Period Of Retreat Research Articles

KAṬHINA ROBE OFFERING FESTIVAL OF THE SOUTHERN BUDDHISM MONKS COMMUNITY IN THUA THIEN - HUE PROVINCE

Kathina Robe Offering Festival is the traditional and biggest festival of the year of Southern Buddhism in Vietnam in particular and Buddhism countries in the world in general. This festival has existed since the time of Buddha Shakyamuni and to be maintained until today. Every year, during the period from the 15th day of the 9th lunar month to the 15th day of the 10th lunar month, at a temple or a place in accordance with Buddhism law, monks and nuns of Theravada Buddhism will hold a Kaṭhina Robe offering festival. The meaning of the festival is to mark the three-month period of retreat and diligent practice of the monks, the robe will be offered to the elders or those who meet the requirements. In Thua Thien - Hue province, the Southern Buddhism community often organizes the Kaṭhina robe offering festival for seven days at seven different pagodas (the remaining three pagodas are newly established and do not have the conditions to organize). This festival has become a cultural feature bearing the mark of the Southern Buddhism monks here, at the same time it is also a place for Buddhists of all walks of life at home and abroad to have the opportunity to participate and do good deeds. This article will clarify the origin, organization process and significance of the Kaṭhina Robe Offering Festival, especially emphasizing some changes in this festival of Southern Buddhism in Thua Thien - Hue province

Present Climate and Future Changes in the Annual Cycle of TC Activity in the WNP Investigated by HighResMIP GCMs

Abstract Atmospheric general circulation models (AGCMs) and coupled general circulation models (CGCMs) in the High Resolution Model Intercomparison Project (HighResMIP) were evaluated on their ability to simulate tropical cyclone (TC) activity in the western North Pacific (WNP) over its annual cycle. Specifically, we examined these models’ ability to simulate the south–north migration of the mean TC genesis location. The results revealed that both types of models realistically captured TC numbers and the south–north migration of TC genesis locations associated with the meridional migration of the WNP subtropical high ridge in response to the annual cycle. However, TC numbers decreased less rapidly in the AGCMs than in both the CGCMs and observed data during the monsoon retreat period (after September). This bias was probably attributed to a low-tropospheric cyclonic anomaly over the Philippine Sea in response to La Niña–like sea surface temperature (SST) differences between the AGCMs and the CGCMs. Because of these differences, the TC genesis frequency in the AGCMs over the Philippine Sea was overestimated. The cyclonic anomaly occurred when the northeasterly trade wind arose and was maintained through wind–evaporation–SST feedback. In future climate (2021–50), the main changes occurred during the monsoon retreat period. A more rapid decrease in TC numbers shown in AGCMs was likely attributed to the decrease (increase) of low-level vorticity (vertical wind shear) modulated by enhanced WNP subtropical high and subsidence anomalies. Conversely, a cyclonic circulation and ascending anomalies projected by CGCMs were identified off-equator, which favored TC genesis location shifting northward. Significance Statement Model performance and future changes in the annual cycle of tropical cyclone (TC) activity in the western North Pacific are investigated. We found that high-resolution uncoupled and coupled models realistically captured the TC numbers and meridional migration of TC genesis locations associated with the meridional migration of subtropical high ridge. However, TC numbers decreased more gradually in the uncoupled models than in the coupled models after September. This lower skill may stem from differences between the uncoupled and coupled models in simulating a cyclonic anomaly over the Philippine Sea in response to the La Niña–like sea surface temperature difference. In future climate (2021–50), TC numbers are significantly projected to decrease more rapidly during the monsoon retreat period in uncoupled models.

Lake surface and downstream river temperature response to the retreat of a lake‐terminating glacier

AbstractGlacier contributions to streamflow moderate summer water temperatures and help keep rivers cool during periods of hot, dry weather. As glaciers retreat, the length of channel exposed to solar radiation above a given point of interest would increase, which should ultimately result in higher water temperatures. However, formation of proglacial lakes may complicate river temperature response to glacier retreat. This study examined river and lake temperature response to the retreat of lake‐terminating Bridge Glacier, British Columbia, using a combination of manual spot and continuous river temperatures at a stream gauge, lake surface temperatures derived from Landsat imagery, and in situ lake temperatures made during a field campaign during summer 2013. Temperature data spanned the period from 1984 to 2022. Lake and river temperatures were relatively constant prior to and during a period of rapid retreat, but exhibited an upward trend following 2012, when iceberg density declined due to an apparent decrease in calving rate, resulting in an increase in lake surface area and river temperature of about 5°C even though the glacier remained lake terminating. In addition to providing the first longitudinal study of water temperature response to the retreat of a lake‐terminating glacier, this study adds to a body of literature that demonstrates that routine spot river temperatures, if collected in a consistent manner over a number of years, can provide valid information about river and stream temperature trends.

Abstract 5204: Exploring the therapeutic potential of EGFR retreatment: A comprehensive analysis of T790m(+) conversion and prognosis in lung cancer patients

Abstract Background: T790M acquired resistance occurs in 30-40% of cases after first- or second-generation EGFR TKI treatment. However, some patients who did not develop T790M mutation are converted to T790M positive through EGFR TKI retreatment. We conducted a Phase II prospective study analyzing T790m (+) conversion and prognosis in patients who were not induced T790M mutation at 2nd biopsy and were re-treated with first-generation EGFR-TKI as the third-line or later therapy. Methods: We re-administered first-generation EGFR-TKI to 63 patients (gefitinib n=34 or erlotinib n=29) who had previously been treated with first- or second- generation EGFR TKIs and cytotoxic chemotherapy because they were T790M-negative at the 2nd biopsy. Results: Among the 63 patients, a new T790m (+) mutation was identified in 20 patients (32%) with EGFR TKI retreatment. The first EGFR TKI treatment period and EGFR TKI retreatment period were significantly longer in the T790m (+) group than in the T790m (-) group (P-value=0.026, P-value=0.029, respectively). The best response to retreatment was also favorable in the T790m (+) group (P-value=0.038). The median overall survival (OS) in the T790m (+) group was 29.3 months, which was significantly better than the 6.0 months observed in the T790m (-) group (P-value<0.001). In an additional NGS analysis conducted on stored plasma samples from the 24 patients who were negative for T790M in the tumor tissue before retreatment, T790M was detected in five patients. These patients, who were subsequently treated with a third EGFR TKI, demonstrated very favorable overall survival (OS). Conclusions: EGFR retreatment could induce T790m (+) conversion in approximately one-third of cases, and these patients exhibited favorable prognosis. Through NGS analysis using plasma samples, approximately 20% cases of T790m mutation, which were not detected through routine PCR tests at the tumor tissue, could be identified. Retreatment-EGFR TKI and NGS analysis through blood samples could improve patient prognosis through the additional discovery of T790m (+) mutation. Citation Format: Joong Jin Ahn, Jae Cheol Lee, Chang Min Choi, In Ae Kim, Kye Young Lee, Jeong Eun Lee, Seung Hoon Jang, Seong Hoon Yoon, In Jae Oh, Sang Hoon Lee, Eun Young Kim, Juwhan Choi, Sung Yong Lee. Exploring the therapeutic potential of EGFR retreatment: A comprehensive analysis of T790m(+) conversion and prognosis in lung cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5204.

Origin and evolution of the surface desalinated layer of the Kara Sea during the ice-free period

This work focuses on the freshwater contribution (water from the Ob’ and Yenisei rivers and ice meltwater) to the surface layer of the Kara Sea according to 2015–2020 expedition data. Salinity and hydrochemical data (total alkalinity and silicates) were used to calculate the proportion of freshwater in the desalinated layer of the Kara Sea. The ratio of the water fractions with the linear mixing of several sources was considered. Our results showed that riverine sources varied greatly, and the total contributions of the Ob’ and Yenisei runoff ranged from 10 to 60%, while the contribution of ice meltwater did not exceed 25%. The relationship between the period of seasonal ice retreat in the Kara Sea and its proportion in the surface desalinated layer was revealed. The interannual variability in freshwater source composition varied greatly from the southwestern to the eastern part of the sea owing to wind forcing and seasonality in river discharge.

Tolerability and Safety of Collagenase Clostridium Histolyticum Injection in Participants with Plantar Fibromatosis

Category: Midfoot/Forefoot; Basic Sciences/Biologics Introduction/Purpose: Plantar fibromatosis (PFi) is a functionally disabling disorder characterized by fibrous collagen-containing nodules along the plantar fascia. Collagenase clostridium histolyticum (CCH) is a nonsurgical treatment approved for Dupuytren’s and Peyronie’s disease; both can coexist with PFi. Composed of two collagenases, CCH specifically hydrolyzes certain collagen types and may disrupt the nodule when injected directly. This proof-of-concept study evaluated pharmacokinetics, immunogenicity, and assessed tolerability and safety of CCH treatment of PFi. Methods: In this Phase 1, multicenter study, participants were randomly allocated (1:1:1) to receive 0.6, 1.2, or 2.25 mg/mL CCH. All participants underwent the initial treatment period (ITP) and received 1–2 intralesional injections per nodule on Day 1 with pharmacokinetic samples collected over 24hrs, followed by 5 follow-up visits. Post-ITP, participants with a remaining, palpable nodule could enter the retreatment period (RP) and receive additional CCH doses (at 2.25 mg/mL) with follow-up at specified intervals. Immunogenicity test sampling occurred at screening and at the end of ITP/RP. Adverse events (AEs) were monitored throughout. Results: Twenty-four participants enrolled into ITP, with 11 continuing into RP. Pharmacokinetic and immunogenicity findings were consistent with previous CCH studies in other therapeutic areas. CCH treatment was generally well tolerated, with no serious treatment emergent adverse events (TEAEs), drug discontinuations, or study withdrawals by study end. Over 70% of participants during ITP (19/24) and RP (8/11) reported at least 1 TEAE. Eighty-six TEAEs occurred during ITP and 35 in RP; most were mild in severity (73%, ITP; 83%, RP), and 67% of ITP and 49% of RP TEAEs were treatment related. TEAEs were reportedly injection site- related, with injection site bruising, pain, and swelling frequently recorded. Conclusion: CCH had an expected pharmacokinetics/immunogenicity profile and was safe and well tolerated in participants with PFi. CCH may be a potential nonsurgical intralesional option for PFi treatment.

Participant Satisfaction and Investigator Assessment of Collagenase Clostridium Histolyticum Injection as a Nonsurgical Intralesional Treatment Option for Plantar Fibromatosis

Category: Midfoot/Forefoot; Basic Sciences/Biologics Introduction/Purpose: Currently, there is no safe and efficacious injectable therapy for symptomatic plantar fibromatosis (PFi) that addresses its pathophysiology. Patients with PFi nodules experience symptoms that reduce quality of life, causing functional disability leading to severe impairment in some patients. Collagenase clostridium histolyticum (CCH) is approved for Dupuytren’s and Peyronie’s disease treatment, which are both fibroproliferative disorders that may coexist in patients with PFi. This first study of CCH treatment for PFi evaluated participant satisfaction and investigator assessment of improvement. Methods: Participants were randomly allocated (1:1:1) in this Phase 1, multicenter study to receive 0.6, 1.2, or 2.25 mg/mL CCH. All participants underwent the initial treatment period (ITP) and received 1–2 intralesional injections per nodule on Day 1 with follow-up assessments at specified intervals. Participants with palpable treated nodules could enter the retreatment period (RP) and receive additional CCH doses (at 2.25 mg/mL), with follow-up at specified intervals. Assessments included the Subject Satisfaction with Treatment Rating Scale (+2: very satisfied; to -2: very dissatisfied), and the Investigator Assessment of Improvement Scale (+3: very much improvement; to -3: very much worse). Results: After ITP, ≥75% of participants reported “very” or “quite” satisfied across all treatment groups, with 2.25 mg/mL group reporting 100% satisfaction. For ≥72.7% of nodules, participants reported satisfaction with outcome. Investigators reported improvement (“minimal”, “much”, or “very much”) in ≥75% of participants and ≥80% of treated nodules. After RP, 63.6% of participants reported treatment satisfaction; participants were satisfied with 66.7% of treated nodules, indicating continued improvement from the ITP. Almost all participants (90.9%) were deemed by investigators to have shown improvement, with 86.7% of treated nodules being assessed as having improvement. Conclusion: CCH-treated PFi participants were satisfied with their improvement; physicians assessed improvement in >90% of participants. Results indicate CCH as a potential nonsurgical intralesional option for PFi treatment.

Efficacy of Collagenase Clostridium Histolyticum Injection, a Potential Nonsurgical Intralesional Treatment Option for Plantar Fibromatosis: A Randomized, Open-Label, Dose-Ranging Study

Category: Midfoot/Forefoot; Basic Sciences/Biologics Introduction/Purpose: Plantar fibromatosis (PFi) is characterized by collagen-containing nodules on the foot along the plantar fascia that can cause pain and functional disability. Current treatments focus on symptom relief, which may become ineffective, or surgery, which can have lengthy recovery times. Collagenase clostridium histolyticum (CCH) is approved for Dupuytren’s and Peyronie’s disease treatment, which are both fibroproliferative disorders that may coexist in patients with PFi. This dose-ranging study assessed the efficacy and safety of CCH treatment of PFi. Methods: In this Phase 1, multicenter study, participants were randomly allocated (1:1:1) to receive 0.6, 1.2, or 2.25 mg/mL CCH. All participants underwent the initial treatment period (ITP) and received 1–2 intralesional injections per nodule on Day 1 with 5 follow-up assessments. Participants with palpable treated nodules could receive additional CCH doses (at 2.25 mg/mL; retreatment period, RP), with follow-up at specified intervals. Assessments included a 5-scale measure of nodule hardness (0 [nonpalpable] to 4 [hard]), and the Foot Function Index-Short Form23 (FFI-SF23) reported as a composite score (0 – 100) of 3 subscale scores (disability, difficulty, and pain subscales). Results: After ITP (n=24), 100% (8/8) of participants receiving 2.25 mg/mL CCH showed improvement in nodule hardness, compared with 87.5% (7/8) and 75% (6/8) of participants receiving 1.2 and 0.6 mg/mL, respectively. FFI-SF23 also showed a negative change from baseline across treatment groups, indicating improvement. Participants that received 2.25 mg/mL reported the largest percent improvement (-83.7%). After RP (n=11), 81.8% (9/11) of participants showed improvement in nodular hardness and an FFI-SF23 score change of -9.3%, indicating further improvement from baseline after ITP. CCH had a consistent safety profile in ITP/RP. Conclusion: CCH caused dose-dependent improvement of nodule hardness after treatment, with 2.25 mg/mL utilized for nodule retreatment; FFI-SF23 scores correlated with this finding, indicating CCH may be a potential nonsurgical intralesional option for PFi treatment.

Long‐term drivers of shoreline change over two centuries on a headland‐embayment beach

AbstractShoreline evolution over the last two centuries was analysed for Dundrum Bay, Co. Down, Northern Ireland, using historical and recent shoreline datasets from 1833 to 2020. The area of interest comprises two sandy beaches and vegetated coastal dune fields, Newcastle–Murlough and Ballykinler, separated by an inlet channel which connects the inner with the outer bay. Twenty‐four temporal shorelines were extracted, and a quantitative assessment of their positional uncertainty was performed. This was combined with analysis of foredune volume variations by applying the Structure‐from‐Motion‐Multi‐View‐Stereo technique to 1963 aerial photography and comparing it with a 2014 Light Detection And Ranging (LiDAR) dataset to better inform on links between the sediment dynamics and the observed shoreline changes. Storm events were identified using recorded extreme water levels (EWLs) (1901–2020) and hindcasted wave data (1948–2020). In the first 87 years, the shoreline was largely stable, and change was focused at the inlet area. In the 20th century, localised retreat characterised the western (Newcastle–Murlough) sector, whereas the eastern sector (Ballykinler) experienced general shoreline advance. The rate and extent of shoreline retreat in the western sector increased post‐1997 in concert with accelerated accretion at Ballykinler. The strongest erosional episodes were recorded in 1920–1951, 1997–2005, and 2012–2014. Although no direct link was established between single storms and shoreline retreat rates, the three major retreat periods coincided with several consecutive EWLs or EWLs with a return period greater than 100 years. These were generated by storm directions ranging from south to southwest. The long‐term pattern of shoreline change points to a complex coastal system that is still evolving.

The Response of Tidewater Glacier Termini Positions in Hornsund (Svalbard) to Climate Forcing, 1992–2020

AbstractMany Arctic marine‐terminating glaciers have undergone rapid retreats in recent decades. Seasonal and year‐to‐year variations in terminus position act on all tidewater glaciers, but the key controls on those changes vary from region to region. Here, we examined seasonal and decadal changes in termini positions of seven tidewater glaciers in the inner part of Hornsund, the southernmost fjord of Spitsbergen (Svalbard Archipelago), based on a variety of data from 1992 to 2020. Combining satellite imagery, basic meteorological data (air temperature, positive degree day index (PDD), liquid precipitation), sea surface temperature (SST), mean temperature in the glacier forefield bays, fast sea ice cover, and bathymetry near the glacier front, we examined the influence of potential controlling parameters on interannual and seasonal variability of the glacier termini. We found regional synchrony between terminus advance/retreat and climate variables. At a regional scale, annual fluctuation changes are related to PDD and SST, while summer fluctuations are linked to PDD, although individual glaciers are shown to have differing sensitivities to potential climate drivers. We also found that the retreat period in Hornsund generally lasts from June to October‐December. Onset of the retreat is related to sea and air temperature, and in some cases follows the disappearance of the ice cover. These results indicate that the expected increase in meltwater runoff in Svalbard, the input of relatively warm Atlantic water to the fjord, and the increasing trend of longer summer and warmer winter periods will have implications for glacier velocity and frontal ablation.

Assessing controls on ice dynamics at Crane Glacier, Antarctic Peninsula, using a numerical ice flow model

AbstractThe Antarctic Peninsula's widespread glacier retreat and ice shelf collapse have been attributed to atmospheric and oceanic warming. Following the initial post-collapse period of retreat, several former tributary glaciers of the Larsen A and B ice shelves have been slowly re-advancing for more than a decade. Here, we use a flowline model of Crane Glacier to gauge the sensitivity of former tributary glaciers to future climate change following this period of long-term dynamic adjustment. The glacier's long-term geometry and speed changes are similar to those of other former Larsen A and B tributaries, suggesting that Crane Glacier is a reasonable representation of regional dynamics. For the unperturbed climate simulations, discharge remains nearly unchanged in 2018–2100, indicating that dynamic readjustment to shelf collapse took ~15 years. Despite large uncertainties in Crane Glacier's past and future climate forcing, a wide range of future climate scenarios leads to a relatively modest range in grounding line discharge (0.8–1.5 Gt a−1) by 2100. Based on the model results for Crane, we infer that although former ice shelf tributaries may readvance following collapse, similar to the tidewater glacier cycle, their dynamic response to future climate perturbations should be less than their response to ice shelf collapse.

Earth, wind and fire: Interactions between Quaternary environmental dynamics and human occupation on the southern coast of Brazil

The southern coast of Brazil has been settled in different episodes between ca. 7.5 and 0.5 ka before the present by hunter-fisher-gatherers, shell mound builders of the pre-colonial Sambaqui cultural tradition. The factors that influenced human migrations in these episodes are diverse. They include cultural changes due to the coming of other groups, chronic food shortages, sea level changes, and lagoon silting. This paper combines geological, geomorphological, meteorological, and archaeological data to show how interactions between environmental dynamics and human settlement played a central role in modeling coastal sedimentary and rocky landscapes on the southern coast of Brazil during the middle Pleistocene to late Holocene. On Costão do Ilhote, a north-south oriented granitic promontory in Laguna County, Santa Catarina State, erosional features such as facets, keels, grooves, flutes, pits, and polished surfaces that developed on granitic boulders and pavements were recognized as ventifacts. In the same context, hundreds of fixed sharpeners/polishers from the production of polished objects by the sambaqui culture have been found crosscutting the ventifacts. Based on crosscut relationships between pre-colonial aged fixed sharpeners/polishers and ventifacts, relative sea-level changes during the Holocene, the age of distinct generation of sand dunes, and the age of shellmounds (sambaquis), four potential intervals of ventifaction are proposed: last 650 ka, last 350 ka, between ca. 115 and 5 ka BP, and between ca. 2.0 and ∼0.5 ka BP, with separated estimated abrasion rates of approximately 3.5 × 10−5 mm/yr, 7.0 × 10−5 mm/yr, 1.7 × 10−4 mm/yr, and 1.3 × 10−2 mm/yr, respectively. The ca. ∼1.5 ka of the last ventifaction interval was synchronous with a period of sambaqui culture retreat in the southern coastal plain of Santa Catarina, and also coincided with a period of abundant sand availability. This period is characterized by a drastic decline in sambaquis construction along the sand barrier and paleolagoon and a migration towards lagoonal and coastal rocky promontories, including Costão do llhote. Based on these pieces of evidence, we propose to add new components to the close interactions between environmental evolution and prehistoric human occupation on the southern coast of Santa Catarina during the Holocene: the strong winds combined with sand availability.

Weekly to monthly terminus variability of Greenland's marine-terminating outlet glaciers

Abstract. Seasonal terminus-position variability of Greenland's marine-terminating outlet glaciers is superimposed on multidecadal trends of glacier retreat. To characterize this seasonal variability, we manually digitized terminus positions for 219 marine-terminating glaciers in Greenland from January 2015 through December 2021 using Sentinel-1 synthetic aperture radar (SAR) mosaics. We digitized at a monthly frequency for 199 glaciers and at a 6 d frequency for 20 glaciers. We found that nearly 80 % of glacier termini in Greenland vary significantly on a seasonal basis. For these seasonally varying glaciers, on average, seasonal retreat typically begins in mid-May, and seasonal advance generally commences in early October. The timing of the initiation of the retreat period may be related to the timing of the onset of ice-sheet surface melt. The rate of retreat events peaks in late summer and reaches a minimum in late winter and early spring. The median magnitude of terminus-position seasonality, the difference between glacier length at the dates of peak advance and retreat, is about 220 m. We find a stronger correlation between this magnitude and glacier velocity than between magnitude and glacier width. Terminus-position seasonality can influence longer-term glacier dynamics and, consequently, ice-sheet mass balance. This study contributes to our understanding of terminus-position seasonality for individual glaciers and collectively for glaciers around the entire Greenland Ice Sheet.

Geological Distribution of the Miocene Carbonate Platform in the Xisha Sea Area of the South China Sea, and Its Implications for Hydrocarbon Exploration

The newly collected seismic data and the existing drilling data provide a good opportunity to better understand the carbonate platform distribution characteristics and the hydrocarbon resource potential in the Xisha sea area of the South China Sea. Based on the seismic data and the reflection characteristics of the carbonate platform’s edge, three boundary indicators were established: abrupt lithological interfaces, fault interfaces, and tidal channels. Combined with the regional geological settings, its spatial and temporal distribution was clearly identified for the first time. The development of the Miocene carbonate platform in the Xisha sea area is divided into six phases, which are further assigned to three evolutionary stages: the bloom stage, the recession stage, and the submerged stage. The sedimentary facies belt of the carbonate platform in each stage is well developed, and the reefs are mainly distributed on the west and southwest edges of the platform. The analysis of the data indicates that the area of the reef and carbonate platform reached 80,000 km2 during the mature period, followed by a retreat period where the scale decreased with the platform’s decline. The Miocene carbonate rocks in the Xisha sea area are widely distributed. They have experienced multiple periods of exposure and infiltration, which further improved the quality of their physical properties for hydrocarbon reservoirs. According to the regional hydrocarbon geological conditions in this area—including the source rock, migration system and the capping layer—the hydrocarbon accumulation potential is preliminarily discussed in this paper. A reservoir model of the reef and carbonate platform is established, which is proposed as typical characteristics of “lower generation, upper accumulation”. It is pointed out that the carbonate platform in the Xisha sea area adjacent to the Huaguang Sag in the Qiongdongnan Basin and the northern Zhongjiannan Basin is a potential area for oil and gas exploration.

A Spanish Medical Record Review of Adults with Relapsed or Refractory CD30+ Malignancies When Re-Treated with Brentuximab Vedotin (BV): Preliminary Analysis of the Believe Study (NCT:04998331)

Background: The efficacy and clinical benefit of BV in patients with CD30+ relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL), cutaneous T cell lymphoma (CTCL) [mycosis fungoides (MF) or primary cutaneous anaplastic large cell lymphoma (pcALCL)] and systemic anaplastic large cell lymphoma (sALCL) have been shown in Ph2-3 pivotal studies (NCT00848926, NCT01578499, NCT00866047). However, the evidence of BV use as a retreatment option is scarce. There are only two studies with available data on the effectiveness and safety of brentuximab vedotin (BV) in the retreatment setting. This research aims to investigate the effectiveness and safety of retreating these populations with BV in the real-world setting in Spain. Methods: Non-interventional, retrospective, multicenter, medical chart review study conducted in 30 public and private Spanish sites. The study included patients aged ≥18, with confirmed diagnosis of cHL, CTCL (MF and pcALCL) and sALCL, CD30 positive, previously treated with BV as monotherapy or as a combination with another antitumor agent, with evidence of objective response and subsequent disease progression, who received ≥2 doses of BV as retreatment and a minimum of ≥6 months of follow-up, discontinuation due to toxicity, or until death. Results: Of the 51 patients enrolled, 43 were eligible for this preliminary analysis (Table 1): 16 with cHL, 12 with MF, 2 pcALCL and 13 with sALCL. The median age of the total population was 47 (33.5-51.5) years, and 58% were women. At retreatment, the Eastern Cooperative Oncology Group performance status (ECOG PS) of the patients was poorer: 18 (52.9%) had ECOG PS of 0; 13 (38.2%) had ECOG PS of 1, 2 (5.9%) had ECOG PS of 2, and 1 (2.9%) had ECOG PS of 3, and 40 patients (93%) presented with comorbidities (Table 1). The median time from the first treatment with BV to the retreatment initiation was 18 (7-108) months, with at least one treatment before BV retreatment in most of the patients (n=40; 93%) (Table 1). At initiation of the retreatment period, more than 50% of patients presented advance clinical stage (III and IV). 27 patients (67.5%) discontinued/terminated retreatment with BV after a median of 5.5 (3.5-7) cycles. The median time from end of BV retreatment until last available follow-up was 8 (6-12) months and 73% of patients were alive. 10 patients were exitus and 43.6% presented with adverse events, mainly peripheral sensory neuropathy (24.2%) (Table 1). Conclusion: This chart review is the first Spanish study to collect information on BV retreatment in patients with CD30+ malignancies, providing information of clinical characteristics and treatment patterns in real-word practice. As BV may become established as a preferred first-line therapeutic option for both untreated stage IV in cHL and sALCL, future research efforts could be aimed at further exploring the efficacy and safety of BV retreatment in patients who progress or relapse after receiving frontline BV treatment. Further analysis of this study will be provided at the congress to determine efficacy and safety results associated to BV retreatment in the Spanish population at clinical practice. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

NIMG-81. EFFECT OF RE-TREATMENT WITH TEMOZOLOMIDE IN GRADE 2/3 IDH MUTANT GLIOMAS AT FIRST PROGRESSION

Abstract BACKGROUND Patients with WHO grade 2 and 3 IDHmt gliomas commonly receive temozolomide, with or without radiation therapy, as initial therapy. At progression, temozolomide is sometimes reinstated despite a paucity of data on effectiveness. METHODS We reviewed imaging outcomes of patients with grade 2/3 IDHmt gliomas re-treated with temozolomide at first progression between 2007 and 2019. RESULTS 15 subjects included six grade 2 and five grade 3 oligodendrogliomas, one grade 2 and three grade 3 astrocytomas. Median time between completion of first temozolomide course and initiation of re-treatment was 47 months (range, 8-126 months). Best treatment response after first progression by RANO criteria was stable disease in 10 and progressive disease in 5 patients. Median progression free survival with temozolomide re-treatment was 27.4 months (95% CI: [13.8, 41.2 months] and median overall survival 47.8 months (95% CI: [31.5, 125.6 months]). In 14 patients who had pre- and post- first tumor progression rate measurements, the mean rate of tumor growth by bidimensional product was 0.29 cm2/month (95% CI: [0.17, 0.42 cm2/month], p< 0.001) prior to first tumor progression versus 0.47 cm2/month (95 CI: [0.08, 0.85 cm2/month], p=0.021) during re-treatment with monotherapy temozolomide (prior vs after, p=0.371). The volumetric mean rate of tumor growth was 1.12 cc/month (95% CI: [0.31, 1.93 cc/month], p=0.010) prior to first tumor progression versus 1.29 cc/month (95% CI: [0.15, 2.43 cc/month], p=0.030) during temozolomide re-treatment (prior vs. after, p=0.802). CONCLUSION Among 15 patients with progressive IDHmt glioma re-treated with temozolomide, there was no radiographic response by RANO criteria nor a decrease in tumor growth rate during the re-treatment period compared to immediate pre-re-treatment period. These findings suggest previously treated, progressive IDHmt gliomas are generally resistant to temozolomide, underscoring the need for novel therapies.

Understanding the crisis of New Municipalism in Spain: The struggle for urban regime power in A Coruña and Santiago de Compostela

New municipalism in Spain arose from a major political wave, now in a period of crisis and electoral retreat. This paper applies a regime-theoretic framework to analyse new municipalist governance in two smaller city cases: A Coruña and Santiago de Compostela. It argues that whilst new municipalist electoral victories inaugurated a crisis for established regimes, the crucial weakness was that they did not consolidate new urban regimes. Municipalists faced severe governability challenges linked to the enduring power of older urban regimes. The paper suggests that this is explained by problems in establishing regime incumbency, the consolidation of the necessary governing capacity by a resource coalition to deliver its agenda and succeed politically. Although established regimes were weakened enough to lose elections, they maintained considerable capacity to constrain the municipalist project and shape urban governance, a significant degree of incumbency. This ultimately enabled them to recover office in 2019. We argue that a critical regime-theoretical perspective assists in understanding the wider crisis of Spanish municipalism and the multi-scalar struggle for hegemony as it plays out in the local state arena.

Seafloor Reveals a Period of Rapid Retreat for Thwaites Glacier

New high-resolution seafloor imagery shows a series of delicate ridges produced by the glacier’s front as it bobbed daily with the tides, revealing a recent period of rapid retreat.New high-resolution seafloor imagery shows a series of delicate ridges produced by the glacier’s front as it bobbed daily with the tides, revealing a recent period of rapid retreat.

An optimized mode of interferon intermittent therapy help improve HBsAg disappearance in chronic hepatitis B patients.

BackgroundTo investigate the effect of intermittent interferon therapy mode on the disappearance of hepatitis B surface antigen (HBsAg) in chronic hepatitis B (CHB) patients.MethodsThis is a retrospective cohort study in CHB patients who were suspended from pegylated interferon α (PEG-IFNα) therapy due to a plateau in HBsAg decline during the initial treatment period, and resumed interferon therapy after an interval of 3–6 months. Patients received entecavir or tenofovir during the interval period. Hepatitis B virus (HBV) virological and serological indexes, clinical biochemical indexes, and blood routine tests were performed at the baseline and every 3 months during follow-up of initial interferon treatment. A functional cure was analyzed as a primary outcome.ResultsA total of 304 patients treated with intermittent PEG-IFNα were included in the statistical analysis, including 215 men and 89 women, aged 37.97 ± 8.53 years, and 73 hepatitis B e antigen (HBeAg)-negative and 231 HBeAg positive patients. In total 59 patients (19.41%) achieved HBsAg disappearance through the initial, intermittent, and retreatment of PEG-IFNα treatment, of whom 43 patients (14.14%) achieved HBsAg seroconversion. Early HBsAg response to initial treatment was significantly associated with HBsAg response at 12 and 24 weeks of retreatment. After the intermission period, the incidence of HBsAg disappearance in patients with early HBsAg response in the retreatment period was 43.87%. The baseline HBsAg and 12-week HBsAg response in the retreatment period had higher predictive value than the initial treatment HBsAg response.ConclusionThe initial, intermittent, and retreatment mode of interferon can help to improve the HBsAg disappearance rate in CHB patients.Clinical trial registration[www.ClinicalTrials.gov], identifier [NCT04028856].

Constraints on Sandstone-Type Uranium Deposits by the Tectonic Uplift and Denudation Process in the Eastern Junggar Basin, Northwest China: Evidence from Apatite Fission Track and Detrital Zircon U-Pb Ages

The uplift and denudation history of the orogenic belt and the basin–mountain coupling process have directly or indirectly affected the generation, scale, and preservation of sandstone-type uranium deposits in the eastern Junggar Basin by controlling the uranium source, lithology, facies, hydrogeology, post-generation modification, and other mineralization conditions. Taking the eastern Junggar Basin as the research area, this study proposes the constraints on sandstone-type uranium deposits by the tectonic uplift and denudation history of the orogenic belt in the basin using the apatite fission track (AFT), detrital zircon geochronology, and other methods. The results of the AFT age test and thermal path simulation indicate that the orogenic belt in the eastern Junggar Basin underwent four rapid uplifts; (from approximately 300 Ma to approximately 250 Ma, from approximately 130 Ma to approximately 90 Ma, from approximately 65 Ma to approximately 30 Ma, and from approximately 20 Ma to 0 Ma). Moreover, the timing of the uplift has a spatial trend of gradually becoming younger from south to north. The detrital zircon U-Pb age test showed that the sediment source area of the basin is mainly distributed in three age intervals, i.e., 460–390, 360–270, and 190–170 Ma. The comprehensive evaluation of the clastic sediment composition, stratigraphic distribution of the erosion source area, and thermal history showed that a large amount of exposed Carboniferous–Permian granites in the Qinglidi and Karameri Mountain erosion source areas contributed dominant sediment material and uranium sources for the Triassic and Middle and Lower Jurassic strata in the basin. The Ordovician–Early Devonian granites only provided sediment sources for the Upper Triassic and Lower Jurassic strata in the basin. Altay Mountain contributed some sediment sources for the Middle and Upper Jurassic strata after the magmatic activity and rapid uplift occurred in the Middle Jurassic. Based on the comprehensive analysis of the influence of the tectonic uplift process of the orogenic belt and the transformation of material source areas on uranium mineralization, the granites in the erosion source areas are proposed to contribute both external and internal uranium sources for uranium mineralization. Uranium mineralization mainly occurred in the tectonic retreat period after the rapid uplifts of the Cretaceous and Paleogene. It was terminated by the intensive uplift-induced stratigraphic deformation in the Miocene.