Does passive sound attenuation affect responses to pitch-shifted auditory feedback?

The role of auditory feedback in vocal production has mainly been investigated by altered auditory feedback (AAF) in real time. In response, speakers compensate by shifting their speech output in the opposite direction. Current theory suggests this is caused by a mismatch between expected and observed feedback. A methodological issue is the difficulty to fully isolate the speaker’s hearing so that only AAF is presented to their ears. As a result, participants may be presented with two simultaneous signals. If this is true, an alternative explanation is that responses to AAF depend on the contrast between the manipulated and the non-manipulated feedback. This hypothesis was tested by varying the passive sound attenuation (PSA). Participants vocalized while auditory feed- back was unexpectedly pitch shifted. The feedback was played through three pairs of headphones with varying amounts of PSA. The participants’ responses were not affected by the different levels of PSA. This suggests that across all three headphones, PSA is either good enough to make the manipulated feedback dominant, or differences in PSA are too small to affect the contribution of non-manipulated feedback. Overall, the results suggest that it is important to realize that non-manipulated auditory feedback could affect responses to AAF

Transcutaneous sentinel lymph node detection in cutaneous melanoma with indocyanine green and near-infrared fluorescence: A diagnostic sensitivity study.

Sentinel lymph node (SLN) biopsy with preoperative radiocolloid-based lymphoscintigraphy and blue dye injection is considered the standard procedure for staging nodal metastases in early-stage cutaneous melanoma patients with clinically uninvolved lymph nodes. While this combination renders good accuracy in SLN detection, radiation exposure and the frequent allergic reactions to the blue dye are considered drawbacks of this technique. Indocyanine green (ICG) is a water-soluble fluorescent dye that can be identified through near-infrared fluorescence imaging (NIRFI). The aim of this prospective diagnostic sensitivity study was to assess the feasibility of ICG and NIRFI to identify SLNs in melanoma transcutaneously ("before skin incision") and to analyze the various factors influencing detection rate, in comparison to lymphoscintigraphy. This study included 93 patients undergoing SLN biopsy for cutaneous melanoma. The region and the number of the SLNs identified with lymphoscintigraphy and with ICG were recorded. Patients' characteristics, as well as tumor details were also recorded preoperatively. One hundred and ninety-four SLNs were identified through lymphoscintigraphy. The sensitivity of ICG for transcutaneous identification of the location of the SLNs was 96.1% overall, while the sensitivity rate for the number of SLNs was 79.4%. Gender and age did not seem to influence detection rate, but a body mass index >30 kg/m2 was associated with a lower identification rate of the number of SLNs (P = .045). Transcutaneous identification of SLNs through ICG and NIRFI technology is a feasible technique that could potentially replace in selected patients the standard SLN detection methodology in cutaneous melanoma

RWE in Europe Paper II: The use of Real World Evidence in the disease context

Real World Evidence (RWE), the use of data not collected via traditional randomised controlled trials (RCT) for decision-making, is becoming more interesting to market-access and reimbursement decision-makers, despite potential methodological issues around its use. This paper, the second in a series looking at the use of Real World Evidence (RWE) in Europe, analyses the opinions of a number of key experts in pricing and reimbursement from a selection of countries across Europe. Discussion centred on the use of RWE in licensing, commissioning, clinical decision-making and patient and outcome related decision-making in the context of three different treatment areas – chronic disease, oncology and rare diseases. Results of discussion sessions with ‘RWE experts’ indicated that the associated benefits of RWE are becoming more relevant but there is a need for a well-organised, high quality system for data generation, interpretation and use. It is likely that different treatment areas will have differing RWE requirements and differing levels of utility. In the rare disease arena, RWE may have a role in licensing based decisions, but this is unlikely for chronic disease or oncology. In order to enhance the role of RWE, and to ensure it meets its full potential in all treatment areas, a multi-stakeholder approach at the EU level is required, with collaboration between national and supranational organisations and all stakeholders including patient organisations, manufacturers and reimbursement agencies

RWE in Europe Paper III: A Roadmap for RWE

Real world evidence (RWE) has been touted as a remedy for current market access issues, facilitating quicker approvals and increased odds of reimbursement at a good price. It is therefore an attractive avenue for pursuit for manufacturers today. This paper, the third in a series looking at the use of RWE in Europe, outlines the discussions held between key opinion leaders in pricing and reimbursement across a number of European countries at a roundtable-style meeting. The aim of the meeting was to develop a 3-year roadmap, and resulting action plan, of initiatives for the enhanced use of RWE in decision-making in the pharmaceutical industry. Following a series of brainstorming sessions across the areas of commissioning and access, clinical evidence and patients and outcomes, contributors were asked to prioritise the importance of a refined set of initiatives identified in these brainstorming sessions to develop the three-year road map. Finally, four key points from the roadmap were identified for initial action: actively engage in early dialogue with payers on RWE needs; consensus exercise on RWD/E in clinical decisions, develop a definition of patient reported/relevant outcomes and develop a model approach for the collection of patient reported/relevant outcomes data. These action points are seen as the most imperative steps for enhancing the role of RWE. If its use is to become more common addressing these steps, as quickly and efficiently as possible, will be vital for all stakeholders in the pharmaceutical arena

Cancer Morbidity of Foundry Workers in Korea

Foundry workers are potentially exposed to a number of carcinogens. This study was conducted to describe the cancer incidence associated with employment in small-sized Korean iron foundries and to compare those findings to the Korean population. Cancer morbidity in 208 Korean foundries was analyzed using the Standardized Incidence Ratio (SIR) and Standardized Rate Ratio (SRR). Overall cancer morbidity in foundry workers (SIR=1.11, 95% confidence interval [CI]=1.01-1.21) was significantly higher than that of Korean general population. Lung cancer (SIR=1.45, 95%CI=1.11-1.87) and lymphohematopoietcic cancer (SIR=1.58, 95%CI=1.00-2.37) in production workers were significantly high compared to Korean general population. Stomach cancer in fettling (SRR=2.10, 95%CI=1.10-4.01) and lung cancer in molding (SRR=3.06, 95%CI=1.22-7.64) and in fettling (SRR=2.63, 95%CI=1.01-6.84) were there significant elevations compared to office workers. In this study, statistically significant excess lung cancer was observed in production workers comparing to Korean general population and office workers. Also, cancer morbidity of overall cancer, lung cancer and stomach cancer was significantly increased with duration of employment at ten and more years comparing to Korean general population. These findings suggest in causal association between exposure to carcinogens during foundry work and cancer morbidity

Exploratory Case‐Control Analysis of Psychosocial Factors and Adult Periodontitis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141163/1/jper1060.pd

The management of desmoid tumours: A joint global consensus-based guideline approach for adult and paediatric patients

Abstract Desmoid tumor (DT; other synonymously used terms: Desmoid-type fibromatosis, aggressive fibromatosis) is a rare and locally aggressive monoclonal, fibroblastic proliferation characterised by a variable and often unpredictable clinical course. Previously surgery was the standard primary treatment modality; however, in recent years a paradigm shift towards a more conservative management has been introduced and an effort to harmonise the strategy amongst clinicians has been made. We present herein an evidence-based, joint global consensus guideline approach to the management of this disease focussing on: molecular genetics, indications for an active treatment, and available systemic therapeutic options. This paper follows a one-day consensus meeting held in Milan, Italy, in June 2018 under the auspices of the European Reference Network for rare solid adult cancers, EURACAN, the European Organisation for Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group (STBSG) as well as Sarcoma Patients EuroNet (SPAEN) and The Desmoid tumour Research Foundation (DTRF). The meeting brought together over 50 adult and pediatric sarcoma experts from different disciplines, patients and patient advocates from Europe, North America and Japan

Transcriptional and Proteomic Analysis of the Aspergillus fumigatus ΔprtT Protease-Deficient Mutant

Aspergillus fumigatus is the most common opportunistic mold pathogen of humans, infecting immunocompromised patients. The fungus invades the lungs and other organs, causing severe damage. Penetration of the pulmonary epithelium is a key step in the infectious process. A. fumigatus produces extracellular proteases to degrade the host structural barriers. The A. fumigatus transcription factor PrtT controls the expression of multiple secreted proteases. PrtT shows similarity to the fungal Gal4-type Zn(2)-Cys(6) DNA-binding domain of several transcription factors. In this work, we further investigate the function of this transcription factor by performing a transcriptional and a proteomic analysis of the ΔprtT mutant. Unexpectedly, microarray analysis revealed that in addition to the expected decrease in protease expression, expression of genes involved in iron uptake and ergosterol synthesis was dramatically decreased in the ΔprtT mutant. A second finding of interest is that deletion of prtT resulted in the upregulation of four secondary metabolite clusters, including genes for the biosynthesis of toxic pseurotin A. Proteomic analysis identified reduced levels of three secreted proteases (ALP1 protease, TppA, AFUA_2G01250) and increased levels of three secreted polysaccharide-degrading enzymes in the ΔprtT mutant possibly in response to its inability to derive sufficient nourishment from protein breakdown. This report highlights the complexity of gene regulation by PrtT, and suggests a potential novel link between the regulation of protease secretion and the control of iron uptake, ergosterol biosynthesis and secondary metabolite production in A. fumigatus