RESULTS: Among 1385 sputum culture-positive cases at baseline, 11

RESULTS: Among 1385 sputum culture-positive cases at baseline, 1146 (83%) experienced at least one culture conversion during treatment. Conversion, however, was not sustained in all patients: 201 (15%) experienced initial culture conversion and at least one subsequent culture reversion

to positive; 1064 (77%) achieved sustained culture conversion. Median time to culture conversion was 3 months. Among 206 patients whose final conversion occurred 7-18 months after the initiation of therapy, 71% were cured or had completed treatment.

CONCLUSIONS: Blebbistatin solubility dmso Prolonged treatment for patients with delayed conversion may be beneficial, as 71% of late converters still achieved cure or completed treatment. This has implications for programs with defined end points for treatment failure. The interval between first and final conversion among patients whose initial conversion is not sustained raises concern with respect to the ongoing debate regarding duration of treatment and the definition of cure.”
“Objective: To compare the diagnostic conclusions between fetal neurosonography

and MK5108 Cell Cycle inhibitor MRI in the cases of congenital neurological abnormalities, and with postnatal clinical and imaging evaluation, when available.

Methods: A retrospective study of 28 patients who underwent a fetal MRI study for suspected congenital neurological anomalies. The diagnoses obtained by neurosonography and MRI were collected and compared. Both of them were compared with the final diagnosis when available by necropsy or postnatal evaluation. Postnatal imaging tests were performed only when clinically indicated.

Results: The indications AZD1208 datasheet for the fetal MRI examination were: fetal ventriculomegaly, posterior fossa anomalies, suspected midline defects, small-for-gestational-age cephalic biometry and confirmed congenital CMV infection. There was a good degree of agreement beyond chance between both techniques (kappa test = 0.76).

Conclusions: Both imaging modalities give a high-diagnostic performance with a good degree of agreement between them, when made by specialized

staff. Fetal MRI is a valuable complementary tool to detailed neurosonography which allows an evaluation of the normal brain maturation from the second trimester. It also offers a higher diagnostic performance for some congenital abnormalities such as cortical development or acquired lesions.”
“The potential for performing truly scarless, safe surgery that at the same time may be less morbid is tempting both patients and physicians alike to seriously consider Natural. Orifice Transluminal Endoscopy Surgery (NOTES) for a range of clinical applications. Given the move towards gastric-preservation by minimally invasive techniques for definitive management of early gastric cancer, this radical approach may find a niche within future clinical care paradigms for early stage malignant lesions of the stomach.

J Heart Lung Transplant 2010;29:86-92 (C) 2010 International Soci

J Heart Lung Transplant 2010;29:86-92 (C) 2010 International Society for Heart and Lung Transplantation. All rights reserved.”
“Dual-process models propose that addictive behaviors are determined by see more an implicit, impulsive system and an explicit, reflective system. Consistent with these models, research has demonstrated implicit affective associations with alcohol, using the Implicit Association Test (IAT), that predict unique variance in drinking behavior above explicit cognitions. However, different IAT versions have been used to measure implicit affective

associations with alcohol, and the present study sought to determine which of these IAT variants showed the highest validity and internal consistencies. in total, 4800 participants completed one of six IAT versions via the Internet: a bipolar IAT (i.e., positive vs. negative), a unipolar positive IAT (i.e., positive vs. neutral), or a unipolar negative IAT (i.e., negative vs. neutral) with general positive and negative stimuli or with positive and negative alcohol-related Rabusertib mw affective states. While the alcohol-related affective bipolar and unipolar positive IAT versions and the

general affective bipolar and unipolar positive IAT versions showed comparable internal consistencies, somewhat lower internal consistencies were found for the unipolar negative IAT versions. Further, alcohol-related affective IAT variants were more strongly related to explicit measures than general affective IAT versions. Also, alcohol-related and general affective bipolar and unipolar positive IAT variants were related to drinking behavior, but not unipolar negative IAT variants. Finally, the bipolar alcohol-related affective IAT, the unipolar alcohol-related positive

IAT and the unipolar general positive IAT predicted drinking behavior above explicit measures. Overall, the bipolar alcohol-related affective IAT outperformed all other IAT variants with respect to its relationship with explicit measures and drinking behavior. (c) 2009 Elsevier Ireland Ltd. All rights reserved.”
“Severe shoulder dystocia (SD) is Panobinostat order associated with neonatal brachial plexus injuries and skeletal fractures, with the former being the commonest cause for litigation related to birth trauma. The aim of this case-control study was to evaluate risk factors for birth injuries in cases presenting with SD.

Between January 2000 and December 2006, 22 babies who sustained brachial nerve paralysis or skeletal fractures following severe SD and requiring admission to Special Care Baby Unit (SCBU) were identified. The control group (n = 22) comprised the next infant delivered who was deemed to have SD but did not suffer significant birth injuries. Antenatal, labour and postnatal data were collected and compared between the two groups.

We present the first successful case of living donor liver transp

We present the first successful case of living donor liver transplantation using a donor with asymptomatic protein S deficiency. Interestingly, whereas the donor continued to have protein S levels approximately 50% of normal, the recipient maintained normal levels of protein S post-transplant, potentially due to compensation by extra-hepatic protein S production. We discuss the prior literature of protein S deficiency acquired via liver transplantation, and we evaluate potential criteria by which the safety of transplants utilizing this pool of donors may be enhanced.”
“A study CFTRinh-172 mw on the effect of secondary electron emission, which strongly affects

the detection of extreme-UV radiation, was performed on diamond detectors. Two different structures were compared: interdigitated contacts and a transverse Schottky diode configuration. Both devices were electrically characterized by I-V measurements and their responsivity was measured Selleck IPI-145 in the extreme UV spectral region (20-120 nm) by using He-Ne gas discharge radiation sources and a toroidal grating vacuum monochromator. Through an ad-hoc

measurement configuration, the contributions of the internal photocurrent and of the photoemission current have been analyzed and separately evaluated. The results showed that secondary electron emission, which clearly depends on the experimental conditions (e. g., external electric field, pressure, etc.), is one of the most relevant processes affecting the spectral responsivity LB-100 nmr in the extreme UV band. In particular, for interdigitated devices, extreme care must be taken in order to obtain an absolute value of their responsivity, while detectors in the transverse configuration can be shielded in such a way to avoid secondary electron current contribution and therefore provide a more correct and reliable response. (C) 2011 American Institute of Physics. [doi:10.1063/1.3602125]“
“Pellet manufacturing

by extrusion/spheronization is quite common in the pharmaceutical field because the obtained product is characterized by a high sphericity as well as a narrow particle size distribution. The established mechanisms only consider deformation of the initially fractured particles but do not account for mass transfer between the particles as a factor in achieving spherical particles. This study dealt with the visualization of mass transfer during spheronization. Therefore, two common pelletization aids, microcrystalline cellulose and kappa-carrageenan, were used alone as well as in combination with lactose as a filler. This study proves that mass transfer between particles must be considered in addition to plastic deformation in order to capture the spheronization mechanism.

Genotypes and mutations were determined by sequencing and phyloge

Genotypes and mutations were determined by sequencing and phylogenetic analysis. All strains belonged to genotype D, and most of them to subgenotype D1. All but two strains specified ayw2, one ayw3 and

one adw2 determinants. Two deletions of 8- or 20-bp were found in the X region in eight strains, six from patients with chronic active hepatitis. Eight of 21 strains from patients with cirrhosis harboured unusual mutations such as a stop codon at position 69 in the S region or a previously not described mutation in the BCP region ((1761)TC/ATTTG(1766)). All patients infected by strains with the stop codon mutation had detectable HBsAg and high viral load. The accumulation of mutations found in the BCP and S regions in HBV strains from patients with Napabucasin selleck kinase inhibitor chronic active hepatitis and cirrhosis may predict disease progression in Iranian HBsAg carriers.”
“The electromagnetic wave through the subwavelength diffraction grating can be largely absorbed by surface-wave plasmas (SWPs). A SWP source is built with two slot-array antennas element. Due to the dissipation of surface waves in overdense plasmas, this source can provide remarkable discharge efficiency of 4.4 cm(2)/W experimentally and 96% of incident power numerically. When the applied power as low as 200 W is supplied to the SWP source, a homogeneous

plasma with the uniform area up to 14×36 cm(2) and the plasma density up to 1.04×10(18) m(-3) is generated under the quartz slab. By varying the incident power and gas pressure, the parameter of plasmas can be easily controlled without density jumping. Moreover, the characters of bi-Maxwellian electron energy distribution prove that our SWP source yield

plasmas by surface heating actually. These excellent performances make the proposed source meet the requirements in CX-6258 manufacturer large-area plasma processing and also give its advices for plasmas heating in next meter-size SWP sources.”
“Interferon (IFN) has been used in the treatment of chronic hepatitis B for decades. Beneficial effects including hepatitis B e antigen/HBV DNA seroclearance have been documented. However, the effect of treatment on the prevention of cirrhosis and hepatocellular carcinoma (HCC) development remains controversial. We conducted a meta-analysis of available literature to evaluate whether IFN reduces the incidence of liver cirrhosis and HCC in patients with chronic hepatitis B. Twelve clinical controlled trials, including 2082 patients and comparing IFN with no treatment, were selected. Data on the incidence of liver cirrhosis and HCC in IFN treated and untreated patients were extracted from each study. The evaluation of preventive effectiveness was performed with an intention-to-treat method. The relative risk (RR) and 95% confidence interval (CI) of the main outcomes as a measure of efficacy were used. Meta-analysis was performed using fixed-effect or random-effect methods, depending on absence or presence of significant heterogeneity.

The present study investigates the

effects of different t

The present study investigates the

effects of different types of ageing on macro fibre, microfibril and nanofibril reinforced PF composites. The effect of chemical modifications of fibres on the degradability of the composites at different environments also has been analysed. (C) 2013 Elsevier B.V. All rights reserved.”
“Objective: The purpose of this study was to verify if the preservation of residual hearing after cochlear implantation in classic adult cochlear implant candidates implanted with a perimodiolar electrode correlates with the electric thresholds and with speech perception measures.

Study Design: Retrospective study.

Setting: Cochlear Implant Center at a tertiary referral University Hospital.

Patients: Forty-one patients with cochlear

implant were involved in our study. They were subdivided into 2 groups according selleck chemicals llc to the average preoperative hearing loss at the frequencies of 125 and 250 Hz (low-frequency pure tone average [LFPTA]). Group A included 21 patients with a mean LFPTA of 90 dB HL or lower; group B included 20 patients with a mean LFPTA of greater than 90 dB HL. They underwent 12 months’ follow-up after cochlear implantation, including standard audiologic investigation, speech discrimination tests, and electrical measurements.

Results: signaling pathway No significant differences were found in speech perception tests among groups. In group A, hearing was preserved in 8 (group A1) and was lost in 13 patients (group A2);

the postoperative LFPTA was significantly better (p < 0.0001) in A1. Group A1 patients present significantly higher C values (p G 0.0001) than the other 2 groups, and the dynamic range was therefore significantly wider (p < 0.001).

Conclusion: Preservation of residual hearing should be attempted in all cases. In fact, although effects on the speech perception are not evident with the standard evaluation, larger electrical dynamic range can be achieved and may represent a sign of cochlear “”well-being,”" potentially allowing a more complex electric stimulation of the nerve.”
“Transcatheter aortic valve implantation (TAVI) is currently reserved for high or prohibitive surgical-risk PD-1/PD-L1 Inhibitor 3 datasheet patients with aortic valve stenosis. We report on successful TAVI in two Jehovah’s witness patients. It offers a simple and effective treatment of severe aortic valve stenosis in high-risk patients who refuse the use of allogeneic blood and blood products.”
“To clarify the clinical symptoms of the influenza A virus during the 2009 pandemic influenza outbreak, we describe the clinical features of outpatients diagnosed with type A influenza by use of the rapid influenza diagnostic test (RIDT) from September to December 2009. Questionnaires were used to collect prospective data on 1,122 cases with influenza-like illness at our medical institutions.

“Growth velocity was determined in 121 boys and 58 girls w

“Growth velocity was determined in 121 boys and 58 girls with constitutional delay of growth and development (CDGD) of familial origin. No data were included from patients suffering from growth hormone insufficiency (i.e. neurosecretory dysfunction for growth hormone) or any disease. From 479 values obtained in boys and 230 values obtained in

girls the 25(th), 50(th) and 75(th) percentiles were calculated. The mean growth velocity in children and adolescents with CDGD before the beginning of puberty was lower than the mean growth velocity see more of other European (British, German or Swiss) standards.

Conclusion: Specific data of growth velocity should be used in patients with CDGD since population-based data may underestimate the normal growth velocity of these patients.”
“Objectives This paper aims to investigate the effect of socioeconomic status, as measured by education, on the survival of breast cancer patients treated on 10 studies conducted by the Cancer and Leukemia Group B. Methods Sociodemographic data,

including education, were reported by the patient at trial enrollment. Cox proportional hazards model stratified by treatment arm/study was used to examine the effect of education on survival among patients with early stage and metastatic breast cancer, after adjustment for known prognostic factors. Results Tariquidar datasheet The patient population included 1020 patients selleck products with metastatic disease and 5146 patients with early stage disease. Among metastatic patients, factors associated with poorer survival in the final multivariable model included African American race, never married, negative estrogen receptor status, prior hormonal therapy, visceral involvement, and bone involvement. Among early stage patients, significant factors associated with poorer survival included African American race, separated/widowed, post/perimenopausal, negative/unknown estrogen receptor status, negative progesterone receptor status, >4 positive nodes, tumor diameter >2cm, and education. Having not completed high

school was associated with poorer survival among early stage patients. Among metastatic patients, non-African American women who lacked a high school degree had poorer survival than other non-African American women, and African American women who lacked a high school education had better survival than educated African American women. Conclusions Having less than a high school education is a risk factor for death among patients with early stage breast cancer who participated in a clinical trial, with its impact among metastatic patients being less clear. Post-trial survivorship plans need to focus on women with low social status, as measured by education. Copyright (c) 2011 John Wiley & Sons, Ltd.”
“Aim: To produce age and gender specific exophthalmos references for Turkish children aged 7-18 years old.

Treatment of selected mutants confirmed that TSF and SOC1 are nec

Treatment of selected mutants confirmed that TSF and SOC1 are necessary for the flowering response to BAP, whereas the activation cascade might partially act independently of FD. These experiments provide a mechanistic basis for the role of cytokinins in flowering, and demonstrate that the redundant genes FT and TSF are differently regulated by distinct floral-inducing DAPT mw signals.”
“The efficacy and safety of combined interferon (IFN) plus ribavirin in patients on long-term dialysis and chronic hepatitis C remains unclear, although a number of small clinical trials have

addressed this issue. We evaluated the efficacy and safety of combination antiviral therapy (conventional or pegylated interferon plus ribavirin) in dialysis patients with chronic hepatitis C by performing a systematic review of the literature with a meta-analysis of clinical trials. The primary outcome was sustained virological response (SVR) (as a measure of efficacy); the secondary outcome was drop-out rate (as a measure of tolerability). We used the random effects model of Der Simonian and Laird, with

heterogeneity and sensitivity analyses. We identified 10 clinical studies (151 selleck screening library unique patients), one (10%) of which was a controlled clinical trial. Most (97.4%) patients were on long-term haemodialysis. The summary estimate for SVR and drop-out rate was 56% [95% Confidence Intervals (95% CI) 28-84] and 25% (95% CI, 10-40), respectively. The most frequent side effects requiring interruption of treatment were anaemia (26%) and heart failure (9%). These results occurred irrespective of type of interferon (conventional or peg-IFN, peg-IFNalfa-2a or alfa-2b), trial design (controlled or cohort study), or clinical characteristics of patients (naive, nonresponders or relapsers). The studies were heterogeneous with regard to SVR and drop-out rate. Combination antiviral therapy (interferon plus ribavirin)

gives encouraging results IWR-1-endo inhibitor in terms of efficacy and safety among dialysis patients even if the limited number of patients enrolled in our meta-analysis hampers definitive conclusions.”
“The use of small molecules has great power to dissect biological processes. This study presents the identification and characterisation of an inhibitor of peroxisome matrix protein import. A mini-screen was carried out to identify molecules that cause alteration in peroxisome morphology, or mislocalization of a peroxisome targeted fluorescent reporter protein. A benzimidazole lead compound (LDS-003655) was identified that resulted in reduced GFP fluorescence in peroxisomes and cytosolic GFP accumulation. The effect of the compound was specific to peroxisomes as Golgi bodies, endoplasmic reticulum and the actin cytoskeleton were unaffected even at 25 mu M, whereas peroxisome import via the PTS1 pathway was compromised at 100 nM.

Copyright (C) 2012 S Karger AG, Basel”
“Objective: To estim

Copyright (C) 2012 S. Karger AG, Basel”
“Objective: To estimate time trends in prevalence of symptoms and reported diagnosis related to asthma, allergic rhinitis/conjunctivitis and eczema among school children in the north-west coastal part of Croatia. Methods: Results of two identical cross-sectional

surveys conducted on the same area 8 years apart (school years 2001/02 versus 2009/10) in complete adherence Selleck MK2206 to the protocol of the International Study of Asthma and Allergies in Childhood were compared. Surveyed population comprised two age groups: 6-7 years (n = 1634 versus n = 1052) and 13-14 years (n = 2194 versus 1181). Results: Significant (p<0.001) increases in prevalence (%) of symptoms related to asthma (8.4 versus 14.0), allergic rhinitis (17.5 versus 25.6), allergic rhinoconjunctivitis (6.7 versus 15.3) and eczema (3.4 versus 5.9) were observed in the 13-14-year-olds. In the 6-7-year-olds there were observed significant (p<0.001) increases in prevalence of symptoms of eczema (5.4 versus 8.7)

and allergic rhinitis (16.9 versus 22.1) whereas prevalence of symptoms related to asthma (9.7 versus 9.4; p = 0.398) and allergic rhinoconjunctivitis (5.6 versus 6.8; p = 0.102) showed to be stable. Significant increases in prevalence of reported diagnosis were observed for asthma (5.2 versus 6.9; p = 0.02) and hay fever (10.5 versus 14.6; p<0.001) in the older, and for eczema (10.6 versus 14.1; p<0.001) in the SBE-β-CD mw younger age group. Conclusion: Prevalence of asthma and allergic diseases among the school children living on the surveyed area showed a rising trend.”
“Aim: To evaluate the urodynamic effects, therapeutic efficacy and safety of solifenacin versus tolterodine treatment for women with overactive bladder syndrome.

Methods: Patients were randomized

to receive either solifenacin 5 mg or tolterodine ER 4 mg once a day for 12 weeks at each SNX-5422 nmr four-week visit in a post-marketing study. Only women (solifenacin [n = 26] vs. tolterodine [n = 22]) were included in this subgroup analysis. Adverse events and changes of urodynamic values and clinical data were compared between the solifenacin and tolterodine groups.

Results: The volume voided per micturition increased in the solifenacin group (n = 21) (P = 0.04). The strong desire to void and pad-test result improved in the tolterodine group (n = 21; P = 0.02 and 0.03, respectively). There were no between-group differences in changes of any urodynamic data, voiding diary values or adverse events after treatment; however, changes of heart rate differed between the two groups (P = 0.0004), especially at visit 2 (solifenacin vs. tolterodine, -4.3 vs. 3.8, P = 0.02) and visit 3 (-3.2 vs. 4.8, P = 0.03).

Methods Ten SOTRs were administered cycles of low-dose oral capec

Methods Ten SOTRs were administered cycles of low-dose oral capecitabine (0.51.5g/m2 per day) for days 1 to 14 of a 21-day treatment cycle. Measurements (skin screenings, laboratory and toxicity monitoring) were performed every 1 to 3months. Incidence rates of squamous cell carcinoma (SCC) before and during treatment were determined and compared using the Wilcoxon signed-rank Birinapant purchase test. Results The average incidence rate (mean +/- SD) of SCC before treatment (0.56 +/- 0.28 SCCs/month, range

0.171.17 SCCs/month) declined to 0.16 +/- 0.11 SCCs/month (range 00.33 SCCs/month) during the first 12months of treatment (mean reduction 68 +/- 30.0%, range 0100%, p<.005). Reduction in actinic keratosis was observed. Common side effects included fatigue, nausea, hand-and-foot syndrome, gout, and poor renal function. Seven of 10 participants required dose adjustment, and two of these were discontinued from the study drug because of side effects. Limitations Case series design, small observational population. Conclusions SOTRs experienced a clinically and statistically significant decline in incident SCCs during treatment with low-dose oral capecitabine, with varying degrees of side effects. Larger randomized trials will determine the dose

and efficacy of capecitabine for adjuvant treatment of NMSC in SOTRs.”
“Although the precise causes of psoriasis are unclear, it is widely accepted that psoriasis is a disorder in which factors in the immune system, enzymes, and other biochemical substances that regulate skin cell division are Sapanisertib ic50 impaired, leading to rapid proliferation of keratinocytes and incomplete keratinization. Expression of the helix-loop-helix transcription factor Id1 JNK inhibitors library (inhibitor of differentiation/DNA binding), functioning as an inhibitor of differentiation, is known to increase in psoriatic skin. However, the molecular involvement of this particular biomarker in the psoriatic immune system remains to be elucidated. We measured Id1 mRNA expression in peripheral blood mononuclear cells (PBMCs) of psoriatic patients

and healthy controls using semi-quantitative reverse transcriptase-PCR. The normalized level of Id1 transcripts in psoriatic patients was about 2-fold higher than that in controls (P < 0.05). When we examined the proliferation rate of PBMCs, the stimulation index obtained from the phytohemagglutinin stimulation assay was not significantly different in psoriatic patients. In patients with psoriasis, there was no correlation between the stimulation index and the psoriasis area severity index. We suggest that Id1 has a role in causing psoriatic immune cell symptoms.”
“Cytoplasmic recognition of pathogen virulence effectors by plant NB-LRR proteins leads to strong induction of defence responses termed effector triggered immunity (ETI). In tomato, a protein complex containing the NB-LRR protein Prf and the protein kinase Pto confers recognition of the Pseudomonas syringae effectors AvrPto and AvrPtoB.

6 +/- 5 7 mu g mL(-1) h, 23 5 +/- 6 3 mu g mL(-1) h and the refer

6 +/- 5.7 mu g mL(-1) h, 23.5 +/- 6.3 mu g mL(-1) h and the reference values were 25.6 +/- 6.6 mu g mL(-1) h, 26.7 +/- 6.8 mu g mL(-1) h, respectively. The 90 % C. I. of AUC(0-t) was 0.83 to 0.94 and AUC(0-8), 0.82 to 0.94. Consequently, all the results fulfilled the standard criteria of bioequivalence, being Smad3 phosphorylation within the 0.80 to 1.25 % range. In addition to the 90 % C. I. of the parameters, a two-way ANOVA showed that there was no significant difference between the two products. Based on these statistical analyses, it is concluded that the test product is bioequivalent to the reference product.”

colitis is a chronic inflammatory disease of the colon. The etiology is unknown. Risk factors GDC-0068 manufacturer include a history of recent infection with Salmonella or Campylobacter, living in Western industrialized nations and at higher latitudes, and a family history of the disease. The incidence peaks in early adulthood,

but patients can develop the disorder from early childhood through adulthood. Ulcerative colitis often presents with abdominal pain, diarrhea, and hematochezia. It is important to exclude infectious etiologies. Anemia and an elevated erythrocyte sedimentation rate or C-reactive protein level may suggest inflammatory bowel disease, but the absence of laboratory abnormalities does not rule out ulcerative colitis. The diagnosis is suspected clinically and confirmed through endoscopic biopsy. First-line treatment is therapy with 5-aminosalicylic acid. Corticosteroids may be added if 5-aminosalicylic acid therapy is ineffective. Infliximab can be added to

induce and sustain remission. Patients with severe or nonresponsive ulcerative colitis should be hospitalized, and intravenous corticosteroids should be given. If medical management has been ineffective, surgical intervention is indicated for severe disease. Patients with ulcerative colitis have an increased risk of colon cancer and should have periodic colonoscopy beginning eight to 10 years after diagnosis. Copyright (C) 2013 American Academy of Family Physicians.”
“The pharmacokinetics of doxycycline hydrochloride (CAS 24390-14-5) Smoothened Agonist inhibitor was investigated In 11 healthy Chinese volunteers after single- and multiple-dose Intravenous (i. v.) Infusion. This study was conducted according to an open, randomized, four-period design with a one-week washout period separating each trial period. Single-dose studies with 100, 200, and 300 mg doxycycline were performed in the first three periods by a replicated 3 x 3 Latin square crossover design. Multiple-dose studies with once-daily 100 mg doxycycline for 7 consecutive days were performed in the last treatment period.

Blood samples for pharmacokinetic profiling were taken up to 48 It post-infusion. Doxycycline hydrochloride plasma concentrations were determined with a validated liquid chromatography-ultraviolet (HPLC-UV) method.