bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene therapy for monogenic disorders of the bone marrow
Authors: Ghosh Sujal , Thrasher Adrian J. , Gaspar H. Bobby 
Published: June 2015

SummaryEx‐vivo gene transfer of autologous haematopoietic stem cells in patients with monogenic diseases of the bone marrow has emerged as a new therapeutic approach, mainly in patients lacking a suitable donor for transplant. The encouraging results of initial clinical trials of gene therapy for primary immunodeficiencies were tempered by the occurrence of genotoxicity in a number of patients. Over the last decade, safer viral vectors have been developed to overcome the risk of insertional mutagenesis and have led to impressive clinical outcomes with considerably improved safety. We review the efforts in specific immunodeficiencies including adenosine deaminase deficiency, X‐linked severe combined immunodeficiency, chronic granulomatous disease and Wiskott Aldrich syndrome. Major recent progress has also been made in haemoglobinopathies, such as beta‐thalassaemia, sickle cell disease and Fanconi anaemia, and also specific lysosomal storage diseases, which, although not strictly bone marrow specific conditions, have been effectively treated by bone marrow‐based treatment. The success of these recent studies and the advent of new technologies, such as gene editing, suggest that gene therapy could become a more generally applied treatment modality for a number of haematopoietic disorders.
Survival of childhood acute lymphoid leukaemia in Yorkshire by clinical trial era, 1990–2011
Authors: van Laar Marlous , Kinsey Sally E. , Feltbower Richard G. 
Published: June 2015

SummaryGender‐specific differences in survival by clinical trial era in Yorkshire were assessed for children with acute lymphoid leukaemia (ALL) enrolled onto UKALLXI, ALL97/99 or UKALL2003 (n = 630; 1990–2011). For males, there was a non‐significant improvement in survival for ALL97/99 [hazard ratio (HR) = 0·77; 95% confidence interval (CI) 0·43–1·42) and a significant improvement for UKALL2003 (HR = 0·50; 95%CI 0·25–0·99) compared to UKALLXI. For females, survival was significantly improved for ALL97/99 (HR = 0·33; 95%CI 0·14–0·78), and non‐significantly improved for UKALL2003 (HR = 0·51; 95%CI 0·25–1·08) compared to UKALLXI. Modest overall survival improvements masked clinically important gender‐specific changes over time by trial era, requiring confirmation in larger population‐based studies.
Immunological and clinical factors associated with adverse systemic reactions during the build‐up phase of honeybee venom immunotherapy
Authors: Korošec P. , Žiberna K. , Šilar M. , Dežman M. , Čelesnik Smodiš N. , Rijavec M. , Kopač P. , Eržen R. , Lalek N. , Bajrović N. , Košnik M. , Zidarn M. 
Published: June 2015

SummaryBackgroundAdverse systemic reactions (SRs) are more common in honeybee venom immunotherapy (VIT) than in wasp VIT. Factors that might be associated with SRs during the honeybee VIT are poorly understood.ObjectiveOur aim was to evaluate risk factors for SRs during the build‐up phase of honeybee venom immunotherapy.MethodsWe included 93 patients who underwent ultra‐rush honeybee VIT. The adverse SRs and their severity was compared to various immunological (sIgE, tIgE, basophil CD63 response, baseline tryptase, and skin tests), patient‐specific (age, sex, cardiovascular conditions and medications, and other allergic diseases), and sting‐specific factors (anaphylaxis severity, time interval to onset of symptoms, and absence of cutaneous symptoms).ResultsTwenty‐three patients (24.7%) experienced mild SRs and 13 patients (14%) severe SRs. In five patients with severe SRs, the build‐up was stopped. High basophil allergen sensitivity, evaluated as dose–response curve metrics of EC15, EC50, CD‐sens, AUC, or the response to submaximal 0.01 μg/mL of venom concentration, was the most significant risk factor and only independent predictor of severe SRs and/or build‐up stop. Time interval of <5 min after sting to onset of symptoms and lower specific IgEs to rApi m1 was also associated with severe SRs. There was no difference in other immunological, patient‐specific, or sting‐specific factors, including the baseline tryptase. None of the studied factors was associated with mild SRs.Conclusion and Clinical RelevanceHigh basophil allergen CD63 sensitivity phenotype was a major indicator of severe adverse SRs during the build‐up phase of honeybee VIT. Possibly role was also showed for short latency to filed sting reaction and low sIgE to rApi m1. Before honeybee VIT, measurement of basophil allergen sensitivity should be used to identify patients with a high risk for severe side‐effects.
Antimicrobial Effect of a Single Dose of Amoxicillin on the Oral Microbiota
Authors: Larsson Wexell Cecilia , Ryberg Henrik , Sjöberg Andersson Wivi‐Anne , Blomqvist Susanne , Colin Pieter , Van Bocxlaer Jan , Dahlén Gunnar 
Published: June 2015

AbstractPurposeAmoxicillin is commonly used in oral surgery for antimicrobial prophylaxis against surgical‐site infection and bacteremia because of its effect on oral streptococci. The aim of this study was to determine whether amoxicillin reaches the break‐point concentrations in saliva and has any effect on the salivary microbiota, colonizing bacteria on mucosal membranes and on the gingival crevice after a single dose of amoxicillin.Material and MethodsTwenty subjects received 2 g of amoxicillin, per os. The facultative and strictly anaerobic microflora, as well as the streptococcal microflora specifically, were followed from baseline and after 1, 4, and 24 hours. Samples were taken for microbial analysis from saliva, the dorsum of the tongue, and the gingival crevice, and were inoculated and cultured. Plasma samples and saliva samples were analyzed for amoxicillin concentrations (free and protein bound) using liquid chromatography and mass‐spectrometry.ResultsAmoxicillin was detected in concentrations over the break‐point (>2 μg/mL) of amoxicillin in plasma after 1 and 4 hours but not after 24 hours. The dose had a significant effect on the streptococci in the gingival crevice.ConclusionA single dose given as prophylaxis to prevent a surgical‐site infection results in a significant reducing effect on the oral streptococcal microflora in the gingival crevice and may have an impact on bacteria spreading into tissues and the bacteremia of streptococci.
Three‐dimensional high‐resolution anorectal manometry: does it allow automated analysis of sphincter defects?
Authors: Benezech A. , Behr M. , Bouvier M. , Grimaud J.‐C. , Vitton V. 
Published: June 2015

AbstractAimAnorectal manometry is the most common test used to explore anorectal disorders. The recent three‐dimensional high‐resolution anorectal manometry (3D‐HRAM) technique appears to be able to provide new topographic information. Our objective was to develop an automated analysis of 3D‐HRAM images to diagnose anal sphincter defects and compare the results with those of endoanal ultrasonography (EUS), which is considered to be the gold standard.MethodAll patients being tested in our department for faecal incontinence or dyschezia by 3D‐HRAM and EUS were eligible for the study. 3D‐HRAM was used to record resting and squeeze pressure, reflecting internal and external anal sphincter function, respectively. A software platform was designed to automatically analyse the 3D‐HRAM images and calculate a diagnostic score for any anal sphincter defect compared with EUS.ResultsA total of 206 (91% female) patients of mean age of 54 years were included in the study. A sphincter defect was diagnosed by EUS in 130 (63%). The diagnostic scores from the 3D‐HRAM automated analysis for an internal anal sphincter defect showed a sensitivity of 65% and a specificity of 65%. For an external anal sphincter defect, the sensitivity was 43% and the specificity 87%.ConclusionOur study developed a method based on 3D‐HRAM to automatically diagnose sphincter defects, allowing a systematic and comprehensive analysis of the test recordings. Compared with EUS, the 3D‐HRAM image analysis procedure revealed poor sensitivity and specificity.
Discrepancies in recommended criteria for grading of carotid stenosis with ultrasound
Authors: Jogestrand Tomas , Fredén‐Lindqvist Johan , Lindqvist Madeleine , Lundgren Susanne , Tillman Ann‐Sofie , Zachrisson Helene 
Published: June 2015

SummaryThe accuracy of duplex ultrasound for grading of internal carotid artery stenosis has been widely tested and shown to be high. However, different methods for measurement of the degree of carotid stenosis with the golden standard conventional angiography have been used in the different studies. This, together with other factors, has led to some confusion regarding the relation between the ultrasonographically measured flow velocity and the angiographically measured degree of stenosis. The ultrasound criteria that are used in Sweden (and in Germany) differ in an important way from the criteria recommended in North America and the United Kingdom for the same degree of angiographic stenoses. Possible reasons for the discrepancies are discussed in this article. The authors recommend absolute agreement locally whether ECST or NASCET criteria shall be used in the communication between radiologists, clinical physiologists, vascular surgeons, neurologists and other physicians involved in patient management decisions. Angle‐dependent ultrasound criteria should be used and flow velocity measurements with ultrasound should be combined with assessment of plaque burden on 2D picture.
Validation of a single‐stage fixed‐rate step test for the prediction of maximal oxygen uptake in healthy adults
Authors: Hansen Dominique , Jacobs Nele , Thijs Herbert , Dendale Paul , Claes Neree 
Published: June 2015

SummaryHealthcare professionals with limited access to ergospirometry remain in need of valid and simple submaximal exercise tests to predict maximal oxygen uptake (VO2max). Despite previous validation studies concerning fixed‐rate step tests, accurate equations for the estimation of VO2max remain to be formulated from a large sample of healthy adults between age 18–75 years (n > 100). The aim of this study was to develop a valid equation to estimate VO2max from a fixed‐rate step test in a larger sample of healthy adults. A maximal ergospirometry test, with assessment of cardiopulmonary parameters and VO2max, and a 5‐min fixed‐rate single‐stage step test were executed in 112 healthy adults (age 18–75 years). During the step test and subsequent recovery, heart rate was monitored continuously. By linear regression analysis, an equation to predict VO2max from the step test was formulated. This equation was assessed for level of agreement by displaying Bland–Altman plots and calculation of intraclass correlations with measured VO2max. Validity further was assessed by employing a Jackknife procedure. The linear regression analysis generated the following equation to predict VO2max (l min−1) from the step test: 0·054(BMI)+0·612(gender)+3·359(body height in m)+0·019(fitness index)−0·012(HRmax)−0·011(age)−3·475. This equation explained 78% of the variance in measured VO2max (F = 66·15, P<0·001). The level of agreement and intraclass correlation was high (ICC = 0·94, P<0·001) between measured and predicted VO2max. From this study, a valid fixed‐rate single‐stage step test equation has been developed to estimate VO2max in healthy adults. This tool could be employed by healthcare professionals with limited access to ergospirometry.
Controlled Rewarming after Hypothermia: Adding a New Principle to Renal Preservation
Authors: Schopp Ina , Reissberg Elmo , Lüer Bastian , Efferz Patrik , Minor Thomas 
Published: June 2015

AbstractEarly graft dysfunction due to preservation/reperfusion injury still represents a notable issue after kidney transplantation, affecting long term prognosis of graft viability. One trigger of postischemic cell dysfunction could be recognized in the abrupt temperature shift from hypo‐ to normothermia, leading to mitochondrial dysfunction and proapoptotic signal transduction.Here we propose a technique to cope with this “rewarming injury” by interposing a period of gentle warming up by hypo‐ to subnormothermic machine perfusion of the isolated graft prior to warm reperfusion. Porcine kidneys were subjected either to 18 hours of hypothermic machine preservation (HMP) or 18 hours static cold storage + 3 hours of gentle, machine controlled oxygenated rewarming (COR). Functional integrity was evaluated in both groups by subsequent normothermic reperfusion in vitro.The functional benefit of COR was documented by an approximately twofold increase in renal clearances of creatinine as well as urea upon warm reperfusion, compared to controls. This was accompanied with a notable mitigation of postischemic mitochondrial dys‐homeostasis. COR significantly improved renal oxygen consumption and maintained total NAD tissue content upon reperfusion. Mitochondrial initiation of cellular apoptosis, as evidenced by activation of caspase 9 was also largely prevented after COR but not in controls.The concept of gentle regenerative graft rewarming could become a valuable adjunct in renal transplantation.
Fitness trade‐offs in pest management and intercropping with colour: an evolutionary framework and potential application
Authors: Farkas Timothy E. 
Published: June 2015

AbstractAn important modern goal of plant science research is to develop tools for agriculturalists effective at curbing yield losses to insect herbivores, but resistance evolution continuously threatens the efficacy of pest management strategies. The high‐dose/refuge strategy has been employed with some success to curb pest adaptation, and has been shown to be most effective when fitness costs (fitness trade‐offs) of resistance are high. Here, I use eco‐evolutionary reasoning to demonstrate the general importance of fitness trade‐offs for pest control, showing that strong fitness trade‐offs mitigate the threat of pest adaptation, even if adaptation were to occur. I argue that novel pest management strategies evoking strong fitness trade‐offs are the most likely to persist in the face of unbridled pest adaptation, and offer the manipulation of crop colours as a worked example of one potentially effective strategy against insect herbivores.
Linear models for cost‐sensitive classification
Authors: Pendharkar Parag C. 
Published: June 2015

AbstractIn this paper, we investigate the performance of statistical, mathematical programming and heuristic linear models for cost‐sensitive classification. In particular, we use five cost‐sensitive techniques including Fisher's discriminant analysis (DA), asymmetric misclassification cost mixed integer programming (AMC‐MIP), cost‐sensitive support vector machine (CS‐SVM), a hybrid support vector machine and mixed integer programming (SVMIP) and heuristic cost‐sensitive genetic algorithm (CGA) techniques. Using simulated datasets of varying group overlaps, data distributions and class biases, and real‐world datasets from financial and medical domains, we compare the performances of our five techniques based on overall holdout sample misclassification cost. The results of our experiments on simulated datasets indicate that when group overlap is low and data distribution is exponential, DA appears to provide superior performance. For all other situations with simulated datasets, CS‐SVM provides superior performance. In case of real‐world datasets from financial domain, CGA and AMC‐MIP hold a slight edge over the two SVM‐based classifiers. However, for medical domains with mixed continuous and discrete attributes, SVM classifiers perform better than heuristic (CGA) and AMC‐MIP classifiers. The SVMIP model is the most computationally inefficient model and poor performing model.
Impact of Coping Resources on the Well‐Being of Custodial Grandmothers and Grandchildren
Authors: Smith Gregory C. , Cichy Kelly E. , Montoro‐Rodriguez Julian 
Published: June 2015

AbstractThe authors blended elements from the Stress Process Model and the Family Stress Model to investigate the direct and indirect effects of custodial grandmothers' (CGMs') coping resources (i.e., active strategies, passive strategies, and social support) on their psychological distress, their parenting practices, and their grandchild's internalizing and externalizing symptoms. Participants included African American and White CGMs (N = 733, Mage = 56) who provided full‐time care to a grandchild (Mage = 9.8). Structural equation modeling revealed that social support and active coping were related to lower CGM distress and less ineffective parenting, whereas passive coping was associated with increased distress and more ineffective parenting. Ineffective parenting had direct effects on grandchildren's outcomes, whereas CGM coping resources had direct effects on ineffective parenting and indirect effects (through ineffective parenting) on grandchildren's externalizing and internalizing difficulties. The authors conclude that CGM coping resources affect the psychological well‐being of both generations.
Microbial physiology and soil CO2 efflux after 9 years of soil warming in a temperate forest – no indications for thermal adaptations
Authors: Schindlbacher Andreas , Schnecker Jörg , Takriti Mounir , Borken Werner , Wanek Wolfgang 
Published: June 2015

AbstractThermal adaptations of soil microorganisms could mitigate or facilitate global warming effects on soil organic matter (SOM) decomposition and soil CO2 efflux. We incubated soil from warmed and control subplots of a forest soil warming experiment to assess whether 9 years of soil warming affected the rates and the temperature sensitivity of the soil CO2 efflux, extracellular enzyme activities, microbial efficiency, and gross N mineralization. Mineral soil (0–10 cm depth) was incubated at temperatures ranging from 3 to 23 °C. No adaptations to long‐term warming were observed regarding the heterotrophic soil CO2 efflux (R10 warmed: 2.31 ± 0.15 μmol m−2 s−1, control: 2.34 ± 0.29 μmol m−2 s−1; Q10 warmed: 2.45 ± 0.06, control: 2.45 ± 0.04). Potential enzyme activities increased with incubation temperature, but the temperature sensitivity of the enzymes did not differ between the warmed and the control soils. The ratio of C : N acquiring enzyme activities was significantly higher in the warmed soil. Microbial biomass‐specific respiration rates increased with incubation temperature, but the rates and the temperature sensitivity (Q10 warmed: 2.54 ± 0.23, control 2.75 ± 0.17) did not differ between warmed and control soils. Microbial substrate use efficiency (SUE) declined with increasing incubation temperature in both, warmed and control, soils. SUE and its temperature sensitivity (Q10 warmed: 0.84 ± 0.03, control: 0.88 ± 0.01) did not differ between warmed and control soils either. Gross N mineralization was invariant to incubation temperature and was not affected by long‐term soil warming. Our results indicate that thermal adaptations of the microbial decomposer community are unlikely to occur in C‐rich calcareous temperate forest soils.
How anthropogenic noise affects foraging
Authors: Luo Jinhong , Siemers Björn M. , Koselj Klemen 
Published: June 2015

AbstractThe influence of human activity on the biosphere is increasing. While direct damage (e.g. habitat destruction) is relatively well understood, many activities affect wildlife in less apparent ways. Here, we investigate how anthropogenic noise impairs foraging, which has direct consequences for animal survival and reproductive success. Noise can disturb foraging via several mechanisms that may operate simultaneously, and thus, their effects could not be disentangled hitherto. We developed a diagnostic framework that can be applied to identify the potential mechanisms of disturbance in any species capable of detecting the noise. We tested this framework using Daubenton's bats, which find prey by echolocation. We found that traffic noise reduced foraging efficiency in most bats. Unexpectedly, this effect was present even if the playback noise did not overlap in frequency with the prey echoes. Neither overlapping noise nor nonoverlapping noise influenced the search effort required for a successful prey capture. Hence, noise did not mask prey echoes or reduce the attention of bats. Instead, noise acted as an aversive stimulus that caused avoidance response, thereby reducing foraging efficiency. We conclude that conservation policies may seriously underestimate numbers of species affected and the multilevel effects on animal fitness, if the mechanisms of disturbance are not considered.
Safety and pharmacokinetics of bapineuzumab in a single ascending‐dose study in Japanese patients with mild to moderate Alzheimer's disease
Authors: Arai Heii , Umemura Kazuo , Ichimiya Yosuke , Iseki Eizo , Eto Ko , Miyakawa Koichi , Kirino Eiji , Shibata Nobuto , Baba Hajime , Tsuchiwata Shinichi 
Published: June 2015

AimTo evaluate the safety, tolerability and pharmacokinetic profile of bapineuzumab after a single intravenous injection in Japanese patients with mild to moderate Alzheimer's disease.MethodsParticipants received either a placebo (n = 8), or bapineuzumab 0.15 (n = 6), 0.5 (n = 6), 1.0 (n = 6) or 2.0 (n = 6) mg/kg. Serum concentrations of bapineuzumab, antibapineuzumab antibody and total plasma β‐amyloidx‐40 were assayed.ResultsAdverse events for bapineuzumab and placebo groups were 71% and 88%, respectively. Treatment‐emergent adverse events (cataract, injection site hemorrhage, nasopharyngitis, pneumonia and muscle twitching) reported for ≥2 participants were mild or moderate in severity and unrelated to bapineuzumab dose. No deaths, serious adverse events or withdrawals were reported. Mean peak concentration for bapineuzumab increased with dose, from 3.3 ± 0.9 μg/mL with the 0.15 mg/kg dose to 61.0 ± 32.8 μg/mL with 2.0 mg/kg. Mean bapineuzumab exposure (area under the curve from time 0 to last measurable concentration; μg·h/mL) increased in a linear manner with increasing dose (mean 1260 for 0.15 mg/kg, 4264 for 0.5 mg/kg, 7818 for 1.0 mg/kg, 15 313 for 2.0 mg/kg). Mean half‐life ranged from 15 to 28 days, and clearance was similar across dose groups (range 0.12–0.17 mL/h/kg).ConclusionsPlasma β‐amyloidx‐40 levels increased with increasing doses of bapineuzumab. Bapineuzumab was safe and well tolerated at all doses in Japanese patients with mild to moderate Alzheimer's disease. Geriatr Gerontol Int 2016; 16: 644–650.
A salutogenic patient‐centred perspective of improved oral health behaviour – a descriptive phenomenological interview study
Authors: Östergård G‐B , Englander M , Axtelius B 
Published: June 2015

AbstractA salutogenic perspective was applied in the study when investigating the patient's perspective of what it means to move in the direction towards health in the treatment of periodontitis.ObjectivesThe study aimed at describing the lived experience of improved oral health‐related behaviour.MethodThe descriptive phenomenological method was chosen for collection and analysis of data. Patients were selected from a private general dental clinic.ResultsThe results described the patient‐centred perspective in the general structure held together by eight constituents: (i) change is increased successively, (ii) a changed view on self‐care at the start of change, (iii) improved self‐care includes understanding and automatic routine, (iv) motivating challenges and feedback are perceived as strengthening, (v) having good thoughts and being satisfied with one's own capacity, (vi) experiencing trust and participation along with an expert, (vii) negative experiences and limitations precedes the change and (viii) relating yourself to past time, present time, future and other people.ConclusionThe complex pattern of interconnected external and internal components in the results calls for the need of a holistic perspective of the change process and for the clinician to practise flexibility.