Using Ecological Momentary Assessment in Testing the Effectiveness of an Alcohol Intervention: A Two-Arm Parallel Group Randomized Controlled Trial

Background

Alcohol consumption of college students has a fluctuating nature, which might impact the measurement of intervention effects. By using 25 follow-up time-points, this study tested whether intervention effects are robust or might vary over time.

Methods

Data were used from a two-arm parallel group randomized controlled trial applying ecological momentary assessment (EMA) with 30 data time-points in total. Students between 18 and 24 years old who reported heavy drinking in the past six months and who were ready to change their alcohol consumption were randomly assigned to the experimental (n = 456: web-based brief alcohol intervention) and control condition (n = 451: no intervention). Outcome measures were weekly alcohol consumption, frequency of binge drinking, and heavy drinking status.

Results

According to the intention-to-treat principle, regression analyses revealed that intervention effects on alcohol consumption varied when exploring multiple follow-up time-points. Intervention effects were found for a) weekly alcohol consumption at 1, 2, 3, 4, and 7 weeks follow-up, b) frequency of binge drinking at 1, 2, 7, and 12 weeks follow-up, and c) heavy drinking status at 1, 2, 7, and 16 weeks follow-up.

Conclusions

This research showed that the commonly used one and six month follow-up time-points are relatively arbitrary and not using EMA might bring forth erroneous conclusions on the effectiveness of interventions. Therefore, future trials in alcohol prevention research and beyond are encouraged to apply EMA when assessing outcome measures and intervention effectiveness.

Trial registration

Netherlands Trial Register NTR2665     

Flow Cytometric Quantification of All Phases of the Cell Cycle and Apoptosis in a Two-Color Fluorescence Plot

An optimal technology for cell cycle analysis would allow the concomitant measurement of apoptosis, G0, G1, S, G2 and M phases in combination with cell surface phenotyping. We have developed an easy method in flow cytometry allowing this discrimination in an only two-color fluorescent plot. It is based on the concomitant use of 7-amino-actinomycin D and the antibodies anti-Ki67 and anti-phospho(Ser10)-histone H3, both conjugated to Alexa Fluor®488 to discriminate G0 and M phases, respectively. The method is particularly valuable in a clinical setting as verified in our laboratory by analyzing human leukemic cells from marrow samples or after exposure to cell cycle modifiers.     

Micro-Geographical Heterogeneity in Schistosoma mansoni and S. haematobium Infection and Morbidity in a Co-Endemic Community in Northern Senegal

Background

Schistosoma mansoni and S. haematobium are co-endemic in many areas in Africa. Yet, little is known about the micro-geographical distribution of these two infections or associated disease within such foci. Such knowledge could give important insights into the drivers of infection and disease and as such better tailor schistosomiasis control and elimination efforts.

Methodology

In a co-endemic farming community in northern Senegal (346 children (0–19 y) and 253 adults (20–85 y); n = 599 in total), we studied the spatial distribution of S. mansoni and S. haematobium single and mixed infections (by microscopy), S. mansoni-specific hepatic fibrosis, S. haematobium-specific urinary tract morbidity (by ultrasound) and water contact behavior (by questionnaire). The Kulldorff''s scan statistic was used to detect spatial clusters of infection and morbidity, adjusted for the spatial distribution of gender and age.

Principal Findings

Schistosoma mansoni and S. haematobium infection densities clustered in different sections of the community (p = 0.002 and p = 0.023, respectively), possibly related to heterogeneities in the use of different water contact sites. While the distribution of urinary tract morbidity was homogeneous, a strong geospatial cluster was found for severe hepatic fibrosis (p = 0.001). Particularly those people living adjacent to the most frequently used water contact site were more at risk for more advanced morbidity (RR = 6.3; p = 0.043).

Conclusions/Significance

Schistosoma infection and associated disease showed important micro-geographical heterogeneities with divergent patterns for S. mansoni and S. haematobium in this Senegalese community. Further in depth investigations are needed to confirm and explain our observations. The present study indicates that local geospatial patterns should be taken into account in both research and control of schistosomiasis. The observed extreme focality of schistosomiasis even at community level, suggests that current strategies may not suffice to move from morbidity control to elimination of schistosomiasis, and calls for less uniform measures at a finer scale.     

KCa3.1 Channel-Blockade Attenuates Airway Pathophysiology in a Sheep Model of Chronic Asthma

Background

The Ca²⁺-activated K⁺ channel K_Ca3.1 is expressed in several structural and inflammatory airway cell types and is proposed to play an important role in the pathophysiology of asthma. The aim of the current study was to determine whether inhibition of K_Ca3.1 modifies experimental asthma in sheep.

Methodology and Principal Findings

Atopic sheep were administered either 30 mg/kg Senicapoc (ICA-17073), a selective inhibitor of the K_Ca3.1-channel, or vehicle alone (0.5% methylcellulose) twice daily (orally). Both groups received fortnightly aerosol challenges with house dust mite allergen for fourteen weeks. A separate sheep group received no allergen challenges or drug treatment. In the vehicle-control group, twelve weeks of allergen challenges resulted in a 60±19% increase in resting airway resistance, and this was completely attenuated by treatment with Senicapoc (0.25±12%; n = 10, P = 0.0147). The vehicle-control group had a peak-early phase increase in lung resistance of 82±21%, and this was reduced by 58% with Senicapoc treatment (24±14%; n = 10, P = 0.0288). Senicapoc-treated sheep also demonstrated reduced airway hyperresponsiveness, requiring a significantly higher dose of carbachol to increase resistance by 100% compared to allergen-challenged vehicle-control sheep (20±5 vs. 52±18 breath-units of carbachol; n = 10, P = 0.0340). Senicapoc also significantly reduced eosinophil numbers in bronchoalveolar lavage taken 48 hours post-allergen challenge, and reduced vascular remodelling.

Conclusions

These findings suggest that K_Ca3.1-activity contributes to allergen-induced airway responses, inflammation and vascular remodelling in a sheep model of asthma, and that inhibition of K_Ca3.1 may be an effective strategy for blocking allergen-induced airway inflammation and hyperresponsiveness in humans.     

Mixing Nulliparous and Multiparous Women in Randomised Controlled Trials of Preeclampsia Prevention Is Debatable: Evidence from a Systematic Review

Background

Nulliparity is a major risk factor of preeclampsia investigated in numerous trials of its prevention.

Objective

We aimed to assess whether these trials considered nulliparity in subject selection or analysis of results.

Search Strategy

01 April 2013 search of MEDLINE via PubMed, EMBASE and the Cochrane Library. 01 April 2013 search of trials registered in Clinicaltrials.gov.

Selection Criteria

Randomised controlled trials and metaanalyses of preeclampsia prevention with no restriction to period of publication or language. Metaanalyses were selected to fully identify relevant trials.

Data Collection and Analysis

One reader appraised each selected article/registered protocol using a pretested, standardized data abstraction form developed in a pilot test. For each article, he recorded whether both nulliparous and multiparous were included and, in case of mixed populations, whether randomisation was stratified, and whether subgroup analyses had been reported. For registered protocols, he only assessed whether it was planned to include mixed populations.

Main Results

88 randomised controlled trials were identified, representing 83,396 included women. In 58 of the 88 articles identified (65.9%), preeclampsia was the primary outcome. In 31 of these (53.4%), the investigation combined nulliparous and multiparous women; only two reports in 31 (6.5%) stated that randomisation was stratified on parity and only four (12.9%) described a subgroup analysis by parity. Of the 30 registered trials, 20 (66.6%) planned to include both nulliparous and multiparous women.

Conclusion

Parity is largely ignored in randomised controlled trials of preeclampsia prevention, which raises difficulties in interpreting the results.     

Smooth Pursuit Eye Movements in Children with Strabismus and in Children with Vergence Deficits

Purpose

The objective of our study was to examine horizontal smooth pursuit performance in strabismic children and in children with vergence deficits, and to compare these data with those recorded in a group of control age-matched children.

Methods

Binocular eye movements were recorded by video-oculography in ten strabismic children (mean age: 9.8±0.8) and seven children with vergence deficits (mean age: 10.8±0.6). Data were compared to that of age-matched control children (mean age: 9.8±0.8 years).

Results

Catch-up saccades amplitude in strabismic children and in children with vergence deficits were significantly higher than in control age-matched children. Moreover, in strabismic children the amplitude of catch-up saccades was significantly higher in rightward than in leftward direction. The number of catch-up saccades was also significantly higher in rightward than in leftward direction. The gain value of pursuits in rightward direction was significantly higher in the right eye than in the left one; for the right eye, the gain value was significantly higher in rightward than in leftward direction. Binocular coordination of pursuit was better in control age-matched children than in children with vergence deficits and than in strabismic children.

Conclusions

Binocular coordination of pursuit is abnormal in children with vergence deficits and worse in strabismic children. Binocular vision plays an important role in improving binocular coordination of pursuit.     

A DNA Metabarcoding Study of a Primate Dietary Diversity and Plasticity across Its Entire Fragmented Range

In tropical regions, most primary ecosystems have been replaced by mosaic landscapes in which species must cope with a large shift in the distribution of their habitat and associated food resources. Primates are particularly vulnerable to habitat modifications. Most species persist in small fragments surrounded by complex human-mediated matrices whose structure and connectivity may strongly influence their dispersal and feeding behavior. Behavioral plasticity appears to be a crucial parameter governing the ability of organisms to exploit the resources offered by new matrix habitats and thus to persist in fragmented habitats. In this study, we were interested in the dietary plasticity of the golden-crowned sifaka (Propithecus tattersalli), an endangered species of lemur, found only in the Daraina region in north-eastern Madagascar. We used a DNA-based approach combining the barcoding concept and Illumina next-generation sequencing to (i) describe the species diet across its entire range and (ii) evaluate the influence of landscape heterogeneity on diet diversity and composition. Faeces from 96 individuals were sampled across the entire species range and their contents were analyzed using the trnL metabarcoding approach. In parallel, we built a large DNA reference database based on a checklist of the plant species of the Daraina region. Our results suggest that golden-crowned sifakas exhibit remarkable dietary diversity with at least 130 plant species belonging to 80 genera and 49 different families. We highlighted an influence of both habitat type and openness on diet composition suggesting a high flexibility of foraging strategies. Moreover, we observed the presence of numerous cultivated and naturalized plants in the faeces of groups living in forest edge areas. Overall, our findings support our initial expectation that P. tattersalli is able to cope with the current level of alteration of the landscape and confirm our previous results on the distribution and the dispersal ability of this species.     

Soluble Guanylate Cyclase α1–Deficient Mice: A Novel Murine Model for Primary Open Angle Glaucoma

Primary open angle glaucoma (POAG) is a leading cause of blindness worldwide. The molecular signaling involved in the pathogenesis of POAG remains unknown. Here, we report that mice lacking the α₁ subunit of the nitric oxide receptor soluble guanylate cyclase represent a novel and translatable animal model of POAG, characterized by thinning of the retinal nerve fiber layer and loss of optic nerve axons in the context of an open iridocorneal angle. The optic neuropathy associated with soluble guanylate cyclase α₁–deficiency was accompanied by modestly increased intraocular pressure and retinal vascular dysfunction. Moreover, data from a candidate gene association study suggests that a variant in the locus containing the genes encoding for the α₁ and β₁ subunits of soluble guanylate cyclase is associated with POAG in patients presenting with initial paracentral vision loss, a disease subtype thought to be associated with vascular dysregulation. These findings provide new insights into the pathogenesis and genetics of POAG and suggest new therapeutic strategies for POAG.     

ITN Mixtures of Chlorfenapyr (Pyrrole) and Alphacypermethrin (Pyrethroid) for Control of Pyrethroid Resistant Anopheles arabiensis and Culex quinquefasciatus

Pyrethroid resistant Anopheles gambiae malaria vectors are widespread throughout sub-Saharan Africa and continued efficacy of pyrethroid ITNs is under threat. Chlorfenapyr is a promising pyrrole insecticide with a unique mechanism of action conferring no cross-resistance to existing public health insecticides. Mixtures of chlorfenapyr (CFP) and alphacypermethrin (alpha) may provide additional benefits over chlorfenapyr or alphacypermethrin used alone. An ITN mixture of CFP 100 mg/m²+alpha 25 mg/m² was compared with CFP 100 mg/m² and alpha 25 mg/m² in a small-scale experimental hut trial in an area of wild An. arabiensis. The same treatments were evaluated in tunnel tests against insectary-reared pyrethroid susceptible and resistant Culex quinquefasciatus. Performance was measured in terms of insecticide-induced mortality, and blood-feeding inhibition. Tunnel tests showed that mixtures of CFP 100+ alpha 25 were 1.2 and 1.5 times more effective at killing susceptible Cx. quinquefasciatus than either Alpha 25 (P = 0.001) or CFP 100 (P = 0.001) ITNs. Mixtures of CFP100+ alpha 25 were 2.2 and 1.2 times more effective against resistant Cx. quinquefasciatus than either alpha 25 (P = 0.001) or CFP100 (P = 0.003) ITNs. CFP 100+ alpha 25 produced higher levels of blood-feeding inhibition than CFP alone for susceptible (94 vs 46%, P = 0.001) and resistant (84 vs 53%, P = 0.001) strains. In experimental huts the mixture of CFP 100+ Alpha 25 killed 58% of An. arabiensis, compared with 50% for alpha and 49% for CFP, though the differences were not significant. Blood-feeding inhibition was highest in the mixture with a 76% reduction compared to the untreated net (P = 0.001). ITN mixtures of chlorfenapyr and alphacypermethrin should restore effective control of resistant populations of An. gambiae malaria vectors, provide protection from blood-feeding, and may have benefits for resistance management, particularly in areas with low or moderate frequency of pyrethroid resistance. A wash-resistant mixture should be developed urgently.