Ventilation history of Nordic Seas overflows during the last (de)glacial period revealed by species-specific benthic foraminiferal 14C dates

Formation of deep water in the high-latitude North Atlantic is important for the global meridional ocean circulation, and its variability in the past may have played an important role in regional and global climate change. Here we study ocean circulation associated with the last (de)glacial period, using water-column radiocarbon age reconstructions in the Faroe-Shetland Channel, southeastern Norwegian Sea, and from the Iceland Basin, central North Atlantic. The presence of tephra layer Faroe Marine Ash Zone II, dated to ~26.7 ka, enables us to determine that the middepth (1179 m water depth) and shallow subsurface reservoir ages were ~1500 and 1100 14C years, respectively, older during the late glacial period compared to modern, suggesting substantial suppression of the overturning circulation in the Nordic Seas. During the late Last Glacial Maximum and the onset of deglaciation (~20–18 ka), Nordic Seas overflow was weak but active. During the early deglaciation (~17.5–14.5 ka), our data reveal large differences between 14C ventilation ages that are derived from dating different benthic foraminiferal species: Pyrgo and other miliolid species yield ventilation ages >6000 14C years, while all other species reveal ventilation ages <2000 14C years. These data either suggest subcentennial, regional, circulation changes or that miliolid-based 14C ages are biased due to taphonomic or vital processes. Implications of each interpretation are discussed. Regardless of this “enigma,” the onset of the Bølling-Allerød interstadial (14.5 ka) is clearly marked by an increase in middepth Nordic Seas ventilation and the renewal of a stronger overflow

Path Size Logit route choice models: Issues with current models, a new internally consistent approach, and parameter estimation on a large-scale network with GPS data

Path Size Logit route choice models attempt to capture the correlation between routes by including correction terms within the route utility functions. This provides a convenient closed-form solution for implementation in traffic network models. The path size terms measure distinctiveness of routes; a route is penalised based on the number of other routes sharing its links, and the costs of those shared links. Typically, real road networks have many very long routes that should be considered unrealistic. Such unrealistic routes are problematic for the Path Size Logit (PSL) model because they negatively impact the choice probabilities of realistic routes when links are shared. The Generalised Path Size Logit (GPSL) model attempts to address this problem by weighting the contributions of routes to path size terms according to the ratio of route travel costs. However, the GPSL model is not internally consistent in how it defines routes as being unrealistic: the path size terms consider only travel cost, whereas the route choice probability relation considers disutility including the correction term. To solve these challenges, this paper formulates a new internally consistent Adaptive Path Size Logit (APSL) model wherein routes contribute to path size terms according to the ratio of route choice probabilities, ensuring that routes defined as unrealistic by the path size terms, are exactly those with very low choice probabilities. The APSL route choice probability relation is an implicit function, naturally expressed as a fixed-point problem. A proof is provided for the guaranteed existence of solutions, as well as conditions for the uniqueness of solutions. A Maximum Likelihood Estimation procedure is given for estimating the APSL model with tracked route observation data, and this procedure is investigated in a simulation study where it is shown it is generally possible to reproduce assumed true parameters. APSL is then estimated using real tracked route GPS data on a large-scale network, and results are compared with other PSL models

Update to the study protocol, including statistical analysis plan for a randomized clinical trial comparing comprehensive cardiac rehabilitation after heart valve surgery with control: the CopenHeartVR trial

Comparative StudyRandomized Controlled TrialThis is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: Heart valve diseases are common with an estimated prevalence of 2.5% in the Western world. The number is rising because of an ageing population. Once symptomatic, heart valve diseases are potentially lethal, and heavily influence daily living and quality of life. Surgical treatment, either valve replacement or repair, remains the treatment of choice. However, post-surgery, the transition to daily living may become a physical, mental and social challenge. We hypothesize that a comprehensive cardiac rehabilitation program can improve physical capacity and self-assessed mental health and reduce hospitalization and healthcare costs after heart valve surgery. METHODS: This randomized clinical trial, CopenHeartVR, aims to investigate whether cardiac rehabilitation in addition to usual care is superior to treatment as usual after heart valve surgery. The trial will randomly allocate 210 patients 1:1 to an intervention or a control group, using central randomization, and blinded outcome assessment and statistical analyses. The intervention consists of 12 weeks of physical exercise and a psycho-educational intervention comprising five consultations. The primary outcome is peak oxygen uptake (VO2 peak) measured by cardiopulmonary exercise testing with ventilatory gas analysis. The secondary outcome is self-assessed mental health measured by the standardized questionnaire Short Form-36. Long-term healthcare utilization and mortality as well as biochemistry, echocardiography and cost-benefit will be assessed. A mixed-method design will be used to evaluate qualitative and quantitative findings, encompassing a survey-based study before the trial and a qualitative pre- and post-intervention study. CONCLUSION: This randomized clinical trial will contribute with evidence of whether cardiac rehabilitation should be provided after heart valve surgery. The study is approved by the local regional Research Ethics Committee (H-1-2011-157), and the Danish Data Protection Agency (j.nr. 2007-58-0015). TRIAL REGISTRATION: Trial registered 16 March 2012; ClinicalTrials.gov ( NCT01558765 ).This work is supported by the Strategic Research Council, The Heart Centre Research Foundation Rigshospitalet, Familien Hede Nielsens Fond, The Regional Research Council of Region Sealand (Denmark), The National Institute of Public Health, and the University of Southern Denmark

Formal Subdivision of the Holocene Series/Epoch: A Summary

The Holocene Series/Epoch is the most recent series/epoch in the geological timescale, spanning the interval from 11,700 yr to the present day. Together with the subadjacent Pleistocene, it comprises the Quaternary System/Period. The Holocene record contains diverse geomorphological, biotic, climatological and archaeological evidence, within sequences that are often continuous and extremely well-preserved at decadal, annual and even seasonal resolution. As a consequence, the Holocene is perhaps the most intensively-studied series/epoch within the entire Geological Time Scale. Yet until recently little attention had been paid to a formal subdivision of the Holocene. Here we describe an initiative by the Subcommission on Quaternary Stratigraphy (SQS) of the International Commission on Stratigraphy (ICS) to develop a formal stratigraphical subdivision of the Holocene, with three new stages/ages, two underpinned by Global Boundary Stratotype Sections and Points (GSSPs) in an ice core, and a third in a speleothem. These stages/ages are defined along with their equivalent subseries/subepochs. The new stages/ages are the Greenlandian with its GSSP in the Greenland NGRIP2 ice core and dated at 11,700 yr b2k (before 2000 CE); the NorthGrippian with its GSSP in the Greenland NGRIP1 ice core and dated to 8236 yr b2k; and the Meghalayan, with its GSSP in a speleothem from Mawmluh Cave, northeastern India, with a date of 4250 yr b2k. This subdivision was formally ratified by the Executive Committee of the International Union of Geological Sciences (IUGS) on 14th June 2018.non

Deep Ocean Storage of Heat and CO<inf>2</inf> in the Fram Strait, Arctic Ocean During the Last Glacial Period

Funder: Tromsø Research Foundation : A31720Abstract: The Fram Strait is the only deep gateway between the Arctic Ocean and the Nordic Seas and thus is a key area to study past changes in ocean circulation and the marine carbon cycle. Here, we study deep ocean temperature, δ18O, carbonate chemistry (i.e., carbonate ion concentration [CO32−]), and nutrient content in the Fram Strait during the late glacial (35,000–19,000 years BP) and the Holocene based on benthic foraminiferal geochemistry and carbon cycle modeling. Our results indicate a thickening of Atlantic water penetrating into the northern Nordic Seas, forming a subsurface Atlantic intermediate water layer reaching to at least ∼2,600 m water depth during most of the late glacial period. The recirculating Atlantic layer was characterized by relatively high [CO32−] and low δ13C during the late glacial, and provides evidence for a Nordic Seas source to the glacial North Atlantic intermediate water flowing at 2,000–3,000 m water depth, most likely via the Denmark Strait. In addition, we discuss evidence for enhanced terrestrial carbon input to the Nordic Seas at ∼23.5 ka. Comparing our δ13C and qualitative [CO32−] records with results of carbon cycle box modeling suggests that the total terrestrial CO2 release during this carbon input event was low, slow, or directly to the atmosphere

Increasing thyroid cancer incidence in Lithuania in 1978–2003

BACKGROUND: The aim of this paper is to analyze changes in thyroid cancer incidence trends in Lithuania during the period 1978–2003 using joinpoint regression models, with special attention to the period 1993–2003. METHODS: The study was based on all cases of thyroid cancer reported to the Lithuanian Cancer Registry between 1978 and 2003. Age group-specific rates and standardized rates were calculated for each gender, using the direct method (world standard population). The joinpoint regression model was used to provide estimated annual percentage change and to detect points in time where significant changes in the trends occur. RESULTS: During the study period the age-standardized incidence rates increased in males from 0.7 to 2.5 cases per 100 000 and in females from 1.5 to 11.4 per 100 000. Annual percentage changes during this period in the age-standardized rates were 4.6% and 7.1% for males and females, respectively. Joinpoint analysis showed two time periods with joinpoint in the year 2000. A change in the trend occurred in which a significant increase changed to a dramatic increase in thyroid cancer incidence rates. Papillary carcinoma and stage I thyroid cancer increases over this period were mainly responsible for the pattern of changes in trend in recent years. CONCLUSION: A moderate increase in thyroid cancer incidence has been observed in Lithuania between the years 1978 and 2000. An accelerated increase in thyroid cancer incidence rates took place in the period 2000–2003. It seems that the increase in thyroid cancer incidence can be attributed mainly to the changes in the management of non palpable thyroid nodules with growing applications of ultrasound-guided fine needle aspiration biopsy in clinical practice

Climigration? Population and climate change in Arctic Alaska

Residents of towns and villages in Arctic Alaska live on “the front line of climate change.” Some communities face immediate threats from erosion and flooding associated with thawing permafrost, increasing river flows, and reduced sea ice protection of shorelines. The term climigration, referring to migration caused by climate change, originally was coined for these places. Although initial applications emphasized the need for government relocation policies, it has elsewhere been applied more broadly to encompass unplanned migration as well. Some historical movements have been attributed to climate change, but closer study tends to find multiple causes, making it difficult to quantify the climate contribution. Clearer attribution might come from comparisons of migration rates among places that are similar in most respects, apart from known climatic impacts. We apply this approach using annual 1990–2014 time series on 43 Arctic Alaska towns and villages. Within-community time plots show no indication of enhanced out-migration from the most at-risk communities. More formally, there is no significant difference between net migration rates of at-risk and other places, testing several alternative classifications. Although climigration is not detectable to date, growing risks make either planned or unplanned movements unavoidable in the near future

Functional Analysis of the Two Brassica AP3 Genes Involved in Apetalous and Stamen Carpelloid Phenotypes

The Arabidopsis homeotic genes APETALA3 (AP3) and PISTILLATA (PI) are B genes which encode MADS-box transcription factors and specify petal and stamen identities. In the current study, the stamen carpelloid (SC) mutants, HGMS and AMS, of B. rapa and B. napus were investigated and two types of AP3 genes, B.AP3.a and B.AP3.b, were functional characterized. B.AP3.a and B.AP3.b share high similarity in amino acid sequences except for 8 residues difference located at the C-terminus. Loss of this 8 residues in B.AP3.b led to the change of PI-derived motifs. Meanwhile, B.AP3.a specified petal and stamen development, whereas B.AP3.b only specified stamen development. In B. rapa, the mutations of both genes generated the SC mutant HGMS. In B. napus that contained two B.AP3.a and two B.AP3.b, loss of the two B.AP3.a functions was the key reason for the apetalous mutation, however, the loss-of-function in all four AP3 was related to the SC mutant AMS. We inferred that the 8 residues or the PI-derived motif in AP3 gene probably relates to petal formation

Oral vitamin B12 for patients suspected of subtle cobalamin deficiency: a multicentre pragmatic randomised controlled trial

BACKGROUND: Evidence regarding the effectiveness of oral vitamin B12 in patients with serum vitamin B12 levels between 125-200 pM/l is lacking. We compared the effectiveness of one-month oral vitamin B12 supplementation in patients with a subtle vitamin B12 deficiency to that of a placebo. METHODS: This multicentre (13 general practices, two nursing homes, and one primary care center in western Switzerland), parallel, randomised, controlled, closed-label, observer-blind trial included 50 patients with serum vitamin B12 levels between 125-200 pM/l who were randomized to receive either oral vitamin B12 (1000 μg daily, N = 26) or placebo (N = 24) for four weeks. The institution's pharmacist used simple randomisation to generate a table and allocate treatments. The primary outcome was the change in serum methylmalonic acid (MMA) levels after one month of treatment. Secondary outcomes were changes in total homocysteine and serum vitamin B12 levels. Blood samples were centralised for analysis and adherence to treatment was verified by an electronic device (MEMS; Aardex Europe, Switzerland). Trial registration: ISRCTN 22063938. RESULTS: Baseline characteristics and adherence to treatment were similar in both groups. After one month, one patient in the placebo group was lost to follow-up. Data were evaluated by intention-to-treat analysis. One month of vitamin B12 treatment (N = 26) lowered serum MMA levels by 0.13 μmol/l (95%CI 0.06-0.19) more than the change observed in the placebo group (N = 23). The number of patients needed to treat to detect a metabolic response in MMA after one month was 2.6 (95% CI 1.7-6.4). A significant change was observed for the B12 serum level, but not for the homocysteine level, hematocrit, or mean corpuscular volume. After three months without active treatment (at four months), significant differences in MMA levels were no longer detected. CONCLUSIONS: Oral vitamin B12 treatment normalised the metabolic markers of vitamin B12 deficiency. However, a one-month daily treatment with 1000 μg oral vitamin B12 was not sufficient to normalise the deficiency markers for four months, and treatment had no effect on haematological signs of B12 deficiency

Targeting RNA Polymerase Primary σ70 as a Therapeutic Strategy against Methicillin-Resistant Staphylococcus aureus by Antisense Peptide Nucleic Acid

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) causes threatening infection-related mortality worldwide. Currently, spread of multi-drug resistance (MDR) MRSA limits therapeutic options and requires new approaches to "druggable" target discovery, as well as development of novel MRSA-active antibiotics. RNA polymerase primary σ⁷⁰ (encoded by gene rpoD) is a highly conserved prokaryotic factor essential for transcription initiation in exponentially growing cells of diverse S. aureus, implying potential for antisense inhibition. METHODOLOGY/PRINCIPAL FINDINGS: By synthesizing a serial of cell penetrating peptide conjugated peptide nucleic acids (PPNAs) based on software predicted parameters and further design optimization, we identified a target sequence (234 to 243 nt) within rpoD mRNA conserved region 3.0 being more sensitive to antisense inhibition. A (KFF)₃K peptide conjugated 10-mer complementary PNA (PPNA2332) was developed for potent micromolar-range growth inhibitory effects against four pathogenic S. aureus strains with different resistance phenotypes, including clinical vancomycin-intermediate resistance S. aureus and MDR-MRSA isolates. PPNA2332 showed bacteriocidal antisense effect at 3.2 fold of MIC value against MRSA/VISA Mu50, and its sequence specificity was demonstrated in that PPNA with scrambled PNA sequence (Scr PPNA2332) exhibited no growth inhibitory effect at higher concentrations. Also, PPNA2332 specifically interferes with rpoD mRNA, inhibiting translation of its protein product σ⁷⁰ in a concentration-dependent manner. Full decay of mRNA and suppressed expression of σ⁷⁰ were observed for 40 µM or 12.5 µM PPNA2332 treatment, respectively, but not for 40 µM Scr PPNA2332 treatment in pure culture of MRSA/VISA Mu50 strain. PPNA2332 (≥1 µM) essentially cleared lethal MRSA/VISA Mu50 infection in epithelial cell cultures, and eliminated viable bacterial cells in a time- and concentration- dependent manner, without showing any apparent toxicity at 10 µM. CONCLUSIONS: The present result suggested that RNAP primary σ⁷⁰ is a very promising candidate target for developing novel antisense antibiotic to treat severe MRSA infections