Delay in diagnosis of patients with head-and-neck cancer in Canada: impact of patient and provider delay.

Background: Head-and-neck cancers (hncs) often present at an advanced stage, leading to poor outcomes. Late presentation might be attributable to patient delays (reluctance to seek treatment, for instance) or provider delays (misdiagnosis, prolonged wait time for consultation, for example). The objective of the present study was to examine the length and cause of such delays in a Canadian universal health care setting. Methods: Patients presenting for the first time to the hnc multidisciplinary team (mdt) with a biopsy-proven hnc were recruited to this study. Patients completed a survey querying initial symptom presentation, their previous medical appointments, and length of time between appointments. Clinical and demographic data were collected for all patients. Results: The average time for patients to have their first appointment at the mdt clinic was 15.1 months, consisting of 3.9 months for patients to see a health care provider (hcp) for the first time since symptom onset and 10.7 months from first hcp appointment to the mdt clinic. Patients saw an average of 3 hcps before the mdt clinic visit (range: 1-7). No significant differences in time to presentation were found based on stage at presentation or anatomic site. Conclusions: At our tertiary care cancer centre, a patient\u27s clinical pathway to being seen at the mdt clinic shows significant delays, particularly in the time from the first hcp visit to mdt referral. Possible methods to mitigate delay include education about hnc for patients and providers alike, and a more streamlined referral system

Morpholino Gene Knockdown in Adult Fundulus heteroclitus: Role of SGK1 in Seawater Acclimation

The Atlantic killifish (Fundulus heteroclitus) is an environmental sentinel organism used extensively for studies on environmental toxicants and salt (NaCl) homeostasis. Previous research in our laboratory has shown that rapid acclimation of killifish to seawater is mediated by trafficking of CFTR chloride channels from intracellular vesicles to the plasma membrane in the opercular membrane within the first hour in seawater, which enhances chloride secretion into seawater, thereby contributing to salt homeostasis. Acute transition to seawater is also marked by an increase in both mRNA and protein levels of serum glucocorticoid kinase 1 (SGK1) within 15 minutes of transfer. Although the rise in SGK1 in gill and its functional analog, the opercular membrane, after seawater transfer precedes the increase in membrane CFTR, a direct role of SGK1 in elevating membrane CFTR has not been established in vivo. To test the hypothesis that SGK1 mediates the increase in plasma membrane CFTR we designed two functionally different vivo-morpholinos to knock down SGK1 in gill, and developed and validated a vivo-morpholino knock down technique for adult killifish. Injection (intraperitoneal, IP) of the splice blocking SGK1 vivo-morpholino reduced SGK1 mRNA in the gill after transition from fresh to seawater by 66%. The IP injection of the translational blocking and splice blocking vivo-morpholinos reduced gill SGK1 protein abundance in fish transferred from fresh to seawater by 64% and 53%, respectively. Moreover, knock down of SGK1 completely eliminated the seawater induced rise in plasma membrane CFTR, demonstrating that the increase in SGK1 protein is required for the trafficking of CFTR from intracellular vesicles in mitochondrion rich cells to the plasma membrane in the gill during acclimation to seawater. This is the first report of the use of vivo-morpholinos in adult killifish and demonstrates that vivo-morpholinos are a valuable genetic tool for this environmentally relevant model organism

Velocity distributions of sputtered excited atoms

The first direct measurements are reported of the velocity distributions of sputtered atoms in excited states with electronic configurations completely different from the ground state. In contrast to previous work, the measured distributions for both the singlet and triplet metastable D states of Ba atoms showed no energy thresholds and had most probable energies similar to those of sputtered ground-state atoms.Peer reviewedElectrical and Computer Engineerin

Functional and quality of life outcomes after partial glossectomy: a multi-institutional longitudinal study of the head and neck research network

Background: While aggressive treatment for oral cancer may optimize survival, decrements in speech and swallowing function and quality of life often result. This exploratory study investigated how patients recover their communicative function, swallowing ability, and quality of life after primary surgery [with or without adjuvant (chemo) radiation therapy] for tongue cancer over the course of the first year post-operation.Methods: Patients treated for oral cancer at three institutions (University of Alberta Hospital, Mount Sinai Beth Israel Medical Center, and Turku University Hospital) were administered patient-reported outcomes assessing speech [Speech Handicap Index (SHI)], swallowing [(M.D. Anderson Dysphagia Inventory (MDADI)] and quality of life [European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module (EORTC-H&N35)]. Outcome measures were completed pre-operatively and at 1-, 6-, and 12-months post-operatively.Results: One hundred and seventeen patients undergoing partial glossectomy with reconstruction participated in this study. Results indicated no significant differences in swallowing function (MDADI and EORTC-H& N35 subscales) between baseline and 6 months post-surgery and no significant differences in speech function (SHI subscales) between baseline and 1 year post-surgery. Most quality of life domains (EORTC-H& N35 subscales) returned to baseline levels by 1 year post-operation, while difficulties with dry mouth and sticky saliva persisted. A clear time trend of adjuvant (chemo) radiation therapy negatively affecting dry mouth scores over time was identified in this study, while negative independent effects of chemoradiation on MDADI swallowing, and EORTC-H& N35 swallowing, eating, and opening mouth subscales were found.Conclusions: Assessment time influenced patient-reported speech, swallowing, and quality of life outcomes, while treatment (by time) effects were found for only swallowing and quality of life outcomes. Results of the present study will help guide clinical care and will be useful for patient counseling on expected short and long-term functional and quality of life outcomes of surgical and adjuvant treatment for oral cavity cancer

The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review.

BACKGROUND: The management of articular cartilage defects presents many clinical challenges due to its avascular, aneural and alymphatic nature. Bone marrow stimulation techniques, such as microfracture, are the most frequently used method in clinical practice however the resulting mixed fibrocartilage tissue which is inferior to native hyaline cartilage. Other methods have shown promise but are far from perfect. There is an unmet need and growing interest in regenerative medicine and tissue engineering to improve the outcome for patients requiring cartilage repair. Many published reviews on cartilage repair only list human clinical trials, underestimating the wealth of basic sciences and animal studies that are precursors to future research. We therefore set out to perform a systematic review of the literature to assess the translation of stem cell therapy to explore what research had been carried out at each of the stages of translation from bench-top (in vitro), animal (pre-clinical) and human studies (clinical) and assemble an evidence-based cascade for the responsible introduction of stem cell therapy for cartilage defects. This review was conducted in accordance to PRISMA guidelines using CINHAL, MEDLINE, EMBASE, Scopus and Web of Knowledge databases from 1st January 1900 to 30th June 2015. In total, there were 2880 studies identified of which 252 studies were included for analysis (100 articles for in vitro studies, 111 studies for animal studies; and 31 studies for human studies). There was a huge variance in cell source in pre-clinical studies both of terms of animal used, location of harvest (fat, marrow, blood or synovium) and allogeneicity. The use of scaffolds, growth factors, number of cell passages and number of cells used was hugely heterogeneous. SHORT CONCLUSIONS: This review offers a comprehensive assessment of the evidence behind the translation of basic science to the clinical practice of cartilage repair. It has revealed a lack of connectivity between the in vitro, pre-clinical and human data and a patchwork quilt of synergistic evidence. Drivers for progress in this space are largely driven by patient demand, surgeon inquisition and a regulatory framework that is learning at the same pace as new developments take place

Experimental – Numerical Analysis of Stress State in Front of the Crack Tip of Modified and Unmodified G17CrMo5-5 Cast Steel by Rare Earth Metals in a Brittle-Ductile Transition Region

In the paper presented experimental data and numerical analysis of stress distribution in front of the crack of two melts of low-alloy G17CrMo5-5 cast steel-modified (M) by rare earth metals and original, unmodified (UM) in the temperature range, according to the brittle-ductile transition region. Experimental tests include determination of the tensile properties and fracture toughness characteristics for the UM and M cast steel. Numerical analysis includes determination of stress distribution in front of the crack at the initial moment of the crack extension. In the numerical computations, experimentally tested specimens SEN(B) were modeled. The true stress-strain curves for the UM and M cast steel were used in the calculation. It was shown that the maximum of the opening stresses at the initial moment of the crack extension occurs in the axis of the specimens and reaches similar level of about 3.5σ0 for both UM and M cast steel. However, the length of the critical distance, measured for stress level equal 3σ0, is great for the M in comparison to the UM cast steel. Also was shown that the UM cast steel increased the level of the stress state triaxiality parameters that resulted in a decrease of fracture toughness