Consensus paper: the role of the cerebellum in perceptual processes.

Various lines of evidence accumulated over the past 30 years indicate that the cerebellum, long recognized as essential for motor control, also has considerable influence on perceptual processes. In this paper, we bring together experts from psychology and neuroscience, with the aim of providing a succinct but comprehensive overview of key findings related to the involvement of the cerebellum in sensory perception. The contributions cover such topics as anatomical and functional connectivity, evolutionary and comparative perspectives, visual and auditory processing, biological motion perception, nociception, self-motion, timing, predictive processing, and perceptual sequencing. While no single explanation has yet emerged concerning the role of the cerebellum in perceptual processes, this consensus paper summarizes the impressive empirical evidence on this problem and highlights diversities as well as commonalities between existing hypotheses. In addition to work with healthy individuals and patients with cerebellar disorders, it is also apparent that several neurological conditions in which perceptual disturbances occur, including autism and schizophrenia, are associated with cerebellar pathology. A better understanding of the involvement of the cerebellum in perceptual processes will thus likely be important for identifying and treating perceptual deficits that may at present go unnoticed and untreated. This paper provides a useful framework for further debate and empirical investigations into the influence of the cerebellum on sensory perception.

A temporal hierarchy for conspecific vocalization discrimination in humans.

Introduction: Discrimination of species-specific vocalizations is fundamental for survival and social interactions. Its unique behavioral relevance has encouraged the identification of circumscribed brain regions exhibiting selective responses (Belin et al., 2004), while the role of network dynamics has received less attention. Those studies that have examined the brain dynamics of vocalization discrimination leave unresolved the timing and the inter-relationship between general categorization, attention, and speech-related processes (Levy et al., 2001, 2003; Charest et al., 2009). Given these discrepancies and the presence of several confounding factors, electrical neuroimaging analyses were applied to auditory evoked-potential (AEPs) to acoustically and psychophysically controlled non-verbal human and animal vocalizations. This revealed which region(s) exhibit voice-sensitive responses and in which sequence. Methods: Subjects (N=10) performed a living vs. man-made 'oddball' auditory discrimination task, such that on a given block of trials 'target' stimuli occurred 10% of the time. Stimuli were complex, meaningful sounds of 500ms duration. There were 120 different sound files in total, 60 of which represented sounds of living objects and 60 man-made objects. The stimuli that were the focus of the present investigation were restricted to those of living objects within blocks where no response was required. These stimuli were further sorted between human non-verbal vocalizations and animal vocalizations. They were also controlled in terms of their spectrograms and formant distributions. Continuous 64-channel EEG was acquired through Neuroscan Synamps referenced to the nose, band-pass filtered 0.05-200Hz, and digitized at 1000Hz. Peri-stimulus epochs of continuous EEG (-100ms to 900ms) were visually inspected for artifacts, 40Hz low-passed filtered and baseline corrected using the pre-stimulus period . Averages were computed from each subject separately. AEPs in response to animal and human vocalizations were analyzed with respect to differences of Global Field Power (GFP) and with respect to changes of the voltage configurations at the scalp (reviewed in Murray et al., 2008). The former provides a measure of the strength of the electric field irrespective of topographic differences; the latter identifies changes in spatial configurations of the underlying sources independently of the response strength. In addition, we utilized the local auto-regressive average distributed linear inverse solution (LAURA; Grave de Peralta Menendez et al., 2001) to visualize and statistically contrast the likely underlying sources of effects identified in the preceding analysis steps. Results: We found differential activity in response to human vocalizations over three periods in the post-stimulus interval, and this response was always stronger than that to animal vocalizations. The first differential response (169-219ms) was a consequence of a modulation in strength of a common brain network localized into the right superior temporal sulcus (STS; Brodmann's Area (BA) 22) and extending into the superior temporal gyrus (STG; BA 41). A second difference (291-357ms) also followed from strength modulations of a common network with statistical differences localized to the left inferior precentral and prefrontal gyrus (BA 6/45). These two first strength modulations correlated (Spearman's rho(8)=0.770; p=0.009) indicative of functional coupling between temporally segregated stages of vocalization discrimination. A third difference (389-667ms) followed from strength and topographic modulations and was localized to the left superior frontal gyrus (BA10) although this third difference did not reach our spatial criterion of 12 continuous voxels. Conclusions: We show that voice discrimination unfolds over multiple temporal stages, involving a wide network of brain regions. The initial stages of vocalization discrimination are based on modulations in response strength within a common brain network with no evidence for a voice-selective module. The latency of this effect parallels that of face discrimination (Bentin et al., 2007), supporting the possibility that voice and face processes can mutually inform one another. Putative underlying sources (localized in the right STS; BA 22) are consistent with prior hemodynamic imaging evidence in humans (Belin et al., 2004). Our effect over the 291-357ms post-stimulus period overlaps the 'voice-specific-response' reported by Levy et al. (Levy et al., 2001) and the estimated underlying sources (left BA6/45) were in agreement with previous findings in humans (Fecteau et al., 2005). These results challenge the idea that circumscribed and selective areas subserve con-specific vocalization processing.

Comparison of in-hospital mortality for acute myocardial infarction in Switzerland with admission during routine duty hours versus admission during out of hours (insight into the AMIS plus registry).

To improve long-term survival, prompt revascularization of the infarct-related artery should be done in patients with acute myocardial infarction (AMI); therefore, a large proportion of these patients would be hospitalized during out of hours. The clinical effects of out-of-hours AMI management were already questioned, with conflicting results. The purpose of this investigation was to compare the in-hospital outcome of patients admitted for AMI during out of hours and working hours. All patients with AMI included in the AMIS Plus Registry from January 1, 1997, to March 30, 2006, were analyzed. The working-hours group included patients admitted from 7 a.m. to 7 p.m. on weekdays, and the out-of-hours group included patients admitted from 7 p.m. to 7 a.m. on weekdays or weekends. Major cardiac events were defined as cardiovascular death, reinfarction, and stroke. The study primary end points were in-hospital death and major adverse cardiac event (MACE) rates. A total of 12,480 patients met the inclusion criteria, with 52% admitted during normal working hours, and 48%, during out of hours. Patients admitted during weekdays included more women (28.1% vs 26%; p = 0.009), older patients (65.5 +/- 13 vs 64.1 +/- 13 years; p = 0.0011), less current smokers (40.1% vs 43.5%; p <0.001), and less patients with a history of ischemic heart disease (31.5% vs 34.5%; p = 0.001). A significantly higher proportion of patients admitted during out of hours had Killip's class III and IV. No differences in terms of in-hospital survival rates between the 2 groups (91.5% vs 91.2%; p = 0.633) or MACE-free survival rates (both 88.5%; p = 1.000) were noted. In conclusion, the outcome of patients with AMI admitted out of hours was the same compared with those with a weekday admission. Of predictors for in-hospital outcome, timing of admission had no significant influence on mortality and/or MACE incidence.

Genetic and environmental effects on early life-history traits in salmonids

Les changements environnementaux, tels la température ou les maladies infectieuses, peuvent influencer l'évolution en induisant de la sélection, mais ceci à la seule condition qu'il y ait assez de diversité génétique pour les traits en question ou pour l'expression plastique de ces traits. Au cours cette thèse, nous avons étudié l'effet de potentielles pressions environnementales sur différents phénotypes de trois représentants des sous familles des salmonidés: l'ombre commun (Thymallus thymallus; Thymallinae), la truite de rivière {Salmo trutta; Salmoninae) et le corégone Coregonus palaea (Coregoninae). Les salmonidés se prêtent particulièrement bien à ce type d'expériences car étant hautement sensibles aux conditions environnementales, ils montrent une large variabilité dans leurs traits morphologiques, comportementaux ainsi que d'histoire de vie, tout en bénéficiant d'un large intérêt général. Nous avons testé si le sexe de l'ombre commun pouvait être modifié par la température, ce qui pourrait ainsi expliquer un changement abrupte de sex ratio observé dans l'une des plus grandes populations de Suisse. Nous n'avons trouvé aucun indice permettant de conclure que la température puisse induire ce changement chez l'ombre commun ou chez la truite de rivière. De plus nous avons étudié la plasticité de développement ainsi que d'éclosion, et avons observé des différences entre familles ainsi qu'entre populations. Alors que ces différences comportementales entre populations suggéraient une adaptation aux conditions environnementales locales, cette prédiction n'a pas été confirmée par une expérience de transplantation réciproque d'embryons entre cinq rivières de la même région. Cette étude a montré que les embryons ne survivaient pas mieux dans leur rivière d'origine, indiquant donc une absence d'adaptation locale. Nous avons aussi montré que la mortalité embryonnaire était influencée autant par des "bons gènes" que par des "gènes compatibles", que la qualité des mâles pouvait être signalée par leur coloration, et que le fait d'élever des poissons dans une pisciculture pouvait aboutir a des relations contre-intuitives entre la coloration des mâles et la qualité de leur jeunes. Nos résultats contribuent ainsi à une meilleure compréhension de l'effet de diverses pressions environnementales sur la morphologie, le comportement ou les traits d'histoire de vie chez les salmonidés. - Environmental changes, such as changes in temperatures or infection levels, can induce selection and drive evolution if there is sufficient genetic variation for the traits or the plasticity in trait expression. In this thesis, we investigated the influence of potential environmental stressors on various phenotypes in representatives of the three salmonid subfamilies: the European grayling (Thymallus thymallus; Thymallinae), the brown trout (,Salmo trutta; Salmoninae), and the whitefish Coregonus palaea (Coregoninae). Salmonids are ideal study species, as they seem sensitive to changing environmental conditions, show considerable variability in morphological, behavioral, and life history traits, and are of broad public interest. We investigated whether temperature-induced sex reversal could explain the sex-ratio distortion found in one of Switzerland's largest grayling populations. We found no evidence of temperature-induced sex reversal in either graylings or brown trout. We also examined plasticity in embryo development and the timing of hatching. We found variation at the level of family and population. Although behavioral differences between populations suggested adaptation to local environmental conditions, no indications of local adaptation could be found in reciprocal transplant experiments carried out over five rivers in the same region. We also demonstrate that embryo development and viability is influenced by 'good genes' and 'compatible genes', that the genetic quality of sires can be signaled by their grey coloration, and that raising larvae in a hatchery environment can produce counter-intuitive relationships between male phenotypes and offspring viability. Our results contribute to the understanding of how changing environmental conditions affect the phenotypes and the heritability of early life-history traits in salmonids.

Respiratory syncytial virus seasonality in Brazil: implications for the immunisation policy for at-risk populations

Respiratory syncytial virus (RSV) infection is the leading cause of hospitalisation for respiratory diseases among children under 5 years old. The aim of this study was to analyse RSV seasonality in the five distinct regions of Brazil using time series analysis (wavelet and Fourier series) of the following indicators: monthly positivity of the immunofluorescence reaction for RSV identified by virologic surveillance system, and rate of hospitalisations per bronchiolitis and pneumonia due to RSV in children under 5 years old (codes CID-10 J12.1, J20.5, J21.0 and J21.9). A total of 12,501 samples with 11.6% positivity for RSV (95% confidence interval 11 - 12.2), varying between 7.1 and 21.4% in the five Brazilian regions, was analysed. A strong trend for annual cycles with a stable stationary pattern in the five regions was identified through wavelet analysis of the indicators. The timing of RSV activity by Fourier analysis was similar between the two indicators analysed and showed regional differences. This study reinforces the importance of adjusting the immunisation period for high risk population with the monoclonal antibody palivizumab taking into account regional differences in seasonality of RSV.

Incidence of HIV-1 drug resistance among antiretroviral treatment-naive individuals starting modern therapy combinations.

BACKGROUND: Estimates of drug resistance incidence to modern first-line combination antiretroviral therapies against human immunodeficiency virus (HIV) type 1 are complicated by limited availability of genotypic drug resistance tests (GRTs) and uncertain timing of resistance emergence. METHODS: Five first-line combinations were studied (all paired with lamivudine or emtricitabine): efavirenz (EFV) plus zidovudine (AZT) (n = 524); EFV plus tenofovir (TDF) (n = 615); lopinavir (LPV) plus AZT (n = 573); LPV plus TDF (n = 301); and ritonavir-boosted atazanavir (ATZ/r) plus TDF (n = 250). Virological treatment outcomes were classified into 3 risk strata for emergence of resistance, based on whether undetectable HIV RNA levels were maintained during therapy and, if not, whether viral loads were >500 copies/mL during treatment. Probabilities for presence of resistance mutations were estimated from GRTs (n = 2876) according to risk stratum and therapy received at time of testing. On the basis of these data, events of resistance emergence were imputed for each individual and were assessed using survival analysis. Imputation was repeated 100 times, and results were summarized by median values (2.5th-97.5th percentile range). RESULTS: Six years after treatment initiation, EFV plus AZT showed the highest cumulative resistance incidence (16%) of all regimens (<11%). Confounder-adjusted Cox regression confirmed that first-line EFV plus AZT (reference) was associated with a higher median hazard for resistance emergence, compared with other treatments: EFV plus TDF (hazard ratio [HR], 0.57; range, 0.42-0.76), LPV plus AZT (HR, 0.63; range, 0.45-0.89), LPV plus TDF (HR, 0.55; range, 0.33-0.83), ATZ/r plus TDF (HR, 0.43; range, 0.17-0.83). Two-thirds of resistance events were associated with detectable HIV RNA level ≤500 copies/mL during treatment, and only one-third with virological failure (HIV RNA level, >500 copies/mL). CONCLUSIONS: The inclusion of TDF instead of AZT and ATZ/r was correlated with lower rates of resistance emergence, most likely because of improved tolerability and pharmacokinetics resulting from a once-daily dosage.

Time processing in visual cortices: How the visual brain encodes and keeps track of time

Time is embedded in any sensory experience: the movements of a dance, the rhythm of a piece of music, the words of a speaker are all examples of temporally structured sensory events. In humans, if and how visual cortices perform temporal processing remains unclear. Here we show that both primary visual cortex (V1) and extrastriate area V5/MT are causally involved in encoding and keeping time in memory and that this involvement is independent from low-level visual processing. Most importantly we demonstrate that V1 and V5/MT are functionally linked and temporally synchronized during time encoding whereas they are functionally independent and operate serially (V1 followed by V5/MT) while maintaining temporal information in working memory. These data challenge the traditional view of V1 and V5/MT as visuo-spatial features detectors and highlight the functional contribution and the temporal dynamics of these brain regions in the processing of time in millisecond range. The present project resulted in the paper entitled: 'How the visual brain encodes and keeps track of time' by Paolo Salvioni, Lysiann Kalmbach, Micah Murray and Domenica Bueti that is now submitted for publication to the Journal of Neuroscience.

Can oxidative damage be treated nutritionally?

BACKGROUND & AIMS: Nutrition and dietary patterns have been shown to have direct impact on health of the population and of selected patient groups. The beneficial effects have been attributed to the reduction of oxidative damage caused by the normal or excessive free radical production. The papers aims at collecting evidence of successful supplementation strategies. METHODS: Review of the literature reporting on antioxidant supplementation trials in the general population and critically ill patients. RESULTS: Antioxidant vitamin and trace element intakes have been shown to be particularly important in the prevention of cancer, cardiovascular diseases, age related ocular diseases and in aging. In animal models, targeted interventions have been associated with reduction of tissue destruction is brain and myocardium ischemia-reperfusion models. In the critically ill antioxidant supplements have resulted in reduction of organ failure and of infectious complications. CONCLUSIONS: Antioxidant micronutrients have beneficial effects in defined models and pathologies, in the general population and in critical illness: ongoing research encourages this supportive therapeutic approach. Further research is required to determined the optimal micronutrient combinations and the doses required according to timing of intervention.

The Life Course Determinants of Vulnerability in Late Careers

Late career is often seen as a more vulnerable life-stage in the labour market, in which workers may experience a deterioration in job quality. Using a life course perspective and longitudinal data, this article analyses the vulnerability associated with late career by focusing on four occupational dimensions: working-time, career continuity, retirement timing and income change. The research is carried out using data from Switzerland, a country where the age profile of the labour force is an increasing issue. The paper also adopts a cumulative disadvantage perspective to examine the impact of previous work and family life experiences on work life vulnerability at older age. Our data come from the Survey of Health, Ageing and Retirement in Europe (SHARELIFE). The paper uses cluster analysis, sequence analysis and ordered logistic regression. Results show that women with previous family responsibilities resulting in long-term unemployment or caring, often with health complications, are more likely to be vulnerable to deterioration in job quality in late career. This suggests that experiences in the last period of the working life may be just as gendered as earlier periods.

International survey on skin patch test procedures, attitudes and interpretation.

BACKGROUND Skin patch test is the gold standard method in diagnosing contact allergy. Although used for more than 100 years, the patch test procedure is performed with variability around the world. A number of factors can influence the test results, namely the quality of reagents used, the timing of the application, the patch test series (allergens/haptens) that have been used for testing, the appropriate interpretation of the skin reactions or the evaluation of the patient's benefit. METHODS We performed an Internet -based survey with 38 questions covering the educational background of respondents, patch test methods and interpretation. The questionnaire was distributed among all representatives of national member societies of the World Allergy Organization (WAO), and the WAO Junior Members Group. RESULTS One hundred sixty-nine completed surveys were received from 47 countries. The majority of participants had more than 5 years of clinical practice (61 %) and routinely carried out patch tests (70 %). Both allergists and dermatologists were responsible for carrying out the patch tests. We could observe the use of many different guidelines regardless the geographical distribution. The use of home-made preparations was indicated by 47 % of participants and 73 % of the respondents performed 2 or 3 readings. Most of the responders indicated having patients with adverse reactions, including erythroderma (12 %); however, only 30 % of members completed a consent form before conducting the patch test. DISCUSSION The heterogeneity of patch test practices may be influenced by the level of awareness of clinical guidelines, different training backgrounds, accessibility to various types of devices, the patch test series (allergens/haptens) used for testing, type of clinical practice (public or private practice, clinical or research-based institution), infrastructure availability, financial/commercial implications and regulations among others. CONCLUSION There is a lack of a worldwide homogeneity of patch test procedures, and this raises concerns about the need for standardization and harmonization of this important diagnostic procedure.

Use of drugs with more than a twenty-four-hour duration of action

AIM: To assess compliance with a drug regimen of two doses a day compared with one a day. PATIENTS AND METHODS: A prospective crossover study was set up in a general practice environment to compare compliance on a drug regimen of once a day versus twice a day. Data were collected by electronic monitoring in 113 patients with hypertension or angina pectoris. All patients were prescribed slow-release nifedipine twice a day during the first month and then crossed to a single daily dose of amlodipine for another month. RESULTS: Compliance, defined as the proportion of days on which the correct dose was taken, improved in 30% of patients (95% confidence interval 19-41%; P < 0.001) when the patients were switched from twice a day to once a day, but at the same time there was a 15% increase (95% confidence interval 5-25%; P < 0.02) in the number of patients with one or more no-dose days. Approximately 8% of patients displayed low compliance, irrespective of the dose regimen. Actual dose intervals were used to estimate the extent and timing of periods with unsatisfactory drug activity for various hypothetical drug durations of action. CONCLUSIONS: The apparent advantage of a single daily dose in terms of compliance appears to be clinically meaningful only when the duration of activity extends beyond the dose interval in all patients.

Characteristics and determinants of outcome of hospital-acquired bloodstream infections in intensive care units: the EUROBACT International Cohort Study.

PURPOSE: The recent increase in drug-resistant micro-organisms complicates the management of hospital-acquired bloodstream infections (HA-BSIs). We investigated the epidemiology of HA-BSI and evaluated the impact of drug resistance on outcomes of critically ill patients, controlling for patient characteristics and infection management. METHODS: A prospective, multicentre non-representative cohort study was conducted in 162 intensive care units (ICUs) in 24 countries. RESULTS: We included 1,156 patients [mean ± standard deviation (SD) age, 59.5 ± 17.7 years; 65 % males; mean ± SD Simplified Acute Physiology Score (SAPS) II score, 50 ± 17] with HA-BSIs, of which 76 % were ICU-acquired. Median time to diagnosis was 14 [interquartile range (IQR), 7-26] days after hospital admission. Polymicrobial infections accounted for 12 % of cases. Among monomicrobial infections, 58.3 % were gram-negative, 32.8 % gram-positive, 7.8 % fungal and 1.2 % due to strict anaerobes. Overall, 629 (47.8 %) isolates were multidrug-resistant (MDR), including 270 (20.5 %) extensively resistant (XDR), and 5 (0.4 %) pan-drug-resistant (PDR). Micro-organism distribution and MDR occurrence varied significantly (p < 0.001) by country. The 28-day all-cause fatality rate was 36 %. In the multivariable model including micro-organism, patient and centre variables, independent predictors of 28-day mortality included MDR isolate [odds ratio (OR), 1.49; 95 % confidence interval (95 %CI), 1.07-2.06], uncontrolled infection source (OR, 5.86; 95 %CI, 2.5-13.9) and timing to adequate treatment (before day 6 since blood culture collection versus never, OR, 0.38; 95 %CI, 0.23-0.63; since day 6 versus never, OR, 0.20; 95 %CI, 0.08-0.47). CONCLUSIONS: MDR and XDR bacteria (especially gram-negative) are common in HA-BSIs in critically ill patients and are associated with increased 28-day mortality. Intensified efforts to prevent HA-BSIs and to optimize their management through adequate source control and antibiotic therapy are needed to improve outcomes.

Successes and limitations of targeted therapies in renal cell carcinoma.

Until recently, the standard treatment for metastatic renal cell carcinoma (RCC) was nonspecific immunotherapy based on interleukin-2 or interferon-α. This was associated with a modest survival benefit and with significant clinical toxicities. The understanding of numerous molecular pathways in RCC, including HIF, VEGF, mTOR, and the consecutive use of targeted therapies since the beginning of 2005 have significantly improved outcomes for patients with metastatic RCC with an overall survival greater than 2 years. At present, at least 7 targeted agents are approved for first and consecutive lines of treatment of clear cell metastatic RCC. Long-term benefit and extended survival may be achieved through the optimal use of targeted therapies: optimal dosing, adverse event management and treatment duration and compliance. Advances in the finding of prognostic factors highlight the potential for personalizing treatment for patients with metastatic RCC. Data regarding the best sequencing of targeted therapies, predictive biomarkers, best timing of surgery, patient risk profiles, understanding of resistance mechanisms and safety of targeted therapies are growing and will provide a further step ahead in the management of advanced RCC. In parallel, a new class of therapeutics is emerging in RCC: immunotherapy; in particular check-point blockade antibodies are showing very promising results.

Evolutionary history of almond tree domestication in the Mediterranean basin.

Genetic diversity of contemporary domesticated species is shaped by both natural and human-driven processes. However, until now, little is known about how domestication has imprinted the variation of fruit tree species. In this study, we reconstruct the recent evolutionary history of the domesticated almond tree, Prunus dulcis, around the Mediterranean basin, using a combination of nuclear and chloroplast microsatellites [i.e. simple sequence repeat (SSRs)] to investigate patterns of genetic diversity. Whereas conservative chloroplast SSRs show a widespread haplotype and rare locally distributed variants, nuclear SSRs show a pattern of isolation by distance with clines of diversity from the East to the West of the Mediterranean basin, while Bayesian genetic clustering reveals a substantial longitudinal genetic structure. Both kinds of markers thus support a single domestication event, in the eastern side of the Mediterranean basin. In addition, model-based estimation of the timing of genetic divergence among those clusters is estimated sometime during the Holocene, a result that is compatible with human-mediated dispersal of almond tree out of its centre of origin. Still, the detection of region-specific alleles suggests that gene flow from relictual wild preglacial populations (in North Africa) or from wild counterparts (in the Near East) could account for a fraction of the diversity observed.

Generalized food-deceptive orchid species flower earlier and occur at lower altitudes than rewarding ones

Aims Food-deceptive pollination, in which plants do not offer any food reward to their pollinators, is common within the Orchidaceae. As food-deceptive orchids are poorer competitors for pollinator visitation than rewarding orchids, their occurrence in a given habitat may be more constrained than that of rewarding orchids. In particular, the success of deceptive orchids strongly relies on several biotic factors such as interactions with co-flowering rewarding species and pollinators, which may vary with altitude and over time. Our study compares generalized food-deceptive (i.e. excluding sexually deceptive) and rewarding orchids to test whether (i) deceptive orchids flower earlier compared to their rewarding counterparts and whether (ii) the relative occurrence of deceptive orchids decreases with increasing altitude. Methods To compare the flowering phenology of rewarding and deceptive orchids, we analysed data compiled from the literature at the species level over the occidental Palaearctic area. Since flowering phenology can be constrained by the latitudinal distribution of the species and by their phylogenetic relationships, we accounted for these factors in our analysis. To compare the altitudinal distribution of rewarding and deceptive orchids, we used field observations made over the entire Swiss territory and over two Swiss mountain ranges. Important Findings We found that deceptive orchid species start flowering earlier than rewarding orchids do, which is in accordance with the hypotheses of exploitation of naive pollinators and/or avoidance of competition with rewarding co-occurring species. Also, the relative frequency of deceptive orchids decreases with altitude, suggesting that deception may be less profitable at high compared to low altitude.