The influence of the vocal tract on the attack transients in clarinet playing.

When playing single-reed woodwind instruments, players can modulate the spectral content of the airflow in their vocal tract, upstream of the vibrating reed. In an empirical study with professional clarinettists ( N p = 11 ), blowing pressure and mouthpiece pressure were measured during the performance of Clarinet Concerto excerpts. By comparing mouth pressure and mouthpiece pressure signals in the time domain, a method to detect instances of vocal tract adjustments was established. Results showed that players tuned their vocal tract in both clarion and altissimo registers. Furthermore, the analysis revealed that vocal tract adjustments support shorter attack transients and help to avoid lower bore resonances.

Somatostatin Analogues in the Treatment of Neuroendocrine Tumors: Past, Present and Future.

In recent decades, the incidence of neuroendocrine tumors (NETs) has steadily increased. Due to the slow-growing nature of these tumors and the lack of early symptoms, most cases are diagnosed at advanced stages, when curative treatment options are no longer available. Prognosis and survival of patients with NETs are determined by the location of the primary lesion, biochemical functional status, differentiation, initial staging, and response to treatment. Somatostatin analogue (SSA) therapy has been a mainstay of antisecretory therapy in functioning neuroendocrine tumors, which cause various clinical symptoms depending on hormonal hypersecretion. Beyond symptomatic management, recent research demonstrates that SSAs exert antiproliferative effects and inhibit tumor growth via the somatostatin receptor 2 (SSTR2). Both the PROMID (placebo-controlled, prospective, randomized study in patients with metastatic neuroendocrine midgut tumors) and the CLARINET (controlled study of lanreotide antiproliferative response in neuroendocrine tumors) trial showed a statistically significant prolongation of time to progression/progression-free survival (TTP/PFS) upon SSA treatment, compared to placebo. Moreover, the combination of SSA with peptide receptor radionuclide therapy (PRRT) in small intestinal NETs has proven efficacy in the phase 3 neuroendocrine tumours therapy (NETTER 1) trial. PRRT is currently being tested for enteropancreatic NETs versus everolimus in the COMPETE trial, and the potential of SSTR-antagonists in PRRT is now being evaluated in early phase I/II clinical trials. This review provides a synopsis on the pharmacological development of SSAs and their use as antisecretory drugs. Moreover, this review highlights the clinical evidence of SSAs in monotherapy, and in combination with other treatment modalities, as applied to the antiproliferative management of neuroendocrine tumors with special attention to recent high-quality phase III trials.

Treatment Strategies for Metastatic Neuroendocrine Tumors of the Gastrointestinal Tract.

OPINION STATEMENT: The therapeutic landscape of gastroenteropancreatic-neuroendocrine tumors (GEP-NETs) has evolved significantly in recent years. Current and emerging treatment options include somatostatin analogs, radiolabeled somatostatin analogs, the mTOR inhibitor everolimus, and the tyrosine kinase inhibitor sunitinib. Although high-quality data from phase III trials are lacking, cytotoxic agents are commonly used for the treatment of poorly differentiated neuroendocrine carcinomas and well-differentiated NETs originating in the pancreas. Hepatic-directed therapies are recommended for patients with slow-growing, liver-predominant disease but have never been compared to systemic agents. Telotristat ethyl, a novel serotonin synthesis inhibitor, has recently demonstrated efficacy in palliating diarrhea in patients with poorly controlled carcinoid syndrome. In the absence of definite predictive biomarkers, therapeutic decisions in most cases rely on clinical and pathological criteria. However, navigating the current therapeutic algorithm may be challenging, and future trials need to address several important questions: what is the best sequence of treatment? Is there a role for combination therapies in GEP-NETs? Are neoadjuvant, adjuvant, or maintenance strategies safe and effective? Do all NET patients require active treatment? What new molecular targets can be clinically exploited? A tight integration between basic and clinical research is needed to further advance the field of NETs.

Current treatment options for gastroenteropancreatic neuroendocrine tumors with a focus on the role of lanreotide.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a large and very diverse group of neoplasms. Clinical presentation of NETs depends on the site of the primary tumor and whether the tumor is functioning (i.e., secreting peptides or neuroamines that produce symptoms). The diagnosis of GEP-NET is further complicated by symptomatic differences that occur depending on the type of secreted peptide or neuroamine. Due to their heterogeneity and unique characteristics, early diagnosis of GEP-NETs is difficult, which increases the likelihood of metastatic disease and reduces the scope of therapeutic possibilities. Thus, a multidisciplinary approach for the treatment of GEP-NETs is necessary. This review is the result of presentations that were delivered during an expert meeting on the treatment of GEP-NETs supported by Ipsen. We summarize the current knowledge on the epidemiology, incidence, diagnosis, and treatment of GEP-NETs. We examined the role of the somatostatin analog (SSA) lanreotide and the impact of the data from the recently published, randomized, double-blind, placebo-controlled CLARINET study (Controlled study of Lanreotide Antiproliferative Response In Neuroendocrine Tumors) on disease management. We also review the recent treatment options and recommendations for GEP-NETs.

Sound analysis of a musical performance to evaluate prosthodontic treatment for a clarinet player.

Some dental patients use the orofacial region to play wind instruments; however, musical performance has not been objectively evaluated following prosthodontic treatment in such patients. The purpose of this report was to describe prosthodontic treatment for a clarinet player using sound analysis. The patient required a removable partial denture for his maxillary anterior teeth. Sound analysis was performed before and after denture adjustment, and the patient completed a questionnaire regarding his perceptions while playing his clarinet. After adjustment, the denture showed better performance, and patient satisfaction increased compared with that before adjustment.

Treatment of neuroendocrine tumors: new recommendations based on the CLARINET study.

Somatostatin analogs (SSAs), including lanreotide, play a fundamental role in treatment of neuroendocrine tumors (NETs) of the gastrointestinal tract. SSAs control the clinical symptoms and are the treatment of choice in functioning NETs. Data indicating that SSAs have anti-proliferative activity has mainly come from prospective or retrospective observational studies. A recently published CLARINET study confirmed the anti-proliferative effect of lanreotide in a much broader range of NET patients than previously reported. As a result, it is now possible for clinicians to use lanreotide to treat patients with well-differentiated metastatic grade 1 and grade 2 GEP NETs (i.e., with a Ki-67 proliferative index < 10%) located in the pancreas, small intestine, or of unknown primary location, regardless of the degree of liver involvement. The results of the CLARINET study also challenge the current "wait and watch" strategy for NET treatment. Instead, it is proposed that SSAs are considered at an early stage of NET management, as already suggested by many organizations and scientific societies.

[Efficacy of somatostatin analogues in the treatment of neuroendocrine tumours based on the results of recent clinical trials]. / A szomatosztatinanalógok hatékonysága a neuroendokrin daganatok kezelésében az új klinikai vizsgálatok tükrében.

Due to their inhibitory effects on hormone secretion, somatostatin analogues are of pivotal importance in the symptomatic treatment of hormone-secreting neuroendocrine tumours. Although several earlier clinical observations supported the view that these biological agents are capable of inhibiting the growth of neuroendocrine tumours, the PROMID study published in 2009 was the first to confirm the inhibitory effect of octreotide on tumour growth and demonstrated the prolongation of progression free survival. These findings have been confirmed and extended by the most recent CLARINET trial with lanreotide published in 2014. Somatostatin analogues are capable of inhibiting tumour growth and stabilizing disease irrespective of the hormonal activity of the tumour and, therefore, their applicability is expected to be extended to the treatment of hormonally inactive neuroendocrine tumours, as well.

Morphology, Taxonomy, Culm Internode and Leaf Anatomy, and Palynology of the Giant Reed (Arundo donax L.), Poaceae, Growing in Thailand.

In this paper, we present the morphology, taxonomy, anatomy, and palynology of Arundo donax. A detailed morphological description and illustrations of the species are provided, along with information about the identification, distribution, the specimens examined, habitat and ecology, the International Union for Conservation of Nature (IUCN) conservation assessment, phenology, etymology, vernacular name, and uses. The species can be distinguished by its large, tall rhizomatous perennial reed; cauline leaves; an open, large, plumose panicle inflorescence; subequal glumes as long as the spikelets; glabrous rachilla; all bisexual florets; and a lemma with a straight awn and with long white hairs outside below the middle part. In this study, two names were lectotypified: Arundo bifaria and A. bengalensis, which are synonyms of A. donax. The culm internodes in the transverse section have numerous vascular bundles scattered in the ground tissue, and the parenchyma cells have significantly lignified cell walls. Vascular bundles are composed of phloem and xylem and are enclosed in a continuous sclerenchymatous bundle sheath. The chloroplasts in the transverse section of the leaf blades are found only in the mesophyll cells but are absent in the bundle sheath cells, which indicates that it is a C3 grass. The leaves have stomata on both surfaces and are confined to the intercostal zones. The stomata are typically paracytic, with two lateral subsidiary cells placed parallel to the guard cells. The stomatal density is higher on the abaxial surface [450-839/mm2 (606.83 ± 72.71)] relative to the adaxial surface [286-587/mm2 (441.27 ± 50.72)]. The pollen grains are spheroidal or subspheroidal [polar axis length/equatorial axis length ratio (P/E ratio) = 0.89-1.16 (1.02 ± 0.07)] with a single pore surrounded by a faint annulus, and the exine sculpturing is granular.

Case Report: Psychoacoustic Analysis of a Clarinet Performance With a Custom-Made Soft Lip Shield Worn to Prevent Mucosal Erosion of Lower Lip.

Introduction: Wind instrument players sometimes suffer from erosion of the mucous membrane of the lip. This is caused by the action and pressure of the mouthpiece of the wind instrument against teeth. To address this problem, a lip shield is fitted over the dental arch to prevent direct contact between the lips and teeth. However, there are a few studies on the influence of the lip shield on the acoustics of wind instruments. The purpose of this study was to analyze the psychoacoustics of a clarinet performance with the player wearing a custom-made soft lip shield to prevent mucosal erosion of the lower lip. Case Description: A lip shield was custom-made with a soft thermoplastic material for a female clarinetist who complained of mucosal erosion and pain of the lower lip. The psychoacoustics of her musical performance played in different dynamics, fortissimo, mezzo forte and pianissimo were analyzed, including loudness and sharpness. A self-evaluation questionnaire with items rated on a 10-point scale was administered. After wearing the lip shield, the patient reported that the mucosal erosion and pain of her lower lip when playing clarinet resolved. The lip shield had little effect on the loudness. There was a slight decrease in sharpness when the lip shield was worn compared to when it was not, describing the reduction of high frequencies. Furthermore, fewer variations in sharpness between the tones were observed. Conclusion: The results suggest that lip shields made of soft materials can eliminate mucosal erosion and pain of the lower lip while having little effect on performance, although, a slight change in timbre is possible.

Facial Muscle Activity Patterns in Clarinet Players: A Key to Understanding Facial Muscle Physiology and Dysfunction in Musicians.

OBJECTIVES: Facial muscle activity is crucial to controlling musical performance in wind instrument playing. Facial muscle dysfunctions are common in wind instrument players, dramatically affecting their professional musical activity and potentially leading to disabling symptoms.The aim of this pilot study on a cohort of healthy clarinetists was to use surface electromyography to identify the facial muscle activity patterns involved in stabilizing the mouthpiece, controlling emission and articulation during musical tasks in physiological conditions, also comparing muscle activity between less and more experienced clarinetists (students vs postgraduates/professionals). METHODS: Surface electromyographic measures of the sternocleidomastoid, masseter, mentalis, mylohyoid and buccinator muscles were obtained from eight healthy clarinet players (four students and four postgraduates/professionals) performing two standardized musical tasks. RESULTS: Overall, mean IEMG activity was significantly lower for the sternocleidomastoid than for the other muscles (P = .000), and for the mouthpiece-stabilizing muscles (masseter and mentalis) than for those directly involved in controlling emission and articulation (buccinator and mylohyoid muscles) (P = .000).Regardless of the musical task, the mean IEMG values were significantly higher in the students for the masseter (P = .0007), buccinator (P = .0001) and mylohyoid (0.000), while they were significantly higher in the postgraduates/professionals for the mentalis (P = .000). No significant differences emerged between the two groups for the sternocleidomastoid (P = .207). CONCLUSIONS: These preliminary data reflect a significantly higher overall facial muscle activity in the less-experienced group, potentially resulting in an overload, whereas the more expert players had more optimized muscle activity patterns.

Integrating piezoresistive sensors on the embouchure analysis of the lower lip in single reed instrumentalists: implementation of the lip pressure appliance (LPA).

Background: It is essential to understand, characterize, and measure the embouchure mechanism of a wind instrumentalists, where the applied forces on the perioral tissues can usually promote discomfort or pain. Methods: The sample consisted of five clarinet players and five saxophone players. The embouchure force measurements at the lower lip area were assessed using a piezoresistive sensor (FlexiForceTM, Tekscan, Boston, USA, 0.07 kgf/cm2) placed on the lower part of the mouthpiece of the single reed instrument. Furthermore, each participant performed three times three different notes at different pitches: high, medium, and low. An intraoral device was manufactured in order to dissipate the existing pressures. Results: The piezoresistive sensors applied to the mouthpiece of the five clarinetists presented values between 16 and 226 g of force. In the case of the five saxophonists, the values registered were between 5 and 320 g of force. Conclusions: Piezoresistive sensors are a valid option to characterize that single reed instrumentalists apply substantial forces at the lower lip that can be equivalent to medium orthodontic forces. The implementation of the Lip Pressure Appliance can be a valid solution on the prevention of eventual lesions resulting from the embouchure forces.

Thermographic Study of the Orofacial Structures Involved in Clarinetists Musical Performance.

INTRODUCTION: Wind instrumentalists like clarinetists, may present a muscular hyperactivity on certain groups of the cranio-cervico-mandibular complex, due to their musical activity. Therefore, the use of infrared thermography can be used to assess and characterize the orofacial structures involved in clarinet performance. AIM: The objective of this study was to analyze and record the thermal patterns using the thermographic camera Flir® E60sc to evaluate anatomically and physiologically certain orofacial structures of the cranio-cervical-mandibular complex, such as the masticatory muscles and the region of the temporomandibular joint. METHODOLOGY: A sample of 30 clarinetists completed an individual questionnaire composed of two components (musical and clinical history of the participant), and were subjected to a clinical examination. Four thermographic images were taken of the cranio-cervical-mandibular complex at a rest position with frontal, right lateral, left lateral and anterior dentoalveolar components views. Each musician performed a piece of music for an uninterrupted period of 10 min. New thermographic images were captured with the same incidences, after the performance, respecting the same protocol. RESULTS: There were statistically significant differences in the areas corresponding to the left temporal muscle, the orbicularis muscle (labial component), the left and right perioral teguments, as well as in the upper central incisors. There was also statistical evidence regarding the initial and final temperature asymmetries regarding temporal muscle and orbicular muscles (labial and marginal components). CONCLUSION: Infrared thermography has been shown to be an effective complementary diagnostic tool in the monitorization of the cranio-cervical-mandibular complex of clarinetists.

Analysis of Tonguing and Blowing Actions During Clarinet Performance.

Articulation on the clarinet is achieved by a combination of precise actions taking place inside the player's mouth. With the aim to analyse the effects of tonguing and blowing actions during playing, several physical variables are measured and parameters related to articulation are studied. Mouth pressure, mouthpiece pressure and reed displacement are recorded in an experiment with clarinet players to evaluate the influence of the player's actions on the selected parameters and on the sound. The results show that different combinations of tongue and blowing actions are used during performance. Portato and legato playing show constant blowing throughout the musical phrase, which varies according to the dynamic level. In portato, short tongue-reed interaction is used homogeneously among players and playing conditions. In staccato playing, where the tongue-reed contact is longer, the mouth pressure is reduced significantly between notes. Such a mouth-pressure decrease might be used to stop the note in slow staccato playing. It is hereby shown that when the note is stopped by the action of the tongue both the attack and release transients are shorter compared to the case where the vibration of the reed is stopped by a decrease of mouth pressure.

Structural observations and biomechanical measurements of clarinet reeds made from Arundo donax.

Plant anatomy was examined for two clarinet reeds made out of Arundo donax by different means of microscopy: light microscopy, low-energy secondary electron scanning electron microscopy (SEM), backscattered electron SEM, and helium ion microscopy (HiM). The local indentation hardness HIT and Young's modulus EIT of different tissues on their cross sections were measured. A vascular bundle (Vb) (HIT = 60-100 MPa, EIT = 1,500-2,000 MPa) that includes soft tissues of phloem and xylem and a vascular bundle sheath (Bs) (HIT = 300-500 MPa, EIT = ∼7,000 MPa) form a pipe of the strong string along the longitudinal direction of the cane. This Vb/Bs string is connected transversally with a net of thin cell-walls of parenchyma cells (Pa) (HIT = 70-200 MPa, EIT = 2,000-3,000 MPa) that also range along the longitudinal direction of the cane. It was turned out that the acoustic quality of a reed is mainly ascribed to the shape and configuration of Vb and the size of Pa. A reed where Vb bundles with continuous Bs rings are homogeneously distributed with higher proportion among a softer network of small Pa cells enables musical performance.

Comparing the Cost of Treatment with Octreotide Long-Acting Release versus Lanreotide in Patients with Metastatic Gastrointestinal Neuroendocrine Tumors.

BACKGROUND: The 2 somatostatin analogs currently recommended by the National Comprehensive Cancer Network for the treatment of gastrointestinal (GI) neuroendocrine tumors (NETs) include octreotide long-acting release (Sandostatin LAR) for injectable suspension and lanreotide (Somatuline Depot) injection for subcutaneous use. OBJECTIVE: To estimate the costs to payers associated with 30-mg octreotide LAR and 120-mg lanreotide treatment among patients with metastatic GI-NETs. METHODS: The costs to payers associated with the 2 drugs were estimated by including the costs of each drug, drug administration, and adverse events. The unit drug costs for octreotide LAR and for lanreotide were obtained from ReadyPrice Wholesale Acquisition Cost; the doses were obtained from published studies. The adverse event rates were obtained from 2 phase 3 clinical trials, PROMID and CLARINET. Deterministic one-way sensitivity analyses were used to assess the impact of modifying assumptions and inputs on the results, including the 2017 Average Sales Price (ASP). All costs were estimated in 2016 US dollars, with a constant discount of 3%. RESULTS: The costs to payers associated with the treatment of GI-NETs during 1-, 3-, and 5-year horizons were $74,566, $180,082, and $262,344, respectively, for octreotide LAR and $84,856, $205,562, and $299,667, respectively, for lanreotide. Thus, octreotide LAR was associated with lower costs by $10,290 (1 year), $25,480 (3 years), and $37,323 (5 years) compared with lanreotide. Over a 5-year horizon, the costs of adverse events and administration accounted for 0.72% of the total cost for octreotide LAR and 0.51% of the total cost for lanreotide. Sensitivity analyses confirmed that the main factor affecting the cost difference was the price of the drugs; analyses using the ASP yielded similar results. CONCLUSION: For the management of metastatic GI-NETs, the cost to payers of treatment with 30-mg octreotide LAR is considerably lower than with 120-mg lanreotide over 1-, 3-, and 5-year horizons. In the presence of healthcare resource constraints, these findings may support decision-making when considering the care of patients with metastatic GI-NETs.

Finger Forces in Clarinet Playing.

Clarinettists close and open multiple tone holes to alter the pitch of the tones. Their fingering technique must be fast, precise, and coordinated with the tongue articulation. In this empirical study, finger force profiles and tongue techniques of clarinet students (N = 17) and professional clarinettists (N = 6) were investigated under controlled performance conditions. First, in an expressive-performance task, eight selected excerpts from the first Weber Concerto were performed. These excerpts were chosen to fit in a 2 × 2 × 2 design (register: low-high; tempo: slow-fast, dynamics: soft-loud). There was an additional condition controlled by the experimenter, which determined the expression levels (low-high) of the performers. Second, a technical-exercise task, an isochronous 23-tone melody was designed that required different effectors to produce the sequence (finger-only, tongue-only, combined tongue-finger actions). The melody was performed in three tempo conditions (slow, medium, fast) in a synchronization-continuation paradigm. Participants played on a sensor-equipped Viennese clarinet, which tracked finger forces and reed oscillations simultaneously. From the data, average finger force (F mean ) and peak force (F max ) were calculated. The overall finger forces were low (F mean = 1.17 N, F max = 3.05 N) compared to those on other musical instruments (e.g., guitar). Participants applied the largest finger forces during the high expression level performance conditions (F mean = 1.21 N). For the technical exercise task, timing and articulation information were extracted from the reed signal. Here, the timing precision of the fingers deteriorated the timing precision of the tongue for combined tongue-finger actions, especially for faster tempi. Although individual finger force profiles were overlapping, the group of professional players applied less finger force overall (F mean = 0.54 N). Such sensor instruments provide useful insights into player-instrument interactions and can also be used in the future to give feedback to students in various learning and practising situations.