Publications by authors named "Jonathan Tyler"

16 Publications

  • Page 1 of 1

Inferring causality in biological oscillators.

Bioinformatics 2021 Aug 31. Epub 2021 Aug 31.

Department of Mathematical Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea.

Motivation: Fundamental to biological study is identifying regulatory interactions. The recent surge in time-series data collection in biology provides a unique opportunity to infer regulations computationally. However, when components oscillate, model-free inference methods, while easily implemented, struggle to distinguish periodic synchrony and causality. Alternatively, model-based methods test the reproducibility of time series given a specific model but require inefficient simulations and have limited applicability.

Results: We develop an inference method based on a general model of molecular, neuronal, and ecological oscillatory systems that merges the advantages of both model-based and model-free methods, namely accuracy, broad applicability, and usability. Our method successfully infers the positive and negative regulations within various oscillatory networks, e.g., the repressilator and a network of cofactors at the pS2 promoter, outperforming popular inference methods.

Availability: We provide a computational package, ION (Inferring Oscillatory Networks), that users can easily apply to noisy, oscillatory time series to uncover the mechanisms by which diverse systems generate oscillations. Accompanying MATLAB code under a BSD-style license and examples are available at ttps://github.com/Mathbiomed/ION. Additionally, the code is available under a CC-BY 4.0 License at https://doi.org/10.6084/m9.figshare.16431408.v1.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btab623DOI Listing
August 2021

High-frequency temperature monitoring for early detection of febrile adverse events in patients with cancer.

Cancer Cell 2021 Sep 12;39(9):1167-1168. Epub 2021 Aug 12.

Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA; Rogel Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:

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http://dx.doi.org/10.1016/j.ccell.2021.07.019DOI Listing
September 2021

Ready2Change: Preliminary effectiveness of a telephone-delivered intervention program for alcohol, methamphetamine and cannabis use problems.

Drug Alcohol Rev 2021 Aug 3. Epub 2021 Aug 3.

Turning Point, Eastern Health, Melbourne, Australia.

Introduction: Telehealth has considerable potential to overcome many of the barriers to accessing care for substance use problems, thereby increasing the opportunity for earlier intervention. The Ready2Change program is a multiple-session outbound telephone-delivered cognitive and behavioural intervention for mild-to-moderate substance use disorders, embedded within a long-established 24/7 alcohol and drug helpline. We sought to analyse routinely collected program data in a preliminary study to examine the effectiveness of Ready2Change in reducing substance use problem severity and psychological distress.

Methods: A retrospective analysis of program data from December 2013 to June 2018 was performed. Analysed cases were 249 clients living in Victoria, Australia with alcohol (n = 191), methamphetamine (n = 40) or cannabis (n = 18) as their primary drug of concern. A within-subjects design was used to examine pre- and post-intervention substance use problem severity and psychological distress.

Results: For alcohol cases, there was a statistically significant decrease in alcohol problem severity [AUDIT, mean difference = -12.7, 95% confidence interval (CI) -14.0, -11.5]. Statistically significant reductions in drug problem severity (DUDIT) were observed for methamphetamine (mean difference = -17.3, 95% CI -20.9, -13.7) and cannabis (mean difference = -15.9, 95% CI -22.3, -9.6) cases. All groups showed reductions in problem severity for other substances used (P < 0.05) and psychological distress (P < 0.001).

Discussion And Conclusions: Results suggest Ready2Change benefits clients with alcohol, methamphetamine and cannabis use problems, with the potential to improve treatment access for health inequity groups including those living in remote areas. These findings warrant further investigation into the effectiveness of this program.
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http://dx.doi.org/10.1111/dar.13363DOI Listing
August 2021

Genomic heterogeneity affects the response to Daylight Saving Time.

Sci Rep 2021 Jul 20;11(1):14792. Epub 2021 Jul 20.

Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI, 48109, USA.

Circadian clocks control the timing of many physiological events in the 24-h day. When individuals undergo an abrupt external shift (e.g., change in work schedule or travel across multiple time zones), circadian clocks become misaligned with the new time and may take several days to adjust. Chronic circadian misalignment, e.g., as a result of shift work, has been shown to lead to several physical and mental health problems. Despite the serious health implications of circadian misalignment, relatively little is known about how genetic variation affects an individual's ability to entrain to abrupt external changes. Accordingly, we used the one-hour advance from the onset of daylight saving time (DST) as a natural experiment to comprehensively study how individual heterogeneity affects the shift of sleep/wake cycles in response to an abrupt external time change. We found that individuals genetically predisposed to a morning tendency adjusted to the advance in a few days, while genetically predisposed evening-inclined individuals had not shifted. Observing differential effects by genetic disposition after a one-hour advance underscores the importance of heterogeneity in adaptation to external schedule shifts. These genetic differences may affect how individuals adjust to jet lag or shift work as well.
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http://dx.doi.org/10.1038/s41598-021-94459-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292316PMC
July 2021

Magnetic resonance imaging analysis of human skull diploic venous anatomy.

Surg Neurol Int 2021 31;12:249. Epub 2021 May 31.

Department of Neurosurgery, University of Alberta, Alberta, Canada.

Background: The skull diploic venous space (DVS) represents a potential route for cerebrospinal fluid (CSF) diversion and absorption in the treatment of hydrocephalus. The goal of this study was to carry out a detailed characterization of the drainage pattern of the DVS of the skull using high-resolution MRI, especially the diploic veins draining to the lacunae laterales (LLs) since the LLs constitute an important channel for the CSF to access the superior sagittal sinus and subsequently the systemic circulation. The objective was to identify those skull regions optimally suited for an intraosseous CSF diversion system.

Methods: High-resolution, T1-weighted MRI scans from 20 adult and 16 pediatric subjects were selected for analysis. Skulls were divided into four regions, that is, frontal, parietal, temporal, and occipital. On each scan, a trained observer counted all diploic veins in every skull region. Each diploic vein was also followed to determine its final drainage pathway (i.e., dural venous sinus, dural vein, LL, or indeterminate).

Results: In the adult age group, the frontal and occipital skull regions showed the highest number of diploic veins. However, the highest number of draining diploic veins connecting to the lacunae lateralis was found in the frontal and parietal skull region, just anterior and just posterior to the coronal suture. In the pediatric age group, the parietal skull region, just posterior to the coronal suture, showed the highest overall number of diploic veins and also the highest number of draining diploic veins connecting to the LL.

Conclusion: This study suggested that diploic venous density across the skull varies with age, with more parietal diploic veins in the pediatric age range, and more occipital and frontal diploic veins in adults. If the DVS is ultimately used for CSF diversion, our anatomical data point to optimal sites for the insertion of specially designed intraosseous infusion devices for the treatment of hydrocephalus. Likely the optimal sites for CSF diversion would be the parietal region just posterior to the coronal suture in children, and in adults, frontal and/or parietal just anterior or just posterior to the coronal suture.
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http://dx.doi.org/10.25259/SNI_532_2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247719PMC
May 2021

Monitoring beliefs and physiological measures in students at risk for COVID-19 using wearable sensors and smartphone technology: Protocol for a mobile health study.

JMIR Res Protoc 2021 Jun 4. Epub 2021 Jun 4.

Division of Pediatric Hematology Oncology, Department of Pediatrics, University of Michigan, 1500 E. Medical Center DrD4118 Medical Professional Building, Ann Arbor, US.

Background: The COVID-19 pandemic has impacted lives significantly and greatly affected an already vulnerable population, college students, in relation to mental health and public safety. Social distancing and isolation have brought about challenges to student's mental health. Mobile health apps and wearable sensors may help to monitor students at risk for COVID-19 and support their mental well-being.

Objective: Through the use of a wearable sensor and smartphone-based survey completion, this study aimed to monitor students at risk for COVID-19.

Methods: We conducted a prospective study of students, undergraduate and graduate, at a public university in the Midwest. Students were instructed to download the Fitbit, Social Rhythms, and Roadmap 2.0 apps onto their personal mobile devices (Android or iOS). Subjects consented to provide up to 10 saliva samples during the study period. Surveys were administered through the Roadmap 2.0 app at five timepoints - at baseline, 1-month later, 2-months later, 3-months later, and at study completion. The surveys gathered information regarding demographics, COVID-19 diagnoses and symptoms, and mental health resilience, with the aim of documenting the impact of COVID-19 on the college student population.

Results: This study enrolled 2,158 college students between September 2020 and January 2021. Subjects are currently being followed on-study for one academic year. Data collection and analysis are ongoing.

Conclusions: This study examined student health and well-being during the COVID-19 pandemic. It also assessed the feasibility of wearable sensor use and survey completion in a college student population, which may inform the role of our mobile health tools on student health and well-being. Finally, using wearable sensor data, biospecimen collection, and self-reported COVID-19 diagnosis, our results may provide key data towards the development of a model for the early prediction and detection of COVID-19.

Clinicaltrial: ClinicalTrials.gov NCT04766788.
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http://dx.doi.org/10.2196/29561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386373PMC
June 2021

Monitoring Health Care Workers at Risk for COVID-19 Using Wearable Sensors and Smartphone Technology: Protocol for an Observational mHealth Study.

JMIR Res Protoc 2021 May 12;10(5):e29562. Epub 2021 May 12.

Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Michigan, Ann Arbor, MI, United States.

Background: Health care workers (HCWs) have been working on the front lines of the COVID-19 pandemic with high risks of viral exposure, infection, and transmission. Standard COVID-19 testing is insufficient to protect HCWs from these risks and prevent the spread of disease. Continuous monitoring of physiological data with wearable sensors, self-monitoring of symptoms, and asymptomatic COVID-19 testing may aid in the early detection of COVID-19 in HCWs and may help reduce further transmission among HCWs, patients, and families.

Objective: By using wearable sensors, smartphone-based symptom logging, and biospecimens, this project aims to assist HCWs in self-monitoring COVID-19.

Methods: We conducted a prospective, longitudinal study of HCWs at a single institution. The study duration was 1 year, wherein participants were instructed on the continuous use of two wearable sensors (Fitbit Charge 3 smartwatch and TempTraq temperature patches) for up to 30 days. Participants consented to provide biospecimens (ie, nasal swabs, saliva swabs, and blood) for up to 1 year from study entry. Using a smartphone app called Roadmap 2.0, participants entered a daily mood score, submitted daily COVID-19 symptoms, and completed demographic and health-related quality of life surveys at study entry and 30 days later. Semistructured qualitative interviews were also conducted at the end of the 30-day period, following completion of daily mood and symptoms reporting as well as continuous wearable sensor use.

Results: A total of 226 HCWs were enrolled between April 28 and December 7, 2020. The last participant completed the 30-day study procedures on January 16, 2021. Data collection will continue through January 2023, and data analyses are ongoing.

Conclusions: Using wearable sensors, smartphone-based symptom logging and survey completion, and biospecimen collections, this study will potentially provide data on the prevalence of COVID-19 infection among HCWs at a single institution. The study will also assess the feasibility of leveraging wearable sensors and self-monitoring of symptoms in an HCW population.

Trial Registration: ClinicalTrials.gov NCT04756869; https://clinicaltrials.gov/ct2/show/NCT04756869.

International Registered Report Identifier (irrid): DERR1-10.2196/29562.
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http://dx.doi.org/10.2196/29562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117956PMC
May 2021

Real-time, personalized medicine through wearable sensors and dynamic predictive modeling: a new paradigm for clinical medicine.

Curr Opin Syst Biol 2020 Apr 7;20:17-25. Epub 2020 Jul 7.

Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI.

Accurately predicting the onset and course of a disease in an individual is a major unmet challenge in medicine due to the complex and dynamic nature of disease progression. Continuous data from wearable technologies and biomarker data with a fine time resolution provide a unique opportunity to learn more about disease evolution and to usher in a new era of personalized and real-time medicine. Herein, we propose the potential of real-time, continuously measured physiological data as a noninvasive biomarker approach for detecting disease transitions, using allogeneic hematopoietic stem cell transplant (HCT) patient care as an example. Additionally, we review a recent computational technique, the landscape dynamic network biomarker method, that uses biomarker data to identify transition states in disease progression and explore how to use it with both biomarker and physiological data for earlier detection of graft-versus-host disease specifically. Throughout, we argue that increased collaboration across multiple fields is essential to realizing the full potential of wearable and biomarker data in a new paradigm of personalized and real-time medicine.
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http://dx.doi.org/10.1016/j.coisb.2020.07.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7515448PMC
April 2020

Persistent influence of obliquity on ice age terminations since the Middle Pleistocene transition.

Science 2020 03;367(6483):1235-1239

Scottish Universities Environmental Research Centre, East Kilbride G75 0QF, Scotland, UK.

Radiometric dating of glacial terminations over the past 640,000 years suggests pacing by Earth's climatic precession, with each glacial-interglacial period spanning four or five cycles of ~20,000 years. However, the lack of firm age estimates for older Pleistocene terminations confounds attempts to test the persistence of precession forcing. We combine an Italian speleothem record anchored by a uranium-lead chronology with North Atlantic ocean data to show that the first two deglaciations of the so-called 100,000-year world are separated by two obliquity cycles, with each termination starting at the same high phase of obliquity, but at opposing phases of precession. An assessment of 11 radiometrically dated terminations spanning the past million years suggests that obliquity exerted a persistent influence on not only their initiation but also their duration.
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http://dx.doi.org/10.1126/science.aaw1114DOI Listing
March 2020

A structured telephone-delivered intervention to reduce problem alcohol use (Ready2Change): study protocol for a parallel group randomised controlled trial.

Trials 2019 Aug 19;20(1):515. Epub 2019 Aug 19.

Department of Law and Criminology, Sheffield Hallam University, Sheffield, UK.

Background: Current population surveys suggest around 20% of Australians meet diagnostic criteria for an alcohol use disorder. However, only a minority seek professional help due to individual and structural barriers, such as low health literacy, stigma, geography, service operating hours and wait lists. Telephone-delivered interventions are readily accessible and ideally placed to overcome these barriers. We will conduct a randomised controlled trial (RCT) to examine the efficacy of a standalone, structured telephone-delivered intervention to reduce alcohol consumption, problem severity and related psychological distress among individuals with problem alcohol use.

Methods/design: This is a single site, parallel group, two-arm superiority RCT. We will recruit 344 participants from across Australia with problem alcohol use. After completing a baseline assessment, participants will be randomly allocated to receive either the Ready2Change (R2C) intervention (n = 172, four to six sessions of structured telephone-delivered intervention, R2C self-help resource, guidelines for alcohol consumption and stress management pamphlets) or the control condition (n = 172, four phone check-ins < 5 min, guidelines for alcohol consumption and stress management pamphlets). Telephone follow-up assessments will occur at 4-6 weeks, 3 months, 6 months and 12 months post-baseline. The primary outcome is the Alcohol Use Disorders Identification Test (AUDIT) score administered at 3 months post-baseline. Secondary outcomes include change in AUDIT score (6 and 12 months post-baseline), change in number of past-month heavy drinking days, psychological distress, health and wellbeing, quality of life, client treatment evaluation and cost effectiveness.

Discussion: This study will be one of the first RCTs conducted internationally to examine the impact of a standalone, structured telephone-delivered intervention to address problem alcohol use and associated psychological morbidity. The proposed intervention is expected to contribute to the health and wellbeing of individuals who are otherwise unlikely to seek treatment through mainstream service models, to reduce the burden on specialist services and primary care providers and to provide an accessible and proportionate response, with resulting cost savings for the health system and broader community.

Trial Registration: Australian New Zealand Clinical Trials Registry, ACTRN12618000828224 . Pre-registered on 16 May 2018.
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http://dx.doi.org/10.1186/s13063-019-3462-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6701125PMC
August 2019

Revisiting a synthetic intracellular regulatory network that exhibits oscillations.

J Math Biol 2019 06 30;78(7):2341-2368. Epub 2019 Mar 30.

Department of Mathematics, Texas A&M University, College Station, TX, 77843, USA.

In 2000, Elowitz and Leibler introduced the repressilator-a synthetic gene circuit with three genes that cyclically repress transcription of the next gene-as well as a corresponding mathematical model. Experimental data and model simulations exhibited oscillations in the protein concentrations across generations. Müller et al. (J Math Biol 53(6):905-937, 2006) generalized the model to an arbitrary number of genes and analyzed the resulting dynamics. Their new model arose from five key assumptions, two of which are restrictive given current biological knowledge. Accordingly, we propose a new repressilator system that allows for general functions to model transcription, degradation, and translation. We prove that, with an odd number of genes, the new model has a unique steady state and the system converges to this steady state or to a periodic orbit. We also give a necessary and sufficient condition for stability of steady states when the number of genes is even and conjecture a condition for stability for an odd number. Finally, we derive a new rate function describing transcription that arises under more reasonable biological assumptions than the widely used single-step binding assumption. With this new transcription-rate function, we compare the model's amplitude and period with that of a model with the conventional transcription-rate function. Taken together, our results enhance our understanding of genetic regulation by repression.
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http://dx.doi.org/10.1007/s00285-019-01346-3DOI Listing
June 2019

Post-mortem oxygen isotope exchange within cultured diatom silica.

Rapid Commun Mass Spectrom 2017 Oct;31(20):1749-1760

NERC Isotope Geosciences Laboratory, British Geological Survey, Nottingham, NG12 5GG, UK.

Rationale: Potential post-mortem alteration to the oxygen isotope composition of biogenic silica is critical to the validity of palaeoclimate reconstructions based on oxygen isotope ratios (δ O values) from sedimentary silica. We calculate the degree of oxygen isotope alteration within freshly cultured diatom biogenic silica in response to heating and storing in the laboratory.

Methods: The experiments used freshly cultured diatom silica. Silica samples were either stored in water or dried at temperatures between 20 °C and 80 °C. The mass of affected oxygen and the associated silica-water isotope fractionation during alteration were calculated by conducting parallel experiments using endmember waters with δ O values of -6.3 to -5.9 ‰ and -36.3 to -35.0 ‰. Dehydroxylation and subsequent oxygen liberation were achieved by stepwise fluorination with BrF . The O/ O ratios were measured using a ThermoFinnigan MAT 253 isotope ratio mass spectrometer.

Results: Significant alterations in silica δ O values were observed, most notably an increase in the δ O values following drying at 40-80 °C. Storage in water for 7 days between 20 and 80 °C also led to significant alteration in δ O values. Mass balance calculations suggest that the amount of affected oxygen is positively correlated with temperature. The estimated oxygen isotope fractionation during alteration is an inverse function of temperature, consistent with the extrapolation of models for high-temperature silica-water oxygen isotope fractionation.

Conclusions: Routinely used preparatory methods may impart significant alterations to the δ O values of biogenic silica, particularly when dealing with modern cultured or field-collected material. The significance of such processes within natural aquatic environments is uncertain; however, there is potential that similar processes also affect sedimentary diatoms, with implications for the interpretation of biogenic silica-hosted δ O palaeoclimate records.
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http://dx.doi.org/10.1002/rcm.7954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5639378PMC
October 2017

Evidence for a bi-partition of the Younger Dryas Stadial in East Asia associated with inversed climate characteristics compared to Europe.

Sci Rep 2017 03 31;7:44983. Epub 2017 Mar 31.

Institute of Geological Sciences, Palaeontology Section, Free University Berlin, Malteserstr, 74-100, Haus D, 12249 Berlin, Germany.

The Younger Dryas Stadial (YDS) was an episode of northern hemispheric cooling which occurred within the Last Glacial Interglacial Transition (LGIT). A major driver for the YDS climate was a weakening of the Atlantic Meridional Overturning Circulation (AMOC). It has been inferred that the AMOC began to strengthen mid-YDS, producing a bipartite structure of the YDS in records from continental Europe. These records imply that the polar front and westerlies shifted northward, producing a warmer second phase of the YDS in Europe. Here we present multi-proxy data from the sediments of Lake Suigetsu (Japan), as evidence that a related bi-partition of the YDS also occurred in East Asia. Besides showing for the first time that the bi-partition was not limited to the North Atlantic/European region, the data also imply a climatic dipole between Europe and East Asia since the cold-warm characteristics are reversed at Lake Suigetsu. We suggest that changes in eastward moisture transport from the North Atlantic are the primary mechanism by which the teleconnection can be explained.
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http://dx.doi.org/10.1038/srep44983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374484PMC
March 2017

Carbon isotope discrimination in leaves of the broad-leaved paperbark tree, Melaleuca quinquenervia, as a tool for quantifying past tropical and subtropical rainfall.

Glob Chang Biol 2016 10 19;22(10):3474-86. Epub 2016 Apr 19.

Queensland Department of Science, Information Technology and Innovation, Brisbane, QLD, Australia.

Quantitative reconstructions of terrestrial climate are highly sought after but rare, particularly in Australia. Carbon isotope discrimination in plant leaves (Δleaf ) is an established indicator of past hydroclimate because the fractionation of carbon isotopes during photosynthesis is strongly influenced by water stress. Leaves of the evergreen tree Melaleuca quinquenervia have been recovered from the sediments of some perched lakes on North Stradbroke and Fraser Islands, south-east Queensland, eastern Australia. Here, we examine the potential for using M. quinquenervia ∆leaf as a tracer of past rainfall by analysing carbon isotope ratios (δ(13) C) of modern leaves. We firstly assess Δleaf variation at the leaf and stand scale and find no systematic pattern within leaves or between leaves due to their position on the tree. We then examine the relationships between climate and Δleaf for a 11-year time series of leaves collected in a litter tray. M. quinquenervia retains its leaves for 1-4 years; thus, cumulative average climate data are used. There is a significant relationship between annual mean ∆leaf and mean annual rainfall of the hydrological year for 1-4 years (i.e. 365-1460 days) prior to leaf fall (r(2)  = 0.64, P = 0.003, n = 11). This relationship is marginally improved by accounting for the effect of pCO2 on discrimination (r(2)  = 0.67, P = 0.002, n = 11). The correlation between rainfall and Δleaf , and the natural distribution of Melaleuca quinquenervia around wetlands of eastern Australia, Papua New Guinea and New Caledonia offers significant potential to infer past rainfall on a wide range of spatial and temporal scales.
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http://dx.doi.org/10.1111/gcb.13277DOI Listing
October 2016

Pliocene reversal of late Neogene aridification.

Proc Natl Acad Sci U S A 2016 Feb 8;113(8):1999-2004. Epub 2016 Feb 8.

School of Life and Environmental Sciences, Deakin University, Burwood, VIC, 3125, Australia.

The Pliocene epoch (5.3-2.6 Ma) represents the most recent geological interval in which global temperatures were several degrees warmer than today and is therefore considered our best analog for a future anthropogenic greenhouse world. However, our understanding of Pliocene climates is limited by poor age control on existing terrestrial climate archives, especially in the Southern Hemisphere, and by persistent disagreement between paleo-data and models concerning the magnitude of regional warming and/or wetting that occurred in response to increased greenhouse forcing. To address these problems, here we document the evolution of Southern Hemisphere hydroclimate from the latest Miocene to the middle Pliocene using radiometrically-dated fossil pollen records preserved in speleothems from semiarid southern Australia. These data reveal an abrupt onset of warm and wet climates early within the Pliocene, driving complete biome turnover. Pliocene warmth thus clearly represents a discrete interval which reversed a long-term trend of late Neogene cooling and aridification, rather than being simply the most recent period of greater-than-modern warmth within a continuously cooling trajectory. These findings demonstrate the importance of high-resolution chronologies to accompany paleoclimate data and also highlight the question of what initiated the sustained interval of Pliocene warmth.
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http://dx.doi.org/10.1073/pnas.1520188113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4776468PMC
February 2016

Intraosseous infusion into the skull: potential application for the management of hydrocephalus.

J Neurosurg 2007 Feb;106(2 Suppl):120-5

Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.

Object: Hydrocephalus results from abnormal cerebrospinal fluid (CSF) volumes or flow patterns. The absorption of CSF is determined largely by pressures within veins and venous sinuses in the head and adjacent to the spine. Most surgical solutions for hydrocephalus involve diversion of excess CSF into alternative absorption sites, and most of these solutions are still suboptimal. The focus of this work has been to recreate more normal CSF absorption into the dural venous sinuses without having to directly access the superior sagittal sinus (SSS).

Methods: Intraosseous skull infusion for the purpose of accessing the SSS and the systemic venous system was tested by experimental skull infusions of tracer fluids into living large animals (14 adult pigs). Compared with control injections into an ear vein, infusions into the skull through specially designed infusion devices had similar systemic absorption characteristics. This suggested that intraosseous skull infusion in a living large animal was successful in gaining access to the SSS and systemic venous system.

Conclusions: This study constitutes the first demonstration of the success of intraosseous skull infusion in gaining rapid access to the systemic venous system and it thus opens the possibility of using this strategy for diversion of CSF back into the intracranial venous system for the treatment of hydrocephalus.
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http://dx.doi.org/10.3171/ped.2007.106.2.120DOI Listing
February 2007
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