Assessing the Relationship between Surgical Timing and Postoperative Seizure Outcomes in Cavernoma-Related Epilepsy: A Single-Institution Retrospective Analysis of 63 Patients with a Review of the Literature.

Background: Patients with supratentorial cavernous malformations (SCMs) commonly present with seizures. First-line treatments for cavernoma-related epilepsy (CRE) include conservative management (antiepileptic drugs (AEDs)) and surgery. We compared seizure outcomes of CRE patients after early (≤6 months) vs. delayed (>6 months) surgery. Methods: We compared outcomes of CRE patients with SCMs surgically treated at our large-volume cerebrovascular center (1 January 2010-31 July 2020). Patients with 1 sporadic SCM and ≥1-year follow-up were included. Primary outcomes were International League Against Epilepsy (ILAE) class 1 seizure freedom and AED independence. Results: Of 63 CRE patients (26 women, 37 men; mean ± SD age, 36.1 ± 14.6 years), 48 (76%) vs. 15 (24%) underwent early (mean ± SD, 2.1 ± 1.7 months) vs. delayed (mean ± SD, 6.2 ± 7.1 years) surgery. Most (32 (67%)) with early surgery presented after 1 seizure; all with delayed surgery had ≥2 seizures. Seven (47%) with delayed surgery had drug-resistant epilepsy. At follow-up (mean ± SD, 5.4 ± 3.3 years), CRE patients with early surgery were more likely to have ILAE class 1 seizure freedom and AED independence than those with delayed surgery (92% (44/48) vs. 53% (8/15), p = 0.002; and 65% (31/48) vs. 33% (5/15), p = 0.03, respectively). Conclusions: Early CRE surgery demonstrated better seizure outcomes than delayed surgery. Multicenter prospective studies are needed to validate these findings.

Indirect potable water reuse to face drought events in Barcelona city. Setting a monitoring procedure to protect aquatic ecosystems and to ensure a safe drinking water supply.

The climate change and increasing anthropogenic pressures are expected to limit the availability of water resources. Hence, active measures must be planned in vulnerable regions to ensure a sustainable water supply and minimize environmental impacts. A pilot test was carried out in the Llobregat River (NE Spain) aiming to provide a useful procedure to cope with severe droughts through indirect water reuse. Reclaimed water was used to restore the minimum flow of the lower Llobregat River, ensuring a suitable water supply downstream for Barcelona. A monitoring was performed to assess chemical and microbiological threats throughout the water treatment train, the river and the final drinking water, including 376 micropollutants and common microbiological indicators. The effects of water disinfection were studied by chlorinating reclaimed water prior to its discharge into the river. Data showed that 10 micropollutants (bromodichloromethane, dibromochloromethane, chloroform, EDDP, diclofenac, iopamidol, ioprimid, lamotrigine, ofloxacin and valsartan) posed a potential risk to aquatic life, whereas one solvent (1,4-dioxane) could affect human health. The chlorination of reclaimed water mitigated the occurrence of pharmaceuticals but, conversely, the concentration of halogenated disinfection by-products increased. From a microbiological perspective, the microbial load decreased along wastewater treatments and, later, along drinking water treatment, ultimately reaching undetectable values in final potable water. Non-chlorinated reclaimed water showed a lower log reduction of E. coli and coliphages than chlorinated water. However, the effect of disinfection vanished once reclaimed water was discharged into the river, as the basal concentration of microorganisms in the Llobregat River was comparable to that of non-chlorinated reclaimed water. Overall, our study indicates that indirect water reuse can be a valid alternative source of drinking water in densely populated areas such as Barcelona (Catalonia - NE Spain). A suitable monitoring procedure is presented to assess the related risks to human health and the aquatic ecosystem.

Printing via Laser-Induced Forward Transfer and the Future of Digital Manufacturing.

In the last decades, digital manufacturing has constituted the headline of what is starting to be known as the 'fourth industrial revolution', where the fabrication processes comprise a hybrid of technologies that blur the lines between fundamental sciences, engineering, and even medicine as never seen before. One of the reasons why this mixture is inevitable has to do with the fact that we live in an era that incorporates technology in every single aspect of our daily lives. In the industry, this has translated into fabrication versatility, as follows: design changes on a final product are just one click away, fabrication chains have evolved towards continuous roll-to roll processes, and, most importantly, the overall costs and fabrication speeds are matching and overcoming most of the traditional fabrication methods. Laser-induced forward transfer (LIFT) stands out as a versatile set of fabrication techniques, being the closest approach to an all-in-one additive manufacturing method compatible with virtually any material. In this technique, laser radiation is used to propel the material of interest and deposit it at user-defined locations with high spatial resolution. By selecting the proper laser parameters and considering the interaction of the laser light with the material, it is possible to transfer this technique from robust inorganic materials to fragile biological samples. In this work, we first present a brief introduction on the current developments of the LIFT technique by surveying recent scientific review publications. Then, we provide a general research overview by making an account of the publication and citation numbers of scientific papers on the LIFT technique considering the last three decades. At the same time, we highlight the geographical distribution and main research institutions that contribute to this scientific output. Finally, we present the patent status and commercial forecasts to outline future trends for LIFT in different scientific fields.

Anticipating Facial Nerve Position Using Three-Dimensional Tractography During the Preoperative Assessment of Cerebellopontine Angle Tumors.

OBJECTIVE: We aim to evaluate the usefulness of preoperative facial nerve tractography in determining the facial nerve position in cerebellopontine angle tumor resection and its value in helping to preserve facial nerve function during surgery. METHODS: A prospective study was designed to include patients presenting with cerebellopontine angle tumors. Three-dimensional reconstruction of facial nerve tractography was performed and added to the usual preoperative testing in all patients. Facial nerve position was compared between tractography results and surgical findings. Moreover, facial nerve function was evaluated at baseline and during follow-up. RESULTS: Fifteen patients were included for analysis. Complete resection was obtained in 5 patients, near-total resection was achieved in 8 patients, and partial resection in 2 patients. We found a strong statistically significant concordance between the preoperative facial nerve tractography reconstruction and the intraoperative findings (complete concordance in 86.66% of all the cases; κ = 0.784; P < 0.0001). Facial nerve anatomic structure was preserved in all patients during surgery. At 6 months follow-up, 66.66% of patients had a facial nerve normal function or a mild dysfunction. CONCLUSIONS: Preoperative facial nerve tractography reconstruction showed a high correlation with intraoperative findings. Preoperative tractography information regarding facial nerve position and its cisternal course is valuable information and could help the surgeon in increasing the safety of the procedure during cerebellopontine angle tumor surgery.

Endobronchial ultrasound guided transbronchial cryobiopsy versus forceps biopsy in peripheral lung lesions.

INTRODUCTION: Radial probe endobronchial ultrasound (RP-EBUS) is a modern technique for diagnosis of peripheral lung lesions. It is assumed that the addition of transbronchial cryobiopsy (TBCB) could increase the diagnostic value for RP-EBUS. OBJECTIVES: The main objectives were to evaluate the efficacy and safety of RP-EBUS-guided TBCB for diagnosis of peripheral lung lesions and comparing it with RP-EBUS-guided transbronchial forceps biopsy. METHODS: Sixty patients with peripheral lung diseases were divided into two groups. Group I included 45 patients who were eligible for TBCB and they subjected to forceps transbronchial biopsy (forceps TBB) and TBCB guided by RP-EBUS. Fifteen patients who were not eligible for TBCB were included in group II and they were subjected to forceps TBB and/or cytology retrieval procedures guided by RP-EBUS. RESULTS: In group I, forceps TBB had sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of; 67.5%, 100%, 100%, 18.8%, and 69.8%, respectively, while TBCB had sensitivity, specificity, PPV, NPV, and accuracy of 75%, 100%, 100%, 23.1%, and 76.7%, respectively. The sensitivity in group II was 80% and the overall results including both groups were sensitivity, specificity, PPV, NPV, and accuracy of 85.2%, 100%, 100%, 42.8%, and 86.7%, respectively. Regarding the complications, only one patient (1.7%) had significant bleeding. One patient (1.7%) had pneumothorax and another patient (1.7%) suffered from hypoxemia. CONCLUSIONS: RP-EBUS-guided TBCB is a safe and effective technique for diagnosis of peripheral lung lesions. TBCB has achieved higher diagnostic values and better quality of samples.

The Combined Use of Gold Nanoparticles and Infrared Radiation Enables Cytosolic Protein Delivery.

Cytosolic protein delivery remains elusive. The inability of most proteins to cross the cellular membrane is a huge hurdle. Here we explore the unique photothermal properties of gold nanorods (AuNRs) to trigger cytosolic delivery of proteins. Both partners, protein and AuNRs, are modified with a protease-resistant cell-penetrating peptide with nuclear targeting properties to induce internalization. Once internalized, spatiotemporal control of protein release is achieved by near-infrared laser irradiation in the safe second biological window. Importantly, catalytic amounts of AuNRs are sufficient to trigger cytosolic protein delivery. To the best of our knowledge, this is the first time that AuNRs with their maximum of absorption in the second biological window are used to deliver proteins into the intracellular space. This strategy represents a powerful tool for the cytosolic delivery of virtually any class of protein.

Is it necessary to sample the contralateral nodal stations by EBUS-TBNA in patients with lung cancer and clinical N0 / N1 on PET-CT?

OBJECTIVES: Systematic mediastinal staging (sampling all visible nodes measuring ≥ 5 mm from N3 station to N1, regardless of PET/CT (positron emission tomography/computed tomography) by endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is a decisive step in patients with non-small cell lung cancer (NSCLC). We analyzed the prevalence of N3 disease and the utility of systematic staging in the subgroup of patients who underwent EBUS-TBNA staging without showing mediastinal lesions on the PET/CT (N0/N1). MATERIAL AND METHODS: We conducted a retrospective analysis of a prospectively collected database that included 174 patients with a final diagnosis of NSCLC, with N0/N1 disease on PET/CT who underwent a systematic EBUS-TBNA staging. RESULTS: 174 consecutive patients were included. Systematic EBUS-TBNA detected N2 mediastinal involvement in 21 (12 %) cases, and no cases of N3 disease were detected (neither hilar nor mediastinal). Of the remaining 153 patients N0/N1 EBUS-TBNA, 122 underwent lung resection that revealed 4 cases of N2 disease while 117 were confirmed to be N0/N1. Thirty-three patients with N0/1 disease after EBUS-TBNA did not undergo surgery and were excluded for the NPV calculation. Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) and overall accuracy of systematic EBUS was 84 %, 100 %, 96.7 %, 100 % and 97 % respectively. CONCLUSION: Systematic EBUS-TBNA is a very accurate method for lymph node staging in patients with NSCLC without mediastinal involvement on PET/CT. Pending more studies, the absence of contralateral hilar nodal involvement in our series, questions the need for a contralateral hilar sampling in this subgroup of patients.

Remotely sensed indicators and open-access biodiversity data to assess bird diversity patterns in Mediterranean rural landscapes.

Biodiversity monitoring at simultaneously fine spatial resolutions and large spatial extents is needed but limited by operational trade-offs and costs. Open-access data may be cost-effective to address those limitations. We test the use of open-access satellite imagery (NDVI texture variables) and biodiversity data, assembled from GBIF, to investigate the relative importance of variables of habitat extent and structure as indicators of bird community richness and dissimilarity in the Alentejo region (Portugal). Results show that, at the landscape scale, forest bird richness is better indicated by the availability of tree cover in the overall landscape than by the extent or structure of the forest habitats. Open-land birds also respond to landscape structure, namely to the spectral homogeneity and size of open-land patches and to the presence of perennial vegetation amid herbaceous habitats. Moreover, structure variables were more important than climate variables or geographic distance to explain community dissimilarity patterns at the regional scale. Overall, summer imagery, when perennial vegetation is more discernible, is particularly suited to inform indicators of forest and open-land bird community richness and dissimilarity, while spring imagery appears to be also useful to inform indicators of open-land bird richness.

Re-urbanizing the European City: A Multivariate Analysis of Population Dynamics During Expansion and Recession Times.

After a long phase of suburbanization promoting economic decentralization and uneven expansion of urban rings, re-urbanization has been observed in an increasing number of European cities. However, a comprehensive analysis of demographic dynamics underlying spatial patterns-and factors-of re-urbanization is still lacking for the European continent. This study contributes to fill this knowledge gap by proposing a comparative analysis of population dynamics at two spatial scales ('inner cities' and 'large urban zones') in 129 European metropolitan regions under economic expansion (2000-2007) and recession (2008-2014). Non-parametric correlations, principal component analysis, and stepwise multiple regressions were used to identify different spatial patterns of population growth at continental and regional scale in Europe. The number of cities studied that showed a trend towards re-urbanization increased from 36 in 2000-2007 to 47% in 2008-2014. Positive rates of population growth in inner cities were found to be associated with high levels of disposable per capita income at the metropolitan scale. During recession, spatial differences in population growth rates were suggestive of a moderate rearrangement towards re-urbanization in northern and central Europe and less polarized metropolitan regions, with declining population in inner cities of southern and eastern Europe. Based on peculiar demographic dynamics found in the study area, the analysis performed brings useful insights to the debate about the future development of European cities.

Urban Growth, Land-use Efficiency and Local Socioeconomic Context: A Comparative Analysis of 417 Metropolitan Regions in Europe.

The present study presents a multidimensional analysis of land-use efficiency in terms of per-capita built-up area over 417 metropolitan regions from 27 European countries. The study period encompasses two urban phases including economic expansion (2000-2007) and crisis (2008-2015). Multiple geographical gradients were identified as relevant predictors of land-use efficiency across Europe. The socioeconomic variables most associated with high land-use efficiency were per-capita disposable income (in Western, Atlantic and Central Europe) and income growth during 2000-2007 (in Eastern Europe), indicating that wealthier cities are characterized by higher land-use efficiency. Land-use efficiency increased in contexts with diversified urban landscapes.

Spraying dynamics in continuous wave laser printing of conductive inks.

Laser-induced forward transfer (LIFT), though usually associated with pulsed lasers, has been recently shown to be feasible for printing liquid inks with continuous wave (CW) lasers. This is remarkable not only because of the advantages that the new approach presents in terms of cost, but also because of the surprising transfer dynamics associated with it. In this work we carry out a study of CW-LIFT aimed at understanding the new transfer dynamics and its correlation with the printing outcomes. The CW-LIFT of lines of Ag ink at different laser powers and scan speeds revealed a range of conditions that allowed printing conductive lines with good electrical properties. A fast-imaging study showed that liquid ejection corresponds to a spraying behavior completely different from the jetting characteristic of pulsed LIFT. We attribute the spray to pool-boiling in the donor film, in which bursting bubbles are responsible for liquid ejection in the form of projected droplets. The droplet motion is then modeled as the free fall of rigid spheres in a viscous medium, in good agreement with experimental observations. Finally, thermo-capillary flow in the donor film allows understanding the evolution of the morphology of the printed lines with laser power and scan speed.

Systematic Compared With Targeted Staging With Endobronchial Ultrasound in Patients With Lung Cancer.

BACKGROUND: To evaluate the accuracy of systematic mediastinal staging by endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) (sampling of all visible nodes measuring ≥5 mm from stations N3 to N1 regardless of their positron emission tomography/computed tomography [PET/CT] features) and compare this staging approach with targeted EBUS-TBNA staging (sampling only 18F-fluorodeoxyglucose [FDG]-avid nodes) in patients with N2 non-small cell lung cancer on PET/CT. METHODS: Retrospective study of 107 patients who underwent systematic EBUS-TBNA mediastinal staging. The results were compared with those of a hypothetical scenario where only FDG-avid nodes on PET/CT would be sampled. RESULTS: Systematic EBUS-TBNA sampling demonstrated N3 disease in 3 patients, N2 disease in 60 (42 single-station or N2a, 18 multiple-station or N2b) and N0/N1 disease in 44. Of these 44, 7 underwent mediastinoscopy, which did not show mediastinal disease; 6 of the 7 proceeded to lung resection, which also showed no mediastinal disease. Thirty-four N0/N1 patients after EBUS-TBNA underwent lung resection directly: N0/N1 was found in 30 and N2 in 4 (1 N2b with a PET/CT showing N2a disease, 3 N2a). Sensitivity, specificity, negative predictive value, positive predictive value, and overall accuracy of systematic EBUS-TBNA were 94%, 100%, 90%, 100% and 96%, respectively. Compared with targeted EBUS-TBNA, systematic EBUS-TBNA sampling provided additional important clinical information in 14 cases (13%): 3 N3 cases would have passed unnoticed, and 11 N2b cases would have been staged as N2a. CONCLUSIONS: In clinical practice, systematic sampling of the mediastinum by EBUS-TBNA, regardless of PET/CT features, is to be recommended over targeted sampling.

Do spatial patterns of urbanization and land consumption reflect different socioeconomic contexts in Europe?

Land-use changes and urban sprawl have transformed European cities, with a direct impact on both metropolitan structures and socioeconomic functions. However, these processes tend to be relatively different across countries, being influenced by place-specific factors associated to socioeconomic, historical, political and cultural factors that influence decisions on the use of land. Considering 155 metropolitan areas in 6 European macro-regions, the present study investigates spatial patterns of land consumption profiling cities according to a large set of territorial variables, with the final objective to identify relevant socioeconomic dimensions characteristic of recent processes of urban growth. Investigating the socioeconomic background underlying land-use changes in metropolitan regions allows identification of place-specific factors improving the design of effective strategies containing land consumption in different European urban typologies. An exhaustive analysis of land-use changes at regional and local spatial scales contributes to find alternative policies for land-use efficiency and long-term environmental sustainability.

Low-Cost Fabrication of Printed Electronics Devices through Continuous Wave Laser-Induced Forward Transfer.

Laser-induced forward transfer (LIFT) is a direct-writing technique that allows printing inks from a liquid film in a similar way to inkjet printing but with fewer limitations concerning ink viscosity and loading particle size. In this work, we prove that liquid inks can be printed through LIFT by using continuous wave (CW) instead of pulsed lasers, which allows a substantial reduction in the cost of the printing system. Through the fabrication of a functional circuit on both rigid and flexible substrates (plastic and paper), we provide a proof-of-concept that demonstrates the versatility of the technique for printed electronics applications.

Cáncer de pulmón en pacientes con combinación de fibrosis pulmonar y enfisema y fibrosis pulmonar idiopática. Estudio descriptivo en una serie española / Lung Cancer in Patients With Combined Pulmonary Fibrosis and Emphysema and Idiopathic Pulmonary Fibrosis. A Descriptive Study in a Spanish Series

Introducción: La información sobre la asociación del cáncer de pulmón (CP) y combinación de fibrosis pulmonar y enfisema (CFPE) es limitada y procedente casi exclusivamente de series asiáticas. El objetivo principal del estudio fue valorar el impacto del CP en la supervivencia en la CFPE y en pacientes diagnosticados de fibrosis pulmonar idiopática (FPI). Métodos: Se realizó un estudio retrospectivo con los datos de pacientes con CFPE y FPI diagnosticados en nuestro centro en un periodo de 5 años. Resultados: Se incluyó a 66 pacientes, 29 en el grupo de CFPE y 37 pacientes con FPI. Nueve tenían un diagnóstico de CP (6 con CFPE y 3 con FPI); 6 pacientes (67%) recibieron tratamiento paliativo a pesar de que 3 de ellos presentaban estadios I y II. No hubo diferencias significativas en la mortalidad global de los 2 grupos; sin embargo, en los pacientes con CP la supervivencia fue significativamente menor con respecto a los que no tenían CP (p = 0,044). Las causas más frecuentes de muerte fue la insuficiencia respiratoria secundaria a la exacerbación de la fibrosis pulmonar (44%). En el análisis multivariante, la odds ratio de morir en los pacientes con CP respecto a los pacientes sin CP fue de 6,20 (p = 0,037, intervalo de confianza [IC] del 95%: 1,11 a 34,48). Conclusión: El CP empeora la supervivencia de estas 2 entidades. El manejo diagnóstico y terapéutico del CP se ve dificultado por el mayor riesgo de complicaciones posteriores al tratamiento elegido, incluso tras el tratamiento paliativo (AU)

Introduction: Information on the association of lung cancer (LC) and combined pulmonary fibrosis and emphysema (CPFE) is limited and derived almost exclusively from series in Asian populations. The main objective of the study was to assess the impact of LC on survival in CPFE patients and in patients with idiopathic pulmonary fibrosis (IPF). Methods: A retrospective study was performed with data from patients with CFPE and IPF diagnosed in our hospital over a period of 5 years. Results: Sixty-six patients were included, 29 with CPFE and 37 with IPF. Nine had a diagnosis of LC (6 with CPFE and 3 with IPF). Six patients (67%) received palliative treatment even though 3 of them were diagnosed atstage I-II. Overall mortality did not differ significantly between groups; however, in patients with LC, survival was significantly lower compared to those without LC (P =.044). The most frequent cause of death was respiratory failure secondary to pulmonary fibrosis exacerbation (44%). In a multivariate analysis, the odds ratio of death among patients with LC compared to patients without LC was 6.20 (P =.037, 95% confidence interval: 1.11 to 34.48). Conclusions: Lung cancer reduces survival in both entities. The diagnostic and therapeutic management of LC is hampered by the increased risk of complications after any treatment modality, even after palliative treatment (AU)

Transbronchial and transesophageal fine-needle aspiration using a single ultrasound bronchoscope in the diagnosis of locoregional recurrence of surgically-treated lung cancer.

BACKGROUND: The present study sought to evaluate the usefulness of EBUS-TBNA in the diagnosis of locoregional recurrence of lung cancer in a cohort of lung cancer patients who were previously treated surgically, and describe our initial experience of EUS-B-FNA in this clinical scenario. METHODS: We retrospectively studied the clinical records of all patients with a previous surgically-treated lung cancer who were referred to our bronchoscopy unit after suspicion of locoregional recurrence. The diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and overall accuracy of EBUS-TBNA for the diagnosis of locoregional recurrence were evaluated. RESULTS: Seventy-three patients were included. EBUS-TBNA confirmed malignancy in 40 patients: 34 confirmed to have locoregional recurrence, six had metachronous tumours. Of the 33 patients with non-malignant EBUS-TBNA; 2 had specific non-malignant diseases, 26 underwent radiological follow up and 5 patients underwent surgery. Of the 26 patients who had radiological follow up; 18 remained stable, three presented thoracic radiological progression and 5 presented extrathoracic progression. Of the 5 patients who underwent surgery; 3 had metachronous tumours, one confirmed to be a true negative and one presented nodal invasion. Seven patients underwent EUS-B-FNA, four of them confirmed to have recurrence. The sensitivity, specificity, NPV, PPV and overall accuracy of EBUS-TBNA for the diagnosis of locoregional recurrence were 80.9, 100, 69.2, 100 and 86.6% respectively. CONCLUSIONS: EBUS-TBNA is an accurate procedure for the diagnosis of locoregional recurrence of surgically-treated lung cancer. EUS-B-FNA combined with EBUS-TBNA broads the diagnostic yield of EBUS-TBNA alone.

Lung Cancer in Patients With Combined Pulmonary Fibrosis and Emphysema and Idiopathic Pulmonary Fibrosis. A Descriptive Study in a Spanish Series. / Cáncer de pulmón en pacientes con combinación de fibrosis pulmonar y enfisema y fibrosis pulmonar idiopática. Estudio descriptivo en una serie española.

INTRODUCTION: Information on the association of lung cancer (LC) and combined pulmonary fibrosis and emphysema (CPFE) is limited and derived almost exclusively from series in Asian populations. The main objective of the study was to assess the impact of LC on survival in CPFE patients and in patients with idiopathic pulmonary fibrosis (IPF). METHODS: A retrospective study was performed with data from patients with CFPE and IPF diagnosed in our hospital over a period of 5 years. RESULTS: Sixty-six patients were included, 29 with CPFE and 37 with IPF. Nine had a diagnosis of LC (6 with CPFE and 3 with IPF). Six patients (67%) received palliative treatment even though 3 of them were diagnosed atstage i-ii. Overall mortality did not differ significantly between groups; however, in patients with LC, survival was significantly lower compared to those without LC (P=.044). The most frequent cause of death was respiratory failure secondary to pulmonary fibrosis exacerbation (44%). In a multivariate analysis, the odds ratio of death among patients with LC compared to patients without LC was 6.20 (P=.037, 95% confidence interval: 1.11 to 34.48). CONCLUSIONS: Lung cancer reduces survival in both entities. The diagnostic and therapeutic management of LC is hampered by the increased risk of complications after any treatment modality, even after palliative treatment.