Non-invasive antidromic neurostimulation:A simple effective method for improving bladder storage

Patients with intractably diminished bladder storage function are encountered frequently by neurourologists, occasionally requiring reconstructive surgery for appropriate resolution. Although sacral neuromodulation is a recognized effective therapeutic modality, present techniques are technically demanding, invasive, and expensive. This study investigated the effect of non-invasive third sacral nerve (S3) stimulation on bladder activity during filling cystometry. One hundred forty-six patients underwent standard urodynamic filling cystometry that was then immediately repeated. Patients in the study group (n = 74) received antidromic transcutaneous sacral neurostimulation during the second fill and the control group (n = 72) underwent a second fill without neurostimulation. A statistically significant increase in bladder storage capacity without a corresponding rise in detrusor pressure was observed in the neurostimulated patients. This improvement in functional capacity is an encouraging finding that further supports the use of this non-invasive treatment modality in clinical practice. Neurourol. Urodynam. 20:73-84. 2001. (C) 2001 Wiley-Liss, Inc.

Susceptibility to Invasive Meningococcal Disease: Polymorphism of Complement System Genes and Neisseria meningitidis Factor H Binding Protein

BACKGROUND: Neisseria meningitidis can cause severe infection in humans. Polymorphism of Complement Factor H (CFH) is associated with altered risk of invasive meningococcal disease (IMD). We aimed to find whether polymorphism of other complement genes altered risk and whether variation of N. meningitidis factor H binding protein (fHBP) affected the risk association.

METHODS: We undertook a case-control study with 309 European cases and 5,200 1958 Birth Cohort and National Blood Service cohort controls. We used additive model logistic regression, accepting P<0.05 as significant after correction for multiple testing. The effects of fHBP subfamily on the age at infection and severity of disease was tested using the independent samples median test and Student's T test. The effect of CFH polymorphism on the N. meningitidis fHBP subfamily was investigated by logistic regression and Chi squared test.

RESULTS: Rs12085435 A in C8B was associated with odds ratio (OR) of IMD (0.35 [95% CI 0.19-0.67]; P = 0.03 after correction). A CFH haplotype tagged by rs3753396 G was associated with IMD (OR 0.56 [95% CI 0.42-0.76], P = 1.6x10-4). There was no bacterial load (CtrA cycle threshold) difference associated with carriage of this haplotype. Host CFH haplotype and meningococcal fHBP subfamily were not associated. Individuals infected with meningococci expressing subfamily A fHBP were younger than those with subfamily B fHBP meningococci (median 1 vs 2 years; P = 0.025).

DISCUSSION: The protective CFH haplotype alters odds of IMD without affecting bacterial load for affected heterozygotes. CFH haplotype did not affect the likelihood of infecting meningococci having either fHBP subfamily. The association between C8B rs12085435 and IMD requires independent replication. The CFH association is of interest because it is independent of known functional polymorphisms in CFH. As fHBP-containing vaccines are now in use, relationships between CFH polymorphism and vaccine effectiveness and side-effects may become important.

The use of water soluble mucoadhesive gels for the intravesical delivery of epirubicin to the bladder for the treatment of non-muscle invasive bladder cancer

Objectives: To develop an epirubicin-loaded, water-soluble mucoadhesive gels that have the correct rheological properties to facilitate their delivery into the bladder via a catheter, while allowing for their spread across the bladder wall with limited expansion of the bladder and increasing the retention of epirubicin in the bladder and flushing with urine.

Methods: Epirubicin-loaded hydroxyl ethyl cellulose (HEC) and hydroxy propyl methyl cellulose (HPMC) gels were manufactured and tested for their rheological properties. Their ability to be pushed through a catheter was also assessed as was their in-vitro drug release, spreading in a bladder and retention of epirubicin after flushing with simulated urine.

Key findings: Epirubicin drug release was viscosity-dependent. The 1 and 1.5% HEC gels and the 1, 1.5 and 2% HPMC gels had the correct viscosity to be administered through a model catheter and spread evenly across the bladder wall under the pressure of the detrusor muscle. The epirubicin-loaded gels had an increased retention time in the bladder when compared with a standard intravesical solution of epirubicin, even after successive flushes with simulated urine.

Conclusion: The increased retention of epirubicin in the bladder by the HEC and HPMC gels warrant further investigation, using an in-vivo model, to assess their potential for use as treatment for non-muscle-invasive bladder cancer.

Ultrasound entropy may be a new non-invasive measure of pre-clinical vascular damage in young hypertensive patients

Background: The identification of pre-clinical microvascular damage in hypertension by non-invasive techniques has proved frustrating for clinicians. This proof of concept study investigated whether entropy, a novel summary measure for characterizing blood velocity waveforms, is altered in participants with hypertension and may therefore be useful in risk stratification.

Methods: Doppler ultrasound waveforms were obtained from the carotid and retrobulbar circulation in 42 participants with uncomplicated grade 1 hypertension (mean systolic/diastolic blood pressure (BP) 142/92 mmHg), and 26 healthy controls (mean systolic/diastolic BP 116/69 mmHg). Mean wavelet entropy was derived from flow-velocity data and compared with traditional haemodynamic measures of microvascular function, namely the resistive and pulsatility indices.

Results: Entropy, was significantly higher in control participants in the central retinal artery (CRA) (differential mean 0.11 (standard error 0.05 cms(-1)), CI 0.009 to 0.219, p 0.017) and ophthalmic artery (0.12 (0.05), CI 0.004 to 0.215, p 0.04). In comparison, the resistive index (0.12 (0.05), CI 0.005 to 0.226, p 0.029) and pulsatility index (0.96 (0.38), CI 0.19 to 1.72, p 0.015) showed significant differences between groups in the CRA alone. Regression analysis indicated that entropy was significantly influenced by age and systolic blood pressure (r values 0.4-0.6). None of the measures were significantly altered in the larger conduit vessel.

Conclusion: This is the first application of entropy to human blood velocity waveform analysis and shows that this new technique has the ability to discriminate health from early hypertensive disease, thereby promoting the early identification of cardiovascular disease in a young hypertensive population.

A spatio-temporal contrast of the predatory impact of an invasive freshwater crustacean

Aim: Impacts of invasive species may vary across invasion gradients, owing to trait-based sorting of individuals through dispersal: those aggregating at invasion fronts may be more aggressive and voracious. We examine, in the field and laboratory, variation in the predatory impacts of an invasive Ponto-Caspian crustacean Hemimysis anomala G.O. Sars, 1907 at two sites along a spatio-temporal gradient of invasion.

Location: Republic of Ireland.

Methods: We used reciprocal transplant field-deployed mesocosms to compare predation rates of invasion front and well-established H. anomala on natural zooplankton assemblages. In the laboratory, we measured the functional response (relationship between predation rate and prey supply) of H. anomala from both sites, for a per capita mechanistic comparison of predation efficiency. We also assessed prey selectivity of H. anomala in the mesocosm experiments to further compare feeding behaviour. Finally, we used a correlative approach to assess the community impact of H. anomala across sites, including a nearby uninvaded site, by comparing zooplankton diversities and densities.

Results: Invasion front H. anomala had higher predation rates than well-established H. anomala at high in situ zooplankton densities. Invasion front H. anomala also had higher functional responses - in particular showing higher 'attack rates' - indicating a heightened ability to locate and capture prey. Prey selectivity was consistent across the spatio-temporal contrast, with positive selection for cladocerans. Zooplankton diversity and density declined with time since H. anomala invasion, both being maximal at the uninvaded site.

Main conclusions: Our study, for the first time, (1) reveals differences in predatory per capita effects and associated behavioural traits between two sites along a spatio-temporal invasion gradient and (2) shows a negative community-level impact of the invasive H. anomala in natural water bodies. Further spatio-temporal comparisons of predatory per capita effects of invaders are needed to assess the generality of these results.

Alien aquatics in Europe: assessing the relative environmental and socio-economic impacts of invasive aquatic macroinvertebrates and other taxa

Invasive alien aquatic species, including marine and freshwater macroinvertebrates, have become increasingly important in terms of both environmental and socio-economic impacts. In order to assess their environmental and economic costs, we applied the Generic Impact Scoring System (GISS) and performed a comparison with other taxa of invaders in Europe. Impacts were scored into six environmental and six socio-economic categories, with each category containing five impact levels. Among 49 aquatic macroinvertebrates, the most impacting species were the Chinese mitten crab, Eriocheir sinensis (Milne-Edwards, 1853) and the zebra mussel, Dreissena polymorpha (Pallas, 1771). The highest impacts found per GISS impact category were, separately; on ecosystems, through predation, as competitors, and on animal production. Eleven species have an impact score > 10 (high impact) and seven reach impact level 5 in at least one impact category (EU blacklist candidates), the maximum score that can be given is 60 impact points. Comparisons were drawn between aquatic macroinvertebrates and vertebrate invaders such as fish, mammals and birds, as well as terrestrial arthropods, revealing invasive freshwater macroinvertebrates to be voracious predators of native prey and damaging to native ecosystems compared with other taxa. GISS can be used to compare these taxa and will aid policy making and targeting of invasive species for management by relevant agencies, or to assist in producing species blacklist candidates.

Aquatic invasive alien species – top issues for their management. Outcomes from the IFI/EIFAAC conference “Freshwater Invasives – Networking for Strategy”

In November 2014, a new EU Regulation to address Invasive Alien Species (IAS) and protect biodiversity was published. This entered into force across the EU in January 2015. The aim of the Regulation is to ‘prevent the introduction of, control or eradicate alien species which threaten ecosystems, habitats or species’. In an effort to provide focus to the Regulation prior to its publishing and to identify the major issues relating to Invasive Alien Species in Europe, the views of invasive species experts from around the world were sought. These were consolidated at an international conference (Freshwater Invasives - Networking for Strategy (FINS)) that was held in Ireland in April 2013. A major outcome from this meeting of experts was the production of the Top 20 IAS issues that relate primarily to freshwater habitats but are also directly relevant to marine and terrestrial ecosystems. This list will support policy makers throughout the EU as preparations are made to implement this important piece of legislation. A further outcome from the conference was the formation of an expert IAS Advisory Group to support EIFAAC in its work on invasive species

Invasive alien species disrupt spatial and temporal ecology and threaten extinction in an insular, small mammal community

The impact of invasive bank vole (Myodes glareolus) and greater white-toothed shrew (Crocidura russula) on indigenous Irish small mammals, varies with season and habitat. We caught bank voles in deciduous woodland, young coniferous plantations and open habitats such as rank grass. The greater white-toothed shrew was absent from deciduous woods and plantations but did use open habitats with low level cover in addition to field margins. Numbers of both invasive species in field margins during summer were higher than in the previous spring. The indigenous wood mouse (Apodemus sylvaticus) and pygmy shrew (Sorex minutus), differed in degrees of negative response to invasive species. Wood mice with bank voles in hedgerows had reduced recruitment and lower peak abundance. This effect was less extreme where both invasive species were present. Wood mice numbers along field margins and open habitats were significantly depressed by the presence of the bank vole with no such effect in deciduous woodland or coniferous plantations. Summer recruitment in pygmy shrews was reduced in hedgerows with bank voles. Where greater white-toothed shrew was present, the pygmy shrew was entirely absent from field margins. Species replacement due to invasive small mammals is occurring in their major habitat i.e. field margins and open habitats where there is good ground cover. Pygmy shrew will probably disappear from these habitats throughout Ireland. Wood mice and possibly pygmy shrew may survive in deciduous woodland and conifer plantations. Mitigation of impacts of invasive species should include expansion of woodland in which native species can survive.

AURKA overexpression accompanies dysregulation of DNA-damage response genes in invasive urothelial cell carcinoma

Invasive urothelial cell carcinoma (UCC) is characterized by increased chromosomal instability and follows an aggressive clinical course in contrast to non-invasive disease. To identify molecular processes that confer and maintain an aggressive malignant phenotype, we used a high-throughput genome-wide approach to interrogate a cohort of high and low clinical risk UCC tumors. Differential expression analyses highlighted cohesive dysregulation of critical genes involved in the G(2)/M checkpoint in aggressive UCC. Hierarchical clustering based on DNA Damage Response (DDR) genes separated tumors according to a pre-defined clinical risk phenotype. Using array-comparative genomic hybridization, we confirmed that the DDR was disrupted in tumors displaying high genomic instability. We identified DNA copy number gains at 20q13.2-q13.3 (AURKA locus) and determined that overexpression of AURKA accompanied dysregulation of DDR genes in high risk tumors. We postulated that DDR-deficient UCC tumors are advantaged by a selective pressure for AURKA associated override of M phase barriers and confirmed this in an independent tissue microarray series. This mechanism that enables cancer cells to maintain an aggressive phenotype forms a rationale for targeting AURKA as a therapeutic strategy in advanced stage UCC.

Impacts of invasive browsers on demographic rates and forest structure in New Zealand

Background/Question/Methods

Assessing the large scale impact of deer populations on forest structure and composition is important because of their increasing abundance in many temperate forests. Deer are invasive animals and sometimes thought to be responsible for immense damage to New Zealand’s forests. We report demographic changes taking place among 40 widespread indigenous tree species over 20 years, following a period of record deer numbers in the 1950s and a period of extensive hunting and depletion of deer populations during the 1960s and 1970s.

Results/Conclusions

Across a network of 578 plots there was an overall 13% reduction in sapling density of our study species with most remaining constant and a few declining dramatically. The effect of suppressed recruitment when deer populations were high was evident in the small tree size class (30 – 80 mm dbh). Stem density decreased by 15% and species with the greatest annual decreases in small tree density were those which have the highest rates of sapling recovery in exclosures indicating that deer were responsible. Densities of large canopy trees have remained relatively stable. There were imbalances between mortality and recruitment rates for 23 of the 40 species, 7 increasing and 16 in decline. These changes were again linked with sapling recovery in exclosures; species which recovered most rapidly following deer exclusion had the greatest net recruitment deficit across the wider landscape, indicating recruitment suppression by deer as opposed to mortality induced by disturbance and other herbivores. Species are not declining uniformly across all populations and no species are in decline across their entire range. Therefore we predict that with continued deer presence some forests will undergo compositional changes but that none of the species tested will become nationally extinct.

Impacts of invasive browsers on demographic rates and forest structure in New Zealand. Available from: http://www.researchgate.net/publication/267285500_Impacts_of_invasive_browsers_on_demographic_rates_and_forest_structure_in_New_Zealand [accessed Oct 9, 2015].

Protocolized versus non-protocolized weaning for reducing the duration of invasive mechanical ventilation in newborn infants: review

Background
Mechanical ventilation is a life-saving intervention for critically ill newborn infants with respiratory failure admitted to a neonatal intensive care unit (NICU). Ventilating newborn infants can be challenging due to small tidal volumes, high breathing frequencies, and the use of uncuffed endotracheal tubes. Mechanical ventilation has several short-term, as well as long-term complications. To prevent complications, weaning from the ventilator is started as soon as possible. Weaning aims to support the transfer from full mechanical ventilation support to spontaneous breathing activity.

Objectives
To assess the efficacy of protocolized versus non-protocolized ventilator weaning for newborn infants in reducing the duration of invasive mechanical ventilation, the duration of weaning, and shortening the NICU and hospital length of stay. To determine efficacy in predefined subgroups including: gestational age and birth weight; type of protocol; and type of protocol delivery. To establish whether protocolized weaning is safe and clinically effective in reducing the duration of mechanical ventilation without increasing the risk of adverse events.

Search methods
We searched the Cochrane Central Register of Controlled trials (CENTRAL; the Cochrane Library; 2015, Issue 7); MEDLINE In-Process and other Non-Indexed Citations and OVID MEDLINE (1950 to 31 July 2015); CINAHL (1982 to 31 July 2015); EMBASE (1988 to 31 July 2015); and Web of Science (1990 to 15 July 2015). We did not restrict language of publication. We contacted authors of studies with a subgroup of newborn infants in their study, and experts in the field regarding this subject. In addition, we searched abstracts from conference proceedings, theses, dissertations, and reference lists of all identified studies for further relevant studies.

Selection criteria
Randomized, quasi-randomized or cluster-randomized controlled trials that compared protocolized with non-protocolized ventilator weaning practices in newborn infants with a gestational age of 24 weeks or more, who were enrolled in the study before the postnatal age of 28 completed days after the expected date of birth.

Data collection and analysis
Four authors, in pairs, independently reviewed titles and abstracts identified by electronic searches. We retrieved full-text versions of potentially relevant studies.

Main results
Our search yielded 1752 records. We removed duplicates (1062) and irrelevant studies (843). We did not find any randomized, quasi-randomized or cluster-randomized controlled trials conducted on weaning from mechanical ventilation in newborn infants. Two randomized controlled trials met the inclusion criteria on type of study and type of intervention, but only included a proportion of newborns. The study authors could not provide data needed for subgroup analysis; we excluded both studies.

Authors' conclusions
Based on the results of this review, there is no evidence to support or refute the superiority or inferiority of weaning by protocol over non-protocol weaning on duration of invasive mechanical ventilation in newborn infants.

An invasive-native mammalian species replacement process captured by camera trap survey random encounter models

Camera traps are used to estimate densities or abundances using capture-recapture and, more recently, random encounter models (REMs). We deploy REMs to describe an invasive-native species replacement process, and to demonstrate their wider application beyond abundance estimation. The Irish hare Lepus timidus hibernicus is a high priority endemic of conservation concern. It is threatened by an expanding population of non-native, European hares L. europaeus, an invasive species of global importance. Camera traps were deployed in thirteen 1 km squares, wherein the ratio of invader to native densities were corroborated by night-driven line transect distance sampling throughout the study area of 1652 km2. Spatial patterns of invasive and native densities between the invader’s core and peripheral ranges, and native allopatry, were comparable between methods. Native densities in the peripheral range were comparable to those in native allopatry using REM, or marginally depressed using Distance Sampling. Numbers of the invader were substantially higher than the native in the core range, irrespective of method, with a 5:1 invader-to-native ratio indicating species replacement. We also describe a post hoc optimization protocol for REM which will inform subsequent (re-)surveys, allowing survey effort (camera hours) to be reduced by up to 57% without compromising the width of confidence intervals associated with density estimates. This approach will form the basis of a more cost-effective means of surveillance and monitoring for both the endemic and invasive species. The European hare undoubtedly represents a significant threat to the endemic Irish hare.