By adjusting the dot-lead coupling in one dot, shot noise in another system can be modulated from sub- to super-Poissonian in the Coulomb blockade regime. Furthermore, spin injection can induce super-Poissonian shot noises in both dots due to the corporation of spin blockade and Coulomb blockade.”
“Purpose: To prospectively correlate multidetector computed tomographic (CT) perfusion measurement of pancreatic endocrine tumors with tumor microvascular density (MVD) assessed by using histologic techniques and to determine whether perfusion CT parameters differ between tumor grades.

Materials and Methods: Institutional review board approval and informed consent were obtained. Thirty-six

patients (15 men, 21 women; mean age, 53 years; range, 18-78 years) with resectable pancreatic endocrine tumors underwent presurgical dynamic perfusion CT. Twenty-eight (78%) of 36 patients were included in the study group; eight were NOV120101 excluded because of artifacts that were not compatible with perfusion postprocessing. Multidetector CT perfusion data were analyzed to calculate tumor and normal pancreatic blood flow, blood volume, mean transit time, and permeability surface area product. Multidetector CT perfusion parameters were compared with intratumoral MVD by using the Spearman correlation coefficient and with World Health Organization (WHO) classification,

tumor size, tumor proliferation index, hormonal profile, and presence of metastases by using Mann-Whitney tests.

Results: High correlation (r = 0.620, P < .001) was observed between tumor blood flow and intratumoral MVD. Blood flow was significantly

higher selleck inhibitor (P = .02) in the group of benign tumors (WHO 1) than in the groups of tumors of indeterminate prognosis (WHO 2) or well-differentiated carcinomas (WHO 3). Blood flow was significantly higher in tumors with a proliferation index of 2% or less (P = .005) and in those without histologic signs of microscopic vascular involvement (P = .008). Mean transit time was longer in tumors with lymph node (P = .02) or liver (P = .05) metastasis.

Conclusion: Perfusion CT is feasible in patients with pancreatic endocrine tumors and reflects MVD. Perfusion CT measurements are Screening Library concentration correlated with histoprognostic factors, such as proliferation index and WHO classification. (C) RSNA, 2008″
“Pathogenicity of strains of the entomopathogenic fungus Beauveria bassiana and endophytic strains of Beauveria sp against the bovine tick Rhipicephalus (Boophilus) microplus was tested in laboratory bioassays and under field conditions. Suspensions containing 10(5), 10(7) and 10(9) conidia/mL were prepared of each fungal strain for laboratory bioassays. The ticks were maintained at 28 degrees C, 90 +/- 5% relative humidity, and the following variables were evaluated: initial female weight, egg weight, hatching percentage, reproductive efficiency, and percentage control.

(C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 117: 2839-2846, 2010″
“We measured the dielectric permittivity of several solutions of ethyl alcohol in water and observed that their spectra follow the Debye model. The

parameters used to adjust the Debye model according to the alcohol concentration in a solution follow a linear law. We tested the resulting model with various alcoholic beverages and found that we can obtain the concentration of alcoholic solutions using our model. (C) 2010 Elsevier Ltd. All rights reserved.”
“Background-

Nitric oxide (NO) plays an important role in cardiovascular health by maintaining and regulating vascular tone and blood flow. Epigenetic regulation of NO synthase (NOS), the genes responsible for NO production, Cyclopamine may affect cardiovascular disease, including the development of atherosclerosis in children.

Methods and Results-

We measured percentage DNA methylation using bisulfite conversion and pyrosequencing assays on DNA from buccal cells provided by 377 participants of the Children’s Health Study on whom carotid artery intima-media thickness (CIMT) measurements were also collected. We examined a total of 16 CpG loci located within NOS1, NOS2A, NOS3, ARG1, and ARG2 genes responsible for NO production. CIMT was www.selleckchem.com/products/Adrucil(Fluorouracil).html measured using high-resolution B-mode carotid ultrasound. The association between percentage DNA

methylation in ARG and NOS genes with CIMT was evaluated using linear regression adjusted for sex, ethnicity, body mass index, age at CIMT, town of residence, and experimental plate for pyrosequencing reactions. Differences in the association by ethnicity and ancestral group were also evaluated. For a 1% increase in average DNA methylation of NOS1, CIMT increased by 1.2

mu m (P=0.02). This association was greater in Hispanic children of Native American descent Z-IETD-FMK price (beta=2.3; P=0.004) than in non-Hispanic whites (beta=0.3; P=0.71) or Hispanic whites (beta=1.0; P=0.35).

Conclusions-

DNA methylation of NOS1 has a plausible role in atherogenesis through regulation of NO production, although ancestry may alter the magnitude of this association.”
“Simian Virus 40 Large Tumor Antigen (LTag) is an efficient helicase motor that unwinds and translocates DNA. The DNA unwinding and translocation of LTag is powered by ATP binding and hydrolysis at the nucleotide pocket between two adjacent subunits of an LTag hexamer. Based on the set of high-resolution hexameric structures of LTag helicase in different nucleotide binding states, we simulated a conformational transition pathway of the ATP binding process using the targeted molecular dynamics method and calculated the corresponding energy profile using the linear response approximation (LRA) version of the semi-macroscopic Protein Dipoles Langevin Dipoles method (PDLD/S).

8%), malignancy in 89 (8.6%), and miscellaneous multiple acquired causes including those due to anticoagulant drug overdose in 282 patients (27.1%). Referrals for isolated prolonged

prothrombin time or thrombocytopenia were common, but were excluded from this study because not all presented with bleeding. Prompt laboratory work-Up and precise identification of acquired causes of bleeding is the key to planning appropriate patient management including transfusion Support.”
“Background: We undertook a cost-effectiveness analysis of the Spanish Renal Replacement Therapy (RRT) program for end-stage renal disease patients from a societal perspective. The current Spanish situation was compared with JIB 04 several hypothetical scenarios.

Methods: A Markov chain model was used as a foundation for simulations of the Spanish RRT program in three temporal horizons (5, 10, and 15 years). The current situation (scenario 1) MEK162 cost was compared with three different scenarios: increased proportion of overall scheduled (planned) incident patients (scenario 2); constant proportion of overall scheduled incident patients, but increased proportion of scheduled incident patients on peritoneal dialysis (PD), resulting in a lower proportion of scheduled incident patients on hemodialysis (HD) (scenario 3); and increased overall proportion of scheduled incident patients together with increased scheduled

incidence of patients on PD (scenario 4).

Results: The incremental cost-effectiveness ratios (ICERs) of scenarios 2, 3, and 4, when compared with scenario 1, were estimated to be, respectively, -(sic)83 150, -(sic)354 977, and -(sic)235 886 per incremental quality-adjusted life year (Delta QALY), evidencing both moderate cost savings and slight effectiveness gains. The net health benefits that would accrue to society were estimated to be, respectively, 0.0045, 0.0211, and 0.0219 Delta QALYs considering a willingness-to-pay threshold of (sic)35 000/Delta QALY.

Conclusions: Scenario 1, the current Spanish situation, was dominated by all the proposed scenarios. Interestingly, scenarios 3 and see more 4 showed the best results

in terms of cost-effectiveness. From a cost-effectiveness perspective, an increase in the overall scheduled incidence of RRT, and particularly that of PD, should be promoted.”
“Object permanence is considered the earliest method for assessing working memory. Factors affecting object permanence performance in a sample of two hundred and thirty-three 18- to 22-month olds born with extremely low birth weight were examined. it was hypothesized that object permanence would be directly related to emotional and attention regulation, that children with lower birth weight and higher illness severity would have more difficulty on the object permanence task, and that no ethnic/racial differences would be found, as this is considered a culturally unbiased task.

Whereas UV-detection is predominant in the larger systems, its sensitivity is inadequate due to the minute pathlengths employed in a chip. This review summarizes the shortcomings of UV detection, and discusses some possible solutions. Besides, it presents an overview of the alternative detection methods that have been employed in pharmaceutical and chiral chip analysis, including their positive and negative aspects as well. Finally,

CH5183284 the applications reported on the chips are discussed.”
“BACKGROUND: Heat removal is one of the major constraints in large-scale solid-state fermentation (SSF) processes. The effect of internal air circulation by forced convection on heat and water transfer has not been studied in SSF tray bioreactors. Formulation of a mathematical LY2835219 inhibitor model for SSF requires a good estimation of the mass and heat transfer coefficients.

RESULTS: A stainless steel tray bioreactor (80.6 L capacity) was used. Aspergillus niger C28B25 was cultivated under SSF conditions on an inert support. Temperature, moisture content, biomass and substrate concentrations were measured. Water and energy integral balances were used

to estimate the heat and mass transfer coefficients involved in the process. The Reynolds number (N(Re)) in the headspace of the tray bioreactor ranged from 2.5 to 2839, which increased the global heat transfer coefficient from 4.2 to 6.9 (Wm(-2) K(-1)) and the mass transfer coefficient from 1.0 to 2.1 (gm(-2) s(-1)). Mathematical model predictions of the temperature and moisture content of the fermentation bed showed a high goodness-of-fit with the experimental results.

CONCLUSIONS: This is the first report describing the effect of N(Re) of air in the headspace of a SSF tray bioreactor on the heat and mass transfer coefficients and temperature regulation in SSF. (C) 2011 Society of Chemical Industry”
“Protrusion of the Amplatzer duct occluder (ADO) II device into the aortic isthmus or the pulmonary artery causing

obstruction and residual flow has been reported, but the same has not been widely studied in small children with a patent ductus arteriosus (PDA) anatomy not considered AL3818 ic50 suitable for closure with the ADO I device. This study aimed to report the safety and efficacy of the ADO II device in children younger than 3 years with a tubular or elongated PDA and to analyze the possible reasons for residual flow in children with such a PDA. In this study, 17 children younger than 3 years (mean age, 10.3 +/- 7 months; mean weight, 6 +/- 3.6 kg) underwent attempted closure of a tubular or elongated PDA (mean diameter at the narrowest point, 4.1 +/- 1.1 mm) with the ADO II device between July 2010 and July 2012. Of the 17 patients, 16 (2 boys and 14 girls) completed the follow-up evaluation.

4 +/- A 2.2, GS-9973 which decreased

to 1.6 +/- A 1.8 postoperatively. Mean preoperative JOA was 11.2 +/- A 3.8, and the JOA at the last visit was 16.3 +/- A 1.0. All patients got bony fusion within 3-8 months after surgery.

One-stage posterior debridement, short-segment fusion, and posterior instrumentation can be an effective treatment method for the treatment of tuberculosis of the upper cervical spine in children.”
“Purpose of review

Fundamental discoveries during the 1990s revolutionized our understanding of transplantation tolerance and our ability to create it in animal models. The Immune Tolerance Network (ITN) and Reprogramming the Immune System for the Establishment of Tolerance (RISET) consortia were created to leverage these advances and work towards the goal of achieving clinical tolerance in transplantation. This article highlights their accomplishments and challenges during the past decade.

Recent findings

In Dactolisib interventional trials, renal allograft tolerance has been achieved using bone marrow transplantation with nonmyeloablative protocols to induce transient hematopoietic chimerism. Drug minimization in renal transplantation was achieved with Campath-1H induction therapy and also with cellular therapy using ‘transplant acceptance inducing cells’. Successful drug withdrawal was accomplished in long-term stable pediatric liver transplant recipients.

Finally, ‘registry’ trials of tolerant kidney

recipients revealed a B-cell signature of tolerance, which will form the basis for future investigations of its use as a biomarker for drug minimization or withdrawal in selected patients.

Summary

Although transplantation tolerance is not yet reliably achieved in a clinical setting, collaborative efforts, such as those of the ITN and RISET networks, are an effective means to synergize intellectual and financial resources to bring this goal closer selleck chemical to reality.”
“This study describes a percutaneous technique for C2 transpedicular screw fixation and evaluates its safety and efficacy in the treatment of patients with hangman’s fracture.

Ten patients with hangman’s fracture were treated by percutaneous C2 transpedicular screw fixation. There are six males and four females, who were, based on the classification of Levine and Edwards, sorted as follows: type I fracture, three cases; type II, five cases; type IIa, two cases. The causes of injury were road traffic accident in six patients and falling injury in four patients. Other associated lesions included rib fractures (7 patients), head injuries (4 patients), and fractures of extremities (6 patients).

The new technique was performed successfully in all cases. The average operation time was 98 min (range 60-130 min) and the estimated blood loss was 25 ml (range 15-40 ml). No complications such as vascular or neural structures injuries were found intraoperatively.

Here we show that the Prf complex is oligomeric, containing at least two molecules of Prf. Within the complex, Prf can associate with Pto or one of several Pto family members including Fen, Pth2, Pth3, or Pth5. The dimerization surface for Prf is the novel N-terminal domain,

which also coordinates an intramolecular interaction with the remainder of the selleck kinase inhibitor molecule, and binds Pto kinase or a family member. Thus, association of two Prf N-terminal domains brings the associated kinases into close promixity. Tomato lines containing Prf complexed with Pth proteins but not Pto possessed greater immunity against P. syringae than tomatoes lacking Prf. This demonstrates that incorporation of non-Pto kinases into the Prf complex extends the number of effector proteins that can be recognized.”
“Background: L-Arginine is an important precursor of nitric oxide (NO) and protein synthesis. Arginine is produced in the body (mainly kidney) by de novo production from citrulline and by protein breakdown. Arginine availability appears to be limited in sepsis.

Objective: The objective was to compare arginine and citrulline metabolism in septic patients and nonseptic control patients in an intensive care unit (ICU) and in healthy control

subjects.

Design: Ten patients with septic shock, 7 critically ill control patients, and 16 healthy elderly subjects were studied. Metabolism was measured by using a primed continuous (2 h) stable-isotope infusion protocol. NO production was calculated

as the conversion rate of arginine to RG7204 citrulline; de novo arginine production was calculated as the conversion rate of citrulline to arginine. Arterial blood (arterialized venous blood in healthy subjects) was collected SYN-117 molecular weight for the measurement of amino acid enrichment and concentrations. Data are reported as means +/- SDs.

Results: Whole-body citrulline production was significantly lower in septic patients (4.5 +/- 2.1 mu mol.kg(-1).h(-1)) than in ICU control patients (10.1 +/- 2.9 mu mol.kg(-1).h(-1); P < 0.01) and in healthy control subjects (13.7 +/- 4.1 mu mol.kg(-1).h(-1); P < 0.001). Accordingly, de novo arginine production was lower in patients with sepsis (3.3 +/- 3.7 mu mol.kg(-1).h(-1)) than in healthy controls (11.9 +/- 6.6 mu mol.kg(-1).h(-1); P < 0.01) and tended to be lower in septic patients than in ICU control patients (10.9 +/- 9.4 mu mol.kg(-1).h(-1); P = 0.05). NO production was lower in septic patients than in healthy control subjects (P < 0.01), whereas a larger part of arginine was converted to urea in sepsis.

Conclusions: Citrulline production is severely low in patients with sepsis and is related to diminished de novo arginine and NO production.

The U.S. government sponsored several organ donation and transplantation collaboratives, leading to check details significant increases in organ donation over several years. The use of organs from donors dying from cardiac death has increased steadily over the past decade, with such donors now exceeding 10% of the total. Revisions of state anatomic death acts allowed persons to declare their intention to donate by enrolling in state donor registries, facilitating the identification of willing donors by organ procurement organization. Despite these initiatives, the disparity between organ demand and supply has continued to grow, primarily as a result of marked

increase in the number of candidates awaiting kidney transplantation.”
“In this paper, a surface-layer model is established to study the axial polarization distributions and critical diameters of nanowires with different surface compositions. Analytical solutions are obtained based

on this model, which are validated by the ab initio results for small-size nanowires and can also predict the behaviors of large-size specimen. Compared to the traditional Landau-Ginzburg-Devonshire theory using an extrapolation length, the present model describes more microstructure information of the surface-layer, and is thus capable of characterizing the influences of different surface compositions. Furthermore, this model may shed insight into the mechanisms of the size effect INCB024360 and polarization distribution patterns in nanoscale ferroelectrics. (C) 2010 American Institute of Physics. [doi:10.1063/1.3525267]“
“P>A recent call for self-sufficiency in transplantation issued by the WHO faces variable worldwide activity, in which Spain occupies a privileged position, with deceased donation rates of 33-35 per million population (pmp)

and 85 transplants pmp. An evaluation of current challenges, including a decrease in deaths because of traffic accidents and cerebrovascular diseases, and a diversity of cultures in Spain, find more has been followed by a comprehensive strategy to increase organ availability. Actions include an earlier referral of possible donors to the transplant coordination teams, a benchmarking project to identify critical success factors in donation after brain death, new family approach and care methods, and the development of additional training courses aimed at specific groups of professionals, supported by their corresponding societies. Consensus documents to improve knowledge about safety limits for organ donation have been developed to minimize inappropriate discarding of organs. Use of organs from expanded criteria donors under an ‘old for old’ allocation policy has resulted from adaptation to the progressive decline of optimal organs. National strategic plans to deal better with organ shortage, while respecting solid ethical standards, are essential, as reflected in the WHO Guiding Principles and the Istanbul Declaration on Organ Trafficking and Transplant tourism.

Recombinant mutanase hydrolyzed insoluble glucans of cariogenic streptococci efficiently. Enzymatic reaction on hydrolysis of mutan, we assumed that the enzyme cleaved the substrate in an endo-catalytic manner. The hydrolysis of alpha-1,3-glucan oligosaccharides gave alpha-1,3-glucan tetrasaccharide as the primary final product but alpha-1,3-glucan pentasaccharide was the minimal size of substrate on which the enzyme catalyzed. Mutanase CCI-779 cost hydrolyzed borohydride-treated alpha-1,3-glucan hexasaccharide into the tetrasaccharide and the disaccharide-alditol. Thus, the enzyme cleaved the fourth alpha-1,3-glucosidic linkage from the non-reducing end of the oligosaccharides. Mutanase in fermented food should be capable of removing

streptococcal insoluble glucans that can induce dental caries.”
“Background To better understand the role of human rhinovirus-associated wheeze as a risk factor for childhood recurrent wheezing, a cohort of young children experiencing their first wheezing episode was followed until

school age. Methods All 111 hospitalized wheezing children Navitoclax research buy (median age, 12months) were initially participated in a randomized, double-blind, placebo-controlled, parallel trial on the efficacy of oral prednisolone. In this 7-yr follow-up, risk factors for recurrent wheezing were analysed, and then, the efficacy of prednisolone was evaluated overall and in pre-specified subgroups post-hoc. The main outcome was time to recurrent wheezing. Results The strongest

independent risk factor for recurrent wheezing was rhinovirus detection (hazard ratio 3.54; 95% confidence interval 1.518.30) followed by sensitization (3.47; 1.558.30, respectively) age <1yr (2.45; 1.294.65) and eczema (2.33; 1.114.90). Overall, prednisolone did not prevent recurrent wheezing. In AC220 solubility dmso subgroup analysis, prednisolone was associated with less recurrent wheezing in children affected by rhinovirus (0.32; 0.120.90, adjusted to sensitization, young age, viral aetiology and parental asthma) and/or with eczema (0.27; 0.080.87, adjusted respectively). Conclusions Our data strengthen the role of rhinovirus-associated wheeze as an important risk factor for recurrent wheezing and asthma in young first-time wheezing children. Prospective randomized trials on the efficacy of corticosteroids in rhinovirus-associated early wheezing are warranted. (ClinicalTrials.gov number, NCT 00494624)”
“Background: Tactical Combat Casualty Care (TCCC) is a system of prehospital trauma care designed for the combat environment. Needle decompression (ND) is a critical TCCC intervention, because previous data suggest that up to 33% of all preventable deaths on the battlefield result from tension pneumothoraces. There has recently been increased interest in performing ND at the fifth intercostal space in the midaxillary line to prevent complications associated with landmarking second intercostal space in the midclavicular line site.

Methods: A descriptive study included 142 women with self-reported PMS, aged 18-45 years, who were recruited by the Outpatient Department of Gynecological Endocrinology, Peking Union Medical College Hospital. Premenstrual

symptoms were retrospectively assessed by using screening MCC950 research buy questionnaires modified with the DSM-IV. In total, 126 eligible subjects were asked to record their daily symptoms during two consecutive menstrual cycles by using a premenstrual syndrome diary (PMSD).

Results: Of 126 eligible subjects, 67 filled in the PMSD for two cycles. The median of total scores of PMSD peaked on the day before menses and dropped after the beginning of the menses. Mood swings were the most common moderate-to-severe symptom prospectively reported by the subjects. The symptoms of PMS were relatively consistent across the two cycles.

Conclusions: Women with moderate-to-severe PMS were vulnerable to psychological symptoms. Further studies are needed to understand the correlations between hormonal changes and the experience of symptoms related to the menstrual cycle.”
“Background 17DMAG purchase and Purpose: Venous thromboembolism (VTE) is a major complication of urologic surgery. Data are limited regarding the benefits of heparin prophylaxis for patients undergoing minimally invasive urologic surgery. The American Urological Association recommends sequential compression devices (SCDs) for urologic

laparoscopic and robot-assisted procedures but provides no clear recommendations for the use of pharmacologic prophylaxis. We compare the rates of postoperative VTE in two groups of patients undergoing robot-assisted prostatectomy (RP) by GSK2879552 mouse two surgeons-one who consistently used heparin with SCDs (group 1) and the other who used SCDs alone (group 2) for prophylaxis.

Patients and Methods: An Institutional Review Board approved, prospectively managed database was analyzed. Group 1 received SCDs just before induction and 5000 units of heparin subcutaneously just after induction. SCDs were continued postoperatively, and heparin was administered

twice a day until discharge. VTE rate, patient age, body mass index (BMI), operative time, lymphocele rate, length of stay (LOS), estimated blood loss (EBL), Gleason score, and pathologic stage were compared. Categorical variables were analyzed with the chi square test of proportions and continuous variables with t test using SPSS v 14 software.

Results: There were 1486 consecutive patients who underwent RP between August 2007 and December 30, 2011. Of these, 922 patients received heparin/SCDs and 564 received SCDs alone. Age, BMI, EBL, medial LOS, Gleason score, and pathologic stage were the same in the two groups. There was a higher rate of positive nodes in group 2 (1.3% vs 3.5%). There was one lymphocele in each group. Although operative times were longer in group 2 (229 vs 170 min, P < 0.001), the incidence of VTE was not statistically different (1.0% vs 0.7%, P = 0.78).

This review discusses the luteal-phase insufficiency seen after GnRHa triggering and the various trials that have been performed to assess the most optimal luteal support in relation to GnRHa triggering. Although more research is needed, GnRHa triggering is now an alternative to HCG triggering, combining a significant reduction in OHSS with high ongoing pregnancy rates. (C) 2011, Reproductive Healthcare Ltd. Published

by Elsevier Ltd. All rights reserved.”
“With the exponential growth of cardiovascular implantable electronic devices (CIEDs) in pediatric patients, a new method of long-term surveillance, remote monitoring (RM), has become the standard of care. The purpose of this study was to determine the usefulness of RM as a monitoring tool in the pediatric population. A retrospective review was performed of 198 patients at the University of Iowa Children’s Hospital BMS-754807 molecular weight who had CIEDs. Data transmitted by RM were analyzed. The following Syk inhibitor data were examined: patient demographics; median interval between transmissions; detection of adverse events requiring corrective measures, including detection of lead failure; detection of arrhythmias and device malfunctions independent

of symptoms; time gained in the detection of events using RM versus standard practice; the validity of RM; and the impact of RM on data management. Of 198 patients, 162 submitted 615 RM transmissions. The median time between remote transmissions was 91 days. Of 615 total transmissions, 16 % had true adverse events with 11 % prompting clinical intervention. Of those events requiring clinical response, 61 % of patients reported symptoms. The median interval between last follow-up and occurrence of events detected by RM was 46 days, representing a gain of 134 days for patients followed-up at 6-month intervals and 44 days for patients followed-up at 3 month-intervals. The sensitivity and specificity of RM were found to be 99 and 72 %, respectively. The positive and negative predictive values were found to be 41 and 99 %, respectively. RM allows for early identification of arrhythmias

and device malfunctions, thus prompting earlier corrective measures and improving care and safety in pediatric patients.”
“BACKGROUND

Botulinum toxin type A (BTX-A) has been applied successfully to treat masseteric hypertrophy, but MLN2238 Proteases inhibitor it can cause muscle weakness.

OBJECTIVE

To measure the change in maximum bite force (MBF) after BTX-A injection into the human masseter muscle and to evaluate the influence of a booster (repeated) injection.

METHODS

Thirty volunteers completed 18-week follow-up, and MBF was measured. At 18 weeks after the first injection, a booster injection was given to 14 patients, and they were followed up until 18 weeks from the booster injection.

RESULTS

Mean MBF was approximately 20% lower at 2 weeks than before the injection, and it recovered gradually after 4 weeks to return to the preinjection level at 12 weeks.