Sharp comparison and maximum principles via horizontal normal mapping in the Heisenberg group

In this paper we solve a problem raised by Gutiérrez and Montanari about comparison principles for H−convex functions on subdomains of Heisenberg groups. Our approach is based on the notion of the sub-Riemannian horizontal normal mapping and uses degree theory for set-valued maps. The statement of the comparison principle combined with a Harnack inequality is applied to prove the Aleksandrov-type maximum principle, describing the correct boundary behavior of continuous H−convex functions vanishing at the boundary of horizontally bounded subdomains of Heisenberg groups. This result answers a question by Garofalo and Tournier. The sharpness of our results are illustrated by examples.

New insights in the pathogenesis of high-altitude pulmonary edema

High-altitude pulmonary edema is a life-threatening condition occurring in predisposed but otherwise healthy individuals. It therefore permits the study of underlying mechanisms of pulmonary edema in the absence of confounding factors such as coexisting cardiovascular or pulmonary disease, and/or drug therapy. There is evidence that some degree of asymptomatic alveolar fluid accumulation may represent a normal phenomenon in healthy humans shortly after arrival at high altitude. Two fundamental mechanisms then determine whether this fluid accumulation is cleared or whether it progresses to HAPE: the quantity of liquid escaping from the pulmonary vasculature and the rate of its clearance by the alveolar respiratory epithelium. The former is directly related to the degree of hypoxia-induced pulmonary hypertension, whereas the latter is determined by the alveolar epithelial sodium transport. Here, we will review evidence that, in HAPE-prone subjects, impaired pulmonary endothelial and epithelial NO synthesis and/or bioavailability may represent a central underlying defect predisposing to exaggerated hypoxic pulmonary vasoconstriction and, in turn, capillary stress failure and alveolar fluid flooding. We will then demonstrate that exaggerated pulmonary hypertension, although possibly a conditio sine qua non, may not always be sufficient to induce HAPE and how defective alveolar fluid clearance may represent a second important pathogenic mechanism.

Increased surfactant protein D fails to improve bacterial clearance and inflammation in serpinB1-/- mice

Previously, we described the protective role of the neutrophil serine protease inhibitor serpinB1 in preventing early mortality of Pseudomonas aeruginosa lung infection by fostering bacterial clearance and limiting inflammatory cytokines and proteolytic damage. Surfactant protein D (SP-D), which maintains the antiinflammatory pulmonary environment and mediates bacterial removal, was degraded in infected serpinB1-deficient mice. Based on the hypothesis that increased SP-D would rescue or mitigate the pathological effects of serpinB1 deletion, we generated two serpinB1(-/-) lines overexpressing lung-specific rat SP-D and inoculated the mice with P. aeruginosa. Contrary to predictions, bacterial counts in the lungs of SP-D(low)serpinB1(-/-) and SP-D(high) serpinB1(-/-) mice were 4 logs higher than wild-type and not different from serpinB1(-/-) mice. SP-D overexpression also failed to mitigate inflammation (TNF-α), lung injury (free protein, albumin), or excess neutrophil death (free myeloperoxidase, elastase). These pathological markers were higher for infected SP-D(high)serpinB1(-/-) mice than for serpinB1(-/-) mice, although the differences were not significant after controlling for multiple comparisons. The failure of transgenic SP-D to rescue antibacterial defense of serpinB1-deficient mice occurred despite 5-fold or 20-fold increased expression levels, largely normal structure, and dose-dependent bacteria-aggregating activity. SP-D of infected wild-type mice was intact in 43-kD monomers by reducing SDS-PAGE. By contrast, proteolytic fragments of 35, 17, and 8 kD were found in infected SP-D(low)serpinB1(-/-), SP-D(high) serpinB1(-/-) mice, and serpinB1(-/-) mice. Thus, although therapies to increase lung concentration of SP-D may have beneficial applications, the findings suggest that therapy with SP-D may not be beneficial for lung inflammation or infection if the underlying clinical condition includes excess proteolysis.

Validation of the LittlEARS((R)) Auditory Questionnaire in children with normal hearing

OBJECTIVES: With more children receiving cochlear implants during infancy, there is a need for validated assessments of pre-verbal and early verbal auditory skills. The LittlEARS Auditory Questionnaire is presented here as the first module of the LittlEARS test battery. The LittlEARS Auditory Questionnaire was developed and piloted to assess the auditory behaviour of normal hearing children and hearing impaired children who receive a cochlear implant or hearing aid prior to 24 months of age. This paper presents results from two studies: one validating the LittlEARS Auditory Questionnaire on children with normal hearing who are German speaking and a second validating the norm curves found after adaptation and administration of the questionnaire to children with normal hearing in 15 different languages. METHODS: Scores from a group of 218 German and Austrian children with normal hearing between 5 days and 24 months of age were used to create a norm curve. The questionnaire was adapted from the German original into English and then 15 other languages to date. Regression curves were found based on parental responses from 3309 normal hearing infants and toddlers. Curves for each language were compared to the original German validation curve. RESULTS: The results of the first study were a norm curve which reflects the age-dependence of auditory behaviour, reliability and homogeneity as a measure of auditory behaviour, and calculations of expected and critical values as a function of age. Results of the second study show that the regression curves found for all the adapted languages are essentially equal to the German norm curve, as no statistically significant differences were found. CONCLUSIONS: The LittlEARS Auditory Questionnaire is a valid, language-independent tool for assessing the early auditory behaviour of infants and toddlers with normal hearing. The results of this study suggest that the LittlEARS Auditory Questionnaire could also be very useful for documenting children's progress with their current amplification, providing evidence of the need for implantation, or highlighting the need for follow-up in other developmental areas.

Normal platelet activation profile in patients with peripheral arterial disease on aspirin.

BACKGROUND Peripheral arterial disease (PAD) is a progressive vascular disease associated with a high risk of cardiovascular morbidity and death. Antithrombotic prevention is usually applied by prescribing the antiplatelet agent aspirin. However, in patients with PAD aspirin fails to provide protection against myocardial infarction and death, only reducing the risk of ischemic stroke. Platelets may play a role in disease development, but this has not been tested by proper mechanistic studies. In the present study, we performed a systematic evaluation of platelet reactivity in whole blood from patients with PAD using two high-throughput assays, i.e. multi-agonist testing of platelet activation by flow cytometry and multi-parameter testing of thrombus formation on spotted microarrays. METHODS Blood was obtained from 40 patients (38 on aspirin) with PAD in majority class IIa/IIb and from 40 age-matched control subjects. Whole-blood flow cytometry and multiparameter thrombus formation under high-shear flow conditions were determined using recently developed and validated assays. RESULTS Flow cytometry of whole blood samples from aspirin-treated patients demonstrated unchanged high platelet responsiveness towards ADP, slightly elevated responsiveness after glycoprotein VI stimulation, and decreased responsiveness after PAR1 thrombin receptor stimulation, compared to the control subjects. Most parameters of thrombus formation under flow were similarly high for the patient and control groups. However, in vitro aspirin treatment caused a marked reduction in thrombus formation, especially on collagen surfaces. When compared per subject, markers of ADP- and collagen-induced integrin activation (flow cytometry) strongly correlated with parameters of collagen-dependent thrombus formation under flow, indicative of a common, subject-dependent regulation of both processes. CONCLUSION Despite of the use of aspirin, most platelet activation properties were in the normal range in whole-blood from class II PAD patients. These data underline the need for more effective antithrombotic pharmacoprotection in PAD.

Unistructed BIAT faking when ego depleted or in normal state: Differential effect on brain and behavior

Background: Deception can distort psychological tests on socially sensitive topics. Understanding the cerebral processes that are involved in such faking can be useful in detection and prevention of deception. Previous research shows that faking a brief implicit association test (BIAT) evokes a characteristic ERP response. It is not yet known whether temporarily available self-control resources moderate this response. We randomly assigned 22 participants (15 females, 24.23 ± 2.91 years old) to a counterbalanced repeated-measurements design. Participants first completed a Brief-IAT (BIAT) on doping attitudes as a baseline measure and were then instructed to fake a negative doping attitude both when self-control resources were depleted and non-depleted. Cerebral activity during BIAT performance was assessed using high-density EEG. Results: Compared to the baseline BIAT, event-related potentials showed a first interaction at the parietal P1, while significant post hoc differences were found only at the later occurring late positive potential. Here, significantly decreased amplitudes were recorded for ‘normal’ faking, but not in the depletion condition. In source space, enhanced activity was found for ‘normal’ faking in the bilateral temporoparietal junction. Behaviorally, participants were successful in faking the BIAT successfully in both conditions. Conclusions: Results indicate that temporarily available self-control resources do not affect overt faking success on a BIAT. However, differences were found on an electrophysiological level. This indicates that while on a phenotypical level self-control resources play a negligible role in deliberate test faking the underlying cerebral processes are markedly different. Electronic supplementary material: The online version of this article (doi:10.1186/s12868-016-0249-8) contains supplementary material, which is available to authorized users.