Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph-nodes

BACKGROUND: Axillary lymph-node dissection is an important staging procedure in the surgical treatment of breast cancer. However, early diagnosis has led to increasing numbers of dissections in which axillary nodes are free of disease. This raises questions about the need for the procedure. We carried out a study to assess, first, whether a single axillary lymph node (sentinel node) initially receives malignant cells from a breast carcinoma and, second, whether a clear sentinel node reliably forecasts a disease-free axilla. METHODS: In a consecutive series of 163 women with operable breast carcinoma, we injected microcolloidal particles of human serum albumin labelled with technetium-99m. This tracer was injected subdermally, close to the tumour site, on the day before surgery, and scintigraphic images of the axilla and breast were taken 10 min, 30 min, and 3 h later. A mark was placed on the skin over the site of the radioactive node (sentinel node). During breast surgery, a hand-held gamma-ray detector probe was used to locate the sentinel node, and make possible its separate removal via a small axillary incision. Complete axillary lymphadenectomy was then done. The sentinel node was tagged separately from other nodes. Permanent sections of all removed nodes were prepared for pathological examination. FINDINGS: From the sentinel node, we could accurately predict axillary lymph-node status in 156 (97.5%) of the 160 patients in whom a sentinel node was identified, and in all cases (45 patients) with tumours less than 1.5 cm in diameter. In 32 (38%) of the 85 cases with metastatic axillary nodes, the only positive node was the sentinel node. INTERPRETATION: In the large majority of patients with breast cancer, lymphoscintigraphy and gamma-probe-guided surgery can be used to locate the sentinel node in the axilla, and thereby provide important information about the status of axillary nodes. Patients without clinical involvement of the axilla should undergo sentinel-node biopsy routinely, and may be spared complete axillary dissection when the sentinel node is disease-free.     

Revenue guarantee in public–private partnerships: a win–win model

Government guarantees are often granted to increase the viability of the Public–Private Partnership projects, although the use of these guarantees can cause problems if they are not properly set. This paper provides a useful tool to define a proper value of public subsidies. In particular, we develop a methodology to calculate the optimal values of the revenue floor (the minimum amount of revenue secured by the government in the minimum revenue guarantee) and revenue ceiling (the upper threshold of revenue that defines the excess revenue to be shared in the revenue sharing) in a way that creates a “win–win” condition for the concessionaire and the government and fairly shares risk between them. The proposed methodology operationalizes minimum revenue guarantee and revenue sharing as real options. The resulting real option-based model is applied to a real case, namely the Strait of Messina Bridge in Italy. The application shows the usefulness of the model in supporting: (a) the government’s decision-making process on assessing values of public subsidies needed to make the project attractive to private investors; and (b) both public and private parties during the negotiation in finding the fair values of the revenue floor and ceiling.     

A Photoresponsive Red‐Hair‐Inspired Polydopamine‐Based Copolymer for Hybrid Photocapacitive Sensors

Inspired by the powerful photosensitizing properties of the red hair pigments pheomelanins, a photoresponsive cysteine‐containing variant of the adhesive biopolymer polydopamine (pDA) is developed via oxidative copolymerization of dopamine (DA) and 5‐S‐cysteinyldopamine (CDA) in variable ratios. Chemical and spectral analysis indicate the presence of benzothiazole/benzothiazine units akin to those of pheomelanins. p(DA/CDA) copolymers display ­impedance properties similar to those of biological materials and a marked photoimpedance response to light stimuli. The use of the p(DA/CDA) copolymer to implement a solution‐processed hybrid photocapacitive/resistive metal‐insulator‐semiconductor (MIS) device disclosed herein is the first example of technological exploitation of photoactive, red‐hair‐inspired biomaterials as soft enhancement layer for silicon in an optoelectronic device. The bio‐inspired materials described herein may provide the active component of new hybrid photocapacitive sensors with a chemically tunable response to visible light.     

Integration of binding peptide selection and multifunctional particles as tool-box for capture of soluble proteins in serum

In this paper, we report on a general approach for the detection of a specific tumoural biomarker directly in serum. Such detection is made possible using a protein-binding peptide selected through an improved phage display technique and then conjugated to engineered microparticles (MPs). Protein biomarkers represent an unlimited source of information for non-invasive diagnostic and prognostic tests; MP-based assays are becoming largely used in manipulation of soluble biomarkers, but their direct use in serum is hampered by the complex biomolecular environment. Our technique overcomes the current limitations as it produces a selective MP—engineered with an antifouling layer—that ‘captures’ the relevant protein staying impervious to the background. Our system succeeds in fishing-out the human tumour necrosis factor alpha directly in serum with a high selectivity degree. Our method could have great impact in soluble protein manipulation and detection for a wide variety of diagnostic applications.     

Efficacy and tolerability of Estraderm MX, a new estradiol matrix patch

Our data (Reddy et al., Radiat. Res. 141, 252-258, 1995) on the kinetics of the repair of potentially lethal damage in log-phase Chinese hamster V79 cells are used to test some predictions which arise from the different assumptions of the repair-misrepair (RMR) (C. A. Tobias, Radiat. Res. 104, S77-S95, 1985), lethal-potentially lethal (LPL) (S. B. Curtis, Radiat. Res. 106, 252-270, 1986) and double-strand break (DSB) (J. Y. Ostashevsky, Radiat. Res. 118, 437-466, 1989) models. The LPL model defines the time available for repair of PLD (t(rep)) as the time taken to reach maximal survival in a delayed-plating recovery experiment. Those data show that after this time has elapsed, contrary to the expectation of the LPL model, survival can be increased by changing the medium used for delayed plating from fresh growth medium to conditioned medium. According to the RMR model, all potentially lethal lesions should also be committed by that time and be unavailable for repair in the new medium. Only the DSB model correctly predicted that PLD (= DSBs) would still be available for repair after that time. Second, data for split-dose recovery are used to predict the first-order kinetics time constant for DSB repair (tau(DSBR)) using the DSB model (24 +/- 1.5 min). This value is nearly identical to the value of 27 +/- 1 min determined from the data obtained by Cheong et al. using pulsed-field gel electrophoresis (PFGE) (Mutat. Res. 274, 111-122, 1992). The value based on PFGE is used to calculate the value of t(rep) predicted by the DSB model (2.6 +/- 0.1 h), which agrees with the value determined experimentally as the time when changing the delayed-plating medium from growth medium to conditioned medium no longer gives the full recovery seen with delayed plating in conditioned medium (2.5 h). However, some recovery was seen for a change in the medium (growth medium to conditioned medium) up to 5-6 h postirradiation. Reanalysis of the original data on DSB repair shows that they are consistent with two first-order repair rates (18 +/- 7 min and about 52 min). These results are consistent with two pools of DSBs (or cells), each with their own t(rep). The early t(rep), associated with tau(fast), is predicted to be 1.7 +/- 0.7 h, and the late t(rep), associated with tau(slow), is predicted to be about 5 h. Both values are in excellent agreement with the times at which changing from growth medium to conditioned medium no longer gives the full recovery seen in conditioned medium only (the early t(rep)), and the time when changing from growth medium to conditioned medium produces no further increase in survival (the late t(rep)), respectively. It is noted that attempts to correlate radiosensitivity with the rates of DSB repair, rather than using an explicit model such as the DSB model, are unlikely to be productive since survival depends on both tau(DSBR) and t(rep) (as defined in the DSB model) and the latter may be the more important determinant of radiosensitivity (as it appears to be for ataxia telangiectasia cells compared to normal fibroblasts and for irs compared to V79 cells).     

Evolution of precipitated phases during prolonged tempering in a 9%Cr1%MoVNb ferritic-martensitic steel: Influence on creep performance

Ferritic-martensitic steels of the 9%Cr1%Mo type have been extensively used in power plant components, heat exchangers, piping and tubing, etc., due to an excellent combination of properties such as creep resistance, toughness and resistance to oxidation at high temperatures. In these steels the stabilizing role of MX carbonitrides (M = Nb, V; X = C, N) is one of the main factors responsible for the resistance under creep conditions. The control of precipitation and coarsening of MX phases during prolonged, high temperature tempering or post-weld heat treatment is then a key point to obtain the desirable microstructure and hence, to achieve high temperature resistance under service conditions.In the present contribution we report the evolution of the precipitated phases during heat treatment at 780 °C for increasing times in the range 40 min to 7 h for an ASTM A213 T91 steel. The Nb and V contents in solid solution were determined as a function of the time of treatment and maxima were observed for 5 and 5.66 h, respectively. Creep tests to rupture were also conducted at 600 °C - 190 MPa for as-treated specimens. A maximum creep rate was observed to occur in coincidence with the maximum values of Nb and V contents in solid solution. We suggest possible relationships between the observed second phase evolution and the creep resistance behavior.     

Nucleation Catalysis in Aluminum Alloy A356 Using Nanoscale Inoculants

Different types of nanoparticles in aluminum (Al) alloy A356 nanocomposites were shown to catalyze nucleation of the primary Al phase. Nanoparticles of SiC β, TiC, Al₂O₃ α, and Al₂O₃ γ were added to and dispersed in the A356 matrix as nucleation catalysts using an ultrasonic mixing technique. Using the droplet emulsion technique (DET), undercoolings in the nanocomposites were shown to be significantly reduced compared to the reference A356. None of the nanocomposites had a population of highly undercooled droplets that were observed in the reference samples. Also, with the exception of the A356/Al₂O₃ α nanocomposite, all nanocomposites showed a reduction in undercooling necessary for the onset of primary Al nucleation. The observed nanocomposite undercoolings generally agreed with the undercooling necessary for free growth. The atomic structure of the particles showed an influence on nucleation potency as A356/Al₂O₃ γ nanocomposites had smaller undercoolings than A356/Al₂O₃ α nanocomposites. The nucleation catalysis illustrates the feasibility of, and basis for, grain refinement in metal matrix nanocomposites (MMNCs).     

Gelatine/PLLA sponge-like scaffolds: morphological and biological characterization

Biodegradable synthetic polymers such as poly(lactic acid) are widely used to prepare scaffolds for cell transplantation and tissue growth, using different techniques set up for the purpose. However the poor hydrophilicity of these polymers represents the main limitation to their use as scaffolds because it causes a low affinity for the cells. An effective way to solve this problem could be represented by the addition of biopolymers that are in general highly hydrophilic. The present work concerns porous biodegradable sponge-like systems based on poly(L-lactic acid) and gelatine. Morphology and porosity characteristics of the sponges were studied by scanning electron microscopy and mercury intrusion porosimetry respectively. Blood compatibility was investigated by bovine plasma fibrinogen adsorption test and platelet adhesion test. The cell culture method was used in order to evaluate the ability of the matrices to work as scaffolds for tissue regeneration. The obtained results indicate that the sponges have interesting porous characteristics, good blood compatibility and above all good ability to support cell adhesion and growth. In fact viable and metabolically active animal cells were found inside the sponges after 8 weeks in culture. On this basis the systems produced seem to be good candidates as scaffolds for tissue regeneration.