Developing a partnership to improve health care delivery to children <18 years with cancer and blood disorders in the English-speaking Caribbean: lessons from the SickKids-Caribbean Initiative (SCI).

In 2013, the SickKids-Caribbean Initiative (SCI) was formalised among The Hospital for Sick Children in Toronto, Canada, the University of the West Indies, and Ministries of Health in six Caribbean countries (Barbados, The Bahamas, Jamaica, St. Lucia, St. Vincent and the Grenadines, and Trinidad and Tobago). The aim was to improve the outcomes and quality of life of children (<18 years) with cancer and blood disorders in the partner countries. Core activities included filling a human resource gap by training paediatric haematologists/oncologists and specialised registered nurses; improving capacity to diagnose and treat diverse haematology/oncology cases; developing and maintaining paediatric oncology databases; creating ongoing advocacy activities with international agencies, decision makers, and civil society; and establishing an integrated administration, management, and funding structure. We describe core program components, successes, and challenges to inform others seeking to improve health service delivery in a multidisciplinary and complex partnership.

Changes in parrot diversity after human arrival to the Caribbean.

Humans did not arrive on most of the world's islands until relatively recently, making islands favorable places for disentangling the timing and magnitude of natural and anthropogenic impacts on species diversity and distributions. Here, we focus on Amazona parrots in the Caribbean, which have close relationships with humans (e.g., as pets as well as sources of meat and colorful feathers). Caribbean parrots also have substantial fossil and archaeological records that span the Holocene. We leverage this exemplary record to showcase how combining ancient and modern DNA, along with radiometric dating, can shed light on diversification and extinction dynamics and answer long-standing questions about the magnitude of human impacts in the region. Our results reveal a striking loss of parrot diversity, much of which took place during human occupation of the islands. The most widespread species, the Cuban Parrot, exhibits interisland divergences throughout the Pleistocene. Within this radiation, we identified an extinct, genetically distinct lineage that survived on the Turks and Caicos until Indigenous human settlement of the islands. We also found that the narrowly distributed Hispaniolan Parrot had a natural range that once included The Bahamas; it thus became "endemic" to Hispaniola during the late Holocene. The Hispaniolan Parrot also likely was introduced by Indigenous people to Grand Turk and Montserrat, two islands where it is now also extirpated. Our research demonstrates that genetic information spanning paleontological, archaeological, and modern contexts is essential to understand the role of humans in altering the diversity and distribution of biota.

Microevolutionary dynamics show tropical valleys are deeper for montane birds of the Atlantic Forest.

Tropical mountains hold more biodiversity than their temperate counterparts, and this disparity is often associated with the latitudinal climatic gradient. However, distinguishing the impact of latitude versus the background effects of species history and traits is challenging due to the evolutionary distance between tropical and temperate assemblages. Here, we test whether microevolutionary processes are linked to environmental variation across a sharp latitudinal transition in 21 montane birds of the southern Atlantic Forest in Brazil. We find that effective dispersal within populations in the tropical mountains is lower and genomic differentiation is better predicted by the current environmental complexity of the region than within the subtropical populations. The concordant response of multiple co-occurring populations is consistent with spatial climatic variability as a major process driving population differentiation. Our results provide evidence for how a narrow latitudinal gradient can shape microevolutionary processes and contribute to broader scale biodiversity patterns.

Structure and ligand binding of As-p18, an extracellular fatty acid binding protein from the eggs of a parasitic nematode.

Intracellular lipid-binding proteins (iLBPs) of the fatty acid-binding protein (FABP) family of animals transport, mainly fatty acids or retinoids, are confined to the cytosol and have highly similar 3D structures. In contrast, nematodes possess fatty acid-binding proteins (nemFABPs) that are secreted into the perivitelline fluid surrounding their developing embryos. We report structures of As-p18, a nemFABP of the large intestinal roundworm Ascaris suum, with ligand bound, determined using X-ray crystallography and nuclear magnetic resonance spectroscopy. In common with other FABPs, As-p18 comprises a ten ß-strand barrel capped by two short α-helices, with the carboxylate head group of oleate tethered in the interior of the protein. However, As-p18 exhibits two distinctive longer loops amongst ß-strands not previously seen in a FABP. One of these is adjacent to the presumed ligand entry portal, so it may help to target the protein for efficient loading or unloading of ligand. The second, larger loop is at the opposite end of the molecule and has no equivalent in any iLBP structure yet determined. As-p18 preferentially binds a single 18-carbon fatty acid ligand in its central cavity but in an orientation that differs from iLBPs. The unusual structural features of nemFABPs may relate to resourcing of developing embryos of nematodes.

A latitudinal phylogeographic diversity gradient in birds.

High tropical species diversity is often attributed to evolutionary dynamics over long timescales. It is possible, however, that latitudinal variation in diversification begins when divergence occurs within species. Phylogeographic data capture this initial stage of diversification in which populations become geographically isolated and begin to differentiate genetically. There is limited understanding of the broader implications of intraspecific diversification because comparative analyses have focused on species inhabiting and evolving in restricted regions and environments. Here, we scale comparative phylogeography up to the hemisphere level and examine whether the processes driving latitudinal differences in species diversity are also evident within species. We collected genetic data for 210 New World bird species distributed across a broad latitudinal gradient and estimated a suite of metrics characterizing phylogeographic history. We found that lower latitude species had, on average, greater phylogeographic diversity than higher latitude species and that intraspecific diversity showed evidence of greater persistence in the tropics. Factors associated with species ecologies, life histories, and habitats explained little of the variation in phylogeographic structure across the latitudinal gradient. Our results suggest that the latitudinal gradient in species richness originates, at least partly, from population-level processes within species and are consistent with hypotheses implicating age and environmental stability in the formation of diversity gradients. Comparative phylogeographic analyses scaled up to large geographic regions and hundreds of species can show connections between population-level processes and broad-scale species-richness patterns.

Isolation with asymmetric gene flow during the nonsynchronous divergence of dry forest birds.

Dry forest bird communities in South America are often fragmented by intervening mountains and rainforests, generating high local endemism. The historical assembly of dry forest communities likely results from dynamic processes linked to numerous population histories among codistributed species. Nevertheless, species may diversify in the same way through time if landscape and environmental features, or species ecologies, similarly structure populations. Here we tested whether six co-distributed taxon pairs that occur in the dry forests of the Tumbes and Marañón Valley of northwestern South America show concordant patterns and modes of diversification. We employed a genome reduction technique, double-digest restriction site-associated DNA sequencing, and obtained 4407-7186 genomewide SNPs. We estimated demographic history in each taxon pair and inferred that all pairs had the same best-fit demographic model: isolation with asymmetric gene flow from the Tumbes into the Marañón Valley, suggesting a common diversification mode. Overall, we also observed congruence in effective population size (Ne ) patterns where ancestral Ne were 2.9-11.0× larger than present-day Marañón Valley populations and 0.3-2.0× larger than Tumbesian populations. Present-day Marañón Valley Ne was smaller than Tumbes. In contrast, we found simultaneous population isolation due to a single event to be unlikely as taxon pairs diverged over an extended period of time (0.1-2.9 Ma) with multiple nonoverlapping divergence periods. Our results show that even when populations of codistributed species asynchronously diverge, the mode of their differentiation can remain conserved over millions of years. Divergence by allopatric isolation due to barrier formation does not explain the mode of differentiation between these two bird assemblages; rather, migration of individuals occurred before and after geographic isolation.

Handoffs in the Intensive Care Unit.

Operating room (OR) to intensive care unit (ICU) handoffs are complex and known to be associated with adverse events and patient harm. The authors hypothesized that handoff quality diminishes during nights/weekends and that bedside handoff practices are similar between ICUs of the same health system. Bedside OR-to-ICU handoffs were directly observed in 2 surgical ICUs with different patient volumes. Handoff quality measures were compared within the ICUs on weekdays versus nights/weekends as well as between the high- and moderate-volume ICUs. In the high-volume ICU, transmitter delivery scores were significantly better during off hours, while other measures were not different. High-volume ICU scores were consistently better than those in the moderate-volume ICU. Bedside handoff practices are not worse during off hours and may be better in ICUs used to a higher patient volume. Specific handoff protocols merit evaluation and training to ensure consistent practices in different ICU models and at different times.

Temporary arterial shunts in damage control: Experience and outcomes.

BACKGROUND: Arterial shunting is a well-described method to control hemorrhage and rapidly reestablish flow, but optimal shunt dwell times remain controversial. We hypothesized that prolonged shunt dwell times of more than 6 hours are related to adverse outcomes after major arterial injury. METHODS: A review (2005-2013) of all patients with arterial shunts placed after traumatic injury at our urban Level I trauma center was undertaken. Patients who died prior to shunt removal (n = 7) were excluded. Shunt complications were defined as dislodgement, thrombosis, and distal ischemia. Patients were compared on the basis of shunt complications with respect to clinical parameters. RESULTS: The 42 patients who underwent arterial shunting after major vascular injury were primarily young (median, 26 years; interquartile range [IQR], 22-31 years) males (97.6%), severely injured (Injury Severity Score, 17.5 [IQR, 14-29]; shunted vessel Abbreviated Injury Scale score, 4 [IQR, 3-4]) by gunshot (85.7%) requiring neck/torso (33.3%) or upper-extremity (19.1%) or lower-extremity (47.6%) shunts. Thirty-five patients survived until shunt removal, and 5 (14.3%) of 35 developed shunt complications. Demographics and clinical characteristics were compared between those with shunt dwell times of less than 6 hours (n = 19) and more than 6 hours (n = 16). While patients appeared to have a greater injury burden overall in the group with dwell times of more than 6 hours, there were no statistical differences between groups with respect to age, gender, initial systolic blood pressure or hemodynamics during the shunt dwell period, use of vasopressors, Abbreviated Injury Scale score of the shunted vessel, Injury Severity Score, or outcomes including limb amputation or mortality. No patients (0/19) with shunt dwell times of less than 6 hours developed complications, whereas 5 (31.3%) of 16 patients with dwell times of more than 6 hours developed shunt complications (p = 0.05). CONCLUSIONS: In this civilian series, 14% of patients with arterial shunts developed shunt complications. Our data suggest that limiting shunt dwell times to less than 6 hours when clinically feasible may decrease adverse outcomes. LEVEL OF EVIDENCE: Therapeutic/care management study, level IV.

Reemergence of Dengue in Southern Texas, 2013.

During a dengue epidemic in northern Mexico, enhanced surveillance identified 53 laboratory-positive cases in southern Texas; 26 (49%) patients acquired the infection locally, and 29 (55%) were hospitalized. Of 83 patient specimens that were initially IgM negative according to ELISA performed at a commercial laboratory, 14 (17%) were dengue virus positive by real-time reverse transcription PCR performed at the Centers for Disease Control and Prevention. Dengue virus types 1 and 3 were identified, and molecular phylogenetic analysis demonstrated close identity with viruses that had recently circulated in Mexico and Central America. Of 51 household members of 22 dengue case-patients who participated in household investigations, 6 (12%) had been recently infected with a dengue virus and reported no recent travel, suggesting intrahousehold transmission. One household member reported having a recent illness consistent with dengue. This outbreak reinforces emergence of dengue in southern Texas, particularly when incidence is high in northern Mexico.

Diversity in the structures and ligand-binding sites of nematode fatty acid and retinol-binding proteins revealed by Na-FAR-1 from Necator americanus.

Fatty acid and retinol-binding proteins (FARs) comprise a family of unusual α-helix rich lipid-binding proteins found exclusively in nematodes. They are secreted into host tissues by parasites of plants, animals and humans. The structure of a FAR protein from the free-living nematode Caenorhabditis elegans is available, but this protein [C. elegans FAR-7 (Ce-FAR-7)] is from a subfamily of FARs that does not appear to be important at the host/parasite interface. We have therefore examined [Necator americanus FAR-1 (Na-FAR-1)] from the blood-feeding intestinal parasite of humans, N. americanus. The 3D structure of Na-FAR-1 in its ligand-free and ligand-bound forms, determined by NMR (nuclear magnetic resonance) spectroscopy and X-ray crystallography respectively, reveals an α-helical fold similar to Ce-FAR-7, but Na-FAR-1 possesses a larger and more complex internal ligand-binding cavity and an additional C-terminal α-helix. Titration of apo-Na-FAR-1 with oleic acid, analysed by NMR chemical shift perturbation, reveals that at least four distinct protein-ligand complexes can be formed. Na-FAR-1 and possibly other FARs may have a wider repertoire for hydrophobic ligand binding, as confirmed in the present study by our finding that a range of neutral and polar lipids co-purify with the bacterially expressed recombinant protein. Finally, we show by immunohistochemistry that Na-FAR-1 is present in adult worms with a tissue distribution indicative of possible roles in nutrient acquisition by the parasite and in reproduction in the male.

Biological evidence supports an early and complex emergence of the Isthmus of Panama.

The linking of North and South America by the Isthmus of Panama had major impacts on global climate, oceanic and atmospheric currents, and biodiversity, yet the timing of this critical event remains contentious. The Isthmus is traditionally understood to have fully closed by ca. 3.5 million years ago (Ma), and this date has been used as a benchmark for oceanographic, climatic, and evolutionary research, but recent evidence suggests a more complex geological formation. Here, we analyze both molecular and fossil data to evaluate the tempo of biotic exchange across the Americas in light of geological evidence. We demonstrate significant waves of dispersal of terrestrial organisms at approximately ca. 20 and 6 Ma and corresponding events separating marine organisms in the Atlantic and Pacific oceans at ca. 23 and 7 Ma. The direction of dispersal and their rates were symmetrical until the last ca. 6 Ma, when northern migration of South American lineages increased significantly. Variability among taxa in their timing of dispersal or vicariance across the Isthmus is not explained by the ecological factors tested in these analyses, including biome type, dispersal ability, and elevation preference. Migration was therefore not generally regulated by intrinsic traits but more likely reflects the presence of emergent terrain several millions of years earlier than commonly assumed. These results indicate that the dramatic biotic turnover associated with the Great American Biotic Interchange was a long and complex process that began as early as the Oligocene-Miocene transition.

The drivers of tropical speciation.

Since the recognition that allopatric speciation can be induced by large-scale reconfigurations of the landscape that isolate formerly continuous populations, such as the separation of continents by plate tectonics, the uplift of mountains or the formation of large rivers, landscape change has been viewed as a primary driver of biological diversification. This process is referred to in biogeography as vicariance. In the most species-rich region of the world, the Neotropics, the sundering of populations associated with the Andean uplift is ascribed this principal role in speciation. An alternative model posits that rather than being directly linked to landscape change, allopatric speciation is initiated to a greater extent by dispersal events, with the principal drivers of speciation being organism-specific abilities to persist and disperse in the landscape. Landscape change is not a necessity for speciation in this model. Here we show that spatial and temporal patterns of genetic differentiation in Neotropical birds are highly discordant across lineages and are not reconcilable with a model linking speciation solely to landscape change. Instead, the strongest predictors of speciation are the amount of time a lineage has persisted in the landscape and the ability of birds to move through the landscape matrix. These results, augmented by the observation that most species-level diversity originated after episodes of major Andean uplift in the Neogene period, suggest that dispersal and differentiation on a matrix previously shaped by large-scale landscape events was a major driver of avian speciation in lowland Neotropical rainforests.

Physical training for asthma

BACKGROUND: People with asthma may show less tolerance to exercise due to worsening asthma symptoms during exercise or other reasons such as deconditioning as a consequence of inactivity. Some may restrict activities as per medical advice or family influence and this might result in reduced physical fitness. Physical training programs aim to improve physical fitness, neuromuscular coordination and self confidence. Subjectively, many people with asthma report that they are symptomatically better when fit, but results from trials have varied and have been difficult to compare because of different designs and training protocols. Also, as exercise can induce asthma, the safety of exercise programmes needs to be considered. OBJECTIVE: To gain a better understanding of the effect of physical training on the respiratory and general health of people with asthma, from randomised trials. METHODS: Search methods: We searched the Cochrane Airways Group Specialised Register of trials up to January 2013. Selection criteria: We included randomised trials of people over eight years of age with asthma who were randomised to undertake physical training or not. Physical training had to be undertaken for at least 20 minutes, two times a week, over a minimum period of four weeks. Data collection and analysis: Two review authors independently assessed eligibility for inclusion and undertook risk of bias assessment for the included studies. MAIN RESULTS: Twenty-one studies (772 participants) were included in this review with two additional 2012 studies identified as 'awaiting classification'. Physical training was well tolerated with no adverse effects reported. None of the studies mentioned worsening of asthma symptoms following physical training. Physical training showed marked improvement in cardiopulmonary fitness as measured by a statistically and clinically significant increase in maximum oxygen uptake (mean difference (MD) 4.92 mL/kg/min; ...

Resonance assignment of As-p18, a fatty acid binding protein secreted by developing larvae of the parasitic nematode Ascaris suum.

As-p18 is produced and secreted by larvae of the parasitic nematode Ascaris suum as they develop within their eggs. The protein is a member of the fatty acid binding protein (FABP) family found in a wide range of eukaryotes, but is distinctive in that it is secreted from the synthesizing cell and has predicted additional structural features not previously seen in other FABPs. As-p18 and similar proteins found only in nematodes have therefore been designated 'nemFABPs'. Sequence-specific (1)H, (13)C and (15)N resonance assignments were established for the 155 amino acid recombinant protein (18.3 kDa) in complex with oleic acid, using a series of three-dimensional triple-resonance heteronuclear NMR experiments. The secondary structure of As-p18 is predicted to be very similar to other FABPs, but the protein has extended loops that have not been observed in other FABPs whose structures have so far been solved.

¹H, ¹³C and ¹5N chemical shift assignments of Na-FAR-1, a helix-rich fatty acid and retinol binding protein of the parasitic nematode Necator americanus.

The fatty acid and retinol-binding (FAR) proteins are a family of unusual helix-rich lipid binding proteins found exclusively in nematodes, and are secreted by a range of parasites of humans, animals and plants. Na-FAR-1 is from the parasitic nematode Necator americanus, an intestinal blood-feeding parasite of humans. Sequence-specific (1)H, (13)C and (15)N resonance assignments have been obtained for the recombinant 170 amino acid protein, using three-dimensional triple-resonance heteronuclear magnetic resonance experiments. Backbone assignments have been obtained for 99.3% of the non-proline HN/N pairs (146 out of 147). The amide resonance of T45 was not observed, probably due to rapid exchange with solvent water. A total of 96.9% of backbone resonances were identified, while 97.7% assignment of amino acid sidechain protons is complete. All Hα(166), Hß(250) and Hγ(160) and 98.4% of the Hδ (126 out of 128) atoms were assigned. In addition, 99.4% Cα (154 out of 155) and 99.3% Cß (143 out of 144) resonances have been assigned. No resonances were observed for the NH(n) groups of R93 NεHε, arginine, N(η1)H2, N(η2)H2, histidine N(δ1)H(δ1), N(ε1)H(ε1) and lysine N(ζ3)H3. Na-FAR-1 has a similar overall arrangement of α-helices to Ce-FAR-7 of the free-living Caeorhabditis elegans, but with an extra C-terminal helix.

Evaluating the role of contracting and expanding rainforest in initiating cycles of speciation across the Isthmus of Panama.

Climatic and geological changes across time are presumed to have shaped the rich biodiversity of tropical regions. However, the impact climatic drying and subsequent tropical rainforest contraction had on speciation has been controversial because of inconsistent palaeoecological and genetic data. Despite the strong interest in examining the role of climatic change on speciation in the Neotropics there has been few comparative studies, particularly, those that include non-rainforest taxa. We used bird species that inhabit humid or dry habitats that dispersed across the Panamanian Isthmus to characterize temporal and spatial patterns of speciation across this barrier. Here, we show that these two assemblages of birds exhibit temporally different speciation time patterns that supports multiple cycles of speciation. Evidence for these cycles is further corroborated by the finding that both assemblages consist of 'young' and 'old' species, despite dry habitat species pairs being geographically more distant than pairs of humid habitat species. The matrix of humid and dry habitats in the tropics not only allows for the maintenance of high species richness, but additionally this study suggests that these environments may have promoted speciation. We conclude that differentially expanding and contracting distributions of dry and humid habitats was probably an important contributor to speciation in the tropics.

Impact of the deepwater horizon oil spill on bioavailable polycyclic aromatic hydrocarbons in Gulf of Mexico coastal waters.

An estimated 4.1 million barrels of oil and 2.1 million gallons of dispersants were released into the Gulf of Mexico during the Deepwater Horizon oil spill. There is a continued need for information about the impacts and long-term effects of the disaster on the Gulf of Mexico. The objectives of this study were to assess bioavailable polycyclic aromatic hydrocarbons (PAHs) in the coastal waters of four Gulf Coast states that were impacted by the spill. For over a year, beginning in May 2010, passive sampling devices were used to monitor the bioavailable concentration of PAHs. Prior to shoreline oiling, baseline data were obtained at all the study sites, allowing for direct before and after comparisons of PAH contamination. Significant increases in bioavailable PAHs were seen following the oil spill, however, preoiling levels were observed at all sites by March 2011. A return to elevated PAH concentrations, accompanied by a chemical fingerprint similar to that observed while the site was being impacted by the spill, was observed in Alabama in summer 2011. Chemical forensic modeling demonstrated that elevated PAH concentrations are associated with distinctive chemical profiles.