Improving therapeutic ratio In head and neck cancer with adjuvant and cisplatin-based treatments

Advanced head and neck cancers are difficult to manage despite the large treatment arsenal currently available. The multidisciplinary effort to increase disease-free survival and diminish normal tissue toxicity was rewarded with better locoregional control and sometimes fewer side effects. Nevertheless, locoregional recurrence is still one of the main reasons for treatment failure. Today, the standard of care in head and neck cancer management is represented by altered fractionation radiotherapy combined with platinum-based chemotherapy. Targeted therapies as well as chronotherapy were trialled with more or less success. The aim of the current work is to review the available techniques, which could contribute towards a higher therapeutic ratio in the treatment of advanced head and neck cancer patients.Loredana G. Marc

Miniaturized side-viewing imaging probe for fluorescence lifetime imaging (FLIM): validation with fluorescence dyes, tissue structural proteins and tissue specimens

Published versio

Quo vadis radiotherapy? Technological advances and the rising problems in cancer management

Extent: 10p.Purpose. Despite the latest technological advances in radiotherapy, cancer control is still challenging for several tumour sites. The survival rates for the most deadly cancers, such as ovarian and pancreatic, have not changed over the last decades. The solution to the problem lies in the change of focus: from local treatment to systemic therapy. The aim of this paper is to present the current status as well as the gaps in radiotherapy and, at the same time, to look into potential solutions to improve cancer control and survival. Methods. The currently available advanced radiotherapy treatment techniques have been analysed and their cost-effectiveness discussed. The problem of systemic disease management was specifically targeted. Results. Clinical studies show limited benefit in cancer control from hadron therapy. However, targeted therapies together with molecular imaging could improve treatment outcome for several tumour sites while controlling the systemic disease. Conclusion. The advances in photon therapy continue to be competitive with the much more expensive hadron therapy. To justify the cost effectiveness of proton/heavy ion therapy, there is a need for phase III randomised clinical trials. Furthermore, the success of systemic disease management lies in the fusion between radiation oncology technology and microbiology.Barry J. Allen, Eva Bezak, and Loredana G. Marc

Search engines and the sex education information practices of LGBTQ+ youth

Online resources are vital to the health information practices of LGBTQ+ youth, especially when finding information related to sex education topics. As LGBTQ+ youth use the internet, particularly Google Search, to meet their sex and sexual health information needs, it is important to understand both the information practices related to this unique search experience and how the affordances of this particular search engine impact the information seeking process. The goal of this project is to study the online information practices of LGBTQ+ youth when searching for sex education information, specifically perceptions of and interactions with search engines. Using semi‐structured interviews, we ask LGBTQ+ youth to discuss their information practices related to sex education information and use Google Search to answer sample questions related to sex and sexual health. In this work in progress poster, we discuss our theoretical framing, methods, and preliminary results.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163483/2/pra2364_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163483/1/pra2364.pd

Contaminants of Emerging Concern (CECs) and male reproductive health: challenging the future with a double-edged sword

Approximately 9% of couples are infertile, with half of these cases relating to male factors. While many cases of male infertility are associated with genetic and lifestyle factors, approximately 30% of cases are still idiopathic. Contaminants of emerging concern (CECs) denote substances identified in the environment for the first time or detected at low concentrations during water quality analysis. Since CEC production and use have increased in recent decades, CECs are now ubiquitous in surface and groundwater. CECs are increasingly observed in human tissues, and parallel reports indicate that semen quality is continuously declining, supporting the notion that CECs may play a role in infertility. This narrative review focuses on several CECs (including pesticides and pharmaceuticals) detected in the nearshore marine environment of False Bay, Cape Town, South Africa, and deliberates their potential effects on male fertility and the offspring of exposed parents, as well as the use of spermatozoa in toxicological studies. Collective findings report that chronic in vivo exposure to pesticides, including atrazine, simazine, and chlorpyrifos, is likely to be detrimental to the reproduction of many organisms, as well as to sperm performance in vitro. Similarly, exposure to pharmaceuticals such as diclofenac and naproxen impairs sperm motility both in vivo and in vitro. These contaminants are also likely to play a key role in health and disease in offspring sired by parents exposed to CECs. On the other side of the double-edged sword, we propose that due to its sensitivity to environmental conditions, spermatozoa could be used as a bioindicator in eco- and repro-toxicology studies

Multiple cyclotron line-forming regions in GX 301-2

We present two observations of the high-mass X-ray binary GX 301-2 with NuSTAR, taken at different orbital phases and different luminosities. We find that the continuum is well described by typical phenomenological models, like a very strongly absorbed NPEX model. However, for a statistically acceptable description of the hard X-ray spectrum we require two cyclotron resonant scattering features (CRSF), one at ~35 keV and the other at ~50 keV. Even though both features strongly overlap, the good resolution and sensitivity of NuSTAR allows us to disentangle them at >=99.9% significance. This is the first time that two CRSFs are seen in GX 301-2. We find that the CRSFs are very likely independently formed, as their energies are not harmonically related and, if it were a single line, the deviation from a Gaussian shape would be very large. We compare our results to archival Suzaku data and find that our model also provides a good fit to those data. We study the behavior of the continuum as well as the CRSF parameters as function of pulse phase in seven phase bins. We find that the energy of the 35 keV CRSF varies smoothly as function of phase, between 30-38 keV. To explain this variation, we apply a simple model of the accretion column, taking the altitude of the line-forming region, the velocity of the in-falling material, and the resulting relativistic effects into account. We find that in this model the observed energy variation can be explained simply due to a variation of the projected velocity and beaming factor of the line forming region towards us.Comment: 18 pages, 10 figures, accepted for publication in A&

Uqosp(2,2)U_q osp(2,2) Lattice Models

In this paper I construct lattice models with an underlying $U_q osp(2,2)$ superalgebra symmetry. I find new solutions to the graded Yang-Baxter equation. These {\it trigonometric} $R$-matrices depend on {\it three} continuous parameters, the spectral parameter, the deformation parameter $q$ and the $U(1)$ parameter, $b$, of the superalgebra. It must be emphasized that the parameter $q$ is generic and the parameter $b$ does not correspond to the `nilpotency' parameter of \cite{gs}. The rational limits are given; they also depend on the $U(1)$ parameter and this dependence cannot be rescaled away. I give the Bethe ansatz solution of the lattice models built from some of these $R$-matrices, while for other matrices, due to the particular nature of the representation theory of $osp(2,2)$, I conjecture the result. The parameter $b$ appears as a continuous generalized spin. Finally I briefly discuss the problem of finding the ground state of these models.Comment: 19 pages, plain LaTeX, no figures. Minor changes (version accepted for publication

Autofluorescence lifetime augmented reality as a means for real-time robotic surgery guidance in human patients.

Due to loss of tactile feedback the assessment of tumor margins during robotic surgery is based only on visual inspection, which is neither significantly sensitive nor specific. Here we demonstrate time-resolved fluorescence spectroscopy (TRFS) as a novel technique to complement the visual inspection of oral cancers during transoral robotic surgery (TORS) in real-time and without the need for exogenous contrast agents. TRFS enables identification of cancerous tissue by its distinct autofluorescence signature that is associated with the alteration of tissue structure and biochemical profile. A prototype TRFS instrument was integrated synergistically with the da Vinci Surgical robot and the combined system was validated in swine and human patients. Label-free and real-time assessment and visualization of tissue biochemical features during robotic surgery procedure, as demonstrated here, not only has the potential to improve the intraoperative decision making during TORS but also other robotic procedures without modification of conventional clinical protocols

New oral anticoagulants and their reversal agents

Atrial fibrillation is a commonly encountered pathology in medical practice, and its prevalence has shown a continuous rise over the past years. Atrial fibrillation has a significant impact on patients\u27 quality of life, not only due to the standard anticoagulant treatment with vitamin K antagonists that require close monitoring and dose adjustment, but also due to the fragile equilibrium between hemorrhagic and thrombotic risks. The introduction of new oral anticoagulants (NOACs) in the treatment guidelines for atrial fibrillation has improved the quality of life, as NOACs do not require close monitoring or dose adjustments. However, even if the safety profile of the NOACs regarding the hemorrhagic risk is superior to vitamin K antagonists, the problem raised by an unexpected hemorrhage (e.g. severe hemorrhage after an accident) and the need for efficient hemostasis in a chronic anticoagulated patient has remained unsolved. To find a solution for this problem, reversal agents for NOACs have been developed and tested, and two of them, idarucizumab and andexanet-alpha, have already been approved by the FDA, thus making NOACs increasingly appealing as a choice of anticoagulation treatment

Assessment of I-125 seed implant accuracy when using the live-planning technique for low dose rate prostate brachytherapy

Extent: 9p.Background: Low risk prostate cancers are commonly treated with low dose rate (LDR) brachytherapy involving I-125 seeds. The implementation of a ‘live-planning’ technique at the Royal Adelaide Hospital (RAH) in 2007 enabled the completion of the whole procedure (i.e. scanning, planning and implant) in one sitting. ‘Live-planning’ has the advantage of a more reliable delivery of the planned treatment compared to the ‘traditional pre-plan’ technique (where patient is scanned and planned in the weeks prior to implant). During live planning, the actual implanted needle positions are updated real-time on the treatment planning system and the dosimetry is automatically recalculated. The aim of this investigation was to assess the differences and clinical relevance between the planned dosimetry and the updated real-time implant dosimetry. Methods: A number of 162 patients were included in this dosimetric study. A paired t-test was performed on the D90, V100, V150 and V200 target parameters and the differences between the planned and implanted dose distributions were analysed. Similarly, dosimetric differences for the organs at risk (OAR) were also evaluated. Results: Small differences between the primary dosimetric parameters for the target were found. Still, the incidence of hotspots was increased with approximately 20% for V200. Statistically significant increases were observed in the doses delivered to the OAR between the planned and implanted data; however, these increases were consistently below 3% thus probably without clinical consequences. Conclusions: The current study assessed the accuracy of prostate implants with I-125 seeds when compared to initial plans. The results confirmed the precision of the implant technique which RAH has in place. Nevertheless, geographical misses, anatomical restrictions and needle displacements during implant can have repercussions for centres without live-planning option if dosimetric changes are not taken into consideration.Joshua Moorrees, John M Lawson and Loredana G Marc