What can we offer to 3 million MDRTB household contacts in 2016?

The diagnosis of multidrug resistant tuberculosis (MDR-TB) in any individual is the beginning of a prolonged and difficult therapeutic journey. It also marks the moment from which to begin consideration of how to manage close contacts. Preventive therapy for drug-susceptible latent tuberculosis infection has been demonstrated to be effective at reducing the risk of future disease; the stakes are higher when considering prevention of MDR-TB because treatment of active disease is more prolonged and toxic and much less effective. This has encouraged exploration of the potential utility of preventive therapy, with second-line agents, in reducing future incident drug-resistant TB.Three clinical trials of preventive therapy for contacts of patients with MDR-TB are starting in 2015/16; results will not be available until at least 2020, so what should be offered to exposed contacts in the interim?A recent policy brief, arising from a global consultation meeting of international experts, recommended preventive therapy based upon very limited available observational data. However the many known unknowns associated with this approach, include the high proportion of index-contact pairs with discordant drug susceptibility profiles and (even if susceptibilities are shared) the lack of data supporting the use of the selected agents in the treatment of latent infection (rather than active disease).It is important to acknowledge that the alternative to offering preventive therapy is not doing nothing. On the contrary, identified contacts should be maintained under close, active surveillance for 24 months, enabling early detection of active disease in the small proportion amongst whom this may occur. Such patients should benefit from less extensive disease at diagnosis and early access to individualized therapeutic regimens with improved treatment outcomes. Moreover the vast majority of contacts that do not develop disease will benefit from avoidance of potentially toxic, unnecessary therapy.Whether preventive therapy or close observation are implemented, national programmes should maintain a register of all contacts, interventions and 24 month outcomes; these will provide important performance metrics for programmatic management of MDRTB. If harmonized and standardized internationally, such a register could rapidly yield a wealth of observational data, to complement the trial results of the future

A monolithic MQW InP-InGaAsP-Based optical comb generator

We report the first demonstration of a monolithic optical-frequency comb generator. The device is based on multi-section quaternary/quaternary eight-quantum-well InP-InGaAsP material in a frequency-modulated (FM) laser design. The modulation is generated using quantum-confined Stark-effect phase-induced refractive index modulation to achieve fast modulation up to 24.4 GHz. The laser was fabricated using a single epitaxial growth step and quantum-well intermixing to realize low-loss phase adjustment and modulation sections. The output was quasicontinuous wave with intensity modulation at less than 20% for a total output power of 2 mW. The linewidth of each line was limited by the linewidth of the free running laser at an optimum of 25 MHz full-width at half-maximum. The comb generator produces a number of lines with a spacing exactly equal to the modulation frequency (or a multiple of it), differential phase noise between adjacent lines of -82 dBc/Hz at 1-kHz offset (modulation source-limited), and a potential comb spectrum width of up to 2 THz (15 nm), though the comb spectrum was not continuous across the full span

Auditory spatial representations of the world are compressed in blind humans

Compared to sighted listeners, blind listeners often display enhanced auditory spatial abilities such as localization in azimuth. However, less is known about whether blind humans can accurately judge distance in extrapersonal space using auditory cues alone. Using virtualization techniques, we show that auditory spatial representations of the world beyond the peripersonal space of blind listeners are compressed compared to those for normally sighted controls. Blind participants overestimated the distance to nearby sources and underestimated the distance to remote sound sources, in both reverberant and anechoic environments, and for speech, music, and noise signals. Functions relating judged and actual virtual distance were well fitted by compressive power functions, indicating that the absence of visual information regarding the distance of sound sources may prevent accurate calibration of the distance information provided by auditory signals.This research was supported by MRC Grant G0701870 and the Vision and Eye Research Unit (VERU), Postgraduate Medical Institute at Anglia Ruskin University

Male burying beetles extend, not reduce, parental care duration when reproductive competition is high

This is the author accepted manuscript. The final version is available on open access from Wiley via the DOI in this recordThe published version is also available in ORE: http://hdl.handle.net/10871/22254Male parents spend less time caring than females in many species with biparental care. The traditional explanation for this pattern is that males have lower confidence of parentage, so they desert earlier in favour of pursuing other mating opportunities. However, one recent alternative hypothesis is that prolonged male parental care might also evolve if staying to care actively improves paternity. If this is the case, an increase in reproductive competition should be associated with increased paternal care. To test this prediction, we manipulated the level of reproductive competition experienced by burying beetles, Nicrophorus vespilloides (Herbst, 1783). We found that caregiving males stayed for longer and mated more frequently with their partner when reproductive competition was greater. Reproductive productivity did not increase when males extended care. Our findings provide support for the increased paternity hypothesis. Extended duration of parental care may be a male tactic both protecting investment (in the current brood) and maximizing paternity (in subsequent brood(s) via female stored sperm) even if this fails to maximize current reproductive productivity and creates conflict of interest with their mate via costs associated with increased mating frequency

Anonymity, Pseudonymity, and Deliberation: Why Not Everything Should Be Connected

The discussion of anonymity and deliberation has repeatedly circled around two contradictory normative positions. One is that anonymity is valuable because it enables expression free from fear of repercussions. The other is that anonymity is destructive because it enables expression free from fear of repercussions. The same feature that enables a teenager from a repressive religious community to talk freely about his sexuality without fear of exposure also enables cruel and abusive responses that may inhibit such expressions.Leverhulme. Grant Number: RP2012-CO1

Behavioral plasticity and G × E of reproductive tactics in Nicrophorus vespilloides burying beetles

Journal Article© 2015 The Author(s). Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.Phenotypic plasticity is important in the evolution of traits and facilitates adaptation to rapid environmental changes. However, variation in plasticity at the individual level, and the heritable basis underlying this plasticity is rarely quantified for behavioral traits. Alternative behavioral reproductive tactics are key components of mating systems but are not often considered within a phenotypic plasticity framework (i.e., as reaction norms). Here, using lines artificially selected for repeated mating rate, we test for genetic (G × E) sources of variation in reproductive behavior of male Nicrophorus vespilloides burying beetles (including signaling behavior), as well as the role of individual body size, in responsiveness to changes in social environment. The results show that body size influences the response of individuals' signaling behavior to changes in the social environment. Moreover, there was G × E underlying the responses of males to variation in the quality of social environment experienced (relative size of focal male compared to his rival). This shows that individual variation in plasticity and social sensitivity of signaling behavior can evolve in response to selection on investment in mating behavior, with males selected for high mating investment having greater social sensitivity.NER

Body size but not warning signal luminance influences predation risk in recently metamorphosed poison frogs.

This is the final version of the article. Available from Wiley via the DOI in this record.During early development, many aposematic species have bright and conspicuous warning appearance, but have yet to acquire chemical defenses, a phenotypic state which presumably makes them vulnerable to predation. Body size and signal luminance in particular are known to be sensitive to variation in early nutrition. However, the relative importance of these traits as determinants of predation risk in juveniles is not known. To address this question, we utilized computer-assisted design (CAD) and information on putative predator visual sensitivities to produce artificial models of postmetamorphic froglets that varied in terms of body size and signal luminance. We then deployed the artificial models in the field and measured rates of attack by birds and unknown predators. Our results indicate that body size was a significant predictor of artificial prey survival. Rates of attack by bird predators were significantly higher on smaller models. However, predation by birds did not differ between artificial models of varying signal luminance. This suggests that at the completion of metamorphosis, smaller froglets may be at a selective disadvantage, potentially because predators can discern they have relatively low levels of chemical defense compared to larger froglets. There is likely to be a premium on efficient foraging, giving rise to rapid growth and the acquisition of toxins from dietary sources in juvenile poison frogs.This study was supported by a PhD scholarship (IFARHU-SENACYT program) and a research grant No. APY-NI-010-006B/ SENACYT both awarded to EEF by the Government of Panama, and by a Royal Society University Research Fellowship to JDB. MS was supported by a Biotechnology and Biological Sciences Research Council David Phillips Research Fellowship (BB/G022887/1). HMR was supported by a Junior Research Fellowship from Churchill College, Cambridge. Special thanks to Rachel Page at STRI for supporting EEF with the grant application, Sistema Nacional de Investigacion de Panama (SNI), and the People of Santa Fe for their collaboration during the stud