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Background: We aimed to quantify patients' benefit-risk preferences for attributes associated with human epidermal growth factor receptor 2 (HER2)-targeted breast cancer treatments and estimate minimum acceptable benefits (MABs), denominated in additional months of progression-free survival (PFS), for given treatment-related adverse events (AEs). Methods: We conducted an online discrete-choice experiment (DCE) among patients with self-reported advanced/metastatic breast cancer in the United States, United Kingdom, and Japan (N = 302). In a series of nine DCE questions, respondents chose between two hypothetical treatment profiles created by an experimental design. Profiles were defined by six attributes with varying levels: PFS, nausea/vomiting, diarrhea, liver function problems, risk of heart failure, and risk of serious lung damage and infections. Data were analyzed using an error component random-parameters logit model. Results: Among the attributes, patients placed the most importance on a change in PFS from 5 to 26 months; change from no diarrhea to severe diarrhea was the least important. Avoiding a 15% risk of heart failure had the largest MAB (5.8 additional months of PFS), followed by avoiding a 15% risk of serious lung damage and infections (4.6 months), possible severe liver function problems (4.2 months), severe nausea/vomiting (3.7 months), and severe diarrhea (2.3 months) compared with having none of the AEs. The relative importance of 21 additional months of PFS (increasing from 5 to 26 months) increased for women with HER2-negative disease and those with children. Conclusions: Patients valued PFS gain higher than the potential risk of AEs when deciding between hypothetical breast cancer treatments. [ABSTRACT FROM AUTHOR]

Purpose: Human epidermal growth factor receptor 2 (HER2)–targeted therapies improve survival for patients with HER2-positive breast cancer but carry risks of hematologic, cardiopulmonary, gastro-hepatobiliary, and other adverse events (AEs). In this review, we describe published AE incidences for HER2-targeted therapies for metastatic breast cancer (mBC). Methods: We searched PubMed and Embase to identify studies on HER2-targeted therapies in HER2-positive mBC, reporting on AEs of special interest, and published between January 1, 2009, and February 6, 2020. Treatment regimens were categorized into mutually exclusive therapy-based categories, with primary therapy determined by worldwide approval date. Results: One hundred and fifty-three included articles assessed a combined 29,238 patients treated with the following therapy-based regimens: trastuzumab or biosimilars (78 studies), lapatinib (40), T-DM1 (ado-trastuzumab emtansine) (20), pertuzumab (14), neratinib (8), MM-302 (1), T-DXd (2), tucatinib (3), and pyrotinib (3). While direct comparisons of AE incidence are not warranted owing to study heterogeneity, proportions of patients experiencing any Grade 3 + AE ranged across therapy-based regimens from 39.4% (lapatinib) to 66.3% (neratinib). The most common hematologic AE of special interest, of any grade and regardless of causality, was leukopenia/white blood cells decreased [21.4% (T-DXd)-46.2% (pyrotinib)]. Cardiopulmonary AEs of special interest included interstitial lung disease [2.7% (trastuzumab)-5.2% (T-DXd)], pneumonitis [0.2% (lapatinib)-7.4% (trastuzumab)], and decreased ejection fraction [1% (T-DXd)-13.6% (trastuzumab)]. Gastro-hepatobiliary AEs of special interest included nausea [33.9% (trastuzumab)-78.3% (T-DXd)], vomiting [19.2% (T-DM1)-48.2% (T-DXd)], diarrhea [19.6% (T-DM1)-96.9% (pyrotinib)], and hepatotoxicity [5.9% (lapatinib)-53.6% (T-DM1)]. Conclusion: Differing AE profiles for anti-HER2 therapies should be considered when assessing benefit-risk profile for treatment options. [ABSTRACT FROM AUTHOR]

Background: The P300 (P3) component of the event related potential has been established as a sensitive risk marker of vulnerability to alcoholism. Most alcoholism studies have focused on men; recent studies indicate that women are equally vulnerable to developing alcoholism. Methods: Visual P3 recorded from 31 electrode positions was evaluated in 44 alcoholic and 60 control women, 24-50 years of age. P3 amplitudes and latencies of the two groups were statistically compared using Analysis of Variance; source localization of surface amplitude values from each group were plotted using a low-resolution brain electromagnetic tomography. Results: The results indicated that alcoholic women had significantly smaller P3 amplitudes in the frontal and central regions compared with controls. Source localization showed lowered activation in alcoholic women in right dorso-lateral prefrontal cortex and the ventro-medial fronto-central regions. Conclusions: The results suggest that P3 is an equally sensitive endophenotypic marker of vulnerability to alcoholism in women. The findings are discussed in terms of functional and physiologic significance of the P3 amplitude in alcoholic women and its relationship to drinking behaviors. [ABSTRACT FROM AUTHOR]

This paper describes a method for estimating a set of spatial components (brain maps) and temporal components (waveforms) of brain potentials. These components play the role of bases of a coordinate system, in the sense that the brain potentials of any subject can be represented as superpositions of these components. The representation is unique given the spatial and temporal components, and this decomposition is particularly appealing for comparing the brain potentials of different subjects (say alcoholics and controls). It can also be used for single trial modeling, clinical classification of patients, and data filtering. The method is based on the topographic component model (TCM, Möcks 1988) which models brain potentials in a trilinear form. We extend the TCM in two aspects. First, the diagonal amplitude matrix is replaced by a general loading matrix based on some neurophysiological considerations. Secondly, the number of spatial components and the number of temporal components can be different. The spatial components and temporal components are obtained respectively by performing singular value decomposition (SVD). This method is illustrated with visual P3 data. [ABSTRACT FROM AUTHOR]

This paper describes a method for estimating the surface Laplacian of brain potentials. The method consists of two steps: local surface approximation by its tangent plane and local polynomial fitting. Compared to previous methods for estimating surface Laplacian, this method has some new features. First, it can estimate the surface Laplacian at any point of the scalp, including the locations of the peripheral electrodes. Secondly, it estimates the brain potential and the surface Laplacian at any point simultaneously. This reduces the risk of error propagation, which occurs when the brain potential is interpolated first and the surface Laplacian is then computed based on the interpolated brain potential. Finally, the method automatically adapts to noisy data by using more or less measurements at neighboring electrodes based on estimated noise level. Simulations suggest that this method is effective. Application to event-related potentials are also presented. [ABSTRACT FROM AUTHOR]

Let S be sums of iid random vectors taking values in a Banach space and F be a smooth function. We study the fluctuations of S under the transformed measure P given by d P/ d P=exp ( nF( S/ n))/ Z. If degeneracy occurs then the projection of S onto the degenerate subspace, properly centered and scaled, converges to a non-Gaussian probability measure with the degenerate subspace as its support. The projection of S onto the non-degenerate subspace, scaled with the usual order $$\sqrt {n,} $$ converges to a Gaussian probability measure with the non-degenerate subspace as its support. The two projective limits are in general dependent. We apply this theory to the critical mean field Heisenberg model and prove a central limit type theorem for the empirical measure of this model. [ABSTRACT FROM AUTHOR]

Multiresolution analysis is a potentially useful tool to enhance the brain's electrical fields (spatial distributions of event-related potentials (ERP)), and to bring out spatial features which may not be seen in the fields before enhancement. For comparing different images (slices from ERP of different subjects or from the same subject but evoked by different stimuli), we define a measure (surface energy) at each decomposition scale and for different wavelets. The best wavelet and the best level for comparing the given images can be chosen based on this measure. Our experiments show that for very similar images, their difference can be brought out at some scale level. Three preprocessing steps are needed in order to carry out this wavelet analysis. First, a wavelet denoising step is needed to remove noise from the raw ERP. Secondly, a one-to-one mapping is needed to map scalp surface into a square, because the current wavelet analysis theory and algorithm are constructed on regular domains. Finally, a fitting or interpolation step is needed to construct an image on a regular grid in order to apply the fast wavelet transform algorithms. [ABSTRACT FROM AUTHOR]