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Background Purpose Methods Findings Conclusions Effective youth sport coaching encompasses the promotion of personal, social, and athletic skills in a deliberate and consistent manner. Coach training protocols that highlight coaches’ best-practices that promote development emphasize the role of the coach as either a developer of athletes’ personal and social potential or as a developer of athletic talent (focusing on techniques and tactics of sport). However, there is a scarcity of literature describing how to train practitioners for this combined role.The purpose of this study was to develop and examine coaches’ experiences in coach training that teaches personal and social development, as well as fundamental movement skills called Coach as a Youth Development Specialist (CAYDS). This was conducted in two phases. First, a pilot study aimed to develop, deliver, and evaluate a coach training curriculum that addressed the needs of youth coaches to improve and finalize the CAYDS curriculum. Second, the final iteration of CAYDS was implemented to examine coaches’ lived experiences while participating in the training.The pilot phase involved five-module training delivered to five graduate students. Thematic analysis was used to analyze a focus group interview and understand what participants learned and how the training helped. The results led to a final version of the CAYDS training. In its final version, the training had seven modules that were delivered to a new cohort of six participants. Hermeneutic phenomenology guided the understanding of the what and how of participating coaches’ lived experiences in the CAYDS training. Data were collected using journal reflections, a focus group interview, and individual interviews; and thematically analyzed.The training successfully helped coaches perform coaching competencies, skills, and behaviors identified in the CAYDS framework (cf. Hellison, D. 2011. Teaching Personal and Social Responsibility Through Physical Activity. 3rd ed. Champaign: Human Kinetics; CCE, ASOIF & LMU. 2013. International Sport Coaching Framework v1.2. Champaign: Human Kinetics; SHAPE America. 2019. National Standards for Sport Coaches. 3rd ed. https://www.shapeamerica.org/standards/coaching/default.aspx) that foster personal, social, and athletic development for youth. Findings from this study provide evidence in support of andragogical approaches that helped coaches learn interpersonal, intrapersonal, and professional knowledge (Côté, J., and W. Gilbert. 2009. “An Integrative Definition of Coaching Effectiveness and Expertise.” International Journal of Sports Science & Coaching 4 (3): 307–323.). Participants built positive relationships with community stakeholders and activities involving outreach to parents/guardians, attending school events, and coach educators’ use of role-play were perceived to be particularly impactful. This study also found the process of learning to teach youth skills related to personal and social development inspired coaches to be more self-aware and motivated to grow personally and act in ways that are aligned with TPSR values. Finally, coaches perceived to have acquired professional knowledge that contributed to their ability to instruct fundamental movement skills for athletic development.The CAYDS framework offers a viable mechanism to support the dual-role youth sport coaches serve as development specialists, while also parting with coach-centered professional models of coaching. Further, there is promise for this type of development-supportive coaching approach to be applied when working with athletes in their late adolescent years situated in high performance contexts. [ABSTRACT FROM AUTHOR]

(1) Background: The radial forearm flap (RFF) has evolved as the flap of choice for intraoral mucosal reconstructions, providing thin and pliable skin with a safe blood supply. Perforator flaps such as the anterolateral thigh (ALT) flap are increasingly being discussed for the same applications. (2) Methods: Patient history, treatment details, and outcome of 12 patents with moderate to extended defects of the lip and/or nose area that were reconstructed by a folded radial forearm flap were retrospectively evaluated for oncologic and functional outcomes. (3) Results: The mean oncologic and functional follow-up were 21.1 (min. 3.8; max. 83.3) and 31.2 (min. 6; max. 96) months, respectively. All flaps survived without revision. In eight cases, major lip defects were reconstructed by an RFF; in six patients, the palmaris longus tendon was included for lip suspension. The functional results in terms of eating, drinking, and mouth opening were good in five cases, while three patients were graded as fair due to moderate drooling. In seven cases, the major parts of the nose were reconstructed with two good and five fair (nostril constriction in three cases) functional results. (4) Conclusions: The folded RFF remains a unique free flap option for complex three-dimensional lip and nose reconstructions in terms of flexibility, versatility, and robustness. [ABSTRACT FROM AUTHOR]

Simple Summary: In recent years, checkpoint inhibitor treatment of tumors has caused a stir. The response of patients with metastases showed outstanding success for some cancer types. However, many tumor types develop resistance strategies to evade this therapeutic application. This review provides an overview of the potential and broader treatment options that have emerged in recent years with immune checkpoint inhibition (ICI) treatment. Here, a major focus is placed on treatment with ICIs and combination therapies for head and neck tumors. This review offers a comprehensive overview of clinical trials for ICI (combination) therapies in advanced stages, as well as clinical trials in their early stages for head and neck tumors. Recently, considerable progress has been achieved in cancer immunotherapy. Targeted immune checkpoint therapies have been established for several forms of cancers, which resulted in a tremendous positive impact on patient survival, even in more advanced tumor stages. With a better understanding of cellular responses to immune checkpoint therapies, it will soon be feasible to find targeted compounds which will make personalized medicine practicable. This is a great opportunity, but it also sets tremendous challenges on both the scientific and clinical aspects. Head and neck tumors evade immune surveillance through various mechanisms. They contain fewer lymphocytes (natural killer cells) than normal tissue with an accumulation of immunosuppressive regulatory T cells. Standard therapies for HNSCC, such as surgery, radiation, and chemotherapy, are becoming more advantageous by targeting immune checkpoints and employing combination therapies. The purpose of this review is to provide an overview of the expanded therapeutic options, particularly the combination of immune checkpoint inhibition with various conventional and novel therapeutics for head and neck tumor patients. [ABSTRACT FROM AUTHOR]

Purpose: Prospectively collected outcome data of patients (pts) whose adjuvant systemic therapy recommendation was based on the clinico-molecular test EndoPredict® (EP) are presented. Methods: Pts with ER-positive, HER2-negative early breast cancer with 0–3 positive lymph nodes were enrolled. The EP was carried out on all tumor samples. Pts were evaluated for treatment compliance, local recurrence, distant metastases and overall survival. Censored time-to-event outcomes were analysed by Cox proportional hazards models. Additional estimates of the event-free-survival were calculated by the Kaplan–Meier method. Hypothesis testing was conducted on two-sided exploratory 5% significance levels. Results: 373 consecutive pts were enrolled. EP classified 238 pts (63.8%) as low risk and 135 pts (36.2%) as high risk. Median follow-up was 41.6 months. Risk for disease recurrence or death in EPclin high-risk patients was twofold higher in comparison with EPclin low-risk patients (hazard ratio (HR) 2.05 (95% CI 0.85–4.96; p = 0.110). Patients with EPclin high risk were at significant higher risk of distant metastases than patients with EPclin low risk (HR 5.18; 95% CI 1.04–25.74; p = 0.0443). EPclin high-risk patients who actually underwent adjuvant CTX had a 3-year-DFS of 96.3% (95% CI 92.2–100) in contrast to EPclin high-risk patients without CTX (3-year-DFS: 91.5% (95% CI 82.7–100%); HR 0.32; 95% CI 0.10–1.05; p = 0.061). Conclusion: These first prospective outcome results show that EP, in clinical routine, is a valid clinico-molecular test, to predict DFS and to guide decision of adjuvant CTX use in ER-positive, HER2-negative early breast cancer pts with 0–3 positive lymph nodes. Adjuvant CTX seems to be beneficial for EPclin high-risk patients. [ABSTRACT FROM AUTHOR]

Objectives: Definition of implant success is unclear in prosthetic implant-based rehabilitation of head neck cancer patients. Materials and methods: Fifty-two patients with 309 inserted implants were included in this prospective observational study. Implant survival (in situ and loaded) and implant success (modified Albrektsson criteria) at 2-year follow-up were evaluated under the influence of patient- and implant-specific variables. Results: Thirty-nine patients with 234 implants finished the study. Overall implant survival after 2 years was 92.3% (216/234) with an osseointegration rate of 94% (220/234). Implant success was 78.6% (184/234). Main reasons for failure were "bone resorption > 1.7mm" (n = 27, 11.5%) and "implant not in situ or not loaded" (n = 18, 7.7%). Smoking (OR 3.1, p = 0.034), bone grafts (OR 2.4, p = 0.021) and radiation dose > 60 Gy (OR 3.8, p = 0.025) revealed as significant predictors for implant failure. Conclusion: Implant survival differs significantly from implant success in head and neck cancer patients. Implant success is mainly determined by radiographic peri-implant bone resorption. Clinical relevance: Dealing with head and neck cancer patients a higher amount of peri-implant bone resorption must be taken into account and warrants for intensified implant monitoring. [ABSTRACT FROM AUTHOR]

• Mesenchymal stem cells (MSCs) express RANK, dental follicle cells (DFCs) do not. • High concentrated denosumab reduces growth of MSCs. • Physiological concentrations of denosumab enhance osteogenic differentiation. The aim of this study was to evaluate the possible influence of denosumab and zoledronate on proliferation and osteogenic differentiation of alveolar bone stem cells. Mesenchymal stem cells (MSCs) and dental follicle cells (DFCs) were grown under osteogenic differentiation with concentrations from 0.25 μM to 10 μM (zoledronate) and to 20 μM (denosumab). Vitality was assessed after 7 days by CCK-8 Kit. Osteogenic differentiation was measured by alkaline phosphatase (ALP) assay and additionally by RT-qPCR of key enzymes COL1, RUNX2 and ALP. MSCs expressed receptor activator of NF-κB (RANK), as requirement to interact with denosumab. DFCs did not express RANK. Denosumab significantly reduced proliferation and ALP activity of MSCs in high concentrations (10 μM and 20 μM). Growth of DFCs was not influenced at all by denosumab. Zoledronate reduced proliferation of DFCs in higher concentrations (5 μM and 10 μM) (p > 0.05). Physiological and medium concentrations of denosumab (0.25 μM, 1 μM 5μM) significantly enhanced ALP activity in MSCs and COL1, RUNX2 and ALP were upregulated. Zoledronate had no effect on ALP activity in DFCs. Our evaluations suggest receptor and dose depending effects of denosumab in MSCs. High concentrations mediate toxic effects, whereas physiological and medium concentrations enhance osteogenic differentiation. [ABSTRACT FROM AUTHOR]

Exhaust gas emissions of combustion engines can be harmful to the environment, climate, and human health. Hence, emission limits have been increasingly reduced over the last few years, and new dynamic test cycles for test stands have been introduced. Recently, emission legislation was extended by adding testing procedures during real-world operations. The recording of so-called real driving emissions (RDE) with portable emission measurement systems (PEMS) is complex, especially for non-road applications, such as tractors. Emission-relevant sites and environmental conditions vary widely, and RDE measurements with PEMS are limited to an observation period of only a few hours. This paper presents a feasible methodology to determine exhaust emissions for specific tractor operations that are representative of longer periods. Based on long-term recorded GPS data, as well as engine control unit (ECU) speed and torque data from a tractor, six work-specific test cycles were developed and transferred to a tractor test stand. By comparing ECU data from test stand operations with ECU data recorded during field operations, the quality of the procedure was assessed. Emission measurements was conducted. Nitrogen oxides (NO X), carbon monoxide (CO), hydrocarbons (HC), particulate matter (PM) and particulate number (PN) emissions for the tractor works considered with rapeseed oil (DIN 51605) and diesel fuel (CEC RF 06-03) were lower under real operation conditions than those when applying the legal non-road transient cycle (NRTC). The results show that using rapeseed oil fuel instead of diesel fuel offers a huge potential for reducing greenhouse gas emissions. Highlights • Six representative tractor test cycles are generated from 206 h of recorded ECU and GPS data. • Successful replication of the in-field recorded engine operation profiles on the tractor test stand. • Real work-based NO X , HC, CO and particle emissions are generally lower than those in legal-based test cycles. • Rapeseed oil fuel features a high potential for greenhouse gas reduction. [ABSTRACT FROM AUTHOR]

Background In the EMBRACA phase III trial, talazoparib (1 mg daily, orally) demonstrated a statistically significant improvement in PFS versus physician's choice of chemotherapy (PCT; capecitabine, eribulin, gemcitabine, or vinorelbine) in patients with HER2-negative advanced breast cancer carrying a germline BRCA1/2 mutation; we evaluated patient-reported outcomes (PROs). Patients and methods Patients were randomized 2 : 1 to receive talazoparib or PCT. PROs were assessed at day 1 (baseline), the start of each treatment cycle (every 3 weeks), and at the end of treatment, using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-30) and its breast cancer module, QLQ-BR23. Prespecified exploratory analyses included a longitudinal mixed-effect model comparing treatment arms and a time to definitive clinically meaningful deterioration (TTD) analysis carried out in the global health status/quality of life (GHS/QoL), and all functional and symptom scales from the EORTC QLQ-C30 and -BR23 questionnaires. Between-arm TTD comparisons were made using a stratified log-rank test and a Cox proportional hazards model. Results Baseline scores were similar between arms. Statistically significant estimated overall improvement from baseline in GHS/QoL was seen for talazoparib compared with statistically significant deterioration for PCT {3.0 [95% confidence interval (CI) 1.2, 4.8] versus −5.4 [95% CI −8.8, −2.0]; between arms, P  <   0.0001}. A statistically significant greater delay was observed in TTD in GHS/QoL, favoring talazoparib over PCT [hazard ratio, 0.38 (95% CI 0.26, 0.55; median, 24.3 versus 6.3 months, respectively; P  <   0.0001)]. A statistically significant overall change and a statistically significant delay in TTD, all favoring talazoparib, were also observed in multiple functions and symptoms. Conclusion Patients who received talazoparib had significant overall improvements and significant delay in TTD in multiple cancer-related and breast cancer-specific symptoms, functions, and GHS/QoL. ClinicalTrials.gov NCT01945775. [ABSTRACT FROM AUTHOR]

Many public high schools in large urban school districts face challenges staffing their sports programs with knowledgeable and well-qualified coaches. Compared to smaller and more suburban districts, these schools have low student participation in sports and high coach attrition rates. These challenges make it difficult for districts to provide equitable educational opportunities for their youth through school-based sports. This article presents a vision for how these issues could be addressed by outlining a conceptual framework for an urban coaching fellowship (UCF) program. Inspired by alternative teaching pathway programs like Teach for America, the New York City Teaching Fellowship, and the Boston Teacher Residency, UCF programs would use partnerships between large urban school districts, colleges and universities, and local nonprofits to recruit, train and staff schools with well-trained coaches. Such UCF programs would aim to help urban schools increase student participation in high school sports by (1) increasing retention rates of coaches, (2) promoting innovative career pathways for youth coaches in urban high schools, and (3) recruiting and supporting a diverse workforce of high school coaches. [ABSTRACT FROM AUTHOR]

This article describes how one strength and conditioning youth development program implements the teaching personal and social responsibility (TPSR) framework with a portfolio-based system. Some scholars have noted that using portfolios helps connect assessment to instruction by promoting individualized learning for students. The purpose of this article is to share how one program is implementing TPSR by using graphic organizers that make up the portfolio system. First, the important components of TPSR, and how they guide the creation of portfolios, are described. Second, each section of a daily program format, and how a graphic organizer called the workout card guides student work in each section, is described. The workout card helps coaches capture physical activity planning, self-reflection, self-assessment, and written coach feedback. Third, a graphic organizer referred to as the zoom out is explained. This tool collects and organizes student work and coach feedback completed over an extended period of time. Finally, some lessons learned from years of developing the program and portfolio-based system are shared. [ABSTRACT FROM AUTHOR]

The expression of the hair follicle stem cell marker CD34 was analyzed in five different head and neck squamous cell carcinoma (HNSCC) cell lines with different antibodies. All HNSCC cell lines expressed CD34 on their cell surface. After cell cycle synchronization via serum starvation, we observed cyclic CD34 expression in HNSCC cells dependent on cell cycle progression via immunofluorescent staining and flow cytometric analysis. Investigation of the CD34(+) and CD34(−) HNSCC populations revealed most of the cells in S-phase and G2/M-Phase in CD34(+) cells in contrast to CD34(−) cells. Knockdown of CD34 in HNSCC cells led to diminished clonal expansion in a colony forming assay after subjecting the cells to ionizing radiation. Furthermore, knockdown of CD34 after cell cycle synchronization induced high CK1, CK4, and CK5 gene expression and downregulation of CK10 gene expression as shown by Taqman quantitative PCR analysis. The expression levels of CK1 and CK10 were verified via western blot analysis. In summary, our study shows that CD34 plays a role during cell cycle progression of head and neck squamous cell carcinoma and additionally is involved in irradiation resistance and differentiation of malignant oral keratinocytes. [ABSTRACT FROM AUTHOR]

Background: Adjuvant therapy decisions in early breast cancer are based on accurate risk assessment. Urokinase plasminogen activator (uPA) and plaminogen activator inhibitor-1 (PAI-1) have been the first biomarkers in hormone receptor (HR) positive breast cancer to reach highest level of evidence. The EndoPredict test (EPclin) combines gene expression information with nodal status and tumor size. The aim of this prospective study was to compare uPA/PAI-1 and EPclin as prognostic biomarkers with regard to feasibility, risk stratification and impact on adjuvant therapy recommendation. Materials and method: 395 patients with HR positive, HER2 negative, intermediate risk breast cancer were enrolled. Relations and concordance of histologic grading as well as EPclin and uPA/PAI-1 values were assessed by Spearman’s rank correlation coefficient and Cohen’s Kappa. To compare decision impact of EPclin and uPA/PAI-1 three independent case discussions were held: One with known uPA/PAI-1 and EPclin results, one blinded to EPclin alone and another one blinded to both EPclin and uPA/PAI-1. Results: EPclin could be determined in all 395 (100%), uPA/PAI-1 in 190 (48%) of the tumor samples. EPclin allocated 250 patients (63%) to the low-risk group and 145 patients (37%) to the high-risk group, whereas uPA/PAI-1 allocated 88 patients (46%) to the low-risk group and 102 patients (54%) to the high-risk group. In 59% of cases, both tests showed concordant results. EPclin resulted more frequently in a change of therapy recommendation than the uPA/PAI-1 test (46% vs 24%). Recommendation of adjuvant chemotherapy (CTX) was abandoned twice as often by EPclin (45%) compared to uPA/PAI-1 (22%). Conclusion: In this first prospective comparison of EPclin and uPA/PAI-1 we found, that EPclin is superior to uPA/PAI-1 with respect to feasibility and decision impact. This leads to substantial avoidance of adjuvant CTX in endocrine-sensitive, HER2-negative breast cancer. Data collection for patients´ clinical outcome is ongoing. [ABSTRACT FROM AUTHOR]

In flat rolling, the lateral position of the product in the rolling mill and the camber (curvature of the product centerline seen in top view) are key process variables. We explore how their evolution can be analytically modeled based on nonlinear geometric relations, material derivatives, balance equations, constitutive equations for the material flow in the roll gap, and a change of coordinates to obtain a time-free formulation. Based on example problems, we verify the developed novel model and further illustrate the mechanisms behind it. Finally, a literature review on models in this field reveals that there is not yet a consensus on the correct analytical model of the evolution of the camber in flat rolling. The literature review shows that most published models are special cases of the model developed in this paper. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to evaluate postoperative complications after removal or retention of the third molar in the line of mandibular angle fractures. Materials and methods: This retrospective study included the data of 98 patients with a molar in the line of a mandibular angle fracture treated with internal reduction and mini-plate fixation at our department over 9 years. Patients were classified into two groups: tooth removal during osteosynthesis ( n = 45) and tooth retention ( n = 55). The primary target criterion was the incidence of minor (outpatient treatment, local measures) and major (surgical revision, rehospitalisation) complications. Time between trauma and surgery was 1.4 days (range 0 to 12), and the average follow-up 291 days (range 66 to 863). Results: Regarding the eruption status, 26 of 52 (50.0 %) impacted third molars, 11 of 19 (57.9 %) incompletely erupted and 8 of 27 (29.6 %) completely erupted molars had been removed during open reduction. Overall, 17 (17.3 %) patients had postoperative minor ( n = 7) or major ( n = 10) complications, in detail 10/45 (22.0 %) patients after tooth removal and 7/55 (13 %) patients after tooth retention ( p = 0.286). Complication rates between impacted and incompletely erupted third molars (impacted molars 15.0 %, incompletely erupted molars 10.0 %) did not differ significantly, but completely erupted molars had a complication rate of 26.0 %. Conclusions: Mandibular angle fractures with a completely erupted third molar show the highest complication rate after open reduction and osteosynthesis. Retention of a non-infectious third molar facilitates open reduction and does not increase the complication risk. Clinical relevance: The study helps with the decision of removing or retention of a third molar during surgical treatment of a mandibular angle fracture. [ABSTRACT FROM AUTHOR]

Background Hereditary angio-oedema ( HAE), C1 inhibitor HAE (C1- INH- HAE) type I and C1- INH- HAE type II, are inherited disorders characterised by potentially life-threatening recurrent swellings, caused by a deficiency of C1 inhibitor. Management includes attack treatment or prevention using prophylaxis/routine prevention. Aim To evaluate the success of self-administration training as part of a home care programme for treatment of HAE using intravenous C1 inhibitor. Methods In total, 18 patients (7 men, 11 women; aged 18-72 years) were trained to self-administer a plasma-derived C1 inhibitor concentrate for acute treatment or routine prevention of HAE attacks. The number of training sessions needed to learn intravenous self-administration, delay in time to treatment and reduction in attack frequency (per month) were evaluated after completion of the training. Results All patients successfully completed training. The median number of training sessions required to be capable of unassisted/independent self-injection was 5 (range 2-30). Time to treatment was reduced from a median of 4.5 h (270 min) by medical professionals to 15 min by patients after self-administration training). Using the treatment as routine prevention resulted in a reduction of median frequency of attacks from 8 to 0.5 attacks/month. Conclusion C1 inhibitor self-administration for the treatment of HAE allows patients to quickly treat attacks at home, potentially reducing attack severity. The results also demonstrate the benefit of self-administered routine prevention therapy in a real-world patient population. Self-administered therapy potentially allows patients to gain greater control over their attacks, resulting in a reduction in healthcare utilization. [ABSTRACT FROM AUTHOR]

The TPSR Alliance has become a vital community of practice for my graduate students and for me personally. During the past decade, I (the first author) have worked with graduate students at Boston University to provide a program for youth development through sports and fitness at a large, high-needs public high school in the Boston area. Our program, “Get Ready,” is inspired by the teaching personal and social responsibility (TPSR) framework and has offered a variety of services to hundreds of students. The Get Ready program is run through the Institute for Athletic Coach Education in the School of Education at Boston University. Our efforts have been supported in part by a collaboration among Boston-area universities named “Step Up.” The goal of this effort is for universities to provide assistance to Boston public schools in closing the achievement gap and “to give our city's students the best education possible and to help them reach their full potential.” The purpose of this article is to describe the aspects of the TPSR Alliance that make it a community of practice for those of us at Boston University involved in the Get Ready program. It will describe the impact the Alliance has had on our youth development program, as well as on us — the coaches and personnel who face the daily challenges of such a program. In particular, I will focus on how the TPSR Alliance is a community of practice that helps us learn about the important aspects of our work. [ABSTRACT FROM PUBLISHER]

Objectives: The purpose of this study was to analyse the impact of surgical margins on tumour recurrence and survival of patients with carcinomas of the head and neck.Material and Methods: A cohort of 156 patients with primary squamous cell carcinoma of the head and neck treated by local resection with negative margins and neck dissection between 2004 and 2012 was investigated. Margin status in frozen sections and permanent paraffin tissues were analysed and compared to clinical and histopathological parameters as well as to tumour recurrence (local, regional and distant) and disease-specific survival (DSS).Results: Close margins (<5mm) on permanent sections were correlated to high-grade differentiation (p=0.070), lymphangiosis (p=0.009) and positive neck nodes (p=0.025) implicating regional and distant recurrence (p=0.001) as well as unfavorable DSS (p=0.002). Positive margins on initial frozen section analysis revised into negative margins during further surgery were the strongest predictor for local recurrence in uni- and multivariate analysis (p<0.001, hazard ratio 3.34). However, positive frozen section margins were not significantly predictive for DSS (p=0.150). Significant predictors for DSS in univariate analysis were local recurrence (p=0.026), T-stage (p=0.02), N-stage (p<0.001), grading (p=0.02) and lymphangiosis (p=0.001). Multivariate DSS analysis revealed lymph node metastasis (p=0.005) and local recurrence (p=0.017) as significant negative predictors.Conclusion: Close margins on permanent sections are associated with aggressive tumour characteristics, regional and distant metastasis implicating worse DSS. The accuracy of frozen section analysis seems limited as positive frozen section margins revised into negative margins bear a high risk of local recurrence. [ABSTRACT FROM AUTHOR]

‘Flying Triangulation’ (FlyTri) is a recently developed principle which allows for a motion-robust optical 3D measurement of rough surfaces. It combines a simple sensor with sophisticated algorithms: a single-shot sensor acquires 2D camera images. From each camera image, a 3D profile is generated. The series of 3D profiles generated are aligned to one another by algorithms, without relying on any external tracking device. It delivers real-time feedback of the measurement process which enables an all-around measurement of objects. The principle has great potential for small-space acquisition environments, such as the measurement of the interior of a car, and motion-sensitive measurement tasks, such as the intraoral measurement of teeth. This article gives an overview of the basic ideas and applications of FlyTri. The main challenges and their solutions are discussed. Measurement examples are also given to demonstrate the potential of the measurement principle. [ABSTRACT FROM PUBLISHER]

The article describes the Library of the District Museum of Vienna's 8th district (Josefstadt). It starts with a short historical review of the museum, followed by a description of the constricted spatial setting of the library and the origin of the library's holdings. The final part deals with cataloguing and the use of „Biblioweb“, a low-cost software product chosen in 2012. [ABSTRACT FROM AUTHOR]

Summary Objectives Induction of apoptosis is a major mechanism of radiosensitivity in different types of cancer. In contrast, EGFR/PI3K/AKT signalling and recently the presence of so-called cancer stem cells are discussed as reasons for radioresistance. Materials and methods The study investigates mechanisms of apoptosis, key oncogenes of the PI3K/AKT pathway and the presence of cancer cells with stem cell properties during irradiation in two cell lines (PCI-9A, and PCI-15) of head and neck squamous cell carcinoma. WST-1-tests, qRT-PCR, western blots and FACS analysis were performed for analysis. Results The two cell lines presented different degrees of cell death upon irradiation. The radiosensitive cell line PCI-9A showed increased apoptosis after irradiation measured by expressed cleaved caspases 3 and 7 while the radioresistant cell line PCI-15 upregulated antiapoptotic Survivin and BCL2A1 mRNA. Besides, increased PI3K/AKT- and ERK1/2-signalling was associated with radioresistance accompanied by loss of PTEN function through phosphorylation on S380. Blockade of pAKT increased radiation-induced cell death, and moreover, led to an upregulation of pMET in the radioresistant cell line. The percentage of ALDH-positive tumour cells was markedly decreased after irradiation in the radiosensitive cell line. Conclusions Functional apoptosis is mandatory for sensitivity to irradiation in head neck cancer cells. Upregulation of the AKT-pathway seems to be one reason for poor radioresponse. Activated MET may also predict radioresistance, possibly through ERK1/2 signalling. Moreover MET may indicate the presence of cancer stem cells facilitating radioresistance as shown by increased ALDH expression. [ABSTRACT FROM AUTHOR]

Although microemulsions are one of the most promising dermal carrier systems, their clinical use is limited due to their skin irritation potential. Therefore, microemulsions based on naturally derived monoacyl phosphatidylcholine (MAPL) were developed. The influence of the water, oil and surfactant content on dermal delivery of flufenamic acid was systematically investigated for the first time. A water-rich microemulsion led to significantly higher in vitro skin penetration of flufenamic acid compared to other microemulsions. The superiority of the water-rich microemulsion over a marketed flufenamic acid containing formulation was additionally confirmed. Differences in drug delivery could be explained by alterations of the microemulsions after application. Evaporation of isopropanol led to crystal-like structures of MAPL on the skin surface from the surfactant- or oleic acid-rich microemulsions. In contrast, the formation of this additional barrier was hindered in case of the water-rich microemulsion. The skin penetration of MAPL was additionally analyzed by combined ATR-FTIR and tape stripping experiments, where MAPL itself penetrated only into the initial layers of the stratum corneum, independent of the microemulsion composition. Since a surfactant must penetrate the skin to cause irritation, MAPL can be presumed as a skin-friendly emulsifier with the ability to stabilize pharmaceutically acceptable microemulsions. [ABSTRACT FROM AUTHOR]

Companies in various industries, including travel, hospitality, and retail, increasingly focus on improving customer relationships and customer loyalty. In this paper, we propose a new systems architecture that combines the textual content in social media messages with product information, such as the descriptions summarized in catalogs, in order to provide marketing campaign recommendations. Companies commonly build user profiles based on purchase histories and other customer-specific information; however, when dealing with social media, we often cannot match the social media users with the customers. In this regard, we address the problem of targeting individual social media messages for which no personalized profile information can be retrieved. Our solution combines two disparate computational toolboxes for text analytics—natural language processing and machine learning—in order to select social media users for whom to target with topic-specific advertisements. Natural language processing is used to analyze the context of social media messages, and machine learning is used to analyze product information, with the goal being to match social media messages to products and ranking potential advertisements. To demonstrate the framework, we detail a real-world application in the travel and tourism industry using Twitter® as the social media platform. [ABSTRACT FROM AUTHOR]

Background: Adenoid cystic carcinoma (ACC) is a rare type of cancer commonly occurring in salivary glands. It is characterized by slow but infiltrative growth, nerve infiltration and overall poor prognosis, with late recurrence and distant metastasis. The treatment of ACC is still limited to surgery and/or (adjuvant) radiotherapy. Till now no promising systemic therapy option exists. However, various studies deliver promising results after treatment with anti-angiogenetic agents, such as anti-EGFR-antibody Cetuximab or Tyrosinkinase inhibitor Lenvatinib. Methods: By using of immunohistological methods we analyzed and compared the macrophage and lymphocyte populations, vascularization, and PD-L1-status in 12 ACC of the salivary glands. Results: All cases showed a significant elevation of macrophages with M2 polarization and a higher vascularization in ACC compared to normal salivary gland tissue. The CD4/CD8 quotient was heterogenous. ACC does not show relevant PD-L1 expression. Conclusions: The predominant M2 polarization of macrophages in ACC could be responsible for elevated vascularization, as already been proved in other cancer types, that M2 macrophages promote angiogenesis. [ABSTRACT FROM AUTHOR]

Summary: Objectives: The PI3K/AKT/mTOR signalling axis controls cell proliferation and survival and has achieved major importance as a target for cancer therapy. This investigation evaluated the expression of the major components P-AKT, P-mTOR, PI3K and P-S6rp in salivary gland cancer. Materials and methods: Immunohistochemical expression of P-AKT, P-mTOR, PI3K and P-S6rp was evaluated and correlated to clinicopathological parameters and survival of 272 patients with salivary gland carcinomas. Results and conclusion: Analysis of all tumours together revealed an increased expression of all components of the pathway in comparison to normal salivary gland control tissue. Nuclear expression of P-AKT was associated with young age, localised tumour stage, absence of lymph node metastases and favourable prognosis. On the contrary, cytoplasmic P-AKT displayed unfavourable tumour characteristics like high-grade malignancy, and worse overall survival. In comparison to cytoplasmic/membrane mTOR expression, nuclear P-mTOR was associated with absence of lymph node metastases and higher survival rates. PI3K and P-S6rp were exclusively found in the cytoplasm. Expression of P-S6rp was correlated to increased age, advanced tumour size and lymph node metastases. In all tumours together, nuclear P-AKT positively correlated with nuclear P-mTOR, whereas P-S6rp was associated with expression of PI3K and cytoplasmic P-AKT. In acinic cell carcinoma, cytoplasmic expression of P-AKT, P-mTOR, PI3K and P-S6rp was positively associated with each other. In conclusion, PI3K/AKT/mTOR signalling is active in salivary gland cancer and might function as a target for personalised therapy. P-AKT and P-mTOR possess distinct molecular functions with impact on prognosis depending on their cellular localisation. [ABSTRACT FROM AUTHOR]

Background:Activity of the tumour-suppressor gene PTEN is reduced in different types of cancer and implicates non-responsiveness to targeted therapy. This study evaluates the gene and protein status of PTEN in salivary gland carcinomas.Methods:A total of 287 carcinomas of the major and minor salivary glands were investigated for phosphatase and tensin homologue located on chromosome 10 (PTEN) deletion and loss of PTEN expression using fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC), respectively. Results were correlated to clinicopathological parameters, long-term survival, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) (IHC and FISH) status of the tumours.Results:Hemizygous deletions of PTEN were found in 35 out of 232 (15.1%) carcinomas, while homozygous deletions were observed in 17 out of 232 (7.3%) tumours. Phosphatase and tensin homologue located on chromosome 10 deletion was common in certain histological subtypes and especially homozygous deletion was associated with high-grade malignancy, lymph node metastases and unfavourable long-term prognosis (P<0.001). Loss of PTEN expression was present in 59 out of 273 (21.6%) carcinomas and was significantly correlated to genomic PTEN deletion, high-grade malignancy (P<0.001), increased tumour size (P=0.036), lymph node metastases (P=0.007) and worse disease-specific survival (P=0.002). Genomic PTEN deletion, in particular homogenous deletion (P<0.001) predominantly occurred in tumours with increased gene copy number of EGFR (60.0%) and/or amplification of HER2 (63.6%). Loss of PTEN expression was frequently found in tumours overexpressing EGFR (28.6%) and/or HER2 (52.6%).Conclusion:PTEN function is reduced in different types of salivary gland cancer indicating unfavourable prognosis. Its association with EGFR and HER2 signalling might affect targeted therapy. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The first-aid training necessary for obtaining a drivers license in Austria has a regulated and predefined curriculum but has been targeted for the implementation of a new course structure with less theoretical input, repetitive training in cardiopulmonary resuscitation (CPR) and structured presentations using innovative media. Methods: The standard and a new course design were compared with a prospective, participant- and observer-blinded, cluster-randomized controlled study. Six months after the initial training, we evaluated the confidence of the 66 participants in their skills, CPR effectiveness parameters and correctness of their actions. Results: The median self-confidence was significantly higher in the interventional group [IG, visual analogue scale (VAS:“0” not-confident at all,“100” highly confident):57] than in the control group (CG, VAS:41). The mean chest compression rate in the IG (98/min) was closer to the recommended 100bpm than in the CG (110/min). The time to the first chest compression (IG:25s, CG:36s) and time to first defibrillator shock (IG:86s, CG:92s) were significantly shorter in the IG. Furthermore, the IG participants were safer in their handling of the defibrillator and started with countermeasures against developing shock more often. The management of an unconscious person and of heavy bleeding did not show a difference between the two groups even after shortening the lecture time. Conclusions: Motivation and self-confidence as well as skill retention after six months were shown to be dependent on the teaching methods and the time for practical training. Courses may be reorganized and content rescheduled, even within predefined curricula, to improve course outcomes. [Copyright &y& Elsevier]

Abstract: Resistance of oral squamous cell carcinomas (OSCC) to conventional chemotherapy or radiation therapy might be due to cancer stem cells (CSCs). The development of novel anticancer drugs requires a simple method for the enrichment of CSCs. CSCs can be enriched from OSCC cell lines, for example, after cultivation in serum-free cell culture medium (SFM). In our study, we analyzed four OSCC cell lines for the presence of CSCs. CSC-like cells could not be enriched with SFM. However, cell lines obtained from holoclone colonies showed CSC-like properties such as a reduced rate of cell proliferation and a reduced sensitivity to Paclitaxel in comparison to cells from the parental lineage. Moreover, these cell lines differentially expressed the CSC-marker CD133, which is also upregulated in OSCC tissues. Interestingly, CD133+ cells in OSCC tissues expressed little to no Ki67, the cell proliferation marker that also indicates reduced drug sensitivity. Our study shows a method for the isolation of CSC-like cell lines from OSCC cell lines. These CSC-like cell lines could be new targets for the development of anticancer drugs under in vitro conditions. [Copyright &y& Elsevier]

Distraction osteogenesis presents an alternative procedure for augmentation of atrophic alveolar bone prior to inserting dental implants. The aim of this retrospective study was to evaluate complications of this method with specific focus on bone resorption during the consolidation period and the follow-up period after dental implant insertion into distracted bone. Thirty partially edentulous patients underwent a total of 36 vertical alveolar distractions with an extraosseous distraction system. Eleven devices were placed in the maxilla and 25 in the mandible. Eighty-two dental implants were inserted after a mean consolidation period of 4.5 months. Treatment results were evaluated by means of panoramic radiographs for distraction follow-up and periapical radiographs for implant follow-up. The mean length of the transport segment was 19 mm. The average alveolar height achieved was 6.4 mm with a mean resorption of 1.8 mm (21.1%) at the time of dental implant insertion. Main problems comprised oral displacement of the transport segment ( n = 15) and inadequate soft tissue extension ( n = 13). Eighty-two dental implants were inserted with an overall survival rate of 95.1% after 45.8 months. For periimplant marginal bone, an average resorption of 3.5 mm was recorded 50.4 months after implant insertion. Although alveolar distraction osteogenesis seems to be an effective tool to treat vertical defects of the alveolar ridge, it is not an uncomplicated procedure. A combination with vestibular augmentation of autogenous bone grafts should be considered. Overcorrection of 20% may compensate bone relapse during the consolidation period of the distracted alveolar bone. Further bone resorption after dental implantation is common. [ABSTRACT FROM AUTHOR]

This paper describes the foundations of a market mechanism that was designed to stimulate more efficient provisions of forest ecosystem services to society. The proposed tool is a competitive multi-unit public goods subscription game of incomplete information. A conceptual and mathematical characterization of the game is followed by an illustrative example where Pareto-efficient bundles of timber, carbon and mature forest habitat services of a real forest are used in a simulated bidding game. Attractive features of the mechanism include the use of multi-criteria optimization to ensure only the most cost-efficient bundles of ecosystem services are offered for bidding, and that it does not rely on regulatory control or on complex valuation exercises that are otherwise needed in alternative methods such as the cap-and-trade scheme. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The aim of this in vitro study was to investigate whether saliva substitute films influence the adhesion of Candida albicans to different dental substrata prior to and after artificial ageing. Design: Specimens of a denture base resin (DB) and a veneering composite (VC) were polished and subjected to an artificial ageing protocol (thermal cycling, 2×3000 cycles 5/55°C). Bovine enamel (BE) and glass were used as reference materials. After determination of surface free energy, specimens were rinsed with commercial saliva substitutes (Aldiamed, Saliva natura, Saliva Orthana, Salinum), a positive control (protein mixture), or a negative control (Phosphate Buffered Saline, PBS) for 2h at 37°C in a flow chamber. Specimens were then exposed to a C. albicans ATCC 10231 suspension for 4h at 37°C. Adherent, viable Candida cells were quantified using a luminometric ATP-based assay. Statistical analysis was performed using 1- and 2-way ANOVA, and post-hocs were analysed using the Tukey–Kramer test (α <.05). Results: Our data indicated that VC (31.1mJ/m2) and DB (33.9mJ/m2) yielded the lowest surface free energy prior to artificial ageing, and BE (43.6mJ/m2) yielded the highest surface free energy. For C. albicans adhesion, both the materials as well as the saliva substitutes influenced relative luminescence intensities, indicating significant differences in C. albicans adhesion between the various materials and after treatment with the saliva substitutes. Conclusions: Saliva substitutes may have a decisive influence on C. albicans adhesion, but their impact appears to be dependent on the properties of the underlying substratum material. [Copyright &y& Elsevier]

In the early twentieth century, the German laboratories of Spielmeyer and the Vogts proposed competing pathogenetic theories for Ammon's horn sclerosis. Spielmeyer's vascular pathogenesis theory was initially preferred, but the Vogts' Pathoklise theory was later favored. From 1925 to 1927, Uchimura worked in the Spielmeyer's laboratory. There, Uchimura first described the detailed vascular anatomy of the hippocampus. His work formed the basis for the vascular theory of Ammon's horn sclerosis. Because of Germany's prominence in medical science and Japan's preference for the German medical system, Uchimura among many young Japanese medical scientists, travelled to the institutes of German-speaking Europe for training. [ABSTRACT FROM AUTHOR]

Relapse rates of surgically treated clubfeet are about 25%. We reviewed 43 patients (57 feet) treated for relapsed clubfoot deformity between 1992 and 2001 in our department. The average age of the patients at the time of revision surgery was 5.1 years, the mean follow-up was 6.6 years. Surgical therapy was performed using an algorithm according to age groups. The mean Atar score at follow-up was 77 points, representing a good outcome. Out of 57 feet, 20 (35%) were rated excellent, 24 (42%) good, 5 (9%) fair, and 8 (14%) poor. The number of previous surgical interventions had no influence on the outcome. Using an age related surgical algorithm, good postoperative results could be achieved in most of our patients, thus improving their functional situation. This emphasises the usefulness of the proposed algorithm in the difficult situation of recurrent clubfoot, while thorough analysis of the underlying deformity remains essential. [ABSTRACT FROM AUTHOR]

Simple Summary: This review provides an overview of the state of knowledge and general understanding of CDK inhibitors currently under development or clinically approved, with a particular focus on the treatment of head and neck cancer. Especially in combination therapy, cyclin-dependent kinase inhibitors exhibit a synergistic effect by attenuating chemo-, radio-, or immune-resistance in some tumor entities, thus improving the success of cancer therapy. Cyclin-dependent kinases (CDK) regulate cell cycle progression. During tumor development, altered expression and availability of CDKs strongly contribute to impaired cell proliferation, a hallmark of cancer. In recent years, targeted inhibition of CDKs has shown considerable therapeutic benefit in a variety of tumor entities. Their success is reflected in clinical approvals of specific CDK4/6 inhibitors for breast cancer. This review provides a detailed insight into the molecular mechanisms of CDKs as well as a general overview of CDK inhibition. It also summarizes the latest research approaches and current advances in the treatment of head and neck cancer with CDK inhibitors. Instead of monotherapies, combination therapies with CDK inhibitors may especially provide promising results in tumor therapy. Indeed, recent studies have shown a synergistic effect of CDK inhibition together with chemo- and radio- and immunotherapy in cancer treatment to overcome tumor evasion, which may lead to a renaissance of CDK inhibitors. [ABSTRACT FROM AUTHOR]

In this article, we propose a novel availability management process called Available-to-Sell (ATS) that incorporates demand shaping and profitable demand response to drive better supply chain efficiency. The proposed process aims at finding marketable product alternatives in a quest to maintain a financially viable and profitable product portfolio, and to avoid costly inventory overages and shortages. The process is directly supported by a mathematical optimization model that enables on demand up-selling, alternative-selling and down-selling to better integrate the supply chain horizontally, connecting the interaction of customers, business partners and sales teams to procurement and manufacturing capabilities of a firm. We outline the business requirements for incorporating such a process into supply chain operations, and highlight the advantages of ATS through simulations with realistic production data in a computer manufacturing environment. The models featured in this paper have contributed to substantial business improvements in industry-size supply chains, including over $100M of inventory reduction in IBM’s server computer supply chain. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the prognostic impact of expression of receptor tyrosine kinases epidermal growth factor receptor (EGFR), HER2, and C-KIT in relation to established clinicopathological parameters in salivary gland carcinomas. Methods and results:  Immunohistochemistry for EGFR, HER2, C-KIT and the proliferation marker Ki67 was performed in 101 cases of salivary gland carcinoma and related to long-term clinical follow-up. Immunopositivity of C-KIT was common in adenoid cystic carcinoma (92%). Lack of C-KIT expression occurred in salivary duct carcinoma ( P < 0.001) and was associated with high-grade tumours ( P = 0.002), positive lymph nodes ( P = 0.002) and high expression of Ki67 ( P = 0.001). HER2 was typically expressed in salivary duct carcinomas (83%), but was not associated with any other parameter. EGFR overexpression occurred independently of histological type and clinical parameters. On univariate survival analysis, overexpression of EGFR ( P = 0.011) and lack of C-KIT ( P = 0.014) were associated with worse prognosis, whereas HER2 was of no prognostic significance. On multivariate analysis, the strongest negative predictor of survival was high proliferative activity measured by Ki67 ( P = 0.002), followed by presence of residual tumour ( P = 0.006), overexpression of EGFR ( P = 0.026) and advanced tumour stage ( P = 0.041). Conclusions: The expression of receptor tyrosine kinases confers additional prognostic impact on disease-specific survival. EGFR overexpression is an independent negative prognostic factor. [ABSTRACT FROM AUTHOR]

Summary: Maspin, a 42kDa protein, belongs to the serine protease inhibitor (serpin) family and is suggested to have inhibitory effects on tumor-induced angiogenesis, tumor cell motility, invasion and metastasis and influences prognosis of tumor patients. The aim of the study was to analyze Maspin expression in salivary gland cancer as well as its prognostic impact on survival in comparison to clinical parameters. Immunohistochemical staining was carried out in 73 cases of salivary gland malignancies. High proportions of Maspin expression were observed in adenoid cystic carcinomas, mucoepidermoid carcinomas and carcinomas ex pleomorphic adenoma, low proportions were seen in salivary duct carcinomas. Acinic cell carcinomas did not show any Maspin expression. Analysis of the prognostic impact of Maspin expression was restricted to salivary gland carcinoma types of intermediate malignancy grade (adenoid cystic carcinoma, mucoepidermoid carcinoma and carcinoma ex pleomorphic adenoma). For these tumors, univariate analyses revealed that T-stage (p =0.025), age⩾70 (p =0.0065), loss of Maspin (p =0.0016) and presence of residual tumor (p <0.001) correlated with poor prognosis. In multivariate analysis age⩾70 (p =0.005) and loss of Maspin (p =0.036) were significant prognostic factors. Moreover, negative Maspin staining was associated with lymph node metastasis and residual tumor. According to these findings, Maspin might be useful as a new prognostic marker in adenoid cystic carcinoma and in salivary gland carcinomas with intermediate grade of malignancy where grading systems are still under debate. [Copyright &y& Elsevier]

Abstract: Soft tissue tumours of the foot are rare and often present a difficult clinical and diagnostic situation. We report of a 15-year-old male with a painless swelling at the lateral margin of the left foot. After X-ray and MRI an excisional biopsy was performed. Histology revealed true muscle hypertrophy without myopathic or degenerative changes, consistent with the diagnosis of congenital hypertrophy of the abductor digiti minimi muscle. At a follow-up of one and a half year there was no recurrence and the patient was satisfied with the shape and the appearance of the foot. [Copyright &y& Elsevier]

Background: A cutaneous angiosarcoma is a rare malignant tumour of vascular endothelial cells with aggressive clinical behaviour and poor prognosis. Diagnosis is often delayed due to its variable and often benign clinical appearance. Case presentation: This case presents a 64-year-old man with a six-month-history of a recurrent diffuse and erythematous painless swelling below the left eye. Several resections with intraoperatively negative resection margins followed, but positive margins were repeatedly detected later on permanent sections. Histopathologic examination of the specimen diagnosed a cutaneous angiosarcoma. Neither, finally achieved negative margins on permanent sections, nor a following chemotherapy could prevent the recurrence of the disease after five months and the patient's dead 21 months after the first diagnosis. Conclusion: The case elucidates the current diagnostic and therapeutic dilemma of this entity, which shows an unfavourable clinical course in spite of multimodal therapy. [ABSTRACT FROM AUTHOR]

Background: With the 2005 WHO classification of salivary gland tumours and its increasingly recognized diagnostic entities, the frequency of adenocarcinoma (NOS) has decreased significantly. Case presentation: This paper describes a fast growing adenocarcinoma (NOS), originating from the minor salivary glands of the left buccal mucosa with a rapid onset of multiple local and distant metastases, especially in the lung. A lung primary was unlikely as the tumour was characterized by positivity for cytokeratin 20 and negativity for the thyroid transcription factor-1 protein (TTF-1) in immunohistochemistry. Conclusion: A rare case of an adenocarcinoma (NOS) of the minor salivary glands with a rapid development and an unfavourable clinical course is reported. It shows that additional immunohistochemical analysis can decisively contribute to determine the site of the primary tumour in cases with unknown primary. [ABSTRACT FROM AUTHOR]

The zebrafish mutation m865 was isolated during a large-scale mutagenesis screen aimed at identifying genes involved in the development and maintenance of subgroups of neurons in the zebrafish central nervous system. The phenotype of m865 mutant embryos shows defects in the development of dopaminergic neurons in the pretectum and of retinal amacrine cells, as well as abnormal caudal dopaminergic cluster in the diencephalon. The effects of the mutation appear not to be restricted to dopaminergic neurons, as development of other neurotransmitter systems (serotonergic and cholinergic) is impaired as well. Furthermore, increased apoptosis is localized to the m865 mutant retina and in the optic tectum starting at 24hpf, and may lead to the observed reduced size of the mutant head and eye. Early patterning is not affected in m865 mutant embryos, and expression of genes known to play a role in dopaminergic cell differentiation is normal except for reduced expression of nurr1 in the mutant retina. Thus the m865 mutation does not specifically affect dopaminergic neuron development. m865 was genetically mapped to linkage group 5, and the critical genomic interval could be narrowed down to a region of 110 kb, containing four candidate genes. For one of these candidate genes, sepiapterin reductase ( spr), a requirement for neuronal survival has previously been implicated, including dopaminergic neurons. Identification of the mutated gene should lead to a more detailed understanding of the defects observed in m865 mutant embryos, and potentially could enhance the understanding of the development and maintenance of specific dopaminergic neuronal populations. [ABSTRACT FROM AUTHOR]

We report a case of a sternal osteoid osteoma in a 39-year-old man. This localization is very rare and to our knowledge not described in literature. [ABSTRACT FROM AUTHOR]

MRI is the imaging method of choice in patients with cranial nerve palsies. However, the nerves are often not seen on MR images and smaller lesions may not be diagnosed on routine brain MRI. The purpose of this study is to show that the oculomotor cranial nerves can be visualized by standard MR sequences and to present an update on clinical applications of cranial nerve imaging. In MR images of normal subjects, it is demonstrated that the oculomotor nerve, the trochlear nerve and the abducens nerve can be identified not only in the subarachnoid space and cavernous sinus, but also in the orbit. However, a precondition is the use of appropriate imaging sequences and planes (e.g., subarachnoid cisterns: T2-weighted fast spin-echo or T2-weighted three-dimensional sequences in oblique-axial and sagittal planes; cavernous sinus: contrast-enhanced T1-weighted coronal images; orbit: T1-weighted images without contrast agent in the coronal plane obtained using surface coils). The capability of imaging cranial nerves is clinically important not only for diagnostic purposes in eye muscle palsies but also for planning surgical procedures at the cranio-orbital junction. [ABSTRACT FROM AUTHOR]

AIM: To investigate the efficacy of verapamil eye drops for inhibition of diabetic cataract in rats. METHODS: Diabetes was induced in 69 male Sprague-Dawley rats by an intraperitoneal injection of streptozotocin (65 mg/kg body weight). One group (DV) of animals was treated by instillation of one drop of 0.2% RS-verapamil hydrochloride in both eyes three times daily for 8 weeks. The placebo treated group (D) received the vehicle solution only. After 8 weeks the lenses were removed, inspected, and photographed using bright and dark field illumination. The transmission of He-Ne laser light was measured in the optical axis of each lens in order to determine the turbidity coefficient (t) as a measure of central lens opacity. Following digital image analysis, the integrated density as a measure of central and mid-peripheral opacities was determined. RESULTS: Lenses of both groups developed peripheral cortical opacities not affecting the optical axis. Advanced and paracentral cortical opacities were present in 10 (16.7%) of the placebo treated lenses (D) and two (3.8%) of the verapamil treated lenses (DV). Complete corticonuclear cataract developed in four (6.7%) of the lenses from group D but none of the lenses from group DV. The mean lens turbidity t was determined to be 0.019 (SEM 0.002) mm(-1) (n = 52) in the verapamil treated diabetic rats (DV) and 0.042 (0.008) mm(-1) (n = 60) in the placebo treated group (D). This difference was statistically significant (p = 0.0054). The mean integrated density was 274.91 (22.5) in group D (n = 60) and 196.28 (20.7) in group DV (n = 37). This difference was also significant (p = 0.0037). CONCLUSION: Verapamil eye drops 0.2% administered three times daily are effective in inhibiting the progression of lens opacities in streptozotocin diabetic rats. [ABSTRACT FROM AUTHOR]

This review article gives a basic introduction to the technical principles of magnetic resonance imaging for ophthalmologists and orbital surgeons and describes the anatomical structures that can be identified on high-resolution magnetic resonance images of the orbit. The meaning of general imaging parameters, specific weighting of the images, and the use of contrast agents, fat suppression techniques and surface coils is explained. Possible artifacts are also described. The advantages and disadvantages of MRI in comparison with computed tomography (CT) are discussed in order to give recommendations for the use of the appropriate imaging modality in patients with orbital disorders. Apart from delineating the course of the extraocular muscles, high-resolution MRI is able to depict not only all important blood vessels and cranial nerves of the orbit but also major septa of the orbital connective tissue system. Clinical applications are also mentioned to show that high-resolution MRI may contribute to a specific diagnosis in orbital disease. [ABSTRACT FROM AUTHOR]

Background: Although adequate physical activity has been shown to be beneficial in early breast cancer, evidence in metastatic breast cancer is sparse and contradictory, which could be related to distinct effects of physical activity on the different molecular cancer subtypes. Therefore, we here evaluated the effect of physical activity on progression-free and overall survival (PFS, OS) in metastatic breast cancer, specifically looking at molecular subtypes. Methods: International Physical Activity Questionnaire (IPAQ) questionnaires, filled out by patients enrolled in the prospective PRAEGNANT registry (NCT02338167; n = 1,270) were used to calculate metabolic equivalent task (MET) minutes, which were subsequently categorized into low (n = 138), moderate (n = 995) or high IPAQ categories (n = 137). Cox regression analyses were used to evaluate the impact of IPAQ categories and its interaction with molecular subtypes on PFS and OS. Results: Patient and tumor characteristics were equally distributed across IPAQ categories. HER2pos, HRpos and TNBC were present in 23.1%, 65.7% and 11.2% of patients, respectively. IPAQ scores did not have an impact on PFS and OS in addition to established prognostic factors, either overall or in particular molecular subtypes (PFS: p = 0.33 and OS: p = 0.08, likelihood ratio test). Exploratory analyses showed higher overall survival rates for high IPAQ categories compared to low/moderate IPAQ categories in luminal B-like breast cancer. Conclusions: Self-reported physical activity using the IPAQ questionnaire did not significantly affect PFS or OS in patients suffering from metastatic breast cancer. Nevertheless, some hypothesis-generating differences between molecular subtypes could be observed, which may be interesting to evaluate further. [ABSTRACT FROM AUTHOR]

Literature suggests that intravenous prophylaxis exceeding 48 h offers no additional benefit in preventing surgical site infections (SSI) in patients with microvascular head and neck reconstruction. However, protocols for antibiotic therapy duration post-reconstruction are not standardized. This study identifies factors predicting prolonged intravenous antibiotic use and antibiotic escalation in patients receiving free flap head neck reconstruction. A retrospective analysis of 446 patients receiving free flap reconstruction was conducted, examining predictors for antibiotic therapy > 10 days and postoperative escalation. 111 patients (24.8%) experienced escalation, while 159 patients (35.6%) received prolonged therapy. Multivariate regression analysis revealed predictors for escalation: microvascular bone reconstruction (p = 0.008, OR = 2.0), clinically suspected SSI (p < 0.001, OR = 5.4), culture-positive SSI (p = 0.03, OR = 2.9), extended ICU stay (p = 0.01, OR = 1.1) and hospital-acquired pneumonia (p = 0.01, OR = 5.9). Prolonged therapy was associated with bone reconstruction (p = 0.06, OR = 2.0), preoperative irradiation (p = 0.001, OR = 1.9) and culture-positive SSI (p < 0.001, OR = 3.5). The study concludes that SSIs are a primary factor driving the escalation of perioperative antibiotic use. Clinical suspicion of infection often necessitates escalation, even in the absence of confirmed microbiological evidence. Microvascular bone reconstruction was a significant predictor for both the escalation and extension of antibiotic therapy beyond 10 days. Furthermore, preoperative radiation therapy, hospital-acquired pneumonia, and prolonged ICU stay were associated with an increased likelihood of escalation, resulting in significantly extended antibiotic administration during hospitalization. Antibiotic stewardship programmes must be implemented to reduce postoperative antibiotic administration time. Trial registration The study was registered approved by the local Ethics Committee (Nr: 18-1131-104). [ABSTRACT FROM AUTHOR]