Health service utilization by people experiencing homelessness and engaging with community paramedics: a pre-post study.

OBJECTIVES: To compare health service utilization of patients interacting with a mobile integrated health care program consisting of advanced care paramedics delivering community paramedic care to people experiencing homelessness before and after their initial visit. METHODS: ED visits, physician claims, and pharmaceutical dispensations were compared in the year prior to and in the year following the initial community paramedic visit. Administrative databases were linked and utilization rates were calculated and analyzed between periods in this pre-post cohort study. RESULTS: The 1360 community paramedic patients included in this study had no significant change in ED visits (IRR: 1.02) following their initial visit. There were 17,699 ED visits in the pre-period and 18,398 visits in the post-period. There was an observed increase in rates of primary care physician claims (IRR 1.22) and pharmaceutical dispensations from community pharmacies (IRR 1.04). Patients who did not have pharmaceutical dispensations and those without physician claims in the pre-period were significantly less likely to not access these services in the post-period. CONCLUSIONS: In the year following the initial community paramedic visit there were small but significant increases in community-based care utilization of people experiencing homelessness. These data suggest that the continued development and implementation of paramedics as part of an interdisciplinary care team can increase access to care for a traditionally underserved population with complex health needs. Patients would likely benefit from the integration of community paramedics in community-based management that aim to improve access to care following ED visits.

RéSUMé: OBJECTIFS: Comparer l'utilisation des services de santé des patients interagissant avec un programme de soins de santé mobile intégrés composé d'ambulanciers paramédicaux de soins avancés fournissant des soins paramédicaux communautaires aux personnes sans domicile fixe avant et après leur visite initiale. MéTHODES: Les visites aux urgences, les demandes de remboursement des médecins et les prescriptions pharmaceutiques ont été comparées dans l'année précédant et dans l'année suivant la visite initiale du personnel paramédical communautaire. Les bases de données administratives ont été reliées, et les taux d'utilisation ont été calculés et analysés entre les périodes dans cette étude de cohorte avant et après. RéSULTATS: Les 1 360 patients paramédicaux communautaires inclus dans cette étude n'ont pas connu de changement significatif dans les visites aux urgences (IRR : 1,02) après leur visite initiale. Il y a eu 17 699 visites aux urgences dans la pré-période et 18 398 visites dans la post-période. On a observé une augmentation des taux de demandes de remboursement des médecins de soins primaires (IRR : 1,22) et des dispensations de produits pharmaceutiques par les pharmacies communautaires (IRR : 1,04). Les patients qui n'ont pas bénéficié d'une dispensation de produits pharmaceutiques et ceux qui n'ont pas fait l'objet d'une demande de remboursement par un médecin au cours de la période précédente étaient significativement moins susceptibles de ne pas avoir accès à ces services au cours de la période suivante. CONCLUSIONS: Au cours de l'année qui a suivi la première visite du personnel paramédical communautaire, on a constaté une augmentation faible mais significative de l'utilisation des soins communautaires par les personnes sans domicile. Ces données suggèrent que le développement et la mise en œuvre continus des ambulanciers paramédicaux au sein d'une équipe de soins interdisciplinaire peuvent accroître l'accès aux soins pour une population traditionnellement mal desservie et présentant des besoins de santé complexes. Les patients bénéficieraient probablement de l'intégration des ambulanciers communautaires dans la gestion communautaire qui vise à améliorer l'accès aux soins après une visite aux urgences.

Simultaneous memory effects in the stress and in the dielectric susceptibility of a stretched polymer glass.

We report experimental evidence that a polymer stretched at constant strain rate λ[over ̇] presents complex memory effects after λ[over ̇] is set to zero at a specific strain λ_{w} for a duration t_{w}, ranging from 100s to 2.2×10^{5}s. When the strain rate is resumed, both the stress and the dielectric constant relax to the unperturbed state nonmonotonically. The relaxations depend on the observable, on λ_{w} and on t_{w}. Relaxation master curves are obtained by scaling the time and the amplitudes by ln(t_{w}). The dielectric evolution also captures the distribution of the relaxation times, so the results impose strong constraints on the relaxation models of polymers under stress and they can be useful for a better understanding of memory effects in other disorder materials.

Ruthenium Metathesis: A Key Step To Access a New Cyclic Tetrasubstituted Olefin Platform.

An rapid and mild synthetic route for the preparation of cyclic tetrasubstituted platforms via ruthenium-catalyzed ring-closing metathesis (RCM) has been developed. This process tolerates a wide range of functionalities such as nitrogen, oxygen, sulfur, silicon, and carbon tethered groups, as well as very challenging fluorine and boron atoms (36 derivatives, up to 96%). This diversity-oriented method was further demonstrated by the postfunctionalization reactions, such as Pd-couplings, N-substitution, and reductive amination introducing a morpholine moiety.

Myocardial Echinococcosis: Rare Manifestation of a Common Parasitic Disease in Northern Tanzania.

Hydatid (Echinococcal) disease often involves the liver and lungs but in sporadic cases, it can involve cardiac structures. A 24-year-old male was referred with symptoms of cough and shortness of breath and a provisional diagnosis of metastatic disease of unknown primary to the lung, which was based on a chest X-ray (CXR). Incidentally, on echocardiogram, he was found to have right ventricular (RV) and myocardial multiseptated cysts, which were compatible with cardiac echinococcosis, as the patient had multiple bilateral lung cysts as well. Imaging with ultrasound, computed tomography (CT) scan, and magnetic resonance imaging (MRI) has ameliorated the diagnosis of hydatid disease location in various body parts. However, for earlier and accurate diagnosis, a high index of suspicion is required in endemic areas, especially in vulnerable populations such as pastoralists.

Developmental plasticity shapes social traits and selection in a facultatively eusocial bee.

Developmental plasticity generates phenotypic variation, but how it contributes to evolutionary change is unclear. Phenotypes of individuals in caste-based (eusocial) societies are particularly sensitive to developmental processes, and the evolutionary origins of eusociality may be rooted in developmental plasticity of ancestral forms. We used an integrative genomics approach to evaluate the relationships among developmental plasticity, molecular evolution, and social behavior in a bee species (Megalopta genalis) that expresses flexible sociality, and thus provides a window into the factors that may have been important at the evolutionary origins of eusociality. We find that differences in social behavior are derived from genes that also regulate sex differentiation and metamorphosis. Positive selection on social traits is influenced by the function of these genes in development. We further identify evidence that social polyphenisms may become encoded in the genome via genetic changes in regulatory regions, specifically in transcription factor binding sites. Taken together, our results provide evidence that developmental plasticity provides the substrate for evolutionary novelty and shapes the selective landscape for molecular evolution in a major evolutionary innovation: Eusociality.

Paternally-biased gene expression follows kin-selected predictions in female honey bee embryos.

The Kinship Theory of Genomic Imprinting (KTGI) posits that, in species where females mate with multiple males, there is selection for a male to enhance the reproductive success of his offspring at the expense of other males and his mating partner. Reciprocal crosses between honey bee subspecies show parent-of-origin effects for reproductive traits, suggesting that males modify the expression of genes related to female function in their female offspring. This effect is likely to be greater in the Cape honey bee (Apis mellifera capensis), because a male's daughters have the unique ability to produce female offspring that can develop into reproductive workers or the next queen without mating. We generated reciprocal crosses between Capensis and another subspecies and used RNA-seq to identify transcripts that are over- or underexpressed in the embryos, depending on the parental origin of the gene. As predicted, 21 genes showed expression bias towards the Capensis father's allele in colonies with a Capensis father, with no such bias in the reciprocal cross. A further six genes showed a consistent bias towards expression of the father's allele across all eight colonies examined, regardless of the direction of the cross. Consistent with predictions of the KTGI, six of the 21 genes are associated with female reproduction. No gene consistently showed overexpression of the maternal allele.

A Neural Circuit Encoding the Experience of Copulation in Female Drosophila.

Female behavior changes profoundly after mating. In Drosophila, the mechanisms underlying the long-term changes led by seminal products have been extensively studied. However, the effect of the sensory component of copulation on the female's internal state and behavior remains elusive. We pursued this question by dissociating the effect of coital sensory inputs from those of male ejaculate. We found that the sensory inputs of copulation cause a reduction of post-coital receptivity in females, referred to as the "copulation effect." We identified three layers of a neural circuit underlying this phenomenon. Abdominal neurons expressing the mechanosensory channel Piezo convey the signal of copulation to female-specific ascending neurons, LSANs, in the ventral nerve cord. LSANs relay this information to neurons expressing myoinhibitory peptides in the brain. We hereby provide a neural mechanism by which the experience of copulation facilitates females encoding their mating status, thus adjusting behavior to optimize reproduction.

Draft Genome Assembly and Population Genetics of an Agricultural Pollinator, the Solitary Alkali Bee (Halictidae: Nomia melanderi).

Alkali bees (Nomia melanderi) are solitary relatives of the halictine bees, which have become an important model for the evolution of social behavior, but for which few solitary comparisons exist. These ground-nesting bees defend their developing offspring against pathogens and predators, and thus exhibit some of the key traits that preceded insect sociality. Alkali bees are also efficient native pollinators of alfalfa seed, which is a crop of major economic value in the United States. We sequenced, assembled, and annotated a high-quality draft genome of 299.6 Mbp for this species. Repetitive content makes up more than one-third of this genome, and previously uncharacterized transposable elements are the most abundant type of repetitive DNA. We predicted 10,847 protein coding genes, and identify 479 of these undergoing positive directional selection with the use of population genetic analysis based on low-coverage whole genome sequencing of 19 individuals. We found evidence of recent population bottlenecks, but no significant evidence of population structure. We also identify 45 genes enriched for protein translation and folding, transcriptional regulation, and triglyceride metabolism evolving slower in alkali bees compared to other halictid bees. These resources will be useful for future studies of bee comparative genomics and pollinator health research.

Conservation Genomics of the Declining North American Bumblebee Bombus terricola Reveals Inbreeding and Selection on Immune Genes.

The yellow-banded bumblebee Bombus terricola was common in North America but has recently declined and is now on the IUCN Red List of threatened species. The causes of B. terricola's decline are not well understood. Our objectives were to create a partial genome and then use this to estimate population data of conservation interest, and to determine whether genes showing signs of recent selection suggest a specific cause of decline. First, we generated a draft partial genome (contig set) for B. terricola, sequenced using Pacific Biosciences RS II at an average depth of 35×. Second, we sequenced the individual genomes of 22 bumblebee gynes from Ontario and Quebec using Illumina HiSeq 2500, each at an average depth of 20×, which were used to improve the PacBio genome calls and for population genetic analyses. The latter revealed that several samples had long runs of homozygosity, and individuals had high inbreeding coefficient F, consistent with low effective population size. Our data suggest that B. terricola's effective population size has decreased orders of magnitude from pre-Holocene levels. We carried out tests of selection to identify genes that may have played a role in ameliorating environmental stressors underlying B. terricola's decline. Several immune-related genes have signatures of recent positive selection, which is consistent with the pathogen-spillover hypothesis for B. terricola's decline. The new B. terricola contig set can help solve the mystery of bumblebee decline by enabling functional genomics research to directly assess the health of pollinators and identify the stressors causing declines.

Camurati-Engelmann disease: a case report from sub-Saharan Africa.

Camurati-Engelmann disease is a rare autosomal dominant inherited condition belonging to the group of craniotubular hyperostosis with characteristic radiological features of the diaphyses of the long bones and the skull. A 35-year-old female is reported presenting with bone pain and waddling gait, since the age of 20 years. Motor activities were limited since the age of 10 years. Palpable bones, muscle weakness and protrusion of eyes were noted. Radiologically, hyperostosis of long bones was seen. Based on history, clinical and radiological features Camurati-Engelmann disease was diagnosed. Sequence analysis of the transforming growth factor ß1 (TGFB1) gene revealed a missense mutation (c.652C>T; p.Arg218Cys). She is the first molecularly confirmed case in sub-Saharan Africa. It is emphasized that Camurati-Engelmann disease is included in the differential diagnosis of persistent bone pain, but also of abnormal childhood motor development in order to avoid unnecessary investigations and inadequate management.

Repetitive aggressive encounters generate a long-lasting internal state in Drosophila melanogaster males.

Multiple studies have investigated the mechanisms of aggressive behavior in Drosophila; however, little is known about the effects of chronic fighting experience. Here, we investigated if repeated fighting encounters would induce an internal state that could affect the expression of subsequent behavior. We trained wild-type males to become winners or losers by repeatedly pairing them with hypoaggressive or hyperaggressive opponents, respectively. As described previously, we observed that chronic losers tend to lose subsequent fights, while chronic winners tend to win them. Olfactory conditioning experiments showed that winning is perceived as rewarding, while losing is perceived as aversive. Moreover, the effect of chronic fighting experience generalized to other behaviors, such as gap-crossing and courtship. We propose that in response to repeatedly winning or losing aggressive encounters, male flies form an internal state that displays persistence and generalization; fight outcomes can also have positive or negative valence. Furthermore, we show that the activities of the PPL1-γ1pedc dopaminergic neuron and the MBON-γ1pedc>α/ß mushroom body output neuron are required for aversion to an olfactory cue associated with losing fights.

Prioritisation of native legume species for further evaluation as potential forage crops in water-limited agricultural systems in South Africa.

In the face of climate change, identification of forage species suitable for dryland farming under low rainfall conditions in South Africa is needed. Currently, there are only a limited number of forage species suitable for dryland farming under such conditions. The objective of this study was to identify and prioritise native legume species that could potentially be used in dryland farming systems in water-limited agro-ecosystems in South Africa. Using a combination of ecological niche modelling techniques, plant functional traits, and indigenous knowledge, 18 perennial herbaceous or stem-woody legume species were prioritised for further evaluation as potential fodder species within water-limited agricultural areas. These species will be evaluated further for their forage quality and their ability to survive and produce enough biomass under water limitation and poor edaphic conditions.

Dissection of the Drosophila neuropeptide F circuit using a high-throughput two-choice assay.

In their classic experiments, Olds and Milner showed that rats learn to lever press to receive an electric stimulus in specific brain regions. This led to the identification of mammalian reward centers. Our interest in defining the neuronal substrates of reward perception in the fruit fly Drosophila melanogaster prompted us to develop a simpler experimental approach wherein flies could implement behavior that induces self-stimulation of specific neurons in their brains. The high-throughput assay employs optogenetic activation of neurons when the fly occupies a specific area of a behavioral chamber, and the flies' preferential occupation of this area reflects their choosing to experience optogenetic stimulation. Flies in which neuropeptide F (NPF) neurons are activated display preference for the illuminated side of the chamber. We show that optogenetic activation of NPF neuron is rewarding in olfactory conditioning experiments and that the preference for NPF neuron activation is dependent on NPF signaling. Finally, we identify a small subset of NPF-expressing neurons located in the dorsomedial posterior brain that are sufficient to elicit preference in our assay. This assay provides the means for carrying out unbiased screens to map reward neurons in flies.

Silver-Catalyzed 7-exo-dig Cyclization of Silylenolether-ynesulfonamides.

Cyclization of silylenolether-ynesulfonamides proceeds at ambient temperature under mild reaction conditions under silver catalysis. Bridged compounds were obtained exclusively through 7-exo-dig reactions. The protocol is applicable to a wide range of substrates, thus leading to azabicyclic frameworks.

Ancient Duplications Have Led to Functional Divergence of Vitellogenin-Like Genes Potentially Involved in Inflammation and Oxidative Stress in Honey Bees.

Protection against inflammation and oxidative stress is key in slowing down aging processes. The honey bee (Apis mellifera) shows flexible aging patterns linked to the social role of individual bees. One molecular factor associated with honey bee aging regulation is vitellogenin, a lipoglycophosphoprotein with anti-inflammatory and antioxidant properties. Recently, we identified three genes in Hymenopteran genomes arisen from ancient insect vitellogenin duplications, named vg-like-A, -B, and -C. The function of these vitellogenin homologs is unclear. We hypothesize that some of them might share gene- and protein-level similarities and a longevity-supporting role with vitellogenin. Here, we show how the structure and modifications of the vg-like genes and proteins have diverged from vitellogenin. Furthermore, all three vg-like genes show signs of positive selection, but the spatial location of the selected protein sites differ from those found in vitellogenin. We show that all these genes are expressed in both long-lived winter worker bees and in summer nurse bees with intermediate life expectancy, yet only vg-like-A shows elevated expression in winter bees as found in vitellogenin. Finally, we show that vg-like-A responds more strongly than vitellogenin to inflammatory and oxidative conditions in summer nurse bees, and that also vg-like-B responds to oxidative stress. We associate vg-like-A and, to lesser extent, vg-like-B to the antiaging roles of vitellogenin, but that vg-like-C probably is involved in some other function. Our analysis indicates that an ancient duplication event facilitated the adaptive and functional divergence of vitellogenin and its paralogs in the honey bee.

Toward an Upgraded Honey Bee (Apis mellifera L.) Genome Annotation Using Proteogenomics.

The honey bee is a key pollinator in agricultural operations as well as a model organism for studying the genetics and evolution of social behavior. The Apis mellifera genome has been sequenced and annotated twice over, enabling proteomics and functional genomics methods for probing relevant aspects of their biology. One troubling trend that emerged from proteomic analyses is that honey bee peptide samples consistently result in lower peptide identification rates compared with other organisms. This suggests that the genome annotation can be improved, or atypical biological processes are interfering with the mass spectrometry workflow. First, we tested whether high levels of polymorphisms could explain some of the missed identifications by searching spectra against the reference proteome (OGSv3.2) versus a customized proteome of a single honey bee, but our results indicate that this contribution was minor. Likewise, error-tolerant peptide searches lead us to eliminate unexpected post-translational modifications as a major factor in missed identifications. We then used a proteogenomic approach with ~1500 raw files to search for missing genes and new exons, to revive discarded annotations and to identify over 2000 new coding regions. These results will contribute to a more comprehensive genome annotation and facilitate continued research on this important insect.

The transcriptomic and evolutionary signature of social interactions regulating honey bee caste development.

The caste fate of developing female honey bee larvae is strictly socially regulated by adult nurse workers. As a result of this social regulation, nurse-expressed genes as well as larval-expressed genes may affect caste expression and evolution. We used a novel transcriptomic approach to identify genes with putative direct and indirect effects on honey bee caste development, and we subsequently studied the relative rates of molecular evolution at these caste-associated genes. We experimentally induced the production of new queens by removing the current colony queen, and we used RNA sequencing to study the gene expression profiles of both developing larvae and their caregiving nurses before and after queen removal. By comparing the gene expression profiles of queen-destined versus worker-destined larvae as well as nurses observed feeding these two types of larvae, we identified larval and nurse genes associated with caste development. Of 950 differentially expressed genes associated with caste, 82% were expressed in larvae with putative direct effects on larval caste, and 18% were expressed in nurses with putative indirect effects on caste. Estimated selection coefficients suggest that both nurse and larval genes putatively associated with caste are rapidly evolving, especially those genes associated with worker development. Altogether, our results suggest that indirect effect genes play important roles in both the expression and evolution of socially influenced traits such as caste.

Characterising an aluminium oxide dosimetry system.

In vivo dosimetry is recommended as a defence-in-depth strategy in radiotherapy treatments and is currently employed by clinics around the world. The characteristics of a new optically stimulated luminescence dosimetry system were investigated for the purpose of replacing an aging thermoluminescence dosimetry system for in vivo dosimetry. The stability of the system was not sufficient to satisfy commissioning requirements and therefore it has not been released into clinical service at this time.

Social evolution. Genomic signatures of evolutionary transitions from solitary to group living.

The evolution of eusociality is one of the major transitions in evolution, but the underlying genomic changes are unknown. We compared the genomes of 10 bee species that vary in social complexity, representing multiple independent transitions in social evolution, and report three major findings. First, many important genes show evidence of neutral evolution as a consequence of relaxed selection with increasing social complexity. Second, there is no single road map to eusociality; independent evolutionary transitions in sociality have independent genetic underpinnings. Third, though clearly independent in detail, these transitions do have similar general features, including an increase in constrained protein evolution accompanied by increases in the potential for gene regulation and decreases in diversity and abundance of transposable elements. Eusociality may arise through different mechanisms each time, but would likely always involve an increase in the complexity of gene networks.

In situ intramolecular catalytic 1,2-addition of allenoates to cyclic ketones towards polycyclic allenoates.

Sequential deprotonation, isomerization of 3-alkynoates and subsequent 1,2-addition led to bicyclic allenoate in the presence of a catalytic amount of Cs2CO3. Cyclization proceeds in a totally stereoselective manner in the case of the two-carbon linker chain. A one-pot reaction starting from alkynyl ketones afforded tricyclic fused ring systems with good yields.