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- Letrozole versus Anastrozole for Height Augmentation in Short Pubertal Males: First Year Data.Neely EK, Kumar RB, Payne SL, Ranadive SA, Suchet DIJ Clin Endocrinol Metab
- In Response.Saidman LJ, Anonymous, AnonymousAnesth Analg
- Positive End-Expiratory Pressure to Increase Internal Jugular Vein Size Is Poorly Tolerated in Obese Anesthetized Adults.Downey LA, Blaine KP, Sliwa J, Macario A, Brock-Utne JAnesth Analg
- A Quantitative Comparison of Single-Cell Whole Genome Amplification Methods.de Bourcy CF, De Vlaminck I, Kanbar JN, Wang J, Gawad C, Quake SRPLoS One
- Simple, standardized incorporation of genetic risk into non-genetic risk prediction tools for complex traits: coronary heart disease as an example.Goldstein BA, Knowles JW, Salfati E, Ioannidis JP, Assimes TLFront Genet
- Computing the Free Energy Barriers for Less by Sampling with a Coarse Reference Potential while Retaining Accuracy of the Target Fine Model.Plotnikov NVJ Chem Theory Comput
- Does aquaculture add resilience to the global food system?Troell M, Naylor RL, Metian M, Beveridge M, Tyedmers PH, Folke C, Arrow KJ, Barrett S, Crépin AS, Ehrlich PR, Gren A, Kautsky N, Levin SA, Nyborg K, Osterblom H, Polasky S, Scheffer M, Walker BH, Xepapadeas T, de Zeeuw AProc Natl Acad Sci U S A
- Optogenetic neuronal stimulation promotes functional recovery after stroke.Cheng MY, Wang EH, Woodson WJ, Wang S, Sun G, Lee AG, Arac A, Fenno LE, Deisseroth K, Steinberg GKProc Natl Acad Sci U S A
- Association Between Vancomycin Trough Concentration and AUC in Neonates.Frymoyer A, Hersh AL, El-Komy MH, Gaskari S, Su F, Drover DR, Van Meurs KAntimicrob Agents Chemother
- Brentuximab Vedotin in the Front-Line Treatment of Patients With CD30+ Peripheral T-Cell Lymphomas: Results of a Phase I Study.Fanale MA, Horwitz SM, Forero-Torres A, Bartlett NL, Advani RH, Pro B, Chen RW, Davies A, Illidge T, Huebner D, Kennedy DA, Shustov ARJ Clin Oncol
- Dual Ambulatory pH Monitoring in Patients with Gastroesophageal Reflux Rendered Asymptomatic with Proton Pump Inhibitor Therapy.Lin D, Triadafilopoulos GDig Dis Sci
- Challenges and solutions to pre- and post-randomization subgroup analyses.Desai M, Pieper KS, Mahaffey KCurr Cardiol Rep
- Are preoperative B-type natriuretic peptide levels associated with outcome after pulmonary artery banding and the double switch operation in patients with congenitally corrected transposition of the great arteries: A pilot study.Char DS, Shiboski SC, Hanley FL, Fineman JRJ Thorac Cardiovasc Surg
- Evidence that Meningeal Mast Cells Can Worsen Stroke Pathology in Mice.Arac A, Grimbaldeston MA, Nepomuceno AR, Olayiwola O, Pereira MP, Nishiyama Y, Tsykin A, Goodall GJ, Schlecht U, Vogel H, Tsai M, Galli SJ, Bliss TM, Steinberg GKAm J Pathol
- Rethinking the potential roles of mast cells in skin wound healing and bleomycin-induced skin fibrosis.Galli SJJ Invest Dermatol
- Genetics of ecological divergence during speciation.Arnegard ME, McGee MD, Matthews B, Marchinko KB, Conte GL, Kabir S, Bedford N, Bergek S, Chan YF, Jones FC, Kingsley DM, Peichel CL, Schluter DNature
- Extending the floor and the ceiling for assessment of physical function.Fries JF, Lingala B, Siemons L, Glas CA, Cella D, Hussain YN, Bruce B, Krishnan EArthritis Rheumatol
- Dual-energy X-ray absorptiometry interpretation and reporting in children and adolescents: the revised 2013 ISCD Pediatric Official Positions.Crabtree NJ, Arabi A, Bachrach LK, Fewtrell M, El-Hajj Fuleihan G, Kecskemethy HH, Jaworski M, Gordon CM, International Society for Clinical DensitometryJ Clin Densitom
- Bone loss in chronic hemiplegia: a longitudinal cohort study.Beaupre GSJ Clin Densitom
- Five-year results of thoracic endovascular aortic repair with the Zenith TX2.Matsumura JS, Melissano G, Cambria RP, Dake MD, Mehta S, Svensson LG, Moore RD, Zenith TX2 Clinical Trial InvestigatorsJ Vasc Surg
- Evaluation of Medicare claims data to ascertain peripheral vascular events in the Women's Health Initiative.Mell MW, Pettinger M, Proulx-Burns L, Heckbert SR, Allison MA, Criqui MH, Hlatky MA, Burwen DR, WHI PVD Writing WorkgroupJ Vasc Surg
- Mechanisms of vitamin D₃ metabolite repression of IgE-dependent mast cell activation.Yip KH, Kolesnikoff N, Yu C, Hauschild N, Taing H, Biggs L, Goltzman D, Gregory PA, Anderson PH, Samuel MS, Galli SJ, Lopez AF, Grimbaldeston MAJ Allergy Clin Immunol
- HE4 (WFDC2) gene overexpression promotes ovarian tumor growth.Moore RG, Hill EK, Horan T, Yano N, Kim K, MacLaughlan S, Lambert-Messerlian G, Tseng YD, Padbury JF, Miller MC, Lange TS, Singh RKSci Rep
- Application of spherical diodes for megavoltage photon beams dosimetry.Barbés B, Azcona JD, Burguete J, Martí-Climent JMMed Phys
- Modality comparison for small animal radiotherapy: a simulation study.Bazalova M, Nelson G, Noll JM, Graves EEMed Phys
- Seeing the invisible: direct visualization of therapeutic radiation beams using air scintillation.Fahimian B, Ceballos A, Türkcan S, Kapp DS, Pratx GMed Phys
- Outcome and clinical significance of delayed endoleaks after endovascular aneurysm repair.Zhou W, Blay E, Varu V, Ali S, Jin MQ, Sun L, Joh JHJ Vasc Surg
- AL amyloidosis or multiple myeloma? An important distinction--response to Falk.Dinner S, Liedtke MBr J Haematol
- Are water precautions necessary after tympanostomy tube placement?Tsao GJ, Goode RLLaryngoscope
- When is the best timing for the second implant in pediatric bilateral cochlear implantation?Santa Maria PL, Oghalai JSLaryngoscope
- Crystal structure of a member of a novel family of dioxygenases (PF10014) reveals a conserved cupin fold and active site.Xu Q, Grant J, Chiu HJ, Farr CL, Jaroszewski L, Knuth MW, Miller MD, Lesley SA, Godzik A, Elsliger MA, Deacon AM, Wilson IAProteins
Letrozole versus Anastrozole for Height Augmentation in Short Pubertal Males: First Year Data.
J Clin Endocrinol Metab. 2014 Aug 19;:jc20142432
Authors: Neely EK, Kumar RB, Payne SL, Ranadive SA, Suchet DI
Context: Aromatase inhibitors are used off-label to treat short stature in peripubertal boys. Objective: To investigate short- and long-term hormonal and auxologic differences in short pubertal boys treated with letrozole (L) or anastrozole (A). Design: Patients are seen for laboratory evaluation and physical examination every 6 months, bone age yearly, DEXA and spine film every 2 years, and will be followed until final height. This is a preliminary report after one year of treatment. Setting: A single academic children's hospital outpatient clinic. Patients: Boys with age >10 years, bone age ≤14 years, clinical and hormonal evidence of central puberty, and either height <fifth percentile or predicted adult height (PAH) more than 10 cm below mid-parental height (MPH). Intervention: Letrozole (2.5mg) or anastrozole (1mg) was administered orally each day. Main outcome measures: Hormonal and clinical parameters, growth velocity and change in bone age and PAH. Results: Thirty-nine boys have completed one year of treatment. Baseline means were age 14.1 years, PAH 166 cm, and testosterone 198 ng/dl. At one year, letrozole resulted in higher LH (L 6.1±2.5 vs A 3.2±1.7 IU/L) and testosterone (1038±348 vs 536±216 ng/dl) with lower estradiol (2.8±2.8 vs 5.6±2.9 pg/ml) and IGF-1 (237±51 vs 331±79 ng/ml). First year growth velocities were identical (7.2 cm/yr), but increase in PAH was greater in the anastrozole group (4.2±3.5 vs 1.4±4.4 cm, p=0.03) after one year. Conclusions: We present first-year data from a direct comparison of anastrozole and letrozole for height augmentation in short pubertal boys. Letrozole was more potent in hormonal manipulation than anastrozole. First-year growth velocities were comparable, but improvement in PAH was greater in the anastrozole group. It remains to be seen if positive PAH trends will translate to increase in final height in either group.
PMID: 25137428 [PubMed - as supplied by publisher]
Anesth Analg. 2014 Sep;119(3):750-751
Authors: Saidman LJ, Anonymous, Anonymous
PMID: 25137011 [PubMed - as supplied by publisher]
Positive End-Expiratory Pressure to Increase Internal Jugular Vein Size Is Poorly Tolerated in Obese Anesthetized Adults.
Anesth Analg. 2014 Sep;119(3):619-621
Authors: Downey LA, Blaine KP, Sliwa J, Macario A, Brock-Utne J
BACKGROUND:: Central venous cannulation is technically challenging in obese patients. We hypothesized that positive end-expiratory pressure (PEEP) increases the size of the internal jugular vein (IJV) in obese adults.
METHODS:: The circumference and cross-sectional area of the IJV were measured in obese patients under general anesthesia at PEEP 0, 5, and 10 cm H2O. Results are reported as means ± SE.
RESULTS:: PEEP at 10 cm H2O was tolerated by 18 of 24 obese patients. Each 5 cm H2O of PEEP increased the cross-sectional area by 0.16 ± 0.02 cm (P < 0.0001) and the circumference by 0.23 ± 0.03 cm (P < 0.0001).
CONCLUSIONS:: PEEP modestly increases the size of the IJV in obese adults but was poorly tolerated because of hypotension.
PMID: 25137000 [PubMed - as supplied by publisher]
A Quantitative Comparison of Single-Cell Whole Genome Amplification Methods.
PLoS One. 2014;9(8):e105585
Authors: de Bourcy CF, De Vlaminck I, Kanbar JN, Wang J, Gawad C, Quake SR
Single-cell sequencing is emerging as an important tool for studies of genomic heterogeneity. Whole genome amplification (WGA) is a key step in single-cell sequencing workflows and a multitude of methods have been introduced. Here, we compare three state-of-the-art methods on both bulk and single-cell samples of E. coli DNA: Multiple Displacement Amplification (MDA), Multiple Annealing and Looping Based Amplification Cycles (MALBAC), and the PicoPLEX single-cell WGA kit (NEB-WGA). We considered the effects of reaction gain on coverage uniformity, error rates and the level of background contamination. We compared the suitability of the different WGA methods for the detection of copy-number variations, for the detection of single-nucleotide polymorphisms and for de-novo genome assembly. No single method performed best across all criteria and significant differences in characteristics were observed; the choice of which amplifier to use will depend strongly on the details of the type of question being asked in any given experiment.
PMID: 25136831 [PubMed - as supplied by publisher]
Simple, standardized incorporation of genetic risk into non-genetic risk prediction tools for complex traits: coronary heart disease as an example.
Front Genet. 2014;5:254
Authors: Goldstein BA, Knowles JW, Salfati E, Ioannidis JP, Assimes TL
PURPOSE: Genetic risk assessment is becoming an important component of clinical decision-making. Genetic Risk Scores (GRSs) allow the composite assessment of genetic risk in complex traits. A technically and clinically pertinent question is how to most easily and effectively combine a GRS with an assessment of clinical risk derived from established non-genetic risk factors as well as to clearly present this information to patient and health care providers.
MATERIALS AND METHODS: We illustrate a means to combine a GRS with an independent assessment of clinical risk using a log-link function. We apply the method to the prediction of coronary heart disease (CHD) in the Atherosclerosis Risk in Communities (ARIC) cohort. We evaluate different constructions based on metrics of effect change, discrimination, and calibration.
RESULTS: The addition of a GRS to a clinical risk score (CRS) improves both discrimination and calibration for CHD in ARIC. RESULTS are similar regardless of whether external vs. internal coefficients are used for the CRS, risk factor single nucleotide polymorphisms (SNPs) are included in the GRS, or subjects with diabetes at baseline are excluded. We outline how to report the construction and the performance of a GRS using our method and illustrate a means to present genetic risk information to subjects and/or their health care provider.
CONCLUSION: The proposed method facilitates the standardized incorporation of a GRS in risk assessment.
PMID: 25136350 [PubMed]
Computing the Free Energy Barriers for Less by Sampling with a Coarse Reference Potential while Retaining Accuracy of the Target Fine Model.
J Chem Theory Comput. 2014 Aug 12;10(8):2987-3001
Authors: Plotnikov NV
Proposed in this contribution is a protocol for calculating fine-physics (e.g., ab initio QM/MM) free-energy surfaces at a high level of accuracy locally (e.g., only at reactants and at the transition state for computing the activation barrier) from targeted fine-physics sampling and extensive exploratory coarse-physics sampling. The full free-energy surface is still computed but at a lower level of accuracy from coarse-physics sampling. The method is analytically derived in terms of the umbrella sampling and the free-energy perturbation methods which are combined with the thermodynamic cycle and the targeted sampling strategy of the paradynamics approach. The algorithm starts by computing low-accuracy fine-physics free-energy surfaces from the coarse-physics sampling in order to identify the reaction path and to select regions for targeted sampling. Thus, the algorithm does not rely on the coarse-physics minimum free-energy reaction path. Next, segments of high-accuracy free-energy surface are computed locally at selected regions from the targeted fine-physics sampling and are positioned relative to the coarse-physics free-energy shifts. The positioning is done by averaging the free-energy perturbations computed with multistep linear response approximation method. This method is analytically shown to provide results of the thermodynamic integration and the free-energy interpolation methods, while being extremely simple in implementation. Incorporating the metadynamics sampling to the algorithm is also briefly outlined. The application is demonstrated by calculating the B3LYP//6-31G*/MM free-energy barrier for an enzymatic reaction using a semiempirical PM6/MM reference potential. These modifications allow computing the activation free energies at a significantly reduced computational cost but at the same level of accuracy compared to computing full potential of mean force.
PMID: 25136268 [PubMed - as supplied by publisher]
Does aquaculture add resilience to the global food system?
Proc Natl Acad Sci U S A. 2014 Aug 18;
Authors: Troell M, Naylor RL, Metian M, Beveridge M, Tyedmers PH, Folke C, Arrow KJ, Barrett S, Crépin AS, Ehrlich PR, Gren A, Kautsky N, Levin SA, Nyborg K, Osterblom H, Polasky S, Scheffer M, Walker BH, Xepapadeas T, de Zeeuw A
Aquaculture is the fastest growing food sector and continues to expand alongside terrestrial crop and livestock production. Using portfolio theory as a conceptual framework, we explore how current interconnections between the aquaculture, crop, livestock, and fisheries sectors act as an impediment to, or an opportunity for, enhanced resilience in the global food system given increased resource scarcity and climate change. Aquaculture can potentially enhance resilience through improved resource use efficiencies and increased diversification of farmed species, locales of production, and feeding strategies. However, aquaculture's reliance on terrestrial crops and wild fish for feeds, its dependence on freshwater and land for culture sites, and its broad array of environmental impacts diminishes its ability to add resilience. Feeds for livestock and farmed fish that are fed rely largely on the same crops, although the fraction destined for aquaculture is presently small (∼4%). As demand for high-value fed aquaculture products grows, competition for these crops will also rise, as will the demand for wild fish as feed inputs. Many of these crops and forage fish are also consumed directly by humans and provide essential nutrition for low-income households. Their rising use in aquafeeds has the potential to increase price levels and volatility, worsening food insecurity among the most vulnerable populations. Although the diversification of global food production systems that includes aquaculture offers promise for enhanced resilience, such promise will not be realized if government policies fail to provide adequate incentives for resource efficiency, equity, and environmental protection.
PMID: 25136111 [PubMed - as supplied by publisher]
Optogenetic neuronal stimulation promotes functional recovery after stroke.
Proc Natl Acad Sci U S A. 2014 Aug 18;
Authors: Cheng MY, Wang EH, Woodson WJ, Wang S, Sun G, Lee AG, Arac A, Fenno LE, Deisseroth K, Steinberg GK
Clinical and research efforts have focused on promoting functional recovery after stroke. Brain stimulation strategies are particularly promising because they allow direct manipulation of the target area's excitability. However, elucidating the cell type and mechanisms mediating recovery has been difficult because existing stimulation techniques nonspecifically target all cell types near the stimulated site. To circumvent these barriers, we used optogenetics to selectively activate neurons that express channelrhodopsin 2 and demonstrated that selective neuronal stimulations in the ipsilesional primary motor cortex (iM1) can promote functional recovery. Stroke mice that received repeated neuronal stimulations exhibited significant improvement in cerebral blood flow and the neurovascular coupling response, as well as increased expression of activity-dependent neurotrophins in the contralesional cortex, including brain-derived neurotrophic factor, nerve growth factor, and neurotrophin 3. Western analysis also indicated that stimulated mice exhibited a significant increase in the expression of a plasticity marker growth-associated protein 43. Moreover, iM1 neuronal stimulations promoted functional recovery, as stimulated stroke mice showed faster weight gain and performed significantly better in sensory-motor behavior tests. Interestingly, stimulations in normal nonstroke mice did not alter motor behavior or neurotrophin expression, suggesting that the prorecovery effect of selective neuronal stimulations is dependent on the poststroke environment. These results demonstrate that stimulation of neurons in the stroke hemisphere is sufficient to promote recovery.
PMID: 25136109 [PubMed - as supplied by publisher]
Association Between Vancomycin Trough Concentration and AUC in Neonates.
Antimicrob Agents Chemother. 2014 Aug 18;
Authors: Frymoyer A, Hersh AL, El-Komy MH, Gaskari S, Su F, Drover DR, Van Meurs K
National treatment guidelines for invasive methicillin-resistant Staphylococcus aureus (MRSA) infections recommend targeting a vancomycin 24-hour area under the curve (AUC24)/MIC >400. The range of vancomycin trough concentrations that best predicts AUC24 >400 in neonates is not known. This understanding would help clarify target trough concentrations for neonates when treating MRSA. A retrospective chart review from a level III neonatal intensive care unit was performed to identify neonates treated with vancomycin over a 5-year period. Vancomycin concentrations and clinical covariates were utilized to develop a one-compartment population pharmacokinetic model and examine relationships between trough and AUC24 in study neonates. Monte Carlo simulations were performed to examine the effect of dose, post-menstrual age (PMA), and serum creatinine on trough and AUC24 achievement. A total of 1702 vancomycin concentrations from 249 neonates were available for analysis. The median [interquartile range] PMA was 39 wks [32-42 wks] and weight was 2.9 kg [1.6-3.7kg]. Vancomycin clearance was predicted by weight, PMA, and creatinine. At a trough of 10 mg/L, 89% of study neonates had an AUC24 >400. Monte Carlo simulations demonstrated that troughs ranging from 7-11 mg/L were highly predictive of an AUC24 >400 across a range of PMA, serum creatinine, and vancomycin doses. However, a trough ≥10 mg/L was not readily achieved in most simulated subgroups using routine starting doses. Higher starting doses frequently resulted in troughs >20 mg/L. A vancomycin trough of ∼10 mg/L is likely adequate for most neonates with invasive MRSA infections based on AUC24 considerations. Due to pharmacokinetic and clinical heterogeneity in neonates, consistently achieving this target vancomycin exposure with routine starting doses will be difficult. More robust clinical dosing support tools are needed to help clinicians with dose individualization.
PMID: 25136027 [PubMed - as supplied by publisher]
Brentuximab Vedotin in the Front-Line Treatment of Patients With CD30+ Peripheral T-Cell Lymphomas: Results of a Phase I Study.
J Clin Oncol. 2014 Aug 18;
Authors: Fanale MA, Horwitz SM, Forero-Torres A, Bartlett NL, Advani RH, Pro B, Chen RW, Davies A, Illidge T, Huebner D, Kennedy DA, Shustov AR
PURPOSE: Front-line treatment of peripheral T-cell lymphomas (PTCL) involves regimens such as cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and results in a 5-year overall survival (OS) rate of less than 50%. This phase I open-label study evaluated the safety and activity of brentuximab vedotin administered sequentially with CHOP or in combination with CHP (CHOP without vincristine) as front-line treatment in patients with CD30(+) PTCL.
PATIENTS AND METHODS: Patients received sequential treatment (once every 3 weeks) with brentuximab vedotin 1.8 mg/kg (two cycles) followed by CHOP (six cycles) or brentuximab vedotin 1.8 mg/kg plus CHP (BV+CHP) for six cycles (once every 3 weeks). Responders received single-agent brentuximab vedotin for eight to 10 additional cycles (for a total of 16 cycles). The primary objective was assessment of safety; secondary end points included objective response rate, complete remission (CR) rate, progression-free survival rate (PFS), and OS. There were no prespecified comparisons of the two treatment approaches.
RESULTS: After sequential treatment, 11 (85%) of 13 patients achieved an objective response (CR rate, 62%; estimated 1-year PFS rate, 77%). Grade 3/4 adverse events occurred in eight (62%) of 13 patients. At the end of combination treatment, all patients (n = 26) achieved an objective response (CR rate, 88%; estimated 1-year PFS rate, 71%). All seven patients without anaplastic large-cell lymphoma achieved CR. Grade 3/4 adverse events (≥ 10%) in the combination-treatment group were febrile neutropenia (31%), neutropenia (23%), anemia (15%), and pulmonary embolism (12%).
CONCLUSION: Brentuximab vedotin, administered sequentially with CHOP or in combination with CHP, had a manageable safety profile and exhibited substantial antitumor activity in newly diagnosed patients with CD30(+) PTCL. A randomized phase III trial is under way, comparing BV+CHP with CHOP (clinical trial No. NCT01777152).
PMID: 25135998 [PubMed - as supplied by publisher]
Dual Ambulatory pH Monitoring in Patients with Gastroesophageal Reflux Rendered Asymptomatic with Proton Pump Inhibitor Therapy.
Dig Dis Sci. 2014 Aug 19;
Authors: Lin D, Triadafilopoulos G
BACKGROUND: Studies have suggested that proton pump inhibitor (PPI) therapy in gastroesophageal reflux disease (GERD) achieves high rates of esophageal acid normalization.
AIMS: Our aims were to investigate the adequacy of esophageal and gastric acid suppression in reflux patients rendered asymptomatic on optimized PPI therapy.
METHODS: We retrospectively analyzed outcomes of dual-sensor, ambulatory 24-h pH monitoring in referred persistent reflux patients rendered asymptomatic on PPI therapy. After optimization, we analyzed esophageal and gastric pH profiles to assess acid suppression and examine differences between PPIs. In patients with repeat studies, comparisons between different PPI doses were made.
RESULTS: Of 172 asymptomatic GERD patients, 75 (43.6 %) achieved symptomatic remission with once-daily dosing PPI, and 97 (56.4 %) patients required twice-daily dosing. Of the entire cohort, 93 (54.1 %) had abnormal and 79 (45.9 %) had normal esophageal pH profiles, with mean percent time pH < 4.0 of 14.3 and 2.4, respectively (p < 0.0001). The percent time esophageal pH was abnormal did not correlate with the percent time gastric pH was abnormal (p = 0.17). Different PPI formulations demonstrated differences in gastric-not esophageal-pH times, with esomeprazole exhibiting superior gastric pH suppression (p < 0.0001). Overall, gastric pH control remained suboptimal, with pH < 4.0 ranging between 30 and 50 %. Among patients with sequential pH studies, those with higher PPI dose had improved esophageal pH profiles (p < 0.01).
CONCLUSIONS: In GERD patients rendered asymptomatic on PPI therapy, most continue to experience abnormal esophageal and gastric acid exposure. The efficacy of acid suppression therapy, in certain patients, may be much lower than previously thought.
PMID: 25135815 [PubMed - as supplied by publisher]
Challenges and solutions to pre- and post-randomization subgroup analyses.
Curr Cardiol Rep. 2014 Oct;16(10):531
Authors: Desai M, Pieper KS, Mahaffey K
Subgroup analyses are commonly performed in the clinical trial setting with the purpose of illustrating that the treatment effect was consistent across different patient characteristics or identifying characteristics that should be targeted for treatment. There are statistical issues involved in performing subgroup analyses, however. These have been given considerable attention in the literature for analyses where subgroups are defined by a pre-randomization feature. Although subgroup analyses are often performed with subgroups defined by a post-randomization feature-including analyses that estimate the treatment effect among compliers-discussion of these analyses has been neglected in the clinical literature. Such analyses pose a high risk of presenting biased descriptions of treatment effects. We summarize the challenges of doing all types of subgroup analyses described in the literature. In particular, we emphasize issues with post-randomization subgroup analyses. Finally, we provide guidelines on how to proceed across the spectrum of subgroup analyses.
PMID: 25135344 [PubMed - in process]
Are preoperative B-type natriuretic peptide levels associated with outcome after pulmonary artery banding and the double switch operation in patients with congenitally corrected transposition of the great arteries: A pilot study.
J Thorac Cardiovasc Surg. 2014 Jul 24;
Authors: Char DS, Shiboski SC, Hanley FL, Fineman JR
PMID: 25135237 [PubMed - as supplied by publisher]
Evidence that Meningeal Mast Cells Can Worsen Stroke Pathology in Mice.
Am J Pathol. 2014 Sep;184(9):2493-504
Authors: Arac A, Grimbaldeston MA, Nepomuceno AR, Olayiwola O, Pereira MP, Nishiyama Y, Tsykin A, Goodall GJ, Schlecht U, Vogel H, Tsai M, Galli SJ, Bliss TM, Steinberg GK
Stroke is the leading cause of adult disability and the fourth most common cause of death in the United States. Inflammation is thought to play an important role in stroke pathology, but the factors that promote inflammation in this setting remain to be fully defined. An understudied but important factor is the role of meningeal-located immune cells in modulating brain pathology. Although different immune cells traffic through meningeal vessels en route to the brain, mature mast cells do not circulate but are resident in the meninges. With the use of genetic and cell transfer approaches in mice, we identified evidence that meningeal mast cells can importantly contribute to the key features of stroke pathology, including infiltration of granulocytes and activated macrophages, brain swelling, and infarct size. We also obtained evidence that two mast cell-derived products, interleukin-6 and, to a lesser extent, chemokine (C-C motif) ligand 7, can contribute to stroke pathology. These findings indicate a novel role for mast cells in the meninges, the membranes that envelop the brain, as potential gatekeepers for modulating brain inflammation and pathology after stroke.
PMID: 25134760 [PubMed - in process]
Rethinking the potential roles of mast cells in skin wound healing and bleomycin-induced skin fibrosis.
J Invest Dermatol. 2014 Jul;134(7):1802-4
Authors: Galli SJ
Skin wound healing and bleomycin-induced skin fibrosis are thought to reflect complex interactions among diverse cell types. Several lines of evidence have implicated mast cells in these tissue responses. However, data from Willenborg et al. (this issue) and from three other groups suggest that, in at least these examples of cutaneous tissue remodeling, mast cells may not have nonredundant roles.
PMID: 24924762 [PubMed - indexed for MEDLINE]
Genetics of ecological divergence during speciation.
Nature. 2014 Jul 17;511(7509):307-11
Authors: Arnegard ME, McGee MD, Matthews B, Marchinko KB, Conte GL, Kabir S, Bedford N, Bergek S, Chan YF, Jones FC, Kingsley DM, Peichel CL, Schluter D
Ecological differences often evolve early in speciation as divergent natural selection drives adaptation to distinct ecological niches, leading ultimately to reproductive isolation. Although this process is a major generator of biodiversity, its genetic basis is still poorly understood. Here we investigate the genetic architecture of niche differentiation in a sympatric species pair of threespine stickleback fish by mapping the environment-dependent effects of phenotypic traits on hybrid feeding and performance under semi-natural conditions. We show that multiple, unlinked loci act largely additively to determine position along the major niche axis separating these recently diverged species. We also find that functional mismatch between phenotypic traits reduces the growth of some stickleback hybrids beyond that expected from an intermediate phenotype, suggesting a role for epistasis between the underlying genes. This functional mismatch might lead to hybrid incompatibilities that are analogous to those underlying intrinsic reproductive isolation but depend on the ecological context.
PMID: 24909991 [PubMed - indexed for MEDLINE]
Extending the floor and the ceiling for assessment of physical function.
Arthritis Rheumatol. 2014 May;66(5):1378-87
Authors: Fries JF, Lingala B, Siemons L, Glas CA, Cella D, Hussain YN, Bruce B, Krishnan E
OBJECTIVE: To improve the assessment of physical function by enhancing precision of physical function assessment as it pertains to subjects at extreme ends of the health continuum (i.e., subjects with extremely poor function ["floor"] or extremely good health ["ceiling"]).
METHODS: Under the Patient-Reported Outcomes Measurement Information System (PROMIS) (a National Institutes of Health initiative), we developed new items to assess floor and ceiling physical function in order to supplement the existing item bank. Using item response theory and standard PROMIS methodology, we developed 31 floor items and 31 ceiling items and administered the items during a 12-month prospective, observational study of 737 subjects whose health status was at either extreme. Effect size was calculated and change over time was compared across anchor instruments and across items. Using the observed changes in scores, we back-calculated sample size requirements for the new and comparison measures.
RESULTS: We studied 444 subjects who had been diagnosed as having a chronic illness and/or were of old age and 293 generally fit subjects (including athletes in training). Item response theory analyses confirmed that the new floor and ceiling items outperformed reference items (P < 0.001). The estimated post hoc sample size requirements were reduced by a factor of 2-4 for the floor population and a factor of 2 for the ceiling population.
CONCLUSION: Extending the range of items by which physical function is measured can substantially improve measurement quality, reduce sample size requirements, and improve research efficiency. The paradigm shift from assessing disability to assessing physical function focuses assessment on the entire spectrum of physical function, signals improvement in the conceptual base of outcome assessment, and may be transformative as medical goals more closely approach societal goals for health.
PMID: 24782194 [PubMed - indexed for MEDLINE]
Dual-energy X-ray absorptiometry interpretation and reporting in children and adolescents: the revised 2013 ISCD Pediatric Official Positions.
J Clin Densitom. 2014 Apr-Jun;17(2):225-42
Authors: Crabtree NJ, Arabi A, Bachrach LK, Fewtrell M, El-Hajj Fuleihan G, Kecskemethy HH, Jaworski M, Gordon CM, International Society for Clinical Densitometry
The International Society for Clinical Densitometry Official Revised Positions on reporting of densitometry results in children represent current expert recommendations to assist health care providers determine which skeletal sites should be measured, which, if any, adjustments should be made, reference databases to be used, and the elements to include in a dual-energy X-ray absorptiometry report. The recommended scanning sites remain the total body less head and the posterior-anterior spine. Other sites such as the proximal femur, lateral distal femur, lateral vertebral assessment, and forearm are discussed but are only recommended for specific pediatric populations. Different methods of interpreting bone density scans in children with short stature or growth delay are presented. The use of bone mineral apparent density and height-adjusted Z-scores are recommended as suitable size adjustment techniques. The validity of appropriate reference databases and technical considerations to consider when upgrading software and hardware remain unchanged. Updated reference data sets for all contemporary bone densitometers are listed. The inclusion of relevant demographic and health information, technical details of the scan, Z-scores, and the wording "low bone mass or bone density" for Z-scores less than or equal to -2.0 standard deviation are still recommended for clinical practice. The rationale and evidence for the development of the Official Positions are provided. Changes in the grading of quality of evidence, strength of recommendation, and worldwide applicability represent a change in current evidence and/or differences in opinion of the expert panelists used to validate the position statements for the 2013 Position Development Conference.
PMID: 24690232 [PubMed - indexed for MEDLINE]
Bone loss in chronic hemiplegia: a longitudinal cohort study.
J Clin Densitom. 2014 Apr-Jun;17(2):325-6
Authors: Beaupre GS
PMID: 24650568 [PubMed - indexed for MEDLINE]
Five-year results of thoracic endovascular aortic repair with the Zenith TX2.
J Vasc Surg. 2014 Jul;60(1):1-10
Authors: Matsumura JS, Melissano G, Cambria RP, Dake MD, Mehta S, Svensson LG, Moore RD, Zenith TX2 Clinical Trial Investigators
BACKGROUND: This trial evaluated thoracic endovascular aortic repair (TEVAR) compared with open surgical repair of descending thoracic aortic aneurysms and large ulcers at 42 international sites. Whereas several studies demonstrate early safety and utility advantages with TEVAR, longer follow-up is important because of concerns about durability of TEVAR.
METHODS: This prospective, nonrandomized study enrolled 160 TEVAR patients treated with the Cook Zenith TX2 and 70 open surgical repair patients.
RESULTS: Although follow-up was limited, 5-year mortality rate was similar at 37% for both groups. Aneurysm-related mortality rate was 5.9% with TEVAR compared with 12% with open surgical repair (P = .11). There were no ruptures of the treated aneurysms in either group or open conversions in the TEVAR group. Predefined severe morbidity occurred at a significantly lower rate in TEVAR (21%) compared with open surgical repair (39%; P < .001). Aneurysm growth was seen by core laboratory in 5.9% of patients and endoleak in 5.7% of patients. Secondary intervention rates were similar between TEVAR (8%) and open surgical repair (12%; P = .49) patients.
CONCLUSIONS: Five-year results indicate similar all-cause mortality and aneurysm-related mortality with TEVAR compared with open repair. There was a persistent reduction of severe complications with TEVAR. Reinterventions occurred with similar frequency. TEVAR with the TX2 is a safe and effective alternative to open surgical repair for the treatment of anatomically suitable descending thoracic aortic aneurysms and ulcers.
PMID: 24636714 [PubMed - indexed for MEDLINE]
Evaluation of Medicare claims data to ascertain peripheral vascular events in the Women's Health Initiative.
J Vasc Surg. 2014 Jul;60(1):98-105
Authors: Mell MW, Pettinger M, Proulx-Burns L, Heckbert SR, Allison MA, Criqui MH, Hlatky MA, Burwen DR, WHI PVD Writing Workgroup
OBJECTIVE: Capturing long-term outcomes from large clinical databases by use of claims data is a potential strategy for improving efficiency while reducing study costs. We sought to compare the use of Medicare data with data from the Women's Health Initiative (WHI) to determine peripheral vascular events, as defined by the WHI study design.
METHODS: We studied participants from the WHI with both adjudicated outcomes and links to Medicare enrollment and utilization data through 2007. Outcomes of interest included hospitalizations for treatment of abdominal aortic aneurysm (AAA), lower extremity peripheral artery disease (LE PAD), and carotid artery stenosis (CAS). Events determined by WHI adjudication were compared with events defined by coding algorithms using diagnosis and procedure codes from Medicare data with a pilot data set and then validated with a test data set. We assessed agreement by a κ statistic and evaluated reasons for disagreement.
RESULTS: In the pilot set, records from 50,511 participants were analyzed. Agreement between the Centers for Medicare and Medicaid Services and WHI for admissions with a diagnosis but no treatment procedures for vascular conditions was poor (κ, 0.02-0.18). On the basis of WHI outcome data collection, vascular treatment procedures occurred in 29 participants for AAA, 204 for LE PAD events, and 281 for CAS. Medicare hospital claims recorded 41 treatments for AAA, 255 for LE PAD, and 317 for CAS. For participants with a Centers for Medicare and Medicaid Services-captured vascular procedure and a record adjudicated by WHI, κ values for treatment procedures were 0.81 for AAA, 0.77 for PAD, and 0.93 for CAS. For vascular procedures identified by WHI but not by Medicare hospital data (n = 82), 55% were captured by Medicare physician claims. Conversely, for treatments identified by Medicare hospital data but not captured by WHI adjudication (n = 57), 74% had physician claims consistent with the procedure. Fifteen participants with AAA or LE PAD procedures in hospital claims had medical records available for review, and nine of these had definitive documentation of procedures that were not captured by the WHI adjudication process. Estimated positive predictive value of Medicare data was 91% to 94% for AAA, 92% to 95% for LE PAD, and 94% to 99% for CAS. Available test set data (n = 50,253) yielded generally similar results with κ of 0.77 for AAA, 0.79 for LE PAD, and 0.94 for CAS.
CONCLUSIONS: Medicare data appear useful for identifying vascular treatment procedures for WHI participants. Medicare hospital claims identify more procedures than WHI does, with high positive predictive value, but also may not capture some procedures identified in WHI.
PMID: 24636641 [PubMed - indexed for MEDLINE]
Mechanisms of vitamin D₃ metabolite repression of IgE-dependent mast cell activation.
J Allergy Clin Immunol. 2014 May;133(5):1356-64, 1364.e1-14
Authors: Yip KH, Kolesnikoff N, Yu C, Hauschild N, Taing H, Biggs L, Goltzman D, Gregory PA, Anderson PH, Samuel MS, Galli SJ, Lopez AF, Grimbaldeston MA
BACKGROUND: Mast cells have gained notoriety based on their detrimental contributions to IgE-mediated allergic disorders. Although mast cells express the vitamin D receptor (VDR), it is not clear to what extent 1α,25-dihydroxyvitamin D3 (1α,25[OH]2D3) or its predominant inactive precursor metabolite in the circulation, 25-hydroxyvitamin D3 (25OHD3), can influence IgE-mediated mast cell activation and passive cutaneous anaphylaxis (PCA) in vivo.
OBJECTIVE: We sought to assess whether the vitamin D3 metabolites 25OHD3 and 1α,25(OH)2D3 can repress IgE-dependent mast cell activation through mast cell-25-hydroxyvitamin D-1α-hydroxylase (CYP27B1) and mast cell-VDR activity.
METHODS: We measured the extent of vitamin D3 suppression of IgE-mediated mast cell degranulation and mediator production in vitro, as well as the vitamin D3-induced curtailment of PCA responses in WBB6F1-Kit(W/W-v) or C57BL/6J-Kit(W-sh/W-sh) mice engrafted with mast cells that did or did not express VDR or CYP27B1.
RESULTS: Here we show that mouse and human mast cells can convert 25OHD3 to 1α,25(OH)2D3 through CYP27B1 activity and that both of these vitamin D3 metabolites suppressed IgE-induced mast cell-derived proinflammatory and vasodilatory mediator production in a VDR-dependent manner in vitro. Furthermore, epicutaneously applied vitamin D3 metabolites significantly reduced the magnitude of skin swelling associated with IgE-mediated PCA reactions in vivo; a response that required functional mast cell-VDRs and mast cell-CYP27B1.
CONCLUSION: Taken together, our findings provide a mechanistic explanation for the anti-inflammatory effects of vitamin D3 on mast cell function by demonstrating that mast cells can actively metabolize 25OHD3 to dampen IgE-mediated mast cell activation in vitro and in vivo.
PMID: 24461581 [PubMed - indexed for MEDLINE]
HE4 (WFDC2) gene overexpression promotes ovarian tumor growth.
Sci Rep. 2014;4:3574
Authors: Moore RG, Hill EK, Horan T, Yano N, Kim K, MacLaughlan S, Lambert-Messerlian G, Tseng YD, Padbury JF, Miller MC, Lange TS, Singh RK
Selective overexpression of Human epididymal secretory protein E4 (HE4) points to a role in ovarian cancer tumorigenesis but little is known about the role the HE4 gene or the gene product plays. Here we show that elevated HE4 serum levels correlate with chemoresistance and decreased survival rates in EOC patients. HE4 overexpression promoted xenograft tumor growth and chemoresistance against cisplatin in an animal model resulting in reduced survival rates. HE4 displayed responses to tumor microenvironment constituents and presented increased expression as well as nuclear translocation upon EGF, VEGF and Insulin treatment and nucleolar localization with Insulin treatment. HE4 interacts with EGFR, IGF1R, and transcription factor HIF1α. Constructs of antisense phosphorothio-oligonucleotides targeting HE4 arrested tumor growth in nude mice. Collectively these findings implicate increased HE4 expression as a molecular factor in ovarian cancer tumorigenesis. Selective targeting directed towards the HE4 protein demonstrates therapeutic benefits for the treatment of ovarian cancer.
PMID: 24389815 [PubMed - indexed for MEDLINE]
Application of spherical diodes for megavoltage photon beams dosimetry.
Med Phys. 2014 Jan;41(1):012102
Authors: Barbés B, Azcona JD, Burguete J, Martí-Climent JM
PURPOSE: External beam radiation therapy (EBRT) usually uses heterogeneous dose distributions in a given volume. Designing detectors for quality control of these treatments is still a developing subject. The size of the detectors should be small to enhance spatial resolution and ensure low perturbation of the beam. A high uniformity in angular response is also a very important feature in a detector, because it has to measure radiation coming from all the directions of the space. It is also convenient that detectors are inexpensive and robust, especially to perform in vivo measurements. The purpose of this work is to introduce a new detector for measuring megavoltage photon beams and to assess its performance to measure relative dose in EBRT.
METHODS: The detector studied in this work was designed as a spherical photodiode (1.8 mm in diameter). The change in response of the spherical diodes is measured regarding the angle of incidence, cumulated irradiation, and instantaneous dose rate (or dose per pulse). Additionally, total scatter factors for large and small fields (between 1 × 1 cm(2) and 20 × 20 cm(2)) are evaluated and compared with the results obtained from some commercially available ionization chambers and planar diodes. Additionally, the over-response to low energy scattered photons in large fields is investigated using a shielding layer.
RESULTS: The spherical diode studied in this work produces a high signal (150 nC/Gy for photons of nominal energy of 15 MV and 160 for 6 MV, after 12 kGy) and its angular dependence is lower than that of planar diodes: less than 5% between maximum and minimum in all directions, and 2% around one of the axis. It also has a moderated variation with accumulated dose (about 1.5%/kGy for 15 MV photons and 0.7%/kGy for 6 MV, after 12 kGy) and a low variation with dose per pulse (± 0.4%), and its behavior is similar to commercial diodes in total scatter factor measurements.
CONCLUSIONS: The measurements of relative dose using the spherical diode described in this work show its feasibility for the dosimetry of megavoltage photon beams. A particularly important feature is its good angular response in the MV range. They would be good candidates for in vivo dosimetry, and quality assurance of VMAT and tomotherapy, and other modalities with beams irradiating from multiple orientations, such as Cyberknife and ViewRay, with minor modifications.
PMID: 24387520 [PubMed - indexed for MEDLINE]
Modality comparison for small animal radiotherapy: a simulation study.
Med Phys. 2014 Jan;41(1):011710
Authors: Bazalova M, Nelson G, Noll JM, Graves EE
PURPOSE: Small animal radiation therapy has advanced significantly in recent years. Whereas in the past dose was delivered using a single beam and a lead shield for sparing of healthy tissue, conformal doses can be now delivered using more complex dedicated small animal radiotherapy systems with image guidance. The goal of this paper is to investigate dose distributions for three small animal radiation treatment modalities.
METHODS: This paper presents a comparison of dose distributions generated by the three approaches-a single-field irradiator with a 200 kV beam and no image guidance, a small animal image-guided conformal system based on a modified microCT scanner with a 120 kV beam developed at Stanford University, and a dedicated conformal system, SARRP, using a 220 kV beam developed at Johns Hopkins University. The authors present a comparison of treatment plans for the three modalities using two cases: a mouse with a subcutaneous tumor and a mouse with a spontaneous lung tumor. A 5 Gy target dose was calculated using the EGSnrc Monte Carlo codes.
RESULTS: All treatment modalities generated similar dose distributions for the subcutaneous tumor case, with the highest mean dose to the ipsilateral lung and bones in the single-field plan (0.4 and 0.4 Gy) compared to the microCT (0.1 and 0.2 Gy) and SARRP (0.1 and 0.3 Gy) plans. The lung case demonstrated that due to the nine-beam arrangements in the conformal plans, the mean doses to the ipsilateral lung, spinal cord, and bones were significantly lower in the microCT plan (2.0, 0.4, and 1.9 Gy) and the SARRP plan (1.5, 0.5, and 1.8 Gy) than in single-field irradiator plan (4.5, 3.8, and 3.3 Gy). Similarly, the mean doses to the contralateral lung and the heart were lowest in the microCT plan (1.5 and 2.0 Gy), followed by the SARRP plan (1.7 and 2.2 Gy), and they were highest in the single-field plan (2.5 and 2.4 Gy). For both cases, dose uniformity was greatest in the single-field irradiator plan followed by the SARRP plan due to the sensitivity of the lower energy microCT beam to target heterogeneities and image noise.
CONCLUSIONS: The two treatment planning examples demonstrate that modern small animal radiotherapy techniques employing image guidance, variable collimation, and multiple beam angles deliver superior dose distributions to small animal tumors as compared to conventional treatments using a single-field irradiator. For deep-seated mouse tumors, however, higher-energy conformal radiotherapy could result in higher doses to critical organs compared to lower-energy conformal radiotherapy. Treatment planning optimization for small animal radiotherapy should therefore be developed to take full advantage of the novel conformal systems.
PMID: 24387502 [PubMed - indexed for MEDLINE]
Seeing the invisible: direct visualization of therapeutic radiation beams using air scintillation.
Med Phys. 2014 Jan;41(1):010702
Authors: Fahimian B, Ceballos A, Türkcan S, Kapp DS, Pratx G
PURPOSE: To assess whether air scintillation produced during standard radiation treatments can be visualized and used to monitor a beam in a nonperturbing manner.
METHODS: Air scintillation is caused by the excitation of nitrogen gas by ionizing radiation. This weak emission occurs predominantly in the 300-430 nm range. An electron-multiplication charge-coupled device camera, outfitted with an f/0.95 lens, was used to capture air scintillation produced by kilovoltage photon beams and megavoltage electron beams used in radiation therapy. The treatment rooms were prepared to block background light and a short-pass filter was utilized to block light above 440 nm.
RESULTS: Air scintillation from an orthovoltage unit (50 kVp, 30 mA) was visualized with a relatively short exposure time (10 s) and showed an inverse falloff (r(2) = 0.89). Electron beams were also imaged. For a fixed exposure time (100 s), air scintillation was proportional to dose rate (r(2) = 0.9998). As energy increased, the divergence of the electron beam decreased and the penumbra improved. By irradiating a transparent phantom, the authors also showed that Cherenkov luminescence did not interfere with the detection of air scintillation. In a final illustration of the capabilities of this new technique, the authors visualized air scintillation produced during a total skin irradiation treatment.
CONCLUSIONS: Air scintillation can be measured to monitor a radiation beam in an inexpensive and nonperturbing manner. This physical phenomenon could be useful for dosimetry of therapeutic radiation beams or for online detection of gross errors during fractionated treatments.
PMID: 24387491 [PubMed - indexed for MEDLINE]
Outcome and clinical significance of delayed endoleaks after endovascular aneurysm repair.
J Vasc Surg. 2014 Apr;59(4):915-20
Authors: Zhou W, Blay E, Varu V, Ali S, Jin MQ, Sun L, Joh JH
OBJECTIVE: Endovascular aneurysm repair (EVAR) is considered the standard therapy for most patients with abdominal aortic aneurysm (AAA). Endoleak is a well-known EVAR-related complication that requires long-term follow-up. However, patient follow-up is often challenging outside clinical trials. We sought to evaluate the incidence and the effect of delayed endoleaks in a Veterans Administration (VA) health care system where long-term follow-up is ensured.
METHODS: We retrospectively evaluated 213 consecutive patients who underwent EVAR at a referral Veterans Administration medical center. Age, aneurysm size, patency of lumbar and inferior mesenteric arteries, and follow-up evaluations were recorded. Type of endoleak, date of detection, and intervention were also documented. Patients who had <1 year of follow-up were excluded. The χ(2) test, Student t-test, Mann-Whitney test, and Spearman correlation were used for data analysis.
RESULTS: The analysis included 183 patients with a mean follow-up of 53 months (range, 12-141 months); of these, 48 patients (26%) had endoleaks, and 31 (17%) had aneurysm progression. The mean diagnosis time for nontype II (n = 14) endoleaks was 45 months (range, 3-127 months), and 71% were diagnosed >1 year after EVAR. All except one nontype II endoleak received prompt secondary interventions, and the one without intervention presented with aneurysm rupture. An isolated type II endoleak was detected in 34 patients at an average of 14.4 months (range, 0-76 months) after EVAR, 41% of which were detected >1 year after EVAR. Patients without a documented endoleak had a significant decrease in aneurysm size at the latest computed tomography evaluation compared to the preoperative size (4.8 vs 5.7 cm; P < .001), whereas those with isolated type II endoleak had an increase at the latest computed tomography follow-up compared to preoperative size (5.8 vs 5.7 cm). Importantly, 59% of the patients with a type II endoleak had significant AAA enlargement (0.8 cm), and delayed type II endoleak was significantly associated with sac enlargement compared to type II endoleaks detected early. No significant correlation was seen between the diameter of inferior mesenteric artery or lumbar to AAA enlargement among the patients with a type II endoleak. Secondary interventions in 12 patients with isolated type II endoleak resulted in overall aneurysm stabilization or regression.
CONCLUSIONS: This long-term outcome study demonstrated that delayed endoleaks appearing >1 year after EVAR contributed to most of the overall endoleaks and were significantly associated with aneurysm sac growth. This study underscores that type II endoleak is not benign and that vigilant lifelong surveillance after EVAR is critical.
PMID: 24360584 [PubMed - indexed for MEDLINE]
AL amyloidosis or multiple myeloma? An important distinction--response to Falk.
Br J Haematol. 2014 Mar;164(5):749-50
Authors: Dinner S, Liedtke M
PMID: 24344936 [PubMed - indexed for MEDLINE]
Are water precautions necessary after tympanostomy tube placement?
Laryngoscope. 2014 Jul;124(7):1513-4
Authors: Tsao GJ, Goode RL
PMID: 24142762 [PubMed - indexed for MEDLINE]
When is the best timing for the second implant in pediatric bilateral cochlear implantation?
Laryngoscope. 2014 Jul;124(7):1511-2
Authors: Santa Maria PL, Oghalai JS
PMID: 24122858 [PubMed - indexed for MEDLINE]
Crystal structure of a member of a novel family of dioxygenases (PF10014) reveals a conserved cupin fold and active site.
Proteins. 2014 Jan;82(1):164-70
Authors: Xu Q, Grant J, Chiu HJ, Farr CL, Jaroszewski L, Knuth MW, Miller MD, Lesley SA, Godzik A, Elsliger MA, Deacon AM, Wilson IA
PF10014 is a novel family of 2-oxyglutarate-Fe(2+) -dependent dioxygenases that are involved in biosynthesis of antibiotics and regulation of biofilm formation, likely by catalyzing hydroxylation of free amino acids or other related ligands. The crystal structure of a PF10014 member from Methylibium petroleiphilum at 1.9 Å resolution shows strong structural similarity to cupin dioxygenases in overall fold and active site, despite very remote homology. However, one of the β-strands of the cupin catalytic core is replaced by a loop that displays conformational isomerism that likely regulates the active site.
PMID: 23852666 [PubMed - indexed for MEDLINE]
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