Entomological Surveillance of Behavioural Resilience and Resistance in Residual Malaria Vector Populations.

The most potent malaria vectors rely heavily upon human blood so they are vulnerable to attack with insecticide-treated nets (ITNs) and indoor residual spraying (IRS) within houses. Mosquito taxa that can avoid feeding or resting indoors, or by obtaining blood from animals, mediate a growing proportion of the dwindling transmission that persists as ITNs and IRS are scaled up. Increasing frequency of behavioural evasion traits within persisting residual vector systems usually reflect the successful suppression of the most potent and vulnerable vector taxa by IRS or ITNs, rather than their failure. Many of the commonly observed changes in mosquito behavioural patterns following intervention scale-up may well be explained by modified taxonomic composition and expression of phenotypically plastic behavioural preferences, rather than altered innate preferences of individuals or populations. Detailed review of the contemporary evidence base does not yet provide any clear-cut example of true behavioural resistance and is, therefore, consistent with the hypothesis presented. Caution should be exercised before over-interpreting most existing reports of increased frequency of behavioural traits which enable mosquitoes to evade fatal contact with insecticides: this may simply be the result of suppressing the most behaviourally vulnerable of the vector taxa that constituted the original transmission system. Mosquito taxa which have always exhibited such evasive traits may be more accurately described as behaviourally resilient, rather than resistant. Ongoing national or regional entomological monitoring surveys of physiological susceptibility to insecticides should be supplemented with biologically and epidemiologically meaningfully estimates of malaria vector population dynamics and the behavioural phenotypes that determine intervention impact, in order to design, select, evaluate and optimize the implementation of vector control measures

Eliminating Malaria Vectors.

Malaria vectors which predominantly feed indoors upon humans have been locally eliminated from several settings with insecticide treated nets (ITNs), indoor residual spraying or larval source management. Recent dramatic declines of An. gambiae in east Africa with imperfect ITN coverage suggest mosquito populations can rapidly collapse when forced below realistically achievable, non-zero thresholds of density and supporting resource availability. Here we explain why insecticide-based mosquito elimination strategies are feasible, desirable and can be extended to a wider variety of species by expanding the vector control arsenal to cover a broader spectrum of the resources they need to survive. The greatest advantage of eliminating mosquitoes, rather than merely controlling them, is that this precludes local selection for behavioural or physiological resistance traits. The greatest challenges are therefore to achieve high biological coverage of targeted resources rapidly enough to prevent local emergence of resistance and to then continually exclude, monitor for and respond to re-invasion from external populations

A falls prevention programme to improve quality of life, physical function and falls efficacy in older people receiving home help services: study protocol for a randomised controlled trial

BACKGROUND: Falls and fall-related injuries in older adults are associated with great burdens, both for the individuals, the health care system and the society. Previous research has shown evidence for the efficiency of exercise as falls prevention. An understudied group are older adults receiving home help services, and the effect of a falls prevention programme on health-related quality of life is unclear. The primary aim of this randomised controlled trial is to examine the effect of a falls prevention programme on quality of life, physical function and falls efficacy in older adults receiving home help services. A secondary aim is to explore the mediating factors between falls prevention and health-related quality of life. METHODS: The study is a single-blinded randomised controlled trial. Participants are older adults, aged 67 or older, receiving home help services, who are able to walk with or without walking aids, who have experienced at least one fall during the last 12 months and who have a Mini Mental State Examination of 23 or above. The intervention group receives a programme, based on the Otago Exercise Programme, lasting 12 weeks including home visits and motivational telephone calls. The control group receives usual care. The primary outcome is health-related quality of life (SF-36). Secondary outcomes are leg strength, balance, walking speed, walking habits, activities of daily living, nutritional status and falls efficacy. All measurements are performed at baseline, following intervention at 3 months and at 6 months' follow-up. Sample size, based on the primary outcome, is set to 150 participants randomised into the two arms, including an estimated 15-20% drop out. Participants are recruited from six municipalities in Norway. DISCUSSION: This trial will generate new knowledge on the effects of an exercise falls prevention programme among older fallers receiving home help services. This knowledge will be useful for clinicians, for health managers in the primary health care service and for policy makers

Extreme genetic fragility of the HIV-1 capsid

Genetic robustness, or fragility, is defined as the ability, or lack thereof, of a biological entity to maintain function in the face of mutations. Viruses that replicate via RNA intermediates exhibit high mutation rates, and robustness should be particularly advantageous to them. The capsid (CA) domain of the HIV-1 Gag protein is under strong pressure to conserve functional roles in viral assembly, maturation, uncoating, and nuclear import. However, CA is also under strong immunological pressure to diversify. Therefore, it would be particularly advantageous for CA to evolve genetic robustness. To measure the genetic robustness of HIV-1 CA, we generated a library of single amino acid substitution mutants, encompassing almost half the residues in CA. Strikingly, we found HIV-1 CA to be the most genetically fragile protein that has been analyzed using such an approach, with 70% of mutations yielding replication-defective viruses. Although CA participates in several steps in HIV-1 replication, analysis of conditionally (temperature sensitive) and constitutively non-viable mutants revealed that the biological basis for its genetic fragility was primarily the need to coordinate the accurate and efficient assembly of mature virions. All mutations that exist in naturally occurring HIV-1 subtype B populations at a frequency >3%, and were also present in the mutant library, had fitness levels that were >40% of WT. However, a substantial fraction of mutations with high fitness did not occur in natural populations, suggesting another form of selection pressure limiting variation in vivo. Additionally, known protective CTL epitopes occurred preferentially in domains of the HIV-1 CA that were even more genetically fragile than HIV-1 CA as a whole. The extreme genetic fragility of HIV-1 CA may be one reason why cell-mediated immune responses to Gag correlate with better prognosis in HIV-1 infection, and suggests that CA is a good target for therapy and vaccination strategies

Influenza H5 Hemagglutinin DNA Primes the Antibody Response Elicited by the Live Attenuated Influenza A/Vietnam/1203/2004 Vaccine in Ferrets

Priming immunization plays a key role in protecting individuals or populations to influenza viruses that are novel to humans. To identify the most promising vaccine priming strategy, we have evaluated different prime-boost regimens using inactivated, DNA and live attenuated vaccines in ferrets. Live attenuated influenza A/Vietnam/1203/2004 (H5N1) candidate vaccine (LAIV, VN04 ca) primed ferrets efficiently while inactivated H5N1 vaccine could not prime the immune response in seronegative ferrets unless an adjuvant was used. However, the H5 HA DNA vaccine alone was as successful as an adjuvanted inactivated VN04 vaccine in priming the immune response to VN04 ca virus. The serum antibody titers of ferrets primed with H5 HA DNA followed by intranasal vaccination of VN04 ca virus were comparable to that induced by two doses of VN04 ca virus. Both LAIV-LAIV and DNA-LAIV vaccine regimens could induce antibody responses that cross-neutralized antigenically distinct H5N1 virus isolates including A/HongKong/213/2003 (HK03) and prevented nasal infection of HK03 vaccine virus. Thus, H5 HA DNA vaccination may offer an alternative option for pandemic preparedness

Activation of ERAD Pathway by Human Hepatitis B Virus Modulates Viral and Subviral Particle Production

Hepatitis B virus (HBV) belongs to the Hepadnaviridae family of enveloped DNA viruses. It was previously shown that HBV can induce endoplasmic reticulum (ER) stress and activate the IRE1-XBP1 pathway of the unfolded protein response (UPR), through the expression of the viral regulatory protein X (HBx). However, it remained obscure whether or not this activation had any functional consequences on the target genes of the UPR pathway. Of these targets, the ER degradation-enhancing, mannosidase-like proteins (EDEMs) are thought to play an important role in relieving the ER stress during UPR, by recognizing terminally misfolded glycoproteins and delivering them to the ER-associated degradation (ERAD). In this study, we investigated the role of EDEMs in the HBV life-cycle. We found that synthesis of EDEMs (EDEM1 and its homologues, EDEM2 and EDEM3) is significantly up-regulated in cells with persistent or transient HBV replication. Co-expression of the wild-type HBV envelope proteins with EDEM1 resulted in their massive degradation, a process reversed by EDEM1 silencing. Surprisingly, the autophagy/lysosomes, rather than the proteasome were involved in disposal of the HBV envelope proteins. Importantly, inhibition of the endogenous EDEM1 expression in HBV replicating cells significantly increased secretion of both, enveloped virus and subviral particles. This is the first report showing that HBV activates the ERAD pathway, which, in turn, reduces the amount of envelope proteins, possibly as a mechanism to control the level of virus particles in infected cells and facilitate the establishment of chronic infections

Outbreak of Pneumonia in the Setting of Fatal Pneumococcal Meningitis among US Army Trainees: Potential Role of Chlamydia pneumoniae Infection

<p>Abstract</p> <p>Background</p> <p>Compared to the civilian population, military trainees are often at increased risk for respiratory infections. We investigated an outbreak of radiologically-confirmed pneumonia that was recognized after 2 fatal cases of serotype 7F pneumococcal meningitis were reported in a 303-person military trainee company (Alpha Company).</p> <p>Methods</p> <p>We reviewed surveillance data on pneumonia and febrile respiratory illness at the training facility; conducted chart reviews for cases of radiologically-confirmed pneumonia; and administered surveys and collected nasopharyngeal swabs from trainees in the outbreak battalion (Alpha and Hotel Companies), associated training staff, and trainees newly joining the battalion.</p> <p>Results</p> <p>Among Alpha and Hotel Company trainees, the average weekly attack rates of radiologically-confirmed pneumonia were 1.4% and 1.2% (most other companies at FLW: 0-0.4%). The pneumococcal carriage rate among all Alpha Company trainees was 15% with a predominance of serotypes 7F and 3. <it>Chlamydia pneumoniae </it>was identified from 31% of specimens collected from Alpha Company trainees with respiratory symptoms.</p> <p>Conclusion</p> <p>Although the etiology of the outbreak remains unclear, the identification of both <it>S. pneumoniae </it>and <it>C. pneumoniae </it>among trainees suggests that both pathogens may have contributed either independently or as cofactors to the observed increased incidence of pneumonia in the outbreak battalion and should be considered as possible etiologies in outbreaks of pneumonia in the military population.</p

Measurement of the Dipion Mass Spectrum in X(3872) -> J/Psi Pi+ Pi- Decays

We measure the dipion mass spectrum in X(3872)--> J/Psi Pi+ Pi- decays using 360 pb-1 of pbar-p collisions at 1.96 TeV collected with the CDF II detector. The spectrum is fit with predictions for odd C-parity (3S1, 1P1, and 3DJ) charmonia decaying to J/Psi Pi+ Pi-, as well as even C-parity states in which the pions are from Rho0 decay. The latter case also encompasses exotic interpretations, such as a D0-D*0Bar molecule. Only the 3S1 and J/Psi Rho hypotheses are compatible with our data. Since 3S1 is untenable on other grounds, decay via J/Psi Rho is favored, which implies C=+1 for the X(3872). Models for different J/Psi-Rho angular momenta L are considered. Flexibility in the models, especially the introduction of Rho-Omega interference, enable good descriptions of our data for both L=0 and 1.Comment: 7 pages, 4 figures -- Submitted to Phys. Rev. Let

Precision measurement of the top quark mass from dilepton events at CDF II

We report a measurement of the top quark mass, M_t, in the dilepton decay channel of $t\bar{t}\to b\ell'^{+}\nu_{\ell'}\bar{b}\ell^{-}\bar{\nu}_{\ell}$ using an integrated luminosity of 1.0 fb^{-1} of p\bar{p} collisions collected with the CDF II detector. We apply a method that convolutes a leading-order matrix element with detector resolution functions to form event-by-event likelihoods; we have enhanced the leading-order description to describe the effects of initial-state radiation. The joint likelihood is the product of the likelihoods from 78 candidate events in this sample, which yields a measurement of M_{t} = 164.5 \pm 3.9(\textrm{stat.}) \pm 3.9(\textrm{syst.}) \mathrm{GeV}/c^2, the most precise measurement of M_t in the dilepton channel.Comment: 7 pages, 2 figures, version includes changes made prior to publication by journa

Measurement of the Ratios of Branching Fractions B(Bs -> Ds pi pi pi) / B(Bd -> Dd pi pi pi) and B(Bs -> Ds pi) / B(Bd -> Dd pi)

Using 355 pb^-1 of data collected by the CDF II detector in \ppbar collisions at sqrt{s} = 1.96 TeV at the Fermilab Tevatron, we study the fully reconstructed hadronic decays B -> D pi and B -> D pi pi pi. We present the first measurement of the ratio of branching fractions B(Bs -> Ds pi pi pi) / B(Bd -> Dd pi pi pi) = 1.05 pm 0.10 (stat) pm 0.22 (syst). We also update our measurement of B(Bs -> Ds pi) / B(Bd -> Dd pi) to 1.13 pm 0.08 (stat) pm 0.23 (syst) improving the statistical uncertainty by more than a factor of two. We find B(Bs -> Ds pi) = [3.8 pm 0.3 (stat) pm 1.3 (syst)] \times 10^{-3} and B(Bs -> Ds pi pi pi) = [8.4 pm 0.8 (stat) pm 3.2 (syst)] \times 10^{-3}.Comment: 7 pages, 2 figure