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Measles is a target for elimination in all six WHO regions by 2020, and over the last decade, there has been considerable progress towards this goal. Surveillance is recognised as a cornerstone of elimination programmes, allowing early identification of outbreaks, thus enabling control and preventing re-emergence. Fever–rash surveillance is increasingly available across WHO regions, and this symptom-based reporting is broadly used for measles surveillance. However, as measles control increases, symptom-based cases are increasingly likely to reflect infection with other diseases with similar symptoms such as rubella, which affects the same populations, and can have a similar seasonality. The WHO recommends that cases from suspected measles outbreaks be laboratory-confirmed, to identify ‘true’ cases, corresponding to measles IgM titres exceeding a threshold indicative of infection. Although serological testing for IgM has been integrated into the fever–rash surveillance systems in many countries, the logistics of sending in every suspected case are often beyond the health system's capacity. We show how age data from serologically confirmed cases can be leveraged to infer the status of non-tested samples, thus strengthening the information we can extract from symptom-based surveillance. Applying an age-specific confirmation model to data from three countries with divergent epidemiology across Africa, we identify the proportion of cases that need to be serologically tested to achieve target levels of accuracy in estimated infected numbers and discuss how this varies depending on the epidemiological context. Our analysis provides an approach to refining estimates of incidence leveraging all available data, which has the potential to improve allocation of resources, and thus contribute to rapid and efficient control of outbreaks.
Background: Continuous video-EEG (cvEEG) monitoring is the standard of care for diagnosis and management of neonatal seizures. However, it is labour-intensive. We aimed to establish consistency in monitoring of newborns utilising NICU nurses. Methods: Neonatal nurses were trained to apply scalp electrodes, troubleshoot technical issues. Guidelines, checklists and visual training modules were developed. A central network system allowed remote access to the cvEEGs by the epileptologist for timely interpretation and feedback. We compared 100 infants with moderate to severe HIE before and after the training program. Results: 192 cvEEGs were performed. Of the 100 infants compared; time to initiate brain monitoring decreased by average of 31.5 hours, in electrographic seizure detection increased(20% compared to 34% a), seizure clinical misdiagnosis decreased (65% compared to 36% ), and Anti-Seizure burden decreased. Conclusions: Training experienced NICU nurses to set-up, start and monitor cvEEG can decrease the time to initiate cvEEG which may lead to better seizure diagnosis and management.
Background: Despite advances in neonatal care, neonates with moderate to severe HIE are at high risk of mortality and morbidity. we report the impact of a dedicated NNCC team on short term mortality and morbidities. Methods: A retrospective cohort study on neonates with moderate to serve HIE between July 1st 2008 and December 31st 2017. primary outcome : a composite of death and/or brain injury on MRI. Secondary outcomes: rate of cooling, length of hospital stay, anti-seizure medication burden, and use of inotropes. A regression analysis was done adjusting for gestational age, birth weight, gender, out-born status, Apgar score at 10 minutes, cord blood pH, and HIE clinical staging Results: 216 neonates were included, 109 before NNCC implementation, and 107 thereafter. NNCC program resulted in reduction in the primary outcome (AOR: 0.28, CI: 0.14-0.54, p<0.001) and brain injury (AOR: 0.28, CI: 0.14-0.55, p<0.001). It decreased average length of stay/infants by 5 days (p=0.03), improved cooling rate (73% compared to 93% , p <0.001), reduced: seizure misdiagnosis (71% compared to 23%, P <0.001), anti-seizure medication burden (P = 0.001), and inotrope use (34% compared to 53%, p=0.004) Conclusions: NNCC program decreased mortality and brain injury , shortened the length of hospital stay and improved care of neonates with significant HIE.
Rubella virus infection typically presents as a mild illness in children; however, infection during pregnancy may cause the birth of an infant with congenital rubella syndrome (CRS). As of February 2017, India began introducing rubella-containing vaccine (RCV) into the public-sector childhood vaccination programme. Low-level RCV coverage among children over several years can result in an increase in CRS incidence by increasing the average age of infection without sufficiently reducing rubella incidence. We evaluated the impact of RCV introduction on CRS incidence across India's heterogeneous demographic and epidemiological contexts. We used a deterministic age-structured model that reflects Indian states’ rural and urban area-specific demography and vaccination coverage levels to simulate rubella dynamics and estimate CRS incidence with and without RCV introduction to the public sector. Our analysis suggests that current low-level private-sector vaccination has already slightly increased the burden of CRS in India. We additionally found that the effect of public-sector RCV introduction depends on the basic reproductive number, R0, of rubella. If R0 is five, a value empirically estimated from an array of settings, CRS incidence post-RCV introduction will likely decrease. However, if R0 is seven or nine, some states may experience short-term or annual increases in CRS, even if a long-term total reduction in cases (30 years) is expected. Investment in population-based serological surveys and India's fever/rash surveillance system will be key to monitoring the success of the vaccination programme.
Horn growth rate does not appear to be related to the amino acid profile of the major protein source for dairy cattle (Offer, Logue & Roberts, 1997), but it is possible that sulphur amino acids are limiting in early lactation, when the homeorhetic drive to milk production is most extreme. Supplementation of a high production ration for dairy cows with protected methionine should increase milk production, and allow any sulphur amino acid limitation on horn growth to be alleviated (Mengal, Galbraith, Souri & Scaife, 1997).
A total of 60 in-calf Holstein heifers were divided into two groups in a randomised block design. The study commenced approximately three weeks pre-calving until 26 weeks post calving, and animals were housed in one of three systems for the duration. Two diets were formulated based on a grass silage:maize silage mixture (50:50 DM basis), with rolled wheat, soya bean meal, sugar beet feed and rapeseed meal and were offered from approximately five days post calving for the remainder of the 26 week period.
To determine the patterns and predictors of treatment response trajectories for veterans with post-traumatic stress disorder (PTSD).
Conditional latent growth mixture modelling was used to identify classes and predictors of class membership. In total, 2686 veterans treated for PTSD between 2002 and 2015 across 14 hospitals in Australia completed the PTSD Checklist at intake, discharge, and 3 and 9 months follow-up. Predictor variables included co-morbid mental health problems, relationship functioning, employment and compensation status.
Five distinct classes were found: those with the most severe PTSD at intake separated into a relatively large class (32.5%) with small change, and a small class (3%) with a large change. Those with slightly less severe PTSD separated into one class comprising 49.9% of the total sample with large change effects, and a second class comprising 7.9% with extremely large treatment effects. The final class (6.7%) with least severe PTSD at intake also showed a large treatment effect. Of the multiple predictor variables, depression and guilt were the only two found to predict differences in response trajectories.
These findings highlight the importance of assessing guilt and depression prior to treatment for PTSD, and for severe cases with co-morbid guilt and depression, considering an approach to trauma-focused therapy that specifically targets guilt and depression-related cognitions.
A randomised controlled trial (RCT) of high-dose v. low-dose fish oil in recent-onset rheumatoid arthritis (RA) demonstrated that the group allocated to high-dose fish oil had increased remission and decreased failure of disease-modifying anti-rheumatic drug (DMARD) therapy. This study examines the relationships between plasma phospholipid levels of the n-3 fatty acids in fish oil, EPA and DHA, and remission and DMARD use in recent-onset RA. EPA and DHA were measured in blood samples from both groups of the RCT. The data were analysed as a single cohort, and Cox proportional hazards models were used to examine relationships between plasma phospholipid (PL) EPA and DHA and various outcome measures. When analysed as a single cohort, plasma PL EPA was related to time to remission, with a one unit increase in EPA (1 % total fatty acids) associated with a 12 % increase in the probability of remission at any time during the study period (hazard ratio (HR)=1·12; 95 % CI 1·02, 1·23; P=0·02). Adjustment for smoking, anti-cyclic citrullinated peptide antibodies and ‘shared epitope’ HLA-DR allele status did not change the HR. Plasma PL EPA, adjusted for the same variables, was negatively related to time to DMARD failure (HR=0·85; 95 % CI 0·72, 0·99; P=0·047). The HR for DHA and time to remission or DMARD failure were similar in magnitude to those for EPA, but not statistically significant. Biomarkers of n-3 status, such as plasma PL EPA, have the potential to predict clinical outcomes relevant to standard drug treatment of RA patients.
Methylation of the fragile X mental retardation 1 (FMR1) exon 1/intron 1 boundary positioned fragile X related epigenetic element 2 (FREE2), reveals skewed X-chromosome inactivation (XCI) in fragile X syndrome full mutation (FM: CGG > 200) females. XCI skewing has been also linked to abnormal X-linked gene expression with the broader clinical impact for sex chromosome aneuploidies (SCAs). In this study, 10 FREE2 CpG sites were targeted using methylation specific quantitative melt analysis (MS-QMA), including 3 sites that could not be analysed with previously used EpiTYPER system. The method was applied for detection of skewed XCI in FM females and in different types of SCA. We tested venous blood and saliva DNA collected from 107 controls (CGG < 40), and 148 FM and 90 SCA individuals. MS-QMA identified: (i) most SCAs if combined with a Y chromosome test; (ii) locus-specific XCI skewing towards the hypomethylated state in FM females; and (iii) skewed XCI towards the hypermethylated state in SCA with 3 or more X chromosomes, and in 5% of the 47,XXY individuals. MS-QMA output also showed significant correlation with the EpiTYPER reference method in FM males and females (P < 0.0001) and SCAs (P < 0.05). In conclusion, we demonstrate use of MS-QMA to quantify skewed XCI in two applications with diagnostic utility.
Solar irradiance and precipitation are the most likely drivers of the seasonal variation of net primary productivity (NPP) in tropical forests. Since their roles remain poorly understood, we use litter traps, dendrometer bands and census data collected from one hectare permanent plots to quantify the seasonality of above-ground NPP components and weather parameters in 13 sites distributed along a 2800-m altitudinal gradient ranging from lowland Amazonia to the high Andes. We combine canopy leaf area index and litterfall data to describe the seasonality of canopy production. We hypothesize that solar irradiance is the primary driver of canopy phenology in wetter sites, whereas precipitation drives phenology in drier systems. The seasonal rhythm of canopy NPP components is in synchrony with solar irradiance at all altitudes. Leaf litterfall peaks in the late dry season, both in lowland (averaging 0.54 ± 0.08 Mg C ha y−1, n = 5) and montane forests (averaging 0.29 ± 0.04 Mg C ha y−1, n = 8). Peaks in above-ground coarse woody NPP appears to be triggered by the onset of rainfall in seasonal lowland rain forests (averaging 0.26 ± 0.04 Mg C ha y−1, n = 5, in November), but not in montane cloud forests.
Surface diffusion has been studied in the Ag/Ge (111) and Cs/Si (100) systems using UHV-SEM based techniques, biassed secondary electron imaging (b-SEI), Micro-AES and RHEED. Ag and Cs were deposited through a mask of holes held close to the substrate at room temperature, and annealed at higher temperatures Ta. Under certain conditions, the Ag and Cs patches split into two distinct regions with different sub-Monolayer (ML) coverages θ, observable using b-SEI; the sensitivity for Cs/Si (100) is below 0.5% ML. These patch widths were measured as f(ø,Ta,t), and effective diffusion coefficients extracted. Both systems were modelled using coupled diffusion equations, involving adatoms in two different surface phases. Comparison with experiment yields activation energies for adsorption (Ea) and diffusion (Ed).
We have measured the internal friction (Q-1) of amorphous silicon nitride (a-Si3Nx) films prepared by a variety of methods, including low-pressure chemical-vapor deposition (LPCVD), plasma-enhanced chemical-vapor deposition (PECVD), and hot-wire chemical-vapor deposition (HWCVD) from 0.5 K to room temperature. The measurements are made by depositing the films onto extremely high-Q silicon double paddle oscillator substrates with a resonant frequency of ~5500 Hz. We find the elastic properties of these a-Si3N4 films resemble those of amorphous silicon (a-Si), demonstrating considerable variation, depending on the film growth methods and post deposition annealing. The internal friction for most of the films shows a broad temperature-independent plateau below 30 K, characteristic of amorphous solids. The values of Q-1, however, vary from film to film in this plateau region by more than one order of magnitude. This is typical for tetrehedrally bonded amorphous thin films, like a-Si, a-Ge, and a-C. The PECVD films have the highest Q-1 just like an ordinary amorphous solid, while LPCVD films have an internal friction more than one order of magnitude lower. All the films show a reduction of Q-1 after annealing at 800°C, even for the LPCVD films which were prepared at 850°C. This can be viewed as a reduction of structural disorder.
The factors underlying the temporal dynamics of rubella outside of Europe and North America are not well known. Here we used 20 years of incidence reports from Mexico to identify variation in seasonal forcing and magnitude of transmission across the country and to explore determinants of inter-annual variability in epidemic magnitude in rubella. We found considerable regional variation in both magnitude of transmission and amplitude of seasonal variation in transmission. Several lines of evidence pointed to stochastic dynamics as an important driver of multi-annual cycles. Since average age of infection increased with the relative importance of stochastic dynamics, this conclusion has implications for the burden of congenital rubella syndrome. We discuss factors underlying regional variation, and implications of the importance of stochasticity for vaccination implementation.
Measles vaccine efficacy is higher at 12 months than 9 months because of maternal immunity, but delaying vaccination exposes the children most vulnerable to measles mortality to infection. We explored how this trade-off changes as a function of regionally varying epidemiological drivers, e.g. demography, transmission seasonality, and vaccination coverage. High birth rates and low coverage both favour early vaccination, and initiating vaccination at 9–11 months, then switching to 12–14 months can reduce case numbers. Overall however, increasing the age-window of vaccination decreases case numbers relative to vaccinating within a narrow age-window (e.g. 9–11 months). The width of the age-window that minimizes mortality varies as a function of birth rate, vaccination coverage and patterns of access to care. Our results suggest that locally age-targeted strategies, at both national and sub-national scales, tuned to local variation in birth rate, seasonality, and access to care may substantially decrease case numbers and fatalities for routine vaccination.
Integrins are transmembrane proteins that facilitate the interaction of cells with the extracellular environment. They have also been implicated in cancer progression. The effects of nutrients thought to be involved in the prevention of prostate cancer on integrin expression have not been determined. Prostate cancer cell lines representing a range of malignancy from normal (RWPE-1) to highly invasive phenotypes (22Rv1 < LNCaP < PC-3) were cultured with or without lycopene (10 nm), vitamin E (5 μm) or fish oil (100 μm) for 48 h. Growth and integrin (α2β1, αvβ3 and αvβ5) expression were assessed using Trypan Blue exclusion and monoclonal antibodies combined with flow cytometry. Vitamin E enhanced (P < 0·001) whereas fish oil reduced the growth of all the cell lines tested (P < 0·001). Lycopene had no effect on growth. All the malignant cell lines exhibited lower expression of α2β1 with the addition of lycopene to culture media. Supplemental fish oil reduced α2β1 in most invasive cell lines (LNCaP and PC-3). Each nutrient at physiological levels reduced integrins αvβ3 and αvβ5 in most invasive cell lines (PC-3). The results suggest that integrins may represent an additional target of bioactive nutrients and that the effects of nutrients may be dependent on the type of cell line used.
A proposed Yield Reserve Program designed to compensate farmers for any reduced yields resulting from nitrogen (N) application rates reduced to below recommended rates is evaluated. Assuming that farmers currently follow Extension recommendations for applying N, Yield Reserve Program participation reduces expected net revenue by $10 to $13/ha. The Yield Reserve Program reduces expected net revenue by $17 to $20/ha for farmers who apply N to maximize expected net revenue. Farmers' costs of participation increase with lower probabilities of inadequate rainfall and higher corn prices and decline with higher N prices. The Yield Reserve Program can significantly reduce N applications to cropland, which may reduce N content of surface waters, but the costs to taxpayers and farmers will depend on how the program is implemented.