Bird Migration Under Climate Change - A Mechanistic Approach Using Remote Sensing

The broad-scale reductions and shifts that may be expected under climate change in the availability and quality of stopover habitat for long-distance migrants is an area of increasing concern for conservation biologists. Researchers generally have taken two broad approaches to the modeling of migration behaviour to understand the impact of these changes on migratory bird populations. These include models based on causal processes and their response to environmental stimulation, "mechanistic models", or models that primarily are based on observed animal distribution patterns and the correlation of these patterns with environmental variables, i.e. "data driven" models. Investigators have applied the latter technique to forecast changes in migration patterns with changes in the environment, for example, as might be expected under climate change, by forecasting how the underlying environmental data layers upon which the relationships are built will change over time. The learned geostatstical correlations are then applied to the modified data layers.. However, this is problematic. Even if the projections of how the underlying data layers will change are correct, it is not evident that the statistical relationships will remain the same, i.e. that the animal organism may not adapt its' behaviour to the changing conditions. Mechanistic models that explicitly take into account the physical, biological, and behaviour responses of an organism as well as the underlying changes in the landscape offer an alternative to address these shortcomings. The availability of satellite remote sensing observations at multiple spatial and temporal scales, coupled with advances in climate modeling and information technologies enable the application of the mechanistic models to predict how continental bird migration patterns may change in response to environmental change. In earlier work, we simulated the impact of effects of wetland loss and inter-annual variability on the fitness of migratory shorebirds in the central fly ways of North America. We demonstrated the phenotypic plasticity of a migratory population of Pectoral sandpipers consisting of an ensemble of 10,000 individual birds in response to changes in stopover locations using an individual based migration model driven by remotely sensed land surface data, climate data and biological field data. With the advent of new computing capabilities enabled hy recent GPU-GP computing paradigms and commodity hardware, it now is possible to simulate both larger ensemble populations and to incorporate more realistic mechanistic factors into migration models. Here, we take our first steps use these tools to study the impact of long-term drought variability on shorebird survival

Real-time RFI Mitigation in Radio Astronomy

As the use of wireless technology has increased around the world, Radio Frequency Interference (RFI) has become more and more of a problem for radio astronomers. Preventative measures exist to limit the presence of RFI, and programs exist to remove it from saved data, but the use of algorithms to detect and remove RFI as an observation is occurring is much less common. Such a method would be incredibly useful for observations in which the data must undergo several rounds of processing before being saved, as in pulsar timing studies. Strategies for real-time mitigation have been discussed and tested with simulated data, but ideally the results of any approach would be validated by a detailed comparison of the final data products with and without mitigation applied. The goal of this project is to develop an RFI mitigation approach based on strategies suggested by Buch et al.(2016) and to test this program on real data from the observation of pulsar J1713+0747 at the Green Bank Observatory in West Virginia. We use a Median Absolute Deviation (MAD) filter to identify interference in the observation and replace the compromised data with random Gaussian noise to match a characteristic radio signal from space. In order to verify our results, we analyze the pulsar’s timing residuals obtained both from the mitigated data and from data processed through offline RFI removal software. Comparing the two, our preliminary findings indicate that our program is able to significantly improve the quality of timing results from the observation

Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM

The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75-78 clinically relevant drugs. We included 132 viable tumor samples from 35 pediatric oncology centers in seven countries. DSP was conducted on multicellular fresh tumor tissue spheroid cultures in 384-well plates with an overall mean processing time of three weeks. In 89 cases (67%), sufficient viable tissue was received; 69 (78%) passed internal quality controls. The DSP results matched the identified molecular targets, including BRAF, ALK, MET, and TP53 status. Drug vulnerabilities were identified in 80% of cases lacking actionable (very) high-evidence molecular events, adding value to the molecular data. Striking parallels between clinical courses and the DSP results were observed in selected patients. Overall, DSP in clinical real-time is feasible in international multicenter precision oncology programs

Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM

The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75–78 clinically relevant drugs. We included 132 viable tumor samples from 35 pediatric oncology centers in seven countries. DSP was conducted on multicellular fresh tumor tissue spheroid cultures in 384-well plates with an overall mean processing time of three weeks. In 89 cases (67%), sufficient viable tissue was received; 69 (78%) passed internal quality controls. The DSP results matched the identified molecular targets, including BRAF, ALK, MET, and TP53 status. Drug vulnerabilities were identified in 80% of cases lacking actionable (very) high-evidence molecular events, adding value to the molecular data. Striking parallels between clinical courses and the DSP results were observed in selected patients. Overall, DSP in clinical real-time is feasible in international multicenter precision oncology programs

Drug sensitivity profiling of 3D tumor tissue cultures in the pediatric precision oncology program INFORM

The international precision oncology program INFORM enrolls relapsed/refractory pediatric cancer patients for comprehensive molecular analysis. We report a two-year pilot study implementing ex vivo drug sensitivity profiling (DSP) using a library of 75-78 clinically relevant drugs. We included 132 viable tumor samples from 35 pediatric oncology centers in seven countries. DSP was conducted on multicellular fresh tumor tissue spheroid cultures in 384-well plates with an overall mean processing time of three weeks. In 89 cases (67%), sufficient viable tissue was received; 69 (78%) passed internal quality controls. The DSP results matched the identified molecular targets, including BRAF, ALK, MET, and TP53 status. Drug vulnerabilities were identified in 80% of cases lacking actionable (very) high-evidence molecular events, adding value to the molecular data. Striking parallels between clinical courses and the DSP results were observed in selected patients. Overall, DSP in clinical real-time is feasible in international multicenter precision oncology programs.Peer reviewe

Transcription Profiling of the Stringent Response in Escherichia coli▿ †

The bacterial stringent response serves as a paradigm for understanding global regulatory processes. It can be triggered by nutrient downshifts or starvation and is characterized by a rapid RelA-dependent increase in the alarmone (p)ppGpp. One hallmark of the response is the switch from maximum-growth-promoting to biosynthesis-related gene expression. However, the global transcription patterns accompanying the stringent response in Escherichia coli have not been analyzed comprehensively. Here, we present a time series of gene expression profiles for two serine hydroxymate-treated cultures: (i) MG1655, a wild-type E. coli K-12 strain, and (ii) an isogenic relAΔ251 derivative defective in the stringent response. The stringent response in MG1655 develops in a hierarchical manner, ultimately involving almost 500 differentially expressed genes, while the relAΔ251 mutant response is both delayed and limited in scope. We show that in addition to the down-regulation of stable RNA-encoding genes, flagellar and chemotaxis gene expression is also under stringent control. Reduced transcription of these systems, as well as metabolic and transporter-encoding genes, constitutes much of the down-regulated expression pattern. Conversely, a significantly larger number of genes are up-regulated. Under the conditions used, induction of amino acid biosynthetic genes is limited to the leader sequences of attenuator-regulated operons. Instead, up-regulated genes with known functions, including both regulators (e.g., rpoE, rpoH, and rpoS) and effectors, are largely involved in stress responses. However, one-half of the up-regulated genes have unknown functions. How these results are correlated with the various effects of (p)ppGpp (in particular, RNA polymerase redistribution) is discussed

Systematic Mutagenesis of the Escherichia coli Genome

A high-throughput method has been developed for the systematic mutagenesis of the Escherichia coli genome. The system is based on in vitro transposition of a modified Tn5 element, the Sce-poson, into linear fragments of each open reading frame. The transposon introduces both positive (kanamycin resistance) and negative (I-SceI recognition site) selectable markers for isolation of mutants and subsequent allele replacement, respectively. Reaction products are then introduced into the genome by homologous recombination via the λRed proteins. The method has yielded insertion alleles for 1976 genes during a first pass through the genome including, unexpectedly, a number of known and putative essential genes. Sce-poson insertions can be easily replaced by markerless mutations by using the I-SceI homing endonuclease to select against retention of the transposon as demonstrated by the substitution of amber and/or in-frame deletions in six different genes. This allows a Sce-poson-containing gene to be specifically targeted for either designed or random modifications, as well as permitting the stepwise engineering of strains with multiple mutations. The promiscuous nature of Tn5 transposition also enables a targeted gene to be dissected by using randomly inserted Sce-posons as shown by a lacZ allelic series. Finally, assessment of the insertion sites by an iterative weighted matrix algorithm reveals that these hyperactive Tn5 complexes generally recognize a highly degenerate asymmetric motif on one end of the target site helping to explain the randomness of Tn5 transposition

The place of rural hospitals in New Zealand’s health system: an exploratory qualitative study

Introduction: In Aotearoa New Zealand (NZ) there is a knowledge gap regarding the place and contribution of rural hospitals in the health system. New Zealanders residing in rural areas have poorer health outcomes than those living in urban areas, and this is accentuated for Māori, the Indigenous people of the country. There is no current description of rural hospital services, no national policies and little published research regarding their role or value. Around 15% of New Zealanders rely on rural hospitals for health care. The purpose of this exploratory study was to understand national rural hospital leadership perspectives on the place of rural hospitals in the NZ health system. Methods: A qualitative exploratory study was undertaken. The leadership of each rural hospital and national rural stakeholder organisations were invited to participate in virtual semi-structured interviews. The interviews explored participants' views of the rural hospital context, the strengths and challenges they faced and how good rural hospital care might look. Thematic analysis was undertaken using a framework-guided rapid analysis method. Results: Twenty-seven semi-structured interviews were conducted by videoconference. Two broad themes were identified, as follows. Theme 1, 'Our place and our people', reflected the local, on-the-ground situation. Across a broad variety of rural hospitals, geographical distance from specialist health services and community connectedness were the common key influencers of a rural hospital's response. Local services were provided by small, adaptable teams across broad scopes and blurred primary-secondary care boundaries, with acute and inpatient care a key component. Rural hospitals acted as a conduit between community-based care and city-based secondary or tertiary hospital care. Theme 2, 'Our positioning in the wider health system', related to the external wider environment that rural hospitals worked within. Rural hospitals operating at the margins of the health system faced multiple challenges in trying to align with the urban-centric regulatory systems and processes they were dependent on. They described their position as being 'at the end of the dripline'. In contrast to their local connectedness, in the wider health system participants felt rural hospitals were undervalued and invisible. While the study found strengths and challenges common to all NZ rural hospitals, there were also variations between them. Conclusion: This study furthers understanding of the place of rural hospitals in the NZ healthcare system as seen through a national rural hospital lens. Rural hospitals are well placed to provide an integrative role in locality service provision, with many already long established in performing this role. However, context-specific national policy for rural hospitals is urgently needed to ensure their sustainability. Further research should be undertaken to understand the role of NZ rural hospitals in addressing healthcare inequities for those living in rural areas, particularly for Māori