Evaluation of alternative mosquito sampling methods for malaria vectors in Lowland South - East Zambia.

Sampling malaria vectors and measuring their biting density is of paramount importance for entomological surveys of malaria transmission. Human landing catch (HLC) has been traditionally regarded as a gold standard method for surveying human exposure to mosquito bites. However, due to the risk of human participant exposure to mosquito-borne parasites and viruses, a variety of alternative, exposure-free trapping methods were compared in lowland, south-east Zambia. Centres for Disease Control and Prevention miniature light trap (CDC-LT), Ifakara Tent Trap model C (ITT-C), resting boxes (RB) and window exit traps (WET) were all compared with HLC using a 3 × 3 Latin Squares design replicated in 4 blocks of 3 houses with long lasting insecticidal nets, half of which were also sprayed with a residual deltamethrin formulation, which was repeated for 10 rounds of 3 nights of rotation each during both the dry and wet seasons. The mean catches of HLC indoor, HLC outdoor, CDC-LT, ITT-C, WET, RB indoor and RB outdoor, were 1.687, 1.004, 3.267, 0.088, 0.004, 0.000 and 0.008 for Anopheles quadriannulatus Theobald respectively, and 7.287, 6.784, 10.958, 5.875, 0.296, 0.158 and 0.458, for An. funestus Giles, respectively. Indoor CDC-LT was more efficient in sampling An. quadriannulatus and An. funestus than HLC indoor (Relative rate [95% Confidence Interval] = 1.873 [1.653, 2.122] and 1.532 [1.441, 1.628], respectively, P < 0.001 for both). ITT-C was the only other alternative which had comparable sensitivity (RR = 0.821 [0.765, 0.881], P < 0.001), relative to HLC indoor other than CDC-LT for sampling An. funestus. While the two most sensitive exposure-free techniques primarily capture host-seeking mosquitoes, both have substantial disadvantages for routine community-based surveillance applications: the CDC-LT requires regular recharging of batteries while the bulkiness of ITT-C makes it difficult to move between sampling locations. RB placed indoors or outdoors and WET had consistently poor sensitivity so it may be useful to evaluate additional alternative methods, such as pyrethrum spray catches and back packer aspirators, for catching resting mosquitoes

An affordable, quality-assured community-based system for high-resolution entomological surveillance of vector mosquitoes that reflects human malaria infection risk patterns.

ABSTRACT: BACKGROUND: More sensitive and scalable entomological surveillance tools are required to monitor low levels of transmission that are increasingly common across the tropics, particularly where vector control has been successful. A large-scale larviciding programme in urban Dar es Salaam, Tanzania is supported by a community-based (CB) system for trapping adult mosquito densities to monitor programme performance. Methodology An intensive and extensive CB system for routine, longitudinal, programmatic surveillance of malaria vectors and other mosquitoes using the Ifakara Tent Trap (ITT-C) was developed in Urban Dar es Salaam, Tanzania, and validated by comparison with quality assurance (QA) surveys using either ITT-C or human landing catches (HLC), as well as a cross-sectional survey of malaria parasite prevalence in the same housing compounds. RESULTS: Community-based ITT-C had much lower sensitivity per person-night of sampling than HLC (Relative Rate (RR) [95% Confidence Interval (CI)] = 0.079 [0.051, 0.121], P < 0.001 for Anopheles gambiae s.l. and 0.153 [0.137, 0.171], P < 0.001 for Culicines) but only moderately differed from QA surveys with the same trap (0.536 [0.406,0.617], P = 0.001 and 0.747 [0.677,0.824], P < 0.001, for An. gambiae or Culex respectively). Despite the poor sensitivity of the ITT per night of sampling, when CB-ITT was compared with QA-HLC, it proved at least comparably sensitive in absolute terms (171 versus 169 primary vectors caught) and cost-effective (153US$versus 187US$ per An. gambiae caught) because it allowed more spatially extensive and temporally intensive sampling (4284 versus 335 trap nights distributed over 615 versus 240 locations with a mean number of samples per year of 143 versus 141). Despite the very low vectors densities (Annual estimate of about 170 An gambiae s.l bites per person per year), CB-ITT was the only entomological predictor of parasite infection risk (Odds Ratio [95% CI] = 4.43[3.027,7. 454] per An. gambiae or Anopheles funestus caught per night, P =0.0373). Discussion and conclusion CB trapping approaches could be improved with more sensitive traps, but already offer a practical, safe and affordable system for routine programmatic mosquito surveillance and clusters could be distributed across entire countries by adapting the sample submission and quality assurance procedures accordingly

Platinum-(IV)-derivative satraplatin induced G2/M cell cycle perturbation via p53-p21(waf1/cip1)-independent pathway in human colorectal cancer cells

Platinum-(IV)-derivative satraplatin represents a new generation of orally available anti-cancer drugs that are under development for the treatment of several cancers. Understanding the mechanisms of cell cycle modulation and apoptosis is necessary to define the mode of action of satraplatin. In this study, we investigate the ability of satraplatin to induce cell cycle perturbation, clonogenicity loss and apoptosis in colorectal cancer (CRC) cells.Platinum-(IV)-derivative satraplatin represents a new generation of orally available anti-cancer drugs that are under development for the treatment of several cancers. Understanding the mechanisms of cell cycle modulation and apoptosis is necessary to define the mode of action of satraplatin. In this study, we investigate the ability of satraplatin to induce cell cycle perturbation, clonogenicity loss and apoptosis in colorectal cancer (CRC) cells

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

Serum amyloid A primes microglia for ATP-dependent interleukin-1\u3b2 release

Acute-phase response is a systemic reaction to environmental/inflammatory insults and involves production of acute-phase proteins, including serum amyloid A (SAA). Interleukin-1\u3b2 (IL-1\u3b2), a master regulator of neuroinflammation produced by activated inflammatory cells of the myeloid lineage, in particular microglia, plays a key role in the pathogenesis of acute and chronic diseases of the peripheral nervous system and CNS. IL-1\u3b2 release is promoted by ATP acting at the purinergic P2X7 receptor (P2X7R) in cells primed with toll-like receptor (TLR) ligands

The SAMI Galaxy Survey: The cluster redshift survey, target selection and cluster properties

We describe the selection of galaxies targeted in eight low redshift clusters (APMCC0917, A168, A4038, EDCC442, A3880, A2399, A119 and A85; $0.029 < z < 0.058$) as part of the Sydney-AAO Multi-Object integral field Spectrograph Galaxy Survey (SAMI-GS). We have conducted a redshift survey of these clusters using the AAOmega multi-object spectrograph on the 3.9m Anglo-Australian Telescope. The redshift survey is used to determine cluster membership and to characterise the dynamical properties of the clusters. In combination with existing data, the survey resulted in 21,257 reliable redshift measurements and 2899 confirmed cluster member galaxies. Our redshift catalogue has a high spectroscopic completeness ($\sim 94\%$) for $r_{\rm petro} \leq 19.4$ and clustercentric distances $R< 2\rm{R}_{200}$. We use the confirmed cluster member positions and redshifts to determine cluster velocity dispersion, $\rm{R}_{200}$, virial and caustic masses, as well as cluster structure. The clusters have virial masses $14.25 \leq {\rm log }({\rm M}_{200}/\rm{M}_{\odot}) \leq 15.19$. The cluster sample exhibits a range of dynamical states, from relatively relaxed-appearing systems, to clusters with strong indications of merger-related substructure. Aperture- and PSF-matched photometry are derived from SDSS and VST/ATLAS imaging and used to estimate stellar masses. These estimates, in combination with the redshifts, are used to define the input target catalogue for the cluster portion of the SAMI-GS. The primary SAMI-GS cluster targets have $R< \rm{R}_{200}$, velocities $|v_{\rm pec}| < 3.5\sigma_{200}$ and stellar masses $9.5 \leq {\rm log(M}^*_{approx}/\rm{M}_{\odot}) \leq 12$. Finally, we give an update on the SAMI-GS progress for the cluster regions

AAV-mediated direct in vivo CRISPR screen identifies functional suppressors in glioblastoma

A causative understanding of genetic factors that regulate glioblastoma pathogenesis is of central importance. Here we developed an adeno-associated virus-mediated, autochthonous genetic CRISPR screen in glioblastoma. Stereotaxic delivery of a virus library targeting genes commonly mutated in human cancers into the brains of conditional-Cas9 mice resulted in tumors that recapitulate human glioblastoma. Capture sequencing revealed diverse mutational profiles across tumors. The mutation frequencies in mice correlated with those in two independent patient cohorts. Co-mutation analysis identified co-occurring driver combinations such as B2m-Nf1, Mll3-Nf1 and Zc3h13-Rb1, which were subsequently validated using AAV minipools. Distinct from Nf1-mutant tumors, Rb1-mutant tumors are undifferentiated and aberrantly express homeobox gene clusters. The addition of Zc3h13 or Pten mutations altered the gene expression profiles of Rb1 mutants, rendering them more resistant to temozolomide. Our study provides a functional landscape of gliomagenesis suppressors in vivo

The SAMI Galaxy Survey: Early Data Release

We present the Early Data Release of the Sydney–AAO Multi-object Integral field spectrograph (SAMI) Galaxy Survey. The SAMI Galaxy Survey is an ongoing integral field spectroscopic survey of _3400 low-redshift (z < 0:12) galaxies, covering galaxies in the field and in groups within the Galaxy And Mass Assembly (GAMA) survey regions, and a sample of galaxies in clusters. In the Early Data Release, we publicly release the fully calibrated datacubes for a representative selection of 107 galaxies drawn from the GAMA regions, along with information about these galaxies from the GAMA catalogues. All datacubes for the Early Data Release galaxies can be downloaded individually or as a set from the SAMI Galaxy Survey website. In this paper we also assess the quality of the pipeline used to reduce the SAMI data, giving metrics that quantify its performance at all stages in processing the raw data into calibrated datacubes. The pipeline gives excellent results throughout, with typical sky subtraction residuals in the continuum of 0.9–1.2 per cent, a relative flux calibration uncertainty of 4.1 per cent (systematic) plus 4.3 per cent (statistical), and atmospheric dispersion removed with an accuracy of 0:0009, less than a fifth of a spaxel

The SAMI Galaxy Survey: Early Data Release

We present the Early Data Release of the Sydney–AAO Multi-object Integral field spectrograph (SAMI) Galaxy Survey. The SAMI Galaxy Survey is an ongoing integral field spectroscopic survey of _3400 low-redshift (z < 0:12) galaxies, covering galaxies in the field and in groups within the Galaxy And Mass Assembly (GAMA) survey regions, and a sample of galaxies in clusters. In the Early Data Release, we publicly release the fully calibrated datacubes for a representative selection of 107 galaxies drawn from the GAMA regions, along with information about these galaxies from the GAMA catalogues. All datacubes for the Early Data Release galaxies can be downloaded individually or as a set from the SAMI Galaxy Survey website. In this paper we also assess the quality of the pipeline used to reduce the SAMI data, giving metrics that quantify its performance at all stages in processing the raw data into calibrated datacubes. The pipeline gives excellent results throughout, with typical sky subtraction residuals in the continuum of 0.9–1.2 per cent, a relative flux calibration uncertainty of 4.1 per cent (systematic) plus 4.3 per cent (statistical), and atmospheric dispersion removed with an accuracy of 0:0009, less than a fifth of a spaxel