To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
A physical oceanographic, geophysical and marine geological survey of Edward VIII Gulf, Kemp Coast, collected data from conductivity–temperature–depth casts, multi-beam bathymetric swath mapping and 3.5 kHz sub-bottom surveying. Modified circumpolar deep water (mCDW) is observed in Edward VIII Gulf, as well as notable bathymetric features including mega-scale glacial lineations and a 1750 m-deep trough. Sedimentological, geochemical, rock-magnetic and micropalaeontological analysis of two kasten cores document regional palaeoclimate and palaeo-oceanographic conditions over the past 8000 years, with a warm period occurring from c. 8 to 4 ka and a shift to cooler conditions beginning at c. 4 ka and persisting until at least 0.9 ka. Sediment packages > 40 m thick within deep troughs in Edward VIII Gulf present potential targets for higher-resolution Holocene and deglacial climate studies. Despite the presence of mCDW on the shelf, inland bed topography consisting of highland terrain suggests the likelihood of relative stability of this sector of the East Antarctic Ice Sheet.
Globally, marine turtles are considered threatened throughout their range, and therefore conservation practitioners are increasingly investing resources in marine protected areas to protect key life history stages and critical habitats, including foraging grounds, nesting beaches and inter-nesting areas. Empirical data on the distribution of these habitats and/or the spatial ecology and behaviour of individuals of many marine turtle populations are often lacking, undermining conservation efforts, particularly along the Atlantic coast of Africa. Here we contribute to the knowledge base in this region by describing patterns of habitat use for nine green turtles Chelonia mydas tagged with satellite platform transmitter terminals at a foraging ground in Loango Bay, Republic of the Congo, one of only a few documented mainland foraging grounds for marine turtles in Central Africa. Analyses of these data revealed that core areas of habitat use and occupancy for a wide range of size/age classes were restricted to shallow waters adjacent to Pointe Indienne in Loango Bay, with most individuals showing periods of high fidelity to this area. These data are timely given the Congolese government recently announced its intention to create a marine conservation zone to protect marine turtles in Loango Bay. Despite the small sample size of this study, these data exemplify the need for comprehensive strategies that span national jurisdictions, as we provide the first documented evidence of linkages between green turtle foraging sites in Central Africa (Loango Bay, Republic of the Congo) and Southern Africa (Mussulo Bay, Angola).
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.
Although measles incidence has reached historic lows in many parts of the world, the disease still causes substantial morbidity globally. Even where control programs have succeeded in driving measles locally extinct, unless vaccination coverage is maintained at extremely high levels, susceptible numbers may increase sufficiently to spark large outbreaks. Human mobility will drive potentially infectious contacts and interact with the landscape of susceptibility to determine the pattern of measles outbreaks. These interactions have proved difficult to characterise empirically. We explore the degree to which new sources of data combined with existing public health data can be used to evaluate the landscape of immunity and the role of spatial movement for measles introductions by retrospectively evaluating our ability to predict measles outbreaks in vaccinated populations. Using inferred spatial patterns of accumulation of susceptible individuals and travel data, we predicted the timing of epidemics in each district of Pakistan during a large measles outbreak in 2012–2013 with over 30 000 reported cases. We combined these data with mobility data extracted from over 40 million mobile phone subscribers during the same time frame in the country to quantify the role of connectivity in the spread of measles. We investigate how different approaches could contribute to targeting vaccination efforts to reach districts before outbreaks started. While some prediction was possible, accuracy was low and we discuss key uncertainties linked to existing data streams that impede such inference and detail what data might be necessary to robustly infer timing of epidemics.
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.
After decades of effort, the solar magnetic cycle is exceptionally well characterized, but it remains poorly understood. Pioneering work at the Mount Wilson Observatory demonstrated that other Sun-like stars also show regular activity cycles, and identified two distinct relationships between the rotation rate and the length of the cycle. The solar cycle appears to be an outlier, falling between the two stellar relationships, potentially threatening the very foundation of the solar-stellar connection. Recent discoveries emerging from NASA’s Kepler space telescope have started to shed light on this perplexing result, suggesting that the Sun’s rotation rate and magnetic field are currently in a transitional phase that occurs in all middle-aged stars. We have recently identified the manifestation of this magnetic transition in the best available data on stellar cycles. These observations suggest that the solar cycle is currently growing longer on stellar evolutionary timescales, and that the global dynamo may shut down entirely sometime in the next 0.8-2.4 Gyr. Future tests of this hypothesis will come from ground-based activity monitoring of Kepler targets that span the magnetic transition, and from asteroseismology with the TESS mission to determine precise masses and ages for bright stars with known cycles.
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.
Measles is a major cause of childhood morbidity and mortality in many parts of the world. Estimates of the case-fatality rate (CFR) of measles have varied widely from place to place, as well as in the same location over time. Amongst populations that have experienced famine or armed conflict, measles CFR can be especially high, although past work has mostly focused on refugee populations. Here, we estimate measles CFR between 1970 and 1991 in a rural region of Bangladesh, which experienced civil war and famine in the 1970s. We use historical measles mortality data and a mechanistic model of measles transmission to estimate the CFR of measles. We first demonstrate the ability of this model to recover the CFR in the absence of incidence data, using simulated mortality data. Our method produces CFR estimates that correspond closely to independent estimates from surveillance data and we can capture both the magnitude and the change in CFR suggested by these previous estimates. We use this method to quantify the sharp increase in CFR that resulted in a large number of deaths during a measles outbreak in the region in 1976. Most of the children who died during this outbreak were born during a famine in 1974, or in the 2 years preceding the famine. Our results suggest that the period of turmoil during and after the 1971 war and the sustained effects of the famine, is likely to have contributed to the high fatality burden of the 1976 measles outbreak in Matlab.
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.
The seasonality and periodicity of infections, and the mechanisms underlying observed dynamics, can have implications for control efforts. This is particularly true for acute childhood infections. Among these, the dynamics of measles is the best understood and has been extensively studied, most notably in the UK prior to the start of vaccination. Less is known about the dynamics of other childhood diseases, particularly outside Europe and the United States. In this paper, we leverage a unique dataset to examine the epidemiology of six childhood infections – measles, mumps, rubella, varicella, scarlet fever and pertussis – across 32 states in Mexico from 1985 to 2007. This dataset provides us with a spatio-temporal probe into the dynamics of six common childhood infections, and allows us to compare them in the same setting over the same time period. We examine three key epidemiological characteristics of these infections – the age profile of infections, spatio-temporal dynamics, and seasonality in transmission – and compare them with predictions from existing theory and past findings. Our analysis reveals interesting epidemiological differences between the six pathogens, and variations across space. We find signatures of term-time forcing (reduced transmission during the summer) for measles, mumps, rubella, varicella, and scarlet fever; for pertussis, a lack of term-time forcing could not be rejected.
As the central component of heightened vascularization in glioblastoma (GBM), endothelial cells (EC) are arguably the most responsive stromal cells in the tumour microenvironment during conventional treatment using ionizing radiation (IR). Although the inherent tumor tropism and angiogenic property of mesenchymal stem cells (MSC) has been documented in many cancer types including GBM, little is known about the function of MSC that are recruited to the GBM tumor microenvironment. The purpose of this study was to elucidate the effect of MSC on irradiated EC. Here we studied the influence of IR, MSC or MSC condition media (CM) on human umbilical vein endothelial cells (HUVECs). IR was found to up-regulate mRNA levels of CXCL5, CXCL10, ICAM1, VCAM1, VEGF-c and tissue factor (TF) in a dose-dependent manner whereas MSC co-culture boosted the expression of ICAM1, VCAM1, VEGF-c, TF, and MCP3. An additive effect of IR and MSC-culture was most detected with respect to ICAM1, TF and CXCL5 under 2Gy. MSC co-culture decreased IR-induced phospho-p53 in HUVECs at 15Gy. In addition, IR decreased the level of phospho-Akt in HUVECs as well as cell proliferation. Notably, both effects were countered by MSC CM. Interestingly, up-regulation of the same set of IR-driven genes in GBM was positively correlated with poor survival in the TCGA GBM database, a correlation that was lost if using gene list that was obtained from IR and MSC combine. These findings suggest that MSC promotes angiogenesis in GBM by overturning the IR-induced active state of endothelial cells and rendering them radio-resistant.
Most plates taken with the UK Schmidt Telescope are hypersensitized before use. The technique for the hyper-sensitization of IIIa-type emulsions has been described by Sim et al. (1976), and for the IV-N emulsion by Hartley and Tritton (1979). Photographic calibration is provided by two sensitometers, a seven-step linear array at the N-W corner and a 4 × 4 spot array in the S-E. During the calibration of this latter sensitometer (Dawe and Metcalfe 1981), which is a copy of a design by Schoening (1976), it became apparent that the sensitivity of the hypersensitized IIIa-emulsions in use was decreasing as a function of time in the plateholder.
Litigation in surgery is increasing and liabilities are becoming unsustainable. This study aimed to analyse trends in claims, and identify areas for potential risk reduction, improved patient safety and a reduction in the number, and cost, of future claims.
Ten years of retrospective data on claims in otorhinolaryngology (2003–2013) were obtained from the National Health Service Litigation Authority via a Freedom of Information request. Data were re-entered into a spreadsheet and coded for analysis.
A total of 1031 claims were identified; of these, 604 were successful and 427 were unsuccessful. Successful claims cost a total of £41 000 000 (mean, £68 000). The most common areas for successful claims were: failure or delay in diagnosis (137 cases), intra-operative problems (116 cases), failure or delay in treatment (66 cases), failure to warn – informed consent issue (54 cases), and inappropriate treatment (47 cases).
Over half of the claims in ENT relate to the five most common areas of liability. Recent policy changes by the National Health Service Litigation Authority, over the level of information divulged, limits our learning from claims.
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.
We investigate seasonal variations in the diet and drinking water of four Great Lakes mastodon (Mammut americanum) specimens using stable isotope analysis of serially sampled inner-enamel bioapatite structural carbonate (δ13Csc, δ18Osc), and previously published bulk analyses. Isotopic analyses and thin section measurements showed that mastodon tooth enamel extension rates (~ 12–4 mm/yr, decreasing toward the cervix) were lower than those of mammoths or modern elephants. Mastodons had distinct and highly regular seasonal variations in δ13Csc and δ18Osc, which we interpret in the context of local glacial history and vegetation changes. Seasonal variations in δ18O were large but variations in δ13C were small, and may have been obscured if coarser sampling methods than our inner-enamel sampling approach were used. Thus, our approach may be particularly useful for understanding relatively small seasonal changes in δ13C within C3 environments. The seasonal patterns, though not entirely conclusive, suggest that the Ontario mastodons did not migrate over very long distances. Rather, the climate and seasonal dietary patterns of mastodons within the region changed over time, from ~ 12,400 to 10,400 14C yr BP (~ 15,000 – 12,000 cal yr BP). Insights gained using these methods can contribute to a better understanding of megafaunal extinctions and Paleoamerican lifeways.
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.