Feasibility of recruitment to an oral dysplasia trial in the United Kingdom

Background: Oral epithelial dysplasia (OED) has a malignant potential. Therapeutic options for OED remain both limited and without good evidence. Despite surgery being the most common method of treating OED, recurrence and potentially significant morbidity remain problematic. Consequently, there has been much interest in non-surgical treatments for OED. Cyclo-oxygenase (COX) up-regulation is known to occur in the dysplasia-carcinoma sequence and evidence now exists that COX-2 is a prognostic marker of malignant transformation in OED. COX-inhibitors are therefore considered a potential therapeutic strategy for treating this condition. We aimed to provide both proof of principal evidence supporting the effect of topical COX inhibition, and determine the feasibility of recruitment to an OED chemoprevention trial in the UK. Methods: Recruitment of 40 patients with oral leukoplakia to 4 study arms was planned. The total daily dose of Aspirin would increase in each group and be used in the period between initial diagnostic and follow-up biopsies. Results: During the 15-month recruitment period, 15/50 screened patients were eligible for recruitment, and 13 (87%) consented. Only 1 had OED diagnosed on biopsy. 16 patients were intolerant of, or already taking Aspirin and 16 patients required no biopsy. Initial recruitment was slow, as detection relied on clinicians identifying potentially eligible patients. Pre-screening new patient letters and directly contacting patients listed for biopsies improved screening of potentially eligible patients. However, as the incidence of OED was so low, it had little impact on trial recruitment. The trial was terminated, as recruitment was unlikely to be achieved in a single centre. Conclusion: This feasibility trial has demonstrated the low incidence of OED in the UK and the difficulties in conducting a study because of this. With an incidence of around 1.5/100,000/year and a high proportion of those patients already taking or intolerant of Aspirin, a large multi-centred trial would be required to fulfil the recruitment for this study. The ability of topical non-steroidal anti-inflammatory drugs to modify COX and prostaglandin expression remains an important but unanswered question. Collaboration with centres in other parts of the world with higher incidences of the disease may be required to ensure adequate recruitment. ISRCTN: 31503555

Proučavanje optičkih vlakana sa skokovitim indeksima loma interferometrijskom metodom s dva snopa

The Pluta polarizing interference microscope is used to measure the refractive index profile and material dispersion of step index optical fibers. The refractive index profile of the fiber has been determined experimentally at different wavelengths using two-beam interference technique. Measuring these values at different wavelengths gives useful information about the structural behavior of highly oriented fibers. Also, the theoretical consideration for determining the refractive index is given. Some optical parameters which characterize the optical fiber such as the numerical aperture NA, normalized frequency ν, the acceptance angle θa and the number of modes MN propagating in the fiber with wavelength have been calculated. Also, the constants of the Cauchy’s dispersion formula were determined.Primijenili smo Plutinov polarizacijski interferometrijski mikroskop u mjerenjima profila indeksa loma i disperzije materijala optičkih vlakana sa skokovitim indeksima loma. Mjerili smo profil indeksa vlakna za više valnih duljina primjenom interferentne metode s dva snopa. Ta mjerenja na više valnih duljina dala su važne podatke o strukturnim svojstvima jako usmjerenih vlakana. Opisuju se također osnove teorije za određivanje indeksa loma u vlaknima. Izračunali smo niz optičkih parametara koji su značajke optičkih vlakana: brojnog otvora, normalizirane frekvencije, ν, kuta prihvaćanja, θa, i broja modova, MN , kojima se na nekoj frekvenciji šire valovi. Također smo odredili konstante Cauchyjeve disperzijske formule

Proučavanje optičkih vlakana sa skokovitim indeksima loma interferometrijskom metodom s dva snopa

The Pluta polarizing interference microscope is used to measure the refractive index profile and material dispersion of step index optical fibers. The refractive index profile of the fiber has been determined experimentally at different wavelengths using two-beam interference technique. Measuring these values at different wavelengths gives useful information about the structural behavior of highly oriented fibers. Also, the theoretical consideration for determining the refractive index is given. Some optical parameters which characterize the optical fiber such as the numerical aperture NA, normalized frequency ν, the acceptance angle θa and the number of modes MN propagating in the fiber with wavelength have been calculated. Also, the constants of the Cauchy’s dispersion formula were determined.Primijenili smo Plutinov polarizacijski interferometrijski mikroskop u mjerenjima profila indeksa loma i disperzije materijala optičkih vlakana sa skokovitim indeksima loma. Mjerili smo profil indeksa vlakna za više valnih duljina primjenom interferentne metode s dva snopa. Ta mjerenja na više valnih duljina dala su važne podatke o strukturnim svojstvima jako usmjerenih vlakana. Opisuju se također osnove teorije za određivanje indeksa loma u vlaknima. Izračunali smo niz optičkih parametara koji su značajke optičkih vlakana: brojnog otvora, normalizirane frekvencije, ν, kuta prihvaćanja, θa, i broja modova, MN , kojima se na nekoj frekvenciji šire valovi. Također smo odredili konstante Cauchyjeve disperzijske formule

Biochemical Characterisation of pre-Replicative Complex Architecture

Pre-replicative complexes (pre-RCs), containing the helicase Mcm2-7, are assembled on origins of replication during G1 phase of the cell cycle. This ‘licenses’ origins for subsequent activation during S-phase. The loading of the Mcm2-7 complex requires ATP hydrolysis and the licensing factors ORC, Cdc6 and Cdt1, and results in the assembly of a head-to-head double hexamer of Mcm2-7 bound around duplex DNA. To understand how the Mcm2-7 complex is loaded into a double hexamer, we need a better understanding of the stoichiometry and positioning of licensing factors relative to each other during pre-RC assembly. To address this, I used a tagging and immunoaffinity purification strategy. For this purpose, I generated purified protein preparations where subunits of the licensing proteins were fused to either a 9x Myc or a 3x FLAG tag. These proteins were tested for their ability to support loading of the Mcm2-7 complex in vitro. I used the tagged proteins in an established in vitro pre-RC assembly assay coupled with an immunoaffinity purification approach. I found that in the absence of ATP hydrolysis, one molecule each of ORC, Cdc6 and Cdt1 recruit a single Mcm2- 7 hexamer to origin DNA. Using an ATPase mutant, I showed that ATP hydrolysis by Cdc6 is not required for Mcm2-7 double hexamer formation. I found that a conserved C-terminal region of Mcm3 is critical for Mcm2-7 recruitment to ORCCdc6- DNA. Mutations in this C-terminal domain were lethal in vivo and inhibited Mcm2-7 loading onto origin DNA in vitro. I used the tagged proteins coupled with crosslinking and denaturing immunoaffinity purifications and found that Mcm3 interacts with Orc2 and Cdc6 during Mcm2-7/Cdt1 recruitment to ORC-Cdc6-DNA. The results of this thesis suggest that Mcm2-7 is recruited to origin DNA via Mcm3 interaction with Orc2 and Cdc6 and that the Mcm2-7 hexamers are loaded in a sequential manner

Células Germinativas E Espermatogênese Do Lagarto Tropidurus Torquatus (tropiduridae) De Uma área Urbana No Bioma Cerrado Do Centro-oeste Brasileiro

Tropidurus comprises a Neotropical genus of lizard that currently has about 30 species widely distributed in the South American. Among these species, Tropidurus torquatus, which has the characteristic of great physiological plasticity, occupying a variety of habitats in open areas and urbanized environments. Considering this, the aim of the study was to investigate the germinative cells and spermatogenesis of a population of T. torquatus in an urban area under Cerrado Biome influences to understand how to establish the temporal development of germinative cells and spermatogenesis during a period of one year. Individuals were obtained in the Zoological Collection of Vertebrates at the Universidade Federal de Mato Grosso (UFMT), and the germinative cells and full spermatogenesis were described with light microscopy. Tropidurus torquatus presented germ cells with similar characteristics already documented for the other species of lizards and reptiles. Spermatogonia type A and B, primary and secondary spermatocytes, and spermatids were present in almost all months evaluated. The gonadosomatic ratio presented its highest value in October, moment in which spermatogenesis presented all the germinative cells and spermatozoa in the lumen, of the seminiferous tubules. In the seasonal climate of the Cerrado Biome, we observe discontinuous spermatogenesis in T. torquatus with the production of spermatozoa in almost every month of the year, however with sperm storage in the epididymis during the phase of testicular regression. © 2016, Universidade Federal de Uberlandia. All rights reserved.3261595160

Biochemical markers as diagnostic/prognostic indicators for ischemic disease

Objective: The use of a biomarker was extremely useful in clinical emergencies such as stroke to aid in triage and early management of cases. The diagnostic accuracy of laboratory biomarkers is run to approve the identification of easy, cheap and fast tests associated with cerebral ischemia and intracranial hemorrhage. The present study was designed to screen serum enolase activity, activities of CK-BB, LDH and lipid profile in patients with ischemic or related diseases as good diagnostic/ prognostic indicator for ischemic diseases. Methods: Sixty male subjects in the age range of (45 ±2years) were divided into four groups each with 15 participants: Group (I) normal . Group (II) patients recently diagnosed as ischemic disease; Group (III) hypertensive patients and Group (IV); diabetic patients enolase activity (p<0.001) and CK-BB (p<0.01) in ischemic and hypertensive patients compared with control and diabetic groups. LDH level was significantly elevated in ischemic, hypertensive and diabetic patients compared with controls (p<0.001). The cut -off value for serum enolase was 62.5 nmol/l showing 90% sensitivity and 93% specificity for differentiation of ischemic disease. Positive correlations were observed between serum enolase (r = 0.56), and CK-BB (r = 0.53). Conclusion: Serum enolase can be considered as a more sensitive and specific marker and used as a sensitive diagnostic or prognostic marker for ischemic related diseases.Keywords: Serum enolase, ischemia, hypertension, diagnosis, prognostic

Recurrent head and neck cancer:United Kingdom national multidisciplinary guidelines

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. Recurrent cancers present some of the most challenging management issues in head and neck surgical and oncological practice. This is rendered even more complex by the poor evidence base to support management options, the substantial implications that treatments can have on the function and quality of life, and the difficult decision-making considerations for supportive care alone. This paper provides consensus recommendations on the management of recurrent head and neck cancer. RECOMMENDATIONS: • Consider baseline and serial scanning with computed tomography and/or magnetic resonance (CT and/or MR) to detect recurrence in high-risk patients. (R) • Patients with head and neck cancer recurrence being considered for active curative treatment should undergo assessment by positron emission tomography combined with computed tomography (PET–CT) scan. (R) • Patients with recurrence should be assessed systematically by a team experienced in the range of management options available for recurrence including surgical salvage, re-irradiation, chemotherapy and palliative care. (R) • Management of patients with laryngeal recurrence should include input from surgeons with experience in transoral surgery and partial laryngectomy for recurrence. (G) • Expertise in transoral surgery and partial laryngectomy for recurrence should be concentrated to a few surgeons within each multidisciplinary teams. (G) • Transoral or open partial laryngectomy should be offered as definitive treatment modality for highly-selected patients with recurrent laryngeal cancer. (R) • Patients with OPC recurrence should have p16 human papilloma virus status assessed. (R) • Patients with OPC recurrence should be considered for salvage surgical treatment by an experienced team, with reconstructive expertise input. (G) • Transoral surgery appears to be an effective alternative to open surgery for the management of OPC recurrence in carefully selected patients. (R) • Consider elective selective neck dissections in patients with recurrent primaries with N0 necks, especially in advanced cases. (R) • Selective neck dissection (with preservation of nodal levels, especially level V, that are not involved by disease) in patients with nodal (N+) recurrence appears to be as effective as modified or radical neck dissections. (R) • Use salivary bypass tubes following salvage laryngectomy. (R) • Use interposition muscle-only pectoralis major or free flap for suture line reinforcement if performing primary closure following salvage laryngectomy. (R) • Use inlaid pedicled or free flap to close wound if there is tension at the anastomosis following laryngectomy. (R) • Perform secondary puncture in post chemoradiotherapy laryngectomy patients. (R) • Triple therapy with platinum, cetuximab and 5-fluorouracil (5-FU) appears to provide the best outcomes for the management of patients with recurrence who have a good performance status and are fit to receive it. If not fit, then combinations of platinum and cetuximab or platinum and 5-FU may be considered. (R) • Patients with non-resectable recurrent disease should be offered the opportunity to participate in phases I–III clinical trials of new therapeutic agents. (R) • Chemo re-irradiation appears to improve locoregional control, and may have some benefit for overall survival, at the risk of considerable acute and late toxicity. Benefit must be weighed carefully against risks, and patients must be counselled appropriately. (R) • Target volumes should be kept tight and elective nodal irradiation should be avoided. (R) • Best supportive care should be offered routinely as part of the management package of all patients with recurrent cancer even in the case of those who are being treated curatively. (R

Study on the Influence of Polymer/Particle Properties on the Resilience of Superhydrophobic Coatings.

Enhancement in the resilience of superhydrophobic coatings is crucial for their future applicability. However, the progress in this aspect is currently limited due to the lack of a consistent resilience analysis methodology/protocol as well as the limited understanding of the influence of the materials components on the resultant coating performance. This study applies a quantitative analysis methodology involving image analysis and mass tracking and utilizes it to investigate how the properties of coating components can influence coating resilience. The factors examined were changing the molecular weight/tensile strength of poly(vinylchloride)/poly(dimethylsiloxane) (PVC/PDMS) polymers and changing the size of the roughening particles. In addition to the examination of resilience data to evaluate degradation patterns, three-dimensional (3D) mapping of the scratches was performed to obtain an insight into how material removal occurs during abrasion. The results can indicate preferential polymer selection (using higher-molecular-weight polymers for PVC) and optimal particle sizes (smaller particles) for maximizing coating resilience. The study, although focused on superhydrophobic materials, demonstrates wide applicability to a range of areas, particularly those focused on the development of high-strength coatings

Concurrent cisplatin or cetuximab with radiotherapy for HPV-positive oropharyngeal cancer : Medical resource use, costs, and quality-adjusted survival from the De-ESCALaTE HPV trial

Background The De-ESCALaTE HPV trial confirmed the dominance of cisplatin over cetuximab for tumour control in patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC). Here, we present the analysis of health-related quality of life (HRQoL), resource use, and health care costs in the trial, as well as complete 2-year survival and recurrence. Materials and methods Resource use and HRQoL data were collected at intervals from the baseline to 24 months post treatment (PT). Health care costs were estimated using UK-based unit costs. Missing data were imputed. Differences in mean EQ-5D-5L utility index and adjusted cumulative quality-adjusted life years (QALYs) were compared using the Wilcoxon signed-rank test and linear regression, respectively. Mean resource usage and costs were compared through two-sample t-tests. Results 334 patients were randomised to cisplatin (n = 166) or cetuximab (n = 168). Two-year overall survival (97·5% vs 90·0%, HR: 3.268 [95% CI 1·451 to 7·359], p = 0·0251) and recurrence rates (6·4% vs 16·0%, HR: 2·67 [1·38 to 5·15]; p = 0·0024) favoured cisplatin. No significant differences in EQ-5D-5L utility scores were detected at any time point. At 24 months PT, mean difference was 0·107 QALYs in favour of cisplatin (95% CI: 0·186 to 0·029, p = 0·007) driven by the mortality difference. Health care costs were similar across all categories except the procurement cost and delivery of the systemic agent, with cetuximab significantly more expensive than cisplatin (£7779 [P < 0.001]). Consequently, total costs at 24 months PT averaged £13517 (SE: £345) per patient for cisplatin and £21064 (SE: £400) for cetuximab (mean difference £7547 [95% CI: £6512 to £8582]). Conclusions Cisplatin chemoradiotherapy provided more QALYs and was less costly than cetuximab bioradiotherapy, remaining standard of care for nonsurgical treatment of HPV-positive OPSCC