(C) 2009 Elsevier Ltd. All rights reserved.”
“Inverse gas chromatography (IGC) has been widely used to determine the Flory-Huggins parameters, X, between solutes (probes) and polymers. This study correlated the Flory-Huggins parameter data using a multiparameter model, which included dispersion, polarity, acidity, and basicity components. The parameters of AC220 Angiogenesis inhibitor poly(E-caprolactone) (PCL) and polyepichlorohydrin (PECH) were calculated from IGC data using a series of probes. The parameters of the polymers were used to evaluate mutual miscibility between PCL and PECH. The results predicted miscibility in agreement with the conclusion of an IGC study using blends of PCL and PECH. A method to estimate the confidence interval

PND-1186 of polymer parameters was proposed. The anomalous solubility parameter of polymer mixtures previously reported was also explained using this model. (C) 2009 Wiley

Periodicals, Inc. J Appl Polym Sci 113: 4085-4091, 2009″
“Objective-To describe echocardiographic and clinical findings in cattle with cardiac manifestation of lymphoma.

Design-Retrospective case series.

Animals-7 adult Holstein dairy cows with cardiac lymphoma.

Procedures-Medical and necropsy records of all cows that underwent transthoracic echocardiography from January 2007 through April 2010 because of clinical signs of cardiac diseases or bovine lymphoma were reviewed. The diagnosis of cardiac manifestation of lymphoma was confirmed by necropsy examination or cytologic evaluation of pericardial fluid obtained by pericardiocentesis.

Results-Most commonly, cows had clinical signs of right-sided congestive heart failure secondary to cardiac tamponade with moderate to severe anechoic pericardial effusion (5/7 cows). In 2 cows, tachycardia was the only clinical sign in relation to cardiac disease and a heterogenic mass was observed protruding into the right atrium.

Conclusions

and Clinical Relevance-The use of transthoracic Acalabrutinib purchase echocardiography aided in the diagnosis of primary cardiac lymphoma in cows. Transthoracic echocardiography may help to quantify the severity of pericardial effusion and to orient needle placement for pericardiocentesis to determine a final diagnosis. A mass within the right atrium was also suggestive of cardiac lymphoma and should be differentiated from mural bacterial endocarditis. (J Am Vet Med Assoc 2012;241:1083-1087)”
“Crimean-Congo hemorrhagic fever (CCHF) is an acute, tick-borne viral disease, affecting only humans and newborn mice, with hemorrhagic manifestations and considerable mortality in humans. CCHF virus circulates in nature in an enzootic tick-vertebrate-tick cycle; migrating birds and livestock transferred from endemic to non-endemic areas may carry large numbers of infected ticks thus spreading the CCHF virus into novel areas. From 2000 through 2008, the infection emerged or re-emerged in Bulgaria, Albania, Kosovo, and Turkey.

The growth of the gabT triple mutant was weakly reduced in Arabidopsis ecotype

Landberg erecta (Ler) and strongly reduced in the Ler pop2-1 GABA transaminase-deficient mutant that accumulates higher levels of GABA. Much of the ability to grow on GABA-amended minimal media or in Arabidopsis pop2-1 leaves could be restored to the gabT triple mutant by expression in trans of just gabT2. Bcr-Abl inhibitor The ability of DC3000 to elicit the hypersensitive response (HR) in tobacco leaves is dependent upon deployment of the type III secretion system, and the gabT triple mutant was less able than wild-type DC3000 to elicit this HR when bacteria were infiltrated along with GABA at levels of 1 mm or more. GABA may have multiple effects on P. syringae-plant interactions, with elevated levels increasing disease resistance.”
“A novel series of tetraethylene glycol (TEG) triazolyl and squaramide containing oxazolidinones were synthesized and tested for their antibacterial activity against a selected panel of Gram-positive and Gram-negative bacteria. The 4-TEG-triazolyl derivatives were prepared by ‘click reaction’. The introduction of the TEG and squaramide groups did not favor

antibacterial activity. The three nucleoside-containing oxazolidinones were also prepared by ‘click’ methodology resulted in weak antibacterial activity.”
“Neurosyphilis remains to be a challenging GDC-0973 purchase diagnostic see more possibility worldwide. The aim of our study was to identify and report the clinical and laboratory profile of neurosyphilis, comparing features of HIV-infected and HIV-negative patients. A retrospective investigation of all cases of neurosyphilis, defined as positive VDRL test on cerebrospinal fluid, diagnosed at Hospital das Clinicas,

Ribeiro Preto School of Medicine between January 1988 and December 2005, was carried out. We identified 35 patients with a mean age of 42.1 years, 28.6% of them HIV infected and 74.3% of them were male. HIV-infected patients were younger (34.6 years), presented with a higher frequency of the early forms of neurosyphilis, higher titers of serum VDRL and higher mean proteinorrachia at the suboccipital level. Neurosyphilis is still characterized by clinical polymorphism and there are significant differences in its epidemiological, clinical and laboratory profile when HIV-infected patients are compared with HIV-negative patients.”
“P>The formation of leaf polarity is critical for leaf morphogenesis. In this study, we characterized and cloned an Arabidopsis gene, AS1/2 ENHANCER7 (AE7), which is required for both leaf adaxial-abaxial polarity formation and normal cell proliferation.

“
“Objectives: To examine the effects of psychological stress on QT dispersion (QTd) among CAD patients and whether these effects are mediated via the development of myocardial ischemia.

Methods: Psychological stress was induced using a public speaking task. Twelve-lead electrocardiograms (ECG) were recorded at rest, during mental stress, and during recovery. QTd was calculated as the difference between the longest and the shortest QT interval check details in the 12-lead ECG. Rest-stress myocardial perfusion imaging was also performed to detect mental stress-induced myocardial ischemia.

Results: Mental stress induced a significant increase in QTd compared to the resting condition (P <

0.001). This effect persisted beyond the first 10 minutes of recovery (P < 0.001). QTd was significantly associated with the development of mental stress ischemia with ischemic patients having significantly higher QTd during mental stress than nonischemic patients (P = 0.006). This finding remained significant after controlling for possible confounding factors (P = 0.01).

Conclusion: An acute psychological stress induces a significant CBL0137 order increase in QTd, which persists for more than 10 minutes after the cessation of the stressor. This effect seems to be,

at least partially, mediated by the development of mental stress-induced myocardial ischemia.

(PACE 2009; 32:1178-1183).”
“The objective of this study was to investigate intestinal function and morphology associated with peri-weaning failure to thrive syndrome (PFTS) in swine. jejunum and distal ileum from control and pigs exhibiting PFTS was harvested at weaning, 4 and 11 days post-weaning (PW) for intestinal barrier function studies and histological analyses (n = 6 pigs per group). Marked disturbances in intestinal barrier function was observed in PETS pigs, compared with controls, indicated by lower (p < 0.05) TER and increased

(p < 0.01) permeability to FITC dextran (4 kDa). Intestines from weaned pigs, subjected to a 4-day fast, exhibited minor disturbances in intestinal barrier function. www.selleckchem.com/products/i-bet151-gsk1210151a.html Villus atrophy and crypt hyperplasia were observed in the PFTS intestine compared with control and fasted pigs. These data demonstrate that PETS is associated with profound disturbances in intestinal epithelial barrier function and alterations in mucosal and epithelial morphology in which anorexia is not the sole factor. (C) 2012 Elsevier Ltd. All rights reserved.”
“Study Design. Prospective clinical study.

Objective. (1) To determine the prevalence of depression at the 1-year postoperative stage among spinal stenosis patients. (2) To assess the predictive value of preoperative and 3-month depressive symptoms regarding the 1-year surgery outcome.

Summary of Background Data. Some studies have found preoperative depressive symptoms to be associated with a poorer spinal stenosis surgery outcome. However, only the effect of preoperative depressiveness has been evaluated.

Preliminary evidence suggests associations between TSH-receptor

variants and fasting glucose level, D1 variants and insulin-like selleck chemicals growth factor I production, and D2 variants and hypertension, psychological well-being and response to T(3) or T(4) treatment. intriguingly, most of these associations are independent of serum thyroid hormone levels, which highlights the importance of local regulation of thyroid hormones in tissues. Future research might reveal novel roles for thyroid hormones in obesity, cardiovascular disease, osteoporosis and depression and could have implications for interpretation of thyroid function tests and individualization of thyroid hormone replacement therapy.”
“We investigated fluorescence from hemicyanine dye molecules in a liquid crystal (4,4′-n-pentylcyanobiphenyl) (5CB) medium at different temperatures. The fluorescence decay lifetime decreased monotonically irrespective of the thermodynamic phases of the host medium

as the temperature was increased. This behavior is due to an intramolecular motion of the dye promoted with the decrease in the viscosity of the medium facilitating a nonradiative decay of the excited dye molecules. By contrast, fluorescence intensity from the dyes in the nematic phase was about 3 times stronger than that in the crystalline or isotropic phase. This fluorescence enhancement in check details the nematic phase was found to be due to an anisotropic alignment of the dye molecules following the anisotropic alignment of the host liquid crystal medium along the pump-beam polarization direction. CP-868596 in vivo This light-induced liquid crystal molecular alignment was markedly enhanced by the guest dyes preferentially excited along the pump-beam polarization direction. The orientational order parameter of the dyes in the liquid-crystalline phase deduced from fluorescence anisotropy measurement was similar to the known order parameter

of the liquid crystalline 5CB. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3642960]“
“There are few dedicated pediatric neurophysiology services in Africa. Optimizing the efficiency of these units is essential for the large populations they serve. Two hundred eighty-seven electroencephalogram (EEG) studies, performed in a sub-Saharan neurophysiology unit, were analyzed for referral sources, appropriateness of referral, reporting consistency, and use in confirming epilepsy or a neurologic process. Pediatric neurologists requested 24% of the electroencephalogram studies and pediatricians 45%. Pediatric neurologists requested more appropriate referrals than pediatricians or nonspecialists. The electroencephalogram studies assisted management in 40% of cases. Electroencephalogram studies for nonepileptic indications, such as syncope, were highly predictable and typically normal. Education and training in the management of children with epilepsy could improve requesting practice and the subsequent usefulness of electroencephalograms in the diagnosis of epilepsy syndromes.

The analysis included HIV-infected subjects enrolled in the ALLRT cohort between 2000 and 2007 who had at least one buy C59 Wnt CD4 count measured and completed at least one resource utilization data collection form (N = 3143). Primary outcomes included the relative risk of hospital nights, emergency department (ED) visits, and disability days for HIV/HCV co-infected vs HIV mono-infected subjects. When controlling for age, sex, race, history of AIDS-defining events, current CD4 count and current HIV RNA, the relative risk of hospitalization, ED visits, and disability days for subjects with HIV/HCV co-infection compared to those with HIV mono-infection

were 1.8 (95% CI: 1.3-2.5), 1.7 (95% CI: 1.4-2.1), and 1.6 (95% CI: 1.3-1.9) respectively.

Programs serving HIV/HCV co-infected patients can expect Batimastat Proteases inhibitor approximately 70% higher rates of utilization than expected from a similar cohort of HIV mono-infected patients.”
“Purpose: To assess how early pleural and/or parenchymal abnormalities consistent with asbestos exposure could be ascertained and to identify factors associated with progression.

Materials and Methods: Informed consent was obtained under an institutional review board-approved protocol. Multiple sequential chest radiographs obtained between 1955 and 2004 in 84 workers exposed to amphiboles associated with vermiculite in the town of Libby, Montana, were studied. A panel of three NIOSH B readers reviewed each worker’s longitudinal chest radiograph series in reverse chronologic order and achieved a consensus reading for each radiograph. Measures of exposure were compared between workers with and those without progression of parenchymal and pleural abnormalities.

Results: Because of the way the study was designed, all subjects had pleural (n = 84) and/or parenchymal (n = 26) abnormalities on the most recent chest radiograph. Compared with other investigations that used different methods, this investigation revealed shorter latency periods (defined as the interval between date of hire

and date of earliest radiographic detection) for circumscribed pleural plaque (median latency, selleck 8.6 years) and pleural calcification (median latency, 17.5 years). Pleural abnormalities progressed in 64 workers, while parenchymal abnormalities progressed in 14. No significant differences were found with regard to measures of exposure between workers with and those without progression.

Conclusion: The latency period for the development of pleural plaques may be shorter than previously reported. Early plaques are subtle and may not be detectable except at retrospective review. (c) RSNA, 2010″
“Self-organized nano-cone arrays are fabricated on Si (100) by means of Ar(+) ion bombardment at normal incidence with ion energy of 1.5 keV and current density of 1000 mu A cm(-2). The nano-structured Si surface appears black as seen by the naked eye.

“
“The objective of this Birinapant in vitro study was to evaluate the susceptibility to cefepime

of a large group of ESBL-producing enterobacteria recently isolated in a Brazilian teaching hospital. The study included 280 strains of ESBL-producing enterobacteria, isolated between 2005 and 2008. The presence of the genes bla(CTX-M), bla(TEM) and bla(SHV) was determined by PCR and confirmed by nucleotide sequencing. Susceptibility testing for cefepime was performed by disc-diffusion, agar dilution method and E-test (R). Among the isolates, 34 (12.1%) presented a cefepime inhibition zone >= 21 and MIC <= 8 mg/L by agar dilution and E-strip methods. The use of cefepime for the treatment of infections caused by ESBL-producing bacteria has been controversial.

Some studies of PD/PK show the probability of achieving the required PD parameters for cefepime, when the MICs were < 8 mg/L, whereas others have reported Sapanisertib cell line therapeutic failure with the same MIC. Additional data is essential to come to terms about the report and treatment with cefepime in ESBL-producing organisms especially when these microorganisms are isolated from sterile sites and from critically ill patients. Keywords: enterobacteriaceae; beta-lactamases; cephalosporin resistance.”
“The adequacy of sitafloxacin clinical dose regimens was assessed by comparing the efficacy of the administration of 100 mg sitafloxacin once daily (100 mg qd group) and 50 mg sitafloxacin twice daily

(50 mg bid group). Patients with respiratory tract infections caused by pneumococci were orally treated with sitafloxacin (100 mg qd or 50 mg bid) for 7 days. The clinical efficacy, pneumococci eradication rate, safety, and selleck chemical pharmacokinetic and pharmacodynamic indices of the two groups were then assessed. The clinical efficacy was 93.5 % in both groups. The pneumococci eradication rate was 98.2 % in the 100 mg qd group and 92.7 % in the 50 mg bid group. The mean of the free AUC(0-24h) divided by the minimum inhibitory concentration (MIC) (fAUC(0-24h)/MIC) did not differ significantly between the 100 mg qd (103.24) and the 50 mg bid groups (105.25). The mean of the free C (peak) divided by the MIC (fC (peak)/MIC) was higher in the 100 mg qd group (10.19) than in the 50 mg bid group (6.53). The pathogen eradication rate was 98.9 % (89/90) when the fAUC(0-24h)/MIC was greater than 30, and the eradication rate was 98.9 % (89/90) when the fC (peak)/MIC was greater than 2. The incidences of adverse drug reactions were 33.7 % in the 100 mg qd group and 40.4 % in the 50 mg bid group. No obvious differences in the efficacy and safety were observed between the dosage groups. For cases in which a sufficiently high C (peak) is necessary to ensure the susceptibility of the pathogens to the drug, 100 mg sitafloxacin once daily should be administered.”
“Background: Ring chromosome 10 is a rare cytogenetic finding.

These ion sources, including but not limited

to desorption electrospray ionization, extractive electrospray ionization, low-temperature plasma probe, electrospray-assisted laser desorption/ionization, and desorption/ionization on porous silicon, offer varied reaction times (several milliseconds to several minutes) and are controlled by corresponding experimental parameters.

We discuss examples of different ion sources coupled with MS for reaction monitoring and highlight some of their unique applications in bioorganic and organic chemical reactions. We believe that, with this abundant toolbox of ion sources as sampling methods, we can be more confident in choosing the most effective technique to address problems of interest in reaction monitoring. (C) 2012 Elsevier Ltd. All rights reserved.”
“The bacterium Bacillus BEZ235 thuringiensis produces a crystal protein with insecticidal

learn more properties; however, crystal proteins can be damaged by ultraviolet (UV) radiation. The aim of this study was to improve the stability of the insecticidal crystal protein (ICP) by constructing a mutant line that expresses high levels of the UV light-protecting pigment, melanin. BMB181, a B. thuringiensis mutant with high melanin production, was obtained after sub-culturing BMB171 for several generations at 42 A degrees C. The melanin yield by BMB181 (without tyrosine supplementation) reached 8.55 mg/ml. The electroporation efficiency of BMB181 reached 10(6) CFU/mu

g when a 6.7-kb foreign plasmid was used. Microscopic and SDS-PAGE analyses revealed that ICP (CryIAc10; GenBank: AAA73077.1), which is highly toxic to Lepidoptera, was synthesized efficiently by strain BMB181. The insecticidal properties of a recombinant line derived from strain BMB181, designated BMB32 (cry1Ac10/BMB181), was tested against the cotton bollworm, Helicoverpa armigera. After UV irradiation for 4 h, BMB32 had a half maximal inhibitory concentration value of 1.37 mu g/ml, whereas the control line BMB31 (cry1Ac10/BMB171) had a median lethal dose value of 25.85 mu g/ml. These results indicate that the B. thuringiensis mutant is a candidate for industrial scale production of light-stable insecticides.”
“Purpose: Blebbistatin supplier To compare the in vitro degree of vaporization in bipolar and monopolar resection.

Materials and Methods: Using either a bipolar system or a monopolar system, samples of chicken muscle and lamb kidney were resected in an isolated basin and then desiccated in an incubator. The percentual degree of vaporization for each sample was obtained as a difference between the total fresh weight of the sample and the calculated fresh weights of the resected tissue and remains.

Results: Reference samples showed that the water content was 73% in muscle and 77% in kidney. More muscle (mean 52%) than kidney (32%; P < 0.0001) tissue was vaporized.

“
“Objective In diagnosing osteomyelitis (OM) both MRI and [18 F]FDG PET-CT proved to be accurate modalities. In anticipation of the advent of hybrid PET/MRI scanners we analyzed our patient group to give direction to future imaging strategies in patients with suspected OM.

In this retrospective study all patients of a tertiary referral center who underwent both an MRI and a PET for the diagnosis of OM were included. The results of those scans were evaluated using patient’s histology,

microbiological findings, and clinical/radiological follow-up. Additionally, ROC curve analysis of the SUVmax and the SUVmax ratio on the PET scans was performed. Two imaging strategies were simulated: first MRI followed by PET, or vice versa.

Twenty-seven localizations in 26 patients PD98059 were included. Both MRI and PET were shown to be accurate in our patients for the qualitative detection of OM. A cut-off value for the SUVmax of 3 gave optimal results (a specificity of 90 % with a sensitivity of 88 %). The SUVmax ratio gave a worse performance. The two simulated imaging strategies showed no difference in the final diagnosis in 20 out of 27 cases. Remarkably, 6 equivocal cases were all correctly diagnosed by the second modality, i.e., PET or MRI.

Both MRI and [18 F]FDG

PET were accurate in diagnosing OM in a tertiary referral hospital population. Simulation of imaging strategies showed that a combined sequential strategy was optimal. It seems preferable to use MRI as a primary imaging tool for uncomplicated unifocal cases, whereas BI 6727 ic50 in cases with (possible) multifocal disease or a contraindication for MRI, PET is preferred. This combined sequential strategy looks promising, but needs to be confirmed in a larger prospective study.”
“CHARGE syndrome is an autosomal Selleck CDK inhibitor dominant disorder

characterized by features represented in its acronym: Coloboma. Heart defect, Atresia of the choanae, Retarded growth and development. Genital abnormalities, Ear anomalies/deafness.

We report two patients with a diagnosis of typical CHARGE syndrome and one with atypical clinical diagnosis. All the three patients had uni- or bilateral choanal atresia and sensorineural hearing loss. The patients were screened for CHD7 gene mutations. Three novel occurring de novo heterozygous mutations were identified: a mutation in the donor splice site of intron 24, a missense mutation in exon 2 and a deletion in exon 11. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“Routine monitoring of relevant environmental viruses is of great importance for public health and quality assessment. Even though cell culture (i.e., viral infectivity assay) is still regarded as the golden standard, use of new strategies based on the molecular techniques significantly increased in the past years. Specific and rapid detection are main advantages of this alternative approach.

The main aim of this AG-881 in vivo study was to identify the relationship between unmet needs, social networks and quality of life of PWD living at home.

Methods: One hundred and fifty two community dwelling PWD and 128 carers were interviewed about PWD’s needs, social networks,

quality of life and other functional and psychological factors. All the interviews with PWD were carried out at their homes. Interviews with carers were undertaken either at PWD’s home, their own home or at the health centre. Whenever possible, PWD and carers were interviewed separately. The data collection took place between November 2005 and July 2007. The majority of participants (129, 84.9%) were recruited from National LY3023414 research buy Health Services (NHS) and the rest (23, 15.1%) were recruited from other organisations such

as social services and voluntary organizations in the UK.

Results: The most frequent unmet needs for PWD were daytime activities (77, 50.7%), company (60, 39.5%), and help with psychological distress (47, 30.9%). Higher number of behavioural and psychological symptoms, low-community involvement social networks, having a younger carer and higher carer’s anxiety were found to be predictors of higher unmet needs in PWD. Social networks and behavioural and psychological symptoms had an indirect effect on PWD’s self-rated quality of life through unmet needs.

Conclusions: Interventions aiming to reduce unmet needs, through the treatment of behavioural and psychological symptoms and the involvement of PWD in the community, would potentially improve find more PWD’s quality of life.”
“The effect of surfactant (sodium dodecyl sulfate) concentration on particle size, molar masses, glass transition, and tacticity of poly(methyl methacrylate) (PMMA) nanoparticles synthesized by semicontinuous heterophase polymerization under monomer-starved condition at constant monomer feeding rate is reported. Starved conditions

are confirmed by the low amount of residual monomer throughout the reaction and by the fact that the instantaneous polymerization rate is similar to the feeding rate of monomer. Under these conditions, polymer particles in the nanometer range (20-30 nm) were obtained with narrow size distribution (1.07 < D(w)/D(n) < 1.18), depending of surfactant concentration. Final particle size diminishes as the surfactant concentration is increased. Glass transition temperatures and syndiotactic content (54%-59%) of the produced polymers are substantially higher than those reported for commercial and bulk-made PMMA. Molar masses are much lower than those expected from termination by chain transfer to monomer, which is the typical termination mechanism in 0-1 emulsion and microemulsion polymerization of this monomer. (C) 2010 Wiley Periodicals, Inc.

In this study, we have investigated the antimicrobial properties of 21 flowering plants from 16 different families

against six bacterial strains consisting of two Gram negative and four Gram positive. Using selleck compound library the pour plate disc diffusion technique, almost all extracts from these plants were found to be active against some of the bacterial strains tested. The most interesting and active plants with broad spectrum activities include Duabanga grandiflora, Acalypha wilkesiana and Pseuduvaria macrophylla where the minimum inhibitory concentration, minimum bactericidal concentration and phytochemical analysis were carried out. This is the first report describing the antimicrobial and phytochemical properties of D. grandiflora and P. macrophylla. Our findings support the utilisation of higher plant species in the search for new antimicrobial molecules to combat new emerging infective diseases and the problem of drug resistant pathogens.”
“We report the case of a pregnancy in a 25-year-old woman who was born with ectopia vesicae and split pelvis, but had not undergone

any reconstructive or diversion surgery in childhood. Her antenatal period was uneventful and the infant was delivered by cesarean section at term due to breech presentation. The baby had no congenital anomalies. The postoperative period was uneventful and they were discharged from the hospital in a good general condition.”
“The antinociceptive activity of Flaveria trinervia extracts by tail-flicking

Belnacasan purchase and writhing methods was evaluated using mice. The abdominal MK-0518 chemical structure writhing method was carried out by administering petroleum ether, chloroform and methanol extracts orally. After 1 h of incubation, 0.6% acetic acid (10 mL kg(-1)) was administered intraperitoneally. After 5 min, each group of mice was observed for the amount of writhing for a duration of 20 min. Acetyl salicylic acid was used as the standard reference. The tail-flick method was carried out using a thermal model and the maximum possible analgesia was calculated. The LD50 values of petroleum ether, chloroform and methanol extracts were 700, 700 and 500 mg kg(-1), respectively. The methanol extract at 50 mg kg(-1) showed significant antinociceptive activity. The petroleum ether and chloroform extracts showed moderate antinociceptive activity at a dose of 70 mg kg(-1). The methanol extract showed more significant antinociceptive activity than the other extracts but was less effective than the standard. This investigation finds support for the ethnomedicinal claims of F. trinervia.”
“Clear cell carcinoma of the ovary has shown an exceedingly chemo-resistant phenotype, especially in cases that are recurrent or refractory to previous therapy.