Methods: In a randomized controlled trial, preterm

ne

\n\nMethods: In a randomized controlled trial, preterm

neonates with Silverman-Anderson score epsilon 4 and oxygen requirement > 30% within first 6 h of life were randomly allocated to BCPAP or VCPAP. Proportion of neonates with success or failure was compared.\n\nResults: In all, 47 of 57 (82.5%) neonates from BCPAP group and 36 of 57 (63.2%) neonates from the VCPAP group completed CPAP successfully (p = 0.03). Neonates who failed CPAP had higher Silverman-Anderson score (p < 0.01), lower arterial to alveolar oxygenation ratio (p < 0.05) and needed surfactant more frequently (p < 0.01).\n\nConclusion: BCPAP has higher success rate than VCPAP for managing preterm neonates with early onset respiratory distress, with comparable safety.”
“Purpose Lateral tilt (radially inclined) radiographs are useful after volar locked GKT137831 clinical trial plate fixation of distal radius fractures to

assess the radiocarpal joint, subchondral bone congruity, and volar tilt. The purpose of our study was to define the reliability of our positioning method using the patient’s opposite hand to position the injured wrist to obtain an inclined lateral radiograph with good visualization of the subchondral bone.\n\nMethods A retrospective review identified adult patients who had a unilateral distal radius fracture treated with a volar locked plate and who had MK-1775 manufacturer an initial postoperative lateral tilt radiograph using the contralateral hand to position the injured wrist. Intraoperative fluoroscopic images were reviewed to confirm the ability to see the extra-articular placement of all hardware. The inclined lateral wrist radiograph was obtained by positioning

the injured wrist at a height determined by the contralateral hand being placed under the ulnar wrist crease. The wrist was then supported VX-809 concentration there with firm blocks in all cases. The radiographic beam was directed perpendicular to the horizontal cassette. Two reviewers (authors) then blindly reviewed postoperative radiographs to determine whether the radiocarpal joint and subchondral bone were visualized and whether any screws or pegs appeared to cross the radiocarpal joint. An accceptable lateral tilt radiograph was defined as good visualization of the subchondral bone while allowing only the most radial peg to appear to cross the joint. We also placed 15 normal volunteers into the lateral tilt position, using their opposite hand, to measure the inclined forearm angle.\n\nResults A total of 24 wrists (24 patients) were identified and 23 patients had lateral tilt radiographs with acceptable visualization of the subchondral bone. The concordance of the subchondral bone visualization was 100% (95% confidence interval, 85.5% to 100%). The mean angle with lateral tilt positioning was 18 degrees from horizontal (range, 15 degrees to 23 degrees; standard deviation, 2.4 degrees).

Of these shared proteins, 126 contained the distinctive repeat re

Of these shared proteins, 126 contained the distinctive repeat regions. Localization of two such proteins in Toxoplasma gondii confirmed their role in the

pellicle and in doing so identified two new proteins of the apicomplexan invasive structure-the MK-4827 cell line apical complex. Screening broadly for these repetitive domains in genomic data revealed large and actively evolving families of such proteins in alveolates, suggesting that these proteins might underpin the diversity and utility of their unique pellicular structure.”
“RecQ helicases are critical for maintaining genome integrity in organisms ranging from bacteria to humans by participating in a complex network of DNA metabolic pathways. Their diverse cellular functions require specialization and coordination of multiple protein domains that integrate catalytic functions with DNA-protein and protein-protein interactions.

The RecQ helicase from Deinococcus radiodurans (DrRecQ) is unusual among RecQ family members in that it has evolved to utilize three ‘Helicase and RNaseD C-terminal’ (HRDC) domains to regulate its activity. In this report, we describe the high-resolution structure of the C-terminal-most HRDC domain of DrRecQ. The structure SBE-β-CD reveals unusual electrostatic surface features that distinguish it from other HRDC domains. Mutation of individual residues in these regions affects the DNA binding affinity of DrRecQ and its ability to unwind a partial duplex DNA substrate. Taken together, the results suggest the unusual electrostatic surface features of the DrRecQ HRDC domain may be important for inter-domain interactions that regulate structure-specific DNA binding and help direct DrRecQ to specific recombination/repair sites.”
“OBJECTIVE-We

compared the effect of insulin lispro protamine suspension (ILPS) with that of insulin glargine and insulin detemir, all given as basal supplementation, in the treatment of patients with type 2 diabetes.\n\nRESEARCH DESIGN AND METHODS-We conducted an electronic search until February 2012, including online registries of ongoing trials and abstract books. All randomized controlled trials comparing ILPS with insulin glargine or detemir click here with a duration of >= 12 weeks were included.\n\nRESULTS-We found four trials lasting 24-36 weeks involving 1,336 persons: three studies compared ILPS with glargine, and one trial compared ILPS with detemir. There was no significant difference in change in HbA(1c) level between ILPS and comparators, in the proportion of patients achieving the HbA(1c) goals of <= 6.5 or <7%, in weight change, or in daily insulin doses. There was no difference in overall hypoglycemia, but nocturnal hypoglycemia occurred significantly more with ILPS than with comparator insulins (mean difference 0.099 events/patient/30 days [95% CI 0.03-0.17]).

(C) 2014 Elsevier Ltd All rights reserved “
“We have employ

(C) 2014 Elsevier Ltd. All rights reserved.”
“We have employed the proteomic approach MRT67307 chemical structure in combination with mass spectrometry to study the immune response of honey bee workers at different developmental stages. Analysis of the hemolymph proteins of noninfected, mock-infected and immune-challenged individuals by polyacrylamide gel electrophoresis showed differences in the protein profiles. We present evidence that in vitro reared honey bee larvae respond with a prominent humoral reaction to aseptic and septic injury as documented by the transient synthesis of the three antimicrobial peptides (AMPs) hymenoptaecin, defensin1, and abaecin. In contrast,

young adult worker bees react with a broader spectrum

of immune reactions that include the activation of prophenoloxidase and humoral immune responses. At least seven proteins appeared consistently in the hemolymph of immune-challenged bees, three of which are identical to the AMPs induced also in larvae. The other four, i.e., phenoloxidase (PO), peptidoglycan recognition protein-S2, carboxylesterase selleck chemicals (CE), and an Apis-specific protein not assigned to any function (HP30), are induced specifically in adult bees and, with the exception of PO, are not expressed after aseptic injury. Structural features of CE and HP30, such as classical leucine zipper motifs, together with their strong simultaneous induction upon challenge with bacteria suggest an important role of the two novel bee-specific immune proteins in response to microbial infections. Arch. Insect Biochem. Physiol. 69:155-167, 2008. (C) 2008 Wiley-Liss, Inc.”
“Oxidative phosphorylation ATP

synthesis by the oxygen-consuming respiratory chain (RC) supplies most organs and tissues with a readily usable energy source, and is already fully functioning at birth. This means that, in theory. RC deficiency can give rise to any symptom in any organ or tissue at any age and with any mode of inheritance, due to the two-fold genetic origin of RC components (nuclear DNA and Crenolanib mitochondrial DNA). It has long been erroneously believed that RC disorders originate from mutations of mtDNA as, for some time, only mutations or deletions of mtDNA could be identified. However, the number of disease-causing mutations in nuclear genes is now steadily growing. These genes not only encode the various subunits of each complex, but also the ancillary proteins involved in the different stages of holoenzyme biogenesis, including transcription, translation, chaperoning, addition of prosthetic groups and assembly of proteins, as well as the various enzymes involved in mtDNA metabolism. (c) 2010 Elsevier Masson SAS. All rights reserved.”
“Carrier geometry is a key parameter of drug delivery systems and has significant impact on the drug release rate and interaction with cells and tissues.

Results: Three tongue samples were studied to assess depth of

\n\nResults: Three tongue samples were studied to assess depth of thermal damage by harmonic scalpel. The mean depth of thermal damage was 0.69 (range, 0.51 -

0.82). Five tongue samples were studied to assess depth of thermal damage by CO2 laser. The mean depth of thermal damage was 0.3 (range, 0.22 to 0.43). As expected, control samples showed 0 mm of thermal damage. There was a statistically significant difference between the depth of thermal injury to tongue resection margins by harmonic scalpel as compared to CO2 laser, (p = 0.003).\n\nConclusion: In a cadaveric model, flexible CO2 laser fiber causes less depth of thermal damage when compared with harmonic scalpel Trk receptor inhibitor at settings utilized in our study. However, the relevance of this information in terms of wound healing, hemostasis, safety, cost-effectiveness, and surgical outcomes needs to be further studied in clinical settings.”
“In the title compound, C(11)H(12)O(2)S,

the C and S atoms of the central thiophene and the methyl groups, and the two carbonyl groups of the cycloheptanedione are almost coplanar [maximum deviation from Z-IETD-FMK mw the mean plane = 0.221 (2) angstrom]. The packing is stabilized by pi-pi interactions between the conjugated thiophenes, the shortest centroid-centroid distance between thiophene rings being 3.9759 (10) angstrom.”
“Ultrasmall SnO2 nanocrystals as anode materials for lithium-ion batteries (LIBs) have been synthesized selleck compound by bubbling an oxidizing gas into hot surfactant solutions containing Sn-oleate complexes. Annealing of the particles in N-2 carbonifies the densely packed surface capping ligands resulting in carbon encapsulated SnO2 nanoparticles (SnO2/C). Carbon encapsulation can effectively buffer the volume changes during the lithiation/delithiation process. The assembled SnO2/C thus deliver extraordinarily high reversible capacity of 908 mA.h.g(-1) at 0.5 C as well as excellent cycling performance in the LIBs. This method demonstrates the great potential of SnO2/C

nanoparticles for the design of high power LIBs.”
“The stereoselective synthesis of 2-isoxazolidine through 1,3-dipolar cycloaddition reaction of nitrile oxide, which is in situ generation from aldoxime in the presence of N-bromosuccinamide and solid-supported reagent KF/Al2O3 at room temperature, is reported. KF/Al2O3 is sufficiently basic such that it can replace organic bases such as Et3N used in typical procedures and it catalyses the reaction to enhance the rate of the reaction.”
“Purpose of review\n\nShortly after the advent of severe acute respiratory syndrome and the avian influenza, the emergence of the influenza A(H1N1) 2009 pandemic caused significant vibrations to the public health authorities and stressed the health systems worldwide. We sought to investigate whether this experience has altered our knowledge and our current and future practice on the management of severe acute respiratory infections (SARI) and community-acquired pneumonia.

To characterize better the roles of the two receptors in hyperalg

To characterize better the roles of the two receptors in hyperalgesia and to obtain ligands whose binding affinity and efficacy differed for the two receptors, we modified the Bv8 molecule in regions essential for

receptor recognition and activation. EXPERIMENTAL APPROACH We modified the Z VAD FMK Bv8 molecule by substituting Trp in position 24 with Ala (A-24) and compared it with Bv8 for binding and activating PK1 and PK2 receptors in cell preparations and in affecting nociceptive thresholds in rodents. KEY RESULTS A-24 preferentially bound to PK2 receptors and activated them with a lower potency (5-fold) than Bv8. When systemically injected, A-24 induced Bv8-like hyperalgesia in rats and in mice, at doses 100 times higher than Bv8. Locally and systemically injected at inactive doses, A-24 antagonized Bv8-induced hyperalgesia. Cyclosporin A in vivo In rat and mouse models of inflammatory and post-surgical pain, A-24 showed potent and long-lasting anti-hyperalgesic activity. Unlike Bv8, A-24 increased -endorphin levels in mouse brain. CONCLUSIONS AND IMPLICATIONS A-24

induced its anti-hyperalgesic effect in rodents by directly blocking nociceptor PK1 receptors and by activating the central opioid system and the descending pain control pathway through brain PK2 receptors.”
“25-Hydroxyvitamin D (25(OH)D) half-life is a potential biomarker for investigating vitamin D metabolism and requirements. IPI-145 We performed a pilot study to assess the approach and practical feasibility of measuring 25(OH)D half-life after an oral dose.

A total of twelve healthy Gambian men aged 18-23 years were divided into two groups to investigate the rate and timing of (1) absorption and (2) plasma disappearance after an 80 nmol oral dose of 25(OH)D-2. Fasting blood samples were collected at baseline and, in the first group, every 2 h postdose for 12 h, at 24 h, 48 h and on day 15. In the second group, fasting blood samples were collected on days 3, 4, 5, 6, 9, 12, 15, 18 and 21. Urine was collected for 2 h after the first morning void at baseline and on day 15. 25(OH)D-2 plasma concentration was measured by ultra-performance liquid chromatography-tandem MS/MS and corrected for baseline. Biomarkers of vitamin D, Ca and P metabolism were measured at baseline and on day 15. The peak plasma concentration of 25(OH)D-2 was 9.6 (SD 0.9) nmol/l at 4.4 (SD 1.8) h. The terminal slope of 25(OH)D-2 disappearance was identified to commence from day 6. The terminal half-life of plasma 25(OH)D-2 was 13.4 (SD 2.7) d. There were no significant differences in plasma 25(OH)D-3, total 1,25(OH)(2)D, parathyroid hormone, P, Ca and ionised Ca and urinary Ca and P between baseline and day 15 and between the two groups. The present study provides data on the plasma response to oral 25(OH)D-2 that will underpin and contribute to the further development of studies to investigate 25(OH)D half-life.

Because the rate of crossover favoring SCS beyond 6 months would

Because the rate of crossover favoring SCS beyond 6 months would bias a long-term randomized group comparison, we present all outcomes ASP2215 in vitro in patients who continued SCS from randomization to 24 months and, for illustrative purposes, the primary outcome (>50% leg pain relief) per randomization and final treatment.\n\nMETHODS:

Patients provided data on pain, quality of life, function, pain medication use, treatment satisfaction, and employment status. Investigators documented adverse events. Data analysis included inferential comparisons and multivariate regression analyses.\n\nRESULTS: The 42 patients continuing SCS (of 52 randomized to SCS) reported significantly improved leg pain relief (P < 0.0001), quality of life (P <= 0.01), and functional capacity (P = 0.0002); and 13 patients (31%) required a device-related surgical revision. At 24 months, of 46 of 52 patients randomized to SCS and 41 of 48 randomized to CMM who were available, the primary outcome was achieved by 17 (37%)

randomized to SCS versus 1 (2%) to CMM www.selleckchem.com/products/pci-32765.html (P = 0.003) and by 34 (47%) of 72 patients who received SCS as final treatment versus 1 (7%) of 15 for CMM (P = 0.02).\n\nCONCLUSION: At 24 months of SCS treatment, selected failed back surgery syndrome patients reported sustained pain relief, clinically important improvements in functional capacity and health-related quality of life, and satisfaction with treatment.”
“In seasonal breeding species, the gene encoding for the melatonin MT(1) receptor (oMT(1)) is highly polymorphic and numerous data have reported the existence of an association between an allele of the receptor and a marked expression of the seasonality

S63845 inhibitor of reproduction in ewes. This allele called “m” (previously named “-” allele) carries a mutation leading to the absence of a MnlI restriction site as opposed to the “M” allele (previously named “+” allele) carrying the MnlI restriction site (previously “+” allele). This allows the determination of the three genotypes “M/M” (+/+),”M/m” (+/-) and “m/m” (-/-). This mutation is conservative and could therefore not be causal. However, it is associated with another mutation introducing the change of a valine to an isoleucine in the fifth transmembrane domain of the receptor. Homozygous “M/M” and “m/m” animals consequently express structurally different receptors respectively named oMT(1) Val(220) and oMT(1) Ile(220). The objective of this study was to test whether these polymorphic variants are functionally different. To achieve this goal, we characterized the binding properties and the transduction pathways associated with both variants of the receptors. Using a pharmacological approach, no variation in binding parameters between the two receptors when transiently expressed in COS-7.

In addition, the effect of G-CSF treatment was examined on the pr

In addition, the effect of G-CSF treatment was examined on the production autoantibodies in the B6.Sle1.Sle2.Sle3 Selleck Pexidartinib (B6.TC) spontaneous model of lupus.\n\nResults: B6.Sle2c2 and B6 leukocytes responded differently to G-CSF. G-CSF binding by B6.Sle2c2

leukocytes was reduced as compared to B6, which was associated with a reduced expansion in response to in vivo G-CSF treatment. G-CSF in vivo treatment also failed to mobilize bone-marrow B6.Sle2c2 neutrophils as it did for B6 neutrophils. In contrast, the expression of G-CSF responsive genes indicated a higher G-CSF receptor signaling in B6.Sle2c2 cells. G-CSF treatment restored the ability of B6.Sle2c2 mice to produce autoantibodies in a dose-dependent manner upon

cGVHD induction, which correlated with restored CD4(+) T cells activation, as well as dendritic cell and granulocyte expansion. Steady-state ROS production was higher in B6.Sle2c2 than in B6 mice. cGVHD induction resulted in a larger increase in ROS production in B6 than in B6. Sle2c2 mice, and this difference was eliminated with G-CSF treatment. Finally, a low dose G-CSF treatment accelerated the production of anti-dsDNA IgG in young B6.TC mice.\n\nConclusion: The different in vivo and in vitro responses of B6.Sle2c2 leukocytes are consistent with the mutation in the G-CSFR having functional consequences. The elimination of Sle2c2 suppression of autoantibody production by exogenous G-CSF indicates that Sle2c2 corresponds to a loss of function of G-CSF receptor. This result was corroborated by the increased anti-dsDNA SB273005 Cytoskeletal Signaling inhibitor IgG production

in G-CSF-treated B6.TC mice, which also carry the Sle2c2 locus. Overall, these results suggest that the G-CSF pathway regulates the production of autoantibodies in murine models of lupus.”
“The majority of peptide-based cancer vaccines under development are for human leukocyte antigen (HLA)-A2- or -A24-positive patients. To overcome this limitation, we conducted a phase I clinical study of peptide vaccines designed for cancer patients with six different HLA-A types. Eligible patients were required to have failed prior standard cancer therapies and to be positive PXD101 in vivo for the HLA-A2, -A24 or -A3 (A3, A11, A31 and A33) supertype. Three sets of 8 candidate peptides (24 peptides in total) were provided for vaccination to HLA-A2(+), HLA-A24(+) and HLA-A3(+) patients, respectively. Personalization of the vaccination peptides from the candidate pool was made by considering the patients HLA types and pre-existing levels of IgGs to the candidate peptides. Seventeen patients were enrolled in this study. The peptide vaccinations were well tolerated in all patients with no vaccine-related severe adverse events. Augmentation of cytotoxic T lymphocyte (CTL) or IgG responses specific to the vaccinated peptides was observed in 11 or 10 out of 13 cases tested, respectively.

An idea is to extract out dynamics of directional fluctuations of

An idea is to extract out dynamics of directional fluctuations of spins explicitly, resorting to the CP1 representation and integrating over their amplitude fluctuations. As a result, we derive an effective field theory for ferromagnetic quantum phase transitions in terms of bosonic spinons and fermionic Adavosertib in vivo holons. We show that this effective field theory reproduces overdamped spin dynamics in a paramagnetic Fermi liquid and magnon spectrum

in a ferromagnetic Fermi liquid. An interesting observation is that the velocity of spinons becomes zero, approaching the ferromagnetic quantum critical point, which implies emergence of local quantum criticality. Based on this scenario, we predict the omega/T scaling behavior near ferromagnetic quantum criticality beyond the conventional scenario of the weak-coupling approach.”
“Brain extraction, also known as skull stripping, selleck is one of the most important preprocessing steps

for many automatic brain image analysis. In this paper we present a new approach called Multispectral Adaptive Region Growing Algorithm (MARGA) to perform the skull stripping process. MARGA is based on a region growing (RG) algorithm which uses the complementary information provided by conventional magnetic resonance images (MRI) such as T1-weighted and T2-weighted to perform the brain segmentation. MARGA can be seen as an extension of the skull stripping method proposed by Park and Lee (2009) [1], enabling their use in both axial views and low quality images. Following the same idea, we first obtain seed regions that are then spread using a 2D RG algorithm which behaves differently JAK inhibitor in specific zones of the brain. This adaptation allows to deal with the fact that middle MRI slices have better image contrast between the brain and non-brain regions than superior and inferior brain slices where the contrast is smaller. MARGA is validated using three different databases: 10 simulated brains from the BrainWeb database; 2 data sets

from the National Alliance for Medical Image Computing (NAMIC) database, the first one consisting in 10 normal brains and 10 brains of schizophrenic patients acquired with a 3T GE scanner, and the second one consisting in 5 brains from lupus patients acquired with a 3T Siemens scanner; and 10 brains of multiple sclerosis patients acquired with a 1.5 T scanner. We have qualitatively and quantitatively compared MARGA with the well-known Brain Extraction Tool (BET), Brain Surface Extractor (BSE) and Statistical Parametric Mapping (SPM) approaches. The obtained results demonstrate the validity of MARGA, outperforming the results of those standard techniques. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

(C) 2009 Elsevier Ireland Ltd All rights reserved “
“BACKGR

(C) 2009 Elsevier Ireland Ltd. All rights reserved.”
“BACKGROUND: The clinical significance of a positive intraoperative frozen section analysis of the pancreatic margin, WH-4-023 especially for adenoma or borderline lesion, is not well understood during operations for intraductal papillary mucinous neoplasm of the pancreas.\n\nSTUDY DESIGN: Data from 130 consecutive patients who underwent intraductal papillary mucinous neoplasm resection in a single institution were retrospectively analyzed.\n\nRESULTS:

In the first intraoperative frozen section analysis, 26 patients were positive for adenoma or borderline lesion, 10 for carcinoma in situ, 2 for cancer cells floating in the duct, and 6 for invasive cancer. Twenty-nine patients underwent additional resection, and 105 patients finally achieved a negative pancreatic margin. Among 18 patients with a positive pancreatic margin for adenoma or borderline lesion, only I had a recurrence. All 20 patients who suffered a recurrence harbored invasive

intraductal papillary mucinous carcinoma in resected specimens. In multivariate analysis, predictive factors of recurrence after intraductal papillary mucinous carcinoma resection were the presence of lymph node metastasis, serosal invasion, and a high level of serum carbohydrate antigen 19-9.\n\nCONCLUSIONS: The presence of adenoma or borderline lesion at the pancreatic margin does not always warrant further resection because of the low recurrence rare in the remnant pancreas. Recurrence after intraductal papillary mucinous neoplasm resection is influenced BI-D1870 primarily by the presence and extent of PHA-848125 inhibitor invasive cancer rather than the status of the pancreatic margin. (J Am Coll Surg 2009; 209:614-621. (C) 2009 by the American College of Surgeons)”
“A series of well-defined thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) macromonomers was prepared by

reversible addition fragmentation chain transfer (RAFT) polymerization followed by aminolysis and nucleophilic Michael addition. 2-(Dodecylthiocarbonothioylthio)-2-methylpropanoic-2-phenoxyethyl ester (CTA) was used as the RAFT chain transfer agent to prepare six PNIPAM-CTA precursors with target degrees of polymerization of 20, 30, 40, 50, 60, and 75. These NIPAM polymerizations were conducted in 1,4-dioxane and proceeded with good control and low polydispersities (M-w/M-n < 1.10) up to more than 90% conversion. The PNIPAM trithiocarbonate end-groups were then converted to methacrylate end-groups by combining (i) aminolysis and (ii) nucleophilic Michael addition using the bifunctional reagent, 3-(acryloyloxy)-2-hydroxypropyl methacrylate (AHPMA), in a one pot reaction. The resulting PNIPAM macromonomers were evaluated as reactive steric stabilizers for latex syntheses.

Methods: The America On the Move study was conducted in 2003 Ind

Methods: The America On the Move study was conducted in 2003. Individuals (N = 2522) aged 13 yr and Napabucasin concentration older consented to fill out a survey, including 1921 adults aged 18 yr and older. Valid pedometer data were collected on 1136 adults with Accusplit AE120 pedometers. Data were weighted to reflect the general U. S. population according to several variables (age, gender, race/ethnicity, education,

income, level of physical activity, and number of 5-to 17-yr-old children in the household). Differences in steps per day between subgroups were analyzed using unpaired t-tests when only two subgroups were involved or one-way ANOVA if multiple subgroups were involved. Results: Adults reported taking an average of 5117 steps per day. Male gender, younger age, higher education level, single marital status, and lower body mass index were all positively associated with steps per day. Steps per day were positively related to other self-reported measures of physical activity

and negatively related to self-reported measures on physical inactivity. Living environment www.selleckchem.com/products/Gefitinib.html (urban, suburban, or rural) and eating habits were not associated with steps per day. Conclusions: In the current study, men and women living in the United States took fewer steps per day than those living in Switzerland, Australia, and Japan. We conclude that low levels of ambulatory physical activity are contributing to the high prevalence of adult obesity in the United States.”
“Non-response rate to cardiac resynchronization therapy (CRT) might be decreased by optimizing device programming. The Clinical Evaluation on Advanced Resynchronization (CLEAR) study aimed to assess the effects of CRT with automatically optimized atrioventricular (AV) and interventricular

(VV) delays, based on a Peak Endocardial Acceleration (PEA) signal system.\n\nThis multicentre, single-blind study randomized patients in a 1 : 1 ratio to CRT optimized either automatically by the PEA-based system, or according to centres’ usual practices, mostly by echocardiography. Patients had heart failure (HF) New York Heart Association (NYHA) functional class III/IV, left ventricular ejection fraction (LVEF) 35, QRS duration 150 or 120 ms with mechanical dyssynchrony. Follow-up was 1 year. The primary SN-38 in vitro endpoint was the proportion of patients who improved their condition at 1 year, based on a composite of all-cause death, HF hospitalizations, NYHA class, and quality of life. In all, 268 patients in sinus rhythm (63 men; mean age: 73.1 9.9 years; mean NYHA: 3.0 0.3; mean LVEF: 27.1 8.1; and mean QRS duration: 160.1 22.0 ms) were included and 238 patients were randomized, 123 to PEA and 115 to the control group. At 1 year, 76 of patients assigned to PEA were classified as improved, vs. 62 in the control group (P 0.0285).