Impact of iceberg melting on Mediterranean thermohaline circulation during Heinrich events

Down-core samples of planktonic and benthic foraminifera were analyzed for oxygen and carbon isotopes in International Marine Past Global Changes Study (IMAGES) core MD99-2343 in order to study the interactions between climate change in the Northern Hemisphere and the western Mediterranean thermohaline circulation at times of Heinrich events (HE). Our results confirm the antiphase correlation between enhanced North Atlantic Deep Water formation and low ventilation in the Mediterranean. However, this study reveals that this antiphase relationship in deepwater formation between the North Atlantic and Mediterranean was interrupted during times of HE when the injection of large volumes of water from melting icebergs reached the entrance to the Mediterranean. These events, which lasted less than 1000 years, are represented by pronounced decreases in both planktonic d18O and benthic d13C signals. Lower salinities of Mediterranean surface water resulted in a slowdown of western Mediterranean deepwater overturn even though cold sea surface temperatures and drier climate should have resulted in enhanced deepwater formation

A notable proportion of liver transplant candidates with alcohol-related cirrhosis can be delisted because of clinical improvement

Background & Aims To what extent patients with alcohol-related decompensated cirrhosis can improve until recovery from decompensation remains unclear. We aimed to investigate the probability of recovery and delisting due to improvement in patients with alcohol-related decompensated cirrhosis on the waiting list (WL) for liver transplantation (LT). Methods We conducted a registry-based, multicenter, retrospective study including all patients admitted to the LT WL in Catalonia (Spain) with the indication of alcohol-, HCV-, cholestasis- or non-alcoholic steatohepatitis-related decompensated cirrhosis between January 2007 and December 2018. Competing-risk analysis was used to investigate variables associated with delisting due to improvement in patients with alcohol-related decompensated cirrhosis. Criteria for delisting after improvement were not predefined. Outcomes of patients after delisting were also studied. Results One-thousand and one patients were included, 420 (37%) with alcohol-related decompensated cirrhosis. Thirty-six (8.6%) patients with alcohol-related decompensated cirrhosis were delisted after improvement at a median time of 29 months after WL admission. Lower model for end-stage liver disease (MELD) score, higher platelets and either female sex or lower height were independently associated with delisting due to improvement, while time of abstinence did not reach statistical significance in multivariate analysis (p = 0.055). Five years after delisting, the cumulative probability of remaining free from liver-related death or LT was 76%, similar to patients with HCV-related decompensated cirrhosis delisted after improvement. Conclusions A significant proportion of LT candidates with alcohol-related cirrhosis can be delisted due to improvement, which is predicted by low MELD score and higher platelet count at WL admission. Women also have a higher probability of being delisted after improvement, partially due to reduced early access to LT for height discrepancies. Early identification of patients with potential for improvement may avoid unnecessary transplants. Lay summary Patients with alcohol-related cirrhosis can improve until being delisted in approximately 9% of cases. Low model for end-stage liver disease score and high platelet levels at admission predict delisting after improvement, and women have higher probabilities of being delisted due to improvement. Long-term outcomes after delisting are generally favorable

Effect of ABCB1 and ABCC3 Polymorphisms on Osteosarcoma Survival after Chemotherapy: A Pharmacogenetic Study

Standard treatment for osteosarcoma patients consists of a combination of cisplatin, adriamycin, and methotrexate before surgical resection of the primary tumour, followed by postoperative chemotherapy including vincristine and cyclophosphamide. Unfortunately, many patients still relapse or suffer adverse events. We examined whether common germline polymorphisms in chemotherapeutic transporter and metabolic pathway genes of the drugs used in standard osteosarcoma treatment may predict treatment response. METHODOLOGY/PRINCIPAL FINDINGS: In this study we screened 102 osteosarcoma patients for 346 Single Nucleotide Polymorphisms (SNPs) and 2 Copy Number Variants (CNVs) in 24 genes involved in the metabolism or transport of cisplatin, adriamycin, methotrexate, vincristine, and cyclophosphamide. We studied the association of the genotypes with tumour response and overall survival. We found that four SNPs in two ATP-binding cassette genes were significantly associated with overall survival: rs4148416 in ABCC3 (per-allele HR = 8.14, 95%CI = 2.73-20.2, p-value = 5.1x10(-)(5)), and three SNPs in ABCB1, rs4148737 (per-allele HR = 3.66, 95%CI = 1.85-6.11, p-value = 6.9x10(-)(5)), rs1128503 and rs10276036 (r(2) = 1, per-allele HR = 0.24, 95%CI = 0.11-0.47 p-value = 7.9x10(-)(5)). Associations with these SNPs remained statistically significant after correction for multiple testing (all corrected p-values [permutation test] </= 0.03). CONCLUSIONS: Our findings suggest that these polymorphisms may affect osteosarcoma treatment efficacy. If these associations are independently validated, these variants could be used as genetic predictors of clinical outcome in the treatment of osteosarcoma, helping in the design of individualized therapy

Registro de la variabilidad climática de escala milenaria durante el último cliclo glaciar en los sedimentos de la cuenca Argelo-Balear

bulk element composition and grain-size distribution to characterize the temporal evolution of the terrigenous input to this area throughout the last 50 ka. The high-resolution elementary profiles show high frequency oscillations, particularly of Si, Ti and K contents, associated with terrigenous input variability. These fluctuations mark significant changes in the source areas and/or in the nature of transport and sedimentation processes most likely related to abrupt changes in oceanographic and atmospheric conditions. The Menorca core records were compared with the geochemical results of a previously studied core from the Alboran Sea, from where it became obvious a similar behaviour in some of the terrigeneous elements at both core locations. The obtained records vary with a clear Dansgaard-Oeschger periodicity reaching higher values during the North Atlantic's Heinrich Events. These results evidence the presence of a millennial-scale synchronous pattern in the Western Mediterranean in terms of deposition of terrigenous material. In addition, grain-size analyses of Menorca core reveal rhythmic episodes of coarser particle inputs during the Holocene likely related to shifts in the intensity of deep-water currents

Impact of iceberg melting on Mediterranean thermohaline circulation during Heinrich events

Down-core samples of planktonic and benthic foraminifera were analyzed for oxygen and carbon isotopes in International Marine Past Global Changes Study (IMAGES) core MD99-2343 in order to study the interactions between climate change in the Northern Hemisphere and the western Mediterranean thermohaline circulation at times of Heinrich events (HE). Our results confirm the antiphase correlation between enhanced North Atlantic Deep Water formation and low ventilation in the Mediterranean. However, this study reveals that this antiphase relationship in deepwater formation between the North Atlantic and Mediterranean was interrupted during times of HE when the injection of large volumes of water from melting icebergs reached the entrance to the Mediterranean. These events, which lasted less than 1000 years, are represented by pronounced decreases in both planktonic d18O and benthic d13C signals. Lower salinities of Mediterranean surface water resulted in a slowdown of western Mediterranean deepwater overturn even though cold sea surface temperatures and drier climate should have resulted in enhanced deepwater formation

Trends in Outcomes for Neonates Born Very Preterm and Very Low Birth Weight in 11 High-Income Countries

OBJECTIVE: To evaluate outcome trends of neonates born very preterm in 11 high-income countries participating in the International Network for Evaluating Outcomes of neonates. STUDY DESIGN: In a retrospective cohort study, we included 154 233 neonates admitted to 529 neonatal units between January 1, 2007, and December 31, 2015, at 24(0/7) to 31(6/7) weeks of gestational age and birth weight <1500 g. Composite outcomes were in-hospital mortality or any of severe neurologic injury, treated retinopathy of prematurity, and bronchopulmonary dysplasia (BPD); and same composite outcome excluding BPD. Secondary outcomes were mortality and individual morbidities. For each country, annual outcome trends and adjusted relative risks comparing epoch 2 (2012-2015) to epoch 1 (2007-2011) were analyzed. RESULTS: For composite outcome including BPD, the trend decreased in Canada and Israel but increased in Australia and New Zealand, Japan, Spain, Sweden, and the United Kingdom. For composite outcome excluding BPD, the trend decreased in all countries except Spain, Sweden, Tuscany, and the United Kingdom. The risk of composite outcome was lower in epoch 2 than epoch 1 in Canada (adjusted relative risks 0.78; 95% CI 0.74-0.82) only. The risk of composite outcome excluding BPD was significantly lower in epoch 2 compared with epoch 1 in Australia and New Zealand, Canada, Finland, Japan, and Switzerland. Mortality rates reduced in most countries in epoch 2. BPD rates increased significantly in all countries except Canada, Israel, Finland, and Tuscany. CONCLUSIONS: In most countries, mortality decreased whereas BPD increased for neonates born very preterm

The International Network for Evaluating Outcomes (iNeo) of neonates: evolution, progress and opportunities

Neonates born very preterm (before 32 weeks’ gestational age), are a significant public health concern because of their high-risk of mortality and life-long disability. In addition, caring for very preterm neonates can be expensive, both during their initial hospitalization and their long-term cost of permanent impairments. To address these issues, national and regional neonatal networks around the world collect and analyse data from their constituents to identify trends in outcomes, and conduct benchmarking, audit and research. Improving neonatal outcomes and reducing health care costs is a global problem that can be addressed using collaborative approaches to assess practice variation between countries, conduct research and implement evidence-based practices. The International Network for Evaluating Outcomes (iNeo) of neonates was established in 2013 with the goal of improving outcomes for very preterm neonates through international collaboration and comparisons. To date, 10 national or regional population-based neonatal networks/datasets participate in iNeo collaboration. The initiative now includes data on >200,000 very preterm neonates and has conducted important epidemiological studies evaluating outcomes, variations and trends. The collaboration has also surveyed >320 neonatal units worldwide to learn about variations in practices, healthcare service delivery, and physical, environmental and manpower related factors and support services for parents. The iNeo collaboration serves as a strong international platform for Neonatal-Perinatal health services research that facilitates international data sharing, capacity building, and global efforts to improve very preterm neonate care