bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-Dose Micafungin for Preterm Neonates and Infants with Invasive and Central Nervous System Candidiasis
Authors: Auriti Cinzia , Falcone Marco , Ronchetti Maria Paola , Goffredo Bianca Maria , Cairoli Sara , Crisafulli Rosamaria , Piersigilli Fiammetta , Corsetti Tiziana , Dotta Andrea , Pai Manjunath P. 
Published: October 2016

ABSTRACT

High doses of micafungin are advocated in neonates with systemic candidiasis, but limited pharmacokinetic (PK) and safety data are available to support their use. Eighteen preterm neonates and infants with systemic candidiasis, three of whom had meningitis, were treated for at least 14 days with 8 to 15 mg/kg of body weight/day of intravenous micafungin. Plasma micafungin concentrations (four measurements for each patient) were determined after the third dose, and the cerebrospinal fluid (CSF) micafungin concentrations in three patients were also obtained. Population PK analyses were used to identify the optimal model, and the model was further validated using external data (
n
= 5). The safety of micafungin was assessed by measurement of the levels of liver and kidney function biomarkers. The mean age and weight at the initiation of treatment were 2.33 months (standard deviation [SD], 1.98 months) and 3.24 kg (SD, 1.61 kg), respectively. The optimal PK model was one that scaled plasma clearance to weight and the transaminase concentration ratio. The CSF of three patients was sampled, and the observed concentrations were between 0.80 and 1.80 mg/liter. The model-predicted mean micafungin area under the concentration-time curve over 24 h was 336 mg · h/liter (SD, 165 mg · h/liter) with the 10-mg/kg/day dosage. Eighteen of the 23 subjects (78.2%) had clinical resolution of their infection, but 5 had neurologic impairments. Among the transaminases, alkaline phosphatase measurements were significantly higher posttreatment, with a geometric mean ratio of 1.17 (90% confidence interval, 1.01, 1.37). Furthermore, marked elevations in the gamma-glutamyltransferase (GGT) level were observed in three patients treated with 10- to 15-mg/kg/day doses, and improvement of the GGT level was noted after a dose reduction. Higher weight-based doses of micafungin were generally well tolerated in neonates and infants and achieved pharmacokinetic profiles predictive of an effect.
Tropical circulation intensification and tectonic extension recorded by Neogene terrestrial δ18O records of the western United States
Authors: Feng Ran , Poulsen Christopher J. , Werner Martin 
Published: October 2016

Abstract
Terrestrial water isotope records preserve a history of hydrological cycling that is influenced by past climate and surface topography. δ18O and δD records from authigenic minerals of the western United States display a long-term increase during the Neogene in the vicinity of the Sierra Nevada and the central Rocky Mountains (Rockies), but a smaller increase or decrease in the northern Great Basin. Interpretations of these isotopic trends require quantitative estimates of the influence of climatic and environmental changes on δ18O and δD of soil water. Here we use a coupled atmosphere-land model with water-isotopologue tracking capabilities, ECHAM5-JSBACH-wiso, to simulate precipitation and δ18O responses to elevation-independent changes in Neogene geography, equator to pole temperature gradient (EPGRAD), grassland expansion, and tropical Pacific sea surface temperatures. Both precipitation and soil water δ18O (δ18Osw) respond strongly to Neogene strengthening of the EPGRAD, but weakly to other forcings. An increase in EPGRAD leads to significant drying and 18O enrichment (3‰–5‰) of soil water over the northern Sierra Nevada and central Rockies as a result of Hadley circulation strengthening and enhanced coastal subtropical subsidence. These large-scale circulation changes reduce inland moisture transport from the Pacific Ocean and Gulf of Mexico. Our simulated δ18Osw responses could explain 50%–100% of the proxy δ18O increases over the Sierra Nevada and central Rockies, suggesting that climate change rather than surface subsidence may have been the dominant climate signal in δ18O records in these regions. On the contrary, δ18O responses to climate changes are small in the Great Basin, indicating that the observed δ18O increase over this region was likely a direct response to surface subsidence with elevation losses of 1–1.5 km. Adding this elevation loss to current Great Basin elevations reveals the former existence of a uniformly high plateau extending from the Sierra Nevada to the central Rockies prior to Neogene extension. This revised elevation history brings Neogene δ18O and δD paleoaltimetry of the western United States in accordance with independent lines of structural evidence and early Cenozoic elevation reconstructions.
Giant landslides and highstands of the Caspian Sea
Authors: Pánek Tomáš , Korup Oliver , Minár Jozef , Hradecký Jan 
Published: October 2016

Abstract
The history of Quaternary sea-level changes in the Caspian Sea, the world’s largest lake, is partly enigmatic, and so is the geomorphic response of its coasts. Late Pleistocene transgressions during the Early Khvalynian (ca. 40–25 ka) inundated extensive portions of the flat, low-lying semi-desert of western Kazakhstan. Cliffs cut during these highstands form a prominent escarpment tens of kilometers to several hundred kilometers from the present coast of the Caspian Sea. Satellite images, digital terrain analysis, and field mapping reveal that &gt;300 giant landslides intersect with this escarpment. More than 100 of these slope failures mobilized volumes &gt;108 m3 along basal failure planes with gradients as low as ∼5°. All landslides share characteristics of lateral rock spreads involving competent limestones overlying weak and plastic claystones. From relative stratigraphy and new 14C data, we infer that catastrophic slope failure of over 41 km3 occurred mostly during Pleistocene Caspian sea-level highstands, while several landslides may have been reactivated or entirely originated during the Holocene. This largest cluster of terrestrial mass wasting in a tectonically quiescent setting offers an opportunity to understand how landslides erode low-relief landscapes subject to oscillating sea levels.
Integrated geochemical-petrographic insights from component-selective δ238U of Cryogenian marine carbonates
Authors: Hood Ashleigh v.S. , Planavsky Noah J. , Wallace Malcolm W. , Wang Xiangli , Bellefroid Eric J. , Gueguen Bleuenn , Cole Devon B. 
Published: October 2016

Abstract
Emerging geochemical proxies have improved our understanding of the broad-scale history of Earth’s oxygenation. However, paleoredox work does not always include extensive consideration of sample preservation and paleoenvironmental setting. This is particularly an issue with marine carbonates, which although being potentially ideal ocean redox archives, are commonly altered during diagenesis. Here we provide new insight into the robustness of uranium isotopes (238U/235U ratios: δ238U values) as paleoredox tracers by determining texture-specific δ238U values from a well-described Cryogenian (Balcanoona) reef complex in South Australia. We found high variability in δ238U values between different carbonate components, even within a single sample. Petrographically, the best-preserved components from the Balcanoona reef are marine cements, which have a mean δ238U value of −0.23‰, essentially unfractionated from riverine inputs. These values are interpreted as reflecting a marine system with widespread anoxic and iron-rich settings. Less-well-preserved phases have δ238U values spanning almost the entire extent of the documented isotopic range. This integrated petrographic-geochemical work demonstrates the need for petrographic analysis and careful sample selection on a case-by-case basis in future carbonate metal isotope geochemistry.
Unraveling alteration histories in serpentinites and associated ultramafic rocks with magnetite (U-Th)/He geochronology
Authors: Cooperdock Emily H.G. , Stockli Daniel F. 
Published: October 2016

Abstract
Serpentinization is a widespread process that affects large-scale geodynamic processes along plate boundaries, including continental breakup, seafloor spreading, and subduction. Documenting the timing of serpentinization is critical for our understanding of these processes, but direct dating of serpentinites has been challenging or impossible. We present the first application of magnetite (U-Th)/He chronometry to date stages of alteration and cooling in ultramafic rocks. In order to demonstrate the viability of magnetite He dating in these lithologies, magnetite ages were obtained from two ultramafic lithologies of the Kampos mélange belt, a high-pressure–low-temperature subduction complex on the island of Syros, Greece. Magnetite (U-Th)/He measurements of internal fragments from large grains within a chlorite schist and a serpentinite record Miocene exhumation-related cooling ages, whereas smaller grains from the serpentinite record mineral growth associated with hydrothermal fluid flow along Pliocene normal faults. These age results with magnetite trace element geochemistry reveal evidence for multiple episodes of fluid-rock alteration, which has implications for the cooling history and local geochemical exchanges of this high-pressure–low-temperature terrane. This method provides a new tool that may be expanded to investigate the processes and time scales of serpentinization from a variety of tectonic settings.
Effects of Myofascial Trigger Point Dry Needling in Patients with Sleep Bruxism and Temporomandibular Disorders: A Prospective Case Series
Authors: Blasco-Bonora Paloma María , Martín-Pintado-Zugasti Aitor 
Published: October 2016

Objectives To investigate the effects of deep dry needling (DN) of myofascial trigger points (MTrPs) of the masseter and temporalis on pain, pressure pain threshold (PPT), pain-free maximal jaw opening and temporomandibular disorder (TMD)-related disability in patients with sleep bruxism (SB) and myofascial TMD. Methods Seventeen subjects (11 women, 6 men) aged 39±13 years (range 23–66) diagnosed with SB and myofascial TMD were invited to participate in this prospective case series study. Each subject received a deep DN intervention in the masseter and temporalis MTrPs. Pain intensity, PPT, pain-free maximal jaw opening and TMD-related disability were assessed before treatment, immediately after treatment and at 1-week follow-up. Jaw disability was assessed using the jaw disability checklist (JDC) at baseline and 1 week post-treatment only. Results One-way analyses of variance showed significant improvements in pain intensity, PPT and jaw opening (p<0.001). Post-hoc analysis revealed significant differences between baseline and post-intervention follow-up time points in pain (immediate: Cohen's d=1.72, p<0.001; 1 week: d=3.24, p<0.001), jaw opening (immediate: d=0.77, p<0.001; 1 week: d=1.02, p<0.001) and PPT in the masseter (immediate: d=1.02, p<0.001; 1 week: d=1.64, p<0.001) and temporalis (immediate: d=0.91, p=0.006; 1 week: d=1.8, p<0.001). A dependent t-test showed a significant improvement in jaw functioning, reflected by a large reduction in 1-week JDC scores relative to baseline (d=3.15, p<0.001). Conclusions Deep DN of active MTrPs in the masseter and temporalis in patients with myofascial TMD and SB was associated with immediate and 1-week improvements in pain, sensitivity, jaw opening and TMD-related disability. Trial registration number Results.
The relationships between golf and health: a scoping review
Authors: Murray A D , Daines L , Archibald D , Hawkes R A , Schiphorst C , Kelly P , Grant L , Mutrie N 
Published: October 2016

ObjectiveTo assess the relationships between golf and health.DesignScoping review.Data sourcesPublished and unpublished reports of any age or language, identified by searching electronic databases, platforms, reference lists, websites and from consulting experts.Review methodsA 3-step search strategy identified relevant published primary and secondary studies as well as grey literature. Identified studies were screened for final inclusion. Data were extracted using a standardised tool, to form (1) a descriptive analysis and (2) a thematic summary.Results and discussion4944 records were identified with an initial search. 301 studies met criteria for the scoping review. Golf can provide moderate intensity physical activity and is associated with physical health benefits that include improved cardiovascular, respiratory and metabolic profiles, and improved wellness. There is limited evidence related to golf and mental health. The incidence of golfing injury is moderate, with back injuries the most frequent. Accidental head injuries are rare, but can have serious consequences.ConclusionsPractitioners and policymakers can be encouraged to support more people to play golf, due to associated improved physical health and mental well-being, and a potential contribution to increased life expectancy. Injuries and illnesses associated with golf have been identified, and risk reduction strategies are warranted. Further research priorities include systematic reviews to further explore the cause and effect nature of the relationships described. Research characterising golf's contribution to muscular strengthening, balance and falls prevention as well as further assessing the associations and effects between golf and mental health are also indicated.
Large-scale survey of rates of achieving targets for blood glucose, blood pressure, and lipids and prevalence of complications in type 2 diabetes (JDDM 40)
Authors: Yokoyama Hiroki , Oishi Mariko , Takamura Hiroshi , Yamasaki Katsuya , Shirabe Shin-ichiro , Uchida Daigaku , Sugimoto Hidekatsu , Kurihara Yoshio , Araki Shin-ichi , Maegawa Hiroshi 
Published: October 2016

ObjectiveThe fact that population with type 2 diabetes mellitus and bodyweight of patients are increasing but diabetes care is improving makes it important to explore the up-to-date rates of achieving treatment targets and prevalence of complications. We investigated the prevalence of microvascular/macrovascular complications and rates of achieving treatment targets through a large-scale multicenter-based cohort.Research design and methodsA cross-sectional nationwide survey was performed on 9956 subjects with type 2 diabetes mellitus who consecutively attended primary care clinics. The prevalence of nephropathy, retinopathy, neuropathy, and macrovascular complications and rates of achieving targets of glycated hemoglobin (HbA1c) <7.0%, blood pressure <130/80 mm Hg, and lipids of low-density/high-density lipoprotein cholesterol <3.1/≥1.0 mmol/L and non-high-density lipoprotein cholesterol <3.8 mmol/L were investigated.ResultsThe rates of achieving targets for HbA1c, blood pressure, and lipids were 52.9%, 46.8% and 65.5%, respectively. The prevalence of microvascular complications was ∼28% each, 6.4% of which had all microvascular complications, while that of macrovascular complications was 12.6%. With an increasing duration of diabetes, the rate of achieving target HbA1c decreased and the prevalence of each complication increased despite increased use of diabetes medication. The prevalence of each complication decreased according to the number achieving the 3 treatment targets and was lower in subjects without macrovascular complications than those with. Adjustments for considerable covariates exhibited that each complication was closely inter-related, and the achievement of each target was significantly associated with being free of each complication.ConclusionsAlmost half of the subjects examined did not meet the recommended targets. The risk of each complication was significantly affected by 1 on-target treatment (inversely) and the concomitance of another complication (directly). Total diabetes care including one-by-one management of modifiable risk factors and complications may be important for high-quality care. The future studies including more subjects and clinics with precise complication status are needed.
Improving the well-being of men by Evaluating and Addressing the Gastrointestinal Late Effects (EAGLE) of radical treatment for prostate cancer: study protocol for a mixed-method implementation project
Authors: Taylor Sophia , Demeyin Weyinmi , Muls Ann , Ferguson Catherine , Farnell Damian J J , Cohen David , Andreyev Jervoise , Green John , Smith Lesley , Ahmedzai Sam , Pickett Sara , Nelson Annmarie , Staffurth John 
Published: October 2016

IntroductionRadiotherapy treatment for prostate cancer can cause bowel problems, which may lead to severe difficulties for cancer survivors including limiting travel, work or socialising. These symptoms can appear at any time following radiotherapy. This study focuses on the early identification and protocol-based management of effects known to cause long-term, or even permanent, changes to the well-being of prostate cancer survivors. The rationale of this study is to improve the care offered to men and their families following pelvic radiotherapy for prostate cancer.Method and analysisImplementation research methodology will be used to adopt a multicomponent intervention at three UK centres. The intervention package comprises a standardised clinical assessment of relevant symptoms in oncology outpatient clinics and rapid referral to an enhanced gastroenterological service for patients identified with bowel problems. Gastroenterology staff will be trained to use an expert-practice algorithm of targeted gastroenterology investigations and treatments. The evaluation of the intervention and its embedding within local practices will be conducted using a mixed-methods design. The effect of the new service will be measured in terms of the following outcomes: acceptability to staff and patients; quality of life; symptom control and cost-effectiveness. Data collection will take place at baseline, 6 months (±2 months), and 12 months (±2 months) after entry into the study.Ethics and disseminationThe study has ethical approval from the North West-Liverpool East Research Ethics Committee and the appropriate NHS governance clearance. All participants provide written informed consent. The study team aim to publish the results of the study in peer-reviewed journals as well as at national and international conferences.Trial registration numberUKCRN16974
Stability of gas measures under perturbations and discretizations
Authors: Fernández Roberto , Groisman Pablo , Saglietti Santiago 
Published: October 2016

For a general class of gas models — which includes discrete and continuous Gibbsian models as well as contour or polymer ensembles — we determine a diluteness condition that implies: (1) uniqueness of the infinite-volume equilibrium measure; (2) stability of this measure under perturbations of parameters and discretization schemes, and (3) existence of a coupled perfect-simulation scheme for the infinite-volume measure together with its perturbations and discretizations. Some of these results have previously been obtained through methods based on cluster expansions. In contrast, our treatment is purely probabilistic and its diluteness condition is weaker than existing convergence conditions for cluster expansions.
The Dual Syk/JAK Inhibitor Cerdulatinib Antagonizes B-cell Receptor and Microenvironmental Signaling in Chronic Lymphocytic Leukemia
Authors: Blunt Matthew D. , Koehrer Stefan , Dobson Rachel C. , Larrayoz Marta , Wilmore Sarah , Hayman Alice , Parnell Jack , Smith Lindsay D. , Davies Andrew , Johnson Peter W.M. , Conley Pamela B. , Pandey Anjali , Strefford Jonathan C. , Stevenson Freda K. , Packham Graham , Forconi Francesco , Coffey Greg P. , Burger Jan A. , Steele Andrew J. 
Published: October 2016

Abstract
Purpose: B-cell receptor (BCR)–associated kinase inhibitors, such as ibrutinib, have revolutionized the treatment of chronic lymphocytic leukemia (CLL). However, these agents are not curative, and resistance is already emerging in a proportion of patients. IL4, expressed in CLL lymph nodes, can augment BCR signaling and reduce the effectiveness of BCR kinase inhibitors. Therefore, simultaneous targeting of the IL4- and BCR signaling pathways by cerdulatinib, a novel dual Syk/JAK inhibitor currently in clinical trials (NCT01994382), may improve treatment responses in patients.
Experimental Design: PBMCs from patients with CLL were treated in vitro with cerdulatinib alone or in combination with venetoclax. Cell death, chemokine, and cell signaling assay were performed and analyzed by flow cytometry, immunoblotting, q-PCR, and ELISA as indicated.
Results: At concentrations achievable in patients, cerdulatinib inhibited BCR- and IL4-induced downstream signaling in CLL cells using multiple readouts and prevented anti-IgM- and nurse-like cell (NLC)–mediated CCL3/CCL4 production. Cerdulatinib induced apoptosis of CLL cells, in a time- and concentration-dependent manner, and particularly in IGHV-unmutated samples with greater BCR signaling capacity and response to IL4, or samples expressing higher levels of sIgM, CD49d+, or ZAP70+. Cerdulatinib overcame anti-IgM, IL4/CD40L, or NLC-mediated protection by preventing upregulation of MCL-1 and BCL-XL; however, BCL-2 expression was unaffected. Furthermore, in samples treated with IL4/CD40L, cerdulatinib synergized with venetoclax in vitro to induce greater apoptosis than either drug alone.
Conclusions: Cerdulatinib is a promising therapeutic for the treatment of CLL either alone or in combination with venetoclax, with the potential to target critical survival pathways in this currently incurable disease. Clin Cancer Res; 23(9); 2313–24. ©2016 AACR.
The Death and Lives of hitchBOT: The Design and Implementation of a Hitchhiking Robot
Authors: Smith David Harris , Zeller Frauke 
Published: October 2016

Abstract
In the early morning hours of 1 August 2015, as it waited for its next ride on a Philly park bench, unknown assailants destroyed hitchBOT. Arms torn from its body, legs broken, gutted of its electronics, it was left discarded in a park, minus its smiley-face LED head. Around the world headlines announced the death of a much-loved robot, children and adults shed tears, haters hated on Philadelphia, cartoonists and musicians paid tribute, journalists wrote obituaries and the publicly minded rallied to support a rebuild. The authors share the story of the life and times of their creation, hitchBOT the hitchhiking robot.