Materials and Methods A total of 46 subjects received doses of 30-3000 mu g i.v. of roledumab or placebo using a double-blind escalating single-dose design; 12 of these subjects also received 300 mu g i.m. of roledumab. Subjects were AZD7762 molecular weight followed for 6 months after administration. Serum roledumab concentrations were determined using flow cytometry. Results Fourteen treatment-emergent adverse events related to treatment were reported in nine subjects, with no apparent difference in their frequency or nature after placebo or roledumab administration. No anti-roledumab

antibodies were detected. AUClast increased from 4.4 ng/ml.day at 30 mu g i.v. to 2257 ng/ml.day at 3000 g i.v. The t(1/2) ranged from 18 to 22 days, and the absolute bioavailability after i.m. administration was between 73% and 80%. Conclusion Roledumab is safe and well tolerated in healthy RhD-negative volunteers and shows a pharmacokinetic profile similar to that of polyclonal anti-RhD immunoglobulin.”
“BACKGROUND: Procaspase activation Mandarins suffer from accumulation of off-flavours after harvest. In this study the sensory quality and aroma profile composition of homogenised segments

of untreated (control) and wax-coated ‘Mor’ mandarins after 7 days at 20 C or 3 or 6 weeks of cold storage at 5 C were examined.\n\nRESULTS: Fruit taste score decreased during storage and following wax coating, and this was attributed to decreases in sourness and QNZ mandarin flavour and accumulation of off-flavours. Aroma profiling identified 31 volatiles that decreased by at least 50% during storage and after waxing and thus may

be involved in the observed flavour loss. In contrast, 13 volatiles, mostly belonging to ethanol fermentation and fatty acid and amino acid catabolism pathways, significantly increased at least twofold and probably contributed to off-flavour enhancement.\n\nCONCLUSION: The results showed that after harvest there was a progressive decrease in sensory quality of ‘Mor’ mandarins. It is proposed that observed decreases in contents of sesqui- and monoterpenes and short-chain oxygenated fatty acids may contribute to the decrease in mandarin flavour, whereas increases in the contents of ethanol fermentation metabolites and derivates of fatty acid and amino acid catabolism are most likely involved in causing the enhanced sensation of off-flavours. (C) 2010 Society of Chemical Industry”
“The present study was the first time to investigate the effects of celastrol, derived from Trypterygium wilfordii Hook F. (“Thunder of God Vine”), a traditional Chinese medicine plant, on the metabolism of model probe substrates of CYP isoforms, CYP1A2, CYP2C11, CYP2D6, CYP2E1 and CYP3A2, which are important in the metabolism of a variety of xenobiotics.

For this, turnaround time is less important than discriminatory power. The potential remains for wider use of genotyping to examine transmission routes.”
“The approach of cell-seeded natural scaffolds holds great promise for tissue engineering complicated soft-tissue organs such as the urinary bladder and heart. However, relatively little is known about cell-natural scaffold interactions or their influence on magnetic resonance imaging (MRI) characterization, which is valuable for noninvasive monitoring. Ideally, MRI should provide information on tissue biochemistry in addition

to structure and function. In this study, quantitative MRI was performed on control and smooth muscle cell-seeded natural bladder matrices at different time points up to 7 days postseeding. Measurements https://www.selleckchem.com/products/iwr-1-endo.html of MR relaxation times (T1 and T2) and diffusion coefficient (D) showed an overall change that was incompatible with cell presence. Multicomponent T2 provided

greater specificity, revealing time-course changes in the short T2 fraction that were consistent with biochemically determined matrix degradation from collagenase released from seeded cells. These matrix alterations are noted for the first time, and their relatively early occurrence may be unique to soft-tissue matrices compared with synthetic materials. More importantly, they are not evident on histology but are revealed on quantitative MRI. We conclude that quantitative Dinaciclib inhibitor MRI may provide specific information on cell-matrix interaction and is a promising noninvasive approach to understand and monitor cell-seeded natural scaffold-based regeneration.”
“The aim of this study was to evaluate gene expression of bone remodeling markers in type 2 diabetic Goto-Kakizaki (GK) nonobese rats after gastrojejunal bypass and sleeve gastroplasty and their relationship with hormonal parameters. We designed an experimental

study in three groups of GK rats (nonoperated gastrojejunal bypass and sleeve gastroplasty). Gene expression of markers of bone remodeling and levels of insulin, 5-Fluoracil cost leptin, and glucagon-like peptide-1 (GLP-1) were determined. GK rats had decreased levels of osteocalcin expression compared with Wistar rats. Gene expression of markers of bone remodeling in GK rats was similar in the three groups studied, although there was a trend to decreased receptor activator for nuclear factor kappa B ligand (RANKL) in gastroplasty rats. Significant differences in the osteocalcin/RANKL ratio were observed between controls and gastrojejunal bypass rats compared with gastroplasty rats. The behavior of gastrointestinal hormones was antagonistic (GLP-1 gastrojejunal bypass 1.54 +/- 0.24 ng/ml vs. GLP-1 gastroplasty 0.673 +/- 0.09, p = 0.0001; leptin gastrojejunal bypass 1,178 +/- 0.474 pg/ml vs. leptin gastroplasty 7,391 +/- 4,054 pg/ml, p = 0.002). There was a reduction in leptin in the bypass group associated with an increase in gastrectomized rats.

g., perception, dissatisfaction, distortion). CONCLUSIONS: Much more is needed to understand body image within the Brazilian population, especially in terms of evaluating different age groups and diversifying the components/dimensions assessed.

However, interest in this theme is increasing, and important steps have been taken in a short space of time.”
“The process of designing and developing discrete choice experiments (DCEs) is often under reported. The need to adequately report the results of qualitative work used to identify attributes and levels used in a DCE is recognised. However, one area that has received relatively little attention is the exploration of the choice question of interest. This paper provides a case study of the process used to design a stated preference PF-04929113 chemical structure check details survey to assess youth preferences for integrated sexual and reproductive health

(SRH) and HIV outreach services in Malawi. Development and design consisted of six distinct but overlapping and iterative stages. Stage one was a review of the literature. Stage two involved developing a decision map to conceptualise the choice processes involved. Stage three included twelve focus group discussions with young people aged 15-24 (n = 113) and three key informant interviews (n = 3) conducted in Ntcheu District, Malawi. Stage four involved analysis of qualitative data and identification of potential attributes and levels. The choice format and experimental design were selected in stages five and six. The results of the literature review were used to develop a decision map outlining the choices that young people accessing SRH services may face. For youth that would like to use services two key choices were identified: the choice between providers and the choice of service delivery attributes within a provider type. Youth preferences for provider type are best explored using a DCE with a labelled design, while preferences for service delivery

attributes associated with a particular provider are better Akt inhibitor understood using an unlabelled design. Consequently, two DCEs were adopted to jointly assess preferences in this context. Used in combination, the results of the literature review, the decision mapping process and the qualitative work provided robust approach to designing the DCEs individually and as complementary pieces of work. (C) 2014 Elsevier Ltd. All rights reserved.”
“Background: The ability of science to produce experimental data has outpaced the ability to effectively visualize and integrate the data into a conceptual framework that can further higher order understanding. Multidimensional and shape-based observational data of regenerative biology presents a particularly daunting challenge in this regard. Large amounts of data are available in regenerative biology, but little progress has been made in understanding how organisms such as planaria robustly achieve and maintain body form.

In reactive sputtering with gas cluster ions, the energy per atom or molecule plays an important role. In this study, the average cluster size (N, the BAY 80-6946 solubility dmso number of atoms or molecules in a cluster ion) was controlled; thereby the dependences of the energy per molecule on the sputtering yields of carbon by CO(2) cluster ions and that of Si by SF(6)/Ar mixed gas cluster ions were investigated. Large CO(2) cluster ions with energy per molecule of 1 eV showed high reactive sputtering yield

of an amorphous carbon film. However, these ions did not cause the formation of large craters on a graphite surface. It is possible to achieve very low damage etching by controlling the energy per molecule of reactive cluster ions. Further, in the case of SF(6)/Ar mixed cluster ions, it was found that reactive

sputtering was enhanced when a small amount of SF(6) gas (similar to 10%) was mixed with Ar. The reactive sputtering EX 527 Epigenetics inhibitor yield of Si by one SF(6) molecule linearly increased with the energy per molecule. (C) 2010 Elsevier B.V. All rights reserved.”
“An experiment with 250 one-day-old male broilers (Ross 308) was conducted to investigate the differences of some blood parameters of cold-induced ascitic and healthy broiler chicks in a 6-wk period. The chickens were divided into 2 groups of 5 replicates each. One group of these chickens was raised in normal temperature (NT) treatment and the other in cold temperature (CT) treatment to induce ascites. Mortality was necropsied daily to determine cause of death. At the end of the experiment (wk NSC 136476 6), 5 chickens from

each replicate were randomly selected and slaughtered. The heart was removed; the right ventricle was dissected away from the left ventricle and septum. Weights of right and left ventricles were determined separately. Average BW gain and average feed intake were measured weekly, and weekly average feed conversion ratio was calculated. Serum glucose, total protein, cholesterol, triglyceride, activity of lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase were determined. Throughout the study, the right ventricle-to-total ventricle ratio and total mortality percentage due to ascites of CT-treated birds at the end of experiment was greater (P <= 0.05) than those of NT-treated ones. Fasting blood sugar of CT-treated birds in wk 4 and 6 was greater (P <= 0.05) than NT-treated birds. Total blood protein of CT treatment was lower than NT-treated birds in every week and whole period, but this difference was only significant (P <= 0.05) in wk 6. There was not a significant difference between 2 treatments for triglyceride and cholesterol, lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase. It was concluded that cold-induced ascites could affect serum protein and fasting blood sugar of broiler chickens.”
“Aims: Bacterial vaginosis (BV) affects millions of women, is extremely prevalent and is frequently chronic.

At baseline, CD152+ expression was lower in patients than in controls (P<10(-6)). After stimulation, there

were an increase in CD152+ T cells and decreases in CD28+ and CD4+ cells in controls (P<0.01). In AT children, CD152+ T cells remained stable. CD4+CD152+ T cells correlated inversely with antithyroglobulin antibodies. We conclude that alterations in lymphocyte markers are associated with AT. Stimulation leads to differing changes in T-lymphocyte subsets in both examined children populations.”
“Alginate encapsulation is a simple and cost-effective technique to preserve plant germplasm but there are only a few BIBF 1120 mouse reports available on preservation of encapsulated explants of two highly valuable groups of tropical trees, the eucalypts (Myrtaceae) and mahoganies (Meliaceae). This study investigated alginate encapsulation for preservation of the eucalypt hybrid, Corymbia torelliana x C. citriodora, and the African mahogany, Khaya senegalensis. We assessed shoot regrowth of encapsulated shoot tips and nodes after storage for 0, 3, 6 and 12 months on media varying in sucrose and nutrient content, under storage conditions of 14 degrees C and zero-irradiance. Encapsulated explants of both trees were preserved most effectively on high-nutrient (half-strength Murashige and Skoog) medium containing 1%

sucrose, which provided very high frequencies of shoot MI-503 regrowth (92-100% for Corymbia and 71-98% for Khaya) and excellent shoot development after 12 months’ storage. This technique provides an extremely efficient means for storage and exchange of eucalypts and mahoganies, ideally suited for incorporation into plant breeding and

germplasm conservation programs.”
“Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and both innate and adaptive immunity contribute to the pathogenesis. Kidney resident cells promote inflammation after IRI by increasing endothelial cell adhesion molecule expression and vascular permeability. Kidney epithelial cells bind complement and express toll-like receptors and resident and infiltrating cells produce cytokines/chemokines. VX-770 clinical trial Early activation of kidney dendritic cells (DCs) initiates a cascade of events leading to accumulation of interferon-gamma-producing neutrophils, infiltrating macrophages, CD4(+) T cells, B cells and invariant natural killer T (NKT) cells. Recent studies from our laboratory now implicate the IL23/IL17 pathway in kidney IRI. Following the initial early phase of inflammation, the late phase involves infiltration of anti-inflammatory cells including regulatory T cells, alternatively activated macrophages and stem cells leading to attenuation of inflammation and initiation of repair. Based upon these immune mechanisms of injury, recent studies hold promise for novel drug therapies. These pharmacological agents have been shown to reduce inflammation or cytotoxicity in rodent models of AKI and some show early promise in clinical trials.

To compare the radiographic results, the following parameters were measured: mean mechanical femorotibial angle, mean femorotibial anatomical angle, mean coronal femoral component angle, mean coronal tibial component angle, mean sagittal femoral component angle, and mean sagittal tibial component angle. The navigation TKA showed better accuracy and consistency in mechanical axis deviation, coronal femoral component angle, and sagittal tibial component angle. The coronal tibial component position was acceptable in both groups. The navigation TKA markedly improved the restoration of mechanical axis, but not so much in sagittal femoral component position.

The fluoroscopy-assisted conventional TKA had a tendency that femoral component was inserted in flexed position than in navigation selleck screening library TKA. Unlike the fluoroscopy-assisted conventional TKA, the femoral component was inserted in slightly extended position in the navigation TKA than expected. In conclusion, even though the use of navigation in TKAs help the surgeon to achieve good results, the surgeon should know the tendency of extension of the femoral component in sagittal plane to avoid anterior notching.”
“Vaccine candidates against Nipah and Hendra viruses, recently emerging zoonotic threats. Renewed interest

in the possibility that the proteins causing neurodegeneration are all prions. Bright and dark sites of complement system. A noninflammatory humoral factor of the coagulation SCH727965 cascade, FX binds to the surface of adenovirus and triggers activation of innate immunity. NLRP6 receptor is a negative regulator of innate immunity against bacterial pathogens. The lung can A-1331852 order serve as a location where autoreactive T

cells become reactivated and gain the competence to enter the CNS. Reactivation of anticancer activity of T cells by blocking PD-1 (programmed cel death – 1) on their surface.”
“The genus Plectranthus (Lamiaceae) is a significant, prolific and extensively used genus in southern Africa. It plays a dominant role in both horticulture and traditional medicine. Some 12 species are documented for their use in treating ailments by various indigenous peoples of southern Africa. It is a firm favourite in gardens and Plectranthus has been bred to further utilise the remarkable diversity of indigenous South African wildflowers with amenity horticultural potential. Although previously subjected to both horticultural (Van Jaarsveld, 2006) and ethnobotanical (Lukhoba et al., 2006) review, Plectranthus is a genus with economic potential in various sectors, and this article aims to review this potential of southern African species. (C) 2011 SAAB. Published by Elsevier B.V. All rights reserved.”
“Systemic atherosclerosis is involved in ischemic damages and cardioembolism after atrial fibrillation (AF)-related ischemic stroke (IS).

“
“Parkinson’s disease (PD) is a neurodegenerative disease that mainly affects dopaminergic https://www.selleckchem.com/products/oligomycin-a.html (DA-ergic) neurons in the substantia nigra pars compacta (SNc). Glutamate modulates neuronal excitability, and a high concentration of glutamatergic receptors is found on DA-ergic neurons in the SNc. Paraquat (PQ) is a putative causative agent for PD. Its effects on synaptic glutamate transmission in SNc DA-ergic neurons were evaluated using whole-cell voltage-clamp recording in brain slices from 7- to 14-day-old Wistar rats. In the presence of bicuculline (BIC), strychnine, and DL-aminophosphonovaleric acid, PQ reversibly suppressed AMPA receptor-mediated

evoked excitatory postsynaptic currents (eEPSCs) in a concentration-dependent manner (P < 0.05). In the presence of tetrodotoxin (1 mu M), PQ (50 mu M) significantly reduced the amplitudes, but not the frequencies, of miniature EPSCs in the SNc, suggesting PQ inhibited eEPSCs through a postsynaptic mechanism. Exogenous application of AMPA to induce AMPA-mediated inward currents excluded involvement of a presynaptic response. The RG7112 AMPA-induced currents in the SNc were significantly reduced by PQ (50 mu M) to 74% of control levels (P < 0.05), supporting that PQ acts on postsynaptic AMPA receptors. No effect of PQ on eEPSCs was seen in the LD thalamic nucleus and hippocampus, showing

PQ specifically inhibited DA-ergic neurons in the SNc. Our results demonstrate a novel mechanism of action of PQ on glutamate-gated postsynaptic AMPA receptors

in SNc DA-ergic neurons. This effect may attenuate the excitability and function of DA-ergic neurons in the SNc, which may contribute to the pathogenesis of PD. (C) 2008 Elsevier Inc. All rights reserved.”
“Fibroblast growth factor-23 (FGF-23) inhibits sodium-dependent phosphate transport in brush border membrane vesicles derived from hormone-treated kidney slices of the mouse and in mouse proximal tubule cells by processes involving mitogen-activated protein kinase (MAPK) but not protein kinase A (PKA) or protein kinase C (PKC). By contrast, phosphate transport selleck kinase inhibitor in brush border membrane vesicles and proximal tubule cells from sodium-hydrogen exchanger regulatory factor-1 (NHERF-1)-null mice were resistant to the inhibitory effect of FGF-23 (10(-9) M). Infection of NHERF-1-null proximal tubule cells with wild-type adenovirus-GFP-NHERF-1 increased basal phosphate transport and restored the inhibitory effect of FGF-23. Infection with adenovirus-GFP-NHERF-1 containing a S77A or T95D mutation also increased basal phosphate transport, but the cells remained resistant to FGF-23 (10(-9) M). Low concentrations of FGF-23 (10(-13) M) and PTH (10(-11) M) individually did not inhibit phosphate transport or activate PKA, PKC, or MAPK.

\n\nObjective To determine whether accreditation performance is associated with self-reported clinical performance and independent ratings of four aspects of organisational performance.\n\nDesign Independent blinded assessment of these variables in a random, stratified sample of health service organisations.\n\nSettings Acute care: large, medium and small health-service organisations in Australia.\n\nStudy participants Nineteen health service organisations employing 16 448 staff treating 321 289 inpatients

and 1 971 087 non-inpatient services selleck chemical annually, representing approximately 5% of the Australian acute care health system.\n\nMain measures Correlations of accreditation performance with organisational culture, organisational climate, consumer involvement, leadership and clinical performance.\n\nResults Accreditation performance was significantly positively correlated with organisational culture (rho=0.618, p=0.005) and leadership (rho=0.616, p=0.005).

There was a trend between accreditation and clinical performance (rho=0.450, p=0.080). Accreditation was unrelated to organisational climate (rho=0.378, p=0.110) and consumer involvement (rho=0.215, p=0.377).\n\nConclusions Accreditation results predict Dactolisib leadership behaviours and cultural characteristics of healthcare organisations but not organisational climate or consumer participation, and a positive trend between accreditation and clinical performance is noted.”
“Recent studies report that multifunctionality-the simultaneous provision of multiple ecosystem functions-in drylands depends on biodiversity. Others report that specific size distributions of vegetation patches indicate overall ecosystem health and function. Using a biocrust BI 2536 (micro-vegetation of mosses, lichens, and cyanobacteria) model system, and multivariate modeling, we determined

the relative importance of biodiversity, patch-size distribution, and total abundance to nutrient cycling and multifunctionality. In most cases we explained at least 20%, and up to 65%, of the variation in ecosystem functions, and 42% of the variation in multifunctionality. Species richness was the most important determinant of C cycling, constituting an uncommonly clear link between diversity and function in a non-experimental field setting. Regarding C cycling in gypsiferous soils, we found that patch size distributions with a greater frequency of small to medium patches, as opposed to very small patches, were more highly functional. Nitrogen cycling was largely a function of biocrust cover in two soil types, whereas in gypsiferous soils, more central-tending patch size distributions were less functional with regards to N cycling. All three community properties were about equally important to multifunctionality.

Because the potency and selectivity of compounds for a given receptor in an in vivo setting can be dissimilar to that observed in an in vitro system, we developed an in vivo assay to simultaneously determine the absolute potency and selectivity of muscarinic receptor antagonists at M-2 and M-3 receptors using the pithed rat. Methacholine (MCh)-induced bradycardia and depressor responses were used as surrogate functional endpoints for M-2 and M-3 receptor activation, respectively. The influence

of the muscarinic antagonists, tolterodine, oxybutynin, darifenacin, Ro 320-6206, solifenacin, or tiotropium on the MCh-induced responses selleckchem were studied. The estimated DR10 values (dose producing a tenfold shift in the MCh curve) of tolterodine, oxybutynin, darifenacin, Ro 320-6206, solifenacin, and tiotropium for the M-2 muscarinic receptor-mediated bradycardia were 0.22, 1.18, similar to 2.6, 0.025, 0.40, and 0.0026 mg/kg, respectively, and 0.14, 0.18, 0.11, 3.0, 0.18, and 0.0017 mg/kg, respectively, for the M-3 muscarinic BMS-777607 ic50 receptor-mediated depressor response. In a separate set of experiments, a single intravenous dose of tiotropium was administered before a MCh curve at 1, 3, 6, or 9 h to determine if tiotropium exhibited time-dependent selectivity for the M-3 receptor as has been reported from in vitro

studies. The results indicate a slight preference of tiotropium for the M-3 receptor at later time points. The pithed rat assay may serve useful for elucidating the functional contribution of M-2 and M-3 receptors to the in vivo pharmacological effects of antagonists in disease selleck screening library animal models.”
“We used a central composite rotatable experimental design and response surface methodology to evaluate the effects of temperature (18-37 degrees C), salinity (0-20 parts per thousand), and their interaction on specific growth rate (SGR), feed efficiency (FE), plasma osmolality, and gill Na+, K+-ATPase activity in GIFT tilapia juveniles. The linear and quadratic effects of temperature and salinity on SGR, plasma osmolality, and gill Na+, K+-ATPase

activity were statistically significant (P < 0.05). The interactive effects of temperature and salinity on plasma osmolality were significant (P < 0.05). In contrast, the interaction term was not significant for SGR, FE, and gill Na+, K+-ATPase activity (()p > 0.05). The regression equations for SGR, FE, plasma osmolality, and gill Na+, K+-ATPase activity against the two factors of interest had coefficients of determination of 0.944, 0.984, 0.966, and 0.960, respectively (P < 0.01). The optimal temperature/salinity combination was 28.9 degrees C/7.8 parts per thousand at which SGR (2.26% d(1)) and FE (0.82) were highest. These values correspond to the optimal temperature/salinity combination (29.1 degrees C/7.5 parts per thousand) and the lowest plasma osmolality (348.38 mOsmol kg(-1)) and gill Na+, K+-ATPase activity (1.31 mu mol Pi.

\n\nIn conclusion, hypermethylation leads to silencing of the Syk gene in human lung carcinoma cell lines. Methylation of the Syk promoter and loss of Syk expression in lung cancer cell lines are independent biomarkers. Syk may be a potential tumor suppressor in human lung cancer.”
“The systemic immune response of Drosophila is known to be induced both by septic

injury and by oral infection check details with certain bacteria, and is characterized by the secretion of antimicrobial peptides (AMPs) into the haemolymph. To investigate other possible routes of bacterial infection, we deposited Erwinia carotovora (Ecc15) on various sites of the cuticle and monitored the immune response via expression of the AMP gene Diptericin. A strong response was observed to deposition on the genital plate of males ( up to 20% of a septic injury response), but not females. We show that the principal response to genital infection is systemic, but that some AMPs, particularly Defensin, are induced locally in the genital tract. At late time points we detected

bacteria in the haemolymph of immune deficient Relish(E20) flies, indicating that the genital buy Cilengitide plate can be a route of entry for pathogens, and that the immune response protects flies against the progression of genital infection. The protective role of the immune response is further illustrated by our observation that Relish(E20) flies exhibit significant lethality in response to genital Ecc15 infections. We next show that

a systemic immune response can be induced by deposition of the bacterial elicitor peptidoglycan (PGN), or its terminal MAPK Inhibitor Library clinical trial monomer tracheal cytotoxin (TCT), on the genital plate. This immune response is downregulated by PGRP-LB and Pirk, known regulators of the Imd pathway, and can be suppressed by the overexpression of PGRP-LB in the haemolymph compartment. Finally, we provide strong evidence that TCT can activate a systemic response by crossing epithelia, by showing that radiolabelled TCT deposited on the genital plate can subsequently be detected in the haemolymph. Genital infection is thus an intriguing new model for studying the systemic immune response to local epithelial infections and a potential route of entry for naturally occurring pathogens of Drosophila.”
“Background: Adjuvant treatment decision-making based on conventional clinical/pathological and prognostic single molecular markers or genomic signatures is a therapeutic area in which over-/under-treatment are still key clinical problems even though substantial and continuous improvement of outcome has been achieved over the past decades. Response to therapy is currently not considered in the decision-making procedure. ADAPT is one of the first new generation (neo) adjuvant trials dealing with individualization of (neo) adjuvant decision-making in early breast cancer and aims to establish early predictive surrogate markers, e. g.