A nipple shield delivery system for oral drug delivery to breastfeeding infants : Microbicide delivery to inactivate HIV

A new drug delivery method for infants is presented which incorporates an active pharmaceutical ingredient (API)-loaded insert into a nipple shield delivery system (NSDS). The API is released directly into milk during breastfeeding. This study investigates the feasibility of using the NSDS to deliver the microbicide sodium dodecyl sulfate (SDS), with the goal of preventing mother-to-child transmission (MTCT) of HIV during breastfeeding in low-resource settings, when there is no safer alternative for the infant but to breastfeed. SDS has been previously shown to effectively inactivate HIV in human milk. An apparatus was developed to simulate milk flow through and drug release from a NSDS. Using this apparatus milk was pulsed through a prototype device containing a non-woven fiber insert impregnated with SDS and the microbicide was rapidly released. The total SDS release from inserts ranged from 70 to 100% of the average 0.07 g load within 50 ml (the volume of a typical breastfeed). Human milk spiked with H9/HIVIIIB cells was also passed through the same set-up. Greater than 99% reduction of cell-associated HIV infectivity was achieved in the first 10 ml of milk. This proof of concept study demonstrates efficient drug delivery to breastfeeding infants is achievable using the NSDS.

Brodifacoum is effective against Norway Rats (Rattus norvegicus) in a tyrosine139cysteine focus of anticoagulant resistance, Westphalia, Germany

BACKGROUND: The single nucleotide polymorphism (SNP), and consequent amino acid exchange from tyrosine to cysteine at location 139 of the vkorc1 gene (i.e. tyrosine139cysteine or Y139C), is the most widespread anticoagulant resistance mutation in Norway rats (Rattus norvegicus Berk.) in Europe. Field trials were conducted to determine incidence of the Y139C SNP at two rat infested farms in Westphalia, Germany, and to estimate the practical efficacy against them of applications, using a pulsed baiting treatment regime, of a proprietary bait (KleratTM) containing 50 ppm brodifacoum. RESULTS: DNA analysis for the Y139C mutation showed that resistant rats were prevalent at the two farms, with an incidence of 80.0% and 78.6% respectively. Applications of brodifacoum bait achieved results of 99.2% and 100.0% control at the two farms, when measured by census baiting, although the treatment was somewhat prolonged at one site due to the abundance of attractive alternative food. CONCLUSION: The study showed that 50 ppm brodifacoum bait is fully effective against the Y139C SNP at the M��nsterland focus and is likely to be so elsewhere in Europe where this mutation is found. The pulsed baiting regime reduced to relatively low levels the quantity of bait required to control these two substantial resistant Norway rat infestations. Previous studies had shown much larger quantities of bromadiolone and difenacoum baits used in ineffective treatments against Y139C resistant rats in the M��nsterland. These results should be considered when making decisions about the use of anticoagulant against resistant Norway rats and their potential environmental impacts.

Natal nest locations of the Asian house rat (Rattus tanezumi) in lowland rice���coconut cropping systems: a coconut penthouse or rice bunds with water frontage?

CONTEXT. Rattus tanezumi is a serious crop pest within the island of Luzon, Philippines. In intensive flood-irrigated rice field ecosystems of Luzon, female R. tanezumi are known to primarily nest within the tillers of ripening rice fields and along the banks of irrigation canals. The nesting habits of R. tanezumi in complex rice���coconut cropping systems are unknown. AIMS. To identify the natal nest locations of R. tanezumi females in rice���coconut systems of the Sierra Madre Biodiversity Corridor (SMBC), Luzon, during the main breeding season to develop a management strategy that specifically targets their nesting habitat. METHODS. When rice was at the booting to ripening stage, cage-traps were placed in rice fields adjacent to coconut habitat. Thirty breeding adult R. tanezumi females were fitted with radio-collars and successfully tracked to their nest sites. KEY RESULTS. Most R. tanezumi nests (66.7%) were located in coconut groves, five nests (16.7%) were located in rice fields and five nests (16.7%) were located on the rice field edge. All nests were located above ground level and seven nests were located in coconut tree crowns. The median distance of nest sites to the nearest rice field was 22.5m. Most nest site locations had good cover of ground vegetation and understorey vegetation, but low canopy cover. Only one nest location had an understorey vegetation height of less than 20 cm. CONCLUSIONS. In the coastal lowland rice���coconut cropping systems of the SMBC, female R. tanezumi showed a preference for nesting in adjacent coconut groves. This is contrary to previous studies in intensive flood-irrigated rice ecosystems of Luzon, where the species nests mainly in the banks of irrigation canals. It is important to understand rodent breeding ecology in a specific ecosystem before implementing appropriate management strategies. IMPLICATIONS. In lowland rice���coconut cropping systems, coconut groves adjacent to rice fields should be targeted for the 20 management of R. tanezumi nest sites during the main breeding season as part of an integrated ecologically based approach to rodent pest management.

Testing the sustainability and sensitivity to climatic change of terrace agricultural systems in the Peruvian Andes: a pilot study

The results of an integrated geoarchaeological and palaeoecological pilot study of a prehistoric agricultural terrace and nearby mire basin are presented. They reveal two stages of terrace construction for the cultivation of Zea mays during the Middle Horizon (615���695 AD) and late, Late Intermediate Period (1200���1400 AD). These stages were strongly associated with evidence for vegetation succession, destabilisation and erosion of the surrounding landscape, and changes in mire surface wetness. The reasons for agricultural terrace abandonment and/or reconstruction are uncertain, with only circumstantial evidence for climatically induced agricultural change.

Pedosedimentary, cultural and environmental significance of palaeosols within Pre-Hispanic agricultural terraces in the southern Peruvian Andes

Paleosols were exposed in sections through four abandoned pre-Hispanic agricultural terraces surrounding an infilled mire basin in the southern Peruvian Andes. The two paleosols beneath the Tocotoccasa terrace represent the original ���natural��� solum and a later soil formed after construction of the agricultural terrace, probably during the early Middle Horizon cultural period (615���695 AD). The soil at the current surface developed subsequent to the building up and reconstruction of the terrace, possibly during the late Late Intermediate period (1200���1400 AD). Micromorphology revealed an unexpected abundance of clay coatings within the upper terrace paleosol and surface terrace soil, a phenonemon attributed to the migration and/or accumulation of neoformed clay produced from the weathering of very unstable volcanic clasts, perhaps fuelled by arid/humid climatic oscillations and/or seasonal input of irrigation waters. The paleosols at Tocotoccasa could not be correlated with any degree of confidence with those beneath the other three terraces due to differences in pedosedimentary properties and uncertainties over chronological controls. Thus, it seems likely that either the terraces were (re)constructed and utilised over different cultural periods or that there is significant variation in the extent of weathering of material used for reconstruction of the terraces. Unfortunately, it cannot be ascertained from the data available whether the terraces were abandoned for any significant period of time prior to reconstruction and, if so, whether this was a regional phenomenon related to climate, social, or economic changes.

Analysis of EEG signal to detect motor command generation towards stroke rehabilitation

Our aim is to reconstruct the brain-body loop of stroke patients via an EEG-driven robotic system. After the detection of motor command generation, the robotic arm should assist patient���s movement at the correct moment and in a natural way. In this study we performed EEG measurements from healthy subjects performing discrete spontaneous motion. An EEG analysis based on the temporal correlation of the brain activity was employed to determine the onset of single motion motor command generation.

A feasible study of EEG-driven assistive robotic system for stroke rehabilitation

Stroke is a medical emergency and can cause a neurological damage, affecting the motor and sensory systems. Harnessing brain plasticity should make it possible to reconstruct the closed loop between the brain and the body, i.e., association of the generation of the motor command with the somatic sensory feedback might enhance motor recovery. In order to aid reconstruction of this loop with a robotic device it is necessary to assist the paretic side of the body at the right moment to achieve simultaneity between motor command and feedback signal to somatic sensory area in brain. To this end, we propose an integrated EEG-driven assistive robotic system for stroke rehabilitation. Depending on the level of motor recovery, it is important to provide adequate stimulation for upper limb motion. Thus, we propose an assist arm incorporating a Magnetic Levitation Joint that can generate a compliant motion due to its levitation and mechanical redundancy. This paper reports on a feasibility study carried out to verify the validity of the robot sensing and on EEG measurements conducted with healthy volunteers while performing a spontaneous arm flexion/extension movement. A characteristic feature was found in the temporal evolution of EEG signal in the single motion prior to executed motion which can aid in coordinating timing of the robotic arm assistance onset.

The utility of aerial pan-trapping for assessing insect pollinators across vertical strata

Insect pollinators provide a critical ecosystem service by pollinating many wild flowers and crops. It is therefore essential to be able to effectively survey and monitor pollinator communities across a range of habitats, and in particular, sample the often stratified parts of the habitats where insects are found. To date, a wide array of sampling methods have been used to collect insect pollinators, but no single method has been used effectively to sample across habitat types and throughout the spatial structure of habitats. Here we present a method of ���aerial pan-trapping��� that allows insect pollinators to be sampled across the vertical strata from the canopy of forests to agro-ecosystems. We surveyed and compared the species richness and abundance of a wide range of insect pollinators in agricultural, secondary regenerating forest and primary forest habitats in Ghana to evaluate the usefulness of this approach. In addition to confirming the efficacy of the method at heights of up to 30 metres and the effects of trap color on catch, we found greatest insect abundance in agricultural land and higher bee abundance and species richness in undisturbed forest compared to secondary forest.

Extensivity of two-dimensional turbulence

This study is concerned with how the attractor dimension of the two-dimensional Navier���Stokes equations depends on characteristic length scales, including the system integral length scale, the forcing length scale, and the dissipation length scale. Upper bounds on the attractor dimension derived by Constantin, Foias and Temam are analysed. It is shown that the optimal attractor-dimension estimate grows linearly with the domain area (suggestive of extensive chaos), for a sufficiently large domain, if the kinematic viscosity and the amplitude and length scale of the forcing are held fixed. For sufficiently small domain area, a slightly ���super-extensive��� estimate becomes optimal. In the extensive regime, the attractor-dimension estimate is given by the ratio of the domain area to the square of the dissipation length scale defined, on physical grounds, in terms of the average rate of shear. This dissipation length scale (which is not necessarily the scale at which the energy or enstrophy dissipation takes place) can be identified with the dimension correlation length scale, the square of which is interpreted, according to the concept of extensive chaos, as the area of a subsystem with one degree of freedom. Furthermore, these length scales can be identified with a ���minimum length scale��� of the flow, which is rigorously deduced from the concept of determining nodes.

Constraints on the spectral distribution of energy and enstrophy dissipation in forced two-dimensional turbulence

We study two-dimensional (2D) turbulence in a doubly periodic domain driven by a monoscale-like forcing and damped by various dissipation mechanisms of the form ����(�����)��. By ���monoscale-like��� we mean that the forcing is applied over a finite range of wavenumbers kmin���k���kmax, and that the ratio of enstrophy injection �����0 to energy injection �����0 is bounded by kmin2����������kmax2��. Such a forcing is frequently considered in theoretical and numerical studies of 2D turbulence. It is shown that for �����0 the asymptotic behaviour satisfies ���u���12���kmax2���u���2, where ���u���2 and ���u���12 are the energy and enstrophy, respectively. If the condition of monoscale-like forcing holds only in a time-mean sense, then the inequality holds in the time mean. It is also shown that for Navier���Stokes turbulence (��=1), the time-mean enstrophy dissipation rate is bounded from above by 2��1kmax2. These results place strong constraints on the spectral distribution of energy and enstrophy and of their dissipation, and thereby on the existence of energy and enstrophy cascades, in such systems. In particular, the classical dual cascade picture is shown to be invalid for forced 2D Navier���Stokes turbulence (��=1) when it is forced in this manner. Inclusion of Ekman drag (��=0) along with molecular viscosity permits a dual cascade, but is incompatible with the log-modified ���3 power law for the energy spectrum in the enstrophy-cascading inertial range. In order to achieve the latter, it is necessary to invoke an inverse viscosity (��<0). These constraints on permissible power laws apply for any spectrally localized forcing, not just for monoscale-like forcing.

Stability of stationary solutions of the forced Navier-Stokes equations on the two-torus

We study the linear and nonlinear stability of stationary solutions of the forced two-dimensional Navier-Stokes equations on the domain [0,2��]x[0,2��/��], where �� ��(0,1], with doubly periodic boundary conditions. For the linear problem we employ the classical energy{enstrophy argument to derive some fundamental properties of unstable eigenmodes. From this it is shown that forces of pure ��2-modes having wavelengths greater than 2�� do not give rise to linear instability of the corresponding primary stationary solutions. For the nonlinear problem, we prove the equivalence of nonlinear stability with respect to the energy and enstrophy norms. This equivalence is then applied to derive optimal conditions for nonlinear stability, including both the high-and low-Reynolds-number limits.

Habitat manipulation in lowland rice-coconut cropping systems of the Philippines: an effective rodent pest management strategy?

BACKGROUND: Reduction of vegetation height is recommended as a management strategy for controlling rodent pests of rice in South-east Asia, but there are limited field data to assess its effectiveness. The breeding biology of the main pest species of rodent in the Philippines, Rattus tanezumi, suggests that habitat manipulation in irrigated rice���coconut cropping systems may be an effective strategy to limit the quality and availability of their nesting habitat. The authors imposed a replicated manipulation of vegetation cover in adjacent coconut groves during a single rice-cropping season, and added artificial nest sites to facilitate capture and culling of young. RESULTS: Three trapping sessions in four rice fields (two treatments, two controls) adjacent to coconut groves led to the capture of 176 R. tanezumi, 12Rattus exulans and seven Chrotomysmindorensis individuals. There was no significant difference in overall abundance between crop stages or between treatments, and there was no treatment effect on damage to tillers or rice yield. Only two R. tanezumi were caught at the artificial nest sites. CONCLUSION: Habitat manipulation to reduce the quality of R. tanezumi nesting habitat adjacent to rice fields is not effective as a lone rodent management tool in rice���coconut cropping systems.

Standardized evaluation of algorithms for computer-aided diagnosis of dementia based on structural MRI: The CADDementia challenge

Algorithms for computer-aided diagnosis of dementia based on structural MRI have demonstrated high performance in the literature, but are difficult to compare as different data sets and methodology were used for evaluation. In addition, it is unclear how the algorithms would perform on previously unseen data, and thus, how they would perform in clinical practice when there is no real opportunity to adapt the algorithm to the data at hand. To address these comparability, generalizability and clinical applicability issues, we organized a grand challenge that aimed to objectively compare algorithms based on a clinically representative multi-center data set. Using clinical practice as the starting point, the goal was to reproduce the clinical diagnosis. Therefore, we evaluated algorithms for multi-class classification of three diagnostic groups: patients with probable Alzheimer's disease, patients with mild cognitive impairment and healthy controls. The diagnosis based on clinical criteria was used as reference standard, as it was the best available reference despite its known limitations. For evaluation, a previously unseen test set was used consisting of 354 T1-weighted MRI scans with the diagnoses blinded. Fifteen research teams participated with a total of 29 algorithms. The algorithms were trained on a small training set (n = 30) and optionally on data from other sources (e.g., the Alzheimer's Disease Neuroimaging Initiative, the Australian Imaging Biomarkers and Lifestyle flagship study of aging). The best performing algorithm yielded an accuracy of 63.0% and an area under the receiver-operating-characteristic curve (AUC) of 78.8%. In general, the best performances were achieved using feature extraction based on voxel-based morphometry or a combination of features that included volume, cortical thickness, shape and intensity. The challenge is open for new submissions via the web-based framework: http://caddementia.grand-challenge.org.

Population ecology of the Asian house rat (Rattus tanezumi) in complex lowland agroecosystems in the Philippines

Context. Rattus tanezumi (the Asian house rat) is the principal rodent pest of rice and coconut crops in the Philippines. Little is known about the population and breeding ecology of R. tanezumi in complex agroecosystems; thus, current methods of rodent control may be inappropriate or poorly implemented. Aims. To investigate the habitat use, population dynamics and breeding biology of R. tanezumi in complex lowland agroecosystems of the Sierra Madre Biodiversity Corridor, Luzon, and to develop ecologically based rodent management (EBRM) strategies that will target specific habitats at specific times to improve cost-efficiency and minimise non-target risks. Methods. An 18-month trapping study was conducted in rice monoculture, rice adjacent to coconut, coconut groves, coconut-based agroforest and forest habitats. Trapped animals were measured, marked and assessed for breeding condition. Key results. Five species of rodent were captured across all habitats with R. tanezumi the major pest species in both the rice and coconut crops. The stage of the rice crop was a major factor influencing the habitat use and breeding biology of R. tanezumi. In rice fields, R. tanezumi abundance was highest during the tillering to ripening stages of the rice crop and lowest during the seedling stage, whereas in coconut groves abundance was highest from the seedling to tillering stage of nearby rice crops. Peaks in breeding activity occurred from the booting stage of the rice crop until just after harvest, but >10% of females were in breeding condition at each month of the year. Conclusions. In contrast with the practices applied by rice farmers in the study region, the most effective time for lethal management based on the breeding ecology of R. tanezumi is likely to be during the early stages of the rice crop, before the booting stage. Farmers generally apply control actions as individuals. We recommend coordinated community action. Continuous breeding throughout the year may necessitate two community campaigns per rice cropping season. To limit population growth, the most effective time to reduce nesting habitat is from the booting stage until harvest. Implications. By adopting EBRM strategies, we expect a reduction in costs associated with rodent control, as well as improved yield and reduced risk to non-target species.