Flying high on low cost: Success in the low-cost airline industry.

Low-cost airlines have embraced diverse business models, yielding varying degrees of success. In our study, we apply a configurational approach that allows us to evaluate business models not as isolated components but as intricate business configurations. Through this lens, we identify two distinct models that successful low-cost airlines adopt: the pure low-cost model and the hybrid model. Each model has its own specific, often contradictory, attributes. Most significantly, our findings indicate that low-cost airlines must choose between offering a broad spectrum of additional services or focusing on high productivity and on-time performance. Our analyses reveal that low-cost airlines cannot sidestep this trade-off, as a simultaneous offering of both models does not lead to success.

Patterns of gene flow and selection across multiple species of Acrocephalus warblers: footprints of parallel selection on the Z chromosome.

BACKGROUND: Understanding the mechanisms and selective forces leading to adaptive radiations and origin of biodiversity is a major goal of evolutionary biology. Acrocephalus warblers are small passerines that underwent an adaptive radiation in the last approximately 10 million years that gave rise to 37 extant species, many of which still hybridize in nature. Acrocephalus warblers have served as model organisms for a wide variety of ecological and behavioral studies, yet our knowledge of mechanisms and selective forces driving their radiation is limited. Here we studied patterns of interspecific gene flow and selection across three European Acrocephalus warblers to get a first insight into mechanisms of radiation of this avian group. RESULTS: We analyzed nucleotide variation at eight nuclear loci in three hybridizing Acrocephalus species with overlapping breeding ranges in Europe. Using an isolation-with-migration model for multiple populations, we found evidence for unidirectional gene flow from A. scirpaceus to A. palustris and from A. palustris to A. dumetorum. Gene flow was higher between genetically more closely related A. scirpaceus and A. palustris than between ecologically more similar A. palustris and A. dumetorum, suggesting that gradual accumulation of intrinsic barriers rather than divergent ecological selection are more efficient in restricting interspecific gene flow in Acrocephalus warblers. Although levels of genetic differentiation between different species pairs were in general not correlated, we found signatures of apparently independent instances of positive selection at the same two Z-linked loci in multiple species. CONCLUSIONS: Our study brings the first evidence that gene flow occurred during Acrocephalus radiation and not only between sister species. Interspecific gene flow could thus be an important source of genetic variation in individual Acrocephalus species and could have accelerated adaptive evolution and speciation rate in this avian group by creating novel genetic combinations and new phenotypes. Independent instances of positive selection at the same loci in multiple species indicate an interesting possibility that the same loci might have contributed to reproductive isolation in several speciation events.

Cutaneous silent periods in multiple system atrophy.

AIM: The cutaneous silent period (CSP) is a spinal inhibitory reflex primarily mediated by A-delta fibers. Prolonged CSPs have been reported in patients with restless legs syndrome (RLS) and idiopathic Parkinson's disease (IPD). Dopaminergic medication normalizes the CSP, concurring with the effect of levodopa on CSPs. To date, CSPs have not been extensively studied in patients with multiple system atrophy (MSA). The purpose of this study was to confirm abnormal CSP findings in a group of MSA patients and to affirm the lack of influence of levodopa on CSPs during long-term treatment. METHODS: We investigated 15 patients (4 males, 11 females, age 58-71 years) who fulfilled the diagnostic criteria for possible MSA. Thirteen patients had predominant parkinsonian symptoms (MSA-P), 2 had predominant cerebellar signs (MSA-C). We recorded CSPs in thenar muscles following noxious digit II stimulation. Sixteen healthy volunteers (6 males, 10 females, range 24-56 years) served as control subjects for CSP recordings. RESULTS: Group average CSP onset was mildly delayed (P<0.01), whereas CSP end latency (P<0.001) were markedly delayed and CSP duration prolonged (P<0.001) in MSA patients compared to healthy controls. MSA patients on levodopa treatment did not differ in their CSPs from those without levodopa. The dose of levodopa did not correlate to any CSP parameter. CONCLUSION: The observed CSP prolongation corroborates previous findings in a limited number of MSA patients. The ineffectiveness of long-term levodopa on CSP abnormalities is consistent with its poor clinical effect in MSA.

Importance of psychiatric examination in predictive genetic testing for Huntington disease.

BACKGROUND AND PURPOSE: Huntington disease (HD) is an au-tosomal dominant hereditary neurodegenerative disease with multiplication of CAG triplet in the short arm of chromoso-me 4, manifested by motor symptoms, cognitive dysfunction progressing to dementia, and various types of neuropsychiat-ric disorders. The diagnosis of HD is confirmed by a gene-tic test, which may also be carried out presymptomatically. MATERIAL AND METHODS: We studied differences in psychiatric examination and psychometric measures among the 52 people at risk of HD, who were recommended to postpone or to continue in the predictive protocol. In addition to the psychiatric examination, we administered the Eysenck Personality Questionnaire (EPQ-A), the Symptom Checklist 90 (SCL-90), and quality of life questionnaire (MANSA). RESULTS: People at risk of HD with the recommended test postponement showed lower rate of neuroticism and EPQ-A lie score, higher values on the phobia and the so-called 'positive symptom distress index' in SCL-90 and lower quality of life than people at risk of HD with the recommendation to continue. CONCLUSIONS: Our results indicate that the formalized testing does not bring significant information whereas the clinical psychiatric examination remains the main decisive factor in the recommendation to perform a predictive genetic test. The motivation of applicants is considered as the most important factor in the decision-making process.

Imprecise vowel articulation as a potential early marker of Parkinson's disease: effect of speaking task.

The purpose of this study was to analyze vowel articulation across various speaking tasks in a group of 20 early Parkinson's disease (PD) individuals prior to pharmacotherapy. Vowels were extracted from sustained phonation, sentence repetition, reading passage, and monologue. Acoustic analysis was based upon measures of the first (F1) and second (F2) formant of the vowels /a/, /i/, and /u/, vowel space area (VSA), F2i/F2u and vowel articulation index (VAI). Parkinsonian speakers manifested abnormalities in vowel articulation across F2u, VSA, F2i/F2u, and VAI in all speaking tasks except sustained phonation, compared to 15 age-matched healthy control participants. Findings suggest that sustained phonation is an inappropriate task to investigate vowel articulation in early PD. In contrast, monologue was the most sensitive in differentiating between controls and PD patients, with classification accuracy up to 80%. Measurements of vowel articulation were able to capture even minor abnormalities in speech of PD patients with no perceptible dysarthria. In conclusion, impaired vowel articulation may be considered as a possible early marker of PD. A certain type of speaking task can exert significant influence on vowel articulation. Specifically, complex tasks such as monologue are more likely to elicit articulatory deficits in parkinsonian speech, compared to other speaking tasks.

Horizontal and vertical eye movement metrics: what is important?

OBJECTIVE: To assist other eye movement investigators in the design and analysis of their studies. METHODS: We examined basic saccadic eye movements and smooth pursuit in the horizontal and vertical directions with video-oculography in a group of 145 healthy subjects between 19 and 82 years of age. RESULTS: Gender and education level did not influence eye movement metrics. With age, the latency of leftward and vertical pro- and antisaccades increased (p<0.001), velocity of upward prosaccades decreased (p<0.001), gain of rightward and upward prosaccades diminished (p<0.001), and the error rate of antisaccades increased (p<0.001). Prosaccades and antisaccades were influenced by the direction of the target, resulting in a right/left and up/down asymmetry. The skewness of the saccade velocity profile was stable throughout the lifespan, and within the range of saccades analyzed in the present study, correlated with amplitude and duration only for antisaccades (p<0.001). CONCLUSIONS: Some eye movement metrics must be separated by the direction of movement, others according to subject age, while others may be pooled. SIGNIFICANCE: This study provides important information for new oculomotor laboratories concerning the constitution of subject groups and the analysis of eye movement metrics.

Objective acoustic quantification of phonatory dysfunction in Huntington's disease.

PURPOSE: Although speech motor changes are reported as a common sign of Huntington's disease (HD), the most prominent signs of voice dysfunction remain unknown. The aim of the current study was to explore specific changes in phonatory function in subjects with HD. METHOD: 34 subjects with HD and 34 age- and sex-matched healthy controls were examined. Participants performed sustained vowel phonation for subsequent analyses of airflow insufficiency, aperiodicity, irregular vibrations of vocal folds, signal perturbations, increased noise, and articulation deficiency. In total, 272 phonations were collected and 12 voice parameters were extracted. Subsequently, a predictive model was built to find the most salient patterns of voice disorders in HD. The results were also correlated with disease severity according to the Unified HD Rating Scale (UHDRS) motor score. RESULTS: Subjects with HD showed deterioration in all investigated phonatory functions. Irregular pitch fluctuations, sudden phonation interruption, increased noise, and misplacement of articulators were found to be most significant patterns of phonatory dysfunction in HD (p<0.001). The combination of these four dysphonia aspects contributed to the best classification performance of 94.1% (sensitivity: 95.1%; specificity: 93.2%) in the separation of HD patients from healthy participants. Our results further indicated stronger associations between sudden phonation interruption and voluntary components of the UHDRS (r = -0.48, p<0.01) and between misplacement of articulators and involuntary components of the UHDRS (r = 0.52, p<0.01). CONCLUSIONS: Our configuration of phonatory features can detect subtle voice abnormalities in subjects with HD. As impairment of phonatory function in HD was found to parallel increasing motor involvement, a qualitative description of voice dysfunction may be helpful to gain better insight into the pathophysiology of the vocal mechanism.

Validity of the Montreal Cognitive Assessment in the detection of cognitive dysfunction in Huntington's disease.

The purpose of this study was to assess the convergent and discriminative validity of the Montreal Cognitive Assessment (MoCA) as a screening tool for cognitive dysfunction in Huntington's disease (HD). Twenty HD patients with cognitive deficit and 23 normal controls (NC) without cognitive deficit were matched for age, sex, and education. The mean MoCA score was 20.5 (SD = 5.5) in HD and 27.5 (SD = 2.2) in NC. The MoCA correlated in both samples with the brief cognitive battery composite score (r = .81, p < .001). With the screening and diagnostic cutoff scores determined at <26 points, the MoCA showed a sensitivity of 94% and a specificity of 84% in the detection of cognitive dysfunction in HD. The area under the receiver-operating characteristics curve (95% confidence interval) for the MoCA was 0.90 (0.809-0.997), p < .001. Our results show that the MoCA is a suitable tool for assessing cognitive dysfunction in patients with HD.

Evaluation of speech impairment in early stages of Parkinson's disease: a prospective study with the role of pharmacotherapy.

Despite the initial reports showing beneficial effects of dopaminergic treatment on speech in Parkinson's disease (PD), more recent studies based upon valid measurements have not approved any improvement of speech performance under pharmacotherapy. The aim of this study was to analyze the effect of treatment initiation on the progression of speech impairment in PD, using novel evaluation criteria. Nineteen de novo patients with PD were tested and retested within 2 years after the introduction of antiparkinsonian therapy. As controls, 19 age-matched individuals were recorded. Speech examination included sustained phonation, fast syllable repetition, reading text, and monolog. Quantitative acoustic analyses of the key aspects of speech based on Gaussian kernel distribution, statistical decision-making theory, and healthy speech observation were used to assess the improvement or deterioration of speech. A trend for speech performances to improve was demonstrated after treatment mainly in quality of voice, intensity variability, pitch variability, and articulation. The treatment-related improvement differed in various aspects of speech for individual PD patients. Improvements in vowel articulation and pitch variability correlated with treatment-related changes in bradykinesia and rigidity, whereas voice quality and loudness variability improved independently. Using a novel approach of acoustic analysis and advanced statistics, improvements in speech performance can be demonstrated in PD patients after the introduction of antiparkinsonian therapy. Moreover, changes in speech articulation and pitch variability appear to be related with dopaminergic responsiveness of bradykinesia and rigidity. Therefore, speech may be a valuable marker of disease progression and treatment efficacy in PD.

Disturbance of real space navigation in moderately advanced but not in early Huntington's disease.

BACKGROUND: Visuospatial skills including spatial navigation are known to be impaired in Huntington's disease. Spatial navigation comprises two navigational frameworks, allocentric and egocentric. Several studies have associated the allocentric navigation with the hippocampus and the egocentric navigation with the striatum. The striatum is predominantly impaired from the early stages of Huntington's disease. OBJECTIVE: To find whether spatial navigation impairment is present in the early stages of Huntington's disease and to test the hypothesis that the egocentric navigation is predominantly affected compared to the allocentric navigation. METHODS: In nineteen patients with Huntington's disease the egocentric and the allocentric navigation skills were tested using the Blue Velvet Arena, a human analog of Morris Water Maze, and compared to nineteen age and gender-matched healthy controls. Cognitive functions, with emphasis on the executive functions, were also assessed. RESULTS: The spatial navigation skills deteriorated with the increasing motor impairment in Huntington's disease. These changes only became apparent in patients with moderate functional impairment. No difference between the egocentric and the allocentric skills was seen. DISCUSSION: Spatial navigation deficit is not an early marker of the cognitive dysfunction in Huntington's disease. We speculate that the striatal circuitry that is known to degenerate early in the course of Huntington's disease is not directly associated with the spatial navigation.

Biochemical oxidative stress-related markers in patients with obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is a condition contributing to oxidative stress. The aim of this study was to ascertain if there is any connection between OSA and novel oxidative stress-related markers. Matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), high sensitive C-reactive protein (hsCRP), pregnancy-associated plasma protein-A (PAPP-A), soluble receptors for advanced glycation end-products (sRAGE), zinc (Zn) and copper (Cu) were measured. Further biochemical markers were evaluated. MATERIAL/METHODS: Fifty-one men suspected for OSA indicated for night polygraphy were included. Apnea/hypopnea index (AHI), oxygen desaturation index (ODI), mean blood hemoglobin oxygen saturation (SpO2) and time of blood hemoglobin oxygen saturation below 90% (SpO2 <90%) were measured. Morning venous blood samples were taken. RESULTS: For body mass index (BMI) we found strong positive correlation with levels of Cu, MMP-9, hsCRP and fibrinogen, and negative correlation with sRAGE. Concerning ventilation parameters, we found positive correlation of ODI and SpO2 <90% with markers MMP-9 and hsCRP. sRAGE level correlated with AHI and ODI negatively. SpO2 correlated negatively with Cu, MMP-9, hsCRP and fibrinogen. There was no correlation between ventilation parameters and markers MMP-2, PAPP-A and Zn. Compared to severity of OSA, there was significant difference in levels of hsCRP and Cu between patients with AHI ≤5 and AHI ≥30 independent of BMI. CONCLUSIONS: MMP-9, hsCRP, sRAGE and Cu seem to be strong predictors of oxidative stress in OSA patients. The strong correlation between oxidative stress-related markers and OSA is elucidated by connection of these to BMI, which is probably a primary condition of oxidative stress, but OSA is an additive condition.

Sleep disturbances in untreated Parkinson's disease.

Sleep abnormalities are frequently found in Parkinson's disease (PD). However, it is unclear if they are present from the initial stages of PD. We thus aimed to assess sleep disturbances in newly diagnosed PD patients. We investigated 20 untreated PD patients using the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI) and the PD Sleep Scale (PDSS). Video-polysomnography and multiple sleep latency test (MSLT) were performed in 15 patients and 15 healthy controls. The ESS score was abnormally high in one patient, while short MSLT times were found in three other patients. The PSQI was higher (p < 0.05) and the PDSS lower (p < 0.001) in patients compared with controls. Video-polysomnography demonstrated a higher percentage of rapid eye movement sleep without atonia (RWA) in patients compared with controls (mean 28 vs. 2.9%, p < 0.001), whereas only one patient had clinically manifested rapid eye movement sleep behavior disorder (RBD). Interestingly, the occurrence of RWA correlated with the motor score (ρ = 0.65, p < 0.05). This study demonstrates that sleep disturbances emerge, in a proportion of patients, from the early stages of PD. RWA is a common finding while RBD is rarely present in early untreated PD.

Effects of ropinirole prolonged-release on sleep disturbances and daytime sleepiness in Parkinson disease.

This study evaluated the effects of ropinirole prolonged-release (RPR) in comparison with ropinirole immediate-release (RIR) on sleep-related disorders in Parkinson disease (PD).Thirty-three PD patients (aged 62.5 [SD, 8] years; PD duration, 9 [SD, 4] years) were evaluated on a stable dose of RIR and 5 to 13 weeks after switch to the closest possible dose of RPR. The following questionnaires were administered: Epworth Sleepiness Scale, PD Sleep Scale, Pittsburgh Sleep Quality Index, REM Sleep Behavior Disorder Screening Questionnaire, and PD Questionnaire 39. We further monitored the occurrence of restless legs syndrome and sleep attacks (SAs). Motor disability was evaluated by PD diary and by Unified Parkinson Disease Rating Scale part 3 on medication (ON) and after medication withdrawal (OFF). In 8 patients with marked subjective sleep disturbance, polysomnography, and multiple sleep latency test were performed.After switching to RPR, there was an improvement in PD Sleep Scale (94.9 [SD, 23] vs 102.2 [SD, 27]; P < 0.05 corrected), Pittsburgh Sleep Quality Index (7.2 [SD, 3] vs 5.8 [SD, 3]; P < 0.05 corrected), Epworth Sleepiness Scale (14.1 [SD, 5] vs 12.0 [SD, 6]; P < 0.05 corrected) and Unified Parkinson Disease Rating Scale part 3 in the ON state (20.9 [SD, 10] 10 vs 17.6 [SD, 10]; P < 0.05 corrected). Thirteen patients reported disappearance of SAs on RPR. Polysomnography and multiple sleep latency test showed no changes in a subgroup of 8 patients after the switch to RPR.Ropinirole prolonged-release compared with RIR improved subjective quality of sleep, reduced daytime sleepiness, and led to disappearance of SAs in some patients possibly due to a more stable plasma level of ropinirole.