Photodynamic therapy: A promising new modality for the treatment of cancer

The first reports on photodynamic therapy (PDT) date back to the 1970s. Since then, several thousands of patients, both with early stage and advanced stage solid tumours, have been treated with PDT and many claims have been made regarding its efficacy. Nevertheless, the therapy has not yet found general acceptance by oncologists. Therefore it seems legitimate to ask whether PDT can still be described as "a promising new therapy in the treatment of cancer". Clinically, PDT has been mainly used for bladder cancer, lung cancer and in malignant diseases of the skin and upper aerodigestive tract. The sensitizer used in the photodynamic treatment of most patients is Photofrin, (Photofrin, the commercial name of dihematoporphyrin ether/ester, containing > 80% of the active porphyrin dimers/oligomers (A.M.R. Fisher, A.L. Murphee and C.J. Gomer, Clinical and preclinical photodynamictherapy, Review Series Article, Lasers Surg. Med., 17 (1995) 2-31). It is a complex mixture of porphyrins derived from hematoporphyrin. Although this sensitizer is effective, it is not the most suitable photosensitizer for PDT. Prolonged skin photosensitivity and the relatively low absorbance at 630 nm, a wavelength where tissue penetration of light is not optimal, have been frequently cited as negative aspects hindering general acceptance. A multitude of new sensitizers is currently under evaluation. Most of these "second generation photosensitizers" are chemically pure, absorb light at around 650 nm or greater and induce no or less general skin photosensitivity. Another novel approach is the photosensitization of neoplasms by the induction of endogenous photosensitizers through the application of 5-aminolevulinic acid (ALA). This article addresses the use of PDT in the disciplines mentioned above and attempts to indicate developments of PDT which could be necessary for this therapy to gain a wider acceptance in the various field

A continuous-discontinuous model for crack branching

This is the peer reviewed version of the following article: Tamayo, E. [et al.]. A continuous-discontinuous model for crack branching. "International journal for numerical methods in engineering", 5 Octubre 2019, vol. 120, núm. 1, p. 86-104, which has been published in final form at https://doi.org/10.1002/nme.6125. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.A new continuous-discontinuous model for fracture that accounts for crack branching in a natural manner is presented. It combines a gradient-enhanced damage model based on nonlocal displacements to describe diffuse cracks and the extended finite element method (X-FEM) for sharp cracks. Its most distinct feature is a global crack tracking strategy based on the geometrical notion of medial axis: the sharp crack propagates following the direction dictated by the medial axis of a damage isoline. This means that, if the damage field branches, the medial axis automatically detects this bifurcation, and a branching sharp crack is thus easily obtained. In contrast to other existing models, no special crack-tip criteria are required to trigger branching. Complex crack patterns may also be described with this approach, since the X-FEM enrichment of the displacement field can be recursively applied by adding one extra term at each branching event. The proposed approach is also equipped with a crack-fluid pressure, a relevant feature in applications such as hydraulic fracturing or leakage-related events. The capabilities of the model to handle propagation and branching of cracks are illustrated by means of different two-dimensional numerical examples.Peer ReviewedPostprint (author's final draft

Introduction, persistence and fade-out of porcine reproductive and respiratory syndrome virus in a Dutch breeding herd: a mathematical analysis.

The objective of this study was to investigate the dynamics of PRRSV infection and to quantify transmission within a breeding herd, and its impact on herd performance. For this purpose a longitudinal study was performed in a closed breeding herd of 115 sows. Statistical methods and Monte Carlo simulations based on stochastic SIR models were used to analyse the observational data. Moreover, a case-control study was performed to determine whether seroconversion of sows during gestation was associated with aberrant litters. The transmission parameter R was estimated to be 3.0 (95% confidence interval 1.5-6.0) for the model version based on the most plausible assumptions that the infectious period lasts 56 days and no lifelong immunity exists after infection. Based on simulations using a breeding herd of equal size the average time-to-extinction was estimated to be 6 years; using a herd of twice the size, it was 80 years. Furthermore, in contrast to the epidemic phase of the disease, the endemic phase was not detrimental to herd performance

Defecation patterns in infants: a prospective cohort study

Data regarding prevalence and natural history of infant dyschezia, defined by the Rome III criteria as straining and crying for at least 10 min before successful passage of soft stools, are lacking. We aimed to investigate prevalence and natural history of infant dyschezia. In 2003, 124 youth healthcare doctors participated in a national study on defecation patterns of infants. Using standardised questionnaires and bowel diaries, these were recorded of infants aged 1, 3 and 9 months old. Out of 1292 infants, 46.4% had no gastrointestinal complaints. At 1 and 3 months old, 3.9% and 0.9% infants, respectively, fulfilled the Rome III criteria for infant dyschezia. However, at the same time points, parents of 17.3% and 6.5% of infants, respectively, reported symptoms preceding defecation while not strictly fulfilling the Rome III criteria ('modified Rome III criteria'). Dyschezia-like symptoms (Rome III criteria) were also reported in 0.9% of 9-month-old infants, with 5.7% having symptoms (modified Rome III criteria). Only 3/61 (4.9%) Rome III dyschezia infants and 1/306 (0.3%) infants with modified Rome III criteria at 1 or 3 months had symptoms fitting the diagnosis of infant functional constipation at 9 months old. The present definition of infant dyschezia seems too strict. We propose to widen the definition in terms of symptoms as well as age in order to better fit the appreciation of the parents. The prevalence of infant dyschezia declines with age. There seems to be no relation to the development of functional constipatio