bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contrasting signals of positive selection in genes involved in human skin-color variation from tests based on SNP scans and resequencing
Authors: de Gruijter Johanna Maria , Lao Oscar , Vermeulen Mark , Xue Yali , Woodwark Cara , Gillson Christopher J , Coffey Alison J , Ayub Qasim , Mehdi S Qasim , Kayser Manfred , Tyler-Smith Chris 
Published: December 2011

Abstract

Background
Numerous genome-wide scans conducted by genotyping previously ascertained single-nucleotide polymorphisms (SNPs) have provided candidate signatures for positive selection in various regions of the human genome, including in genes involved in pigmentation traits. However, it is unclear how well the signatures discovered by such haplotype-based test statistics can be reproduced in tests based on full resequencing data. Four genes (oculocutaneous albinism II (OCA2), tyrosinase-related protein 1 (TYRP1), dopachrome tautomerase (DCT), and KIT ligand (KITLG)) implicated in human skin-color variation, have shown evidence for positive selection in Europeans and East Asians in previous SNP-scan data. In the current study, we resequenced 4.7 to 6.7 kb of DNA from each of these genes in Africans, Europeans, East Asians, and South Asians.

Results
Applying all commonly used neutrality-test statistics for allele frequency distribution to the newly generated sequence data provided conflicting results regarding evidence for positive selection. Previous haplotype-based findings could not be clearly confirmed. Although some tests were marginally significant for some populations and genes, none of them were significant after multiple-testing correction. Combined P values for each gene-population pair did not improve these results. Application of Approximate Bayesian Computation Markov chain Monte Carlo based to these sequence data using a simple forward simulator revealed broad posterior distributions of the selective parameters for all four genes, providing no support for positive selection. However, when we applied this approach to published sequence data on SLC45A2, another human pigmentation candidate gene, we could readily confirm evidence for positive selection, as previously detected with sequence-based and some haplotype-based tests.

Conclusions
Overall, our data indicate that even genes that are strong biological candidates for positive selection and show reproducible signatures of positive selection in SNP scans do not always show the same replicability of selection signals in other tests, which should be considered in future studies on detecting positive selection in genetic data.
Women with knee osteoarthritis have more pain and poorer function than men, but similar physical activity prior to total knee replacement
Authors: Tonelli Shalome M , Rakel Barbara A , Cooper Nicholas A , Angstom Whitney L , Sluka Kathleen A 
Published: December 2011

Abstract

Background
Osteoarthritis of the knee is a major clinical problem affecting a greater proportion of women than men. Women generally report higher pain intensity at rest and greater perceived functional deficits than men. Women also perform worse than men on function measures such as the 6-minute walk and timed up and go tests. Differences in pain sensitivity, pain during function, psychosocial variables, and physical activity levels are unclear. Further the ability of various biopsychosocial variables to explain physical activity, function and pain is unknown.

Methods
This study examined differences in pain, pain sensitivity, function, psychosocial variables, and physical activity between women and men with knee osteoarthritis (N = 208) immediately prior to total knee arthroplasty. We assessed: (1) pain using self-report measures and a numerical rating scale at rest and during functional tasks, (2) pain sensitivity using quantitative sensory measures, (3) function with self-report measures and specific function tasks (timed walk, maximal active flexion and extension), (4) psychosocial measures (depression, anxiety, catastrophizing, and social support), and (5) physical activity using accelerometry. The ability of these mixed variables to explain physical activity, function and pain was assessed using regression analysis.

Results
Our findings showed significant differences on pain intensity, pain sensitivity, and function tasks, but not on psychosocial measures or physical activity. Women had significantly worse pain and more impaired function than men. Their levels of depression, anxiety, pain catastrophizing, social support, and physical activity, however, did not differ significantly. Factors explaining differences in (1) pain during movement (during gait speed test) were pain at rest, knee extension, state anxiety, and pressure pain threshold; (2) function (gait speed test) were sex, age, knee extension, knee flexion opioid medications, pain duration, pain catastrophizing, body mass index (BMI), and heat pain threshold; and (3) physical activity (average metabolic equivalent tasks (METS)/day) were BMI, age, Short-Form 36 (SF-36) Physical Function, Kellgren-Lawrence osteoarthritis grade, depression, and Knee Injury and Osteoarthritis Outcome Score (KOOS) pain subscale.

Conclusions
Women continue to be as physically active as men prior to total knee replacement even though they have significantly more pain, greater pain sensitivity, poorer perceived function, and more impairment on specific functional tasks.
Dystrophin deficiency exacerbates skeletal muscle pathology in dysferlin-null mice
Authors: Han Renzhi , Rader Erik P , Levy Jennifer R , Bansal Dimple , Campbell Kevin P 
Published: December 2011

Abstract

Background
Mutations in the genes coding for either dystrophin or dysferlin cause distinct forms of muscular dystrophy. Dystrophin links the cytoskeleton to the sarcolemma through direct interaction with β-dystroglycan. This link extends to the extracellular matrix by β-dystroglycan's interaction with α-dystroglycan, which binds extracellular matrix proteins, including laminin α2, agrin and perlecan, that possess laminin globular domains. The absence of dystrophin disrupts this link, leading to compromised muscle sarcolemmal integrity. Dysferlin, on the other hand, plays an important role in the Ca2+-dependent membrane repair of damaged sarcolemma in skeletal muscle. Because dysferlin and dystrophin play different roles in maintaining muscle cell integrity, we hypothesized that disrupting sarcolemmal integrity with dystrophin deficiency would exacerbate the pathology in dysferlin-null mice and allow further characterization of the role of dysferlin in skeletal muscle.

Methods
To test our hypothesis, we generated dystrophin/dysferlin double-knockout (DKO) mice by breeding mdx mice with dysferlin-null mice and analyzed the effects of a combined deficiency of dysferlin and dystrophin on muscle pathology and sarcolemmal integrity.

Results
The DKO mice exhibited more severe muscle pathology than either mdx mice or dysferlin-null mice, and, importantly, the onset of the muscle pathology occurred much earlier than it did in dysferlin-deficient mice. The DKO mice showed muscle pathology of various skeletal muscles, including the mandible muscles, as well as a greater number of regenerating muscle fibers, higher serum creatine kinase levels and elevated Evans blue dye uptake into skeletal muscles. Lengthening contractions caused similar force deficits, regardless of dysferlin expression. However, the rate of force recovery within 45 minutes following lengthening contractions was hampered in DKO muscles compared to mdx muscles or dysferlin-null muscles, suggesting that dysferlin is required for the initial recovery from lengthening contraction-induced muscle injury of the dystrophin-glycoprotein complex-compromised muscles.

Conclusions
The results of our study suggest that dysferlin-mediated membrane repair helps to limit the dystrophic changes in dystrophin-deficient skeletal muscle. Dystrophin deficiency unmasks the function of dysferlin in membrane repair during lengthening contractions. Dystrophin/dysferlin-deficient mice provide a very useful model with which to evaluate the effectiveness of therapies designed to treat dysferlin deficiency.
Severe metabolic or mixed acidemia on intensive care unit admission: incidence, prognosis and administration of buffer therapy. a prospective, multiple-center study
Authors: Jung Boris , Rimmele Thomas , Le Goff Charlotte , Chanques Gérald , Corne Philippe , Jonquet Olivier , Muller Laurent , Lefrant Jean-Yves , Guervilly Christophe , Papazian Laurent , Allaouchiche Bernard , Jaber Samir ,   The AzuRea Group
Published: December 2011

Abstract
Introduction
In this study, we sought describe the incidence and outcomes of severe metabolic or mixed acidemia in critically ill patients as well as the use of sodium bicarbonate therapy to treat these illnesses.

Methods
We conducted a prospective, observational, multiple-center study. Consecutive patients who presented with severe acidemia, defined herein as plasma pH below 7.20, were screened. The incidence, sodium bicarbonate prescription and outcomes of either metabolic or mixed severe acidemia were analyzed.

Results
Among 2, 550 critically ill patients, 200 (8%) presented with severe acidemia, and 155 (6% of the total admissions) met the inclusion criteria. Almost all patients needed mechanical ventilation and vasopressors during their ICU stay, and 20% of them required renal replacement therapy within the first 24 hours of their ICU stay. Severe metabolic or mixed acidemia was associated with a mortality rate of 57% in the ICU. Delay of acidemia recovery as opposed to initial pH value was associated with increased mortality in the ICU. The type of acidemia did not influence the decision to administer sodium bicarbonate.

Conclusions
The incidence of severe metabolic or mixed acidemia in critically ill patients was 6% in the present study, and it was associated with a 57% mortality rate in the ICU. In contradistinction with the initial acid-base parameters, the rapidity of acidemia recovery was an independent risk factor for mortality. Sodium bicarbonate prescription was very heterogeneous between ICUs. Further studies assessing specific treatments may be of interest in this population.
Presence of tobramycin in blood and urine during selective decontamination of the digestive tract in critically ill patients, a prospective cohort study
Authors: Oudemans-van Straaten Heleen M , Endeman Henrik , Bosman Robert J , Attema-de Jonge Milly E , van Ogtrop Marc L , Zandstra Durk F , Franssen Eric JF 
Published: December 2011

Abstract
Introduction
Tobramycin is one of the components used for selective decontamination of the digestive tract (SDD), applied to prevent colonization and subsequent infections in critically ill patients. Tobramycin is administered in the oropharynx and gastrointestinal tract and is normally not absorbed. However, critical illness may convey gut barrier failure. The aim of the study was to assess the prevalence and amount of tobramycin leakage from the gut into the blood, to quantify tobramycin excretion in urine, and to determine the association of tobramycin leakage with markers of circulation, kidney function and other organ failure.

Methods
This was a prospective observational cohort study. The setting was the 20-bed closed format-mixed ICU of a teaching hospital. The study population was critically ill patients with an expected stay of more than two days, receiving SDD with tobramycin, polymyxin-E and amphotericin-B four times daily in the oropharynx and stomach. Tobramycin concentration was measured in serum (sensitive high performance liquid chromatography - mass spectrometry/mass spectrometry (HLPC-MS/MS) assay) and 24-hour urine (conventional immunoassay), in 34 patients, 24 hours after ICU admission, and in 71 patients, once daily for 7 days. Tobramycin leakage was defined as tobramycin detected in serum at least once (> 0.05 mg/L). Ototoxicity was not monitored.

Results
Of the 100 patients with available blood samples, 83 had tobramycin leakage. Median highest serum concentration for each patient was 0.12 mg/L; 99% of the patients had at least one positive urinary sample (> 0.5 mg/L), 49% had a urinary concentration ≥ 1 mg/L. The highest tobramycin serum concentration was significantly associated with vasopressor support, renal and hepatic dysfunction, and C-reactive protein. At binary logistic regression analysis, high dopamine dose and low urinary output on Day 1 were the significant predictors of tobramycin leakage. Nephrotoxicity could not be shown.

Conclusions
The majority of acute critically ill patients treated with enteral tobramycin as a component of SDD had traces of tobramycin in the blood, especially those with severe shock, inflammation and subsequent acute kidney injury, suggesting loss of gut barrier and decreased renal removal. Unexpectedly, urinary tobramycin was above the therapeutic trough level in half of the patients. Nephrotoxicity could not be demonstrated.
Contrast-induced nephropathy: controlled study by differential GFR measurement in hospitalized patients
Authors: Erselcan Taner , Egilmez Hulusi , Hasbek Zekiye , Tandogan Izzet 
Published: December 2011

Background Without appropriate control measures, contrast-induced nephropathy (CIN) incidence has been claimed to be overestimated. Purpose To evaluate the relationship and the difference between differential serum creatinine (DsCr), which is currently surrogating as a marker of CIN, and measured differential GFR values as a control measure (DGFR) in hospitalized patients. Material and Methods GFR was measured two times by Tc-99m DTPA, before and 48 h after contrast media (CM), along with sCr and BUN in 35 inpatients (22 men, 13 women, mean age ± SD = 61 ± 14) with no known chronic kidney disease. Results Relationship was moderate between GFR and sCr (R = 0.50, P < 0.01) in the study population. Pre-CM vs. post-CM values of GFR, sCr and BUN were not statistically different as (mean ± SD); 78 ± 36 vs. 73 ± 35 mL/min/1.73m2, 0.95 ± 0.26 vs. 0.94 ± 0.26 mg/dl and 21 ± 16 vs. 19 ± 13 mg/dl, respectively, in the study group. According to basal GFR values, 14 patients (40%) seemed carrying risk of CIN (GFR < 60 mL/min/1.73m2) in whom only two had sCr >1.5 mg/dl. Twenty-five patients (71%) had discordant results in relation to DsCr and DGFR and two of them had CIN according to classical definition of DsCr, although having basal sCr <1.1 mg/dl. Yet, both had low, but stable GFR values. None of patient from the study group underwent hemodialysis. Conclusion Significant discordance was observed between differential serum creatinine and measured differential GFR in hospitalized patients, suggesting that CIN incidence calculations only based on hospital registry may carry risk of error.
Dynamic splinting for paediatric contracture reduction of the upper limb
Authors: Menzes Melissa , Willis F Buck 
Published: December 2011

Background This report is based on a case of ‘shaken baby syndrome,’ and clinical manifestations of this injury often include hypertonicity, spasticity and joint contracture. Shaken baby syndrome affects over 1 million children and resembles symptoms of traumatic brain injury. Methods The patient was a five-year-old boy who had suffered a traumatic brain injury with right spastic hemiplegia. Over the course of treatment, multiple modalities were used to manage his tone, spasticity and to reduce wrist and elbow contractures, which included Botox® (Allergan Co., Irvine, CA, USA), manual therapy and dynamic splinting as home therapy. The main outcome measured was change in maximal range of motion(s) (ROMs) in the elbow and wrist. Results After dynamic splinting was initiated, the child's passive ROM increased by 65° in wrist extension and 45° in elbow extension. Ulnar deviation progressed by 15–30°. Conclusion Dynamic splinting contributed over 900 hours of end-range, home therapy for wrist extension and 700 hours in end-range home therapy for elbow extension. It is hypothesized that this prolonged duration of passive stretching at the end-range is responsible for the substantial gains in ROM.
Outcrop Characterization of an Early Miocene Slope Fan System, Chelif Basin, Algeria
Authors: Zhang Yuanfu , Jiang Zaixing 
Published: December 2011

The study on outcrop characterization is very useful for geologists and oil finders. There is a complex slope fan system of early Miocene in Chelif Basin. We divided the superimposed basin into two main development stages: an expanding rifting stage (early Miocene) and depression-extrusion transition stage. Comparison of the outcrops with typical subsurface data sets (logs, core, and seismic reflection data) provided criteria for a detailed study of the stratigraphic and lithologic features of the slope fan system. Based on these research methods, a sedimentary model was built. The slope fan system was an integrated series comprising two parts, the lower (S1) and the upper (S2), from the sequence stratigraphy study. S1 was progradational but had both rolling transport and gravity transport attributes. Similar to the Bouma sequence, S1 can be divided into four parts, A, B, C and D, from bottom to top. S2 was retrogradational but comprised four internal-progradational cycles. Some layers comprise planar-laminated and climbing-ripple–laminated sandstone with many fossils. The upper part of S2 was a thick marl bed and an obvious flooding surface. Each part had different lithofacies and sedimentary interpretations. Some formations could be good reservoirs based on both self-attributes and outer properties. Considerable evidence suggested that the slope fan have great hydrocarbon potential.
Absolute and Relative Kinetic Changes of High-Sensitivity Cardiac Troponin T in Acute Coronary Syndrome and in Patients with Increased Troponin in the Absence of Acute Coronary Syndrome
Authors: Mueller Matthias , Biener Moritz , Vafaie Mehrshad , Doerr Susanne , Keller Till , Blankenberg Stefan , Katus Hugo A , Giannitsis Evangelos 
Published: December 2011

Abstract

BACKGROUND
We evaluated kinetic changes of high-sensitivity cardiac troponin T (hs-cTnT) in patients with acute coronary syndrome (ACS) and patients with hs-cTnT increases not due to ACS to rule in or rule out non–ST-segment elevation myocardial infarction (STEMI).

METHODS
hs-cTnT was measured serially in consecutive patients presenting to the emergency department. Patients with ACS who had at least 2 hs-cTnT measurements within 6 h and non-ACS patients with hs-cTnT concentrations above the 99th percentile value (14 ng/L) were enrolled to compare absolute and relative kinetic changes of hs-cTnT.

RESULTS
For discrimination of non-STEMI (n = 165) in the entire study population (n = 784), the absolute δ change with the ROC-optimized value of 9.2 ng/L yielded an area under the curve of 0.898 and was superior to all relative δ changes (P &lt; 0.0001). The positive predictive value for the absolute δ change was 48.7%, whereas the negative predictive value was 96.5%. In a specific ACS population with exclusion of STEMI (n = 342), the absolute δ change with the ROC-optimized value of 6.9 ng/L yielded a positive predictive value of 82.8% and a negative predictive value of 93.0%. In comparison to the ≥20% relative δ change, the ROC-optimized absolute δ change demonstrated a significantly added value for the entire study population and for the ACS cohort (net reclassification index 0.331 and 0.499, P &lt; 0.0001).

CONCLUSIONS
Absolute δ changes appear superior to relative δ changes in discriminating non-STEMI. A rise or fall of at least 9.2 ng/L in the entire study population and 6.9 ng/L in selected ACS patients seems adequate to rule-out non-STEMI. However, δ-values are useful to rule-in non-STEMI only in a specific ACS population.
Hybrides Steuerungs- und Regelungskonzept für das hochautomatisierte Fahren auf Autobahnen
Authors: Ardelt Michael , Waldmann Peter 
Published: December 2011

Zusammenfassung
Es wird eine neuartige hybride Systemarchitektur für kontinuierliche Steuerungs- und Regelungssysteme mit diskreten Entscheidungsfindungsprozessen vorgestellt. Die Funktionsweise wird beispielhaft für das hochautomatisierte Fahren auf Autobahnen und den Nothalteassistenten dargestellt. Da für einen zukünftigen Einsatz derartiger Systeme deren Robustheit entscheidend ist, wurde diese bei der Entwicklung des Ansatzes in den Mittelpunkt gestellt.
Mehrgrößenregelung mit Entkopplung von Banddicke und Bandplanheit in 20-Rollen-Kaltwalzwerken
Authors: Polzer Jan , Jelali Mohieddine 
Published: December 2011

Zusammenfassung
Die Produktion von Edelstahlfeinblech erfolgt meist an 20-Rollenwalzenwerken. Diese stellen komplexe und totzeitbehaftete Mehrgrößensysteme dar, bei denen Banddicke und Bandplanheit als wichtigste Qualitätsmerkmale in optimaler Weise geregelt werden müssen. Dabei ist die gegenseitige Kopplung zwischen den beiden Qualitätsgrößen, insbesondere bei festen und dünnen Bändern, zu berücksichtigen. Dieser Beitrag stellt eine integrierte Dicken- und Planheitsregelung basiert auf einem umfassenden Reglerentwurf vor, der die Querkopplungen zwischen beiden Regelgrößen berücksichtigt und kompensiert. Es handelt sich um eine Mehrgrößenregelung mit Entkopplung, wobei die Reglerparameter mit Hilfe der Online-Linearisierung eines physikalisch basierten Gerüstmodells adaptiert werden. Der Einsatz der Regelung an einem industriellen Sendzimir-Gerüst zeigt, dass alle Stellglieder mit maximaler Geschwindigkeit von der Regelung betätigt werden dürfen, ohne dass (wie bisher) negative Auswirkungen auf die jeweils andere Qualitätsgröße auftreten.
Zur regelungsorientierten Ableitung von Takagi-Sugeno-Modellen
Authors: Kroll Andreas 
Published: December 2011

Zusammenfassung
Die Erstellung und Bewertung von Modellen orientiert sich i. d. R. am Prädiktionsfehler oder an der Approximationsgüte — unabhängig vom Einsatzzweck eines Modells. Dies liegt an den üblichen Methoden sowie daran, dass Modellbildung und Reglerentwurf häufig von unterschiedlichen Spezialisten durchgeführt werden. Da selten ein exaktes Modell erstellt werden kann, sollten die Freiheitsgrade bei der Modellbildung genutzt werden, um ein für die geplante Anwendung optimiertes Modell zu erhalten. Beim modellbasierten Reglerentwurf ist die Prädiktionsgüte eines Modells kein primäres Kriterium; vielmehr sollte das Modell gut für den Reglerentwurf geeignet sein. Diese Einsicht führte im Bereich der linearen Systemidentifikation zu neuen Methoden. In diesem Beitrag wird eine Methodik zur Ableitung regelungsorientierter Takagi-Sugeno-Fuzzy-Modelle aus physikalischen Modellen vorgestellt und am Benchmark-Beispiel des inversen Pendels demonstriert.
Control Design for Generalized Platoon Problems
Authors: Maschuw Jan P. , Diab Hilal , Abel Dirk , Kowalewski Stefan 
Published: December 2011

Abstract
This paper presents a generalized description of linear transport processes that allows for a derivation of common dynamic properties and a control layout for a wide set of applications. Based on the introduction of the system description of platoons and a proposition of suitable performance criteria a control layout is formulated which reduces the synchronization of a common motion of sub-systems to a stabilization problem of the platoon and optimizes the corresponding performance measures. Furthermore, the influence of communication topology and switching information access among platoon members is investigated. The proposed approach is applied to a vehicle platoon with one leading and three following vehicles and is analyzed through both simulations and physical experiments with model scale vehicles. The results show that the approach is also applicable to physical plants that can only be approximated by a linear platoon model.