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The great lakes of Europa The Galileo spacecraft revealed a number of 'chaos' regions on Jupiter's moon Europa, where the surface terrain appears to have been disrupted from below. In many places, the surface contains sharp-edged blocks or rafts of ice that have at some point been flipped or rotated. Some characteristics of these regions have been hard to explain, such as the fact that the archetypal Conamara Chaos stands above its surroundings and contains matrix domes. Schmidt et al . apply lessons learned from analogous processes within Earth's subglacial volcanoes and ice shelves to an analysis of archival data that suggests chaos terrain forms above liquid water 'lenses' that are perched only 3 kilometres deep within the ice shell. The data suggest that ice–water interactions and freeze-out give rise to the varied morphology of chaos terrains, implying that more water is involved than has been previously appreciated — for instance, the sunken topography of Thera Macula, a large chaos area, may indicate that Europa is actively resurfacing over a lens comparable in volume to North America's Great Lakes. Europa, the innermost icy satellite of Jupiter, has a tortured young surface 1 , 2 , 3 , 4 and sustains a liquid water ocean 1 , 2 , 3 , 4 , 5 , 6 below an ice shell of highly debated thickness 1 , 2 , 3 , 4 , 5 , 7 , 8 , 9 , 10 . Quasi-circular areas of ice disruption called chaos terrains are unique to Europa, and both their formation and the ice-shell thickness depend on Europa's thermal state 1 , 2 , 3 , 4 , 5 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 . No model so far has been able to explain why features such as Conamara Chaos stand above surrounding terrain and contain matrix domes 10 , 18 . Melt-through of a thin (few-kilometre) shell 3 , 7 , 8 is thermodynamically improbable and cannot raise the ice 10 , 18 . The buoyancy of material rising as either plumes of warm, pure ice called diapirs 1 , 9 , 10 , 11 , 12 , 13 , 14 , 15 or convective cells 16 , 17 in a thick (>10 kilometres) shell is insufficient to produce the observed chaos heights, and no single plume can create matrix domes 10 , 18 . Here we report an analysis of archival data from Europa, guided by processes observed within Earth's subglacial volcanoes and ice shelves. The data suggest that chaos terrains form above liquid water lenses perched within the ice shell as shallow as 3 kilometres. Our results suggest that ice–water interactions and freeze-out give rise to the diverse morphologies and topography of chaos terrains. The sunken topography of Thera Macula indicates that Europa is actively resurfacing over a lens comparable in volume to the Great Lakes in North America.

As the first radiopharmaceutical for Peptide Receptor Radionuclide Therapy (PRRT), Lutathera® was approved by the EMA in 2017 and the FDA in 2018 for the treatment of somatostatin receptor (SSTR) positive gastroenteropancreatic neuroendocrine tumors. Using the concept of PRRT, Lutathera® combines the radionuclide 177Lu with the somatostatin analogue DOTA-TATE, thus delivering ionizing radiation specifically to tumor cells expressing somatostatin receptors. As a result, DNA single- and double-strand breaks are provoked, in case of double-strand breaks leading to cell death of the tumor and its SSTR-positive lesions.

Calendar-dated tree-ring sequences offer an unparalleled resource for high-resolution paleoenvironmental reconstruction. Where such records exist for a few limited geographic regions over the last 8,000 to 12,000 years, they have proved invaluable for creating precise and accurate timelines for past human and environmental interactions. To expand such records across new geographic territory or extend data for certain regions further backward in time, new applications must be developed to secure “floating” (not yet absolutely dated) tree-ring sequences, which cannot be assigned single-calendar year dates by standard dendrochronological techniques. This study develops two approaches to this problem for a critical floating tree-ring chronology from the East Mediterranean Bronze–Iron Age. The chronology is more closely fixed in time using annually resolved patterns of 14C, modulated by cosmic radiation, between 1700 and 1480 BC. This placement is then tested using an anticorrelation between calendardated tree-ring growth responses to climatically effective volcanism in North American bristlecone pine and the Mediterranean trees. Examination of the newly dated Mediterranean tree-ring sequence between 1630 and 1500 BC using X-ray fluorescence revealed an unusual calcium anomaly around 1560 BC. While requiring further replication and analysis, this anomaly merits exploration as a potential marker for the eruption of Thera.

Lung cancer is the leading cancer killer worldwide, imposing grievous challenges for patients and clinicians. The incidence of lung adenocarcinoma (LUAD), the main histologic subtype of lung cancer, is still increasing in current-, ex-, and even non-smokers, whereas its five-year survival rate is approximately 15% as the vast majority of patients usually present with advanced disease at the time of diagnosis. The generation of novel drugs targeting key disease driver mutations has created optimism for the treatment of LUAD, but, as these mutations are not universal, this therapeutic line benefits only a subset of patients. More recently, the advent of targeted immunotherapies and their documented clinical efficacy in many different cancers, including LUAD, have started to change cancer management. Immunotherapies have been developed in order to overcome the cancer’s ability to develop mechanisms of immune resistance, i.e., to adapt to and evade the host inflammatory and immune responses. Identifying a cancer’s immune resistance mechanisms will likely advance the development of personalized immunotherapies. This review examines the key pathways of immune resistance at play in LUAD and explores therapeutic strategies which can unleash potent antitumor immune responses and significantly improve therapeutic efficacy, quality of life, and survival in LUAD.

Diffuse large B-cell lymphoma (DLBCL) is one of the most common types of non-Hodgkin lymphoma in adults. In most of the cases a complete remission is possible to obtain by applying conventional immunochemotherapy (rituximab in combination with cyclophosphamide, doxorubicin, vincristine, methylprednisolone or R-CHOP). Its effect depends on some risk factors, cellular origin of the lymphoma and to some extend – the localization when extranodal involvement is confirmed.We present the case of a patient with DLBCL of small intestine and non-specific clinical manifestation. Following treatment with standard therapy R-CHOP patient fail to achieve disease response and gastrointestinal track (GIT) complications were registered.

Chronic venous disease (CVD) is a multifactorial condition affecting an important percentage of the global population. It ranges from mild clinical signs, such as telangiectasias or reticular veins, to severe manifestations, such as venous ulcerations. However, varicose veins (VVs) are the most common manifestation of CVD. The explicit mechanisms of the disease are not well-understood. It seems that genetics and a plethora of environmental agents play an important role in the development and progression of CVD. The exposure to these factors leads to altered hemodynamics of the venous system, described as ambulatory venous hypertension, therefore promoting microcirculatory changes, inflammatory responses, hypoxia, venous wall remodeling, and epigenetic variations, even with important systemic implications. Thus, a proper clinical management of patients with CVD is essential to prevent potential harms of the disease, which also entails a significant loss of the quality of life in these individuals. Hence, the aim of the present review is to collect the current knowledge of CVD, including its epidemiology, etiology, and risk factors, but emphasizing the pathophysiology and medical care of these patients, including clinical manifestations, diagnosis, and treatments. Furthermore, future directions will also be covered in this work in order to provide potential fields to explore in the context of CVD.

A study of pre-eruptive magmatic processes at a caldera volcano shows that, although such a volcano may have been dormant for a long period, its magma reserves may be replenished in a comparatively very short time and it may move rapidly from a quiescent state to one on the verge of eruption. Foreshadowing 'supervolcano' eruptions Timothy Druitt and co-authors have studied pre-eruptive magmatic processes and their timescales using chemically zoned crystals from the late-1600s BC 'Minoan' caldera-forming eruption on the island of Santorini, Greece. Despite the large volume of erupted magma and the 18,000-year gestation period between the Minoan and the previous major eruption, recharge of the magma reservoir seems to have occurred during the century before eruption, and mixing between different magma batches was still taking place during the final months. These observations have implications for monitoring strategies at long-dormant but potentially active caldera systems, such as Long Valley in California, Yellowstone in Wyoming and Campi Flegrei in Italy. Caldera-forming volcanic eruptions are low-frequency, high-impact events capable of discharging tens to thousands of cubic kilometres of magma explosively on timescales of hours to days, with devastating effects on local and global scales 1 . Because no such eruption has been monitored during its long build-up phase, the precursor phenomena are not well understood. Geophysical signals obtained during recent episodes of unrest at calderas such as Yellowstone, USA, and Campi Flegrei, Italy, are difficult to interpret, and the conditions necessary for large eruptions are poorly constrained 2 , 3 . Here we present a study of pre-eruptive magmatic processes and their timescales using chemically zoned crystals from the ‘Minoan’ caldera-forming eruption of Santorini volcano, Greece 4 , which occurred in the late 1600s bc . The results provide insights into how rapidly large silicic systems may pass from a quiescent state to one on the edge of eruption 5 , 6 . Despite the large volume of erupted magma 4 (40–60 cubic kilometres), and the 18,000-year gestation period between the Minoan eruption and the previous major eruption, most crystals in the Minoan magma record processes that occurred less than about 100 years before the eruption. Recharge of the magma reservoir by large volumes of silicic magma (and some mafic magma) occurred during the century before eruption, and mixing between different silicic magma batches was still taking place during the final months. Final assembly of large silicic magma reservoirs may occur on timescales that are geologically very short by comparison with the preceding repose period, with major growth phases immediately before eruption. These observations have implications for the monitoring of long-dormant, but potentially active, caldera systems.

Lutathera[sup.®] is the first EMA- and FDA-approved radiopharmaceutical for radioligand therapy (RLT). Currently, on the legacy of the NETTER1 trial, only adult patients with progressive unresectable somatostatin receptor (SSTR) positive gastroenteropancreatic (GEP) neuroendocrine neoplasms (NET) can be treated with Lutathera[sup.®] . Conversely, patients with SSTR-positive disease arising from outside the gastroenteric region do not currently have access to Lutathera[sup.®] treatment despite several papers in the literature reporting the effectiveness and safety of RLT in these settings. Moreover, patients with well-differentiated G3 GEP-NET are also still “Lutathera orphans”, and retreatment with RLT in patients with disease relapse is currently not approved. The aim of this critical review is to summarize current literature evidence assessing the role of Lutathera[sup.®] outside the approved indications. Moreover, ongoing clinical trials evaluating new possible applications of Lutathera[sup.®] will be considered and discussed to provide an updated picture of future investigations.

Given the practicality and low cost of using elastic resistance in training for different populations and its effectiveness in a range of outcomes, a comparison with conventional devices could clarify and quantify the benefits provided by both mode. To compare the effects of resistance training with elastic devices (tubes and Thera-Bands) and conventional devices (weight machines and dumbbells) on the outcome muscular strength. A search was performed in the databases PubMed/MEDLINE, EMBASE, PEDro (Physiotherapy Evidence Database), and CENTRAL (Cochrane Central Register of Controlled Trials) from the earliest records up to 20 December 2017. Data were pooled into a meta-analysis and described as standardized mean difference with a 95% confidence interval (registration number: CRD42016042152). Eight studies were included. The results of the meta-analysis demonstrated no superiority between the methods analyzed for upper limb (standardized mean difference = −0.011; 95% confidence interval = −0.40, 0.19; p = 0.48) or lower limb muscular strength (standardized mean difference = 0.09; 95% confidence interval = −0.18, 0.35; p = 0.52). Elastic resistance training is able to promote similar strength gains to conventional resistance training, in different population profiles and using diverse protocols.

Determining calendar ages for radiocarbon dates, or ordered sequences of radiocarbon dates, that intersect with a plateau on the radiocarbon calibration curve can be problematic since, without additional prior constraints, the calendar age ranges determined will tend to spread across the plateau, yielding wide and less than useful calendar age probability densities and age ranges. Where possible, modeling analysis should seek to identify informative priors that act to restrict the otherwise poorly controlled spread of probability across plateaus. Such additional information may be available, among other sources, from the stratigraphy, the context, or the samples themselves. The recent dating of ordered sequences of radiocarbon dates on sections of branches of the same olive ( Olea europaea ) shrub from Therasia (southern Aegean) associated with the Minoan eruption of the Thera (Santorini) volcano (Pearson et al. 2023), which intersect with the plateau in the radiocarbon calibration curve ca. 1620–1540 BC, offers an example of the problem. A re-analysis adding some plausible informative priors offers a substantially better defined likely dating range and different conclusions. Instead of finding an inconclusive probability range “encompassing the late 17th and entire 16th century BC” followed by arguments for “indications of increased probabilities for a mid-16th century BC date for the eruption,” a re-analysis incorporating appropriate informative priors identifies the likely date range as falling between the late 17th to early 16th centuries BC.