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The reconstruction of glacier fluctuations during the latest Holocene (<1000 years) is necessary for understanding the climate context preceding the warmer conditions of the 20th and 21st centuries. The glacier records in the Andes of central Chile are suitably located to track former latitudinal changes of the Southern Westerly Winds (SSW), which are mostly unknown at this middle latitude region. Here, we present a reconstruction of the glacial fluctuations using Terrestrial Cosmogenic Nuclides (10Be) dating of boulders resting on moraines and other glacial landforms that make up the moraine complex in the forefield of the Universidad Glacier (34° S). This massive and chaotic-looking moraine was built during the latest Holocene ice advances and subsequent decay of the Universidad Glacier to its present position. Geomorphological mapping and 10Be surface exposure ages (n = 20) show that the Universidad Glacier advanced at least twice to nearly the same maximum extent, first by the 13th to 16th centuries and then by the early to the mid-19th century. Since then, eight moraine ridges denote a rather active and gradual ice demise. We interpret the glacier advances as a response to an equatorward shift of the SWW linked to a long-term negative phase of the Southern Annular Mode (SAM), which embraced net humid and cold atmospheric conditions in central Chile between the 13th century and the mid-19th century. Our glacier chronology is comparable to others from Patagonia and New Zealand, altogether exposing the culmination of the latest Holocene glacial maximum by the mid-19th century, before overall ice decay in a global warming world, with accelerated ice loss since the mid-20th century. • The fluctuations of the Universidad Glacier are 10Be reconstructed for the last millennium. • Glacier advances culminated by the 13th-16th centuries and early-to-mid 19th century. • A northward shift of the Southern Westerly Winds (SWW) triggered the glacier advances. • Glacier advances are linked to a negative phase of the Southern Annular Mode (SAM). • Southern glacier expansions seem to be near-synchronous in the last millennium. [ABSTRACT FROM AUTHOR]

Objective: To analyze changes in body mass index (BMI) in a group of obese patients after a nurse-based intervention to promote changes in their lifestyle through low- calorie diet, exercise and behavioral therapy. Method: quasi-experimental study with a non-probabilistic sample of 32 patients whose inclusion criteria were healthy patients, with autonomy for activities of daily living without dementia. The intervention was based on a nurse-based intervention to promote changes in their lifestyle and was subsequently evaluated by the decrease in BMI. Results: The mean value of the BMR was 34, 2 at the beginning of the study. After the nursing intervention there is a progressive decrease in BMI which was statistically significant after 6 months of treatment, which resulted in an mean value of 32,7. That is, a reduction in BMI of around 4%. Conclusions: personalized nursing intervention and intensive follow-up favor good acceptance or accession to the program and allow us to observe changes in the lifestyle of patients which is essential for controlling obesity. [ABSTRACT FROM AUTHOR]

• Rituximab is an effective treatment for multiple sclerosis patients. • During follow-up, a substantial increase of BL counts was preceded by initial values of 0.2–0.3%. • Rituximab retreatment guided by this cut-off BL showed high effectiveness in MS patients. • This approach may reduce adverse such as infections or hypogammaglobulinemia, thus allowing long-term therapy. Rituximab is extensively used for multiple sclerosis (MS) treatment. However, the best dosage remains to be established. It has been proposed that retreatment could be guided by B lymphocyte (BL) percentages. To establish the best BL value for retreatment with rituximab in MS and to confirm the safety and efficacy of this approach. A prospective study was done with an exploratory cohort and a confirmatory cohort of MS patients treated with rituximab between 2017 and 2021. The first one comprised 10 MS patients with BL assessed every 3 months after rituximab infusion and retreatment done when BL values were ≥0.5%. The confirmatory cohort included 41 MS patients (41.5% women, 87.8% with secondary progressive MS, median age = 46.3 (interquartile range: 41.3–52.1) years, disease duration = 14.1 (9–19.6) years, EDSS score = 5.5 (4.0–6.5)). The confirmatory cohort was treated with rituximab following the pattern established in the exploratory cohort. In the exploratory cohort, ≥0.2% BL was established as the best value for retreatment because in most cases, a substantial increase of BL counts was preceded by initial values of 0.2–0.3%. In the confirmatory cohort, rituximab reduced the annualized relapse rate (ARR 0.56 vs. 0.125, p < 0.001), proportion of patients with appearance of new/enlarged T2 lesions (63.4% vs. 12.2%, p < 0.001), gadolinium-enhancing lesions (39% vs. 0%, p < 0.001), and confirmed disability progression (55% vs. 27.5%, p = 0.037). There were 22 patients (53.7%) who achieved NEDA-3. No patients had severe infections, and 10.7% cases had reduced IgG levels. Rituximab treatment guided by BL showed high effectiveness and a good safety profile for MS patients after one year of treatment. [ABSTRACT FROM AUTHOR]

• The longer the disease has been on high efficacy therapy, the better the cognitive evolution evolves. • Each year of delay in starting a high efficacy therapy is associated with cognitive worsening. • Early high efficacy treatment protects from cognitive decline from the disease onset. • High efficacy therapy could particularly benefit those patients with high T2 lesion load. The potential influence of the timing of high-efficacy disease-modifying therapies (heDMTs) on processing speed (PS) performance is critically lacking in current literature. To assess the extent to which early commencement of heDMTs would be associated with a better PS evolution as compared to moderate efficacy disease-modifying therapies (meDMTs) and delayed commencement of heDMTs. In this ongoing prospective longitudinal study, the 695 MS patients that have received a PS evaluation at 12-month of follow-up measured by the iPad®-based Processing Speed Test (PST) were retained for the analysis. All patients who had ever been prescribed a high efficacy disease-modifying therapy (heDMT) were classified in tertiles according to the proportion of their disease duration that had been on heDMTs. Based on these tertiles and the time to the first heDMT from the disease onset, patients were divided into the early heDMT group and the delayed heDMT group. Between-group differences in mean PST standardized (Z-score) change from baseline were analyzed using a linear mixed model. In the multivariable model, each year of delay in starting a heDMT was associated with increased odds of cognitive worsening at 12-month (OR = 1.0324, 95% CI = 1.014-1.062, p<0.05). MeDMT-treated patients were at a significantly higher risk for cognitive worsening than early heDMT patients (OR= 2.57, 95%CI = 1.02-6.17). Linear mixed model-based adjusted mean change in PST Z-score from baseline was significantly better in those patients with the longest proportion of their disease duration treated with heDMT (highest tertile) compared to the lowest tertile (difference 0.37 [95%CI 0.02-0.92;p=0.036) and medium tertile (difference 0.39 [95%CI 0.06-0.31;p=0.037). Early he-DMT-treated patients are at significantly lower risk for cognitive worsening. Early administration of heDMTs is associated with greater cognitive functioning improvements than delayed commencement or meDMTs. [Display omitted] [ABSTRACT FROM AUTHOR]

To assess the presence of genetic imbalances in patients with myeloproliferative neoplasms (MPNs), 38 patients with chronic eosinophilia were studied by array comparative genomic hybridization ( aCGH): seven had chronic myelogenous leukaemia (CML), BCR-ABL1 positive, nine patients had myeloproliferative neoplasia Ph− (MPN-Ph−), three had a myeloid neoplasm associated with a PDGFRA rearrangement, and the remaining two cases were Lymphoproliferative T neoplasms associated with eosinophilia. In addition, 17 patients had a secondary eosinophilia and were used as controls. Eosinophilic enrichment was carried out in all cases. Genomic imbalances were found in 76% of all MPN patients. Losses on 20q were the most frequent genetic abnormality in MPNs (32%), affected the three types of MPN studied. This study also found losses at 11q13.3 in 26% of patients with MPN-Ph− and in 19p13.11 in two of the three patients with an MPN associated with a PDGFRA rearrangement. In addition, 29% of patients with CML had losses on 8q24. In summary, aCGH revealed clonality in eosinophils in most MPNs, suggesting that it could be a useful technique for defining clonality in these diseases. The presence of genetic losses in new regions could provide new insights into the knowledge of these MPN associated with eosinophilia. [ABSTRACT FROM AUTHOR]

TET2 is involved in a variety of hematopoietic malignancies, mainly in myeloid malignancies. Most mutations of TET2 have been identified in myeloid disorders, but some have also recently been described in mature lymphoid neoplasms. In contrast to the large amount of data about mutations of TET2, some data are available for gene expression. Moreover, the role of TET2 in chronic lymphocytic leukemia (CLL) is unknown. This study analyzes both TET2 expression and mutations in 48 CLL patients. TET2 expression was analyzed by exon arrays and quantitative real-time polymerase chain reaction (qRT-PCR). Next-generation sequencing (NGS) technology was applied to investigate the presence of TET2 variations. Overexpression of TET2 was observed in B-cell lymphocytes from CLL patients compared with healthy donors (P = 0.004). In addition, in CLL patients, an overexpression of TET2 was also observed in the clonal B cells compared with the nontumoral cells (P = 0.002). However, no novelmutations were observed. Therefore, overexpression of TET2 in CLL seems to be unrelated to the presence of genomic TET2 variations. [ABSTRACT FROM AUTHOR]

This essay analyzes several issues relating to Philip V's art collections, beginning with the influence of his grandfather Louis XIV. Together with dynastic tradition, the awareness of the academic doctrines of Félibien and Le Brun, the closeness to the quietism of Madame Guyon and the familiarity with amateurs such as Piles or Fénelon unquestionably furnished his cultural makeup. Another aspect that I will deal with is the presumed process of españolización of Philip d'Anjou's manners and portraits and the corresponding afrancesamiento of the royal court and its artists. Finally, I will look at the role of Antiquity in the definition of King Philip's collecting preferences. [ABSTRACT FROM AUTHOR]

Reconstructing latest Holocene (<1000 years) glacial landscape development in the Central Andes of Chile (30–35° S) is key for understanding the response of the cryosphere during periods of negative glacier mass balance, such as the current one. The excellently preserved glacial landscape produced during the latest ice advance and retreat cycle is of particular interest for examining the detailed response of glaciers to deglaciation. To establish a conceptual model of glacier behavior under warm and dry climatic conditions, we reconstructed and dated the recent glacial history of the Universidad Glacier (34° S) through detailed geomorphological mapping and 10Be cosmogenic surface exposure dating. Our mapping describes a landsystem that spans from the current ice front to ~3 km down-valley, where a mosaic of glacial landforms includes mounded relief; sinkholes; debris-filled stripes; moraine belts; flutings; and a prominent basal till plain. Our 10Be ages suggest that the Universidad Glacier has fluctuated in its forefield since the 13th – 15th centuries CE. We propose that the glacier evolved from a clean glacier to a debris-covered glacier, to an ice-cored moraine, and finally, to a massive dead-ice topography. This deglacial evolution intermittent and potentially reset by multiple standstills and/or re-advances during the overall retreat. The implication is that phases of active ice were followed by stagnation associated with progressive melting of dead ice under the supraglacial debris layer. Similar geomorphic features and processes are recorded in the present-day Universidad Glacier ablation zone, denoting a recurrent reconditioning over time analogous to the glacier's evolution during the latest Holocene. • We present a deglaciation model for Universidad Glacier in the Central Andes of Chile. • The glacier front progresses to an ice-cored moraine and then to hummocky terrain. • De-icing was interrupted by eight standstills/re-advances of the ice front. • The landsytem includes juxtaposed active and stagnant glacier-derived landforms. • The supraglacial debris layer affects ice dynamics in warm and dry periods. [ABSTRACT FROM AUTHOR]

Climatic and vegetation features of the mid-latitudes of the Southern Hemisphere before the global Last Glacial Maximum (gLGM) are still a matter of discussion. The signatures of Marine Isotope Stage (MIS) 3 show strong variability at the poles that has not yet been resolved at lower latitudes. This work discusses one of the first terrestrial records that reflects the vegetation, glacier, and climate conditions in southern South America during this period. The stratigraphic, palynological, and geomorphological features of the Punta Pihuío, Río Huicha, Punta Pirquén and Punta Detico sites (41–42° S) on the Isla Grande de Chiloé (southern Chile) are described and discussed. Glacially sourced sediment intercalated with peat soils constrained by single-grain feldspar (SGIR50) luminescence and radiocarbon (14C) dating show that the Late MIS 5 and the MIS 3 were periods of high environmental variability at these locations. Pollen records from peat layers indicate an open forest with conifers, Nothofagus and thermophilic elements, such as Myrtaceae, representing interstadial conditions that were abruptly interrupted by glacial expansions during stadials. High variability between arboreal and herbaceous taxa is also interpreted as environmental instability. Moreover, we show that the Patagonian Ice Sheet (PIS) reached full glacial extent during Early to Middle MIS 3, as is also observed in other Southern Hemisphere glacier records on both sides of the Pacific Ocean. Our data support that millennial-to multi-millennial-scale climate changes characterized the pre-gLGM not only at the poles, but also at the southern mid-latitudes. • Interstadial and stadial events are well preserved in terrestrial sediments of Chiloé Island. • The pollen record allows for reconstruction of Late MIS 5 and MIS 3 paleoclimate for southern South America. • We record an early to middle MIS 3 local LGM. • High pre-gLGM environmental variability is recorded at mid-latitudes of South America. [ABSTRACT FROM AUTHOR]

Giant cell tumour (GCT) remains one of the most obscure and intensely studied bone tumours. In an effort to resolve questions regarding the genesis and clinical outcome of GCT, advances have been made recently in the identification of chromosomal abnormalities implicated in the tumour. Fusion of telomeres is very frequent in GCT, and this process may be associated with chromosome instability and tumour development. However, little emphasis has been placed on chromosomal imbalances in the molecular characterization of this disease. Here, we report the case of an 83-year-old woman diagnosed with GCT where local recurrence was observed after 11 months of the resection. Cytogenetic studies of the GCT showed a modal number of 46 chromosomes with telomeric associations on 11p and dicentric chromosomes. Moreover, clonal abnormalities, such as del(17p) and losses of chromosomes 4, 13 and 18 and gains on chromosome 7, were also detected. Interestingly, comparative genomic hybridisation (CGH) analysis revealed chromosomal imbalances with gains on chromosomes 1p31-q44, 6q12-q23 and 12q15-q22. Thus, the use of CGH expanded the information obtained by conventional cytogenetics and demonstrated that chromosomal imbalances were associated with the recurrence of the GCT. [ABSTRACT FROM AUTHOR]