp., G. hamdii n. sp., G. hanseni n. sp., G. huyseae n. sp., G. kuchtai n. sp., G. lummei n. sp., G. mendeli n. sp., G. prikrylovae n. sp., G. scholzi n. sp., and G. steineri n. sp.), seven already known species, and finally eight undescribed species. Overall, Nearctic Gyrodactylus spp. exhibited haptoral morphotypes known from fish hosts worldwide and those apparently restricted to Nearctic Gyrodactylus lineages like the typical ventral bar with a median knob and a plate-like membrane, or the additional filament attached to the handles of marginal hooks. The integrative approach further evidenced possible ongoing gene flow, host-switching in generalist Gyrodactylus spp., and regional translocation of monogenean fauna through fish introductions. The study highlights the hitherto underexplored morphological and genetic diversity of viviparous monogeneans throughout the Nearctic region.
Introduction/Background High-grade serous carcinoma of the ovary, fallopian tube and peritoneum (HGSC), the most common type of ovarian cancer, ranks among the deadliest malignancies in women. Many HGSC patients present with ascites at the time of diagnosis. Malignant ascites is a complex tumor microenvironment (TME) containing various cells, proteins and extracellular vesicles (EVs). EVs are small membrane-bound particles that convey proteins, lipids and nucleic acids between cells and their cargo reflects the cell of origin. EVs play important role in cancerogenesis and hold great promise as biomarkers. Small size and polydispersity of EVs bring various challenges to their isolation and characterization, including method-dependent enrichment of different EV subtypes as well as contaminants. Methodology We isolated EVs from malignant ascites of eleven patients by two orthogonal methods and analyzed them by tandem mass spectrometry (MS/MS). We also included MS/MS analysis of EVs from related non-malignant control patient fluids and analysis of ascitic cells by spectral flow cytometry (FC). Results We identified a set of ‘core ascitic EV proteins’ and also described proteins present only on EVs from HGSC patients. We believe this list contains important players of HGSC progression as well as potential biomarkers. Using single cell RNA sequencing data, we mapped the origin of EVs to different types of cells present in ascites. EVs in ascites did not come predominantly from tumor cells, but rather from a variety of non-malignant cell types. FC of ascitic cells in combination with the analysis of EV cells of origin incriminate critical contribution of macrophages to the ascitic TME, including the association of macrophage-derived EVs with patient prognosis. Conclusion This is the first study attempting to link EV composition to the cell types producing it. As such it opens numerous avenues both for a better understanding of EV role in tumor promotion/prevention and for improved HGSC diagnostics. Disclosures The authors disclose no potential conflict of interest.
Introduction/Background SENTIX is a prospective, single-arm, international study of sentinel lymph node (SLN) biopsy without pelvic lymph node dissection (PLND) in patients with early-stage cervical cancer. We report the sensitivity of magnetic resonance imaging (MRI) and expert ultrasound (EUS) in preoperative clinical staging. Methodology Forty-seven sites from 18 countries participated in the study. Patients with stages 1A1/LVSI+ to 1B2 (FIGO 2018), usual histological types, and no suspicious lymph nodes on imaging were prospectively enrolled between May 2016 and October 2020. One imaging method, either pelvic MRI or EUS, was mandatory for preoperative local staging and was chosen at the investigator’s discretion. Results Among 690 prospectively enrolled patients fulfilling the inclusion criteria, MRI and EUS were performed as the staging imaging modality in 46.7% and 43.1% of patients, respectively, and 10.1% underwent both. Preoperatively unrecognized parametrial involvement was detected by pathology in 26 patients (3.8%) and SLN metastatic involvement in 68 (9.9%) patients, of which 54.4% and 45.6% had micrometastasis and macrometastasis, respectively, as the largest type of metastasis. MRI and EUS showed comparable sensitivity for tumour size measurement and for the failure to detect parametrial, or macrometastatic LN involvement (table 1). Combining both imaging methods did not increase the outcome (table 1). Conclusion Pelvic MRI and EUS are equally sensitive methods for assessing clinically relevant parameters in preoperative clinical staging of cervical cancer, including tumour size, parametrial involvement, and macrometastatic nodal involvement. Disclosures The authors declare no conflict of interest. Trial registration ClinicalTrials.gov: NCT02494063View this table: • View inline • View popup • Download powerpoint Abstract #451 Table 1 Sensitivity of pelvic MRI and EUS in preoperative staging of patients with cervical cancer Funding This work was supported by Charles University in Prague (UNCE 204065 and PROGRES Q28/LF1) and by a grant from the Czech Health Research Council (NV19–03-00023). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the presentation; or in the decision to publish the results.
Introduction/Background The program of the applied precision oncology approach using combined genomic and immunohistochemical (IHC) analyses to develop individual treatment plans in adult patients (pts) with solid tumors has been established in University Hospital Brno since March 2021. We hereby report the results achieved in patients with gynecological tumors. Methodology Patients undergoing systemic treatment with palliative intent are referred to Molecular Tumor Board (MTB). Whenever possible, the molecular analyses using next-gene sequencing (NGS) together with IHC analyses of key potential targets as requested by the referring physician are performed. The patients whose tumors show an aberration are treated with matched targeted therapy proposed by MTB, when available. Results Between March 2021 and April 2023, 76 pts with gynecological tumors were referred to MTB; 45 (59%) with ovarian cancer, 15 (20%) uterine cancer, 11 (14%) cervical cancer, 4 (5%) with vaginal/vulvar cancer and 1 (1%) with both ovarian and uterine cancer. Median age at the time of profiling was 59 years, median time from the tumor sampling to profiling was 17 months. Results of profiling were available for 68 tumors with actionable aberrations detected in 49 samples (72%). Based on NGS, actionable genomic signature was found in 13/68 tumors (19%) and gene alterations with targeted therapy available in 30/68 tumors (44%). In total, only 2 samples (3%) did not meet the quality criteria for NGS. By IHC, PDL1 positivity (≥1 either by TPS or CPS) was detected in 32/58 examined tumors (57%), MMR-deficiency in 5/56 tumors (9%) and HER-2 positivity in 2/19 tumors (11%). So far, proposed matched therapy has been started in 16/49 patients (33%) with median time of duration 74.5 days compared to 63.5 days within the prior line of treatment. Conclusion Combined genomic and immunohistochemical profiling of gynecological tumors is an efficient approach to match patients with targeted therapy. Disclosures This research was funded by the Ministry of Health of the Czech Republic (MHCR), grant number NU21–03-00306, and MHCR-Development of Research Organization (FNBr, 65269705).
Introduction/Background In addition to the diagnostic accuracy of imaging methods, patient-reported satisfaction with imaging methods is important. The aim is to report patients‘ experience with ultrasound, whole-body computed tomography (CT) and whole-body diffusion-weighted magnetic resonance imaging (WB-DWI/MRI) for preoperative ovarian cancer staging. Methodology 144 patients with suspected ovarian cancer at four institutions in two countries (Italy, Czech Republic) underwent ultrasound, CT and WB-DWI/MRI for staging purposes between January 2020 and November 2022. After having undergone all three examinations, the patients filled in a questionnaire evaluating their experience in five domains: overall experience, preparation before the examination, duration of examination, noise during the procedure, radiation load of CT, surrounding space. Pain perception, examination-related patient perceived adverse events, and preferred method were also noted. Results Ultrasound was the preferred method by 49% (70/144) of responders, followed by CT (38%, 55/144), and WB-DWI/MRI (13%, 19/144). CT was the preferred method regarding overall experience and duration of examination. Ultrasound was preferred concerning preparation before examination, noise and surrounding space. The poorest experience in all domains was reported for WB-DWI/MRI, which was also associated with the largest number of patient reported adverse events (e.g. dyspnea). Patients reported higher levels of pain during the ultrasound examination than during CT and WB-DWI/MRI (P<0.001): 78% (112/144) reported no pain or mild pain, 19% (27/144) moderate pain, and 3% (5/144) reported severe pain (pain score >7 of 10) during the ultrasound examination. We did not identify any factors related to patients‘ preferred method. Conclusion Ultrasound was the imaging method preferred by most patients despite being the most painful when compared with CT and WB-DWI/MRI. Disclosures This work was funded by the Ministry of Health of the Czech Republic (Czech Health Research Council), grant number NV19–03-00552.
Bleeding is one of the most commonly occurring injuries; it can be painful and even life-threatening condition. The hemostats are substances that promote blood clotting and fasten hemostasis. In this paper, we evaluated the hemostatic effect of freeze-dried wound dressings based on equine collagen, porcine collagen, fibrous carboxymethyl cellulose (CMC) and their mixtures. The wound dressings were investigated for their morphological structure, chemical structure, absorption properties, in vitro hemostasis, cytotoxicity assay and lastly, for in vivo hemostasis. We have found out that adding fibrous CMC into collagen-based hemostatic wound dressings creates a strong synergistic effect, which significantly improves absorption capacity by almost doubling it, as well as supports clotting time. Based on the in vivo studies on partial nephrectomy in rats, the time needed for achieving hemostasis was significantly lower due to the synergy of collagen and CMC. Our materials were compared to the commonly used hemostatic sealing patch on the market (Tachosil) during the in vivo testing, and sample of a mixture of equine collagen and CMC showed better hemostatic efficacy. Graphical abstract
Most sap-feeding insects maintain obligate relationships with endosymbiotic bacteria that provide their hosts with essential nutrients. However, knowledge about the dynamics of endosymbiont titers across seasons in natural host populations is scarce. Here, we used quantitative PCR to investigate the seasonal dynamics of the dual endosymbionts “Candidatus Carsonella ruddii” and “Ca. Psyllophila symbiotica” in a natural population of the pear psyllid Cacopsylla pyricola (Hemiptera: Psylloidea: Psyllidae). Psyllid individuals were collected across an entire year, covering both summer and overwintering generations. Immatures harboured the highest titers of both endosymbionts, while the lowest endosymbiont density was observed in males. The density of Carsonella remained high and relatively stable across the vegetative period of the pear trees, but significantly dropped during the non-vegetative period, overlapping with C. pyricola’s reproductive diapause. In contrast, the titer of Psyllophila was consistently higher than Carsonella’s and exhibited fluctuations throughout the sampling year, which might be related to host age. Despite a tightly integrated metabolic complementarity between Carsonella and Psyllophila, our findings highlight differences in their density dynamics throughout the year, that might be linked to their metabolic roles at different life stages of the host.
This chapter is focused on radiobiological aspects at the molecular, cellular, and tissue level which are relevant for the clinical use of ionizing radiation (IR) in cancer therapy. For radiation oncology, it is critical to find a balance, i.e., the therapeutic window, between the probability of tumor control and the probability of side effects caused by radiation injury to the healthy tissues and organs. An overview is given about modern precision radiotherapy (RT) techniques, which allow optimal sparing of healthy tissues. Biological factors determining the width of the therapeutic window are explained. The role of the six typical radiobiological phenomena determining the response of both malignant and normal tissues in the clinic, the 6R’s, which are Reoxygenation, Redistribution, Repopulation, Repair, Radiosensitivity, and Reactivation of the immune system, is discussed. Information is provided on tumor characteristics, for example, tumor type, growth kinetics, hypoxia, aberrant molecular signaling pathways, cancer stem cells and their impact on the response to RT. The role of the tumor microenvironment and microbiota is described and the effects of radiation on the immune system including the abscopal effect phenomenon are outlined. A summary is given on tumor diagnosis, response prediction via biomarkers, genetics, and radiomics, and ways to selectively enhance the RT response in tumors. Furthermore, we describe acute and late normal tissue reactions following exposure to radiation: cellular aspects, tissue kinetics, latency periods, permanent or transient injury, and histopathology. Details are also given on the differential effect on tumor and late responding healthy tissues following fractionated and low dose rate irradiation as well as the effect of whole-body exposure.
The manuscript provides an overview of treatment and its changes in adult patients with haemophilia A without inhibitors in the Czech Republic between 2013 and 2021 using data from the registry of the Czech National Haemophilia Programme (CNHP). Over a 9-year period, we focused on the reduction in the annual bleeding rate (ABR), joint bleeding rate (AJBR) and factor VIII consumption when patients with severe haemophilia A switched from on-demand treatment to prophylaxis. The ABR and AJBR include both patient-reported home treatment and treated hospitalisation episodes. All adult patients with severe haemophilia A were categorised into three groups according to the therapeutic regimen. The first group was patients on prophylaxis during the follow-up period, the second group consisted of patients on on-demand treatment, and the third group was patients who received both treatment regimens during follow-up. With an increase in the proportion of patients with severe haemophilia A on prophylaxis from 37 to 74% between 2013 and 2021, the ABR for all patients with severe haemophilia A decreased approximately 6.9-fold, and the AJBR decreased 8.7-fold. Expectedly, the factor consumption increased by approximately 68.5%. In the group of patients with severe haemophilia A who had switched from an on-demand to a prophylactic regimen, the total number of bleeding events decreased 3.5-fold, and the number of joint bleeding episodes decreased 3.9-fold. Factor VIII consumption increased by 78.4%. Our study supports a previously reported positive effect of prophylaxis on bleeding control. We believe that the substantial improvement in ABR justifies the increased treatment costs.
The chapter deals with the historical development, the recent character, and the core principles of eco-extremism. The author summarizes the academic and political debate on this topic. The term eco-extremism is defined with the help of the terminological apparatus of research on extremism. The authoritarian and totalitarian elements in eco-extremist thoughts are explained, including their overlaps with various streams of left-wing extremism (anarchism, ideas of autonomous movements, communism, etc.), (quasi-)religious extremism, and other forms of extremism. The recent trends of intolerant and apocalyptic agendas in the politics of a part of the environmental movement are assessed from the point of view of extremism. The author also deals with governmental reaction to these new trends. The future perspective of eco-extremist movements is outlined within the context of various scenarios of the social development of modern societies in the coming years.
Application of neural networks in industrial settings, such as automated factories with bin-picking solutions requires costly production of large labeled datasets. This paper presents an automatic data generation tool with a procedural model of a cardboard box. We briefly demonstrate the capabilities of the system, and its various parameters and empirically prove the usefulness of the generated synthetic data by training a simple neural network. We make sample synthetic data generated by the tool publicly available.
Purpose Auditory complications are potential side effects from childhood cancer treatment. Yet, limited evidence exists about the impact of auditory complications—particularly tinnitus—on health-related quality of life (HRQoL) among childhood cancer survivors (CCS). We determined the prevalence of hearing loss and tinnitus in the European PanCareLIFE cohort of CCS and examined its effect on HRQoL. Methods We included CCS from four European countries who were diagnosed at age ≤ 18 years; survived ≥ 5 years; and aged 25–44 years at study. We assessed HRQoL (Short Form 36), hearing loss, and tinnitus using questionnaires. We used multivariable linear regression to examine associations between these two auditory complications and HRQoL adjusting for socio-demographic and clinical factors. Results Our study population consisted of 6,318 CCS (53% female; median age at cancer diagnosis 9 years interquartile range [IQR] 5–13 years) with median age at survey of 31 years (IQR 28–35 years). Prevalence was 7.5% (476/6,318; confidence interval [CI]: 6.9–8.2) for hearing loss and 7.6% (127/1,668; CI: 6.4–9.0) for tinnitus. CCS with hearing loss had impaired physical (coefficient [coef.] -4.3, CI: -7.0 to -1.6) and mental (coef. -3.2, CI: -5.5 to -0.8) HRQoL when compared with CCS with normal hearing. Tinnitus was associated with impaired physical (coef. -8.2, CI: -11.8 to -4.7) and mental (coef. -5.9, CI: -8.8 to -3.1) HRQoL. Conclusion We observed reduced HRQoL among CCS with hearing loss and tinnitus. Our findings indicate timely treatment of hearing loss and tinnitus may contribute to quality of life of survivors. Implications for cancer survivors CCS who experience auditory complications should be counseled about possible therapeutic and supportive measures during follow-up care.
Background Filarial infections have been understudied in bats. Likewise, little is known about pathogens associated with the reproductive system in chiropterans. While semen quality is critical for reproductive success, semen-borne pathogens may contribute to reproductive failure.Methods For the first time we performed electroejaculation and used computer-assisted semen analysis to provide baseline data on semen quality in a parti-coloured bat (Vespertilio murinus).ResultsThe semen quality values measured in the V. murinus male appeared high (semen concentration = 305.4 × 106/mL; progressive and motile sperm = 46.58 and 60.27%, respectively). As an incidental finding, however, microfilariae were observed in the bat semen examined. At necropsy, eight adult filarial worms, later genetically identified as Litomosa sp., were found in the peritoneal cavity, close to the stomach, of the same particoloured bat male dying as a result of dysmicrobia and haemorrhagic gastroenteritis in a wildlife rescue centre. Histopathology revealed microfilariae in the testicular connective tissue and the epidydimal connective and fat tissues. A PCR assay targeting cytochrome c oxidase subunit 1 confirmed that adult worms from the peritoneal cavity and testicular microfilariae were of the same filarial species. Mildly engorged argasid mite larvae attached to the bat skin proved negative for filarial DNA and the adult filarial worms proved negative for endosymbiont Wolbachia.Conclusion While the standard filarial life cycle pattern involves a vertebrate definitive host and an invertebrate vector, represented by a blood-sucking ectoparasite, our finding suggests that microfilariae of this nematode species may also be semen-borne, with transmission intensity promoted by the polygynous mating system of vespertilionid bats in which an infected male mates with many females during the autumn swarming. Presence of microfilariae may be expected to decrease semen quality and transmission via this route may challenge the success of reproductive events in females after mating. Further investigation will be necessary to better understand the bat-parasite interaction and the life cycle of this filarial worm.
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