The PET-CT and MRI data were co-registered based on mutual inform

The PET-CT and MRI data were co-registered based on mutual information. The residual tumor volume defined on the F-18-FLT PET (Vol-PET) was compared with that of gadolinium [Gd] enhancement on T1-weighted MRI (Vol-T1) and areas of hyperintensity on T2-weighted MRI (Vol-T2). Results The mean 4 Vol-PET (14.61 cm(3)) and Vol-T1 (13.60 cm(3)) were comparable and smaller than the mean Vol-T2 (32.93 cm(3)). The regions of F-18-FLT uptake exceeded the contrast find more enhancement and the hyperintense area on the MRI in 14 (73.68%) and 8 patients (42.11%), respectively. In 5 (26.32%) of the 19 patients, Vol-PET extended beyond 25 mm from the margin of Vol-T1; in 2 (10.53%) patients, Vol-PET

extended 20 mm from the margin of Vol-T2. Vol-PET was detected up to 35 mm away from the edge of Vol-T1 and 24 mm away from the edge of Vol-T2. In 16 (84.21%) of the 19 patients, the Vol-T1 extended beyond the Vol-PET. In all of the patients, at least some of

the Vol-T2 was located outside of the Vol-PET. Conclusions The volumes of post-operative residual tumor in patients with malignant glioma defined by F-18-FLT uptake on PET are not always consistent with the abnormalities shown on post-operative MRI. Incorporation of F-18-FLT-PET in tumor delineation may have the potential to improve the definition of target volume in post-operative radiotherapy.”
“Biornphalaria glabrala snails are known to display a wide rangeof check details susceptibility phenotypes to Schistosoma mansoni infection depending on the genetics of both the snail and the invading parasite. Evidence exists for a role of hydrolytic enzymes in the defense of molluscs against invading parasites. To elucidate the role of these enzymes in the outcome of infection in the snail, proteolysis was examined in parasite-resistant

and -susceptible snails. Zymographs of extracts from the whole snail or hepatopancreas indicated higher proteolytic activity in resistant, compared AZD6094 mouse with susceptible, snails. Lytic activity coincided with a high-molecular-weight smear (220 to 66 kDa) that was abrogated by the cysteine protease inhibitor trans-epoxysuccinyl-L-leucyl amido-(4-guanidino) butane. Quantitative flourimetric assays showed 3.5-fold higher activity in resistant than in susceptible snails. From a hepatopancreas cDNA library, several cysteine protease encoding expressed sequence tags including the full-length cDNA for cathepsin B were identified. Sequence analysis revealed that this cathepsin B belonged to the C I A family of peptidases characterized by the presence of the catalytic cysteine-histicline dyad, the “Occluding loop,” signal sequence, and cleavage sites for the prepro and propeptides. Quantitative real-time reverse transcriptase-polymerase chain reaction showed higher up-regulation of cathepsin B transcript in resistant than in the susceptible snail after parasite exposure.

Combining these high-resolution imaging techniques with the expre

Combining these high-resolution imaging techniques with the expression of fluorescent cytoskeletal fusion proteins in live cells using correlative microscopy procedures will usher in an radical change in our understanding of the molecular dynamics that underpin the organization and function of the cytoskeleton.”
“Mating plugs have been described GSK1838705A in many species, and their presence often implies a function in protecting a male’s ejaculate. Yet, explicit functions are not always tested.

In this study, we test whether fragments of male genitalia lodged in the female genital opening of the St Andrew’s Cross spider (Argiope keyserlingi) are mating plugs and 432 prevent female remating. Further, we test whether copulation duration, cannibalism, and male or female size affect the lodgement and persistence of these genital fragments. We show that males always break off a genital fragment, which when lodged in the female genital opening, can successfully prevent female remating. However,

the lodgement of a genital fragment is not always successful and it may not persist for a prolonged period. Whether a genital fragment is successfully retained is influenced by female control over copulation duration. We have PF-03084014 molecular weight previously shown that females can terminate copulation duration by attacking the male, which may or may not lead to cannibalism. If females terminate copulations early, genital fragments are either

not lodged or do not persist. Male size can offset female control with larger males lodging more persistent fragments. Contrary to predictions, sexual cannibalism was not related to how long the fragment persisted within the female. We demonstrate the existence of mating selleck screening library plugs in St Andrew’s Cross spiders and document considerable variation in the formation and persistence of mating plugs that is likely to reflect male and female conflict over mate plugging.”
“In addition to its antibacterial activity, the cathelicidin-derived LL-37 peptide induces multiple immunomodulatory effects on host cells. Atomic force microscopy, F-actin staining with phalloidin, passage of FITC-conjugated dextran through a monolayer of lung epithelial cells, and assessment of bacterial outgrowth from cells subjected to Pseudomonas aeruginosa infection were used to determine LL-37′s effect on epithelial cell mechanical properties, permeability, and bacteria uptake. A concentration-dependent increase in stiffness and F-actin content in the cortical region of A549 cells and primary human lung epithelial cells was observed after treatment with LL-37 (0.5-5 mu M), sphingosine 1-phosphate (1 mu M), or LPS (1 mu g/ml) or infection with PAO1 bacteria.

“Background: The regulatory

“Background: The regulatory

SHP099 price information encoded in the DNA of promoter regions usually enforces a minimal, non-zero distance between the coding regions of neighboring genes. However, the size of this minimal regulatory space is not generally known. In particular, it is unclear if minimal promoter size differs between species and between uni- and bi-directionally acting regulatory regions.\n\nResults: Analyzing the genomes of 11 yeasts, we show that the lower size limit on promoter-containing regions is species-specific within a relatively narrow range (80-255 bp). This size limit applies equally to regions that initiate transcription on one or both strands, indicating that bi-directional promoters and uni-directional promoters are constrained similarly. We further find that young, species-specific regions are on average much longer than older regions, suggesting either a bias Torin 1 towards deletions or selection for genome compactness in yeasts. While the length evolution of promoter-less intergenic regions is well described by a simplistic, purely neutral model, regions containing promoters typically show an excess of unusually long regions. Regions

flanked by divergently transcribed genes have a 432 bi-modal length distribution, with short lengths found preferentially among older regions. These old, short regions likely harbor evolutionarily conserved bi-directionally active promoters. Surprisingly, some of the evolutionarily youngest regions in two of the eleven species (S. cerevisiae and K. waltii) are shorter than the lower limit observed in older regions.\n\nConclusions: The minimal chromosomal space required for transcriptional regulation appears to be relatively similar across yeast species, and is the

same for uni-directional and bi-directional promoters. New intergenic this website regions created by genome rearrangements tend to evolve towards the more narrow size distribution found among older regions.”
“The rapid diagnosis of tuberculosis (TB) and latent tuberculosis infections (LTBI) is a significant problem in clinical practice. The aim of this study was to evaluate the diagnostic value of an enzyme-linked immunosorbent spot (ELISPOT) assay measuring interferon-gamma in hepatitis C patients with LTBI. A total of 160 hepatitis C patients at the Jilin University Hospital, Changchun, China, were prospectively enrolled from January 2009 to December 2010; 43 had been positively diagnosed with TB, 38 with non-TB diseases, and 79 with a history of TB. All patients were evaluated by the tuberculin skin test (TST) and ELISPOT assays. Among the 43 diagnosed TB patients, the ELISPOT assay had a sensitivity of 92.1%, compared to a sensitivity of 60.5% for the TST. Among the 79 TB exposure patients, the ELISPOT assay was more sensitive (90%) than the TST (61.5%), the specificity of the ELISPOT assay was 90%, and the specificity of the TST was 61.5% in LTBI.

For this reason the design of dendrimers with modulated size, sha

For this reason the design of dendrimers with modulated size, shape, branching length/density,

and their surface functionality, clearly distinguishes these structures as unique and optimum carriers for medical applications. The bioactive agents may be encapsulated into the interior of the dendrimers or chemically attached/physically adsorbed onto the dendrimer surface, with the option of tailoring the carrier to the specific needs of the active material selleck chemicals and its therapeutic applications. In this regard one area with growing attention is photodynamic therapy (PDT) where a photosensitizer combined with light and molecular oxygen can easily cause irreversible damage to the target tissue. Nevertheless most of the photosensitizers have solubility issues when attempts are made to dissolve them in aqueous environments, hampering in most cases their medical applicability. Currently, investigations are running towards the combination of these photosensitizers with dendrimers increasing their organization, solubility and specificity to the target tissues. In this communication we review the latest advancements in the synthesis of porphyrin and phthalocyanine dendrimer architectures, regarding

their utility as biomedical agents.”
“It has been known for several decades that cyclic AMP (cAMP), a prototypical second messenger, transducing BI 6727 molecular weight the action of a variety of G-protein-coupled receptor ligands, has potent immunosuppressive and anti-inflammatory actions. These actions have been attributed in part to the CCI-779 PI3K/Akt/mTOR inhibitor ability of cAMP-induced signals to interfere with the function of the proinflammatory transcription factor Nuclear Factor-kappaB (NF-kappa B). NF-kappa B plays a 3 crucial role in switching on the gene expression of a plethora of inflammatory

and immune mediators, and as such is one of the master regulators of the immune response and a key target for anti-inflammatory drug design. A number of fundamental molecular mechanisms, contributing to the overall inhibitory actions of cAMP on NF-kappa B function, are well established. Paradoxically, recent reports indicate that cAMP, via its main effector, the protein kinase A (PKA), also promotes NF-kappa B activity. Indeed, cAMP actions appear to be highly cell type- and context-dependent. Importantly, several novel players in the cAMP/NF-kappa B connection, which selectively direct cAMP action, have been recently identified. These findings not only open up exciting new research avenues but also reveal novel opportunities for the design of more selective, NF-kappa B-targeting, anti-inflammatory drugs.”
“Salinity stress is known to modify the plasma membrane lipid and protein composition of plant cells.

(C) 2014 Baishideng Publishing Group Inc All rights reserved “

(C) 2014 Baishideng Publishing Group Inc. All rights reserved.”
“The definition of trans-fatty acids (TFA) was established by the Codex Alimentarius to guide nutritional and legislative regulations to reduce TFA consumption. Currently, conjugated linoleic acid (CLA) is excluded from the TFA definition based on evidence (primarily preclinical studies) implying health benefits on weight find more management and cancer prevention. While the efficacy of CLA supplements remains inconsistent in randomised clinical trials, evidence has emerged to associate supplemental CLA with negative health outcomes, including increased subclinical inflammation and oxidative

stress (particularly at high doses). This has resulted in concerns regarding the correctness of excluding CLA from the TFA definition. Here we review recent clinical and preclinical literature on health implications of CLA and ruminant TFA, and highlight several issues surrounding the current Codex definition of TFA and how it may influence interpretation for public health. We find that CLA derived from ruminant foods differ from 4 commercial CLA supplements in their isomer composition/distribution,

consumption level and bioactivity. We conclude that health concerns associated with the use of supplemental CLA do not repudiate the exclusion of all forms of CLA from the Codex TFA definition, particularly when using the definition for food-related purposes. Given the emerging differential bioactivity of TFA from industrial v. ruminant sources, we advocate WH-4-023 that regional nutrition guidelines/policies should focus on eliminating industrial forms of trans-fat from processed foods as opposed to all TFA per se.”
“Extended-spectrum BI-D1870 mouse beta-lactamase (ESBL) production and quinolone resistance are often associated in enterobacteria. Prior exposure to 3G cephalosporins/quinolones accelerates the risk of resistance to both these groups of antibiotics. Hence, information on the antimicrobial resistance pattern of uropathogenic Escherichia coli (UPEC) isolates is important to better formulate the guidelines for the empirical therapy of urinary tract infection

in the context of HIV/AIDS. The aim of this study was to determine the incidence of ESBL/AmpC and fluoroquinolone (FQ) resistance among urinary E. coli isolates and to establish the association of extraintestinal virulence and phylogenetic distribution with antibiotic resistance and host immunocompromisation. Accordingly, 118 urinary Escherichia coli isolates from HIV (n=76) and non-HIV antenatal patients (n=42) from Chennai, South India, were analysed for the presence of five virulence-associated genes (VAGs): pap, sfa/foc, afa/dra, iutA and kpsMII. Compared with the susceptible HIV isolates, the majority of the ESBL(+)AmpC(+)FQ(R) isolates harboured iutA (66.7%) and pap (40%). The Fa-resistant HIV isolates were significantly enriched for iutA (67.8%) and kpsMII (47.

It yielded myocardial T-1 values consistent with expected T-1 and

It yielded myocardial T-1 values consistent with expected T-1 and an increasing homogenization of myocardial segments owing to B-1 correction. The mean myocardial T-1 value was 134142 ms.\n\nConclusionMyocardial 3D T-1 mapping using the variable flip angle approach can potentially be useful for evaluating learn more fibrosis on the entire myocardium using a standard clinical sequence. Magn Reson Med 71:823-829, 2014. (c) 2013 Wiley Periodicals, Inc.”
“Background: Acute hyperglycaemia is an adverse prognostic factor

in patients with acute coronary syndrome (ACS). It is unclear whether these negative effects apply equally to patients with diabetes mellitus (DM) and non-DM patients.\n\nAim: To evaluate the short-term (in-hospital) and long-term (four-year) prognostic value of acute hyperglycaemia in ACS patients with or without DM.\n\nMethods: The study involved 116 ACS patients admitted between 2004 and 2006 to our department, who were SB203580 solubility dmso selected for invasive treatment and who had both admission and first fasting glucose levels measured. Patients were classified as DM (n = 23), on the basis of a known history of diabetes or newly detected diabetes, or non-DM (n = 93). Acute hyperglycaemia was defined as an

admission glycaemia >= 10.0 mmol/L (180 mg/dL) for non-DM patients, or >= 7.8 mmol/L (140 mg/dL) for DM patients, or a first fasting glucose level >= 5.6 mmol/L (100 mg/dL) for both DM and Baf-A1 nmr non-DM patients. The primary end-point was defined as mortality during follow-up. The secondary end-points were death, cardiac arrest or repeated ACS occurrence, stroke or transient ischaemic attack, and the need for repeat percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) procedure during the in-hospital and four-year

post-hospital periods. During follow-up, patients were assessed for a composite end-point defined as all-cause death, repeated ACS occurrence, repeat PCI or CABG procedure, and stroke.\n\nResults: Acute hyperglycaemia was present in 28 non-DM and 14 DM patients. The mean follow-up time was 4 +/- 0.6 years. For DM patients, there was no significant difference in four-year mortality between hyperglycaemic and normoglycaemic patients (14.3% vs 11.1%, respectively; NS). The occurrence of secondary end-points and composite end-point frequency was also similar for these subgroups, both for in-hospital and four-year observations. For non-DM patients, the four-year mortality was similar for hyperglycaemic and normoglycaemic subjects (17.9% vs 10.8%, respectively; NS), whereas cardiac arrest during the in-hospital period was more common for hyperglycaemic than normoglycaemic patients (3.6% vs 0.0%, respectively; n = 1 vs 0; p = 0.01). The composite end-point for the in-hospital period was reached by 17.6% of hyperglycaemic and 13.

Increased mood lability has been reported in BP However, mood la

Increased mood lability has been reported in BP. However, mood lability is ubiquitous across psychiatric disorders and may be a marker of severe psychopathology and not specific to BP. To clarify this issue, this

study examined the prevalence of mood lability and its components in offspring of BP parents and offspring of community control parents recruited through the Pittsburgh Bipolar Offspring Study. Methods Forty-one school-age BP offspring of 38 BP parents, 257 healthy or non-BP offspring of 174 BP parents, and 192 offspring of 117 control parents completed a scale that was developed to evaluate mood lability in youth, i.e., the Children’s Affective Lability Scale (CALS). Results A 3 factor analysis of the parental CALS, and in part the child CALS, revealed Irritability, Mania, and

Anxiety/Depression factors, with most of the variance explained by the Irritability factor. After adjusting for confounding factors (e.g., parental and offspring non-BP psychopathology), BP offspring of BP parents showed the highest parental and child total and factor scores, followed by the non-BP offspring of BP parents, and then the offspring of the controls. Conclusions Mood lability overall and mania-like, anxious/depressed, and particularly irritability symptoms may be a prodromal phenotype of BP among offspring of parents with BP. Prospective studies are warranted to clarify

whether these symptoms will predict the development of BP and/or other psychopathology. If confirmed, these selleck compound symptoms may become a target of treatment and biological studies before BP develops.”
“Fluorite-structured materials are known to exhibit an excellent structural stability under irradiation. The radiation stability of urania and yttria-stabilised cubic zirconia single crystals submitted to intense electronic excitations induced by 944-MeV Pb(53+) ions was investigated. Various analytical tools (TEM, AFM, RBS/C, XRD) were employed to examine the modifications induced at the surface and in the crystal bulk. At low fluence irradiation Dinaciclib datasheet leads to the formation of localised ion tracks whose centre is hollowed in the surface region over a depth of similar to 100 nm and to the formation of nanometer-sized hillocks. Both features are interpreted as resulting from an ejection of matter in the wake of the projectile. Track overlapping at high fluence results in the formation of micrometer-sized domains (similar to 50 nm) in the crystal bulk characterised by a slight disorientation (similar to 0.2 degrees) with respect to the main crystallographic orientation of the crystal. (C) 2009 Elsevier B.V. All rights reserved.”
“(Comparative thallus anatomy of two Parmotrema (Parmeliaceae, lichenized Ascomycota) with reticulate maculae).

Advanced fibrosis (F3 or F4) could be efficiently

Advanced fibrosis (F3 or F4) could be efficiently Crenigacestat predicted by a FibroScan cut-off value of 15 kPa.

The FibroScan sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 100%, 73.9%, 77.8%, 100%, and 86.4%, respectively.\n\nFibroScan values gave a good correlation with various markers of fibrosis and increased proportionally with the progression of the hepatic fibrosis stage. A FibroScan value of 15 kPa was found to be a significant separation limit for differentiating advanced fibrosis stages (F3 and F4) from the milder stages (F0-F2). FibroScan values are clinically useful for predicting the fibrosis stages and helpful in managing interferon therapy in patients with chronic hepatitis C.”
“Laryngeal radionecrosis is one of the most troublesome late complications of radiotherapy, because it is frequently resistant to treatment and laryngectomy is required in the worst case. Here, we Nepicastat report a case of laryngeal radionecrosis, successfully treated by use of hyperbaric oxygen (HBO) therapy, in which laryngectomy was avoided. A 67-year-old male received radical chemoradiotherapy (CRT) for mesopharyngeal cancer, which included radiotherapy with a total

dose of 71.4 Gy/38 Fr and chemotherapy with CDDP + S-1. He developed dyspnea and throat pain 9 months after completion of CRT. Laryngoscopy revealed vocal cord impairment because of severe laryngeal edema. He was diagnosed as having laryngeal radionecrosis and initially received

conservative therapy combined with antibiotics, steroids, and prostaglandins. Because his dyspnea was persistent despite this treatment, HBO therapy was administered 20 times, and resulted in complete remission of the dyspnea. HBO therapy, therefore, is regarded as an effective conservative therapeutic option for laryngeal radionecrosis.”
“A new diamine containing a bulky diphenylquinoxalin pendant, 3,5-diamino-N-(2,3-diphenylquinoxalin-7-yl)benzamide (DQB), was synthesized selleck inhibitor in four steps through the nucleophilic aromatic substitution of 3,5-dinitrobenzoylchloride with 2,3-diphenylquinoxalin-6-amine and subsequent catalytic 3 reduction. All intermediates and DQB were fully characterized by FTIR, NMR and elemental analysis. A series of polyamides PA(a-e) was synthesized from this diamine by direct polycondensation with various dicarboxylic acids, triphenyl phosphate and pyridine in N-methyl-2-pyrrolidynone (NMP). Three polyimides PI(a-c) were synthesized from this diamine using commercial dianhydrides in two-step polycondensation. Characterization of polymers was accomplished by FTIR, H NMR, elemental analysis, DSC, DMTA, GPC, and TGA. The intrinsic viscosities of PAs ranged from 0.54 to 0.67 dL/g. PAs displayed T (g) values of 140-298 degrees C and 10% weight loss of 415-485 degrees C in N(2).

Driving with the left arm in an above-the-elbow thumb spica splin

Driving with the left arm in an above-the-elbow thumb spica splint had the highest perceived difficulty (median, 8.0) and lowest perceived safety (median, 3.0).\n\nConclusions: Driving performance as measured with a standardized track and scoring system was significantly degraded with splint immobilization of the left arm. Further studies are required to determine the effect of arm immobilization on normal driving conditions.”
“Background and purpose

of the study: The goal was to evaluate and compare the effects of aqueous extract of the seeds of chicory, Cichorium intybus L., on glucose tolerance test (GTT) and blood biochemical indices of experimentally-induced hyperglycemic rats.\n\nMethods: Late stage and early stage of Type 2 diabetes mellitus (T2DM) were induced in rats by streptozotocin (STZ) and a combination of STZ and niacinamide (NIA/STZ), respectively. Within each group, one subgroup received daily i.p. injections of chicory extract

(125 mg/kg body weight, for 28 days). Body weight and fasting blood sugar (FBS) were measured weekly. Blood was analyzed for glycosylated hemoglobin (HbA1c) and sera for alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO), triacylglycerol (TG), total cholesterol (TC), total protein, and insulin on days 10 and 28 after treatment. Intraperitoneal glucose tolerance test (IPGTT) along with insulin determination was performed on a different set of rats in which the chicory-treated groups received the extract for 10 days.\n\nResults: During 4 weeks of treatment, chicory prevented body-weight loss and decreased FBS. ALT activities and levels of JNK-IN-8 inhibitor TG, TC and HbA1c decreased, and concentration of NO increased in the chicory treated groups (p < 0.05). Unlike late-stage diabetes, fasting serum insulin concentrations were higher and GTT pattern approximated to normal in chicory-treated early-stage Galardin diabetic rats.\n\nConclusions: Chicory appeared to have short-term (about 2 hours, as far as GTT is concerned) and long-term (28 days, in this study) effects on diabetes. Chicory may be useful

as a natural dietary supplement for slowing down the pace of diabetes progress, and delaying the development of its complications.”
“Many home-based and leisure activities can generate hazardous respirable exposures. Routine domestic activities and a variety of hobbies, avocations, and leisure pursuits have been associated with a spectrum of respiratory tract disorders. Indoor environments present a special risk for high-intensity exposures and adverse health effects. There are important knowledge gaps regarding the prevalence of specific health hazards within and across communities, exposure-response effects, population and individual susceptibilities, best management strategies, the adverse health effects of mixed exposures, and long-term clinical outcomes following exposures.

Of 27 patients with available information, 11 (41%) had objective

Of 27 patients with available information, 11 (41%) had objective

evidence of reflux disease. Nineteen patients (70%) had concomitant typical reflux symptoms. 432 despite a frequently negative DeMeester score, abnormal proximal exposure, which occurred in the upright position, was observed in 19 patients (70%). Of 20 patients who subsequently underwent ARS, asthma symptoms improved in 18 (90%), and 6 of LY2157299 in vivo them discontinued or reduced pulmonary medications at a mean (range) follow-up of 4.6 (0.6-15.2) months. Pulmonary function test results before and after ARS revealed that of 5 patients, 4 (80%) had improvement of the forced expiratory volume in the first second of expiration and/or the peak expiratory flow rate, which correlated with symptomatic NVP-AUY922 improvement.\n\nConclusions: Adult-onset asthma is associated with abnormal proximal

exposure of the aerodigestive tract to refluxate; these patients respond to ARS despite negative pH test results. Patients with AOA should undergo testing with HMII because they would not be detected with conventional pH testing. JAMA Surg. 2013;148(1):50-58″
“Vaccination and antimicrobial therapy remain the cornerstones of the management of pneumococcal pneumonia. Despite significant successes, the capacity of the pneumococcus to evolve in the face of the selective pressure of anticapsular immunity challenges immunization programs. Treatment focuses on antimicrobial therapy but ignores the central role of the dysregulated inflammatory response during pneumonia. Future

therapeutic approaches buy JQ-EZ-05 need to build on the considerable recent advances in our understanding of the pathogenesis of pneumococcal pneumonia, including those from models of pneumonia. Enhancement of the essential components of the host response that prevents most colonized individuals from developing pneumonia and strategies to limit inappropriate inflammatory responses to lower respiratory tract infection are approaches that could be exploited to improve disease outcome. This review highlights recent discoveries relating to the microbial and host determinants of microbial clearance and regulation of the inflammatory response, which provide clues as to how this could be achieved in the future. CHEST 2012; 142(2):482-491″
“We briefly review the characteristics of several established health technology assessment (HTA) programs in industrialized societies including Germany, the UK and France. Special attention is paid on two issues: the position of HTA in coverage decision making and the role of economic assessment in evaluation processes.