Measurement of competing pathways in a shock-induced phase transition in zirconium by femtosecond diffraction

The traditional picture of solid-solid phase transformations assumes an ordered parent phase transforms into an ordered daughter phase via a single unique pathway. Zirconium and its prototypical phase transition from hexagonal close-packed (hcp) to simple hexagonal (hex-3) structure has generated considerable controversy over several decades regarding which mechanism mediates the transformation. However, a lack of in situ measurements over the relevant atomistic timescales has hindered our ability to identify the true pathway. In this study, we exploit femtosecond X-ray diffraction coupled with nanosecond laser compression to give unprecedented insights into the complexities of how materials transform at the lattice level. We observe single-crystal zirconium changing from hcp to a hex-3 structure via not one but three competing pathways simultaneously. Concurrently, we also observe a broad diffuse background underlying the sharp Bragg diffraction during the transition. We corroborate our observation of the diffuse signal with multimillion-atom molecular dynamics simulations using a machine-learned interatomic potential. Our study demonstrates that the traditional mechanistic view of transitions may fail for even an elemental metal and that the mechanisms by which materials transform are far more intricate than generally thought

Community level digital mental health interventions:A policy and practice brief

The prevalence of mental ill-health is increasing worldwide and brings adverse consequences at both the individual and societal level. Treatments and interventions for the symptoms that represent mental health conditions may target biological, behavioural and cognitive factors. Traditionally, treatments have included psychotropic medication, and/or psychological therapies which are delivered on a one to one or group basis. Both have a high economic cost, and efficacy varies. In addition, help seeking behaviour is impacted by stigma, symptom recognition &amp; understanding, and a host of factors associated with the disorders themselves, such as avoidance behaviour. The delivery of face-to-face interventions for those who are most marginalised and most at risk from mental ill-health, can also be impacted by barriers, such as knowledge of the services available and time, connectivity or travel constraints. The research presented here is co-produced with service providers, end users and academic experts across the disciplines of psychology, business, medicine, healthcare, interaction design and computer science. This briefing is based on the findings from our research programme on a community level digital mental health intervention.<br/

The skin is a significant but overlooked anatomical reservoir for vector-borne African trypanosomes

International audienceThe role of mammalian skin in harbouring and transmitting arthropod-borne protozoan parasites has been overlooked for decades as these pathogens have been regarded primarily as blood-dwelling organisms. Intriguingly, infections with low or undetected blood parasites are common, particularly in the case of Human African Trypanosomiasis caused by Trypanosoma brucei gambiense. We hypothesise, therefore, the skin represents an anatomic reservoir of infection. Here we definitively show that substantial quantities of trypanosomes exist within the skin following experimental infection, which can be transmitted to the tsetse vector, even in the absence of detectable parasitaemia. Importantly, we demonstrate the presence of extravascular parasites in human skin biopsies from undiagnosed individuals. The identification of this novel reservoir requires a re-evaluation of current diagnostic methods and control policies. More broadly, our results indicate that transmission is a key evolutionary force driving parasite extravasation that could further result in tissue invasion-dependent pathology

Multidisciplinary Baseline Assessment of Homosexual Men with and without Human Immunodeficiency Virus Infection. I. Overview of Study Design

Although much is known about the virus believed by most experts to be the cause of the acquired immunodeficiency syndrome and about its pathogenic actions, major areas of ignorance remain. Among these are the reasons for the varying time between infection with human immunodeficiency virus and development of acquired imunodeficiency syndrome, the relationship between neurologic and medical aspects of the disease, the time course of neuropsychological findings, and the prevalence of psychiatric morbidity. We assessed 124 homosexual men who were positive for human immunodeficiency virus and 84 who were negative for the virus. In this article we describe the study design, method of recruitment, and medical and demographic characteristics of the cohort, which will be followed up for 5 years

A structural study of hcp and liquid iron under shock compression up to 275 GPa

We combine nanosecond laser shock compression with \emph{in-situ} picosecond X-ray diffraction to provide structural data on iron up to 275 GPa. We constrain the extent of hcp-liquid coexistence, the onset of total melt, and the structure within the liquid phase. Our results indicate that iron, under shock compression, melts completely by 258(8) GPa. A coordination number analysis indicates that iron is a simple liquid at these pressure-temperature conditions. We also perform texture analysis between the ambient body-centered-cubic (bcc) $\alpha$, and the hexagonal-closed-packed (hcp) high-pressure $\epsilon-$phase. We rule out the Rong-Dunlop orientation relationship (OR) between the $\alpha$ and $\epsilon-$phases. However, we cannot distinguish between three other closely related ORs: Burger's, Mao-Bassett-Takahashi, and Potter's OR. The solid-liquid coexistence region is constrained from a melt onset pressure of 225(3) GPa from previously published sound speed measurements and full melt (246.5(1.8)-258(8) GPa) from X-ray diffraction measurements, with an associated maximum latent heat of melting of 623 J/g. This value is lower than recently reported theoretical estimates and suggests that the contribution to the earth's geodynamo energy budget from heat release due to freezing of the inner core is smaller than previously thought. Melt pressures for these nanosecond shock experiments are consistent with gas gun shock experiments that last for microseconds, indicating that the melt transition occurs rapidly

The skin is a significant but overlooked anatomical reservoir for vector-borne African trypanosomes

The role of mammalian skin in harbouring and transmitting arthropod-borne protozoan parasites has been overlooked for decades as these pathogens have been regarded primarily as blood-dwelling organisms. Intriguingly, infections with low or undetected blood parasites are common, particularly in the case of Human African Trypanosomiasis caused by Trypanosoma brucei gambiense. We hypothesise, therefore, the skin represents an anatomic reservoir of infection. Here we definitively show that substantial quantities of trypanosomes exist within the skin following experimental infection, which can be transmitted to the tsetse vector, even in the absence of detectable parasitaemia. Importantly, we demonstrate the presence of extravascular parasites in human skin biopsies from undiagnosed individuals. The identification of this novel reservoir requires a re-evaluation of current diagnostic methods and control policies. More broadly, our results indicate that transmission is a key evolutionary force driving parasite extravasation that could further result in tissue invasion-dependent pathology

Spatial-genetic structuring in a red-breasted merganser (Mergus serrator) colony in the Canadian Maritimes

The clustering of kin is widespread across the animal kingdom and two of the primary mechanisms underlying the formation of these patterns in adult kin are (1) philopatric tendencies and (2) actively maintained kin associations. Using polymorphic microsatellites, we had set out to characterize the level of genetic-spatial organization within a colony of female red-breasted mergansers (Mergus serrator) breeding on a series of small barrier islands in Kouchibouguac National Park, NB, Canada. Additionally, using nesting data from this colony, we explored possibilities for the existence of kin associations and/or cooperative interactions between these individuals; specifically in the form of the synchronization of breeding activities (i.e., incubation initiation). Our results include: (1) the detection of broad-scale genetic structuring over the entire colony, as females nesting on separate islands were to some extent genetically distinct; (2) the detection of weak, yet significant, positive spatial autocorrelation of kin at the fine scale, but only in the more densely-populated areas of this colony; and (3) the synchrony of breeding activities among proximally nesting females, apart from any factors of relatedness. While these results confirm the existence of genetic-spatial organization within this colony, the underlying mechanisms producing such a signal are inconclusive

Using Non-Homogeneous Models of Nucleotide Substitution to Identify Host Shift Events: Application to the Origin of the 1918 ‘Spanish’ Influenza Pandemic Virus

Nonhomogeneous Markov models of nucleotide substitution have received scant attention. Here we explore the possibility of using nonhomogeneous models to identify host shift nodes along phylogenetic trees of pathogens evolving in different hosts. It has been noticed that influenza viruses show marked differences in nucleotide composition in human and avian hosts. We take advantage of this fact to identify the host shift event that led to the 1918 ‘Spanish’ influenza. This disease killed over 50 million people worldwide, ranking it as the deadliest pandemic in recorded history. Our model suggests that the eight RNA segments which eventually became the 1918 viral genome were introduced into a mammalian host around 1882–1913. The viruses later diverged into the classical swine and human H1N1 influenza lineages around 1913–1915. The last common ancestor of human strains dates from February 1917 to April 1918. Because pigs are more readily infected with avian influenza viruses than humans, it would seem that they were the original recipient of the virus. This would suggest that the virus was introduced into humans sometime between 1913 and 1918

100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care — Preliminary Report

BACKGROUND: The U.K. 100,000 Genomes Project is in the process of investigating the role of genome sequencing in patients with undiagnosed rare diseases after usual care and the alignment of this research with health care implementation in the U.K. National Health Service. Other parts of this project focus on patients with cancer and infection. METHODS: We conducted a pilot study involving 4660 participants from 2183 families, among whom 161 disorders covering a broad spectrum of rare diseases were present. We collected data on clinical features with the use of Human Phenotype Ontology terms, undertook genome sequencing, applied automated variant prioritization on the basis of applied virtual gene panels and phenotypes, and identified novel pathogenic variants through research analysis. RESULTS: Diagnostic yields varied among family structures and were highest in family trios (both parents and a proband) and families with larger pedigrees. Diagnostic yields were much higher for disorders likely to have a monogenic cause (35%) than for disorders likely to have a complex cause (11%). Diagnostic yields for intellectual disability, hearing disorders, and vision disorders ranged from 40 to 55%. We made genetic diagnoses in 25% of the probands. A total of 14% of the diagnoses were made by means of the combination of research and automated approaches, which was critical for cases in which we found etiologic noncoding, structural, and mitochondrial genome variants and coding variants poorly covered by exome sequencing. Cohortwide burden testing across 57,000 genomes enabled the discovery of three new disease genes and 19 new associations. Of the genetic diagnoses that we made, 25% had immediate ramifications for clinical decision making for the patients or their relatives. CONCLUSIONS: Our pilot study of genome sequencing in a national health care system showed an increase in diagnostic yield across a range of rare diseases. (Funded by the National Institute for Health Research and others.)