Effectiveness of less than three doses of quadrivalent human papillomavirus vaccine against cervical intraepithelial neoplasia when administered using a standard dose spacing schedule: Observational cohort of young women in Australia

AbstractBackgroundOptimised two-dose human papillomavirus (HPV) vaccine schedules are now endorsed for young adolescents by the World Health Organization. Limited data are available about effectiveness of <3 doses using a standard dose schedule.MethodsDeterministic data linkage was undertaken between the Victorian Cervical Cytology Registry and National HPV Vaccination Program Register to determine quadrivalent HPV vaccination status and incidence of cervical pathology among vaccine eligible women (aged 26 years or younger in 2007) screened in Victoria, Australia between April 2007 and December 2011. Proportional hazards regression was used to estimate hazard ratios (HR) adjusted for age, socioeconomic status and area of residence. Women were stratified into those vaccinated before or after first screen.ResultsAny number of doses (1, 2 or 3) were associated with lower rates of high grade and low grade cytology diagnoses as long as doses were given before screening commencement (one dose HR high grade 0.44 (95% CI 0.32–0.59), one dose low grade 0.48 (95% CI 0.40–0.58); two doses HR high grade 0.63 (95% CI 0.50–0.80), HR low grade 0.52 (95% CI 0.44–0.61); three doses HR high grade 0.53 (95% CI 0.47–0.60), HR low grade 0.73 (95% CI 0.68–0.78)). Three doses of vaccine, but not fewer, were associated with reduced risk of high grade histologically confirmed abnormality in this cohort, regardless of whether vaccination occurred before or after screening (HR before 0.71 (95% CI 0.64–0.80), HR after 0.87 (95% CI 0.82–0.93)). Secondary analyses censoring end points occurring within 1, 6, 12, or 24 months of final vaccine dose suggested an increasing effect of partial vaccination courses over time.ConclusionOur data suggest that less than three doses of quadrivalent HPV vaccine provides some protection against cervical intraepithelial neoplasia, even when measured within 5 years in a population including those who were sexually active at the time of vaccination

Elevation of gangliosides in four brain regions from Parkinson’s disease patients with a GBA mutation

A number of genetic risk factors have been identified over the past decade for Parkinson's Disease (PD), with variants in GBA prominent among them. GBA encodes the lysosomal enzyme that degrades the glycosphingolipid, glucosylceramide (GlcCer), with the activity of this enzyme defective in Gaucher disease. Based on the ill-defined relationship between glycosphingolipid metabolism and PD, we now analyze levels of various lipids by liquid chromatography/electrospray ionization-tandem mass spectrometry in four brain regions from age- and sex-matched patient samples, including idiopathic PD, PD patients with a GBA mutation and compare both to control brains (n = 21 for each group) obtained from individuals who died from a cause unrelated to PD. Of all the glycerolipids, sterols, and (glyco)sphingolipids (251 lipids in total), the only lipid class which showed significant differences were the gangliosides (sialic acid-containing complex glycosphingolipids), which were elevated in 3 of the 4 PD-GBA brain regions. There was no clear correlation between levels of individual gangliosides and the genetic variant in Gaucher disease [9 samples of severe (neuronopathic), 4 samples of mild (non-neuronopathic) GBA variants, and 8 samples with low pathogenicity variants which have a higher risk for development of PD]. Most brain regions, i.e. occipital cortex, cingulate gyrus, and striatum, did not show a statistically significant elevation of GlcCer in PD-GBA. Only one region, the middle temporal gyrus, showed a small, but significant elevation in GlcCer concentration in PD-GBA. We conclude that changes in ganglioside, but not in GlcCer levels, may contribute to the association between PD and GBA mutations

Independent Ion Migration in Suspensions of Strongly Interacting Charged Colloidal Spheres

We report on sytematic measurements of the low frequency conductivity in aequous supensions of highly charged colloidal spheres. System preparation in a closed tubing system results in precisely controlled number densities between 1E16/m3 and 1E19/m^3 (packing fractions between 1E-7 and 1E-2) and electrolyte concentrations between 1E-7 and 1E-3 mol/l. Due to long ranged Coulomb repulsion some of the systems show a pronounced fluid or crystalline order. Under deionized conditions we find s to depend linearily on the packing fraction with no detectable influence of the phase transitions. Further at constant packing fraction s increases sublinearily with increasing number of dissociable surface groups N. As a function of c the conductivity shows pronounced differences depending on the kind of electrolyte used. We propose a simple yet powerful model based on independent migration of all species present and additivity of the respective conductivity contributions. It takes account of small ion macro-ion interactions in terms of an effectivly transported charge. The model successfully describes our qualitatively complex experimental observations. It further facilitates quantitative estimates of conductivity over a wide range of particle and experimental parameters.Comment: 32 pages, 17 figures, 2 tables, Accepted by Physical Review

[Accepted Manuscript] Smartphone tool to collect repeated 24 h dietary recall data in Nepal.

To outline the development of a smartphone-based tool to collect thrice-repeated 24 h dietary recall data in rural Nepal, and to describe energy intakes, common errors and researchers' experiences using the tool. We designed a novel tool to collect multi-pass 24 h dietary recalls in rural Nepal by combining the use of a CommCare questionnaire on smartphones, a paper form, a QR (quick response)-coded list of foods and a photographic atlas of portion sizes. Twenty interviewers collected dietary data on three non-consecutive days per respondent, with three respondents per household. Intakes were converted into nutrients using databases on nutritional composition of foods, recipes and portion sizes. Dhanusha and Mahottari districts, Nepal. Pregnant women, their mothers-in-law and male household heads. Energy intakes assessed in 150 households; data corrections and our experiences reported from 805 households and 6765 individual recalls. Dietary intake estimates gave plausible values, with male household heads appearing to have higher energy intakes (median (25th-75th centile): 12 079 (9293-14 108) kJ/d) than female members (8979 (7234-11 042) kJ/d for pregnant women). Manual editing of data was required when interviewers mistook portions for food codes and for coding items not on the food list. Smartphones enabled quick monitoring of data and interviewer performance, but we initially faced technical challenges with CommCare forms crashing. With sufficient time dedicated to development and pre-testing, this novel smartphone-based tool provides a useful method to collect data. Future work is needed to further validate this tool and adapt it for other contexts

Beyond ratios - flexible and resilient nurse staffing options to deliver cost-effective hospital care and address staff shortages: a simulation and economic modelling study

This is the final version. Available on open access from Elsevier via the DOI in this recordData availability statement: This paper draws on research and data reported in more detail in the NIHR Journals Library Health Services and Delivery Research. The data for this paper consist of anonymous ward and hospital parameters and simulation results. All data requests should be submitted to the corresponding author for consideration. Access to available anonymised data may be granted following review. The simulation model and accompanying documentation are available from the author on reasonable request.Background In the face of pressure to contain costs and make best use of scarce nurses, flexible staff deployment (floating staff between units and temporary hires) guided by a patient classification system may appear an efficient approach to meeting variable demand for care in hospitals. Objectives We modelled the cost-effectiveness of different approaches to planning baseline numbers of nurses to roster on general medical/surgical units while using flexible staff to respond to fluctuating demand. Design and setting We developed an agent-based simulation, where hospital inpatient units move between being understaffed, adequately staffed or overstaffed as staff supply and demand (as measured by the Safer Nursing Care Tool patient classification system) varies. Staffing shortfalls are addressed by floating staff from overstaffed units or hiring temporary staff. We compared a standard staffing plan (baseline rosters set to match average demand) with a higher baseline ‘resilient’ plan set to match higher than average demand, and a low baseline ‘flexible’ plan. We varied assumptions about temporary staff availability and estimated the effect of unresolved low staffing on length of stay and death, calculating cost per life saved. Results Staffing plans with higher baseline rosters led to higher costs but improved outcomes. Cost savings from lower baseline staff mainly arose because shifts were left understaffed and much of the staff cost saving was offset by costs from longer patient stays. With limited temporary staff available, changing from low baseline flexible plan to the standard plan cost £13,117 per life saved and changing from the standard plan to the higher baseline ‘resilient’ plan cost £8,653 per life saved. Although adverse outcomes from low baseline staffing reduced when more temporary staff were available, higher baselines were even more cost-effective because the saving on staff costs also reduced. With unlimited temporary staff, changing from low baseline plan to the standard cost £4,520 per life saved and changing from the standard plan to the higher baseline cost £3,693 per life saved. Conclusion Shift-by-shift measurement of patient demand can guide flexible staff deployment, but the baseline number of staff rostered must be sufficient. Higher baseline rosters are more resilient in the face of variation and appear cost-effective. Staffing plans that minimise the number of nurses rostered in advance are likely to harm patients because temporary staff may not be available at short notice. Such plans, which rely heavily on flexible deployments, do not represent an efficient or effective use of nurses.National Institute for Health Research (NIHR

Enhancement of tunneling from a correlated 2D electron system by a many-electron Mossbauer-type recoil in a magnetic field

We consider the effect of electron correlations on tunneling from a 2D electron layer in a magnetic field parallel to the layer. A tunneling electron can exchange its momentum with other electrons, which leads to an exponential increase of the tunneling rate compared to the single-electron approximation. Explicit results are obtained for a Wigner crystal. They provide a qualitative and quantitative explanation of the data on electrons on helium. We also discuss tunneling in semiconductor heterostructures.Comment: published version, 4 pages, 2 figures, RevTeX 3.

Xenon improves long-term cognitive function, reduces neuronal loss and chronic neuroinflammation, and improves survival after traumatic brain injury in mice

Background.Xenon is a noble gas with neuroprotective properties. We previously showed that xenon improves short and long-term outcomes in young adult mice after controlled cortical impact (CCI). This is a follow-up study investigating xenon’s effect on very long-term outcome and survival. Methods.C57BL/6N (n=72) young adult male mice received single CCI or sham surgery and were treated with either xenon (75%Xe:25%O2) or control gas (75% N2:25%O2). The outcomes used were: 1) 24-hour lesion volume and neurological outcome score; 2)contextual fear-conditioning at 2 weeks and 20 months; 3) corpus callosum white matter quantification; 4) immunohistological assessment of neuroinflammation and neuronal loss; 5) long-term survival. Results.Xenon treatment significantly reduced secondary injury development (p<0.05), improved short-term vestibulomotor function (p<0.01),and prevented development of very late-onset traumatic brain injury (TBI)-related memory deficits. Xenon treatment reducedwhite matter loss in the contralateral corpus callosum and neuronal loss in the contralateral hippocampal CA1 andDG areas at 20 months. Xenon’s long-term neuroprotective effects were associated with a significant (p<0.05) reduction in neuroinflammation in multiple brain areas involved in associative memory, including reduction in reactive astrogliosis and microglial cell proliferation. Survival was improved significantly (p<0.05) in xenon-treated animals, compared to untreated animals up to 12 months after injury.Conclusions.These results show that xenon treatment after TBI results in very long-term improvements in clinically relevant outcomes and survival. Our findings support the idea that xenon treatment shortly after TBI may have long-term benefits in the treatment of brain trauma patients

Tunneling from a correlated 2D electron system transverse to a magnetic field

We show that, in a magnetic field parallel to the 2D electron layer, strong electron correlations change the rate of tunneling from the layer exponentially. It results in a specific density dependence of the escape rate. The mechanism is a dynamical Mossbauer-type recoil, in which the Hall momentum of the tunneling electron is partly transferred to the whole electron system, depending on the interrelation between the rate of interelectron momentum exchange and the tunneling duration. We also show that, in a certain temperature range, magnetic field can enhance rather than suppress the tunneling rate. The effect is due to the magnetic field induced energy exchange between the in-plane and out-of-plane motion. Magnetic field can also induce switching between intra-well states from which the system tunnels, and a transition from tunneling to thermal activation. Explicit results are obtained for a Wigner crystal. They are in qualitative and quantitative agreement with the relevant experimental data, with no adjustable parameters.Comment: 16 pages, 9 figure

Reduced cerebral vascularization in experimental neuronopathic Gaucher disease.

The glycosphingolipidosis, Gaucher disease, in which a range of neurological manifestations occur, results from a deficiency of acid β-glucocerebrosidase, with subsequent accumulation of β-glucocerebroside, its upstream substrates, and the non-acylated congener β-glucosylsphingosine. However, the mechanisms by which end-organ dysfunction arise are poorly understood. Here, we report strikingly diminished cerebral microvascular density in a murine model of disease, and provide a detailed analysis of the accompanying cerebral glycosphingolipidome in these animals, with marked elevations of β-glucosylsphingosine. Further in vitro studies confirmed a concentration-dependent impairment of endothelial cytokinesis upon exposure to quasi-pathological concentrations of β-glucosylsphingosine. These findings support a premise for pathogenic disruption of cerebral angiogenesis as an end-organ effect, with potential for therapeutic modulation in neuronopathic Gaucher disease. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd

A network approach for managing ecosystem services and improving food and nutrition security on smallholder farms

Smallholder farmers are some of the poorest and most food insecure people on Earth. Their high nutritional and economic reliance on home-grown produce makes them particularly vulnerable to environmental stressors such as pollinator loss or climate change which threaten agricultural productivity. Improving smallholder agriculture in a way that is environmentally sustainable and resilient to climate change is a key challenge of the 21st century. Ecological intensification, whereby ecosystem services are managed to increase agricultural productivity, is a promising solution for smallholders. However, smallholder farms are complex socio-ecological systems with a range of social, ecological and environmental factors interacting to influence ecosystem service provisioning. To truly understand the functioning of a smallholder farm and identify the most effective management options to support household food and nutrition security, a holistic, systems-based understanding is required. In this paper, we propose a network approach to understand, visualise and model the complex interactions occurring among wild species, crops and people on smallholder farms. Specifically, we demonstrate how networks may be used to (a) identify wild species with a key role in supporting, delivering or increasing the resilience of an ecosystem service; (b) quantify the value of an ecosystem service in a way that is relevant to the food and nutrition security of smallholders; and (c) understand the social interactions that influence the management of shared ecosystem services. Using a case study based on data from rural Nepal, we demonstrate how this framework can be used to connect wild plants, pollinators and crops to key nutrients consumed by humans. This allows us to quantify the nutritional value of an ecosystem service and identify the wild plants and pollinators involved in its provision, as well as providing a framework to predict the effects of environmental change on human nutrition. Our framework identifies mechanistic links between ecosystem services and the nutrients consumed by smallholder farmers and highlights social factors that may influence the management of these services. Applying this framework to smallholder farms in a range of socio-ecological contexts may provide new, sustainable and equitable solutions to smallholder food and nutrition security. A free Plain Language Summary can be found within the Supporting Information of this article