Community response grids: using information technology to help communities respond to bioterror emergencies

Access to accurate and trusted information is vital in preparing for, responding to, and recovering from an emergency. To facilitate response in large-scale emergency situations, Community Response Grids (CRGs) integrate Internet and mobile technologies to enable residents to report information, professional emergency responders to disseminate instructions, and residents to assist one another. CRGs use technology to help residents and professional emergency responders to work together in community response to emergencies, including bioterrorism events. In a time of increased danger from bioterrorist threats, the application of advanced information and communication technologies to community response is vital in confronting such threats. This article describes CRGs, their underlying concepts, development efforts, their relevance to biosecurity and bioterrorism, and future research issues in the use of technology to facilitate community response.     

The evolution of law in biopreparedness

The decade following the terrorist attacks on September 11, 2001, and ensuing anthrax exposures that same fall has seen significant legal reforms designed to improve biopreparedness nationally. Over the past 10 years, a transformative series of legal changes have effectively (1) rebuilt components of federal, state, and local governments to improve response efforts; (2) created an entire new legal classification known as "public health emergencies"; and (3) overhauled existing legal norms defining the roles and responsibilities of public and private actors in emergency response efforts. The back story as to how law plays an essential role in facilitating biopreparedness, however, is pocked with controversies and conflicts between law- and policymakers, public health officials, emergency managers, civil libertarians, scholars, and others. Significant legal challenges for the next decade remain. Issues related to interjurisdictional coordination; duplicative legal declarations of emergency, disaster, and public health emergency; real-time legal decision making; and liability protections for emergency responders and entities remain unresolved. This article explores the evolving tale underlying the rise and prominence of law as a pivotal tool in national biopreparedness and response efforts in the interests of preventing excess morbidity and mortality during public health emergencies.     

Genes involved in glucose repression and oxidative stress response in the fission yeast Schizosaccharomyces pombe

We looked for changes in gene expression and novel genes that could be involved in the interaction between glucose repression and oxidative stress response in the fission yeast, Schizosaccharomyces pombe, using a constitutive invertase mutant, ird11, which is resistant to glucose. BLAST analysis was made of the S. pombe genome database of cDNAs whose expression ratios differentially decreased or increased upon exposure to mild oxidative stress in this mutant compared to the wild type. Genes with this type of activity were identified as rpl302, encoding 60S ribosomal protein L3, and mpg1, encoding mannose-1-phosphate guanyltransferase; their expression patterns were measured using quantitative real-time PCR. We found that the expression levels of rpl302 and mpg1 genes in ird11 under unstressed conditions were increased compared to those of the wild type. Under stress conditions, the expression levels of the rpl302 gene were decreased in both strains, while mpg1 expression levels remained unchanged. These results suggest that these genes play a role in the response to oxidative stress in this mutant strain.     

Maximising survival by shifting the daily timing of activity

Maximising survival requires animals to balance the competing demands of maintaining energy balance and avoiding predation. Here, quantitative modelling shows that optimising the daily timing of activity and rest based on the encountered environmental conditions enables small mammals to maximise survival. Our model shows that nocturnality is typically beneficial when predation risk is higher during the day than during the night, but this is reversed by the energetic benefit of diurnality when food becomes scarce. Empirical testing under semi‐natural conditions revealed that the daily timing of activity and rest in mice exposed to manipulations in energy availability and perceived predation risk is in line with the model’s predictions. Low food availability and decreased perceived daytime predation risk promote diurnal activity patterns. Overall, our results identify temporal niche switching in small mammals as a strategy to maximise survival in response to environmental changes in food availability and perceived predation risk.     

The representation of arm movements in postcentral and parietal cortex

Considerable experimental evidence supports the hypothesis that the neocortical processes underlying kinesthetic sensation form a hierarchical series of cells signalling increasingly complex patterns of movement of the body. However, this view has been criticized and the data lack quantitative verification under controlled conditions. These studies have also typically used one-dimensional (reciprocal) movements, even of multiple degree-of-freedom joints such as the wrist or shoulder, and have been restricted to passive movements. This latter limitation is particularly critical, since the response of many muscle receptors is affected by fusimotor activity while that of many articular receptors is sensitive to the level of muscle contractile activity. Both factors introduce significant kinesthetic ambiguity to the signals arising from these receptors during active movement. This ambiguity is evident in the discharge of primary somatosensory cortex proprioceptive cells. Studies in area 5 show that single cells signal shoulder joint movements in the form of broad directional tuning curves. The pattern of activity of the entire population encodes movement direction. The cells appear to encode spatial aspects of movement unambiguously, since their discharge is relatively insensitive to the changes in muscle activity required to produce the same movements under different load conditions. It is not yet certain whether the somesthetic activity in area 5 is a kinesthetic representation that is sequential to and hierarchically superior to that in SI, or whether it is a parallel representation with separate and distinct function.     

Volunteer health professionals and emergencies: assessing and transforming the legal environment

Volunteer health professionals (VHPs) are essential in emergencies to fill surge capacity and provide needed medical expertise. While some VHPs are well-organized and trained, others arrive spontaneously at the site of a disaster. Lacking organization, training, and identification, they may actually impede emergency efforts. Complications involving medical volunteers in New York City after September 11, 2001, led Congress to authorize federal authorities to assist states and territories in developing emergency systems for the advance registration of volunteer health professionals (ESARVHP). Through advance registration, volunteers can be vetted, trained, and mobilized more effectively during emergencies. The use of VHPs, however, raises multiple legal questions: What constitutes an emergency, how is it declared, and what are the consequences? When are volunteers liable for their actions? When may volunteers who are licensed or certified in one state legally practice their profession in another state? Are volunteers entitled to compensation for harms they incur? This article examines the legal framework underlying the registration and use of volunteers during emergencies and offers recommendations for legal reform, including: (1) establish minimum standards to facilitate interjurisdictional emergency response, improve coordination, and enhance reciprocity of licensing and credentialing; (2) develop liability provisions for VHPs that balance their need to respond without significant fear of civil liability with patients' rights to legal recourse for egregious harms; and (3) provide basic levels of protections for VHPs harmed, injured, or killed while responding to emergencies.     

Muscle recruitment and coordination with an ankle exoskeleton

Exoskeletons have the potential to assist and augment human performance. Understanding how users adapt their movement and neuromuscular control in response to external assistance is important to inform the design of these devices. The aim of this research was to evaluate changes in muscle recruitment and coordination for ten unimpaired individuals walking with an ankle exoskeleton. We evaluated changes in the activity of individual muscles, cocontraction levels, and synergistic patterns of muscle coordination with increasing exoskeleton work and torque. Participants were able to selectively reduce activity of the ankle plantarflexors with increasing exoskeleton assistance. Increasing exoskeleton net work resulted in greater reductions in muscle activity than increasing exoskeleton torque. Patterns of muscle coordination were not restricted or constrained to synergistic patterns observed during unassisted walking. While three synergies could describe nearly 95% of the variance in electromyography data during unassisted walking, these same synergies could describe only 85–90% of the variance in muscle activity while walking with the exoskeleton. Synergies calculated with the exoskeleton demonstrated greater changes in synergy weights with increasing exoskeleton work versus greater changes in synergy activations with increasing exoskeleton torque. These results support the theory that unimpaired individuals do not exclusively use central pattern generators or other low-level building blocks to coordinate muscle activity, especially when learning a new task or adapting to external assistance, and demonstrate the potential for using exoskeletons to modulate muscle recruitment and coordination patterns for rehabilitation or performance.     

Developmental responses of subdominant grassland species to current weather conditions and their relevance for annual vegetation changes

Year-to-year vegetation changes have been observed many times in temperate grasslands. Ordinarily, variation in annual weather patterns is considered responsible for these changes. However, the exact mechanisms of vegetation dynamics have seldom been studied. In order to analyse the direct response of plants to distinct weather situations, the shoot growth rates of three subdominant grassland species were determined during three growing seasons and tested for significant relationships to meteorological variables measured simultaneously in the study site. Half of the shoots grew in the natural community with competition from neighbouring plants. For the other half, above-ground interference was avoided by regularly clipping the surrounding vegetation. The results lead to the distinction of three different impact patterns of current weather conditions on the growth of subdominant grassland species: (i) As a consequence of extraordinary weather conditions, e.g. lasting periods of drought in the summer, plants die completely or partially or pass into secondary dormancy. Such weather situations may cause quantitative or even qualitative changes in species composition by altering the density and frequency of the species involved. (ii) Major divergences from average weather conditions, such as unusually warm or cold periods in the spring, affect the growth of subdominant species and may therefore lead to quantitative annual variation of the species involved in terms of cover or biomass. (iii) Average weather conditions with slight deviations from the long-term means of the weather variables do not produce detectable direct growth responses and therefore average weather conditions are not key factors for year-to-year variations in the quantitative or qualitative performance of subdominant species.     

Functional Regulation of Choline Acetyltransferase by Phosphorylation

Choline acetyltransferase (ChAT) catalyzes synthesis of acetylcholine (ACh) in cholinergic neurons. ACh synthesis is regulated by availability of precursors choline and acetyl coenzyme A or by activity of ChAT; ChAT regulates ACh synthesis under some conditions. Posttranslational phosphorylation is a common mechanism for regulating the function of proteins. Analysis of the primary sequence of 69-kD human ChAT indicates that it has putative phosphorylation consensus sequences for multiple protein kinases. ChAT is phosphorylated on serine-440 and threonine-456 by protein kinase C and CaM kinase II, respectively. These phosphorylation events regulate activity of the enzyme, as well as its binding to plasma membrane and interaction with other cellular proteins. It is relevant to investigate differences in constitutive and inducible patterns of phosphorylation of ChAT under physiological conditions and in response to challenges that cholinergic neurons may be exposed to, and to determine how changes in phosphorylation relate to changes in neurochemical transmission.     

Current Management of Surgical Oncologic Emergencies

ObjectivesFor some oncologic emergencies, surgical interventions are necessary for dissolution or temporary relieve. In the absence of guidelines, the most optimal method for decision making would be in a multidisciplinary cancer conference (MCC). In an acute setting, the opportunity for multidisciplinary discussion is often not available. In this study, the management and short term outcome of patients after surgical oncologic emergency consultation was analyzed.MethodA prospective registration and follow up of adult patients with surgical oncologic emergencies between 01-11-2013 and 30-04-2014. The follow up period was 30 days.ResultsIn total, 207 patients with surgical oncologic emergencies were included. Postoperative wound infections, malignant obstruction, and clinical deterioration due to progressive disease were the most frequent conditions for surgical oncologic emergency consultation. During the follow up period, 40% of patients underwent surgery. The median number of involved medical specialties was two. Only 30% of all patients were discussed in a MCC within 30 days after emergency consultation, and only 41% of the patients who underwent surgery were discussed in a MCC. For 79% of these patients, the surgical procedure was performed before the MCC. Mortality within 30 days was 13%.ConclusionIn most cases, surgery occurred without discussing the patient in a MCC, regardless of the fact that multiple medical specialties were involved in the treatment process. There is a need for prognostic aids and acute oncology pathways with structural multidisciplinary management. These will provide in faster institution of the most appropriate personalized cancer care, and prevent unnecessary investigations or invasive therapy.     

Selected expression profiling of full-length proteins and their variants in human plasma

With increased interest in clinical proteomics—the comparative investigation of differential protein expression patterns for use in the diagnostic and prognostic assessment of disease states—the demand for techniques that can readily identify changes in select proteome components is greater than ever before. This article describes a targeted proteomics approach to recover and quantify C-reactive protein (CRP) directly from human plasma. CRP, a putative biomarker for cardiac health, was isolated from microliter volumes of human plasma by using novel proteomics tools that combine micro-scale affinity capture with matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) detection. Native CRP was analyzed along with serum amyloid P component (SAP) and retinol binding protein (RBP), that were intentionally targeted to generate a selected protein expression profile. A number of qualitative changes were readily observed within these profiles, including micro heterogeneity in the SAP glycan, C-terminally truncated versions of RBP, and detection of a novel truncated variant of CRP. After quantitative validation of increasing plasma CRP concentrations, the approach was applied to the analysis of eight plasma samples obtained from individuals with known medical histories. The result of the analyses are eight protein profiles, revealing increasing CRP levels that can be associated with individuals ailing from post-surgery inflammation, chronic rheumatoid arthritis, and recent acute myocardial infarction. The technique described in this article lays the foundation for selected protein profiling for use in biomarker discovery, as well as in clinical and diagnostic applications.     

Impact of human disturbance in Japan on the distribution and diel activity pattern of terrestrial mammals

Human disturbance has been identified as a contributing factor to the worldwide changes in wildlife ecology. Particularly, the human disturbance forced wildlife from diurnal to nocturnal activity patterns. However, the impact of human disturbances on the spatiotemporal patterns small- and medium-sized terrestrial mammals is unknown. In this study, we then aimed to evaluate the impact of anthropogenic factors on spatial pattern and to clarify the differences in temporal patterns between human disturbed and undisturbed habitats. Our camera trap survey was conducted in northern Gifu Prefecture in central Japan from November 2019 to April 2021. We investigated the impact of human activity on relative abundance indices and the influence of the quantitative difference in human activities on diel activity patterns of 12 terrestrial mammals. In this study, the human population and bamboo forest category negatively affected the RAIs of sika deer and wild boars. Moreover, Asian black bears and wild boars showed crepuscular/nocturnal and cathemeral activity in the human undisturbed habitat, respectively, and nocturnal activity in the human disturbed habitat. Consequently, three large mammals avoided human activity temporally (Asian black bears), spatially (sika deer), and spatiotemporally (wild boars). On the other hand, there was no significant impact of human activity on the spatiotemporal patterns of other mammals. However, it is necessary for residents in the human disturbed habitat to be recognize the risk of human-wildlife conflicts.     

Investigating the Autonomic Nervous System Response to Anxiety in Children with Autism Spectrum Disorders

Assessment of anxiety symptoms in autism spectrum disorders (ASD) is a challenging task due to the symptom overlap between the two conditions as well as the difficulties in communication and awareness of emotions in ASD. This motivates the development of a physiological marker of anxiety in ASD that is independent of language and does not require observation of overt behaviour. In this study, we investigated the feasibility of using indicators of autonomic nervous system (ANS) activity for this purpose. Specially, the objectives of the study were to 1) examine whether or not anxiety causes significant measurable changes in indicators of ANS in an ASD population, and 2) characterize the pattern of these changes in ASD. We measured three physiological indicators of the autonomic nervous system response (heart rate, electrodermal activity, and skin temperature) during a baseline (movie watching) and anxiety condition (Stroop task) in a sample of typically developing children (n = 17) and children with ASD (n = 12). The anxiety condition caused significant changes in heart rate and electrodermal activity in both groups, however, a differential pattern of response was found between the two groups. In particular, the ASD group showed elevated heart rate during both baseline and anxiety conditions. Elevated and blunted phasic electrodermal activity were found in the ASD group during baseline and anxiety conditions, respectively. Finally, the ASD group did not show the typical decrease in skin temperature in response to anxiety. These results suggest that 1) signals of the autonomic nervous system may be used as indicators of anxiety in children with ASD, and 2) ASD may be associated with an atypical autonomic response to anxiety that is most consistent with sympathetic over-arousal and parasympathetic under-arousal.     

MassSQUIRM

In eukaryotes, DNA is wrapped around proteins called histones and is condensed into chromatin. Post-translational modification of histones can result in changes in gene expression. One of the most well-studied histone modifications is the methylation of lysine 4 on histone H3 (H3K4). This residue can be mono-, di- or tri-methylated and these varying methylation states have been associated with different levels of gene expression. Understanding exactly what the purpose of these methylation states is, in terms of gene expression, has been a topic of much research in recent years. Enzymes that can add (methyltransferases) and remove (demethylases) these modifications are of particular interest. The first demethylase discovered, LSD1, is the most well-classified and has been implicated in contributing to human cancers and to DNA damage response pathways. Currently, there are limited methods for accurately studying the activity of demethylases in vitro or in vivo. In this work, we present MassSQUIRM (mass spectrometric quantitation using isotopic reductive methylation), a quantitative method for studying the activity of demethylases capable of removing mono- and di-methyl marks from lysine residues. We focus specifically on LSD1 due to its potential as a prime therapeutic target for human disease. This quantitative approach will enable better characterization of the activity of LSD1 and other chromatin modifying enzymes in vitro, in vivo or in response to inhibitors.     

Fundamental motor patterns of the mammalian fetus.

Techniques that permit direct observation of fetuses in vivo recently have expanded our understanding of prenatal behavioral development in mammals. Although fetal motor activity seems to lack the dynamic, goal-directed character of postnatal behavior, the dimensions that define behavioral organization after birth are applicable to the movements expressed by fetuses. Fetal activity exhibits temporal, sequential, and spatial organization that emerges between the inception of movement and term. Fetal rodents, for example, exhibit coordinated motor patterns antecedent to postnatal righting, locomotion, suckling, maternal-infant communication and grooming behavior, while other action patterns appear to be functional adaptations to the intrauterine niche. Fetuses also are behaviorally responsive to sensory stimulation and changes in environmental conditions in utero. Expression of these behavioral properties emphasizes continuity between prenatal and postnatal life while implying an adaptive role for behavior before birth.     

Effects of environmental factors on circadian activity in the flesh fly, Sarcophaga crassipalpis

Abstract.The diel locomotor activity patterns of wandering larvae in the flesh fly, Sarcophaga crassipalpis Macquart (Diptera: Sarcophagidae), were examined using a novel apparatus and shown to be primarily diurnal, but with a minority (37%) showing nocturnal activity. In response to the environmental stress of heat shock, a significantly larger proportion (72%) of the larvae became nocturnal. In comparison, adult circadian activity also was predominantly diurnal, but not correlated with the larval activity patterns. In addition, adult patterns showed age-related changes in entrainment and free running period. Finally, the phase of circadian-gated adult eclosion was shown to be entrained by a 3-day exposure to light–dark cycles delivered prior to pupariation, with the phase maintained throughout pupal–adult metamorphosis under constant dark conditions. These results demonstrate that environmental changes may have profound effects on the expression of 24-h activity patterns and circadian rhythms during different life stages throughout development.     

A CLADISTIC TEST OF THE TAXON CYCLE AND TAXON PULSE HYPOTHESES

Abstract— A species' habitat preference is intcrpretablc both as a response to present-day conditions and as a result of evolutionary response to historical conditions. The taxon cycle and taxon pulse have been proposed as hypotheses that allow prediction of patterns of habitat specialization within a lineage. Both are based on common assumptions: (1) habitat specialization is largely irreversible in a lineage, (2) ecological specializations arise in a center of origin, and (3) dispersal events leading to current distributions can be ascertained. Eight taxa of Antillean, Mexican, and Central American Carabidae, for which cladistic hypotheses of relationship have been proposed, are used to test the generality of the taxon cycle and pulse. The patterns of habitat utilization predicted by the taxon cycle and taxon pulse hypotheses are tested by comparing cladistic transformations of habitat preference to randomly generated patterns of data generated under a null hypothesis. Evolutionary changes in habitat are interpreted using Camin-Sokal coding, which assumes irreversible habitat shifts and a predetermined ecological ground state (assumptions of the taxon cycle and taxon pulse). An observed pattern is considered to demonstrate the taxon cycle or pulse when it results in an explanation of the habitat shifts that is more parsimonious than 95 % of the randomly generated patterns. Of the eight carabid groups, only one exhibits a statistically significant pattern supporting the taxon cycle and pulse. The failure of the taxon cycle and pulse as generally predictive hypotheses may be due to historical changes in climate that permit episodes of range expansion for species previously restricted to small ranges, and habitat shifts and specialization that do not progress in a linear transformation series. Habitat shifts are also analyzed using Farris optimization, resulting in the most parsimonious transformation series of habitats, subject to a predefined ordering of habitats, while allowing reversals. Significance of an observed pattern of habitat shifts under Farris optimization implies habitat constancy relative to cladogenesis, and step-wise changes in habitat preference. Two of the eight groups exhibit significant patterns of habitat utilization under Farris optimization, indicating that vicariance of areas of like habitat has been the predominant factor generating species diversity in these groups. The other groups do not exhibit habitat constancy, suggesting rapid changes in habitat preference relative to speciation.     

The Identification of Protein Kinase C Iota as a Regulator of the Mammalian Heat Shock Response Using Functional Genomic Screens

Background

The heat shock response is widely used as a surrogate of the general protein quality control system within the cell. This system plays a significant role in aging and many protein folding diseases as well as the responses to other physical and chemical stressors.

Methods/Principal Findings

In this study, a broad-based functional genomics approach was taken to identify potential regulators of the mammalian heat shock response. In the primary screen, a total of 13724 full-length genes in mammalian expression vectors were individually co-transfected into human embryonic kidney cells together with a human HSP70B promoter driving firefly luciferase. A subset of the full-length genes that showed significant activation in the primary screen were then evaluated for their ability to hyper-activate the HSP70B under heat shock conditions. Based on the results from the secondary assay and gene expression microarray analyses, eight genes were chosen for validation using siRNA knockdown. Of the eight genes, only PRKCI showed a statistically significant reduction in the heat shock response in two independent siRNA duplexes compared to scrambled controls. Knockdown of the PRKCI mRNA was confirmed using quantitative RT-PCR. Additional studies did not show a direct physical interaction between PRKCI and HSF1.

Conclusions/Significance

The results suggest that PRKCI is an indirect co-regulator of HSF1 activity and the heat shock response. Given the underlying role of HSF1 in many human diseases and the response to environmental stressors, PRKCI represents a potentially new candidate for gene-environment interactions and therapeutic intervention.     

Intact pancreatic islets and dispersed beta-cells both generate intracellular calcium oscillations but differ in their responsiveness to glucose

Pancreatic islets produce pulses of insulin and other hormones that maintain normal glucose homeostasis. These micro-organs possess exquisite glucose-sensing capabilities, allowing for precise changes in pulsatile insulin secretion in response to small changes in glucose. When communication among these cells is disrupted, precision glucose sensing falters. We measured intracellular calcium patterns in 6-mM-steps between 0 and 16 mM glucose, and also more finely in 2-mM-steps from 8 to 12 mM glucose, to compare glucose sensing systematically among intact islets and dispersed islet cells derived from the same mouse pancreas in vitro. The calcium activity of intact islets was uniformly low (quiescent) below 4 mM glucose and active above 8 mM glucose, whereas dispersed beta-cells displayed a broader activation range (2-to-10 mM). Intact islets exhibited calcium oscillations with 2-to-5-min periods, yet beta-cells exhibited longer 7–10 min periods. In every case, intact islets showed changes in activity with each 6-mM-glucose step, whereas dispersed islet cells displayed a continuum of calcium responses ranging from islet-like patterns to stable oscillations unaffected by changes in glucose concentration. These differences were also observed for 2-mM-glucose steps. Despite the diversity of dispersed beta-cell responses to glucose, the sum of all activity produced a glucose dose-response curve that was surprisingly similar to the curve for intact islets, arguing against the importance of “hub cells” for function. Beta-cells thus retain many of the features of islets, but some are more islet-like than others. Determining the molecular underpinnings of these variations could be valuable for future studies of stem-cell-derived beta-cell therapies.