Progress in HPV vaccination in low- and lower-middle-income countries.

The past 10 years have seen remarkable progress in the global scale-up of human papillomavirus (HPV) vaccinations. Forty-three low- and lower-middle-income countries (LLMICs) have gained experience in delivering this vaccine to young adolescent girls through pilot programs, demonstration programs, and national introductions and most of these have occurred in the last 4 years. The experience of Senegal is summarized as an illustrative country case study. Publication of numerous delivery experiences and lessons learned has demonstrated the acceptability and feasibility of HPV vaccinations in LLMICs. Four areas require dedicated action to overcome remaining challenges to national scaling-up: maintaining momentum politically, planning successfully, securing financing, and fostering sustainability. Advances in policy, programming, and science may help accelerate reaching 30 million girls in LLMICs with HPV vaccine by 2020

Influence of a knot on the strength of a polymer strand

Many experiments have been done to determine the relative strength of different knots, and these show that the break in a knotted rope almost invariably occurs at a point just outside the `entrance' to the knot. The influence of knots on the properties of polymers has become of great interest, in part because of their effect on mechanical properties. Knot theory applied to the topology of macromolecules indicates that the simple trefoil or `overhand' knot is likely to be present with high probability in any long polymer strand. Fragments of DNA have been observed to contain such knots in experiments and computer simulations. Here we use {\it ab initio} computational methods to investigate the effect of a trefoil knot on the breaking strength of a polymer strand. We find that the knot weakens the strand significantly, and that, like a knotted rope, it breaks under tension at the entrance to the knot.Comment: 3 pages, 4 figure

Do acute elevations of serum creatinine in primary care engender an increased mortality risk?

Background: The significant impact Acute Kidney Injury (AKI) has on patient morbidity and mortality emphasizes the need for early recognition and effective treatment. AKI presenting to or occurring during hospitalisation has been widely studied but little is known about the incidence and outcomes of patients experiencing acute elevations in serum creatinine in the primary care setting where people are not subsequently admitted to hospital. The aim of this study was to define this incidence and explore its impact on mortality. Methods: The study cohort was identified by using hospital data bases over a six month period. Inclusion criteria: People with a serum creatinine request during the study period, 18 or over and not on renal replacement therapy. The patients were stratified by a rise in serum creatinine corresponding to the Acute Kidney Injury Network (AKIN) criteria for comparison purposes. Descriptive and survival data were then analysed. Ethical approval was granted from National Research Ethics Service (NRES) Committee South East Coast and from the National Information Governance Board. Results: The total study population was 61,432. 57,300 subjects with ‘no AKI’, mean age 64.The number (mean age) of acute serum creatinine rises overall were, ‘AKI 1’ 3,798 (72), ‘AKI 2’ 232 (73), and ‘AKI 3’ 102 (68) which equates to an overall incidence of 14,192 pmp/year (adult). Unadjusted 30 day survival was 99.9% in subjects with ‘no AKI’, compared to 98.6%, 90.1% and 82.3% in those with ‘AKI 1’, ‘AKI 2’ and ‘AKI 3’ respectively. After multivariable analysis adjusting for age, gender, baseline kidney function and co-morbidity the odds ratio of 30 day mortality was 5.3 (95% CI 3.6, 7.7), 36.8 (95% CI 21.6, 62.7) and 123 (95% CI 64.8, 235) respectively, compared to those without acute serum creatinine rises as defined. Conclusions: People who develop acute elevations of serum creatinine in primary care without being admitted to hospital have significantly worse outcomes than those with stable kidney function

Semantic aware Bayesian network model for actionable knowledge discovery in linked data

The majority of the conventional mining algorithms treat the mining process as an isolated data-driven procedure and overlook the semantic of the targeted data. As a result, the generated patterns are abundant and end users cannot act upon them seamlessly. Furthermore, interdisciplinary knowledge can not be obtained from domain-specific silo of data. The emergence of Linked Data (LD) as a new model for knowledge representation, which intertwines data with its semantics, has introduced new opportunities for data miners. Accordingly, this paper proposes an ontology-based Semantic-Aware Bayesian network (BN) model. In contrast to the existing mining algorithms, the proposed model does into transform the original format of the LD set. Therefore, it not only accommodates the semantic aspects in LD, but also caters to the need of connecting different data-sets from different domains. We evaluate the proposed model on a Bone Dysplasia dataset, Experimental results show promising performance

The development of path integration: combining estimations of distance and heading

Efficient daily navigation is underpinned by path integration, the mechanism by which we use self-movement information to update our position in space. This process is well-understood in adulthood, but there has been relatively little study of path integration in childhood, leading to an underrepresentation in accounts of navigational development. Previous research has shown that calculation of distance and heading both tend to be less accurate in children as they are in adults, although there have been no studies of the combined calculation of distance and heading that typifies naturalistic path integration. In the present study 5-year-olds and 7-year-olds took part in a triangle-completion task, where they were required to return to the startpoint of a multi-element path using only idiothetic information. Performance was compared to a sample of adult participants, who were found to be more accurate than children on measures of landing error, heading error, and distance error. 7-year-olds were significantly more accurate than 5-year-olds on measures of landing error and heading error, although the difference between groups was much smaller for distance error. All measures were reliably correlated with age, demonstrating a clear development of path integration abilities within the age range tested. Taken together, these data make a strong case for the inclusion of path integration within developmental models of spatial navigational processing

Elevated CO₂ does not increase eucalypt forest productivity on a low-phosphorus soil

Rising atmospheric CO2 stimulates photosynthesis and productivity of forests, offsetting CO2 emissions. Elevated CO2 experiments in temperate planted forests yielded ~23% increases in productivity over the initial years. Whether similar CO2 stimulation occurs in mature evergreen broadleaved forests on low-phosphorus (P) soils is unknown, largely due to lack of experimental evidence. This knowledge gap creates major uncertainties in future climate projections as a large part of the tropics is P-limited. Here,we increased atmospheric CO2 concentration in a mature broadleaved evergreen eucalypt forest for three years, in the first large-scale experiment on a P-limited site. We show that tree growth and other aboveground productivity components did not significantly increase in response to elevated CO2 in three years, despite a sustained 19% increase in leaf photosynthesis. Moreover, tree growth in ambient CO2 was strongly P-limited and increased by ~35% with added phosphorus. The findings suggest that P availability may potentially constrain CO2-enhanced productivity in P-limited forests; hence, future atmospheric CO2 trajectories may be higher than predicted by some models. As a result, coupled climate-carbon models should incorporate both nitrogen and phosphorus limitations to vegetation productivity in estimating future carbon sinks

Risk factors for hospital admission with RSV bronchiolitis in England: a population-based birth cohort study.

OBJECTIVE: To examine the timing and duration of RSV bronchiolitis hospital admission among term and preterm infants in England and to identify risk factors for bronchiolitis admission. DESIGN: A population-based birth cohort with follow-up to age 1 year, using the Hospital Episode Statistics database. SETTING: 71 hospitals across England. PARTICIPANTS: We identified 296618 individual birth records from 2007/08 and linked to subsequent hospital admission records during the first year of life. RESULTS: In our cohort there were 7189 hospital admissions with a diagnosis of bronchiolitis, 24.2 admissions per 1000 infants under 1 year (95%CI 23.7-24.8), of which 15% (1050/7189) were born preterm (47.3 bronchiolitis admissions per 1000 preterm infants (95% CI 44.4-50.2)). The peak age group for bronchiolitis admissions was infants aged 1 month and the median was age 120 days (IQR = 61-209 days). The median length of stay was 1 day (IQR = 0-3). The relative risk (RR) of a bronchiolitis admission was higher among infants with known risk factors for severe RSV infection, including those born preterm (RR = 1.9, 95% CI 1.8-2.0) compared with infants born at term. Other conditions also significantly increased risk of bronchiolitis admission, including Down's syndrome (RR = 2.5, 95% CI 1.7-3.7) and cerebral palsy (RR = 2.4, 95% CI 1.5-4.0). CONCLUSIONS: Most (85%) of the infants who are admitted to hospital with bronchiolitis in England are born at term, with no known predisposing risk factors for severe RSV infection, although risk of admission is higher in known risk groups. The early age of bronchiolitis admissions has important implications for the potential impact and timing of future active and passive immunisations. More research is needed to explain why babies born with Down's syndrome and cerebral palsy are also at higher risk of hospital admission with RSV bronchiolitis

Persistence of the immune response induced by BCG vaccination.

BACKGROUND: Although BCG vaccination is recommended in most countries of the world, little is known of the persistence of BCG-induced immune responses. As novel TB vaccines may be given to boost the immunity induced by neonatal BCG vaccination, evidence concerning the persistence of the BCG vaccine-induced response would help inform decisions about when such boosting would be most effective. METHODS: A randomised control study of UK adolescents was carried out to investigate persistence of BCG immune responses. Adolescents were tested for interferon-gamma (IFN-gamma) response to Mycobacterium tuberculosis purified protein derivative (M.tb PPD) in a whole blood assay before, 3 months, 12 months (n = 148) and 3 years (n = 19) after receiving teenage BCG vaccination or 14 years after receiving infant BCG vaccination (n = 16). RESULTS: A gradual reduction in magnitude of response was evident from 3 months to 1 year and from 1 year to 3 years following teenage vaccination, but responses 3 years after vaccination were still on average 6 times higher than before vaccination among vaccinees. Some individuals (11/86; 13%) failed to make a detectable antigen-specific response three months after vaccination, or lost the response after 1 (11/86; 13%) or 3 (3/19; 16%) years. IFN-gamma response to Ag85 was measured in a subgroup of adolescents and appeared to be better maintained with no decline from 3 to 12 months. A smaller group of adolescents were tested 14 years after receiving infant BCG vaccination and 13/16 (81%) made a detectable IFN-gamma response to M.tb PPD 14 years after infant vaccination as compared to 6/16 (38%) matched unvaccinated controls (p = 0.012); teenagers vaccinated in infancy were 19 times more likely to make an IFN-gamma response of > 500 pg/ml than unvaccinated teenagers. CONCLUSION: BCG vaccination in infancy and adolescence induces immunological memory to mycobacterial antigens that is still present and measurable for at least 14 years in the majority of vaccinees, although the magnitude of the peripheral blood response wanes from 3 months to 12 months and from 12 months to 3 years post vaccination. The data presented here suggest that because of such waning in the response there may be scope for boosting anti-tuberculous immunity in BCG vaccinated children anytime from 3 months post-vaccination. This supports the prime boost strategies being employed for some new TB vaccines currently under development

Neuroimaging Evidence of Major Morpho-Anatomical and Functional Abnormalities in the BTBR T+TF/J Mouse Model of Autism

BTBR T+tf/J (BTBR) mice display prominent behavioural deficits analogous to the defining symptoms of autism, a feature that has prompted a widespread use of the model in preclinical autism research. Because neuro-behavioural traits are described with respect to reference populations, multiple investigators have examined and described the behaviour of BTBR mice against that exhibited by C57BL/6J (B6), a mouse line characterised by high sociability and low self-grooming. In an attempt to probe the translational relevance of this comparison for autism research, we used Magnetic Resonance Imaging (MRI) to map in both strain multiple morpho-anatomical and functional neuroimaging readouts that have been extensively used in patient populations. Diffusion tensor tractography confirmed previous reports of callosal agenesis and lack of hippocampal commissure in BTBR mice, and revealed a concomitant rostro-caudal reorganisation of major cortical white matter bundles. Intact inter-hemispheric tracts were found in the anterior commissure, ventro-medial thalamus, and in a strain-specific white matter formation located above the third ventricle. BTBR also exhibited decreased fronto-cortical, occipital and thalamic gray matter volume and widespread reductions in cortical thickness with respect to control B6 mice. Foci of increased gray matter volume and thickness were observed in the medial prefrontal and insular cortex. Mapping of resting-state brain activity using cerebral blood volume weighted fMRI revealed reduced cortico-thalamic function together with foci of increased activity in the hypothalamus and dorsal hippocampus of BTBR mice. Collectively, our results show pronounced functional and structural abnormalities in the brain of BTBR mice with respect to control B6 mice. The large and widespread white and gray matter abnormalities observed do not appear to be representative of the neuroanatomical alterations typically observed in autistic patients. The presence of reduced fronto-cortical metabolism is of potential translational relevance, as this feature recapitulates previously-reported clinical observations