Articles were eligible for inclusion if algorithms were developed to convert components from disease-specific measures into utility scores.

Of 1,029 articles identified, 50 studies satisfied the inclusion criteria. The most frequent conditions where DSPMs were developed included Z-IETD-FMK supplier cancer (12 studies), coronary artery disease (4 studies), osteoarthritis, rheumatoid arthritis (3 studies of each), obesity, and stroke (2 studies of each). Most studies involved mapping items or scores from disease-specific non-preference-based measures onto a preference-based measure of health such as the EQ-5D. A substantial number of DSPMs appeared to include unique content

not covered by EQ-5D dimensions.

Several conditions were identified as potential areas where the richness of the EQ-5D descriptive system could be enhanced. It is yet unclear whether added dimension(s) would contribute unique explained variance to a utility score. Given the resources required to rigorously develop a utility measure, the need for such measures should be carefully vetted.”
“Background: The island of Timor lies at the south-eastern edge of Indonesia on the boundary of the Oriental and Australian faunal regions.

The country of Timor-Leste, which occupies Sotrastaurin cell line the eastern part of the island, is malarious but anopheline faunal surveys and malaria vector incrimination date back to the 1960 s. Over the last decade the malaria vectors of south-east Asia and the south-west Pacific have been intensely studied using molecular techniques that can confirm identification within complexes of isomorphic

species. The aim of this study is to accurately identify GSK-3 inhibitor the Anopheles fauna of Timor-Leste using these techniques.

Methods: The survey was carried out over the period February to June 2001. Standard entomological techniques human landing collections, larval collections and CO2 baited light traps – were used to collect anophelines from the main geographical regions: coastal plains, inland plains, and highlands. Specimens were processed for identification by morphology and genotyped for the ribosomal DNA ITS2 by restriction analysis and/or DNA sequencing. Phylogenetic relationship of Anopheles sundaicus and Anopheles subpictus individuals was also assessed using DNA sequences from the ITS2 and mitochondrial cytochrome-b. All specimens, other than those from larval surveys, were processed to detect the presence of the Plasmodium parasite circumsporozoite protein by ELISA for vector incrimination.

Results: Of 2,030 specimens collected, seven species were identified by morphology: Anopheles barbirostris, Anopheles aconitus, Anopheles annularis, Anopheles maculatus, Anopheles peditaeniatus, An. sundaicus and Anopheles vagus. These were confirmed by molecular analysis with the addition of Anopheles flavirostris and an unidentified species designated here as An. vagus genotype B.

1000 datasets were simulated for each of these and all methods applied. Selection bias was observed in simple methods when the difference in survival between switchers and DAPT research buy non-switchers were large. A number of methods, particularly the AFT method of Branson and Whitehead were found to give less biased estimates of the true treatment effect in these situations.

Conclusions: Simple methods are often not appropriate to deal with treatment switching. Alternative approaches such as the Branson & Whitehead method to adjust for switching should be considered.”
“Objective: To record with video-otoscopy the appearance of the tympanic membranes of a cross section of children aged 9 to 10 years.

Study Design:

Cross-sectional study nested within an established longitudinal study of childhood development, the Avon Longitudinal Study of Parents and Children.

Setting: South West England, U. K.

Participants: Approximately 6908 of 7261 children with ages ranging from 105 to 140 months born between April 1, 1991, and

December 31, 1992, were examined www.selleckchem.com/products/ON-01910.html by trained technicians with video-otoscopy.

Main Outcome Measures: Two photographs were taken of each child’s tympanic membranes to show the features of the pars tensa and the pars flaccida.

Results: In just less than three quarters of the children, both ears were normal. Retraction of the pars flaccida was present in 9.6% of children, and that of the pars tensa was present in 7.9%. Most of these changes were mild with few severe retractions. There were 15 cases of overt or suspected cholesteatoma.

Conclusion: The tympanic membrane changes reflect most of the middle ear disease seen in 9- to 10-year-old children. The prevalence

is low, and few children have serious disease at this stage.”
“There is no consensus on Adriamycin molecular weight which patient characteristics are the most suitable to report or to be used as stratification factors in clinical trials for advanced gastric cancer (AGC), to our knowledge.

We conducted a comprehensive review of published randomized trials for AGC to examine the patient characteristics that were reported.

Among the 67 analyzed trials, age, gender, performance status, proportion of patients with measurable disease, and previous gastrectomy were frequently reported (> 69%). Histology, number of disease sites, and adjuvant treatment were reported in less than 50% of trials. Although the reporting of second-line chemotherapy has increased in recent trials, it remains at less than 50%. Notably, recent trials have tended to include patients with better performance status and less locally advanced disease, with Asian trials more frequently including patients with more diffuse histology and less locally advanced disease or liver metastasis than non-Asian trials. Stratification was conducted in approximately 60% of the trials, using quite variable stratifying factors.

Results: www.selleckchem.com/HIF.html The release of zoledronic acid was greatest during the first twenty-four hours for all concentrations and decreased rapidly during the next forty-eight hours to reach a plateau after four days. The proliferation assay

(MTT) showed zoledronic acid to have significant cytotoxicity in cultures of stromal giant cell tumor, multiple myeloma, and renal cell carcinoma cells. In addition, zoledronic acid decreased the number of viable tumor cells in a dose-dependent manner. Renal cell carcinoma from bone (RBM1-IT4) and stromal giant cell tumor of bone were more susceptible to zoledronic acid than was multiple myeloma.

Conclusions: The method presented in our study is a reproducible technique for evaluating zoledronic acid elution from bone cement and determining its impact on tumor growth. Zoledronic acid is released from bone cement, remains biologically active despite the polymerization of cement, and inhibits the in vitro growth of cell lines from giant cell tumor of bone, myeloma, and renal cell carcinoma.”
“Objective: There is increasing evidence that the addition of O-linked N-acetylglucosamine (O-GlcNAc) to proteins plays an important role in cell signaling pathways. In

chondrocytes, accumulation of O-GlcNAcmodified proteins induces hypertrophic EVP4593 differentiation. Osteoarthritis (OA) is characterized by cartilage degradation, and hypertrophic-like changes in hyaline chondrocytes. However, the mechanisms responsible for these changes have not been described. Our aim was to study whether O-GlcNAcylation and the enzymes responsible for this modification are dysregulated in the cartilage

of patients with knee OA and whether interleukin-1 could induce these modifications in cultured human OA chondrocytes (HOC).

Design: Human cartilage was obtained from patients with knee OA and from age and sex-matched healthy donors. HOC were cultured and stimulated with the catabolic cytokine IL-1 alpha. Global protein O-GlcNAcylation and the synthesis of the key KPT-8602 cell line enzymes responsible for this modification, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), were assessed by western blot.

Results: OA was associated with a 4-fold increase in the global O-GlcNAcylation in the cartilage. OA cartilage showed a re-distribution of the OGT and OGA isoforms, with a net increase in the presence of both enzymes, in comparison to healthy cartilage. In HOC, IL-1 alpha stimulation rapidly increased O-GlcNAcylation and OGT and OGA synthesis.

onclusions: Our results indicate that a proinflammatory milieu could favor the accumulation of O-GlcNAcylated proteins in OA cartilage, together with the dysregulation of the enzymes responsible for this modification.

However, periodical liver function monitoring is required, especially when PT is used for longer periods or at higher doses.”
“An experimental and theoretical study is presented for n-type Bi-doped PbTe composites with different grain sizes and doping levels. The bulk polycrystalline Selleckchem Adavosertib composites were prepared by spark plasma sintering of the nanocrystals synthesized via micro-emulsion and direct precipitation. This technique is particularly attractive due to its low cost, its reproducibility,

and the control of the composition and nanocrystal size that it affords. The thermoelectric properties of the synthesized specimens were experimentally measured and theoretically modeled. Our calculations reveal that the inclusion of electron/grain and phonon/grain interface scattering is crucial for the correct description and interpretation of the measured properties. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3586240]“
“This investigation was aimed to probe the pharmacological base of medicinal use of Acorus calamus in ischemic heart diseases. Effect on heart parameters was studied in isolated rabbit heart while coronary vasodilator effect was studied in isolated bovine coronary arterial rings, suspended in tissue

baths filled with Krebs solution, maintained at 37A degrees C, aerated with carbogen and responses were RG-7388 in vitro measured on PowerLab data acquisition system. In Langendorrf’s perfused rabbit heart, the crude

extract of Acorus calamus (Ac.Cr) at 0.01-10 mg/mL partially suppressed force Fedratinib cost of ventricular contractions (FVC), heart rate (HR) and coronary flow (CF). The ethylacetate fraction completely suppressed FVC, partially suppressed HR and CF, while the nHexane fraction exhibited similar effect on FVC and HR but increased CF, similar to methacholine and arachidonic acid. In bovine coronary arterial preparations, Ac.Cr caused inhibition of U46619 (20 nM)-precontractions, which was blocked in presence of increasing concentration of K+ (4.8-20 mM), tetraethylammonium (1 mu M) and SKF525A (10 mu M), similar to arachidonic acid and methacholine, indicating K+ channels activation and possible involvement of endothelial-derived hyperpolarizing factor (EDHF). Activity-directed fractionation revealed that EDHF-mediated activity is concentrated in the nHexane fraction. When tested against high K+, the ethylacetate fraction was found more potent than parent crude extract and nHexane fraction. These data indicate that Ac.Cr mediates coronary vasodilator effect primarily through EDHF, responsible for the increase in CF, while the cardiac depressant effects may be due to the presence of additional cardiac depressant constituent(s), thus provides possible mechanistic basis to its medicinal use in ischemic heart diseases.”
“Bisphosphonates are the current standard of care for treatment of osteoporosis.

These results demonstrate the strong potentiality of hyper-Raman

scattering as structural probe of complex perovskites. (C) 2011 American Institute of Physics. [doi:10.1063/1.3599863]“
“A limited backcross procedure was utilized to introgress genes associated with grain quality traits from Oryza rufipogon (Accession No. IRGC 105491), a wild rice from Malaysia, to the cultivated rice O. sativa cv. MR219, a popular high yielding Malaysian rice cultivar. A set of 10 BC2F7 progenies were selected based on the field performance and phenotypic appearance in BC2F5 and BC2F6 generations, phosphatase inhibitor library which initially started with 266 progenies in the BC2F2 generation. These 10 advanced breeding lines are similar to each other but differ in several important grain quality traits, which can be traced to O. rufipogon introgressions. Phenotyping and genotyping of BC2F7 variants were considered for QTL analysis. The introgressed lines did not show any significant changes compared to the recurrent parent MR219 for the traits grain density and milled rice percentage. All 10 progenies showed significantly higher head rice percentages (70-88%) than

the recurrent parent MR219. Variants G13 and G15 had higher amylose contents than MR219. All variants were analyzed using polymorphic SSR markers. Of the OSI-744 concentration 34 SSR markers, only 18 showed introgression from O. rufipogon for GDC-0068 ic50 chromosomes 1, 2, 3, 5, 6, 8, 10, and 11. Graphical genotypes were prepared for each variant, and association between the introgression regions and the traits that increased grain quality was visualized. Based

on marker trait association, some of the QTLs are stable across environments and genetic backgrounds and could be used universally.”
“We demonstrate active voltage-controlled spectral tuning of mid-infrared plasmonic structures. Extraordinary optical transmission gratings were fabricated on n-doped GaAs epilayers with a HfO(2) gate dielectric between the grating and the doped semiconductor. The permittivity of the GaAs was tuned by depleting charge carriers below the top grating gate upon the application of a reverse bias to the gate. Devices were characterized both electrically and optically, and resonant transmission peak spectral and transmitted intensity shifts were achieved. Possible applications for, as well as the limitations of, the demonstrated technology are discussed. (C) 2011 American Institute of Physics. [doi:10.1063/1.3600230]“
“Background: Safety of a sixth consecutive dose of acellular pertussis vaccine in adolescents was assessed in a 2-armed, randomized study.

Methods: Adolescents who had received 5 doses of acellular pertussis vaccine combined with diphtheria and tetanus toxoids (6-dose group) received 1 dose of reduced 5-component acellular pertussis vaccine combined with tetanus toxoid and reduced diphtheria toxoid (Tdap).

The paper learn more ends with a discussion of the behavioural mechanisms of spatial constancy for arm motor control and their physiological implications for the brain. Taken together, the emerging picture is that the brain computes an evolving representation of three-dimensional action space, whose internal metric

is updated in a nonlinear way, by optimally integrating noisy and ambiguous afferent and efferent signals.”
“Introduction and hypothesis When incontinence accompanies detrusor overactivity (DO), the pressure at which it occurs may have important predictive value and should be termed DO leak point pressure (DOLPP).

Methods A retrospective review of our video urodynamics database (n=222) including validated questionnaires was performed. DOLPP was defined as detrusor pressure the moment DO incontinence occurred. Statistical analysis was performed using Student’s t-test.

Results Women with DO leakage (47) and with DO without leakage (15) were analyzed. Urgency and urgency incontinence (UUI) were greater among patients with DO leakage. A link between sphincter

deficiency and greater severity of UUI was noted. Among patients with DO leakage, those Fosbretabulin with subjective mixed incontinence had a lower mean DOLPP than those with pure UUI (p=0.004). The detrusor pressure at peak flow was lower in the DO leakage group (versus DO alone, p=0.05) likely reflecting a measure of outlet resistance.

Conclusion DOLPP has predictive meaning in women and should be further studied for possible inclusion in standard urodynamic terminology.”
“To determine the diagnostic accuracy of 3D-CTA using volume rendering (VR) in the detection ZD1839 order of residual or recurrent cerebral aneurysms after clipping.

Between

January 2006 and November 2007, 45 patients (20 female, 25 male) with 50 intracranial aneurysms treated using titanium clips were enrolled in this study. IADSA and 3D-CTA were performed within 1 month after surgery in 27 (60%) patients, after 1 year in 12 (26%) patients and after 5 years in six (13%) patients. In blinded fashion, CTA and DSA images were independently interpreted by two senior neuroradiologists with 7 years of experience in vascular diagnostic neuroradiology. The diagnostic performance of MDCTA compared with DSA for the detection of aneurysm remnants was measured by receiver operating characteristic (ROC) analysis. The area under the ROC curve, 95% confidence interval (CI), sensitivity, and specificity were calculated.

For the detection of residue-recurrent aneurysm; the sensitivity and specificity of MDCTA were 87.5% (95% CI = 52.9-97.8%) and 97.4% (95% CI = 86.5-99.5%) for the first reader and 87.5% (95% CI = 52.9-97.8%) and 100% (95% CI = 90.8-100%) for the second reader respectively. Receiver operating characteristic (ROC) analysis revealed good diagnostic performance for 3D-CTA (mean area under ROC curve (Az) = 0.98 and 0.

Methods: A cross-sectional survey was conducted using the Missoula Vitas Quality of Life Index (MVQOLI), a 26-item QOL questionnaire with five subscales (Function, Symptom, Interpersonal, Well being, Transcendent) covering physical, social, psychological and spiritual domains and one global QOL item. One item in each subscale assesses the subjective importance of the domain on a

score from 1 (least important) to 5 (most important), used to weight the contribution of the subscale towards the Total QOL score. The tool was translated into 6 languages and administered to consecutively recruited patients at four facilities in South Africa and one in Uganda.

Results: 285 patients were recruited, with a mean age of 40.1; 197 (69.1%) were female. Patients’ primary diagnoses were HIV (80.7%), cancer selleck chemicals (17.9%) and other conditions (1.4%). PF-03084014 The mean global QOL score was 2.81

(possible range 0 (worst) to 5 (best)); mean Total score 17.32 (possible range 0 to 30). Patients scored most poorly on Function (mean 0.21), followed by Well being (2.59), Symptoms (5.38), Transcendent (5.50), Interpersonal (9.53) (possible range for subscale scores -30 to 30). Most important to patients were: close relationships (mean 4.13), feeling at peace (4.12), sense of meaning in life (4.10), being active (3.84), physical comfort (2.58). Cancer patients were predominantly recruited at three of the sites; hence comparison with HIV-infected patients

was restricted to these sites. HIV+ patients (n = 115) scored significantly worse than cancer patients (n = 50) on Well being (Z = -2.778, p = 0.005), Transcendence (Z = -2.693, p = 0.007) and Total QOL (Z = -2.564, p = 0.01). Global QOL score was most weakly correlated with Total QOL (r = 0.37) and the Transcendent subscale was most highly correlated (r = 0.77) (both p < 0.001). Patients receiving palliative care in South Africa and Uganda exhibited significantly poorer QOL compared to similar populations in the USA.

Conclusions: Feeling at peace and having a sense of meaning in life were more important to patients than being active or physical comfort, S63845 order and spiritual wellbeing correlated most highly with overall QOL. It is therefore vital to identify and meet the psychological and spiritual care needs of patients, as well as to assess and treat pain and other symptoms. Our finding that patients scored most poorly on the Function domain warrants further research.”
“Background: In the United States, more children are being vaccinated against influenza in August and September, months before peak influenza activity. Sustained vaccine efficacy through 12 months postvaccination has been demonstrated in children for live attenuated influenza vaccine (LAIV) but not trivalent inactivated influenza vaccine (TIV).

We demonstrated that both dehydroparishin-B and dehydroleucodine blocked cell proliferation of B16 melanoma cells, but not normal murine Melan-A melanocytes, in a dose-dependent manner without affecting cell viability. We also found that both dehydroparishin-B and dehydroleucodine inhibited migration of B16 melanoma cells. These results suggest that dehydroleucodine and dehydroparishin-B could represent potential candidates for the treatment of metastatic melanomas. (C) 2012 Phytochemical Society of Europe. Published

by Elsevier B. V. All rights reserved.”
“We propose KU-57788 clinical trial a novel global optimization-based approach to segmentation of 3-D prostate transrectal ultrasound (TRUS) and T2 weighted magnetic resonance (MR) images, enforcing inherent axial symmetry of prostate shapes to simultaneously adjust a series of 2-D slice-wise segmentations in a “”global”" 3-D sense. We show that the introduced challenging combinatorial optimization problem can be solved globally and exactly by means of convex relaxation. Selleck BLZ945 In this regard, we propose a novel coherent continuous max-flow model (CCMFM), which derives a new and efficient duality-based algorithm, leading to a GPU-based implementation to achieve high computational speeds. Experiments with 25 3-D TRUS images and 30 3-D T2w MR images from our dataset, and 50 3-D T2w MR images from a public dataset,

demonstrate that the proposed approach can segment a 3-D prostate TRUS/MR image within 5-6 s including 4-5 s for initialization, yielding a mean Dice similarity coefficient of 93.2% +/- 2.0% P505-15 for 3-D TRUS images and 88.5% +/- 3.5% for 3-D MR images. The proposed method also yields relatively low intra-and inter-observer variability introduced by user manual initialization, suggesting a high reproducibility, independent of observers.”
“Volatile compounds of Chinese traditional pickled peppers (CTPPs) were extracted by solid-phase micro-extraction (SPME) and analysed by gas chromatography-mass spectrometry (GC-MS) and gas chromatography-olfactometry (GC-O) to visually compare their

volatile compositions by applying principal component analysis (PCA). A total of 67 volatile components were identified by GC-MS, including 7 acids, 6 alkanes, 14 alcohols, 9 esters, 11 terpenes, 3 aldehydes, 5 ketones, 7 phenols and 5 miscellaneous compounds, tentatively identified or identified by comparing with mass spectra and retention indices of the standards or from literature. Of 45 volatile compounds detected in the sniffing port of GC-O, the majority of odour-active components included acetic acid, 2-ethyl phenol, L-linalool, tridecane, butyl butanoate, -3-carene. The individual concentrations of the volatile compounds such as acetic acid, ethanol, 1-propanol, L-linalool, hexyl 2-methyl butyrate and hexyl pentanoate corresponded well to the intensities of related attributes in the correlation analysis.

Subjects showing a higher breakfast score appeared to be younger, more frequently women or smokers, with higher social status but less likely practicing physical activity. After multivariable analyses, subjects with a higher breakfast food consumption had a lower risk to have high body mass index, abdominal obesity, systolic and diastolic blood pressure, blood glucose, triglycerides, total cholesterol (P < 0.0001 for all) and C Reactive Protein (P = 0.022). The associations

were unrelated to age, sex, smoking, obesity, physical activity and social status. Subjects with a higher food breakfast score also showed a better physical healthy status score, a lower risk of metabolic syndrome (OR = 0.63; 0.55-0.72 95% CI) and of future CVD (P < 0.0001 for both women and men).

Conclusion: VX-680 cost Consumption of typical Italian breakfast foods positively affects CVD risk profile in an adult Italian population. (c) 2010 Elsevier B.V. All rights reserved.”
“Connectedness among animals in separate flocks selleck inhibitor reduces the risk of biased comparisons when selecting across flocks on EBV. The objective in

this study was to assess levels of connectedness in the genetic evaluation of weaning weight among Targhee and Suffolk flocks participating in the US National Sheep Improvement Program (NSIP). Among flocks currently participating in the NSIP, a total of 25,404 weaning weight and 35,794 pedigree

records were available for 16 Targhee flocks, find more and 14,017 weaning weight and 18,311 pedigree records were available for 24 Suffolk flocks. Connectedness was measured by using 2 different methods. First, numbers of progeny with recorded weaning weights from linking sires (defined as sires with progeny in multiple flocks or sires born in one flock with progeny in another flock) were counted. Second, connectedness was measured by calculating the average prediction error correlation of mean flock EBV (flock r(ij)). Benchmarks for flock r(ij) were established, with 0.10 and 0.05 representing low and moderate risk of bias associated with comparing EBV among flocks, respectively. From 1995 through 2004, 44% of Targhee lambs with weaning weights were born to linking sires; in Suffolk lambs, that value was 23%. In 1990, 1995, and 2005, average flock r(ij) were 0.10, 0.19, and 0.28, respectively, among Targhee flocks, and 0.02, 0.02, and 0.04, respectively, among Suffolk flocks that participated in NSIP in all 3 yr. Among all active flocks in 2005, flock r(ij) averaged 0.13 in Targhees and 0.03 in Suffolks. Hierarchical clustering of flocks based on flock r(ij) revealed that all active Targhee flocks connected at a level near or above 0.10. In Suffolk flocks, 2 distinct clusters had formed, in which connectedness was relatively high within each cluster (flock r(ij) near 0.10) but was near zero between clusters.

Results: Of the NSCLC patients, 51.85% exhibited lower expression levels of chemerin protein. The chemerin expression was significantly correlated with histological grade and the infiltration of NK cells. Non-small cell lung cancer patients with a lower

chemerin expression had poorer survival rates than those with a higher expression. Multi-variable Cox regression analysis revealed that the chemerin expression level was an independent factor for prognosis.

Conclusions: A greater expression of chemerin is an independent predictor of a better prognosis for patients with NSCLC.”
“Trigeminal neuralgia is the worst pain that human beings have ever experienced. Surgery might be the only solution for some patients because no other SBC-115076 inhibitor way can relieve their severe pain. They experience intolerable pain before operation and during radiofrequency thermocoagulation

of the gasserian ganglion. The aim of the current study was to prospectively evaluate the preoperative and perioperative analgesic effects of preoperative single peripheral nerve block. Sixty patients with classic trigeminal neuralgia who were scheduled to undergo radiofrequency thermocoagulation of the gasserian ganglion were randomly divided into a check details control group (n = 30) and a nerve block group (n = 30). Patients in the nerve block group were treated with single peripheral nerve block using 1% lidocaine and betamethasone on the day of admission. Average pain, worst pain, quality of sleep, and analgesia satisfaction

were evaluated before surgery. The incidence CAL-101 manufacturer and intensity of perioperative episodic pain were determined before the needle reached the gasserian ganglion. Compared with the control group, a single peripheral nerve block significantly attenuated average pain (P < 0.01) and worst pain (P < 0.01), ameliorated the quality of sleep (P < 0.01), and increased analgesia satisfaction (P < 0.01). Moreover, patients in the nerve block group experienced a decrease in incidence (P < 0.01) and intensity (P < 0.01) of episodic pain during surgery as compared with the participants in the control group. These results demonstrate that a single peripheral nerve block may be an effective way to relieve preoperative and perioperative intolerable pain of trigeminal neuralgia.”
“The purpose of this study was to investigate the tensile strength of the bond between a silicone lining material and heat-cured polymethyl methacrylate (PMMA) denture base resin after Er:YAG laser treatment with different pulse durations and energy levels. PMMA test specimens were fabricated and each received one of six surface treatments: no treatment (control), and five Er:YAG laser treatments comprising (1) 100 mJ, 1 W, long pulse duration, (2) 200 mJ, 2 W, long pulse duration, (3) 200 mJ, 2 W, very short pulse duration, (4) 300 mJ, 3 W, long pulse duration, and (5) 400 mJ, 4 W, long pulse duration.