A perturbative approach to multireference equation-of-motion coupled cluster

We introduce a variant of the multireference equation-of-motion coupled-cluster (MR-EOMCC) method where the amplitudes used for the similarity transformations are estimated from perturbation theory. Consequently, the new variant retains the many-body formalism, a reliance on at most two-body densities, and the state-universal character. As a non-iterative variant, computational costs are reduced, and no convergence difficulties with near-singular amplitudes can arise. Its performance was evaluated on several test sets covering transition metal atoms, small diatomics, and organic molecules against (near-)full CI quality reference data. We further highlight its efficacy on the weakly avoided crossing of LiF and place MR-EOMCC and the new variant into context with linear response theory. The accuracy of the variant was found to be at least on par with expectations for multireference perturbation theories, judging by the NEVPT2 method. The variant can be especially useful in multistate situations where the high accuracy of the iterative MR-EOMCC method is not required

The \gamma function in quantum theory II. Mathematical challenges and paradoxa

While the square root of Dirac’s [Formula: see text] is not defined in any standard mathematical formalism, postulating its existence with some further assumptions defines a generalized function called [Formula: see text] which permits a quasi-classical treatment of simple systems like the H atom or the 1D harmonic oscillator for which accurate quantum mechanical energies were previously reported. The so-defined [Formula: see text] is neither a traditional function nor a distribution, and it remains to be seen that any consistent mathematical approaches can be set up to deal with it rigorously. A straightforward use of [Formula: see text] generates several paradoxical situations which are collected here. The help of the scientific community is sought to resolve these paradoxa

Synergistic effects of TNF-alpha and melphalan in an isolated limb perfusion model of rat sarcoma: a histopathological, immunohistochemical and electron microscopical study.

Isolated limb perfusion (ILP) with tumour necrosis factor alpha (TNF-alpha) and melphalan has shown impressive results in patients with irresectable soft tissue sarcomas and stage III melanoma of the extremities. The mechanisms of the reported in vivo synergistic anti-tumour effects of TNF-alpha and melphalan are not precisely understood. We have developed an ILP model in the rat using a non-immunogenic sarcoma in which similar in vivo synergy is observed. The aim of this present study was to analyse the morphological substrate for this synergistic response of TNF-alpha in combination with melphalan to shed more light on the pathomechanisms involved. Histology of the tumours from saline- (n = 14) and melphalan-treated (n = 11) rats revealed apparently vital tumour cells in over 80% of the cross-sections. Interstitial oedema and coagulation necrosis were observed in the remaining part of the tumour. Haemorrhage was virtually absent. TNF-alpha (n = 22) induced marked oedema, hyperaemia, vascular congestion, extravasation of erythrocytes and haemorrhagic necrosis (20-60% of the cross-sections). Oedema and haemorrhage suggested drastic alterations of permeability and integrity of the microvasculature. Using light and electron-microscopy, we observed that haemorrhage preceded generalised platelet aggregation. Therefore, we suggest that the observed platelet aggregation was the result of the microvascular damage rather than its initiator. Remarkably, these events hardly influenced tumour growth. However, perfusion with the combination of TNF-alpha and melphalan (n = 24) showed more extensive haemorrhagic necrosis (80-90% of the cross-sections) and revealed a prolonged remission (mean 11 days) in comparison with the other groups of rats. Electron microscopical analysis revealed similar findings as described after TNF-alpha alone, although the effects were more prominent at all time points after perfusion. In conclusion, our findings suggest that the enhanced anti-tumour effect after the combination of TNF-alpha with melphalan results from potentiation of the TNF-alpha-induced vascular changes accompanied by increased vascular permeability and platelet aggregation. This may result in additive cytotoxicity or inhibition of growth of residual tumour cells

Spatio-temporal gait analysis based on human-smart rollator interaction

The ability to walk is typically related to several biomechanical components that are involved in the gait cycle (or stride), including free mobility of joints, particularly in the legs; coordination of muscle activity in terms of timing and intensity; and normal sensory input, such as vision and vestibular system. As people age, they tend to slow their gait speed, and their balance is also affected. Also, the retirement from the working life and the consequent reduction of physical and social activity contribute to the increased incidence of falls in older adults. Moreover, older adults suffer different kinds of cognitive decline, such as dementia or attention problems, which also accentuate gait disorders and its consequences. In this paper we present a methodology for gait identification using the on-board sensors of a smart rollator: the i-Walker. This technique provides the number of steps performed in walking exercises, as well as the time and distance travelled for each stride. It also allows to extract spatio-temporal metrics used in medical gait analysis from the interpretation of the interaction between the individual and the i-Walker. In addition, two metrics to assess users’ driving skills, laterality and directivity, are proposed.Peer ReviewedPostprint (author's final draft

The effectiveness and satisfaction of web-based physiotherapy in people with spinal cord injury: a pilot randomised controlled trial

Study Design: Pilot randomised controlled trial. Objectives: The aims of this study were to evaluate the effectiveness and participant satisfaction of web-based physiotherapy for people with Spinal Cord Injury (SCI). Setting: Community patients of a national spinal injury unit in a university teaching hospital, Scotland, UK. Methods: Twenty-four participants were recruited and randomised to receive eight weeks of web-based physiotherapy (intervention), twice per week, or usual care (control). Individual exercise programmes were prescribed based upon participant’s abilities. The intervention was delivered via a website (www.webbasedphysio.com) and monitored and progressed remotely by the physiotherapist. Results: Participants logged on to the website an average of 1.4±0.8 times per week. Between-group differences, although not significant were more pronounced for the 6 minute walk test. Participants were positive about using web-based physiotherapy and stated they would be happy to use it again and would recommend it to others. Overall it was rated as either good or excellent. Conclusions: Web-based physiotherapy was feasible and acceptable for people with SCI. Participants achieved good compliance with the intervention, rated the programme highly and beneficial for health and well-being at various states post injury. The results of this study warrant further work with a more homogenous sample

Review of biorthogonal coupled cluster representations for electronic excitation

Single reference coupled-cluster (CC) methods for electronic excitation are based on a biorthogonal representation (bCC) of the (shifted) Hamiltonian in terms of excited CC states, also referred to as correlated excited (CE) states, and an associated set of states biorthogonal to the CE states, the latter being essentially configuration interaction (CI) configurations. The bCC representation generates a non-hermitian secular matrix, the eigenvalues representing excitation energies, while the corresponding spectral intensities are to be derived from both the left and right eigenvectors. Using the perspective of the bCC representation, a systematic and comprehensive analysis of the excited-state CC methods is given, extending and generalizing previous such studies. Here, the essential topics are the truncation error characteristics and the separability properties, the latter being crucial for designing size-consistent approximation schemes. Based on the general order relations for the bCC secular matrix and the (left and right) eigenvector matrices, formulas for the perturbation-theoretical (PT) order of the truncation errors (TEO) are derived for energies, transition moments, and property matrix elements of arbitrary excitation classes and truncation levels. In the analysis of the separability properties of the transition moments, the decisive role of the so-called dual ground state is revealed. Due to the use of CE states the bCC approach can be compared to so-called intermediate state representation (ISR) methods based exclusively on suitably orthonormalized CE states. As the present analysis shows, the bCC approach has decisive advantages over the conventional CI treatment, but also distinctly weaker TEO and separability properties in comparison with a full (and hermitian) ISR method

High-dose carboplatin, thiotepa and cyclophosphamide (CTC) with peripheral blood stem cell support in the adjuvant therapy of high-risk breast cancer: a practical approach.

In 29 chemotherapy-naive patients with stage II-III breast cancer, peripheral blood stem cells (PBSCs) were mobilised following fluorouracil 500 mg m-2, epirubicin 90-120 mg m-2 and cyclophosphamide 500 mg m-2 (FEC) and granulocyte colony-stimulating factor (G-CSF; Filgrastim) 300 microgram s.c. daily. In all but one patient, mobilisation was successful, requiring three or fewer leucocytopheresis sessions in 26 patients; 28 patients subsequently underwent high-dose chemotherapy consisting of carboplatin 1600 mg m-2, thiotepa 480 mg m-2 and cyclophosphamide 6 g m-2 (CTC) followed by PBSC transplantation. Haemopoietic engraftment was rapid with a median time to neutrophils of 500 x 10(6) l(-1) of 9 days (range 8-10) in patients who received G-CSF after PBSC-transplantation; platelet transfusion independence was reached within a median of 10 days (range 7-16). Neutropenic fever occurred in 96% of patients. Gastrointestinal toxicity was substantial but reversible. Renal, neural or ototoxicity was not observed. Complications related to the central venous catheter were encountered in 64% of patients, with major vein thrombosis occurring in 18%. High-dose CTC-chemotherapy with PBSC-transplantation, harvested after mobilisation with FEC and G-CSF, is reasonably well tolerated without life-threatening toxicity and is a suitable high-dose strategy for the adjuvant treatment of breast cancer

Prognostic and predictive value of human equilibrative nucleoside transporter 1 (hENT1) in extrahepatic cholangiocarcinoma:a translational study

Introduction: Effective (neo) adjuvant chemotherapy for cholangiocarcinoma is lacking due to chemoresistance and the absence of predictive biomarkers. Human equilibrative nucleoside transporter 1 (hENT1) has been described as a potential prognostic and predictive biomarker. In this study, the potential of rabbit-derived (SP120) and murine-derived (10D7G2) antibodies to detect hENT1 expression was compared in tissue samples of patients with extrahepatic cholangiocarcinoma (ECC), and the predictive value of hENT1 was investigated in three ECC cell lines.Methods: Tissues of 71 chemonaïve patients with histological confirmation of ECC were selected and stained with SP120 or 10D7G2 to assess the inter-observer variability for both antibodies and the correlation with overall survival. Concomitantly, gemcitabine sensitivity after hENT1 knockdown was assessed in the ECC cell lines EGI-1, TFK-1, and SK-ChA-1 using sulforhodamine B assays.Results: Scoring immunohistochemistry for hENT1 expression with the use of SP120 antibody resulted in the highest interobserver agreement but did not show a prognostic role of hENT1. However, 10D7G2 showed a prognostic role for hENT1, and a potential predictive role for gemcitabine sensitivity in hENT1 in SK-ChA-1 and TFK-1 cells was found.Discussion: These findings prompt further studies for both preclinical validation of the role of hENT1 and histochemical standardization in cholangiocarcinoma patients treated with gemcitabine-based chemotherapy