Project ASPIRE: A feasibility randomized controlled trial of a brief intervention for reducing risk of depression and alcohol-related harms among South African adolescents.

OBJECTIVE: Brief interventions could reduce adolescents' risk of depression and alcohol-related harms, but evidence of their feasibility and acceptability for low-and middle-income countries is lacking. To address this gap, we conducted a feasibility trial of the ASPIRE intervention, a four-session multi-component counselling intervention for South African adolescents. METHOD: We recruited 117 adolescents who met our inclusion criteria. Participants were randomly assigned to the ASPIRE intervention or a comparison condition. Outcomes were assessed at baseline, six-week, and three-month post-randomization time points. Primary outcomes were based on feasibility of study procedures and intervention delivery (assessed on seven predetermined progression criteria). Clinical outcomes (risk of depression and alcohol harms) were secondary. RESULTS: Despite modifications to all study procedures arising from Covid-19 restrictions, five of the seven key progression criteria were fully met, including: feasibility of data collection and outcome measures, counsellor competencies, randomization and blinding, adverse advents, and acceptability of the intervention. The progression criterion for recruitment and intervention retention were not fully met. CONCLUSION: Findings suggest that the ASPIRE intervention was generally feasible to deliver and acceptable to adolescents. However, modifications to the trial design and intervention delivery are needed to optimize the validity of a definitive randomized controlled trial of the ASPIRE intervention.

Humpback whale song revolutions continue to spread from the central into the eastern South Pacific.

Cultural transmission of behaviour is an important aspect of many animal communities ranging from humans to birds. Male humpback whales (Megaptera novaeangliae) sing a repetitive, stereotyped, socially learnt and culturally transmitted song display that slowly evolves each year. Most males within a population sing the same, slow-evolving song type; but in the South Pacific, song 'revolutions' have led to rapid and complete replacement of one song type by another introduced from a neighbouring population. Songs spread eastwards, from eastern Australia to French Polynesia, but the easterly extent of this transmission was unknown. Here, we investigated whether song revolutions continue to spread from the central (French Polynesia) into the eastern (Ecuador) South Pacific region. Similarity analyses using three consecutive years of song data (2016-2018) revealed that song themes recorded in 2016-2018 French Polynesian song matched song themes sung in 2018 Ecuadorian song, suggesting continued easterly transmission of song to Ecuador, and vocal connectivity across the entire South Pacific Ocean basin. This study demonstrates songs first identified in western populations can be transmitted across the entire South Pacific, supporting the potential for a circumpolar Southern Hemisphere cultural transmission of song and a vocal culture rivalled in its extent only by our own.

Fundamental dissipation due to bound fermions in the zero-temperature limit.

The ground state of a fermionic condensate is well protected against perturbations in the presence of an isotropic gap. Regions of gap suppression, surfaces and vortex cores which host Andreev-bound states, seemingly lift that strict protection. Here we show that in superfluid 3He the role of bound states is more subtle: when a macroscopic object moves in the superfluid at velocities exceeding the Landau critical velocity, little to no bulk pair breaking takes place, while the damping observed originates from the bound states covering the moving object. We identify two separate timescales that govern the bound state dynamics, one of them much longer than theoretically anticipated, and show that the bound states do not interact with bulk excitations.

Migratory convergence facilitates cultural transmission of humpback whale song.

Cultural transmission of behaviour is important in a wide variety of vertebrate taxa from birds to humans. Vocal traditions and vocal learning provide a strong foundation for studying culture and its transmission in both humans and cetaceans. Male humpback whales (Megaptera novaeangliae) perform complex, culturally transmitted song displays that can change both evolutionarily (through accumulations of small changes) or revolutionarily (where a population rapidly adopts a novel song). The degree of coordination and conformity underlying song revolutions makes their study of particular interest. Acoustic contact on migratory routes may provide a mechanism for cultural revolutions of song, yet these areas of contact remain uncertain. Here, we compared songs recorded from the Kermadec Islands, a recently discovered migratory stopover, to multiple South Pacific wintering grounds. Similarities in song themes from the Kermadec Islands and multiple wintering locations (from New Caledonia across to the Cook Islands) suggest a location allowing cultural transmission of song eastward across the South Pacific, active song learning (hybrid songs) and the potential for cultural convergence after acoustic isolation at the wintering grounds. As with the correlations in humans between genes, communication and migration, the migration patterns of humpback whales are written into their songs.

Oceanographic barriers, divergence, and admixture: Phylogeography and taxonomy of two putative subspecies of short-finned pilot whale.

Genomic phylogeography plays an important role in describing evolutionary processes and their geographic, ecological, or cultural drivers. These drivers are often poorly understood in marine environments, which have fewer obvious barriers to mixing than terrestrial environments. Taxonomic uncertainty of some taxa (e.g., cetaceans), due to the difficulty in obtaining morphological data, can hamper our understanding of these processes. One such taxon, the short-finned pilot whale, is recognized as a single global species but includes at least two distinct morphological forms described from stranding and drive hunting in Japan, the "Naisa" and "Shiho" forms. Using samples (n = 735) collected throughout their global range, we examine phylogeographic patterns of divergence by comparing mitogenomes and nuclear SNP loci. Our results suggest three types within the species: an Atlantic Ocean type, a western/central Pacific and Indian Ocean (Naisa) type, and an eastern Pacific Ocean and northern Japan (Shiho) type. mtDNA control region differentiation indicates these three types form two subspecies, separated by the East Pacific Barrier: Shiho short-finned pilot whale, in the eastern Pacific Ocean and northern Japan, and Naisa short-finned pilot whale, throughout the remainder of the species' distribution. Our data further indicate two diverging populations within the Naisa subspecies, in the Atlantic Ocean and western/central Pacific and Indian Oceans, separated by the Benguela Barrier off South Africa. This study reveals a process of divergence and speciation within a globally-distributed, mobile marine predator, and indicates the importance of the East Pacific Barrier to this evolutionary process.

The devil is in the detail: Quantifying vocal variation in a complex, multi-levelled, and rapidly evolving display.

Identifying and quantifying variation in vocalizations is fundamental to advancing our understanding of processes such as speciation, sexual selection, and cultural evolution. The song of the humpback whale (Megaptera novaeangliae) presents an extreme example of complexity and cultural evolution. It is a long, hierarchically structured vocal display that undergoes constant evolutionary change. Obtaining robust metrics to quantify song variation at multiple scales (from a sound through to population variation across the seascape) is a substantial challenge. Here, the authors present a method to quantify song similarity at multiple levels within the hierarchy. To incorporate the complexity of these multiple levels, the calculation of similarity is weighted by measurements of sound units (lower levels within the display) to bridge the gap in information between upper and lower levels. Results demonstrate that the inclusion of weighting provides a more realistic and robust representation of song similarity at multiple levels within the display. This method permits robust quantification of cultural patterns and processes that will also contribute to the conservation management of endangered humpback whale populations, and is applicable to any hierarchically structured signal sequence.

Operating Nanobeams in a Quantum Fluid.

Microelectromechanical (MEMS) and nanoelectromechanical systems (NEMS) are ideal candidates for exploring quantum fluids, since they can be manufactured reproducibly, cover the frequency range from hundreds of kilohertz up to gigahertz and usually have very low power dissipation. Their small size offers the possibility of probing the superfluid on scales comparable to, and below, the coherence length. That said, there have been hitherto no successful measurements of NEMS resonators in the liquid phases of helium. Here we report the operation of doubly-clamped aluminium nanobeams in superfluid 4He at temperatures spanning the superfluid transition. The devices are shown to be very sensitive detectors of the superfluid density and the normal fluid damping. However, a further and very important outcome of this work is the knowledge that now we have demonstrated that these devices can be successfully operated in superfluid 4He, it is straightforward to apply them in superfluid 3He which can be routinely cooled to below 100 µK. This brings us into the regime where nanomechanical devices operating at a few MHz frequencies may enter their mechanical quantum ground state.

Song hybridization events during revolutionary song change provide insights into cultural transmission in humpback whales.

Cultural processes occur in a wide variety of animal taxa, from insects to cetaceans. The songs of humpback whales are one of the most striking examples of the transmission of a cultural trait and social learning in any nonhuman animal. To understand how songs are learned, we investigate rare cases of song hybridization, where parts of an existing song are spliced with a new one, likely before an individual totally adopts the new song. Song unit sequences were extracted from over 9,300 phrases recorded during two song revolutions across the South Pacific Ocean, allowing fine-scale analysis of composition and sequencing. In hybrid songs the current and new songs were spliced together in two specific ways: (i) singers placed a single hybrid phrase, in which content from both songs were combined, between the two song types when transitioning from one to the other, and/or (ii) singers spliced complete themes from the revolutionary song into the current song. Sequence analysis indicated that both processes were governed by structural similarity rules. Hybrid phrases or theme substitutions occurred at points in the songs where both songs contained "similar sounds arranged in a similar pattern." Songs appear to be learned as segments (themes/phrase types), akin to birdsong and human language acquisition, and these can be combined in predictable ways if the underlying structural pattern is similar. These snapshots of song change provide insights into the mechanisms underlying song learning in humpback whales, and comparative perspectives on the evolution of human language and culture.

Population structure of humpback whales in the western and central South Pacific Ocean as determined by vocal exchange among populations.

For cetaceans, population structure is traditionally determined by molecular genetics or photographically identified individuals. Acoustic data, however, has provided information on movement and population structure with less effort and cost than traditional methods in an array of taxa. Male humpback whales (Megaptera novaeangliae) produce a continually evolving vocal sexual display, or song, that is similar among all males in a population. The rapid cultural transmission (the transfer of information or behavior between conspecifics through social learning) of different versions of this display between distinct but interconnected populations in the western and central South Pacific region presents a unique way to investigate population structure based on the movement dynamics of a song (acoustic) display. Using 11 years of data, we investigated an acoustically based population structure for the region by comparing stereotyped song sequences among populations and years. We used the Levenshtein distance technique to group previously defined populations into (vocally based) clusters based on the overall similarity of their song display in space and time. We identified the following distinct vocal clusters: western cluster, 1 population off eastern Australia; central cluster, populations around New Caledonia, Tonga, and American Samoa; and eastern region, either a single cluster or 2 clusters, one around the Cook Islands and the other off French Polynesia. These results are consistent with the hypothesis that each breeding aggregation represents a distinct population (each occupied a single, terminal node) in a metapopulation, similar to the current understanding of population structure based on genetic and photo-identification studies. However, the central vocal cluster had higher levels of song-sharing among populations than the other clusters, indicating that levels of vocal connectivity varied within the region. Our results demonstrate the utility and value of using culturally transmitted vocal patterns as a way of defining connectivity to infer population structure. We suggest vocal patterns be incorporated by the International Whaling Commission in conjunction with traditional methods in the assessment of structure.

Estructura Poblacional de las Yubartas en el Centro y Occidente del Sur del Océano Pacífico, Determinada por el Intercambio Vocal entre las Poblaciones Resumen La estructura poblacional de los cetáceos se determina tradicionalmente por medio de genética molecular o individuos identificados fotográficamente. Sin embargo, los datos acústicos han proporcionado información sobre el movimiento y la estructura poblacional de una variedad de taxones con menos esfuerzo y menos costo que los métodos tradicionales. Las yubartas macho (Megaptera novaeangliae) producen una demostración vocal sexual, o canto, en continua evolución que es similar entre todos los machos en una población. La transmisión cultural rápida (la transferencia de información o comportamientos entre co-específicos por medio del aprendizaje social) de diferentes versiones de esta demostración entre poblaciones distintas pero interconectadas en el centro y occidente en la región del sur del Pacífico presenta una manera única para investigar la estructura poblacional con base en las dinámicas de movimiento de la demostración del canto (acústico). Al usar once años de datos, con base en la acústica investigamos a una estructura poblacional de la región al comparar secuencias estereotipadas de cantos entre las poblaciones y los años. Usamos la técnica de la distancia Levenshtein para agrupar poblaciones previamente definidas en grupos (con base vocal) basados en la similitud general de su canto en el espacio y el tiempo. Identificamos a los siguientes grupos vocales perceptibles: grupo occidental, una población al este de Australia; grupo central, poblaciones alrededor de Nueva Caledonia, Tonga y Samoa Americana; y región oriental, ya sea un grupo único o dos grupos, uno alrededor de las Islas Cook y el otro cerca de la Polinesia Francesa. Estos resultados son consistentes con la hipótesis de que cada conjunto reproductivo representa a una población distinta (cada una ocupó un nodo terminal único) en una meta-población, similar al entendimiento actual de la estructura poblacional con base en los estudios genéticos y de foto-identificación. Sin embargo, el grupo vocal central tuvo niveles más altos de cantos compartidos entre las poblaciones que en los otros grupos, lo que indica que los niveles de conectividad vocal variaron dentro de la región. Nuestros resultados demuestran la utilidad y el valor de usar patrones vocales transmitidos culturalmente como una forma de definir la conectividad para inferir la estructura poblacional. Sugerimos que los patrones vocales sean incorporados por la Comisión Internacional de Caza de Ballenas en conjunto con los métodos tradicionales de evaluación de la estructura.

Quantifying humpback whale song sequences to understand the dynamics of song exchange at the ocean basin scale.

Humpback whales have a continually evolving vocal sexual display, or "song," that appears to undergo both evolutionary and "revolutionary" change. All males within a population adhere to the current content and arrangement of the song. Populations within an ocean basin share similarities in their songs; this sharing is complex as multiple variations of the song (song types) may be present within a region at any one time. To quantitatively investigate the similarity of song types, songs were compared at both the individual singer and population level using the Levenshtein distance technique and cluster analysis. The highly stereotyped sequences of themes from the songs of 211 individuals from populations within the western and central South Pacific region from 1998 through 2008 were grouped together based on the percentage of song similarity, and compared to qualitatively assigned song types. The analysis produced clusters of highly similar songs that agreed with previous qualitative assignments. Each cluster contained songs from multiple populations and years, confirming the eastward spread of song types and their progressive evolution through the study region. Quantifying song similarity and exchange will assist in understanding broader song dynamics and contribute to the use of vocal displays as population identifiers.

Dynamic horizontal cultural transmission of humpback whale song at the ocean basin scale.

Cultural transmission, the social learning of information or behaviors from conspecifics, is believed to occur in a number of groups of animals, including primates, cetaceans, and birds. Cultural traits can be passed vertically (from parents to offspring), obliquely (from the previous generation via a nonparent model to younger individuals), or horizontally (between unrelated individuals from similar age classes or within generations). Male humpback whales (Megaptera novaeangliae) have a highly stereotyped, repetitive, and progressively evolving vocal sexual display or "song" that functions in sexual selection (through mate attraction and/or male social sorting). All males within a population conform to the current version of the display (song type), and similarities may exist among the songs of populations within an ocean basin. Here we present a striking pattern of horizontal transmission: multiple song types spread rapidly and repeatedly in a unidirectional manner, like cultural ripples, eastward through the populations in the western and central South Pacific over an 11-year period. This is the first documentation of a repeated, dynamic cultural change occurring across multiple populations at such a large geographic scale.

Molecular basis of chemosensitivity of platinum pre-treated ovarian cancer to chemotherapy.

BACKGROUND: Ovarian cancer shows considerable heterogeneity in its sensitivity to chemotherapy both clinically and in vitro. This study tested the hypothesis that the molecular basis of this difference lies within the known resistance mechanisms inherent to these patients' tumours. METHODS: The chemosensitivity of a series of 31 ovarian tumours, all previously treated with platinum-based chemotherapy, was assessed using the ATP-based tumour chemosensitivity assay (ATP-TCA) and correlated with resistance gene expression measured by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) in a TaqMan Array following extraction of mRNA from formalin-fixed paraffin-embedded tissue. The results were standardised against a housekeeping gene (PBGD), and assessed by multiple linear regression. RESULTS: Predictive multiple linear regression models were derived for four single agents (cisplatin, gemcitabine, topotecan, and treosulfan), and for the combinations of cisplatin+gemcitabine and treosulfan+gemcitabine. Particularly strong correlations were obtained for cisplatin, gemcitabine, topotecan, and treosulfan+gemcitabine. No individual gene expression showed direct correlation with activity in the ATP-TCA. Genes involved in DNA repair and apoptosis were strongly represented, with some drug pumps also involved. CONCLUSION: The chemosensitivity of ovarian cancer to drugs is related to the expression of genes involved in sensitivity and resistance mechanisms.

Image reconstructions with the rotating RF coil.

Recent studies have shown that rotating a single RF transceive coil (RRFC) provides a uniform coverage of the object and brings a number of hardware advantages (i.e. requires only one RF channel, averts coil-coil coupling interactions and facilitates large-scale multi-nuclear imaging). Motion of the RF coil sensitivity profile however violates the standard Fourier Transform definition of a time-invariant signal, and the images reconstructed in this conventional manner can be degraded by ghosting artifacts. To overcome this problem, this paper presents Time Division Multiplexed-Sensitivity Encoding (TDM-SENSE), as a new image reconstruction scheme that exploits the rotation of the RF coil sensitivity profile to facilitate ghost-free image reconstructions and reductions in image acquisition time. A transceive RRFC system for head imaging at 2 Tesla was constructed and applied in a number of in vivo experiments. In this initial study, alias-free head images were obtained in half the usual scan time. It is hoped that new sequences and methods will be developed by taking advantage of coil motion.

Stages of homogeneous nucleation in solid isotopic helium mixtures.

We have made pressure and NMR measurements during the evolution of phase separation in solid helium isotopic mixtures. Our observations indicate clearly all three stages of the homogeneous nucleation-growth process: (1) creation of nucleation sites; (2) growth of the new-phase component at these nucleation sites; and (3) coarsening: the dissolution of subcritical droplets with the consequent further late-stage growth of the supercritical droplets. The time exponent for the coarsening, a=1/3, is consistent with the conserved order parameter Lifshitz-Slezov evaporation-condensation mechanism.

A genome segment on mouse chromosome 12 determines maxillary growth.

The primary and modifier genes that regulate normal maxillofacial development are unknown. Previous quantitative trait locus (QTL) analyses using the F2 progeny of 2 mouse strains, DBA/2J (short snout/wide face) and C57BL/6J (long snout/narrow face), revealed a significant logarithm-of-odds (LOD) score for snout length on mouse chromosome 12 at 44 centimorgan (cM). We further sought to validate this locus contributing to anterior-posterior dimensions of the upper mid-face at the D12Mit7 marker in a 44-centimorgan portion of chromosome 12. Congenic mice carrying introgressed DNA from DBA/2J on a C57BL/6J background were selected for submental vertex cephalometric imaging. Results confirmed QTLs, determining that short snout length (P < 0.05) and face width relative to snout length (P < 0.01) were present in the 44-cM region of chromosome 12. We conclude that one or more genes contributing to the shape of the maxillary complex are located near 44 cM of mouse chromosome 12.

Development and usefulness of an instrument for the standard description and comparison of services for disabilities (DESDE).

OBJECTIVE: Mental health research has made significant progress in international comparison and instrument development. This study reports the adaptation of the European Service Mapping Schedule (ESMS) to the assessment of services for persons with disabilities. METHOD: Qualitative groups were used to develop the Description and Evaluation of Services for Disabilities in Europe (DESDE). The psychometric analysis of DESDE covered: feasibility, inter-rater reliability, descriptive validity and internal validity. A demonstration study was also carried out. RESULTS: Compared to the original ESMS, a new main branch and several sub-branches were added. We identified 826 services for persons with disabilities, which provided 1284 main types of care. The feasibility and reliability was good for the majority of codes. Only 6% of services were not properly classified. The Boolean factor analysis supported the internal validity of DESDE. CONCLUSION: DESDE is a useful and reliable instrument for the assessment of services for persons with disabilities.

Spinodal decomposition in solid isotopic helium mixtures.

We report the first observations of spinodal decomposition in solid helium isotopic mixtures, using NMR measurements. The experiments were performed at a 3He concentration of 50% where the transition proceeds through the critical point. We used an initial pressure such that the system remained solid. Our observations indicate that the transition occurs by the mechanism of spinodal decomposition and we are able to study its evolution in real time.

Harmonic lasing in a free-electron-laser amplifier.

A method is demonstrated that allows a planar wiggler high-gain Free-Electron-Laser (FEL) amplifier to lase so that the interaction with an odd harmonic of the radiation field dominates that of the fundamental. This harmonic lasing of the FEL is achieved by disrupting the electron interaction with the usually dominant fundamental while allowing that of a harmonic interaction to evolve unhindered. The disruption is achieved by a series of relative phase changes between the electrons and the ponderomotive potentials of both the fundamental and harmonic fields. Such phase changes are relatively easy to implement and some current FEL designs would require little or no structural modification to test the scheme.

Gene therapy in plastic and reconstructive surgery.

Gene therapy has been investigated in many aspects of plastic and reconstructive surgery. These areas ultimately involve various forms of tissue healing and the manipulation of bony and soft tissues to reconstruct defects secondary to neoplastic and congenital disorders and trauma. Most research has been limited to animal studies with the exception of clinical trials on the use of gene therapy in lower leg ulcer healing and as an adjunct to advanced recurrent squamous cell carcinoma of the head and neck. Overall, these preliminary studies have produced optimistic results. With the development of more efficient and safer delivery systems, the application of gene therapy in plastic surgery could become more widespread, especially in combination with tissue engineering technology.

Development of homogeneous high-affinity agonist binding assays for 5-HT2 receptor subtypes.

The serotonin (5-hydroxytryptamine) 5-HT2 receptor subfamily consists of three members, 5-HT2A, 5-HT2B, and 5-HT2C. These receptors share high homology in their amino acid sequence, have similar signaling pathways, and have been indicated to play important roles in feeding, anxiety, aggression, sexual behavior, mood, and pain. Subtype-selective agonists and antagonists have been explored as drugs for hypertension, Parkinson's disease, sleep disorders, anxiety, depression, schizophrenia, and obesity. In this study, we report the development of homogeneous agonist binding assays in a scintillation proximity assay (SPA) format to determine the high-affinity binding state of agonist compounds for the human 5-HT2C, 5-HT2A, and 5-HT2B receptors. The 5-HT2 agonist 1-(4- [125I]iodo-2,5-dimethoxyphenyl)-2-aminopropane ([125I]DOI) was used to label the high-affinity sites for the 5-HT2A and 5-HT2C receptors. The high-affinity sites for the 5-HT2B receptor were labeled with [3H]lysergic acid diethylamide. Total receptor expression was determined with the 5-HT2 antagonist [3H]mesulergine for the 5-HT2B and 5-HT2C receptors, and [3H]ketanserin for the 5-HT2A receptor. The agonist high-affinity binding sites accounted for 2.3% (5-HT(2C) receptor), 4.0% (5-HT2A receptor), and 22% (5-HT2B receptor) of the total receptor population. Competition binding studies using known agonists indicated high Z' values of the agonist binding assays in SPA format (Z' > 0.70). The Ki values of 5-HT, (R)(-)DOI, and VER-3323 for the 5-HT2A, 5-HT2B, and 5-HT2C receptors by SPA format were equivalent to published data determined by filtration binding assays. These results indicate that agonist binding assays in SPA format can be easily adapted to a high throughput assay to screen for selective 5-HT2C receptor agonists, as well as for selectivity profiling of the compounds.