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Background: Tinnitus severity is generally assessed by psychometric and audiological instruments. However, no objective measure exists to evaluate the subjective discomfort and suffering caused by this hearing phenomenon. The objective of this work was to determine the possible blood parameters for diagnostics and therapy. Methods: We measured tinnitus distress by using the Tinnitus Questionnaire (TQ) and collected tinnitus-related audiological measures, namely the hearing threshold (HT), tinnitus loudness (TL), and sensation level (SL, i.e., the tinnitus loudness/hearing threshold at a tinnitus frequency). Blood samples were taken from 200 outpatients of the Tinnitus Centre of the Charité, and 46 routine blood count parameters were examined. The possible interactions were determined by (robust) linear models. Results: Tinnitus distress and audiological measurements were largely uncorrelated but could partly be predicted by selected blood parameters. First, the erythrocyte counts predicted tinnitus distress to a small extent. Second, the levels of vitamin D3 explained about 6% of tinnitus loudness and, age-dependently, the hearing threshold variability. Last, the levels of uric acid explained about 5% of the sensation level variability. Conclusions: Tinnitus is a multidimensional phenomenon. The marginal influences of blood markers suggest the possible roles of inflammation and oxidative stress produced by psychological or somatic burdens. Clinically, a vitamin D substitution (in older patients) might have a hearing-protective effect.

2 Universit e de Caen Abstract: Two methods for clustering data and choosing a mixture model are proposed. First, we derive a new classication algorithm based on the classication likelihood. Then, the likelihood conditional on these clusters is written as the product of likelihoods of each cluster, and AIC- respectively BIC-type approximations are applied. The resulting criteria turn out to be the sum of the AIC or BIC relative to each cluster plus an entropy term. The performance of our methods is evaluated by Monte-Carlo methods and on a real data set, showing in particular that the iterative estimation algorithm converges quickly in general, and thus the computational load is rather low.

Hidden Markov and semi-Markov models (H(S)MMs) constitute useful tools for modeling observations subject to certain dependency structures. The hidden states render these models very flexible and allow them to capture many different types of latent patterns and dynamics present in the data. This has led to the increased popularity of these models, which have been applied to a variety of problems in various domains and settings, including longitudinal data. In many longitudinal studies, the response variable is categorical or count-type. Generalized linear mixed models (GLMMs) can be used to analyze a wide range of variables, including categorical and count. The present study proposes a model that combines HSMMs with GLMMs, leading to generalized linear mixed hidden semi-Markov models (GLM-HSMMs). These models can account for time-varying unobserved heterogeneity and handle different response types. Parameter estimation is achieved using a Monte Carlo Newton-Raphson (MCNR)-like algorithm. In our proposed model, the distribution of the random effects depends on hidden states. We illustrate the applicability of GLM-HSMMs with an example in the field of occupational health, where the response variable consists of count values. Furthermore, we assess the performance of our MCNR-like algorithm through a simulation study.

Zusammenfassung Patienten mit nordafrikanischem und subsaharischem Migrationshintergrund sind im Vergleich zu ihrem Anteil an der Allgemeinbevölkerung im baden-württembergischen Maßregelvollzug überrepräsentiert. Internationale Studien legen nahe, dass Migranten mit sichtbarem Minderheitenstatus und von der Bevölkerungsmehrheit abweichender Ethnizität ein höheres Risiko haben, an psychotischen Störungen zu erkranken. Zu den psychosozialen Erklärungsansätzen gehören soziale Benachteiligung und geringe ethnische Dichte. In der vorliegenden Studie wurden nach Paragraph 63 StGB untergebrachte Patienten aus Nord- und Subsahara-Afrika (N = 71) untersucht, um Anhaltspunkte für die Erklärung der hohen Zuweisungsraten zu finden. Zwei Vergleichsgruppen aus westeuropäischen (N = 73) und kasachischen (N = 32) Patienten wurden ausgewählt. Die afrikanischen Patienten hatten signifikant weniger abgeschlossene Berufsausbildungen und waren zum Zeitpunkt der Straftat häufiger obdachlos. Außerdem war der Anteil der F20.0 Diagnosen signifikant höher (87 %). In Bezug auf die psychiatrische und kriminologische Vorgeschichte, Alter bei Erstdelinquenz und Abhängigkeitsstörungen wurden keine Unterschiede gefunden. Diskutiert wird die Rolle migrationsbedingter sozialer Benachteiligung für die hohen Psychose-Raten in einigen Migrantengruppen. Ferner werden potenzielle Wege für Gewaltdelinquenz betrachtet. Die Relevanz kultursensibler Prävention und Intervention wird in Anbetracht der steigenden Zahlen von Migranten aus den untersuchten Regionen betont.

In this article, we describe critical epidemiological trends in forensic psychiatric care in the German federal state of Baden-Württemberg. For some years, there has been a marked increase in the number of patients with psychoses and with a migration background in the high-security hospitals of Baden-Württemberg. We present a number of studies exploring hypotheses as to why this is the case. Taking into account a set of person-related and non-person (forensic system)-related variables, we suggest that rising treatment figures may be understood in terms of system variables rather than individual patient characteristics. Findings regarding predictors of treatment length and legal outcome, as well as characteristics of migrant patients and patients assigned to forensic aftercare, are discussed.

BackgroundTinnitus is a heterogeneous condition associated with moderate to severe disability, but the reasons why only a subset of individuals is burdened by the condition are not fully clear. Ecological momentary assessment (EMA) allows a better understanding of tinnitus by allowing individualized models and by capturing the fluctuations of tinnitus symptoms and other behavioral dynamics as they occur, and therefore minimizing the risk of recollection bias. The TrackYourTinnitus (TYT) mobile app provides a platform for collecting ecologically valid time series data from tinnitus users and can be used to address questions like how mood, concentration, tinnitus distress, or loudness relate over time. Whether any of those variables have an influence over the next day, that is, whether any of these variables are auto- or cross-correlated, is still unanswered.ObjectivesAssess whether behavioral and symptom-related data from tinnitus users from the TYT app auto- and cross-correlate in different time lags, both within and between individuals.MethodsAnonymized data was collected from 278 users of the iOS or Android TYT apps between 2014 and 2020. Tinnitus-related distress, tinnitus loudness, concentration level, overall mood, emotional arousal, and overall stress level were assessed using a 10-point visual analog scale via a daily survey. Auto- and cross-correlations were calculated for participants who used the app for at least 10 consecutive days. Lagged cross-correlation was used to investigate the dynamics of each of these variables over time at the group level, followed by linear regression with elastic net regularization for each user. Additionally, subgrouping within group iterative multiple model estimation (S-GIMME) was used to model the behavioral dynamics at the group, subgroup, and individual levels with data collected from 32 users.ResultsNo autocorrelation or cross-correlation was observed at the group level between the variables assessed. However, application of the regression models with elastic net regularization identified individualized predictors of tinnitus loudness and distress for most participants, with the models including contemporaneous and lagged information from the previous day. The finding that a subset of users experienced lagged and contemporaneous dynamics was corroborated by the models from S-GIMME. The models had adequate fits, with both contemporaneous and lagged coefficients obtained for most individuals. Two subgroups were identified, the first consisting of users where both contemporaneous and lagged effects were observed, and a second subgroup consisting of users whose dynamics were mainly of contemporaneous effects.DiscussionWe showed that tinnitus loudness and tinnitus distress are affected by the contemporaneous and lagged dynamics of behavioral and emotional processes measured through EMA. These effects were seen at the group, subgroup, and individual levels. The relevance EMA and the implications of the insights derived from it for tinnitus care are discussed, especially considering current trends towards the individualization of tinnitus care.

In this paper, we report robust evidence that the process of corporate defaults is time-dependent and can be modelled by extending an autoregressive count time series model class via the introduction of regime-switching. That is, some of the parameters of the model depend on the regime of an unobserved Markov chain, capturing the model changes during clusters observed for count time series in corporate defaults. Thus, the process of corporate defaults is more dynamic than previously believed. Moreover, the contagion effect—that current defaults affect the probability of other firms defaulting in the future—is reduced compared to models without regime-switching, and is only present in one regime. A two-regime model drives the counts of monthly corporate defaults in the United States. To estimate the model, we introduce a novel quasi-maximum likelihood estimator by adapting the extended Hamilton–Gray algorithm for the Poisson autoregressive model.

A very common way to estimate the parameters of a hidden Markov model (HMM) is the relatively straightforward computation of maximum likelihood (ML) estimates. For this task, most users rely on user-friendly implementation of the estimation routines via an interpreted programming language such as the statistical software environment R (R Core Team, 2021). Such an approach can easily require time-consuming computations, in particular for longer sequences of observations. In addition, selecting a suitable approach for deriving confidence intervals for the estimated parameters is not entirely obvious (see, e.g., Zucchini et al., 2016; Lystig and Hughes, 2002; Visser et al., 2000), and often the computationally intensive bootstrap methods have to be applied. In this tutorial, we illustrate how to speed up the computation of ML estimates significantly via the R package TMB. Moreover, this approach permits simple retrieval of standard errors at the same time. We illustrate the performance of our routines using different data sets. First, two smaller samples from a mobile application for tinnitus patients and a well-known data set of fetal lamb movements with 87 and 240 data points, respectively. Second, we rely on larger data sets of simulated data of sizes 2000 and 5000 for further analysis. This tutorial is accompanied by a collection of scripts which are all available on GitHub. These scripts allow any user with moderate programming experience to benefit quickly from the computational advantages of TMB., For supporting information, see https://timothee-bacri.github.io/HMM_with_TMB/

Retailers are experiencing a systematic shift in the buying habits of their customers as more customers buy across different channels. Marketing managers face the daunting task of embracing online and offline channels to engage consumers, influence choice, and create habits to sustain a competitive advantage. We develop a dynamic segmentation model of channel choice and purchase frequency to assess the responsiveness of segments to catalogues and email communications. In addition, we perform profitability analysis to offer insights on the profitability of using catalogues and emails to reach customers. For certain firms, especially those with a history of using catalogue mailings, the findings suggest that catalogues remain relevant and are an effective tool at influencing purchases across both online and offline channels despite the increasing trend toward digital marketing. In addition, we found a segment of digital consumers respond favorably to both emails and catalogues. We argue catalogues have retained their competitive advantage over email marketing communication because the catalogue may not compete for attention with consumers' other digital distractions.

This research presents an application of a mixed hidden Markov model to data from a multichannel retailer. The objective of this research is to develop a dynamic model of channel choice and purchasing behavior that accounts for consumer heterogeneity, changes in behavior over time, and the influence of marketing activities on managerially relevant consumer behaviors. The model allows marketers to reduce their direct mailing spending while controlling for potential negative effects on their sales. More specifically, we develop a model that captures the evolution of a consumer’s buying behavior over time across retail channels and compare our model to several other approaches. We find our model outperforms existing models including standard latent class models, including those belonging to the latent transition analysis framework. Using several criteria of model performance and fit, we find a hierarchical clustering structure in the data. Each cluster responds differentially to marketing activities. We find catalogs, on average, are an effective tool to keep consumers active whereas retail promotions are more likely to influence consumers to migrate to another channel.

Twin and adoption studies point towards a genetic contribution to tinnitus; however, how the genetic risk applies to different forms of tinnitus is poorly understood. Here, we perform a familial aggregation study and determine the relative recurrence risk for tinnitus in siblings (λs). Four different Swedish studies (N = 186,598) were used to estimate the prevalence of self-reported bilateral, unilateral, constant, and severe tinnitus in the general population and we defined whether these 4 different forms of tinnitus segregate in families from the Swedish Tinnitus Outreach Project (STOP, N = 2305). We implemented a percentile bootstrap approach to provide accurate estimates and confidence intervals for λs. We reveal a significant λs for all types of tinnitus, the highest found being 7.27 (95% CI (5.56–9.07)) for severe tinnitus, with a higher susceptibility in women (10.25; 95% CI (7.14–13.61)) than in men (5.03; 95% CI (3.22–7.01)), suggesting that severity may be the most genetically influenced trait in tinnitus in a sex-dependent manner. Our findings strongly support the notion that genetic factors impact on the development of tinnitus, more so for severe tinnitus. These findings highlight the importance of considering tinnitus severity and sex in the design of large genetic studies to optimize diagnostic approaches and ultimately improve therapeutic interventions.

Twin and adoption studies point towards a genetic contribution to tinnitus; however, how the genetic risk applies to different forms of tinnitus is poorly understood. Here, we perform a familial aggregation study and determine the relative recurrence risk for tinnitus in siblings (λs). Four different Swedish studies (N = 186,598) were used to estimate the prevalence of self-reported bilateral, unilateral, constant, and severe tinnitus in the general population and we defined whether these 4 different forms of tinnitus segregate in families from the Swedish Tinnitus Outreach Project (STOP, N = 2305). We implemented a percentile bootstrap approach to provide accurate estimates and confidence intervals for λs. We reveal a significant λs for all types of tinnitus, the highest found being 7.27 (95% CI (5.56–9.07)) for severe tinnitus, with a higher susceptibility in women (10.25; 95% CI (7.14–13.61)) than in men (5.03; 95% CI (3.22–7.01)), suggesting that severity may be the most genetically influenced trait in tinnitus in a sex-dependent manner. Our findings strongly support the notion that genetic factors impact on the development of tinnitus, more so for severe tinnitus. These findings highlight the importance of considering tinnitus severity and sex in the design of large genetic studies to optimize diagnostic approaches and ultimately improve therapeutic interventions.

The heterogeneity of tinnitus is likely accounting for the lack of efective treatment approaches. Headaches have been related to tinnitus, yet little is known on how headaches impact tinnitus. We use cross-sectional data from the Swedish Tinnitus Outreach Project to i) evaluate the association between headaches and tinnitus (n=1,984 cases and 1,661 controls) and ii) investigate the phenotypic characteristics of tinnitus subjects with tinnitus (n=660) or without (n=1,879) headaches. In a multivariable logistic regression model, headache was signifcantly associated with any tinnitus (odds ratio, OR=2.61) and more so with tinnitus as a big problem (as measured by the tinnitus functional index, TFI≥48; OR=5.63) or severe tinnitus (using the tinnitus handicap inventory, THI ≥58; OR=4.99). When focusing on subjects with tinnitus, the prevalence of headaches was 26% and reached 40% in subjects with severe tinnitus. A large number of socioeconomic, phenotypic and psychological characteristics difered between headache and non-headache subjects with any tinnitus. With increasing tinnitus severity, fewer diferences were found, the major ones being vertigo, neck pain and other pain syndromes, as well as stress and anxiety. Our study suggests that headaches could contribute to tinnitus distress and potentially its severity., GENDER-NET Co-Plus Fund GNP-182, Decibel Therapeutics, Inc., Svenska Lakaresallskapet SLS-779681, Tysta Skolan, Horselforskningsfonden 503, European Union's Horizon 2020 research and innovation programme under the Marie Skodowska-Curie grant 72204655, Swedish Medical Research Council (SMRC) K2014-99x-22478-01-3, Karolinska Institutet

Gait is one of the most basic movements, and walking activity accomplished in dual task conditions realistically represents daily life mobility. Much is known about diurnal variations of gait components such as muscle power, postural control, and attention. However, paradoxically only little is known about gait itself. The aim of this study was to analyze whether gait parameters show time-of-day fluctuation in simple and dual task conditions. Sixteen young subjects performed sessions at five specific hours (06:00, 10:00, 14:00, 18:00 and 22:00 h), performing a single (walking or counting) and a dual (walking and counting) task. When performing gait in dual task conditions, an additional cognitive task had to be carried out. More precisely, the participants had to count backwards from a two-digit random number by increments of three while walking. Spatio-temporal gait parameters and counting performance data were recorded for analysis. Walking speed significantly decreased, while stride length variability increased when the task condition switched from single to dual. In the single-task condition, diurnal variations were observed in both walking speed and counting speed. Walking speed was higher in the afternoon and in the evening (14:00 and 22:00 h) and lower in the morning (10:00 h). Counting speed was maximum at 10:00 and 14:00 h and minimum at 18:00 h. Nevertheless, no significant diurnal fluctuation was substanytiated in the dual task condition. These results confirm the existing literature about changes in gait between single and dual task conditions. A diurnal pattern of single-task gait could also be highlighted. Moreover, this study suggests that diurnal variations faded in complex dual task gait, when the cognitive load nearly reached its maximum. These findings might be used to reduce the risk for falls, especially of the elderly. acceptedVersion

International audience; The vestibular system is responsible for sensing every angular and linear head acceleration, mainly during periods of motor activity. Previous animal and human experiments have shown biological rhythm disruptions in small rodents exposed to a hypergravity environment, but also in patients with bilateral vestibular loss compared to a control population. This raised the hypothesis of the vestibular afferent influence on circadian rhythm synchronization. The present study aimed to test the impact of vestibular stimulation induced by a rotatory chair on the rest/activity rhythm in human subjects. Thirty-four healthy adults underwent both sham (SHAM) and vestibular stimulation (STIM) sessions scheduled at 18:00 h. An off-vertical axis rotation on a rotatory chair was used to ecologically stimulate the vestibular system by head accelerations. The rest/activity rhythm was continuously registered by actigraphy. The recording started one week before the first session (BASELINE), continued in the week between the two sessions and one week after the second session. Vestibular stimulation caused a significant decrease in the average activity level in the evening following the vestibular stimulation. A significant phase advance in the rest/activity rhythm occurred two days after the 18:00 h vestibular stimulation session. Moreover, the level of motion sickness symptoms increased significantly after vestibular stimulation. The present study confirms previous results on the effect of vestibular stimulation and the role of vestibular afferents on circadian biological rhythmicity. Our results support the hypothesis of the implication of vestibular afferents as non-photic stimuli acting on circadian rhythms.

The aim of the study was to test the effect of total sleep deprivation on performance and time-of-day pattern of subjective visual vertical (SVV) and postural control. Nineteen healthy, young participants (4 women and 15 men 21.9 ± 1.2 yr) were engaged in two counterbalanced experimental sessions with or without total sleep deprivation. Oral temperature, Karolinska Sleepiness Scale, and visual analogic scale for fatigue, postural control, and SVV were randomly measured every 4 h, from 0600 to 2200. A linear mixed model was used to capture the effect of time of day and sleep condition as factors. A classical adjusted COSINOR function was then used to modelize this daily variation. After the control night of sleep, SVV as well as oral temperature, sleepiness, and fatigue showed significant time-of-day variation, contrasting with measures of postural control which remained stable across the day. After sleep deprivation, SVV showed no diurnal variation, but its mean deviation value increased by 29%. Postural control capability also decreased after sleep deprivation, with a higher center of pressure surface (+70.4%) and total length (+7.37%) but remained stable throughout the day. These results further confirm the negative effect of sleep loss on postural control capability. Even if a direct relationship cannot be confirmed, the disruption of SVV capacity after sleep deprivation could strongly play a role in postural control capacity changes. Sleep deprivation should be considered as a potent factor involved in balance loss and subsequent fall. NEW & NOTEWORTHY The topic of sleep deprivation and postural control is not understood, with discrepancy among results. This study described that postural control displays a stable level throughout the day and that sleep deprivation, even if it increases postural sway, does not affect this stable diurnal pattern. The modification of the perception of the vertical level after sleep deprivation could strongly play a role in the observed changes in postural control capacity.

This study aimed to evaluate whether the elapsed time after release to first re-offense is longer for those who complete coerced forensic addiction treatment than for those who fail to complete the...

Rainfall is a continuous-time phenomenon typically characterised by precipitation states such as rain, showers and dry whose dependence varies over a variety of space-time scales. Here attention is focussed on the effective identification of rain and shower precipitation states over a region where these states have been determined by a hidden semi-Markov model of continuous-time precipitation. The states identified provide an accurate description of precipitation dynamics and can be regarded as close proxies to synoptic weather types of the same name. The stochastic properties and structure of these states (rather than precipitation amounts) are explored and delineated. A primary objective of the paper is to better understand the impact of conventional space-time aggregation on the dynamics of rainfall. What aggregation time scales result in more faithful descriptions of the space-time dynamics of continuous-time rainfall? While rain might be expected to be more spatially coherent than showers and involve longer time scales, dry periods involve much longer time and space scales again than either rain or showers. These issues are discussed and conclusions drawn which provide guidance and insights useful for the development of space-time precipitation models and, more generally, the design of rainfall observation networks and data archives.

Background: Migrants with mental hospital orders according to section 63 of the German criminal code are overrepresented in relation to their numbers in the general population. Subgroups originating from certain world regions are diagnosed with schizophrenia at a much higher rate than others. In the present literature, there is a strong evidence for a substantial correlation between migration, social disadvantage and the prevalence of schizophrenia. Aims: This study investigates the relationship between countries of origin, the risk of becoming a forensic patient and the proportion of schizophrenia spectrum disorders. Method: Data from a comprehensive evaluation tool of forensic inpatients in the German federal state of Baden-Württemberg (FoDoBa) were compared with population statistics and correlated with the Human Development Index (HDI) and Multidimensional Poverty Index (MPI). Results: For residents with migration background, the risk ratio to receive a mental hospital order is 1.3 in comparison to non-migrants. There was a highly significant correlation between the HDI of the country of origin and the risk ratio for detention in a forensic psychiatric hospital. The proportion of schizophrenia diagnoses also correlated significantly with the HDI. In contrast, the MPI country rankings were not associated with schizophrenia diagnoses. Conclusion: Two lines of explanations are discussed: first, higher prevalence of schizophrenia in migrants originating from low-income countries, and second, a specific bias in court rulings with regard to involuntary forensic treatment orders for these migrant groups.

International audience; Earth's gravity acts both as a mechanical stimulus on the body and as a sensory stimulus to the vestibular organ, which is transmitted into the brain. The vestibular system has been recently highlighted as the cornerstone of the multisensory cortex and of the dorsal hippocampus related to spatial cognition. Consequently, we have hypothesized that the vestibular sensory perception of gravity by the otoliths might also play a crucial role during the first stages of development in both sensorimotor and cognitive functions and the construction and perception of the 'self' and related functions of orientation and navigation. We have investigated an original mouse model (Head Tilted mice, B6Ei.GL-Nox3het/J) suffering from a selective congenital absence of vestibular otolithic gravisensors. We report that mouse pups suffered from a delay in the acquisition of sensorimotor reflexes, spatial olfactory guidance, path integration, and ultrasonic communication, while maternal care remained normal. We demonstrate that development has a critical period dependent on the vestibular otolithic sensory perception of gravity, probably temporally between the somesthetic and visual critical periods. The symptoms expressed by the congenital otolithic-deficient mice are similar to validated mouse models of autism and highlight the significance of vestibular graviception in the pathophysiology of development.

Two monovalent vaccines against pasteurellosis were developed and tested for efficacy using a previously established bath challenge model. High levels of specific antibodies were detected following vaccination. While the vaccine efficacy trial indicated that some level of protection was obtained, high mortality was still observed. qPCR analysis of head kidney tissues from surviving fish post challenge showed no difference in bacterial numbers in vaccinated and non-vaccinated fish. Clinical symptoms observed in moribund and diseased fish included white spots on the skin and around the eyes, frayed fins and redness around the mouth and fin bases. Despite production of specific antibodies, the protection against experimental challenge was relatively weak. A reason for this could potentially be that the specific antibodies produced are not alone enough to provide complete protection against pasteurellosis in lumpsuckers. Confocal and scanning electron microscopy of head kidney leucocytes exposed to Pasteurella sp. in vitro gave indications of the interactions between the pathogen and leucocytes. The results indicate that parts of the immune system other than humoral antibodies could be important for protection against pasteurellosis. Our combined results highlight the need for further work on host-pathogen interaction between Pasteurella sp. and lumpsuckers.

Ototoxicity is one of the major side-effects of platinum-based chemotherapy, in particular cisplatin (cis-diammine dichloroplatinum II). To our knowledge, no systematic review has previously provided a quantitative summary estimate of the impact of genetics upon the risk of developing hearing loss. We searched Embase, Medline, ASSIA, Pubmed, Scopus, and Web of Science, for studies documenting the genetic risk of ototoxicity in patients with cancer treated with cisplatin. Titles/abstracts and full texts were reviewed for inclusion. Meta-analytic estimates of risk (Odds Ratio) from the pooled data were calculated for studies that have been repeated twice or more. The search identified 3891 papers, of which 30 were included. The majority were retrospective (44%), ranging from n = 39 to n = 317, some including only patients younger than 25 years of age (33%), and some on both genders (80%). The most common cancers involved were osteosarcoma (53%), neuroblastoma (37%), prostate (17%) and reproductive (10%). Most studies performed genotyping, though only 5 studies performed genome-wide association studies. Nineteen single-nucleotide polymorphisms (SNPs) from 15 genes were repeated more than twice. Meta-analysis of group data indicated that rs1872328 on ACYP2, which plays a role in calcium homeostasis, increases the risk of ototoxicity by 4.61 (95% CI: 3.04–7.02; N = 696, p LRP2 rs4668123 shows a cumulated Odds Ratio of 3.53 (95% CI: 1.48–8.45; N = 118, p = 0.0059), which could not be evidenced in individual studies. Despite the evidence of heterogeneity across studies, these meta-analytic results from 30 studies are consistent with a view of a genetic predisposition to platinum-based chemotherapy mediated ototoxicity. These new findings are informative and encourage the genetic screening of cancer patients in order to identify patients with greater vulnerability of developing hearing loss, a condition having a potentially large impact on quality of life. More studies are needed, with larger sample size, in order to identify additional markers of ototoxic risk associated with platinum-based chemotherapy and investigate polygenic risks, where multiple markers may exacerbate the side-effects.

Reports about luxury categories and premium brands growing during recession are multiple. This marketplace behavior, however, is counterintuitive to what traditional economics would predict. The authors propose and test a theory to explain why demand for premium brands may grow despite a contraction in the economy. They define cross-category indulgence as the strategy of moving across categories (in contrast to moving within category) to satisfy the desire to indulge while dealing with budgetary constraints. The authors test empirically for cross-category indulgence using a unique dataset that compares dining in with dining out. They find support for cross-category indulgence and rule out other possible explanations for the increase in demand for a premium brand. The authors discuss that premium brand managers that understand this marketplace behavior and create opportunities for their brand to be the leader in their category may alleviate a decrease in demand for their brand during tough economic times.

Interference of ongoing neuronal activity and brain stimulation motivated this study to combine repetitive transcranial magnetic stimulation (rTMS) and relaxation techniques in tinnitus patients. Forty-two patients were enrolled in this one-arm proof-of-concept study to receive ten sessions of rTMS applied to the left dorsolateral prefrontal cortex and temporo-parietal cortex. During stimulation, patients listened to five different kinds of relaxation audios. Variables of interest were tinnitus questionnaires, tinnitus numeric rating scales, depressivity, and quality of life. Results were compared to results of historical control groups having received the same rTMS protocol (active control) and sham treatment (placebo) without relaxation techniques. Thirty-eight patients completed the treatment, drop-out rates and adverse events were low. Responder rates (reduction in tinnitus questionnaire (TQ) score ≥5 points 10 weeks after treatment) were 44.7 % in the study, 27.8 % in the active control group, and 21.7 % in the placebo group, differing between groups on a near significant level. For the tinnitus handicap inventory (THI), the main effect of group was not significant. However, linear mixed model analyses showed that the relaxation/rTMS group differed significantly from the active control group showing steeper negative THI trend for the relaxation/rTMS group indicating better amelioration over the course of the trial. Deepness of relaxation during rTMS and selection of active relaxation vs. passive listening to music predicted larger TQ. All remaining secondary outcomes turned out non-significant. This combined treatment proved to be a safe, feasible and promising approach to enhance rTMS treatment effects in chronic tinnitus.