bluuebunny/crossref_metadata_2025 huggingface dataset:
Superior Labrum Anterior Posterior Lesions and Associated Injuries
Authors: Beyzadeoglu Tahsin , Circi Esra
Published: April 2015

Background:

Superior labrum anterior posterior (SLAP) lesions often cause shoulder pain, dysfunction, and instability. Professional athletes require a high level of shoulder function for competition and overhead activities.

Purpose:

To evaluate elite athletes who had arthroscopic surgery for common shoulder pathologies and SLAP lesions with a follow-up of more than 3 years. The associated intra-articular pathologies and return to play were documented.

Study Design:

Case series; Level of evidence, 4.

Methods:

Thirty-five shoulders in 34 elite athletes (4 women and 30 men; mean age, 25 years [range, 18-32 years]) had arthroscopic repair of SLAP lesions and accompanying Bankart or rotator cuff tears between January 2008 and November 2011. The documentation included patient symptoms, physical examination, radiological analysis with radiographs, and magnetic resonance imaging. Shoulder function was evaluated preoperatively and at follow-up using American Shoulder and Elbow Surgeons (ASES) and Kerlan Jobe Orthopaedic Clinic (KJOC) scores. The mean follow-up was 52 months.

Results:

Isolated SLAP lesions were seen in 17.1% of patients, SLAP lesions and partial cuff tear occurred in 25.7%, associated Bankart lesions in 37.1%, full-thickness rotator cuff tears in 8.6%, Bankart and posterior labrum lesions in 8.6%, and Bankart and full-thickness rotator cuff tears in 2.9%. Return to play was a mean 6.4 ± 1.5 months. The mean postoperative ASES and KJOC scores were 89.6 ± 4.6 and 80.9 ± 6.8, respectively, compared with preoperative scores of 64.0 ± 7.2 and 50.5 ± 10.3 ( t test, P < .01).

Conclusion:

The majority (88.2%) of professional athletes returned to their preinjury levels. SLAP lesions may frequently occur with Bankart lesions and rotator cuff tears. A high rate of return to sport at the same level of athletic performance can be achieved by anatomic repair and effective rehabilitation.
Effects of different sterilisation methods on antibacterial Cu–TiO2 coatings
Authors: Mauerer A. , Henkel M. , Welsch G. H. , Forst R. , Richter R. H. , Heidenau F.
Published: April 2015

Implant related infection is a serious problem in orthopaedic surgery. An antibacterial and biocompatible copper with a sol–gel derived titania coating (Cu–TiO2) could be an appropriate approach for the treatment of such infections. Before clinical application, the coatings must be sterilised. The effects of autoclaving and gamma irradiation on the antibacterial coating have not yet been fully investigated. Titanium alloy (TiAl4V6) plates with different numbers of Cu–TiO2 coatings applied were analysed after autoclaving or gamma irradiation. Scanning electron microscopy (SEM) was used to investigate the surface structure of the coating and energy dispersive X-ray spectroscopy (EDX) was used to investigate the distribution of copper ions in three different areas. Examinations by SEM and EDX showed more significant changes to the surface of the coating after autoclaving compared to gamma irradiation. Gamma irradiation seems to be the most appropriate method of sterilisation for the tested antibacterial Cu–TiO2 coatings.
Varied longitudinal microstructure of μc-Si: H films by tuning substrate temperature
Authors: Lu Y. , Li H. , Yang G.
Published: April 2015

Hydrogenated silicon thin films were deposited using plasma enhanced chemical vapour deposition method. The effects of substrate temperature on the microstructure and electrical properties of the films were investigated. Results show that the as received crystalline silicon thin film is a typical two-phase structure consisting of an amorphous phase and a crystalline phase. At a lower substrate temperature, the thickness of the initial amorphous incubation layer is dozens of nanometers, and few crystalline grains inset in the film after phase transition. As the substrate temperature increases, the initial incubation stage shortens to several nanometers, and the phase transition to crystalline starts earlier. After the phase transition, abundant crystallites appear, and the amorphous phase exists in the film just as the grain boundary. However, at overhigh substrate temperature, the average crystallinity and grain size of the film decrease. Deposition rate abidingly decreases with the increase in substrate temperature. The films with more ordered structure exhibit superior electrical properties.
Multiwall carbon nanotube/copper porous coating for heat transfer application
Authors: Zheng X. , Kim J. S. , Park C. W.
Published: April 2015

This paper describes the production of porous surfaces using multiwall carbon nanotube (MWCNT)/copper composite powders, as well as the investigation of the pore characteristics and mechanical properties of the MWCNT coated porous surfaces for boiling heat transfer application. The influence of MWCNT content, milling time and sintering temperature on porosity was investigated. When MWCNT content increased, it resulted in a decrease in porosity and microhardness; however, adhesion is improved. With the increase in milling time, the porosity of coatings increased; meanwhile, the mechanical properties enhanced. The high temperature diffusion and shrinkage of Cu particles resulted in removal of the small pores. Thus, with an increase in sintering temperature, the porosity percentage and average pore diameter decreased.
Protective coatings for mechanical aluminum–magnesium joints
Authors: Dzhurinskiy D. , Leshchinsky V. , Strumban E. , Maeva E. , Maev R. G.
Published: April 2015

AZ31 alloy is used as a lightweight material for structural application in the automobile and aircraft production. However, alloy AZ31 is known to have poor corrosion resistant due to high electrochemical activity. In this study, the possibility of improving the corrosion resistance by applying protective coatings deposited by the low pressure cold spray process was investigated. The relative performance of each cold sprayed corrosion preventive coatings was assessed in accordance with American Society for Testing and Materials standards. The data for the bare AZ31 alloy were initially obtained and used as a reference point to compare the corrosion protective performance of different preventive coatings. Electrochemical behaviour of each coating composition was analyzed after a given time period of the accelerated corrosion test. Microstructure and mechanical properties of the deposited preventive coatings are also discussed. The cold sprayed preventive coatings provide sufficient protection to substantially reduce the corrosion rate of alloy AZ31.
Effects of temperature on PO and resistivity of ScAlN film
Authors: Yang YX. , Li XM. , Zhou D. , Yang CT. , Feng F. , Yang JS. , Hu QJ.
Published: April 2015

Sc doped AlN (ScAlN) films were prepared by dc reactive magnetron sputtering. The crystal quality, surface topography, cross-sectional view and the resistivity of ScAlN thin films grown on Si (100) substrates at various substrate temperatures from room temperature to 650°C have been investigated. Results show that the temperature has a significant effect on the properties of ScAlN thin films. According to the research, the crystal quality of ScAlN film first increases and then decreases, reaching the best crystalline state at 600°C. The best surface morphology and cross-sectional view of ScAlN thin film was obtained at 600°C. The resistivity first increased to a maximum value of 3·36 × 1012 Ω·cm and then decreased with the temperature increasing.
The oncogenic transcription factor IRF4 is regulated by a novel CD30/NF-κB positive feedback loop in peripheral T-cell lymphoma
Authors: Boddicker Rebecca L. , Kip N. Sertac , Xing Xiaoming , Zeng Yu , Yang Zhi-Zhang , Lee Jeong-Heon , Almada Luciana L. , Elsawa Sherine F. , Knudson Ryan A. , Law Mark E. , Ketterling Rhett P. , Cunningham Julie M. , Wu Yanhong , Maurer Matthew J. , O’Byrne Megan M. , Cerhan James R. , Slager Susan L. , Link Brian K. , Porcher Julie C. , Grote Deanna M. , Jelinek Diane F. , Dogan Ahmet , Ansell Stephen M. , Fernandez-Zapico Martin E. , Feldman Andrew L.
Published: April 2015

Key Points

The NF-κB subunits p52 and RelB increase IRF4 promoter activity and expression in PTCL cells. A positive feedback loop involving CD30, NF-κB, and IRF4 drives PTCL cell proliferation and can be blocked by NF-κB inhibitors.
Fatal autoimmunity in mice reconstituted with human hematopoietic stem cells encoding defective FOXP3
Authors: Goettel Jeremy A. , Biswas Subhabrata , Lexmond Willem S. , Yeste Ada , Passerini Laura , Patel Bonny , Yang Siyoung , Sun Jiusong , Ouahed Jodie , Shouval Dror S. , McCann Katelyn J. , Horwitz Bruce H. , Mathis Diane , Milford Edgar L. , Notarangelo Luigi D. , Roncarolo Maria-Grazia , Fiebiger Edda , Marasco Wayne A. , Bacchetta Rosa , Quintana Francisco J. , Pai Sung-Yun , Klein Christoph , Muise Aleixo M. , Snapper Scott B.
Published: April 2015

Key Points

Improved adaptive immune responses in humanized mice lacking murine MHC II and expressing human HLADR1. NOD.PrkdcscidIl2rγ−/−H2-Ab1−/− Tg(HLA-DR1) mice reconstituted with hematopoietic stem cells from an IPEX syndrome patient develop fatal autoimmunity.
Intravenous fish oil lipid emulsions in critically ill patients: an updated systematic review and meta-analysis
Authors: Manzanares William , Langlois Pascal L , Dhaliwal Rupinder , Lemieux Margot , Heyland Daren K
Published: April 2015

Introduction

Intravenous fish oil (FO) lipid emulsions (LEs) are rich in ω-3 polyunsaturated fatty acids, which exhibit anti-inflammatory and immunomodulatory effects. We previously demonstrated that FO-containing LEs may be able to decrease mortality and ventilation days in patients who are critically ill. Since 2014, several additional randomized controlled trials (RCTs) of FO-containing LEs have been published. Therefore, the purpose of this systematic review was to update our previous systematic review with the aim of elucidating the efficacy of FO-containing LEs on clinical outcomes of patients who are critically ill.

Methods

We searched electronic databases from 1980 to 2014. We included four new RCTs conducted in critically ill adult patients in which researchers evaluated FO-containing LEs in parenterally or enterally fed patients.

Results

A total of 10 RCTs (n = 733) met inclusion criteria. The mean methodological score was 8 (range, 3 to 12). No effect on overall mortality was found. When we aggregated the results of five RCTs in which infections were reported, we found that FO-containing LEs significantly reduced infections (risk ratio (RR) = 0.64; 95% confidence interval (CI), 0.44 to 0.92; P = 0.02; heterogeneity I2 = 0%). Subgroup analysis demonstrated that predominantly enteral nutrition–based trials showed a tendency toward a reduction in mortality (RR = 0.69; 95% CI, 0.40 to 1.18; P =0.18; heterogeneity I2 =35%). High-quality trials showed a significant reduction in hospital length of stay (LOS) (weighted mean difference = −7.42; 95% CI, −11.89 to −2.94; P = 0.001), whereas low-quality trials had no effect (P = 0.45). The results of the test for subgroup differences in hospital LOS was significant (P = 0.001).

Conclusion

FO-containing LEs may be associated with a reduction in infections and also could be associated with a reduction in duration of ventilation and hospital LOS. Further large-scale RCTs are warranted and should be aimed at consolidating potential positive treatment effects.
A pilot study of change in fracture risk in patients with acute respiratory distress syndrome
Authors: Rawal Jaikitry , McPhail Mark JW , Ratnayake Gamumu , Chan Pearl , Moxham John , Harridge Stephen DR , Hart Nicholas , Montgomery Hugh E , Puthucheary Zudin A
Published: April 2015

Introduction

Acute skeletal muscle wasting is a major contributor to post critical illness physical impairment. However, the bone response remains uncharacterized. We prospectively investigated the early changes in bone mineral density (BMD) and fracture risk in critical illness.

Methods

Patients were prospectively recruited ≤24 hours following intensive care unit (ICU) admission to a university teaching or a community hospital (August 2009 to April 2011). All were aged >18 years and expected to be intubated for >48 hours, spend >7 days in critical care and survive ICU admission. Forty-six patients were studied (55.3% male), with a mean age of 54.4 years (95% confidence interval (CI): 49.1 to 59.6) and an APACHE II score of 23.9 (95% CI: 22.4 to 25.5). Calcaneal dual X-ray absorptiometry (DXA) assessment of BMD was performed on day 1 and 10. Increase in fracture risk was calculated from the change in T-score.

Results

BMD did not change between day 1 and 10 in the cohort overall (0.434 (95% CI: 0.405 to 0.463) versus 0.425 g/cm2 (95% CI: 0.399 to 0.450), P = 0.58). Multivariable logistical regression revealed admission corrected calcium (odds ratio (OR): 1.980 (95% CI: 1.089 to 3.609), P = 0.026) and admission PaO2-to-FiO2 ratio (OR: 0.916 (95% CI: 0.833 to 0.998), P = 0.044) to be associated with >2% loss of BMD. Patients with acute respiratory distress syndrome had a greater loss in BMD than those without (−2.81% (95% CI: −5.73 to 0.118%), n = 34 versus 2.40% (95% CI: 0.204 to 4.586%), n = 12, P = 0.029). In the 34 patients with acute respiratory distress syndrome, fracture risk increased by 19.4% (95% CI: 13.9 to 25.0%).

Conclusions

Patients with acute respiratory distress syndrome demonstrated early and rapid bone demineralisation with associated increase in fracture risk.
Acute kidney injury after cardiac arrest
Authors: Tujjar Omar , Mineo Giulia , Dell’Anna Antonio , Poyatos-Robles Belen , Donadello Katia , Scolletta Sabino , Vincent Jean-Louis , Taccone Fabio Silvio
Published: April 2015

Introduction

The aim of this study was to evaluate the incidence and determinants of AKI in a large cohort of cardiac arrest patients.

Methods

We reviewed all patients admitted, for at least 48 hours, to our Dept. of Intensive Care after CA between January 2008 and October 2012. AKI was defined as oligo-anuria (daily urine output <0.5 ml/kg/h) and/or an increase in serum creatinine (≥0.3 mg/dl from admission value within 48 hours or a 1.5 time from baseline level). Demographics, comorbidities, CA details, and ICU interventions were recorded. Neurological outcome was assessed at 3 months using the Cerebral Performance Category scale (CPC 1–2 = favorable outcome; 3–5 = poor outcome).

Results

A total of 199 patients were included, 85 (43%) of whom developed AKI during the ICU stay. Independent predictors of AKI development were older age, chronic renal disease, higher dose of epinephrine, in-hospital CA, presence of shock during the ICU stay, a low creatinine clearance (CrCl) on admission and a high cumulative fluid balance at 48 hours. Patients with AKI had higher hospital mortality (55/85 vs. 57/114, p = 0.04), but AKI was not an independent predictor of poor 3-month neurological outcome.

Conclusions

AKI occurred in more than 40% of patients after CA. These patients had more severe hemodynamic impairment and needed more aggressive ICU therapy; however the development of AKI did not influence neurological recovery.
5-hydroxymethylcytosine marks promoters in colon that resist DNA hypermethylation in cancer
Authors: Uribe-Lewis Santiago , Stark Rory , Carroll Thomas , Dunning Mark J , Bachman Martin , Ito Yoko , Stojic Lovorka , Halim Silvia , Vowler Sarah L , Lynch Andy G , Delatte Benjamin , de Bony Eric J , Colin Laurence , Defrance Matthieu , Krueger Felix , Silva Ana-Luisa , ten Hoopen Rogier , Ibrahim Ashraf EK , Fuks François , Murrell Adele
Published: April 2015

Background

The discovery of cytosine hydroxymethylation (5hmC) as a mechanism that potentially controls DNA methylation changes typical of neoplasia prompted us to investigate its behaviour in colon cancer. 5hmC is globally reduced in proliferating cells such as colon tumours and the gut crypt progenitors, from which tumours can arise.

Results

Here, we show that colorectal tumours and cancer cells express Ten-Eleven-Translocation (TET) transcripts at levels similar to normal tissues. Genome-wide analyses show that promoters marked by 5hmC in normal tissue, and those identified as TET2 targets in colorectal cancer cells, are resistant to methylation gain in cancer. In vitro studies of TET2 in cancer cells confirm that these promoters are resistant to methylation gain independently of sustained TET2 expression. We also find that a considerable number of the methylation gain-resistant promoters marked by 5hmC in normal colon overlap with those that are marked with poised bivalent histone modifications in embryonic stem cells.

Conclusions

Together our results indicate that promoters that acquire 5hmC upon normal colon differentiation are innately resistant to neoplastic hypermethylation by mechanisms that do not require high levels of 5hmC in tumours. Our study highlights the potential of cytosine modifications as biomarkers of cancerous cell proliferation.
The novel S59P mutation in the TNFRSF1A gene identified in an adult onset TNF receptor associated periodic syndrome (TRAPS) constitutively activates NF-κB pathway
Authors: Greco Eliana , Aita Ada , Galozzi Paola , Gava Alessandra , Sfriso Paolo , Negm Ola H , Tighe Patrick , Caso Francesco , Navaglia Filippo , Dazzo Emanuela , De Bortoli Marzia , Rampazzo Alessandra , Obici Laura , Donadei Simona , Merlini Giampaolo , Plebani Mario , Todd Ian , Basso Daniela , Punzi Leonardo
Published: April 2015

Introduction

Mutations in the TNFRSF1A gene, encoding tumor necrosis factor receptor 1 (TNF-R1), are associated with the autosomal dominant autoinflammatory disorder, called TNF receptor associated periodic syndrome (TRAPS). TRAPS is clinically characterized by recurrent episodes of long-lasting fever and systemic inflammation. A novel mutation (c.262 T > C; S59P) in the TNFRSF1A gene at residue 88 of the mature protein was recently identified in our laboratory in an adult TRAPS patient. The aim of this study was to functionally characterize this novel TNFRSF1A mutation evaluating its effects on the TNF-R1-associated signaling pathways, firstly NF-κB, under particular conditions and comparing the results with suitable control mutations.

Methods

HEK-293 cell line was transfected with pCMV6-AC construct expressing wild-type (WT) or c.262 T > C (S59P), c.362G > A (R92Q), c.236C > T (T50M) TNFRSF1A mutants. Peripheral blood mononuclear cells (PBMCs) were instead isolated from two TRAPS patients carrying S59P and R92Q mutations and from five healthy subjects. Both transfected HEK-293 and PBMCs were stimulated with tumor necrosis factor (TNF) or interleukin 1β (IL-1β) to evaluate the expression of TNF-R1, the activation of TNF-R1-associated downstream pathways and the pro-inflammatory cytokines by means of immunofluorescent assay, array-based technique, immunoblotting and immunometric assay, respectively.

Results

TNF induced cytoplasmic accumulation of TNF-R1 in all mutant cells. Furthermore, all mutants presented a particular set of active TNF-R1 downstream pathways. S59P constitutively activated IL-1β, MAPK and SRC/JAK/STAT3 pathways and inhibited apoptosis. Also, NF-κB pathway involvement was demonstrated in vitro by the enhancement of p-IκB-α and p65 nuclear subunit of NF-κB expression in all mutants in the presence of TNF or IL-1β stimulation. These in vitro results correlated with patients’ data from PBMCs. Concerning the pro-inflammatory cytokines secretion, mainly IL-1β induced a significant and persistent enhancement of IL-6 and IL-8 in PBMCs carrying the S59P mutation.

Conclusions

The novel S59P mutation leads to defective cellular trafficking and to constitutive activation of TNF-R1. This mutation also determines constitutive activation of the IL-1R pathway, inhibition of apoptosis and enhanced and persistent NF-κB activation and cytokine secretion in response to IL-1β stimulation.
Evaluation of the effect of tofacitinib on measured glomerular filtration rate in patients with active rheumatoid arthritis: results from a randomised controlled trial
Authors: Kremer Joel M , Kivitz Alan J , Simon-Campos Jesus A , Nasonov Evgeny L , Tony Hans-Peter , Lee Soo-Kon , Vlahos Bonnie , Hammond Constance , Bukowski Jack , Li Huihua , Schulman Seth L , Raber Susan , Zuckerman Andrea , Isaacs John D
Published: April 2015

Introduction

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). During the clinical development programme, increases in mean serum creatinine (SCr) of approximately 0.07 mg/dL and 0.08 mg/dL were observed which plateaued early. This study assessed changes in measured glomerular filtration rate (mGFR) with tofacitinib relative to placebo in patients with active RA.

Methods

This was a randomised, placebo-controlled, Phase 1 study (NCT01484561). Patients were aged ≥18 years with active RA. Patients were randomised 2:1 to oral tofacitinib 10 mg twice daily (BID) in Period 1 then placebo BID in Period 2 (tofacitinib → placebo); or oral placebo BID in both Periods (placebo → placebo). Change in mGFR was evaluated by iohexol serum clearance at four time points (run-in, pre-dose in Period 1, Period 1 end, and Period 2 end). The primary endpoint was the change in mGFR from baseline to Period 1 end. Secondary endpoints included: change in mGFR at other time points; change in estimated GFR (eGFR; Cockcroft–Gault equation) and SCr; efficacy; and safety.

Results

148 patients were randomised to tofacitinib → placebo (N = 97) or placebo → placebo (N = 51). Baseline characteristics were similar between groups. A reduction of 8% (90% confidence interval [CI]: 2%, 14%) from baseline in adjusted geometric mean mGFR was observed during tofacitinib treatment in Period 1 vs placebo. During Period 2, mean mGFR returned towards baseline during placebo treatment, and there was no difference between the two treatment groups at the end of the study – ratio (tofacitinib → placebo/placebo → placebo) of adjusted geometric mean fold change of mGFR was 1.04 (90% CI: 0.97, 1.11). Post-hoc analyses, focussed on mGFR variability in placebo → placebo patients, were consistent with this conclusion. At study end, similar results were observed for eGFR and SCr. Clinical efficacy and safety were consistent with prior studies.

Conclusion

Increases in mean SCr and decreases in eGFR in tofacitinib-treated patients with RA may occur in parallel with decreases in mean mGFR; mGFR returned towards baseline after tofacitinib discontinuation, with no significant difference vs placebo, even after post-hoc analyses. Safety monitoring will continue in ongoing and future clinical studies and routine pharmacovigilance.

Trial registration

Clinicaltrials.gov NCT01484561. Registered 30 November 2011.
Comparing recruitment, retention, and safety reporting among geographic regions in multinational Alzheimer’s disease clinical trials
Authors: Grill Joshua D , Raman Rema , Ernstrom Karin , Aisen Paul , Dowsett Sherie A , Chen Yun-Fei , Liu-Seifert Hong , Hake Ann Marie , Miller David S , Doody Rachelle S , Henley David B , Cummings Jeffrey L
Published: April 2015

Introduction

Most Alzheimer’s disease (AD) clinical trials enroll participants multinationally. Yet, few data exist to guide investigators and sponsors regarding the types of patients enrolled in these studies and whether participant characteristics vary by region.

Methods

We used data derived from four multinational phase III trials in mild to moderate AD to examine whether regional differences exist with regard to participant demographics, safety reporting, and baseline scores on the Mini Mental State Examination (MMSE), the 11-item Alzheimer’s Disease Assessment Scale–Cognitive subscale (ADAS-cog11), the Clinical Dementia Rating scale Sum of Boxes (CDR-SB), the Alzheimer’s Disease Cooperative Study–Activities of Daily Living Inventory (ADCS-ADL), and the Neuropsychiatric Inventory (NPI). We assigned 31 participating nations to 7 geographic regions: North America, South America/Mexico, Western Europe/Israel, Eastern Europe/Russia, Australia/South Africa, Asia, and Japan.

Results

North America, Western Europe/Israel, and Australia/South Africa enrolled similar proportions of men, apolipoprotein E ε4 carriers, and participants with spouse study partners, whereas Asia, Eastern Europe/Russia, and South America/Mexico had lower proportions for these variables. North America and South America/Mexico enrolled older subjects, whereas Asia and South America/Mexico enrolled less-educated participants than the remaining regions. Approved AD therapy use differed among regions (range: 73% to 92%) and was highest in North America, Western Europe/Israel, and Japan. Dual therapy was most frequent in North America (48%). On the MMSE, North America, Western Europe/Israel, Japan, and Australia/South Africa had higher (better) scores, and Asia, South America/Mexico, and Eastern Europe/Russia had lower scores. Eastern Europe/Russia had more impaired ADAS-cog11 scores than all other regions. Eastern Europe/Russia and South America/Mexico had more impaired scores for the ADCS-ADL and the CDR-SB. Mean scores for the CDR-SB in Asia were milder than all regions except Japan. NPI scores were lower in Asia and Japan than in all other regions. Participants in North America and Western Europe/Israel reported more adverse events than those in Eastern Europe/Russia and Japan.

Conclusions

These findings suggest that trial populations differ across geographic regions on most baseline characteristics and that multinational enrollment is associated with sample heterogeneity. The data provide initial guidance with regard to the regional differences that contribute to this heterogeneity and are important to consider when planning global trials.
Prospective adherence to specific immunotherapy in Europe (PASTE) survey protocol
Authors: Makatsori Melina , Senna Gianenrico , Pitsios Constantinos , Lleonart Ramon , Klimek Ludger , Nunes Carlos , Rukhadze Maia , Rogala Barbara , Gawlik Radoslaw , Panzner Petr , Pfaar Oliver , Calderon Moises
Published: April 2015

Background

Adherence to allergen immunotherapy is important for its effectiveness. There is currently limited data available on allergen immunotherapy adherence outside of clinical trials i.e. in real‐life clinical practice. As part of a European Academy of Allergy and Clinical Immunology Immunotherapy Interest group initiative, we endeavoured to design a survey in order to prospectively evaluate adherence to subcutaneous and sublingual immunotherapy across different European countries.

Method/Design

The inclusion criteria for this prospective, multi‐country survey were set as: adults, starting clinically indicated allergen immunotherapy for respiratory allergic disorders or Hymenoptera venom allergy. An online survey was designed in order to enrol participants and assess adherence to immunotherapy.

Eight countries (Czech Republic, Georgia, Germany, Greece, Italy, Poland, Portugal, Spain) were selected to reflect different parts of Europe and differences in allergens and routes of immunotherapy administration. Each country has an allocated National co‐ordinator that has identified local Allergy departments willing to enrol participants in this survey.

Each participant will be followed up for a total of three years. In order to assess adherence, a 4‐monthly follow‐up form detailing any missed doses and reasons will be completed online. In case of a participant discontinuing treatment, reasons for this will be recorded.

Discussion

The use of online survey software has enabled us to make this survey a reality and reach clinicians in different countries. Forty‐five centres have enrolled a total of over 1,350 participants. It is hoped that this prospective real life survey will enable us to gain a better understanding of reasons that affect adherence to subcutaneous and sublingual immunotherapy and assist in developing ways to improve this.
An innovative technique for contrast enhancement of computed tomography images using normalized gamma-corrected contrast-limited adaptive histogram equalization
Authors: Al-Ameen Zohair , Sulong Ghazali , Rehman Amjad , Al-Dhelaan Abdullah , Saba Tanzila , Al-Rodhaan Mznah
Published: April 2015

Image contrast is an essential visual feature that determines whether an image is of good quality. In computed tomography (CT), captured images tend to be low contrast, which is a prevalent artifact that reduces the image quality and hampers the process of extracting its useful information. A common tactic to process such artifact is by using histogram-based techniques. However, although these techniques may improve the contrast for different grayscale imaging applications, the results are mostly unacceptable for CT images due to the presentation of various faults, noise amplification, excess brightness, and imperfect contrast. Therefore, an ameliorated version of the contrast-limited adaptive histogram equalization (CLAHE) is introduced in this article to provide a good brightness with decent contrast for CT images. The novel modification to the aforesaid technique is done by adding an initial phase of a normalized gamma correction function that helps in adjusting the gamma of the processed image to avoid the common errors of the basic CLAHE of the excess brightness and imperfect contrast it produces. The newly developed technique is tested with synthetic and real-degraded low-contrast CT images, in which it highly contributed in producing better quality results. Moreover, a low intricacy technique for contrast enhancement is proposed, and its performance is also exhibited against various versions of histogram-based enhancement technique using three advanced image quality assessment metrics of Universal Image Quality Index (UIQI), Structural Similarity Index (SSIM), and Feature Similarity Index (FSIM). Finally, the proposed technique provided acceptable results with no visible artifacts and outperformed all the comparable techniques.
The contraction principle for mappings on a modular metric space with a graph
Authors: Alfuraidan Monther Rashed
Published: April 2015

We give a generalization of the Banach contraction principle on a modular metric space endowed with a graph. The notion of a modular metric on an arbitrary set and the corresponding modular spaces, generalizing classical modulars over linear spaces like Orlicz spaces, were recently introduced. This paper can be seen as the modular metric version of Jachymski’s fixed point result for mappings on a metric space with a graph.
Prolonged exposure to neutrophil extracellular traps can induce mitochondrial damage in macrophages and dendritic cells
Authors: Donis-Maturano Luis , Sánchez-Torres Luvia E , Cerbulo-Vázquez Arturo , Chacón-Salinas Rommel , García-Romo Gina S , Orozco-Uribe Mariana C , Yam-Puc Juan C , González-Jiménez Marco A , Paredes-Vivas Yuriria L , Calderón-Amador Juana , Estrada-Parra Sergio , Estrada-García Iris , Flores-Romo Leopoldo
Published: April 2015

Neutrophils are one the earliest, crucial innate defenses against innumerable pathogens. Their main microbicidal activities include phagocytosis and degranulation, with many pharmacologically active molecules contributing to inflammation. Recently, a novel antimicrobial mechanism was discovered; the Neutrophil Extracelullar Traps (NETs) formed by extrusion of DNA and associated molecules (histones, elastase, antimicrobial peptides, among others) which trap and kill microorganisms. Since NETs were recently described, research has focused on their induction and microbicidal properties, and recently on disease involvement. However, the functional consequences of NETs interacting with other immune cells, either resident or recruited during early inflammation, have not been assessed.

We therefore investigated the consequences of exposing two major APCs, macrophages (Mfs) and conventional Dendritic Cells (cDCs) to NETs. Our data revealed that at early times (30 min), both Antigen Presenting Cells (APCs) showed induction of important costimulatory molecules (CD80, CD86). Unexpectedly, however, at later times (6 and 24 hours) NETs apparently triggered a cell death process in these APCs by a caspase- and Apoptosis induced factor (AIF)-dependent pathway, suggesting mitochondrial damage. By rhodamine-123 labelling we found that in both APCs, relatively prolonged exposure to NETs or their components importantly decreased the mitochondrial membrane potential. Ultrastructural analysis confirmed mitochondrial alterations in both APCs.

Our results would suggest that early in inflammation, NETs can activate the two main APCs (Mfs and cDCs), but as the process continues, NETs can then initiate apoptosis of these cells through mitochondrial harm. Conceivable, this “late” induction of cell death in these two APCs might start limiting an ongoing inflammatory process to control it.
Using quality mapping to predict spatial variation in local properties and component performance in Mg alloy thin-walled high-pressure die castings: an ICME approach and case study
Authors: Forsmark Joy H , Zindel Jacob W , Godlewski Larry , Zheng Jiang , Allison John E , Li Mei
Published: April 2015

This paper explores the use of quality mapping for the prediction of the spatial variation in local properties in thin-walled high-pressure die castings (HPDC) of the magnesium alloy AM60. The work investigates the role of casting parameters on local ductility and yield strength and presents a model for predicting local ductility and yield strength in a cast component. A design of experiment (DOE) was created to examine the role of various casting parameters on local properties such as ductility and yield strength. Over 1,200 tensile samples were excised from cast parts and tested. Casting simulations were also conducted for each experimental condition. Local properties were predicted, and the local property (quality map) model was compared with a prototype production component. The results of this model were used as input to a performance simulation software code to simulate the component-level behavior under two different loading conditions. In this study, the authors bypassed the traditional Integrated Computational Materials Engineering (ICME; process-microstructure-properties) approach in favor of a semi-empirical quality mapping approach to provide estimates of manufacturing sensitive local properties for use in process and component design.
Who will benefit from antidepressants in the acute treatment of bipolar depression? A reanalysis of the STEP-BD study by Sachs et al. 2007, using Q-learning
Authors: Wu Fan , Laber Eric B , Lipkovich Ilya A , Severus Emanuel
Published: April 2015

Background

There is substantial uncertainty regarding the efficacy of antidepressants in the treatment of bipolar disorders.

Methods

Traditional randomized controlled trials and statistical methods are not designed to discover if, when, and to whom an intervention should be applied; thus, other methodological approaches are needed that allow for the practice of personalized, evidence-based medicine with patients with bipolar depression.

Results

Dynamic treatment regimes operationalize clinical decision-making as a sequence of decision rules, one per stage of clinical intervention, that map patient information to a recommended treatment. Using data from the acute depression randomized care (RAD) pathway of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study, we estimate an optimal dynamic treatment regime via Q-learning.

Conclusions

The estimated optimal treatment regime presents some evidence that patients in the RAD pathway of STEP-BD who experienced a (hypo)manic episode before the depressive episode may do better to forgo adding an antidepressant to a mandatory mood stabilizer.
Postoperative abnormal response of C-reactive protein as an indicator for infectious complications after oral oncologic surgery with primary reconstruction
Authors: Akashi Masaya , Furudoi Shungo , Hashikawa Kazunobu , Sakakibara Akiko , Hasegawa Takumi , Shigeta Takashi , Minamikawa Tsutomu , Komori Takahide
Published: April 2015

Background

C-reactive protein (CRP) screening has been reported to be reliable for detection of infectious complications. Postoperative abnormal response of CRP can predict wound infection in colorectal surgery. This study aimed to determine the efficacy of CRP monitoring to detect infectious complications in oral oncologic surgery.

Methods

One hundred patients who underwent oral cancer resection with primary reconstruction were enrolled. Postoperative kinetics of CRP were classified into a normal or abnormal response.

Results

A normal CRP response after surgery was observed in 61 patients and an abnormal response was observed in 39. There were postoperative infectious complications in 21 patients, with surgical site infections in 13 patients (early onset in six and late onset in seven). Non-wound infections were found in nine patients. Sensitivity, specificity, the positive predictive value, and the negative predictive value for abnormal CRP response as a predictor for early infectious complications were 100%, 70.1%, 35.9%, and 100%, respectively.

Conclusion

Postoperative serial CRP screening is a useful test as an indicator of infectious complications in oral oncologic surgery. Normal CRP responses can rule out almost all early infectious complications.
Acoustic-gravity waves in the atmosphere generated by infragravity waves in the ocean
Authors: Godin Oleg A , Zabotin Nikolay A , Bullett Terence W
Published: April 2015

Infragravity waves are surface gravity waves in the ocean with periods longer than approximately 30 s. Infragravity waves propagate transoceanic distances and, because of their long wavelengths, provide a mechanism for coupling wave processes in the ocean, atmosphere, and the solid Earth. Here, we present a strict physical justification for the hypothesis that background ocean waves may generate waves in the upper atmosphere. We show that, at frequencies below a certain transition frequency of about 3 mHz, infragravity waves continuously radiate their energy into the upper atmosphere in the form of acoustic-gravity waves. Based on ionospheric observations and estimates of the fluxes of the mechanical energy and momentum from the deep ocean, we conclude that acoustic-gravity waves of oceanic origin may have an observable impact on the upper atmosphere. We anticipate our work to be a starting point for a detailed analysis of global manifestations of the ocean-generated background acoustic-gravity waves.
Assembly of cellulases with synthetic protein scaffolds in vitro
Authors: Yu Ting , Gao Xin , Ren Yuhong , Wei Dongzhi
Published: April 2015

Background

Enzymatic cascades in metabolic pathways are spatially organized in such a way as to facilitate the flow of substrates. The construction of artificial cellulase complexes that mimic natural multienzyme assemblies can potentially enhance the capacity for cellulose hydrolysis. In this study, an artificial cellulase complex was constructed by tethering three cellulases to a synthetic protein scaffold.

Results

Three pairs of interacting proteins were selected and characterized. The artificial protein scaffolds were constructed by fusing three interacting proteins. Cellulases were tethered to these synthetic scaffolds in different orders. The optimal assembly resulted in a 1.5-fold higher hydrolysis of cellulose than that achieved by unassembled cellulases.

Conclusions

A novel artificial protein scaffold was constructed and used to assemble three cellulases. The resultant increase in enzymatic activity suggests that this can be used as a strategy for enhancing the biocatalytic capacity of enzyme cascades.
Benefits and Harms of Citrate Locking Solutions for Hemodialysis Catheters: A Systematic Review and Meta-Analysis
Authors: Grudzinski Alexa , Agarwal Arnav , Bhatnagar Neera , Nesrallah Gihad
Published: April 2015

Background:

Citrate has theoretical advantages over heparin for locking hemodialysis central venous catheters (CVCs), but the comparative effectiveness of these agents is not clear.

Objectives:

1) To compare the benefits and harms of citrate versus heparin locking solutions among patients undergoing hemodialysis through CVCs; 2) to appraise methodological quality of the supporting evidence.

Data sources:

CENTRAL, MEDLINE, EMBASE, CINAHL, ISI Web of Science, and nephrology conference abstracts.

Study eligibility, participants, and interventions:

We included randomized, parallel arm clinical trials that enrolled adult patients (>18 years) receiving chronic hemodialysis through CVCs using a citrate locking solution. We excluded studies in which citrate was combined with other agents, such as antibiotics.

Appraisal and synthesis methods:

We used the GRADE approach to systematic reviews and quality appraisal. Two reviewers performed data extraction independently and in duplicate. We pooled count data using generic inverse variance with random-effects models, and used fixed-effect models when only two studies were available for pooling. Subgroups included low (≤5%) vs. higher (≥30%) citrate.

Results:

We screened 600 citations. Forty-one proceeded to full-text screen; 5 met inclusion criteria. Studies included between 19 and 291 participants (Median N = 61) followed for a total of 174.6 catheter-years; 2 were multi-centred trials. Three studies assessed all-cause mortality; the pooled relative risk for death was 0.71 (95% CI = 0.42–1.24; p = 0.21; I2 = 0%). The rate ratio for bacteremic episodes was 0.54 (95% CI = 0.23–1.29; p = 0.16; I2 = 65%) while the rate ratio for bleeding was 0.48 (95% CI = 0.3–0.75; p = 0.001;I I2 = 5%). Rates of catheter exchange/replacement, all-cause hospitalization and in-situ thrombolysis were not significantly different between groups in any of the pooled analyses. Risk of bias within pooled studies was low.

Limitations:

Outcome definitions varied across studies. Imprecision due to small sample sizes and low event rates reduce our overall confidence in the pooled effect estimates.

Implications:

Benefits and harms of citrate vs. heparin locking solutions remain unclear; larger studies and standardization of outcome measurement and reporting are warranted.

Trial registration:

Protocol Registration Number: CRD42013004781
Determination of parameters of viscoelastic anisotropy from ray velocity and ray attenuation: Theory and numerical modeling
Authors: Vavryčuk Václav
Published: April 2015

We have developed and numerically tested a method for determining parameters of homogeneous viscoelastic anisotropy from measurements of wavefields generated by point sources. The method is based on complex algebra and consists of several steps. First, a complex energy velocity surface is constructed from the directionally dependent velocity and attenuation measured along a set of ray directions. Second, a complex slowness surface is computed using the relation of polar reciprocity between the energy velocity and slowness vectors. The energy velocity vectors are homogeneous, but the corresponding slowness vectors are inhomogeneous. Finally, the complex phase velocity surface is calculated and inverted using the Christoffel equation. The inversion is nonlinear and can be performed in iterations. Numerical tests for the P-wave in transversely isotropic media showed that the method performed well for a wide range of models covering strong as well as weak velocity anisotropy and various levels of attenuation. The method was compared with a simplified approximate inversion when the inhomogeneity of the complex slowness vector is neglected. The neglect of the slowness vector inhomogeneity results in a significantly lower accuracy of the retrieved attenuation parameters. Accuracy with errors less than 10% is achieved only if the attenuation anisotropy is weak. This condition is, however, strongly restrictive because attenuation anisotropy is usually significant being more pronounced than the velocity anisotropy for most of rocks.
Gas-prospective area optimization for Silurian shale gas of Longmaxi Formation in southern Sichuan Basin, China
Authors: Yuqiang Jiang , Qichen Zhang , Hu Zhang , Hui Gan , Mingsheng Luo , Yongbin Huang
Published: April 2015

We investigated the development of a new criterion to quantify and rank marine shale reservoirs of the Lower Silurian Longmaxi Formation and to identify the most prospective area in the southern Sichuan Basin by examining the correlation of various parameters and forming a regionally consistent set. These reliable parameters in our model included geologic factors (rock properties), engineering factors (rock brittleness, in situ stress, and pressure gradient), and topographic factors (pipeline availability and land accessibility). In addition to the common parameters (thickness, depth, porosity, and gas in place), our system used some critical factors associated with complex tectonic evolution and gas preservation in detail, such as in situ stress, pressure gradient, and topographic conditions. An integrated data set was used for designing the well trajectory, creating large volume-induced fractures networks, and increasing the initial production of shale gas. Our integrated approach was used to classify into three ranking levels of Silurian Longmaxi marine shale reservoirs in the Changning area in the southern Sichuan Basin. The integrated approach incorporated a prediction model of pressure gradient and the distribution of in situ stress. The initial production from horizontal wells resulted in a positive assessment as high-performing affordable wells, and served as validation of the methodology used to rank prospective areas.
Slicing and dicing HR seismic acquisition: Varied approaches to delivery of high-resolution 3D seismic data volumes for drilling-hazard studies
Authors: Hill Andrew W. , Arogunmati Adeyemi , Wood Gareth A. , Attoe Duncan , Fiske Mike , Dingler Alison , Dingler Jeff A. , Hobson Mark , Robertshaw Alistair , Allinson Craig , Kjos Einar , Higson Mark , Manning Ted , Kassarie Kern , Lewis Stephen M.
Published: April 2015

Experiences are described in delivering high-resolution 3D (HR3D) volumes to support the definition of drilling hazards for exploration and development drilling in different geologic settings around the world using differing levels of acquisition and processing intensity. The robustness of the HR3D approach delivers high-resolution volumetric imaging for the study of potential drilling hazards. Through acquisition trials and processing simulations, starting with a single-streamer, single-source approach to acquisition of HR3D, data can be delivered at equivalent effort to standard HR2D approaches but as a volume that allows all the advantages of 3D spatial analysis to be applied. Increasing the acquisition intensity increases the quality of the final processed volume and allows more advanced analysis approaches to be applied to the data. Use of multistreamer and multisource approaches offers the opportunity to improve acquisition efficiency with careful consideration of spread designs to maintain high frequencies without introducing directivity effects into the final data. In cases in which there is a need for HR data to support drilling-hazard or development studies, there is now no reason to not always acquire HR3D data. Similarly, in the processing of HR3D data, the full power of modern processing approaches, up to and including prestack depth migration, can be applied to provide further improvements in imaging in complex geologic settings to the benefit of drilling-hazard identification and ongoing improvements to drilling safety and operational integrity.
A GIS-based decision-support approach to deepwater drilling-hazard maps
Authors: Haneberg William C. , Kelly Joshua T. , Graves Hallie L. , Dan Gabriela
Published: April 2015

Drilling-hazard maps — sometimes known as drilling-favorability maps — derived from geophysical data are important tools for communicating the spatial variability of geohazards that might be encountered during deepwater operations. Multiattribute utility theory (MAUT) can be generalized to GIS-based map environments to produce drilling-hazard maps within a structured logical framework that allows for more flexibility and easier sensitivity analysis than simple rule-based approaches. The method is applied in a deepwater area that covers about 2000 km2 of complicated seafloor and shallow-subsurface conditions.