Mosaic effectiveness: measuring the impact of novel PrEP methods

Various ongoing trials seek to evaluate long-acting pre-exposure prophylaxis (PrEP) agents by showing that they are non-inferior to daily oral tenofovir disoproxil fumarate and emtricitabine. Trials comparing oral PrEP to new methods examine effectiveness in a setting where only one or the other is provided; however, a new product will probably be delivered in a context where oral PrEP is also available. The effectiveness of a new PrEP product is best measured by its potential effect in a context that also includes oral tenofovir disoproxil fumarate and emtricitabine as an option. We offer an alternative standard for long-acting products—a measure of the effectiveness of the new product in addition to oral tenofovir disoproxil fumarate and emtricitabine as compared with oral PrEP alone. We term this measure mosaic effectiveness. We illustrate scenarios where a novel product can fail to show non-inferiority but show substantial mosaic effectiveness, thus implying the public health value of the novel product even if it is less effective than oral PrEP. Regulatory standards should consider mosaic effectiveness, not just comparative effectiveness. We assert that measurements that combine rigor with public health relevance can accelerate progress against the HIV epidemic

Photoconductive Arrays on Insulating Substrates for High-Field Terahertz Generation

We report on the design, fabrication and characterisation of large-area photoconductive THz array structures, consisting of a thin LT-GaAs active region transferred to an insulating substrate using a wafer-scale bonding process. The electrically insulating, transparent substrate reduces the parasitic currents in the devices, allowing peak THz-fields as high as 120 kV cm−1 to be generated over a bandwidth >5 THz. These results are achieved using lower pulse energies than demanded by conventional photoconductive arrays and other popular methods of generating high-field THz radiation. Two device sizes are fully characterised and the emission properties are compared to generation by optical rectification in ZnTe. The device can be operated in an optically saturated regime in order to suppress laser noise

On the Relation Between Jupiter's Aurora and the Dawnside Current Sheet

Jupiter's auroral emission is a spectacular phenomenon that provides insight into energy release processes related to the coupling of its magnetosphere and ionosphere. This energy release is influenced by solar wind conditions. Using joint observations from Juno and the Hubble Space Telescope (HST), we statistically investigate the relationship between auroral power and current sheet variations under different solar wind conditions. In this study, we reveal that during global main auroral brightening events that are closely connected to solar wind compressions, the dawn side current sheet is substantially thinner than during times when a quiet auroral morphology is present. Furthermore, the total current intensity in the current sheet is found to increase under solar wind compression conditions compared to the quiet period. These findings provide important observational evidence for how magnetospheric dynamics driven by solar wind behavior affect auroral activity, deepening our understanding of the coupling between Jupiter's magnetosphere and ionosphere

High-Speed Modulation of a Terahertz Quantum Cascade Laser by Coherent Acoustic Phonon Pulses

The fast modulation of lasers is a fundamental requirement for applications in optical communications, high-resolution spectroscopy and metrology. In the terahertz-frequency range, the quantum-cascade laser (QCL) is a high-power source with the potential for high-frequency modulation. However, conventional electronic modulation is limited fundamentally by parasitic device impedance, and so alternative physical processes must be exploited to modulate the QCL gain on ultrafast timescales. Here, we demonstrate an alternative mechanism to modulate the emission from a QCL device, whereby optically-generated acoustic phonon pulses are used to perturb the QCL bandstructure, enabling fast amplitude modulation that can be controlled using the QCL drive current or strain pulse amplitude, to a maximum modulation depth of 6% in our experiment. We show that this modulation can be explained using perturbation theory analysis. While the modulation rise-time was limited to ~800 ps by our measurement system, theoretical considerations suggest considerably faster modulation could be possible

High-speed modulation of a terahertz-frequency quantum-cascade laser using coherent acoustic phonon pulses

We demonstrate a new method for high-speed modulation of the electron transport and photon generation within a terahertz-frequency quantum-cascade laser (THz QCL). An amplified femtosecond laser is used to generate coherent acoustic-phonon pulses, which are injected into the device, resulting in an electronic bandstructure perturbation, with ~1-ns rise-time. The corresponding change in optical gain allows up to ~6% amplitude modulation, with results explained accurately using a perturbation-theory model

Language abilities in children with autism and language impairment: using narrative as a additional source of clinical information

Autistic Spectrum Disorder (ASD) and Specific Language Impairment (SLI) are disorders of communication that are sometimes thought to show similar structural language difficulties. Recent research has even suggested that they might be aetiologically related. However, it may be that standardized language tasks are not sensitive enough to detect similarities and differences accurately. This study involved 26 Greek children with either ASD or SLI and compared them on standardized measures of structural and pragmatic language as well as using a structured narrative task. Children with ASD were more impaired on receptive but not expressive scores from standardized language tests. In contrast, narrative measures showed significantly poorer ASD performance in expressive skills involving wider story-telling skill and in some sentence-level skills, in particular referencing, compared to peers with SLI. ASD and SLI groups also showed different relationships between structural language and other measures. The data suggests that narrative is a useful tool for revealing qualitative differences in language between overlapping communication disorders both at the clinical and theoretical level, since it provides information that is lost in more formalized testing. This may be particularly true where norms are not available or testing is difficult

MaxMin Linear Initialization for Fuzzy C-Means

International audienceClustering is an extensive research area in data science. The aim of clustering is to discover groups and to identify interesting patterns in datasets. Crisp (hard) clustering considers that each data point belongs to one and only one cluster. However, it is inadequate as some data points may belong to several clusters, as is the case in text categorization. Thus, we need more flexible clustering. Fuzzy clustering methods, where each data point can belong to several clusters, are an interesting alternative. Yet, seeding iterative fuzzy algorithms to achieve high quality clustering is an issue. In this paper, we propose a new linear and efficient initialization algorithm MaxMin Linear to deal with this problem. Then, we validate our theoretical results through extensive experiments on a variety of numerical real-world and artificial datasets. We also test several validity indices, including a new validity index that we propose, Transformed Standardized Fuzzy Difference (TSFD)

Postcopulatory Sexual Selection Is Associated with Reduced Variation in Sperm Morphology

The evolutionary role of postcopulatory sexual selection in shaping male reproductive traits, including sperm morphology, is well documented in several taxa. However, previous studies have focused almost exclusively on the influence of sperm competition on variation among species. In this study we tested the hypothesis that intraspecific variation in sperm morphology is driven by the level of postcopulatory sexual selection in passerine birds.Using two proxy measures of sperm competition level, (i) relative testes size and (ii) extrapair paternity level, we found strong evidence that intermale variation in sperm morphology is negatively associated with the degree of postcopulatory sexual selection, independently of phylogeny.Our results show that the role of postcopulatory sexual selection in the evolution of sperm morphology extends to an intraspecific level, reducing the variation towards what might be a species-specific 'optimum' sperm phenotype. This finding suggests that while postcopulatory selection is generally directional (e.g., favouring longer sperm) across avian species, it also acts as a stabilising evolutionary force within species under intense selection, resulting in reduced variation in sperm morphology traits. We discuss some potential evolutionary mechanisms for this pattern

Sponge non-metastatic Group I Nme gene/protein - structure and function is conserved from sponges to humans

<p>Abstract</p> <p>Background</p> <p>Nucleoside diphosphate kinases NDPK are evolutionarily conserved enzymes present in Bacteria, Archaea and Eukarya, with human Nme1 the most studied representative of the family and the first identified metastasis suppressor. Sponges (Porifera) are simple metazoans without tissues, closest to the common ancestor of all animals. They changed little during evolution and probably provide the best insight into the metazoan ancestor's genomic features. Recent studies show that sponges have a wide repertoire of genes many of which are involved in diseases in more complex metazoans. The original function of those genes and the way it has evolved in the animal lineage is largely unknown. Here we report new results on the metastasis suppressor gene/protein homolog from the marine sponge <it>Suberites domuncula</it>, NmeGp1Sd. The purpose of this study was to investigate the properties of the sponge Group I Nme gene and protein, and compare it to its human homolog in order to elucidate the evolution of the structure and function of Nme.</p> <p>Results</p> <p>We found that sponge genes coding for Group I Nme protein are intron-rich. Furthermore, we discovered that the sponge NmeGp1Sd protein has a similar level of kinase activity as its human homolog Nme1, does not cleave negatively supercoiled DNA and shows nonspecific DNA-binding activity. The sponge NmeGp1Sd forms a hexamer, like human Nme1, and all other eukaryotic Nme proteins. NmeGp1Sd interacts with human Nme1 in human cells and exhibits the same subcellular localization. Stable clones expressing sponge NmeGp1Sd inhibited the migratory potential of CAL 27 cells, as already reported for human Nme1, which suggests that Nme's function in migratory processes was engaged long before the composition of true tissues.</p> <p>Conclusions</p> <p>This study suggests that the ancestor of all animals possessed a NmeGp1 protein with properties and functions similar to evolutionarily recent versions of the protein, even before the appearance of true tissues and the origin of tumors and metastasis.</p