Lithostratigraphy of the Cretaceous–Paleocene Nuussuaq Group, Nuussuaq Basin, West Greenland

The Nuussuaq Basin is the only exposed Cretaceous–Paleocene sedimentary basin in West Greenland and is one of a complex of linked rift basins stretching from the Labrador Sea to northern Baffin Bay. These basins developed along West Greenland as a result of the opening of the Labrador Sea in Late Mesozoic to Early Cenozoic times. The Nuussuaq Basin is exposed in West Greenland between 69°N and 72°N on Disko, Nuussuaq, Upernivik Ø, Qeqertarsuaq, Itsaku and Svartenhuk Halvø and has also been recorded in a number of shallow and deep wells in the region. The sediments are assigned to the more than 6 km thick Nuussuaq Group (new) which underlies the Palaeogene plateau basalts of the West Greenland Basalt Group. The sediment thickness is best estimated from seismic data; in the western part of the area, seismic and magnetic data suggest that the succession is at least 6 km and possibly as much as 10 km thick. The exposed Albian–Paleocene part of the succession testifies to two main episodes of regional rifting and basin development: an Early Cretaceous and a Late Cretaceous – Early Paleocene episode prior to the start of sea-floor spreading in mid-Paleocene time. This exposed section includes fan delta, fluviodeltaic, shelfal and deep marine deposits. The Nuussuaq Group is divided into ten formations, most of which have previously been only briefly described, with the exception of their macrofossil content. In ascending stratigraphic order, the formations are: the Kome Formation, the Slibestensfjeldet Formation (new), the Upernivik Næs Formation, the Atane Formation (including four new members – the Skansen, Ravn Kløft, Kingittoq and Qilakitsoq Members – and one new bed, the Itivnera Bed), the Itilli Formation (new, including four new members, the Anariartorfik, Umiivik, Kussinerujuk and Aaffarsuaq Members), the Kangilia Formation (including the redefined Annertuneq Conglomerate Member and the new Oyster–Ammonite Conglomerate Bed), the Quikavsak Formation (including three new members: the Tupaasat, Nuuk Qiterleq and Paatuutkløften Members), the Agatdal Formation, the Eqalulik Formation (new, including the Abraham Member), and the Atanikerluk Formation (including five members: the Naujât, Akunneq (new), Pingu (new), Umiussat and Assoq (new) Members)

A Look at the Generalized Heron Problem through the Lens of Majorization-Minimization

In a recent issue of this journal, Mordukhovich et al.\ pose and solve an interesting non-differentiable generalization of the Heron problem in the framework of modern convex analysis. In the generalized Heron problem one is given $k+1$ closed convex sets in \Real^d equipped with its Euclidean norm and asked to find the point in the last set such that the sum of the distances to the first $k$ sets is minimal. In later work the authors generalize the Heron problem even further, relax its convexity assumptions, study its theoretical properties, and pursue subgradient algorithms for solving the convex case. Here, we revisit the original problem solely from the numerical perspective. By exploiting the majorization-minimization (MM) principle of computational statistics and rudimentary techniques from differential calculus, we are able to construct a very fast algorithm for solving the Euclidean version of the generalized Heron problem.Comment: 21 pages, 3 figure

An in Vivo Mouse Model to Investigate the Effect of Local Anesthetic Nanomedicines on Axonal Conduction and Excitability

Peripheral nerve blocks (PNBs) using local anesthetic (LA) are superior to systemic analgesia for management of post-operative pain. An insufficiently short PNB duration following single-shot LA can be optimized by development of extended release formulations among which liposomes have been shown to be the least toxic. In vivo rodent models for PNB have focused primarily on assessing behavioral responses following LA. In a previous study in human volunteers, we found that it is feasible to monitor the effect of LA in vivo by combining conventional conduction studies with nerve excitability studies. Here, we aimed to develop a mouse model where the same neurophysiological techniques can be used to investigate liposomal formulations of LA in vivo. To challenge the validity of the model, we tested the motor PNB following an unilamellar liposomal formulation, filled with the intermediate-duration LA lidocaine. Experiments were carried out in adult transgenic mice with fluorescent axons and with fluorescent tagged liposomes to allow in vivo imaging by probe-based confocal laser endomicroscopy. Recovery of conduction following LA injection at the ankle was monitored by stimulation of the tibial nerve fibers at the sciatic notch and recording of the plantar compound motor action potential (CMAP). We detected a delayed recovery in CMAP amplitude following liposomal lidocaine, without detrimental systemic effects. Furthermore, CMAP threshold-tracking studies of the distal tibial nerve showed that the increased rheobase was associated with a sequence of excitability changes similar to those found following non-encapsulated lidocaine PNB in humans, further supporting the translational value of the model

A computational analysis of lower bounds for big bucket production planning problems

In this paper, we analyze a variety of approaches to obtain lower bounds for multi-level production planning problems with big bucket capacities, i.e., problems in which multiple items compete for the same resources. We give an extensive survey of both known and new methods, and also establish relationships between some of these methods that, to our knowledge, have not been presented before. As will be highlighted, understanding the substructures of difficult problems provide crucial insights on why these problems are hard to solve, and this is addressed by a thorough analysis in the paper. We conclude with computational results on a variety of widely used test sets, and a discussion of future research

Benefit of pazopanib in advanced gastrointestinal stromal tumours : results from a phase II trial (SSG XXI, PAGIST)

Background: Patients with advanced gastrointestinal stromal tumours (GISTs) resistant to the tyrosine kinase inhibitors imatinib and sunitinib may be treated with regorafenib, which resulted in a median progression-free survival (PFS) of 4.8 months in the GRID trial. Also, pazopanib, another tyrosine kinase inhibitor, has been studied in a randomized, placebo-controlled trial (PAZOGIST) in the third line, which showed a PFS of 45.2% 4 months after study entry, but patients intolerant to sunitinib were also included. We designed another trial evaluating pazopanib, enrolling only patients with progression on both imatinib and sunitinib. Patients and methods: Since all eligible patients had progressive disease, we preferred a non-randomized, phase II multicentre trial so that all patients could receive a potentially active drug. Patients had a progressive metastatic or locally advanced GIST and were >= 18 years of age, with a performance status of 0-2, and sufficient organ functions. The primary endpoint was disease control rate (defined as complete remission thorn partial remission thorn stable disease) at 12 weeks on pazopanib. A Simon's two-stage analysis was used with an interim analysis 12 weeks after enrollment of the first 22 patients, and if passed, there was a full enrolment of 72 patients. GIST mutational analysis was done, and most patients had pazopanib plasma concentration measured after 12 weeks. Results: Seventy-two patients were enrolled. The disease control rate after 12 weeks was 44%, and the median PFS was 19.6 weeks (95% confidence interval 12.6-23.4 weeks). Pazopanib-related toxicity was moderate and manageable. No statistically significant differences were found related to mutations. Plasma concentrations of pazopanib had a formal but weak correlation with outcome. Conclusion: Pazopanib given in the third line to patients with GIST progressing on both imatinib and sunitinib was beneficial for about half of the patients. The PAGIST trial confirms the results from the PAZOGIST trial, and the median PFS achieved seems comparable to the PFS achieved with regorafenib in the third-line setting.Peer reviewe

The pattern-recognition molecule H-ficolin in relation to diabetic kidney disease, mortality, and cardiovascular events in type 1 diabetes

H-ficolin recognizes patterns on microorganisms and stressed cells and can activate the lectin pathway of the complement system. We aimed to assess H-ficolin in relation to the progression of diabetic kidney disease (DKD), all-cause mortality, diabetes-related mortality, and cardiovascular events. Event rates per 10-unit H-ficolin-increase were compared in an observational follow-up of 2,410 individuals with type 1 diabetes from the FinnDiane Study. DKD progression occurred in 400 individuals. The unadjusted hazard ratio (HR) for progression was 1.29 (1.18-1.40) and 1.16 (1.05-1.29) after adjustment for diabetes duration, sex, HbA(1c), systolic blood pressure, and smoking status. After adding triglycerides to the model, the HR decreased to 1.07 (0.97-1.18). In all, 486 individuals died, including 268 deaths of cardiovascular causes and 192 deaths of complications to diabetes. HRs for all-cause mortality and cardiovascular mortality were 1.13 (1.04-1.22) and 1.05 (0.93-1.17), respectively, in unadjusted analyses. These estimates lost statistical significance in adjusted models. However, the unadjusted HR for diabetes-related mortality was 1.19 (1.05-1.35) and 1.18 (1.02-1.37) with the most stringent adjustment level. Our results, therefore, indicate that H-ficolin predicts diabetes-related mortality, but neither all-cause mortality nor fatal/non-fatal cardiovascular events. Furthermore, H-ficolin is associated with DKD progression, however, not independently of the fully adjusted model.Peer reviewe

Mixed integer programming in production planning with backlogging and setup carryover : modeling and algorithms

This paper proposes a mixed integer programming formulation for modeling the capacitated multi-level lot sizing problem with both backlogging and setup carryover. Based on the model formulation, a progressive time-oriented decomposition heuristic framework is then proposed, where improvement and construction heuristics are effectively combined, therefore efficiently avoiding the weaknesses associated with the one-time decisions made by other classical time-oriented decomposition algorithms. Computational results show that the proposed optimization framework provides competitive solutions within a reasonable time