Trackways of the American Crocodile (Crocodylus acutus) in Northwestern Costa Rica: Implications for Crocodylian Ichnology

We documented trackways of free-living Crocodylus acutus on beaches at the mouths of Tamarindo and Ventanas estuaries, Costa Rica. Our crocodiles had estimated total lengths of 1–3 meters or more. Manus prints have five digits, with digits I–III bearing claw marks. Pes prints have four digits, with claw marks on digits I–III. The pes is plantigrade. Claws generally dig into the substrate. Apart from claw marks, digit I and the heel of the pes are usually the most deeply impressed parts of footprints. Trackways are wide-gauge. Pes prints are usually positioned just behind ipsilateral manus prints of the same set and may overlap them. Manus and pes prints angle slightly outward with respect to the crocodile’s direction of movement. Claw-bearing digits of both the manus and pes may create curved, concave-toward-the-midline drag marks as the autopodium is protracted. The tail mark varies in depth and clarity, and in shape from nearly linear to markedly sinuous. Sometimes the tail mark hugs the trackway midline, but sometimes it is closer to, or even cuts across, prints of one side. American crocodile footprints and trackways are similar to those observed in other extant crocodylian species, indicating substantial trackway conservatism across the grou

From error bounds to the complexity of first-order descent methods for convex functions

This paper shows that error bounds can be used as effective tools for deriving complexity results for first-order descent methods in convex minimization. In a first stage, this objective led us to revisit the interplay between error bounds and the Kurdyka-\L ojasiewicz (KL) inequality. One can show the equivalence between the two concepts for convex functions having a moderately flat profile near the set of minimizers (as those of functions with H\"olderian growth). A counterexample shows that the equivalence is no longer true for extremely flat functions. This fact reveals the relevance of an approach based on KL inequality. In a second stage, we show how KL inequalities can in turn be employed to compute new complexity bounds for a wealth of descent methods for convex problems. Our approach is completely original and makes use of a one-dimensional worst-case proximal sequence in the spirit of the famous majorant method of Kantorovich. Our result applies to a very simple abstract scheme that covers a wide class of descent methods. As a byproduct of our study, we also provide new results for the globalization of KL inequalities in the convex framework. Our main results inaugurate a simple methodology: derive an error bound, compute the desingularizing function whenever possible, identify essential constants in the descent method and finally compute the complexity using the one-dimensional worst case proximal sequence. Our method is illustrated through projection methods for feasibility problems, and through the famous iterative shrinkage thresholding algorithm (ISTA), for which we show that the complexity bound is of the form $O(q^{k})$ where the constituents of the bound only depend on error bound constants obtained for an arbitrary least squares objective with $\ell^1$ regularization

Role of liraglutide in Alzheimer's disease pathology

Background The described relationship between Alzheimer's disease (AD) and type 2 diabetes (T2D) and the fact that AD has no succesful treatment has led to the study of antidiabetic drugs that may limit or slow down AD pathology. Main body Although T2D treatment has evident limitations, options are increasing including glucagon-like peptide 1 analogs. Among these, liraglutide (LRGT) is commonly used by T2D patients to improve beta cell function and suppress glucagon to restore normoglycaemia. Interestingly, LRGT also counterbalances altered brain metabolism and has anti-inflammatory properties. Previous studies have reported its capacity to reduce AD pathology, including amyloid production and deposition, tau hyperphosphorylation, or neuronal and synaptic loss in animal models of AD, accompanied by cognitive improvement. Given the beneficial effects of LRGT at central level, studies in patients have been carried out, showing modest beneficial effects. At present, the ELAD trial (Evaluating Liraglutide in Alzheimer's Disease NCT01843075) is an ongoing phase IIb study in patients with mild AD. In this minireview, we resume the outcomes of LRGT treatment in preclinical models of AD as well as the available results in patients up to date. Conclusion The effects of LRGT on animal models show significant benefits in AD pathology and cognitive impairment. While studies in patients are limited, ongoing clinical trials will probably provide more definitive conclusions on the role of LRGT in AD patients

An additional muscle belly of the first lumbrical muscle

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Conservative management versus open reduction and internal fixation for mid-shaft clavicle fractures in adults - The Clavicle Trial: Study protocol for a multicentre randomized controlled trial

Background: Clavicle fractures account for around 4% of all fractures and up to 44% of fractures of the shoulder girdle. Fractures of the middle third (or mid-shaft) account for approximately 80% of all clavicle fractures. Management of this group of fractures is often challenging and the outcome can be unsatisfactory. In particular it is not clear whether surgery produces better outcomes than non-surgical management. Currently there is much variation in the use of surgery and a lack of good quality evidence to inform our decision.Methods/Design: We aim to undertake a multicentre randomised controlled trial evaluating the effectiveness and safety of conservative management versus open reduction and internal fixation for displaced mid-shaft clavicle fractures in adults. Surgical treatment will be performed using the Acumed clavicle fixation system. Conservative management will consist of immobilisation in a sling at the side in internal rotation for 6 weeks or until clinical or radiological union. We aim to recruit 300 patients. These patients will be followed-up for at least 9 months. The primary endpoint will be the rate of non-union at 3 months following treatment. Secondary endpoints will be limb function measured using the Constant-Murley Score and the Disabilities of the Arm, Shoulder and Hand (DASH) Score at 3 and 9 months post-operatively.Discussion: This article presents the protocol for a multicentre randomised controlled trial. It gives extensive details of, and the basis for, the chosen methods, and describes the key measures taken to avoid bias and to ensure validity.Trial Registration: United Kingdom Clinical Research Network ID: 8665. The date of registration of the trial is 07/09/2006. The date the first patient was recruited is 18/12/2007. © 2011 Longo et al; licensee BioMed Central Ltd

Key clinical benefits of neuroimaging at 7 T

The growing interest in ultra-high field MRI, with more than 35.000 MR examinations already performed at 7 T, is related to improved clinical results with regard to morphological as well as functional and metabolic capabilities. Since the signal-to-noise ratio increases with the field strength of the MR scanner, the most evident application at 7 T is to gain higher spatial resolution in the brain compared to 3 T. Of specific clinical interest for neuro applications is the cerebral cortex at 7 T, for the detection of changes in cortical structure, like the visualization of cortical microinfarcts and cortical plaques in Multiple Sclerosis. In imaging of the hippocampus, even subfields of the internal hippocampal anatomy and pathology may be visualized with excellent spatial resolution. Using Susceptibility Weighted Imaging, the plaque-vessel relationship and iron accumulations in Multiple Sclerosis can be visualized, which may provide a prognostic factor of disease. Vascular imaging is a highly promising field for 7 T which is dealt with in a separate dedicated article in this special issue. The static and dynamic blood oxygenation level-dependent contrast also increases with the field strength, which significantly improves the accuracy of pre-surgical evaluation of vital brain areas before tumor removal. Improvement in acquisition and hardware technology have also resulted in an increasing number of MR spectroscopic imaging studies in patients at 7 T. More recent parallel imaging and short-TR acquisition approaches have overcome the limitations of scan time and spatial resolution, thereby allowing imaging matrix sizes of up to 128×128. The benefits of these acquisition approaches for investigation of brain tumors and Multiple Sclerosis have been shown recently. Together, these possibilities demonstrate the feasibility and advantages of conducting routine diagnostic imaging and clinical research at 7 T

The 1999 international emergency humanitarian evacuation of the Kosovars to Canada: A qualitative study of service providers' perspectives at the international, national and local levels

BACKGROUND: In response to the Kosovo crisis, Canada received 5,500 Albanian Kosovar refugees in 1999 as part of the emergency humanitarian evacuation and settlement effort. This study attempts to describe the experiences of service providers at the international, national, and local levels, involved in the organization and delivery of health and settlement services in Canada for the Kosovar refugees. METHODS: A qualitative case study design using key informant interviews was used. Nominated sampling was used to identify 17 individuals involved in the organization and delivery of health and settlement. Key themes were identified and recommendations made to provide a framework for the development of policy to guide response to future humanitarian emergencies. RESULTS: Six themes emerged: (1) A sense of being overwhelmed, (2) A multitude of health issues, (3) critical challenges in providing health care, (4) access to health and settlement services, (5) overall successes and (6) need for a coordinated approach to migration health. CONCLUSIONS: For those involved, the experience was overwhelming but rewarding. Interviewees' major concerns were the need for a more comprehensive and coordinated approach to the flow of medical information and handling of specific health problems

Electrophysiological Heterogeneity of Fast-Spiking Interneurons: Chandelier versus Basket Cells

In the prefrontal cortex, parvalbumin-positive inhibitory neurons play a prominent role in the neural circuitry that subserves working memory, and alterations in these neurons contribute to the pathophysiology of schizophrenia. Two morphologically distinct classes of parvalbumin neurons that target the perisomatic region of pyramidal neurons, chandelier cells (ChCs) and basket cells (BCs), are generally thought to have the same "fast-spiking" phenotype, which is characterized by a short action potential and high frequency firing without adaptation. However, findings from studies in different species suggest that certain electrophysiological membrane properties might differ between these two cell classes. In this study, we assessed the physiological heterogeneity of fast-spiking interneurons as a function of two factors: species (macaque monkey vs. rat) and morphology (chandelier vs. basket). We showed previously that electrophysiological membrane properties of BCs differ between these two species. Here, for the first time, we report differences in ChCs membrane properties between monkey and rat. We also found that a number of membrane properties differentiate ChCs from BCs. Some of these differences were species-independent (e.g., fast and medium afterhyperpolarization, firing frequency, and depolarizing sag), whereas the differences in the first spike latency between ChCs and BCs were species-specific. Our findings indicate that different combinations of electrophysiological membrane properties distinguish ChCs from BCs in rodents and primates. Such electrophysiological differences between ChCs and BCs likely contribute to their distinctive roles in cortical circuitry in each species. © 2013 Povysheva et al

KeV Warm Dark Matter and Composite Neutrinos

Elementary keV sterile Dirac neutrinos can be a natural ingredient of the composite neutrino scenario. For a certain class of composite neutrino theories, these sterile neutrinos naturally have the appropriate mixing angles to be resonantly produced warm dark matter (WDM). Alternatively, we show these sterile neutrinos can be WDM produced by an entropy-diluted thermal freeze-out, with the necessary entropy production arising not from an out-of-equilibrium decay, but rather from the confinement of the composite neutrino sector, provided there is sufficient supercooling.Comment: 12 pages, 2 figures, published versio

Hedgehog pathway mutations drive oncogenic transformation in high-risk T-cell acute lymphoblastic leukemia.

The role of Hedgehog signaling in normal and malignant T-cell development is controversial. Recently, Hedgehog pathway mutations have been described in T-ALL, but whether mutational activation of Hedgehog signaling drives T-cell transformation is unknown, hindering the rationale for therapeutic intervention. Here, we show that Hedgehog pathway mutations predict chemotherapy resistance in human T-ALL, and drive oncogenic transformation in a zebrafish model of the disease. We found Hedgehog pathway mutations in 16% of 109 childhood T-ALL cases, most commonly affecting its negative regulator PTCH1. Hedgehog mutations were associated with resistance to induction chemotherapy (P = 0.009). Transduction of wild-type PTCH1 into PTCH1-mutant T-ALL cells induced apoptosis (P = 0.005), a phenotype that was reversed by downstream Hedgehog pathway activation (P = 0.007). Transduction of most mutant PTCH1, SUFU, and GLI alleles into mammalian cells induced aberrant regulation of Hedgehog signaling, indicating that these mutations are pathogenic. Using a CRISPR/Cas9 system for lineage-restricted gene disruption in transgenic zebrafish, we found that ptch1 mutations accelerated the onset of notch1-induced T-ALL (P = 0.0001), and pharmacologic Hedgehog pathway inhibition had therapeutic activity. Thus, Hedgehog-activating mutations are driver oncogenic alterations in high-risk T-ALL, providing a molecular rationale for targeted therapy in this disease