Infection and Transmission of Rift Valley Fever Viruses Lacking the NSs and/or NSm Genes in Mosquitoes: Potential Role for NSm in Mosquito Infection

Rift Valley fever virus is transmitted mainly by mosquitoes and causes disease in humans and animals throughout Africa and the Arabian Peninsula. The impact of disease is large in terms of human illness and mortality, and economic impact on the livestock industry. For these reasons, and because there is a risk of this virus spreading to Europe and North America, it is important to develop a vaccine that is stable, safe and effective in preventing infection. Potential vaccine viruses have been developed through deletion of two genes (NSs and NSm) affecting virus virulence. Because this virus is normally transmitted by mosquitoes we must determine the effects of the deletions in these vaccine viruses on their ability to infect and be transmitted by mosquitoes. An optimal vaccine virus would not infect or be transmitted. The viruses were tested in two mosquito species: Aedes aegypti and Culex quinquefasciatus. Deletion of the NSm gene reduced infection of Ae. aegypti mosquitoes indicating a role for the NSm protein in mosquito infection. The virus with deletion of both NSs and NSm genes was the best vaccine candidate since it did not infect Ae. aegypti and showed reduced infection and transmission rates in Cx. quinquefasciatus

Truncated and Helix-Constrained Peptides with High Affinity and Specificity for the cFos Coiled-Coil of AP-1

Protein-based therapeutics feature large interacting surfaces. Protein folding endows structural stability to localised surface epitopes, imparting high affinity and target specificity upon interactions with binding partners. However, short synthetic peptides with sequences corresponding to such protein epitopes are unstructured in water and promiscuously bind to proteins with low affinity and specificity. Here we combine structural stability and target specificity of proteins, with low cost and rapid synthesis of small molecules, towards meeting the significant challenge of binding coiled coil proteins in transcriptional regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues, strategically incorporating i-->i+4 helix-inducing constraints, and positioning unnatural amino acids, we have produced short, water-stable, alpha-helical peptides that bind cFos. A three-dimensional NMR-derived structure for one peptide (24) confirmed a highly stable alpha-helix which was resistant to proteolytic degradation in serum. These short structured peptides are entropically pre-organized for binding with high affinity and specificity to cFos, a key component of the oncogenic transcriptional regulator Activator Protein-1 (AP-1). They competitively antagonized the cJun–cFos coiled-coil interaction. Truncating a Jun-based peptide from 37 to 22 residues decreased the binding enthalpy for cJun by ~9 kcal/mol, but this was compensated by increased conformational entropy (TDS ≤ 7.5 kcal/mol). This study demonstrates that rational design of short peptides constrained by alpha-helical cyclic pentapeptide modules is able to retain parental high helicity, as well as high affinity and specificity for cFos. These are important steps towards small antagonists of the cJun-cFos interaction that mediates gene transcription in cancer and inflammatory diseases

Evaluating the importance of metamorphism in the foundering of continental crust

The metamorphic conditions and mechanisms required to induce foundering in deep arc crust are assessed using an example of representative lower crust in SW New Zealand. Composite plutons of Cretaceous monzodiorite and gabbro were emplaced at ~1.2 and 1.8 GPa are parts of the Western Fiordland Orthogneiss (WFO); examples of the plutons are tectonically juxtaposed along a structure that excised ~25 km of crust. The 1.8 GPa Breaksea Orthogneiss includes suitably dense minor components (e.g. eclogite) capable of foundering at peak conditions. As the eclogite facies boundary has a positive dP/dT, cooling from supra-solidus conditions (T > 950 ºC) at high-P should be accompanied by omphacite and garnet growth. However, a high monzodioritic proportion and inefficient metamorphism in the Breaksea Orthogneiss resulted in its positive buoyancy and preservation. Metamorphic inefficiency and compositional relationships in the 1.2 GPa Malaspina Pluton meant it was never likely to have developed densities sufficiently high to founder. These relationships suggest that the deep arc crust must have primarily involved significant igneous accumulation of garnet–clinopyroxene (in proportions >75%). Crustal dismemberment with or without the development of extensional shear zones is proposed to have induced foundering of excised cumulate material at P > 1.2 GPa

An evaluation of gender equity in different models of primary care practices in Ontario

Background: The World Health Organization calls for more work evaluating the effect of health care reforms on gender equity in developed countries. We performed this evaluation in Ontario, Canada where primary care models resulting from reforms co-exist. // Methods: This cross sectional study of primary care practices uses data collected in 2005-2006. Healthcare service models included in the study consist of fee for service (FFS) based, salaried, and capitation based. We compared the quality of care delivered to women and men in practices of each model. We performed multi-level, multivariate regressions adjusting for patient socio-demographic and economic factors to evaluate vertical equity, and adjusting for these and health factors in evaluating horizontal equity. We measured seven dimensions of health service delivery (e.g. accessibility and continuity) and three dimensions of quality of care using patient surveys (n = 5,361) and chart abstractions (n = 4,108). // Results: Health service delivery measures were comparable in women and men, with differences ≤ 2.2% in all seven dimensions and in all models. Significant gender differences in the health promotion subjects addressed were observed. Female specific preventive manoeuvres were more likely to be performed than other preventive care. Men attending FFS practices were more likely to receive influenza immunization than women (Adjusted odds ratio: 1.75, 95% confidence intervals (CI) 1.05, 2.92). There was no difference in the other three prevention indicators. FFS practices were also more likely to provide recommended care for chronic diseases to men than women (Adjusted difference of -11.2%, CI -21.7, -0.8). A similar trend was observed in Community Health Centers (CHC). // Conclusions: The observed differences in the type of health promotion subjects discussed are likely an appropriate response to the differential healthcare needs between genders. Chronic disease care is non equitable in FFS but not in capitation based models. We recommend that efforts to monitor and address gender based differences in the delivery of chronic disease management in primary care be pursued.Funding for the original study on which this research is based was provided by the Ontario Ministry of Health and Long Term Care Primary Health Care Transition Fund. The views expressed in this report are the views of the authors and do not necessarily reflect those of the Ontario Ministry of Health and Long Term Care

Effect of lutein and antioxidant dietary supplementation on contrast sensitivity in age-related macular disease:A randomized controlled trial

Objective: The aim of the study is to determine the effect of lutein combined with vitamin and mineral supplementation on contrast sensitivity in people with age-related macular disease (ARMD). Design: A prospective, 9-month, double-masked randomized controlled trial. Setting: Aston University, Birmingham, UK and a UK optometric clinical practice. Subjects: Age-related maculopathy (ARM) and atrophic age-related macular degeneration (AMD) participants were randomized (using a random number generator) to either placebo (n = 10) or active (n=15) groups. Three of the placebo group and two of the active group dropped out. Interventions: The active group supplemented daily with 6 mg lutein combined with vitamins and minerals. The outcome measure was contrast sensitivity (CS) measured using the Pelli-Robson chart, for which the study had 80% power at the 5% significance level to detect a change of 0.3log units. Results: The CS score increased by 0.07 ± 0.07 and decreased by 0.02 ± 0.18 log units for the placebo and active groups, respectively. The difference between these values is not statistically significant (z = 0.903, P = 0.376). Conclusion: The results suggest that 6 mg of lutein supplementation in combination with other antioxidants is not beneficial for this group. Further work is required to establish optimum dosage levels

Study of Bc+B_c^+ decays to the K+K−π+K^+K^-\pi^+ final state and evidence for the decay Bc+→χc0π+B_c^+\to\chi_{c0}\pi^+

A study of $B_c^+\to K^+K^-\pi^+$ decays is performed for the first time using data corresponding to an integrated luminosity of 3.0 $\mathrm{fb}^{-1}$ collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of $7$ and $8$ TeV. Evidence for the decay $B_c^+\to\chi_{c0}(\to K^+K^-)\pi^+$ is reported with a significance of 4.0 standard deviations, resulting in the measurement of $\frac{\sigma(B_c^+)}{\sigma(B^+)}\times\mathcal{B}(B_c^+\to\chi_{c0}\pi^+)$ to be $(9.8^{+3.4}_{-3.0}(\mathrm{stat})\pm 0.8(\mathrm{syst}))\times 10^{-6}$. Here $\mathcal{B}$ denotes a branching fraction while $\sigma(B_c^+)$ and $\sigma(B^+)$ are the production cross-sections for $B_c^+$ and $B^+$ mesons. An indication of $\bar b c$ weak annihilation is found for the region $m(K^-\pi^+)<1.834\mathrm{\,Ge\kern -0.1em V\!/}c^2$, with a significance of 2.4 standard deviations.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-022.html, link to supplemental material inserted in the reference

Landmark Recognition in Alzheimer’s Dementia: Spared Implicit Memory for Objects Relevant for Navigation

Contains fulltext : 97074.pdf (publisher's version ) (Open Access)BACKGROUND: In spatial navigation, landmark recognition is crucial. Specifically, memory for objects placed at decision points on a route is relevant. Previous fMRI research in healthy adults showed higher medial-temporal lobe (MTL) activation for objects placed at decision points compared to non-decision points, even at an implicit level. Since there is evidence that implicit learning is intact in amnesic patients, the current study examined memory for objects relevant for navigation in patients with Alzheimer's dementia (AD). METHODOLOGY/PRINCIPAL FINDINGS: 21 AD patients participated with MTL atrophy assessed on MRI (mean MMSE = 21.2, SD = 4.0), as well as 20 age- and education-matched non-demented controls. All participants watched a 5-min video showing a route through a virtual museum with 20 objects placed at intersections (decision points) and 20 at simple turns (non-decision points). The instruction was to pay attention to the toys (half of the objects) for which they were supposedly tested later. Subsequently, a recognition test followed with the 40 previously presented objects among 40 distracter items (both toys and non-toys). Results showed a better performance for the non-toy objects placed at decision points than non-decision points, both for AD patients and controls. CONCLUSION/SIGNIFICANCE: Our findings indicate that AD patients with MTL damage have implicit memory for object information relevant for navigation. No decision point effect was found for the attended items. Possibly, focusing attention on the items occurred at the cost of the context information in AD, whereas the controls performed at an optimal level due to intact memory function.5 p

Process evaluation of a peer-led antenatal breastfeeding class for fathers: perceptions of facilitators and participants

Background: The Parent Infant Feeding Initiative (PIFI) was a factorial, randomised controlled trial that aimed to prolong exclusive breastfeeding by targeting expecting fathers. One of the intervention strategies evaluated was a father-focused breastfeeding class facilitated by a male peer facilitator. The aim of this mixed-methods descriptive study was to 1) evaluate the feedback provided from participants of the class and 2) explore the motivations and experiences of volunteer male peer facilitators trained to deliver the class. Methods: Father-focused breastfeeding antenatal (FFAB) classes were conducted in six Western Australian hospitals between August 2015 and December 2016. Following each peer facilitated FFAB class, expecting father participants completed an evaluation form to assess their satisfaction with the format, facilitation and content, in addition to whether their expectations and confidence to manage breastfeeding problems had changed. Feedback to open-ended questions was analysed using content analysis to identify learnings and suggestions for improvements. At the completion of PIFI, individual telephone interviews were undertaken with 14 peer facilitators to gain insight into their motivations for volunteering and experiences of conducting the classes. Transcripts from interviews were analysed using Braun and Clarke’s six phases for thematic analysis. Results: Participant evaluation forms were completed by 678 of the 697 father participants (98%). Overall satisfaction with class format, facilitation and content was high with 90% or more of fathers either strongly agreeing or agreeing with each positively-phrased evaluation item. Class participants enjoyed interacting with other fathers, appreciated validation of their role, were not always aware of the importance of breastfeeding or potential difficulties, valued the anticipatory guidance around what to expect in the early weeks of parenting and appreciated learning practical breastfeeding support strategies. Peer facilitators indicated they felt well prepared and supported to conduct FFAB classes. Analysis of interview transcripts revealed common experiences of the peer facilitators incorporating four themes: ‘Highlights of being a facilitator’, ‘Challenges’, ‘Mourning the project completion’ and ‘Satisfaction with training and support’. Conclusion: Father-focused breastfeeding classes supported by volunteer male peer facilitators are a feasible and acceptable way of engaging fathers as breastfeeding supporters. Trial registration: ACTRN12614000605695. Registered 6 June 2014

The Natural History of Trachoma Infection and Disease in a Gambian Cohort with Frequent Follow-Up

Trachoma is an infectious disease of the eye that causes blindness in many of the poorest parts of the world. In this paper, we use a novel statistical approach to estimate the characteristics of this disease among people living in The Gambia who were examined every 2 weeks over a 6-month period. We found that the typical duration of infection with Chlamydia trachomatis and of clinically active disease were significantly longer than previously estimated. We tested different hypotheses about the natural history of trachoma that explain the relationship between infection and disease observed in the field. We also confirmed that disease lasts significantly longer among young children under 5 years old compared with older children and adults, even after accounting for high rates of re-infection in this age group, consistent with the development of immunity with age. The long duration of infection, especially among younger children, contributes to the persistence and gradual return of trachoma after community-wide treatment with azithromycin. This implies the need for high treatment coverage if infection is to be eliminated from a community, even where the return of infection after treatment is seen to be slow