Characterization of male breast cancer: results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program.

Background: Male breast cancer (BC) is rare, managed by extrapolation from female BC. The International Male BC Program aims to better characterize and manage this disease. We report the results of part I, a retrospective joint analysis of cases diagnosed during a 20-year period. Methods: Patients with follow-up and tumor samples, treated between 1990 and 2010, in 93 centers/9 countries. Samples were centrally analyzed in three laboratories (the United Kingdom, the Netherlands and the United States). Results: Of 1822 patients enrolled, 1483 were analyzed; 63.5% were diagnosed between 2001 and 2010, 57 (5.1%) had metastatic disease (M1). Median age at diagnosis: 68.4 years. Of 1054 M0 cases, 56.2% were node-negative (N0) and 48.5% had T1 tumors; 4% had breast conserving surgery (BCS), 18% sentinel lymph-node biopsy; half received adjuvant radiotherapy; 29.8% (neo)adjuvant chemotherapy and 76.8% adjuvant endocrine therapy (ET), mostly tamoxifen (88.4%). Per central pathology, for M0 tumors: 84.8% ductal invasive carcinomas, 51.5% grade 2; 99.3% estrogen receptor (ER)-positive; 81.9% progesterone receptor (PR)-positive; 96.9% androgen receptor (AR)-positive [ER, PR or AR Allred score ≥3]; 61.1% Ki67 expression low (<14% positive cells); using immunohistochemistry (IHC) surrogates, 41.9% were Luminal-A-like, 48.6% Luminal-B-like/HER-2-negative, 8.7% HER-2-positive, 0.3% triple negative. Median follow-up: 8.2 years (0.0-23.8) for all, 7.2 years (0.0-23.2), for M0, 2.6 years (0.0-12.7) for M1 patients. A significant improvement over time was observed in age-corrected BC mortality. BC-specific-mortality was higher for men younger than 50 years. Better overall (OS) and recurrence-free survival (RFS) were observed for highly ER+ (P = 0.001), highly PR+ (P = 0.002), highly AR+ disease (P = 0.019). There was no association between OS/RFS and HER-2 status, Ki67, IHC subtypes nor grade. Conclusions: Male BC is usually ER, PR and AR-positive, Luminal B-like/HER2-negative. Of note, 56% patients had T1 tumors but only 4% had BCS. ER was highly positive in >90% of cases but only 77% received adjuvant ET. ER, PR and AR were associated with OS and RFS, whereas grade, Ki67 and IHC surrogates were not. Significant improvement in survival over time was observed.

Marital status and stage of cancer at diagnosis: A systematic review.

Early cancer detection is fundamental to the promotion of better health in the community, but disparities remain in the likelihood of cancer being detected at an early stage, some of which relate to socio-demographic factors such as marital status. The aim of this study was to conduct a systematic review of research on the association between marital status and stage at diagnosis of different types of cancer. A comprehensive systematic literature search was run in the Medline and Scopus databases (from January 1990 to June 2014), identifying 245 and 208 articles on PubMed and Scopus respectively. Of these 453 studies, 18 were judged eligible for this systematic review. A quality assessment was performed on the studies using the 22 items in the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist. This review confirmed the important influence of being married on the earlier detection of cancer. None of the studies considered identified more cases of cancer in a later stage among married patients, and the majority of them reported a statically significant association between marital status and stage at diagnosis, with a positive effect of marriage on the likelihood of cancer being diagnosed at an early stage, for various types of malignancy. In particular, our meta-analysis showed that the unmarried have higher odds of having a later stage of breast cancer (OR = 1.287 95% CI: 1.025-1.617) or melanoma (OR = 1.350 95% CI: 1.161-1.570) at diagnosis. Specific interventions should be developed for the unmarried population to improve their chances of any neoplasms being diagnosed at an early stage, thereby reducing health disparities in the population at large.

A velocity map imaging study of the photodissociation of the methyl iodide cation.

The photodissociation dynamics of the methyl iodide cation has been studied using the velocity map imaging technique. A first laser pulse is used to ionize methyl iodide via a (2 + 1) REMPI scheme through the 5pπ → 6p Rydberg state two-photon transition. The produced CH3I+(X[combining tilde]2E3/2) ions are subsequently excited at several wavelengths between 242 and 260 nm. The reported translational energy distributions for the methyl and iodine ions present a Boltzmann-type unstructured distribution at low excitation energies as well as a recoiled narrow structure at higher excitation energies highlighting two different dissociation processes. High level ab initio calculations have been performed in order to obtain a deeper understanding of the photodissociation dynamics of the CH3I+ ion. Direct dissociation on a repulsive state from the manifold of states representing the B[combining tilde] excited state leads to CH3+(X[combining tilde]1A1') + I*(2P1/2), while the CH3 + I+(3P2) channel is populated through an avoided crossing outside the Franck-Condon region. In contrast, an indirect process involving the transfer of energy from highly excited electronic states to the ground state of the ion is responsible for the observed Boltzmann-type distributions.

Guidelines for time-to-event end point definitions in breast cancer trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†.

BACKGROUND: Using surrogate end points for overall survival, such as disease-free survival, is increasingly common in randomized controlled trials. However, the definitions of several of these time-to-event (TTE) end points are imprecisely which limits interpretation and cross-trial comparisons. The estimation of treatment effects may be directly affected by the definitions of end points. The DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for randomized cancer clinical trials (RCTs) in breast cancer. PATIENTS AND METHODS: A literature review was carried out to identify TTE end points (primary or secondary) reported in publications of randomized trials or guidelines. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points based on a validated consensus method that formalize the degree of agreement among experts. RESULTS: Recommended guidelines for the definitions of TTE end points commonly used in RCTs for breast cancer are provided for non-metastatic and metastatic settings. CONCLUSION: The use of standardized definitions should facilitate comparisons of trial results and improve the quality of trial design and reporting. These guidelines could be of particular interest to those involved in the design, conducting, reporting, or assessment of RCT.

Resolving the forbidden band of SF6.

Sulfur hexafluoride is an important molecule for modeling thermophysical and polarizability properties. It is also a potent greenhouse gas of anthropogenic origin, whose concentration in the atmosphere, although very low is increasing rapidly; its global warming power is mostly conferred by its strong infrared absorption in the ν3 S-F stretching region near 948 cm(-1). This heavy species, however, features many hot bands at room temperature (at which only 31% of the molecules lie in the ground vibrational state), especially those originating from the lowest, v6 = 1 vibrational state. Unfortunately, the ν6 band itself (near 347 cm(-1)), in the first approximation, is both infrared- and Raman-inactive, and no reliable spectroscopic information could be obtained up to now and this has precluded a correct modeling of the hot bands. It has been suggested theoretically and experimentally that this band might be slightly activated through Coriolis interaction with infrared-active fundamentals and appears in high pressure measurements as a very faint, unresolved band. Using a new cryogenic multipass cell with 93 m optical path length and regulated at 163 ± 2 K temperature, coupled to synchrotron radiation and a high resolution interferometer, the spectrum of the ν6 far-infrared region has been recorded. Low temperature was used to avoid the presence of hot bands. We are thus able to confirm that the small feature in this region, previously viewed at low-resolution, is indeed ν6. The fully resolved spectrum has been analyzed, thanks to the XTDS software package. The band appears to be activated by faint Coriolis interactions with the strong ν3 and ν4 fundamental bands, resulting in the appearance of a small first-order dipole moment term, inducing unusual selection rules. The band center (ν6 = 347.736707(35) cm(-1)) and rovibrational parameters are now accurately determined for the v6 = 1 level. The ν6 perturbation-induced dipole moment is estimated to be 33 ± 3 µD and the ν6 integrated intensity to be 0.0035 km mol(-1).

Direct evidence of hydrogen-atom tunneling dynamics in the excited state hydrogen transfer (ESHT) reaction of phenol-ammonia clusters.

The photodynamics of phenol-ammonia clusters, PhOH(NH3)(3-5), after one UV photon absorption, has been investigated using velocity map imaging of the NH4(NH3)(2-4) cluster products. The dependence of the NH4(NH3)2 translational energy distributions on the available energy reveals three dynamical regions in close correspondence with the photodissociation of bare phenol. At low excitation energies (between 282 and 260 nm), the NH4(NH3)2 distribution mirrors the hydrogen-atom passage through the 1(1)ππ*-1(1)πσ* barrier, constituting the first evidence of hydrogen-atom tunneling dynamics in an excited state hydrogen transfer (ESHT) reaction. At excitation wavelengths below 260 nm, the product distributions are consistent with two separate barrierless dissociation processes associated, respectively, with excitation to the 1(1)ππ* and 2(1)ππ* excited electronic states. Similar conclusions can be derived from the velocity map imaging results on the larger NH4(NH3)(3,4) cluster products.

Survey on current clinical practice in geriatric oncology: the individual experience in five European Cancer Centers.

PURPOSE: To gather information from clinicians on how geriatric oncology models of care have emerged in different European countries and describe current practice in this clinical area. METHODS: A semi-structured online interview was performed, exploring aspects related to implementation, perceived quality of care, and professional satisfaction. RESULTS: The centers participating in this interview showed significant differences in terms of resource allocation, team members, components of the comprehensive geriatric assessment (CGA), and CGA-driven interventions. High levels of professional satisfaction were expressed by all participants. This was deemed a consequence of a perception of increased quality in the provision of care and enhanced educational and academic opportunities. CONCLUSION: Interdisciplinary models of care in geriatric oncology, regardless of implementation details, seem to provide grounds for increased professional satisfaction and perception of better provision of quality of care. These characteristics could support promoting and further developing similar collaborations on a wider scale.

Stereodynamics of the photodissociation of nitromethane at 193 nm: unravelling the dissociation mechanism.

The photodissociation of nitromethane at 193 nm is reviewed in terms of new stereodynamical information provided by the measurement of the first four Dixon's bipolar moments, ß0(2)(20), ß0(0)(22), ß0(2)(02), and ß0(2)(22), using slice imaging. The measured speed-dependent ß0(2)(20) (directly related with the spatial anisotropy parameter ß) indicates that after one-photon absorption to the S3(2 (1)A″) state by an allowed perpendicular transition, two reaction pathways can compete with similar probability, a direct dissociation process yielding ground-state CH3 and NO2(1 (2)A2) radicals and a indirect dissociation through conical intersections in which NO2 radicals are formed in lower-lying electronic states. A particularly important result from our measurements is that the low recoil energy part of the methyl fragment translational energy distribution presents a contribution with parallel character, irrespective of the experimental conditions employed, that we attribute to parent cluster dissociation. Moreover, the positive values found for the ß0(0)(22) bipolar moment indicates some propensity for the fragment's recoil velocity and angular momentum vectors to be parallel.

20 THz-bandwidth continuous-wave fiber optical parametric amplifier operating at 1 µm using a dispersion-stabilized photonic crystal fiber.

We report the experimental demonstration of a continuous-wave all-fiber optical parametric amplifier in the 1 µm band with a record bandwidth of more than 20 THz and a peak gain of almost 40 dB. This is achieved by using a photonic crystal fiber with a high figure of merit and strongly reduced longitudinal dispersion fluctuations. Due to their unique bandwidth and gain characteristics, fiber parametric amplifiers at 1 µm provide an interesting alternative to solid-state or ytterbium-doped fiber amplifiers for ultrafast optical pulse and signal processing.

Imaging the molecular channel in acetaldehyde photodissociation: roaming and transition state mechanisms.

The roaming dynamics in the photodissociation of acetaldehyde is studied through the first absorption band, in the wavelength interval ranging from 230 nm to 325 nm. Using a combination of the velocity-map imaging technique and rotational resonance enhanced multiphoton ionization (REMPI) spectroscopy of the CO fragment, the branching ratio between the canonical transition state and roaming dissociation mechanisms is obtained at each of the photolysis wavelengths studied. Upon one photon absorption, the molecule is excited to the first singlet excited S(1) state, which, depending on the excitation wavelength, either converts back to highly vibrationally excited ground S(0) state or undergoes intersystem crossing to the first excited triplet T(1) state, from where the molecule can dissociate over two main channels: the radical (CH(3) + HCO) and the molecular (CO + CH(4)) channels. Three dynamical regions are characterized: in the red edge of the absorption band, at excitation energies below the T(1) barrier, the ratio of the roaming dissociation channel increases, largely surpassing the transition state contribution. As the excitation wavelength is increased, the roaming propensity decreases reaching a minimum at wavelengths ∼308 nm. Towards the blue edge, at 230 nm, an upper limit of ∼50% has been estimated for the contribution of the roaming channel. The experimental results are interpreted in terms of the interaction between the different potential energy surfaces involved by means of ab initio stationary points and intrinsic reaction coordinate paths calculations.

Photodissociation of pyrrole-ammonia clusters below 218 nm: quenching of statistical decomposition pathways under clustering conditions.

The excited state hydrogen transfer (ESHT) reaction in pyrrole-ammonia clusters (PyH·(NH(3))(n), n = 2-5) at excitation wavelengths below 218 nm down to 199 nm, has been studied using a combination of velocity map imaging and non-resonant detection of the NH(4)(NH(3))(n-1) products. Special care has been taken to avoid evaporation of solvent molecules from the excited clusters by controlling the intensity of both the excitation and probing lasers. The high resolution translational energy distributions obtained are analyzed on the base of an impulsive mechanism for the hydrogen transfer, which mimics the direct N-H bond dissociation of the bare pyrrole. In spite of the low dissociation wavelengths attained (~200 nm) no evidence of hydrogen-loss statistical dynamics has been observed. The effects of clustering of pyrrole with ammonia molecules on the possible statistical decomposition channels of the bare pyrrole are discussed.

Slice imaging and wave packet study of the photodissociation of CH3I in the blue edge of the A-band: evidence of reverse 3Q0 ← 1Q1 non-adiabatic dynamics.

The photodissociation of CH(3)I in the blue edge (217-230 nm) of the A-band has been studied using a combination of slice imaging and resonance enhanced multiphoton ionization (REMPI) detection of the CH(3) fragment in the vibrational ground state (ν = 0). The profiles of the CH(3) (ν = 0) kinetic energy distributions and the photofragment anisotropies are interpreted in terms of the contribution of the excited surfaces involved in the photodissociation process, as well as the probability of non-adiabatic curve crossing between the (3)Q(0) and (1)Q(1) states. In the studied region, unlike in the central part of the A-band where absorption to the (3)Q(0) state dominates, the I((2)P(J)), with J = 1/2, 3/2, in correlation with CH(3) (ν = 0) kinetic energy distributions show clearly two contributions of different anisotropy, signature of the competing adiabatic and non-adiabatic dynamics, whose ratio strongly depends on the photolysis wavelength. The experimental results are compared with multisurface wave packet calculations carried out using the available ab initio potential energy surfaces, transition moments, and non-adiabatic couplings, employing a reduced dimensionality model. A good qualitative agreement is found between experiment and theory and both show evidence of reverse (3)Q(0)←(1)Q(1) non-adiabatic dynamics at the bluest excitation wavelengths both in the fragment kinetic energy and angular distributions.

Photodissociation of pyrrole-ammonia clusters by velocity map imaging: mechanism for the H-atom transfer reaction.

The photodissociation dynamics of pyrrole-ammonia clusters (PyH·(NH(3))(n), n = 2-6) has been studied using a combination of velocity map imaging and non-resonant detection of the NH(4)(NH(3))(n-1) products. The excited state hydrogen-atom transfer mechanism (ESHT) is evidenced through delayed ionization and presents a threshold around 236.6 nm, in agreement with previous reports. A high resolution determination of the kinetic energy distributions (KEDs) of the products reveals slow (∼0.15 eV) and structured distributions for all the ammonia cluster masses studied. The low values of the measured kinetic energy rule out the existence of a long-lived intermediate state, as it has been proposed previously. Instead, a direct N-H bond rupture, in the fashion of the photodissociation of bare pyrrole, is proposed. This assumption is supported by a careful analysis of the structure of the measured KEDs in terms of a discrete vibrational activity of the pyrrolyl co-fragment.

A slice imaging and multisurface wave packet study of the photodissociation of CH3I at 304 nm.

The role of the conical intersection between the (1)Q(1) and (3)Q(0) excited states in the photodissociation of CH(3)I at 304 nm is investigated drawing a comparison between the adiabatic--through direct absorption to the (3)Q(1) state--and non-adiabatic--via the (1)Q(1)→(3)Q(0) conical intersection--production of I atoms in the ground (2)P(3/2) state. The versatility of the slice imaging technique in combination with resonance enhanced multiphoton ionization (REMPI) detection of I((2)P(3/2)) atoms allow distinct measurements of the competing processes. The I((2)P(3/2)) atom kinetic energy distributions (KEDs) obtained in both cases reflect inverted vibrational progressions of the ν(2) umbrella mode of the CH(3) co-product. The experimental results show a satisfactory agreement with multisurface wave packet calculations using a reduced dimensionality (pseudotriatomic) model carried out on the available ab initio potential energy surfaces.

Communication: First observation of ground state I(2P(3/2)) atoms from the CH3I photodissociation in the B-band.

The photodissociation of CH(3)I in the second absorption band (the B-band) has been studied at the wavelength 199.11 nm, coincident with the 3(0)(1) (3)R(1)(E)←X((1)A(1)) CH(3)I vibronic transition, using a combination of slice imaging and resonance enhanced multiphoton ionization detection of the CH(3) fragment. The kinetic energy and angular distributions of the recoiling CH(3) fragment confirm a major predissociation dynamics channel as a result of the interaction between the bound (3)R(1) Rydberg state and the repulsive (3)A(1)(E) state--ascribed to the A-band--yielding CH(3) fragments in correlation with spin-orbit excited I*((2)P(1/2)) atoms. In addition, first evidence of a non-negligible population of ground state I((2)P(3/2)) atoms in the CH(3) fragment slice images, suggests a secondary predissociation mechanism via interaction between the (3)R(1) Rydberg state and the repulsive A-band (1)Q(1) state.

Vitamin retention during the canning of swordfish (Xiphias gladius) with different filling media.

Swordfish (Xiphias gladius) is an economically and nutritionally important fish. The aims of this study were to determine the effects of the various steps of the canning process and of different filling media (olive oil, corn oil, sunflower oil, and high oleic sunflower oil) on the fat- and water-soluble vitamin contents of swordfish. An HPLC-based method was used for this purpose. The canning process led to loss of some vitamins, particularly of vitamin D3 . Loss of this vitamin mainly occurred during storage and although important (89.34% to 91.36%), canned swordfish can be considered a good source of vitamin D3 , providing between 50% and 64% of the RDI. The frying process also caused significant loss of vitamin B9 (73.7%). However, the vitamin E content increased due to contributions from the frying and filling oils. The canned swordfish packed in olive oil had lower vitamin A (107.35 µg/100 g) and E (1.58 mg/100 g) contents than the fish packed in sunflower oil (193.28 µg/100 g and 2.28 mg/100 g, respectively). The swordfish packed in sunflower oil also had the highest B2 (0.036 mg/100 g) content. The swordfish packed in corn oil had the lowest vitamin A (80.17 µg/100 g) and B2 (0.012 mg/100 g) contents, while the samples packed in high oleic sunflower oil had the lowest contents of vitamins B9 (0.14 µg/100 g) and B12 (2.37 mg/100 g). PRACTICAL APPLICATION: Swordfish (Xiphias gladius) is consumed worldwide and is economically very important in the seafood industry. The canning process caused losses of some vitamins, particularly of vitamins D3 and B9 ; however, the vitamin E content increased due to the frying and filling oils. The study findings may contribute to increasing knowledge about how processing, storage and the filling medium influence the composition of canned fish.

Imaging the radical channel in acetaldehyde photodissociation: competing mechanisms at energies close to the triplet exit barrier.

The photodissociation of acetaldehyde in the radical channel has been studied at wavelengths between 315 and 325 nm using the velocity-map imaging technique. Upon one-photon absorption at 315 nm, the molecule is excited to the first singlet excited state S(1), which, in turn, undergoes intersystem crossing to the first excited triplet state T(1). On the triplet surface, the molecule dissociates into CH(3) and HCO radicals with large kinetic energy release (KER), in accordance with the well characterized exit barrier on T(1). However, at longer wavelengths (>320 nm), which correspond to excitation energies just below the triplet barrier, a sudden change in KER is observed. At these photolysis wavelengths, there is not enough energy to surpass the exit barrier on the triplet state, which leaves the possibility of unimolecular dissociation on S(0) after internal conversion from S(1). We have characterized the fragments' KER at these wavelengths, as well as determined the energy partitioning for the radical fragments. A new accurate estimate of the barrier height on T(1) is presented.

The photodissociation of CH(3)I in the red edge of the A-band: Comparison between slice imaging experiments and multisurface wave packet calculations.

The photodissociation of methyl iodide at different wavelengths in the red edge of the A-band (286-333 nm) has been studied using a combination of slice imaging and resonance enhanced multiphoton ionization detection of the methyl fragment in the vibrational ground state (nu=0). The kinetic energy distributions (KED) of the produced CH(3)(nu=0) fragments show a vibrational structure, both in the I((2)P(3/2)) and I( *)((2)P(1/2)) channels, due to the contribution to the overall process of initial vibrational excitation in the nu(3)(C-I) mode of the parent CH(3)I. The structures observed in the KEDs shift toward upper vibrational excited levels of CH(3)I when the photolysis wavelength is increased. The I((2)P(3/2))/I( *)((2)P(1/2)) branching ratios, photofragment anisotropies, and the contribution of vibrational excitation of the parent CH(3)I are explained in terms of the contribution of the three excited surfaces involved in the photodissociation process, (3)Q(0), (1)Q(1), and (3)Q(1), as well as the probability of nonadiabatic curve crossing (1)Q(1)<--(3)Q(0). The experimental results are compared with multisurface wave packet calculations carried out using the available ab initio potential energy surfaces, transition moments, and nonadiabatic couplings, employing a reduced dimensionality (pseudotriatomic) model. A general qualitative good agreement has been found between theory and experiment, the most important discrepancies being in the I((2)P(3/2))/[I((2)P(3/2))+I( *)((2)P(1/2))] branching ratios. Inaccuracies of the available potential energy surfaces are the main reason for the discrepancies.