"Every breath you take": evaluating sound levels and acoustic characteristics of various neonatal respiratory support and ventilation modalities.

Background: Early sensory experiences have a significant impact on the later life of preterm infants. The NICU soundscape is profoundly influenced by various modalities of respiratory support or ventilation, which are often mandatory early in the care. The incubator, believed to shield from external noise, is less effective against noise originating inside. The objective of this study was to evaluate the sound levels and characteristics of frequently used respiratory support and ventilation modalities, taking into consideration the developing auditory system of premature infants. Methods: To evaluate sound dynamics inside and outside an incubator during respiratory support/ventilation, experimental recordings were conducted at the Center for Pediatric Simulation Training of the Medical University Vienna. The ventilator used was a FABIAN HFOI®. Results: Jet CPAP (Continuous positive airway pressure), whether administered via mask or prongs, generates significantly higher sound levels compared to High-flow nasal cannula (HFNC) and to High-frequency oscillatory ventilation (HFOV) delivered through an endotracheal tube. Upon evaluating the sound spectrum of jet CPAP support, a spectral peak is observed within the frequency range of 4 to 8 kHz. Notably, this frequency band aligns with the range where the hearing threshold of preterm infants is at its most sensitive. Conclusion: Non-invasive HFNC and invasive HFOV generate lower sound levels compared to those produced by jet CPAP systems delivered via masks or prongs. Moreover, HFNC and HFOV show a reduced acoustic presence within the frequency range where the preterm infant's hearing is highly sensitive. Therefore, it is reasonable to speculate that the potential for auditory impairment might be more pronounced in preterm infants who require prolonged use of jet CPAP therapy during their time in the incubator.

Neuromagnetic representation of musical roundness in chord progressions.

Introduction: Musical roundness perception relies on consonance/dissonance within a rule-based harmonic context, but also on individual characteristics of the listener. The present work tackles these aspects in a combined psychoacoustic and neurophysiological study, taking into account participant's musical aptitude. Methods: Our paradigm employed cadence-like four-chord progressions, based on Western music theory. Chord progressions comprised naturalistic and artificial sounds; moreover, their single chords varied regarding consonance/dissonance and harmonic function. Thirty participants listened to the chord progressions while their cortical activity was measured with magnetoencephalography; afterwards, they rated the individual chord progressions with respect to their perceived roundness. Results: Roundness ratings differed according to the degree of dissonance in the dominant chord at the progression's third position; this effect was pronounced in listeners with high musical aptitude. Interestingly, a corresponding pattern occurred in the neuromagnetic N1m response to the fourth chord (i.e., at the progression's resolution), again with somewhat stronger differentiation among musical listeners. The N1m magnitude seemed to increase during chord progressions that were considered particularly round, with the maximum difference after the final chord; here, however, the musical aptitude effect just missed significance. Discussion: The roundness of chord progressions is reflected in participant's psychoacoustic ratings and in their transient cortical activity, with stronger differentiation among listeners with high musical aptitude. The concept of roundness might help to reframe consonance/dissonance to a more holistic, gestalt-like understanding that covers chord relations in Western music.

Exploring the Surface Oxidation and Environmental Instability of 2H-/1T'-MoTe2 Using Field Emission-Based Scanning Probe Lithography.

An unconventional approach for the resistless nanopatterning 2H- and 1T'-MoTe2 by means of scanning probe lithography is presented. A Fowler-Nordheim tunneling current of low energetic electrons (E = 30-60 eV) emitted from the tip of an atomic force microscopy (AFM) cantilever is utilized to induce a nanoscale oxidation on a MoTe2 nanosheet surface under ambient conditions. Due to the water solubility of the generated oxide, a direct pattern transfer into the MoTe2 surface can be achieved by a simple immersion of the sample in deionized water. The tip-grown oxide is characterized using Auger electron and Raman spectroscopy, revealing it consists of amorphous MoO3 /MoOx as well as TeO2 /TeOx . With the presented technology in combination with subsequent AFM imaging it is possible to demonstrate a strong anisotropic sensitivity of 1T'-/(Td )-MoTe2 to aqueous environments. Finally the discussed approach is used to structure a nanoribbon field effect transistor out of a few-layer 2H-MoTe2 nanosheet.

Living in a box: Understanding acoustic parameters in the NICU environment.

Background: In the last years, a significant body of scientific literature was dedicated to the noisy environment preterm-born infants experience during their admission to Neonatal Intensive Care Units (NICUs). Nonetheless, specific data on sound characteristics within and outside the incubator are missing. Therefore, this study aimed to shed light on noise level and sound characteristics within the incubator, considering the following domain: environmental noise, incubator handling, and respiratory support. Methods: The study was performed at the Pediatric Simulation Center at the Medical University of Vienna. Evaluation of noise levels inside and outside the incubator was performed using current signal analysis libraries and toolboxes, and differences between dBA and dBSPL values for the same acoustic noises were investigated. Noise level results were furthermore classed within previously reported sound levels derived from a literature survey. In addition, sound characteristics were evaluated by means of more than 70 temporal, spectral, and modulatory timbre features. Results: Our results show high noise levels related to various real-life situations within the NICU environment. Differences have been observed between A weighted (dBA) and unweighted (dBSPL) values for the same acoustic stimulus. Sonically, the incubator showed a dampening effect on sounds (less high frequency components, less brightness/sharpness, less roughness, and noisiness). However, a strong tonal booming component was noticeable, caused by the resonance inside the incubator cavity. Measurements and a numerical model identified a resonance of the incubator at 97 Hz and a reinforcement of the sound components in this range of up to 28 dB. Conclusion: Sound characteristics, the strong low-frequency incubator resonance, and levels in dBSPL should be at the forefront of both the development and promotion of incubators when helping to preserve the hearing of premature infants.

Randomized Phase II Cabazitaxel Dose Individualization and Neutropenia Prevention Trial in Patients with Metastatic Castration-Resistant Prostate Cancer.

PURPOSE: There is ongoing controversy about the recommended dose of cabazitaxel in patients with metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: This multicenter phase II open-label, randomized, parallel-group study compared 3-weekly cabazitaxel at 25 mg/m2 (conventional arm A) with cabazitaxel therapeutic drug monitoring (experimental arm B) in mCRPC. The primary objective was to improve the clinical feasibility rate (CFR), defined as the absence of grade 4 neutropenia or thrombocytopenia, any thrombocytopenia with bleeding, febrile neutropenia, severe nonhematologic toxicity, withdrawal for cabazitaxel-related toxicity, or death. A total of 60 patients had to be randomized to detect a difference in CFR of 35% (power 80%, two-sided alpha 10%). RESULTS: A total of 40 patients were randomized to arm A and 33 patients to arm B. CFR was 69.4% in arm A and 64.3% in arm B (P = 0.79). Week-12 PSA response was 38.5% in both arms. A radiological response by RECIST v.1.1 was seen in 3 (9.7%) patients in arm A versus 6 (23.1%) patients in arm B (P = 0.28), disease progression was higher in arm A compared with arm B (61.3% vs. 30.8%, P = 0.05). Median progression-free survival was longer in arm B compared with arm A (9.5 vs. 4.4 months; HR = 0.46; P = 0.005). Median overall survival was higher in arm B compared with arm A (16.2 vs. 7.3 months; HR = 0.33; P < 0.0001). CONCLUSIONS: Pharmacokinetic-guided dosing of cabazitaxel in patients with mCRPC is feasible and improves clinical outcome due to individual dose escalations in 55% of patients.

Audio Feature Analysis for Acoustic Pain Detection in Term Newborns.

INTRODUCTION: Crying newborns signal a need or discomfort as part of the innate communication system. Exposure to pain is related to infants' unfavorable neurodevelopmental outcomes. There is a tremendous need for more objective methods to assess neonatal pain. An audio analysis of acoustic utterances could provide specific information on the patient's pain level. METHODS: We analyzed 67 videos of 33 term-born newborns recorded during a planned capillary blood sample, including the stimuli, non-noxious thermal stimulus, short noxious stimulus, and prolonged unpleasant stimulus, between December 2020 and March 2021. Two expert raters evaluated the infants' pain responses using the Neonatal Facial Coding System (NFCS). The mean values of 123 timbre features of the recorded audio data were analyzed by using specific toolboxes and libraries from the following programming environments: MIRtoolbox (MATLAB), MiningSuite (MATLAB), Essentia (Python), AudioCommons timbral models (Python), and Librosa (Python). RESULTS: The NFCS values were significantly higher during the short noxious stimulus (p < 0.001) and prolonged unpleasant stimulus (p < 0.001) than during the non-noxious thermal stimulus, whereas NFCS values during the short noxious stimulus and prolonged unpleasant stimulus were similar (p = 0.79). Brightness, roughness, percussive energy, and attack times were identified as the features having the highest impact on the NFCS. CONCLUSION: This hypothesis-generating study identified several salient acoustic features highly associated with pain responses in term newborns. Our analysis is an encouraging starting point for the targeted analysis of pain-specific acoustic features of neonatal cries and vocalizations from the perspective of real-time acoustic processing.

Shewanella algae bacteraemia in a patient with a chronic ulcer after contact with seawater on vacation in Turkey: A case report from a German maximum-care hospital.

After seawater baths in Antalya, Turkey, a 55-year-old man suffered from Shewanella algae bacteraemia. Imported/travel-related S. algae infections should be kept in mind, also in usually rather cold geographical areas, as patterns of seawater-associated bacilli infections might change due to warming of seawater caused by climate change.

Associations Between Ancillary Body Movements and Acoustic Parameters of Pitch, Dynamics and Timbre in Clarinet Playing.

When playing an instrument, there are two main categories of body movements: instrumental movements, which are necessary for the sound production, and ancillary movements, which are associated with individual musical intentions and expressions. In this study, the particular purpose of ancillary movements of clarinet player was investigated especially in respect to how these movements were related to the musical structure of the piece and to specific audio parameters. 3D motion capture data of 19 clarinet players performing the same piece were analyzed regarding common motion patterns during the performance and in accordance with acoustic features related to pitch, dynamics (RMS energy) and timbre (spectral centroid and flux). A focus of the body movements was on the arms and the knees. The results showed that there were certain motion patterns performed by the players depending on specific musical structures. When playing a melodic part, the players often did so by bending their knees. At musical transitions, however, the knees were mainly stretched. Similarly, arm movements were more pronounced during playing melodious parts. At transitions, the arms were put closer to the torso. Considering the connection with the acoustics, a larger range of knee motions was correlated with a larger variation of the timbre. Moreover, at specific moments during the performance, when some players strongly bent their knees or lifted the arms, the RMS energy of the signal was significantly higher. The correlations of the body movements and the acoustic features showed that some players synchronized their movements with particular audio parameters more than others did. In summary, the ancillary movements of the clarinetists pursued both musical expressive intentions and physiologically necessary movements and tended to be performed with individual differences in terms of visual and auditory expression.

Improving survival in metastatic renal cell carcinoma (mRCC) patients: do elderly patients benefit from expanded targeted therapeutic options?

INTRODUCTION: Treatment advances in metastatic renal cell carcinoma (mRCC) have improved overall survival (OS) in mRCC patients over the last two decades. This single center retrospective analysis assesses if the purported survival benefits are also applicable in elderly mRCC patients. METHODS: 401 patients with mRCC treated at Hannover Medical School from 01/2003-05/2016 were identified and evaluated by chart review. Treatment periods were defined as 01.01.2003-31.12.2009 (P1) and 01.01.2010-31.05.2016 (P2). Age groups were defined according to WHO classes (≤ 60 years: younger, > 60-75 years: elderly and > 75 years: old). Descriptive statistics, Kaplan-Meier analysis and logistic regression were performed. RESULTS: Median OS improved from 35.1 months in P1 to 59.1 months in P2. Sub-division into the respective age groups revealed median survival of 38.1 (95%-CI: 28.6-47.6) months in younger patients, 42.9 (95%-CI: 29.5-56.3) months among elderly patients and 27.3 (95%-CI: 12.8-41.8) months among old patients. Risk reduction for death between periods was most evident among old patients (young: HR 0.71 (95%-CI: 0.45-1.13, p = 0.2); elderly: HR 0.62 (95%-CI: 0.40-0.97, p = 0.04); old: HR 0.43 (95%-CI: 0.18-1.05, p = 0.06)). Age ≥ 75 years was an independent risk factor for death in P1 but not in P2. CONCLUSION: Improved OS in the targeted treatment period was confirmed. Surprisingly elderly and old patients seem to profit the most form expansion of therapeutic armamentarium, within the TKI-dominated observation period.

The Effects of Pitch Manipulation on Male Ratings of Female Speakers and Their Voices.

Vocal and facial cues typically co-occur in natural settings, and multisensory processing of voice and face relies on their synchronous presentation. Psychological research has examined various facial and vocal cues to attractiveness as well as to judgements of sexual dimorphism, health, and age. However, few studies have investigated the interaction of vocal and facial cues in attractiveness judgments under naturalistic conditions using dynamic, ecologically valid stimuli. Here, we used short videos or audio tracks of females speaking full sentences and used a manipulation of voice pitch to investigate cross-modal interactions of voice pitch on facial attractiveness and related ratings. Male participants had to rate attractiveness, femininity, age, and health of synchronized audio-video recordings or voices only, with either original or modified voice pitch. We expected audio stimuli with increased voice pitch to be rated as more attractive, more feminine, healthier, and younger. If auditory judgements cross-modally influence judgements of facial attributes, we additionally expected the voice pitch manipulation to affect ratings of audiovisual stimulus material. We tested 106 male participants in a within-subject design in two sessions. Analyses revealed that voice recordings with increased voice pitch were perceived to be more feminine and younger, but not more attractive or healthier. When coupled with video recordings, increased pitch lowered perceived age of faces, but did not significantly influence perceived attractiveness, femininity, or health. Our results suggest that our manipulation of voice pitch has a measurable impact on judgements of femininity and age, but does not measurably influence vocal and facial attractiveness in naturalistic conditions.

Prognostic role of docetaxel-induced suppression of free testosterone serum levels in metastatic prostate cancer patients.

To date, only few data concerning the biologically active, free form of testosterone (FT) are available in metastatic prostate cancer (mPC) and the impact of FT on disease, therapy and outcome is largely unknown. We retrospectively studied the effect of docetaxel on FT and total testosterone (TT) serum levels in 67 mPC patients monitored between April 2008 and November 2020. FT and TT levels were measured before and weekly during therapy. The primary endpoint was overall survival (OS). Secondary endpoints were prostate-specific antigen response and radiographic response (PSAR, RR), progression-free survival (PFS), FT/TT levels and safety. Median FT and TT serum levels were completely suppressed to below the detection limit during docetaxel treatment (FT: from 0.32 to < 0.18 pg/mL and TT: from 0.12 to < 0.05 ng/mL, respectively). Multivariate Cox regression analyses identified requirement of non-narcotics, PSAR, complete FT suppression and FT nadir values < 0.18 pg/mL as independent parameters for PFS. Prior androgen-receptor targeted therapy (ART), soft tissue metastasis and complete FT suppression were independent prognostic factors for OS. FT was not predictive for treatment outcome in mPC patients with a history of ART.

Spectral envelope position and shape in sustained musical instrument sounds.

It has been argued that the relative position of spectral envelopes along the frequency axis serves as a cue for musical instrument size (e.g., violin vs viola) and that the shape of the spectral envelope encodes family identity (violin vs flute). It is further known that fundamental frequency (F0), F0-register for specific instruments, and dynamic level strongly affect spectral properties of acoustical instrument sounds. However, the associations between these factors have not been rigorously quantified for a representative set of musical instruments. Here, we analyzed 5640 sounds from 50 sustained orchestral instruments sampled across their entire range of F0s at three dynamic levels. Regression of spectral centroid (SC) values that index envelope position indicated that smaller instruments possessed higher SC values for a majority of instrument classes (families), but SC also correlated with F0 and was strongly and consistently affected by the dynamic level. Instrument classification using relatively low-dimensional cepstral audio descriptors allowed for discrimination between instrument classes with accuracies beyond 80%. Envelope shape became much less indicative of instrument class whenever the classification problem involved generalization to different dynamic levels or F0-registers. These analyses confirm that spectral envelopes encode information about instrument size and family identity and highlight their dependence on F0(-register) and dynamic level.

Impact of sarcopenia in advanced and metastatic soft tissue sarcoma.

INTRODUCTION: Advanced or metastatic soft tissue sarcoma (a/mSTS) is associated with a dismal prognosis. Patient counseling on treatment aggressiveness is pivotal to avoid over- or undertreatment. Recently, evaluation of body composition markers like the skeletal muscle index (SMI) became focus of interest in a variety of cancers. This study focuses on the prognostic impact of SMI in a/mSTS, retrospectively. METHODS: 181 a/mSTS patients were identified, 89 were eligible due to prespecified criteria for SMI assessment. Baseline CT-Scans were analyzed using an institutional software solution. Sarcopenia defining cut-off values for the SMI were established by optimal fitting method. Primary end point was overall survival (OS) and secondary endpoints were progression free survival (PFS), disease control rate (DCR), overall response rate (ORR). Descriptive statistics as well as Kaplan Meier- and Cox regression analyses were administered. RESULTS: 28/89 a/mSTS patients showed sarcopenia. Sarcopenic patients were significantly older, generally tended to receive less multimodal therapies (62 vs. 57 years, P = 0.025; respectively median 2.5 vs. 4, P = 0.132) and showed a significantly lower median OS (4 months [95%CI 1.9-6.0] vs. 16 months [95%CI 8.8-23.2], Log-rank P = 0.002). Sarcopenia was identified as independent prognostic parameter of impaired OS (HR 2.40 [95%-CI 1.4-4.0], P < 0.001). Moreover, DCR of first palliative medical treatment was superior in non-sarcopenic patients (49.2% vs. 25%, P = 0.032). CONCLUSION: This study identifies sarcopenia as a prognostic parameter in a/mSTS. Further on, the data suggest that sarcopenia shows a trend of being associated with first line therapy response. SMI is a promising prognostic parameter, which needs further validation.

Questions and Controversies in the Clinical Application of Tyrosine Kinase Inhibitors to Treat Patients with Radioiodine-Refractory Differentiated Thyroid Carcinoma: Expert Perspectives.

Notwithstanding regulatory approval of lenvatinib and sorafenib to treat radioiodine-refractory differentiated thyroid carcinoma (RAI-R DTC), important questions and controversies persist regarding this use of these tyrosine kinase inhibitors (TKIs). RAI-R DTC experts from German tertiary referral centers convened to identify and explore such issues; this paper summarizes their discussions. One challenge is determining when to start TKI therapy. Decision-making should be shared between patients and multidisciplinary caregivers, and should consider tumor size/burden, growth rate, and site(s), the key drivers of RAI-R DTC morbidity and mortality, along with current and projected tumor-related symptomatology, co-morbidities, and performance status. Another question involves choice of first-line TKIs. Currently, lenvatinib is generally preferred, due to greater increase in progression-free survival versus placebo treatment and higher response rate in its pivotal trial versus that of sorafenib; additionally, in those studies, lenvatinib but not sorafenib showed overall survival benefit in subgroup analysis. Whether recommended maximum or lower TKI starting doses better balance anti-tumor effects versus tolerability is also unresolved. Exploratory analyses of lenvatinib pivotal study data suggest dose-response effects, possibly favoring higher dosing; however, results are awaited of a prospective comparison of lenvatinib starting regimens. Some controversy surrounds determination of net therapeutic benefit, the key criterion for continuing TKI therapy: if tolerability is acceptable, overall disease control may justify further treatment despite limited but manageable progression. Future research should assess potential guideposts for starting TKIs; fine-tune dosing strategies and further characterize antitumor efficacy; and evaluate interventions to prevent and/or treat TKI toxicity, particularly palmar-plantar erythrodysesthesia and fatigue.

Usability of Individualized Head-Related Transfer Functions in Virtual Reality: Empirical Study With Perceptual Attributes in Sagittal Plane Sound Localization.

BACKGROUND: In order to present virtual sound sources via headphones spatially, head-related transfer functions (HRTFs) can be applied to audio signals. In this so-called binaural virtual acoustics, the spatial perception may be degraded if the HRTFs deviate from the true HRTFs of the listener. OBJECTIVE: In this study, participants wearing virtual reality (VR) headsets performed a listening test on the 3D audio perception of virtual audiovisual scenes, thus enabling us to investigate the necessity and influence of the individualization of HRTFs. Two hypotheses were investigated: first, general HRTFs lead to limitations of 3D audio perception in VR and second, the localization model for stationary localization errors is transferable to nonindividualized HRTFs in more complex environments such as VR. METHODS: For the evaluation, 39 subjects rated individualized and nonindividualized HRTFs in an audiovisual virtual scene on the basis of 5 perceptual qualities: localizability, front-back position, externalization, tone color, and realism. The VR listening experiment consisted of 2 tests: in the first test, subjects evaluated their own and the general HRTF from the Massachusetts Institute of Technology Knowles Electronics Manikin for Acoustic Research database and in the second test, their own and 2 other nonindividualized HRTFs from the Acoustics Research Institute HRTF database. For the experiment, 2 subject-specific, nonindividualized HRTFs with a minimal and maximal localization error deviation were selected according to the localization model in sagittal planes. RESULTS: With the Wilcoxon signed-rank test for the first test, analysis of variance for the second test, and a sample size of 78, the results were significant in all perceptual qualities, except for the front-back position between own and minimal deviant nonindividualized HRTF (P=.06). CONCLUSIONS: Both hypotheses have been accepted. Sounds filtered by individualized HRTFs are considered easier to localize, easier to externalize, more natural in timbre, and thus more realistic compared to sounds filtered by nonindividualized HRTFs.

The "Sound of Silence" in a Neonatal Intensive Care Unit-Listening to Speech and Music Inside an Incubator.

Background: The intrauterine hearing experience differs from the extrauterine hearing exposure within a neonatal intensive care unit (NICU) setting. Also, the listening experience of a neonate drastically differs from that of an adult. Several studies have documented that the sound level within a NICU exceeds the recommended threshold by far, possibly related to hearing loss thereafter. The aim of this study was, first, to precisely define the dynamics of sounds within an incubator and, second, to give clinicians and caregivers an idea about what can be heard "inside the box." Methods: Audio recordings within an incubator were conducted at the Pediatric Simulation Center of the Medical University Vienna. They contained recorded music, speech, and synthesized sounds. To understand the dynamics of sounds around and within the incubator, the following stimuli were used: broadband noise with decreasing sound level in 10 steps of 6 dB, sine waves (62.5, 125, 250, 500, 1000, 2000, 4000, 8000, and 16,000 Hz), logarithmic sweep (Chirp) over the frequency band 20 Hz to 21 kHz, singing male voice, singing, and whispering female voice. Results: Our results confirm a protective effect of the incubator from noises above 500 Hz in conditions of "no-flow" and show almost no protective effect of an incubator cover. We, furthermore, observed a strong boost of low frequencies below 125 Hz within the incubator, as well as a notable increase of higher frequency noises with open access doors, a significant resonant effect of the incubator, and a considerable masking effect of the respiratory support against any other source of noise or sound stimulation even for "low-flow" conditions. Conclusion: Our study reveals high noise levels of air supply at high flow rates and the boost of low frequencies within the incubator. Education of medical staff and family members as well as modifications of the physical environment should aim at reducing noise exposure of preterm infants in the incubator. Audiovisual material is provided as Supplementary Material.

Lights Out! Nano-Scale Topography Imaging of Sample Surface in Opaque Liquid Environments with Coated Active Cantilever Probes.

Atomic force microscopy is a powerful topography imaging method used widely in nanoscale metrology and manipulation. A conventional Atomic Force Microscope (AFM) utilizes an optical lever system typically composed of a laser source, lenses and a four quadrant photodetector to amplify and measure the deflection of the cantilever probe. This optical method for deflection sensing limits the capability of AFM to obtaining images in transparent environments only. In addition, tapping mode imaging in liquid environments with transparent sample chamber can be difficult for laser-probe alignment due to multiple different refraction indices of materials. Spurious structure resonance can be excited from piezo actuator excitation. Photothermal actuation resolves the resonance confusion but makes optical setup more complicated. In this paper, we present the design and fabrication method of coated active scanning probes with piezoresistive deflection sensing, thermomechanical actuation and thin photoresist polymer surface coating. The newly developed probes are capable of conducting topography imaging in opaque liquids without the need of an optical system. The selected coating can withstand harsh chemical environments with high acidity (e.g., 35% sulfuric acid). The probes are operated in various opaque liquid environments with a custom designed AFM system to demonstrate the imaging performance. The development of coated active probes opens up possibilities for observing samples in their native environments.

Don't drink and chill: Effects of alcohol on subjective and physiological reactions during music listening and their relationships with personality and listening habits.

Recent research indicates that favorite music can induce chills and alters physiological reactions. People frequently listen to music when they drink alcohol, for example in bars or discotheques. Alcohol has numerous effects on emotions, peripheral physiological and neural reactions. We investigated whether alcohol intake influences chill experiences and physiological reactions during music listening. 39 participants took part in the study and were tested twice: Once in a sober condition and once when they had drunken alcohol. Participants listened to two pieces of music in each of the two conditions: A favorite self-selected song and a control-song that was selected by the research group. Participants had to indicate when they experienced a chill and electrodermal activity and heart rate were measured during music listening. In addition, participants filled out questionnaires concerning the big five personality dimensions, music listening habits and general chill experiences. Results indicate that participants experienced most chills when they were sober and listened to their self-selected song. Electrodermal activity was highest when participants were sober. In addition, alcohol intake led to a dedifferentiation in heart rate activity. After alcohol intake, participants had similar heart rates, no matter whether they listened to their self-selected song or to the control-song. Extraversion was negatively related with physiological reactions, while openness to experiences was positively related with physiological reactions. Music listening habits also showed various relationships with chill experiences and physiological reactions, while general chill experiences did not. We conclude that alcohol intake reduces subjective chill experiences during music listening and alters the physiological reactions to music. Music listening habits and personality seem to influence these effects.

Role of free testosterone levels in patients with metastatic castration-resistant prostate cancer receiving second-line therapy.

A range of new treatment options has recently become available for patients with advanced metastatic castration-resistant prostate cancer (mCRPC). Androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone is continued when performing chemotherapy or androgen deprivation with new second-generation therapeutic agents such as enzalutamide or abiraterone acetate. Despite the fact that free testosterone (FT) is the biologically active form, it is common practice that androgen suppression is monitored via total testosterone levels only. The aim of the present study was to evaluate the role of FT as a prognostic biomarker for cancer-specific survival (CSS) and its feasibility as an ADT monitoring biomarker in patients with mCRPC for the first time. The requirement for continued ADT in mCRPC patients is discussed within the basis of the current literature. A total of 34 patients with continuous measurements of FT levels and mCRPC status underwent therapy with docetaxel, abiraterone acetate, enzalutamide, cabozantinib, carboplatin or cabazitaxel. Data were obtained from the Departments of Urology and Urological Oncology, Hannover Medical School (Hannover, Germany) between March 2009 and April 2014. A cutoff point of 0.5 pg/ml was used to discriminate between patients according to FT levels. Statistical evaluation of CSS was performed by applying Kaplan Meier survival estimates, multivariate Cox regression analyses and log-rank tests. The median age of all 34 patients was 72 years (range, 51-86 years). The mean follow-up interval was 16.1 months (range, 0.7-55.6 months). Despite the fact that all patients were undergoing androgen deprivation, the mean serum FT levels for each patient varied; the mean FT concentration in the cohort was 0.328 pg/ml, ranging from 0.01-9.1 pg/ml. A notable difference with regard to CSS was observed for patients with regard to serum FT concentration; CSS was significantly longer for patients with a serum FT level below the cutoff level (43.6 vs. 17.3 months, respectively, P=0.0063). Upon multivariate Cox regression analysis, the mean FT concentration during treatment remained a significant prognostic factor for CSS (hazard ratio, 1.22; 95% confidence interval, 1.03-1.43; P=0.0182). In conclusion, in patients with mCRPC, the serum FT level is a strong predictor of CSS in patients under therapy with second-line anti-hormonal therapeutic medication and chemotherapy. It may be concluded that FT levels should be included into the routine control of androgen suppression while under treatment with ADT and second-generation hormonal therapy.

Lack of noncanonical RAS mutations in cytogenetically normal acute myeloid leukemia.

Transforming mutations in RAS genes are commonly found in human malignancies, including myeloid leukemias. To investigate the incidence, spectrum, and distribution of activating K- and N-RAS mutations in cytogenetically normal acute myeloid leukemia (CN-AML) patients, 204 CN-AML patients were screened. Activating K- and N-RAS mutations were detected in 3 of 204 (1.5 %) and 22 of 204 (10.8 %) CN-AML samples, respectively. RAS mutated patients presented with a lower percentage of bone marrow blasts (65 vs 80 %, P = 0.022). RAS mutations tended to occur with nucleophosmin-1 (NPM1) mutations (P = 0.079), and all three samples containing K-RAS mutations had concomitant NPM1 mutations. There was no significant overlap between K-RAS mutations and N-RAS, FLT3, CEBPA, IDH1/2, WT1 or MLL mutations. RAS mutation status did not impact relapse-free or overall survival of CN-AML patients. In contrast to reports of noncanonical RAS mutations in other cancers, including some leukemia subtypes, we only observed K- and N-RAS mutations in codons 12, 13, or 61 in CN-AML samples. Our findings suggest that while K-RAS mutations are infrequent in CN-AML, activating K-RAS mutations may cooperate with mutated NPM1 to induce leukemia.