Advances in testing for human papillomavirus-mediated head and neck cancer

Purpose of review New evidence has recently emerged regarding the utility and benefits of dual p16INKa (p16) and Human papillomavirus (HPV) status testing when determining the diagnosis and prognosis of patients with oropharyngeal cancer. Recent findings HPV RNA polymerase chain reaction (PCR) is the most accurate diagnostic test. The other assays (HPV DNA PCR, HPV DNA/RNA in-situ hybridization (ISH) and p16) applied to formalin fixed tumour tissue have varying but high sensitivities and specificities. Dual p16 and HPV testing identifies discordant (p16+/HPV- or p16-/HPV+) results in 9.2% of cases, who have significantly poorer prognoses than p16+/HPV+, particularly in smokers. The proportion of discordant cases varies by region, and appears to be highest in regions with lowest attributable (p16+/HPV+) fractions. Dual testing improves prognostication for oropharyngeal cancer cases by identifying discordant cases and improving the prognostic power of the Tumour Node Metastasis (TNM) classification, especially in regions with high discordant rates. Summary Dual testing is essential when considering patients for clinical trials of treatment de-escalation, and may be important when counselling patients on prognosis, especially in regions with high discordant rates and in smokers

Advances in testing for human papillomavirus-mediated head and neck cancer

PURPOSE OF REVIEW: New evidence has recently emerged regarding the utility and benefits of dual p16 INKa (p16) and Human papillomavirus (HPV) status testing when determining the diagnosis and prognosis of patients with oropharyngeal cancer.RECENT FINDINGS: HPV RNA polymerase chain reaction (PCR) is the most accurate diagnostic test. The other assays (HPV DNA PCR, HPV DNA/RNA in-situ hybridization (ISH) and p16) applied to formalin fixed tumour tissue have varying but high sensitivities and specificities. Dual p16 and HPV testing identifies discordant (p16+/HPV- or p16-/HPV+) results in 9.2% of cases, who have significantly poorer prognoses than p16+/HPV+, particularly in smokers. The proportion of discordant cases varies by region, and appears to be highest in regions with lowest attributable (p16+/HPV+) fractions. Dual testing improves prognostication for oropharyngeal cancer cases by identifying discordant cases and improving the prognostic power of the Tumour Node Metastasis (TNM) classification, especially in regions with high discordant rates.SUMMARY: Dual testing is essential when considering patients for clinical trials of treatment de-escalation, and may be important when counselling patients on prognosis, especially in regions with high discordant rates and in smokers.</p

Average transmission probability of a random stack

The transmission through a stack of identical slabs that are separated by gaps with random widths is usually treated by calculating the average of the logarithm of the transmission probability. We show how to calculate the average of the transmission probability itself with the aid of a recurrence relation and derive analytical upper and lower bounds. The upper bound, when used as an approximation for the transmission probability, is unreasonably good and we conjecture that it is asymptotically exact.Comment: 10 pages, 6 figure

Vertikale Höhe des Nasenbodens in Vergleich zu Basion

Die Datenerhebung erfolgte anhand von zwei Untersuchungsgruppen. Es wurde eine Querschnittsstudie anhand der Marburger Schädelsammlung, bestehend aus 236 Schädeln ausgewertet. Die Datenerfassung erfolgte mit Hilfe einer speziellen Messgabel. Außerdem wurden im Rahmen einer Longitudinalstudie insgesamt 1536 FRS-Durchzeichnungen von holländischen Kindern ausgewertet. Ergebnisse 1. Die im Rahmen dieser Studie durchgeführten Messungen ergaben, dass sich die Lage des harten Gaumens gegenüber dem Punkt Basion in der Vertikalen während des Wachstums nur um 3 mm ändert. Diese Erkenntnis hat Einfluss auf skelettale Funktionstherapien, die darauf abzielen, das vertikale Wachstum der Maxilla auszunutzen. 2. Durch Interpolation der Rohdaten und trigonometrische Berechnungen konnte das Wachstum des harten Gaumens genauer untersucht werden und eine Aussage über den Einfluss der Rotation auf die gemessene Strecke gemacht werden. Die Interpolation ermöglichte außerdem, eine genauere Aussage über die individuelle Zunahme der untersuchten Strecke zu machen, die ohne diese nicht angegeben werden kann. Nur so konnte gezeigt werden, dass das vertikale Wachstum bei den Jungen größer ist. Dieses Berechnungsverfahren kann auch für andere Wachstumsanalysen verwendet werden. 3. Die trigonometrischen Berechnungen ergaben, dass Spina nasalis posterior konstanter ist, als Spina nasalis anterior. Spina nasalis anterior kann seine Lage sogar nach kranial ändern. Dies vergrößert die gemessene Strecke zusätzlich

Association between Hashimoto's Thyroiditis and Thyroid Cancer in 64,628 Patients

BACKGROUND: The incidence of thyroid cancer (TC) is increasing although explanatory causes are lacking. A link between cancer and inflammation is well documented but unclear for autoimmune thyroid diseases and TC. We aimed to systematically review the association between Hashimoto’s thyroiditis (HT) and papillary, follicular, medullary, anaplastic thyroid carcinoma, and thyroid lymphoma (TL). METHODS: PubMed, OVID Medline, Google Scholar, and the Cochrane Library were searched from 1955 to 2016. The inclusion criteria were age >18 years, ≥20 cases of HT or TC. We collectively examined the incidence of HT in TC and of TC in HT. RESULTS: We identified 36 studies (64,628 subjects) published between 1955 and 2016 from 13 countries. We found a relative risk (RR) of HT among papillary thyroid cancer (PTC) of 2.36 [95% confidence intervals (CIs) 1.55–3.29, p < 0.001], an RR of PTC among HT of 1.40 (95% CI 1.07–1.85, p = 0.016), and an RR of TL among HT of 9.74 (95% CI 3.93–24.13, p < 0.001). CONCLUSION: We report an association between HT and PTC and between HT and TL. No association was found between HT and follicular, medullary, or anaplastic thyroid cancer

Development of a Marslander with crushable shock absorber by virtual and experimental testing

Since the beginning of space exploration, probes have been sent to other planets or moons with the associated challenge of landing on these bodies. For a soft landing several damping methods like landing legs or airbags have been used. A new and potentially less complex and lighter way to reduce the shock loads at touchdown is the use of a crushable shield underneath the lander platform. This crushable shield could be made for example out of an energy absorbing materials like an aluminum honeycomb core with a High Performance Polyethylene cover sheet. The design is particularly advantageous since no moving parts nor other mechanisms are required, thus making the shield very robust and fail safe. The only mission that is currently planned to use this technique is the ESA-mission “ExoMars” which is planned to start in 2016. The development of such a crushable shock absorber implies and requires assessment of materials, manufacturing processes, the setup of a numerical simulation and the experimental validation in a test lab. In an independent research project (Marslander1) a representative engineering mockup of the landing platform has been build and tested at the Landing & Mobility Test Facility (LAMA) to support the numerical simulation model with experimental data. The simulations are based on the explicit Finite Element Method, which discretizes the structure into a defined number of elements, such that each element is assigned a set of equations describing the material properties and applied loads. The goal is to generate a simplified but still accurate model to predict landing scenarios by running Monte Carlo simulations. Results of the above stated development and testing processes will be presented and discussed in this paper

Decoy oligodeoxynucleotide againstactivator protein-1 reducesneointimal proliferation after coronaryangioplasty in hypercholesterolemic minipigs

AbstractObjectivesWe sought to demonstrate, in an appropriate animal model, that co-medication with a transcription factor-blocking agent limits restenosis after percutaneous transluminal coronary angioplasty (PTCA).BackgroundEnhanced synthesis in the vessel wall of endothelin-1 (ET-1), a powerful co-mitogen for vascular smooth muscle cells, appears to be one mechanism that promotes restenosis after PTCA. Deformation-induced expression of prepro-ET-1 is governed by the transcription factor, activator protein-1 (AP-1).MethodsAn anti-AP-1 decoy oligodeoxynucleotide (dODN) strategy was devised in which the dODN-containing solution (20 nmol) was administered locally through a Dispatch catheter into the coronary arteries of hypercholesterolemic minipigs at the time of PTCA (AVE-GFX stent).ResultsTreatment with an AP-1 dODN, mimicking the consensus binding site of the transcription factor, significantly reduced neointimal formation in the coronary arteries of hypercholesterolemic minipigs (n = 10 to 12), compared with vehicle-treated coronary arteries, after four weeks of follow-up (neointimal area 2.64 ± 0.33 vs. 4.81 ± 1.04 mm2[mean ± SEM]; p < 0.05). This effect was maintained after eight weeks (neointimal area 2.04 ± 0.22 mm2; n = 3) and correlated with a reduction in both nuclear translocation of AP-1 and ET-1 synthesis in the vessel wall 48 h after PTCA (n = 4). In contrast, an AP-1 mutant dODN, to which the transcription factor does not bind, showed no effect on neointimal formation at either time point (n = 3 to 7). Moreover, a consensus dODN directed against CCAAT/enhancer binding protein (C/EBP), another deformation-sensitive transcription factor, did not significantly affect neointimal formation after four weeks (n = 3).ConclusionsThese findings demonstrate the feasibility, efficacy and specificity of the anti-AP-1 dODN approach to the treatment of restenosis, which principally but not exclusively targets deformation-induced ET-1 synthesis in the vessel wall. Provided that these findings can be extrapolated to the situation of patients with coronary artery disease, the observed extent of the inhibitory effect of the AP-1 dODN treatment suggests that this co-medication may greatly reduce the incidence of in-stent restenosis

Impact of Low-Dose Dronabinol Therapy on Cognitive Function in Cancer Patients Receiving Palliative Care: A Case-Series Intervention Study

BACKGROUND: Cannabis may offer therapeutic benefits to patients with advanced cancer not responding adequately to conventional palliative treatment. However, tolerability is a major concern. Cognitive function is a potential adverse reaction to tetrahydrocannabinol containing regimens. The aim of this study was to test cognitive function in patients being prescribed dronabinol as an adjuvant palliative therapy.METHODS: Adult patients with advanced cancer and severe related pain refractory to conventional palliative treatment were included in this case-series study. Patients were examined at baseline in conjunction with initiation of dronabinol therapy and at a two-week follow-up using three selected Wechsler's adult intelligence scale III neurocognitive tests: Processing Speed Index (PSI), Perceptual Organization Index (POI), and Working Memory Index (WMI). Patients were also assessed using pain visual analog scale, Major Depression Inventory, and Brief Fatigue Inventory.RESULTS: Eight patients consented to take part in the study. Two patients discontinued dronabinol therapy, one due to a complaint of dizziness and another critical progression of cancer disease, respectively. The remaining six patients were successfully treated with a daily dosage of 12.5 mg dronabinol (p = 0.039). PSI (p = 0.020), POI (p = 0.034.), and WMI (p = 0.039).CONCLUSIONS: Cognitive function improved in this group of patients with advanced cancer in conjunction with low-dose dronabinol therapy. The cause is likely multifactorial including reported relief of cancer-associated symptoms. Further clinical investigation is required.</p