Increased markers of cardiac vagal activity in leucine-rich repeat kinase 2-associated Parkinson's disease.

PurposeCardiac autonomic dysfunction manifests as reduced heart rate variability (HRV) in idiopathic Parkinson's disease (PD), but no significant reduction has been found in PD patients who carry the LRRK2 mutation. Novel HRV features have not been investigated in these individuals. We aimed to assess cardiac autonomic modulation through standard and novel approaches to HRV analysis in individuals who carry the LRRK2 G2019S mutation.MethodsShort-term electrocardiograms were recorded in 14 LRRK2-associated PD patients, 25 LRRK2-non-manifesting carriers, 32 related non-carriers, 20 idiopathic PD patients, and 27 healthy controls. HRV measures were compared using regression modeling, controlling for age, sex, mean heart rate, and disease duration. Discriminant analysis highlighted the feature combination that best distinguished LRRK2-associated PD from controls.ResultsBeat-to-beat and global HRV measures were significantly increased in LRRK2-associated PD patients compared with controls (e.g., deceleration capacity of heart rate: p = 0.006) and idiopathic PD patients (e.g., 8th standardized moment of the interbeat interval distribution: p = 0.0003), respectively. LRRK2-associated PD patients also showed significantly increased irregularity of heart rate dynamics, as quantified by Rényi entropy, when compared with controls (p = 0.002) and idiopathic PD patients (p = 0.0004). Ordinal pattern statistics permitted the identification of LRRK2-associated PD individuals with 93% sensitivity and 93% specificity. Consistent results were found in a subgroup of LRRK2-non-manifesting carriers when compared with controls.ConclusionsIncreased beat-to-beat HRV in LRRK2 G2019S mutation carriers compared with controls and idiopathic PD patients may indicate augmented cardiac autonomic cholinergic activity, suggesting early impairment of central vagal feedback loops in LRRK2-associated PD

Epidemiological characterization of Plasmodium falciparum in the Republic of Cabo Verde: implications for potential large-scale re-emergence of malaria

BACKGROUND: Malaria has come near eradication at archipelago of Cabo Verde in 1970. Infections are now only observed in Santiago, where outbreaks occur. In these islands, malaria is considered by the international community as being of limited risk and, therefore, no prophylaxis is recommended. Since the understanding of factors that determine malaria outbreaks are crucial for controlling the disease, the present study aimed to investigate if the malaria infections observed in Santiago Island are maintained in isolated foci and in asymptomatic individuals. METHODS: The occurrence of asymptomatic carriers in villages with history of malaria as well as the level of exposure of these populations were investigated using PCR and serological analyses. RESULTS: Results indicate that malaria is maintained as asymptomatic and sub-patent infections and that the majority of the circulating parasite populations harbour chloroquine-resistant mutations. CONCLUSION: These observations highlight the alarming prospect of malaria to become a serious public health problem and underscore the need for a tighter surveillance

Allomonal effect of breath contributes to differential attractiveness of humans to the African malaria vector Anopheles gambiae

BACKGROUND: Removal of exhaled air from total body emanations or artificially standardising carbon dioxide (CO(2)) outputs has previously been shown to eliminate differential attractiveness of humans to certain blackfly (Simuliidae) and mosquito (Culicidae) species. Whether or not breath contributes to between-person differences in relative attractiveness to the highly anthropophilic malaria vector Anopheles gambiae sensu stricto remains unknown and was the focus of the present study. METHODS: The contribution to and possible interaction of breath (BR) and body odours (BO) in the attraction of An. gambiae s.s. to humans was investigated by conducting dual choice tests using a recently developed olfactometer. Either one or two human subjects were used as bait. The single person experiments compared the attractiveness of a person's BR versus that person's BO or a control (empty tent with no odour). His BO and total emanations (TE = BR+BO) were also compared with a control. The two-person experiments compared the relative attractiveness of their TE, BO or BR, and the TE of each person against the BO of the other. RESULTS: Experiments with one human subject (P(1)) as bait found that his BO and TE collected more mosquitoes than the control (P = 0.005 and P < 0.001, respectively), as did his BO and the control versus his BR (P < 0.001 and P = 0.034, respectively). The TE of P(1 )attracted more mosquitoes than that of another person designated P(8 )(P < 0.021), whereas the BR of P(8 )attracted more mosquitoes than the BR of P(1 )(P = 0.001). The attractiveness of the BO of P(1 )versus the BO of P(8 )did not differ (P = 0.346). The BO from either individual was consistently more attractive than the TE from the other (P < 0.001). CONCLUSIONS: We demonstrated for the first time that human breath, although known to contain semiochemicals that elicit behavioural and/or electrophysiological responses (CO(2), ammonia, fatty acids) in An. gambiae also contains one or more constituents with allomonal (~repellent) properties, which inhibit attraction and may serve as an important contributor to between-person differences in the relative attractiveness of humans to this important malaria vector

Inducing Probabilistic Grammars by Bayesian Model Merging

We describe a framework for inducing probabilistic grammars from corpora of positive samples. First, samples are {\em incorporated} by adding ad-hoc rules to a working grammar; subsequently, elements of the model (such as states or nonterminals) are {\em merged} to achieve generalization and a more compact representation. The choice of what to merge and when to stop is governed by the Bayesian posterior probability of the grammar given the data, which formalizes a trade-off between a close fit to the data and a default preference for simpler models (`Occam's Razor'). The general scheme is illustrated using three types of probabilistic grammars: Hidden Markov models, class-based $n$-grams, and stochastic context-free grammars.Comment: To appear in Grammatical Inference and Applications, Second International Colloquium on Grammatical Inference; Springer Verlag, 1994. 13 page