Publications by authors named "Rachel Wood"

85 Publications

Effects of augmented somatosensory input using vibratory insoles to improve walking in individuals with chronic post-stroke hemiparesis.

Gait Posture 2021 May 23;86:77-82. Epub 2021 Jan 23.

Department of Industrial Engineering and Engineering Management, National Tsing-Hua University, Hsinchu, Taiwan.

Background: Stroke survivors suffer from hemiparesis and somatosensory impairments, which adversely impact walking performance, placing them at higher risks for trips and falls. Post-stroke, somatosensory deficits are commonly observed as impaired interpretation of afferent input and increased threshold. Diminishing or augmenting somatosensory inputs via various techniques have been demonstrated to be able to modify static and dynamic balance, postural and locomotor control in non-neurologically impaired as well as neurologically impaired individuals.

Research Question: We sought to investigate whether enhancing somatosensory input using vibratory insoles, can improve post-stroke gait. We hypothesized that with augmentation of somatosensory input at the soles via vibratory insoles would improve post-stroke gait via increased propulsive forces, decreased braking forces and increased ankle angle movements in the paretic legs of individuals with chronic post-stroke hemiparesis.

Methods: Fifteen individuals with chronic post-stroke hemiparesis and 15 age-similar non-neurologically impaired controls participated in this cross-sectional study. Enhanced somatosensory stimulation was delivered using a pair of tactor-embedded insoles, providing suprathreshold vibratory stimulation to the bottom of the feet. Participants walked over an instrumented treadmill with self-selected speeds, under 5 conditions: no insole in shoe (NT), insoles in shoe with no vibration (BOFF), vibration under both feet (BON), vibration under one foot only (ION, CON). Kinetics and kinematics during walking were recorded and analyzed offline.

Results: Suprathreshold vibratory stimulations did not alter gait kinetics under any stimulation conditions. We observed increased paretic ankle dorsiflexions in the paretic legs, when vibratory stimuli were applied unilaterally.

Significance: Vibratory stimulations applied at suprathreshold intensity to the bottom of the feet to augment somatosensory feedback can potentially be used as a low-cost solution to address the inadequate toe clearance during walking in people post-stroke, which is an important goal in post-stroke rehabilitation.
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http://dx.doi.org/10.1016/j.gaitpost.2021.01.016DOI Listing
May 2021

Sunitinib and Imatinib Display Differential Cardiotoxicity in Adult Rat Cardiac Fibroblasts That Involves a Role for Calcium/Calmodulin Dependent Protein Kinase II.

Front Cardiovasc Med 2020 1;7:630480. Epub 2021 Feb 1.

Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.

Tyrosine kinase inhibitors (TKIs) have dramatically improved cancer treatment but are known to cause cardiotoxicity. The pathophysiological consequences of TKI therapy are likely to manifest across different cell types of the heart, yet there is little understanding of the differential adverse cellular effects. Cardiac fibroblasts (CFs) play a pivotal role in the repair and remodeling of the heart following insult or injury, yet their involvement in anti-cancer drug induced cardiotoxicity has been largely overlooked. Here, we examine the direct effects of sunitinib malate and imatinib mesylate on adult rat CF viability, Ca handling and mitochondrial function that may contribute to TKI-induced cardiotoxicity. In particular, we investigate whether Ca/calmodulin dependent protein kinase II (CaMKII), may be a mediator of TKI-induced effects. CF viability in response to chronic treatment with both drugs was assessed using MTT assays and flow cytometry analysis. Calcium mobilization was assessed in CFs loaded with Fluo4-AM and CaMKII activation oxidation was measured quantitative immunoblotting. Effects of both drugs on mitochondrial function was determined by live mitochondrial imaging using MitoSOX red. Treatment of CFs with sunitinib (0.1-10 μM) resulted in concentration-dependent alterations in CF phenotype, with progressively significant cell loss at higher concentrations. Flow cytometry analysis and MTT assays revealed increased cell apoptosis and necrosis with increasing concentrations of sunitinib. In contrast, equivalent concentrations of imatinib resulted in no significant change in cell viability. Both sunitinib and imatinib pre-treatment increased Angiotensin II-induced intracellular Ca mobilization, with only sunitinib resulting in a significant effect and also causing increased CaMKII activation oxidation. Live cell mitochondrial imaging using MitoSOX red revealed that both sunitinib and imatinib increased mitochondrial superoxide production in a concentration-dependent manner. This effect in response to both drugs was suppressed in the presence of the CaMKII inhibitor KN-93. Sunitinib and imatinib showed differential effects on CFs, with sunitinib causing marked changes in cell viability at concentrations where imatinib had no effect. Sunitinib caused a significant increase in Angiotensin II-induced intracellular Ca mobilization and both TKIs caused increased mitochondrial superoxide production. Targeted CaMKII inhibition reversed the TKI-induced mitochondrial damage. These findings highlight a new role for CaMKII in TKI-induced cardiotoxicity, particularly at the level of the mitochondria, and confirm differential off-target toxicity in CFs, consistent with the differential selectivity of sunitinib and imatinib.
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http://dx.doi.org/10.3389/fcvm.2020.630480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882511PMC
February 2021

Preterm Birth During the Coronavirus Disease 2019 (COVID-19) Pandemic in a Large Hospital System in the United States.

Obstet Gynecol 2021 03;137(3):403-404

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, and the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, Massachusetts.

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http://dx.doi.org/10.1097/AOG.0000000000004237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884087PMC
March 2021

2000 Year-old Bogong moth (Agrotis infusa) Aboriginal food remains, Australia.

Sci Rep 2020 12 17;10(1):22151. Epub 2020 Dec 17.

School of Earth Sciences, University of Melbourne, Parkville, VIC, Australia.

Insects form an important source of food for many people around the world, but little is known of the deep-time history of insect harvesting from the archaeological record. In Australia, early settler writings from the 1830s to mid-1800s reported congregations of Aboriginal groups from multiple clans and language groups taking advantage of the annual migration of Bogong moths (Agrotis infusa) in and near the Australian Alps, the continent's highest mountain range. The moths were targeted as a food item for their large numbers and high fat contents. Within 30 years of initial colonial contact, however, the Bogong moth festivals had ceased until their recent revival. No reliable archaeological evidence of Bogong moth exploitation or processing has ever been discovered, signalling a major gap in the archaeological history of Aboriginal groups. Here we report on microscopic remains of ground and cooked Bogong moths on a recently excavated grindstone from Cloggs Cave, in the southern foothills of the Australian Alps. These findings represent the first conclusive archaeological evidence of insect foods in Australia, and, as far as we know, of their remains on stone artefacts in the world. They provide insights into the antiquity of important Aboriginal dietary practices that have until now remained archaeologically invisible.
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http://dx.doi.org/10.1038/s41598-020-79307-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747710PMC
December 2020

Sample adequacy controls for infectious disease diagnosis by oral swabbing.

PLoS One 2020 30;15(10):e0241542. Epub 2020 Oct 30.

Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington, United States of America.

Oral swabs are emerging as a non-invasive sample type for diagnosing infectious diseases including Ebola, tuberculosis (TB), and COVID-19. To assure proper sample collection, sample adequacy controls (SACs) are needed that detect substances indicative of samples collected within the oral cavity. This study evaluated two candidate SACs for this purpose. One detected representative oral microbiota (Streptococcus species DNA) and the other, human cells (human mitochondrial DNA, mtDNA). Quantitative PCR (qPCR) assays for the two target cell types were applied to buccal swabs (representing samples collected within the oral cavity) and hand swabs (representing improperly collected samples) obtained from 51 healthy U.S. volunteers. Quantification cycle (Cq) cutoffs that maximized Youden's index were established for each assay. The streptococcal target at a Cq cutoff of ≤34.9 had 99.0% sensitivity and specificity for oral swab samples, whereas human mtDNA perfectly distinguished between hand and mouth swabs with a Cq cutoff of 31.3. The human mtDNA test was then applied to buccal, tongue, and gum swabs that had previously been collected from TB patients and controls in South Africa, along with "air swabs" collected as negative controls (total N = 292 swabs from 71 subjects). Of these swabs, 287/292 (98%) exhibited the expected Cq values. In a paired analysis the three oral sites yielded indistinguishable amounts of human mtDNA, however PurFlockTM swabs collected slightly more human mtDNA than did OmniSwabsTM (p = 0.012). The results indicate that quantification of human mtDNA cannot distinguish swabs collected from different sites within the mouth. However, it can reliably distinguish oral swabs from swabs that were not used orally, which makes it a useful SAC for oral swab-based diagnosis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241542PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598519PMC
December 2020

F1 simcalls: an simulation programme for new doctors.

Future Healthc J 2020 Feb;7(Suppl 1):s114

Royal United Hospitals Bath NHS Foundation Trust.

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http://dx.doi.org/10.7861/fhj.7.1.s114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241182PMC
February 2020

Extinction of eastern Sahul megafauna coincides with sustained environmental deterioration.

Nat Commun 2020 05 18;11(1):2250. Epub 2020 May 18.

Geosciences, Queensland Museum, 122 Gerler Rd., Hendra, QLD, 4011, Australia.

Explanations for the Upper Pleistocene extinction of megafauna from Sahul (Australia and New Guinea) remain unresolved. Extinction hypotheses have advanced climate or human-driven scenarios, in spite of over three quarters of Sahul lacking reliable biogeographic or chronologic data. Here we present new megafauna from north-eastern Australia that suffered extinction sometime after 40,100 (±1700) years ago. Megafauna fossils preserved alongside leaves, seeds, pollen and insects, indicate a sclerophyllous forest with heathy understorey that was home to aquatic and terrestrial carnivorous reptiles and megaherbivores, including the world's largest kangaroo. Megafauna species diversity is greater compared to southern sites of similar age, which is contrary to expectations if extinctions followed proposed migration routes for people across Sahul. Our results do not support rapid or synchronous human-mediated continental-wide extinction, or the proposed timing of peak extinction events. Instead, megafauna extinctions coincide with regionally staggered spatio-temporal deterioration in hydroclimate coupled with sustained environmental change.
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http://dx.doi.org/10.1038/s41467-020-15785-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231803PMC
May 2020

Dynamic and synchronous changes in metazoan body size during the Cambrian Explosion.

Sci Rep 2020 04 22;10(1):6784. Epub 2020 Apr 22.

School of GeoSciences, University of Edinburgh, James Hutton Road, Edinburgh, EH9 3FE, UK.

Many aspects of the drivers for, and evolutionary dynamics of, the Cambrian Explosion are poorly understood. Here we quantify high-resolution changes in species body size in major metazoan groups on the Siberian Platform during the early Cambrian (ca. 540-510 Million years ago (Ma)). Archaeocyath sponges, hyolith lophophorates, and helcionelloid mollusc species show dynamic and synchronous trends over million-year timescales, with peaks in body size during the latest Tommotian/early Atbadanian and late Atdabanian/early Botoman, and notably small body sizes in the middle Atdabanian and after the Sinsk anoxic extinction event, starting ca. 513 Ma. These intervals of body size changes are also mirrored in individual species and correlate positively with increased rates of origination and broadly with total species diversity. Calcitic brachiopods (rhynchonelliformeans), however, show a general increase in body size following the increase in species diversity through this interval: phosphatic brachiopods (linguliformeans) show a body size decrease that negatively correlates with diversity. Both brachiopod groups show a rapid recovery at the Sinsk Event. The synchronous changes in these metrics in archaeocyath, hyoliths and helcionelloids suggest the operation of external drivers through the early Cambrian, such as episodic changes in oxygenation or productivity. But the trends shown by brachiopods suggests a differing physiological response. Together, these dynamics created both the distinct evolutionary record of metazoan groups during the Cambrian Explosion and determined the nature of its termination.
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http://dx.doi.org/10.1038/s41598-020-63774-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176670PMC
April 2020

FosSahul 2.0, an updated database for the Late Quaternary fossil records of Sahul.

Sci Data 2019 11 19;6(1):272. Epub 2019 Nov 19.

Global Ecology Lab, College of Science and Engineering and ARC Centre of Excellence for Australian Biodiversity and Heritage, Flinders University, GPO Box 2100, Adelaide, South Australia, 5001, Australia.

The 2016 version of the FosSahul database compiled non-human vertebrate megafauna fossil ages from Sahul published up to 2013 in a standardized format. Its purpose was to create a publicly available, centralized, and comprehensive database for palaeoecological investigations of the continent. Such databases require regular updates and improvements to reflect recent scientific findings. Here we present an updated FosSahul (2.0) containing 11,871 dated non-human vertebrate fossil records from the Late Quaternary published up to 2018. Furthermore, we have extended the information captured in the database to include methodological details and have developed an algorithm to automate the quality-rating process. The algorithm makes the quality-rating more transparent and easier to reproduce, facilitating future database extensions and dissemination. FosSahul has already enabled several palaeoecological analyses, and its updated version will continue to provide a centralized organisation of Sahul's fossil records. As an example of an application of the database, we present the temporal pattern in megafauna genus richness inferred from available data in relation to palaeoclimate indices over the past 180,000 years.
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http://dx.doi.org/10.1038/s41597-019-0267-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6864098PMC
November 2019

Micro Methods for Megafauna: Novel Approaches to Late Quaternary Extinctions and Their Contributions to Faunal Conservation in the Anthropocene.

Bioscience 2019 Nov 2;69(11):877-887. Epub 2019 Oct 2.

Department of Archaeology, Max Planck Institute for the Science of Human History, Jena, Germany.

Drivers of Late Quaternary megafaunal extinctions are relevant to modern conservation policy in a world of growing human population density, climate change, and faunal decline. Traditional debates tend toward global solutions, blaming either dramatic climate change or dispersals of Homo sapiens to new regions. Inherent limitations to archaeological and paleontological data sets often require reliance on scant, poorly resolved lines of evidence. However, recent developments in scientific technologies allow for more local, context-specific approaches. In the present article, we highlight how developments in five such methodologies (radiocarbon approaches, stable isotope analysis, ancient DNA, ancient proteomics, microscopy) have helped drive detailed analysis of specific megafaunal species, their particular ecological settings, and responses to new competitors or predators, climate change, and other external phenomena. The detailed case studies of faunal community composition, extinction chronologies, and demographic trends enabled by these methods examine megafaunal extinctions at scales appropriate for practical understanding of threats against particular species in their habitats today.
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http://dx.doi.org/10.1093/biosci/biz105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829010PMC
November 2019

Somewhere beyond the sea: Human cranial remains from the Lesser Sunda Islands (Alor Island, Indonesia) provide insights on Late Pleistocene peopling of Island Southeast Asia.

J Hum Evol 2019 09 1;134:102638. Epub 2019 Aug 1.

Jurusan Arkeologi, Fakultas Ilmu Budaya, Universitas Gadja Madja, Bulaksumur, Yogjakarta, 55281, Indonesia.

The migration of anatomically modern humans (AMH) from Africa to every inhabitable continent included their dispersal through Island Southeast Asia (ISEA) to Australia. Significantly, this involved overwater dispersal through the Lesser Sunda Islands between Sunda (continental Southeast Asia) and Sahul (Australia and New Guinea). However, the timing and direction of this movement is still debated. Here, we report on human skeletal material recovered from excavations at two rockshelters, known locally as Tron Bon Lei, on Alor Island, Indonesia. The remains, dated to the Late Pleistocene, are the first anatomically modern human remains recovered in Wallacea dated to this period and are associated with cultural material demonstrating intentional burial. The human remains from Tron Bon Lei represent a population osteometrically distinct from Late Pleistocene Sunda and Sahul AMH. Instead, morphometrically, they appear more similar to Holocene populations in the Lesser Sundas. Thus, they may represent the remains of a population originally from Sunda whose Lesser Sunda Island descendants survived into the Holocene.
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http://dx.doi.org/10.1016/j.jhevol.2019.07.002DOI Listing
September 2019

Microbiological diagnosis of pulmonary tuberculosis in children by oral swab polymerase chain reaction.

Sci Rep 2019 07 25;9(1):10789. Epub 2019 Jul 25.

Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, WA, USA.

Microbiological diagnosis of pediatric pulmonary tuberculosis (TB) is challenging due to the difficulty of collecting and testing sputum from children. We investigated whether easily-obtained oral swab samples are useful alternatives or supplements to sputum. Oral swabs and induced sputum (IS) were collected from 201 South African children with suspected pulmonary TB. IS samples were tested by mycobacterial culture and Xpert MTB/RIF. Oral swabs were tested by PCR targeting IS6110. Children were categorized as Confirmed TB (microbiologic confirmation on IS), Unconfirmed TB (clinical diagnosis only), or Unlikely TB (recovery without TB treatment). Relative to Confirmed TB, PCR on two oral swabs per child was 43% sensitive and 93% specific. This sensitivity fell below that of sputum Xpert (64%). Among children with either Confirmed or Unconfirmed TB, PCR on two oral swabs per child was 31% sensitive and 93% specific, which was more sensitive than sputum testing among this group (21%). Although oral swab analysis had low sensitivity in sputum-positive children, it detected TB in a significant proportion of sputum-negative children who were clinically diagnosed with TB. Specificity at 93% was suboptimal but may improve with the use of automated methods. With further development, oral swabs may become useful supplements to sputum as samples for diagnosis of pulmonary TB in children.
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http://dx.doi.org/10.1038/s41598-019-47302-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658562PMC
July 2019

Provider Education and Vaporizer Labeling Lead to Reduced Anesthetic Agent Purchasing With Cost Savings and Reduced Greenhouse Gas Emissions.

Anesth Analg 2019 06;128(6):e97-e99

From the Department of Anesthesiology.

Anesthetic agents are known greenhouse gases with hundreds to thousands of times the global warming impact compared with carbon dioxide. We sought to mitigate the negative environmental and financial impacts of our practice in the perioperative setting through multidisciplinary staff engagement and provider education on flow rate reduction and volatile agent choice. These efforts led to a 64% per case reduction in carbon dioxide equivalent emissions (163 kg in Fiscal Year 2012, compared with 58 kg in Fiscal Year 2015), as well as a cost savings estimate of $25,000 per month.
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http://dx.doi.org/10.1213/ANE.0000000000003771DOI Listing
June 2019

Author Correction: Integrated records of environmental change and evolution challenge the Cambrian Explosion.

Nat Ecol Evol 2019 May;3(5):858

Finnish Museum of Natural History, University of Helsinki, Helsinki, Finland.

In the version of this article initially published, the reference "Mitchell, E. G., & Kenchington, C. G. The utility of height for the Ediacaran organisms of Mistaken Point. Nat. Ecol. Evol. 2, 1218-1222 (2018)." was missing. A callout to the reference should have been placed at the end of this sentence: "For biotic replacement to occur, taxa must be both spatially collocated and have similar resource requirements, yet spatial analyses of contemporary communities find only very limited instances of resource competition." The reference has been added to the list, and the error has been corrected in the PDF and HTML versions of the article.
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http://dx.doi.org/10.1038/s41559-019-0897-zDOI Listing
May 2019

Integrated records of environmental change and evolution challenge the Cambrian Explosion.

Nat Ecol Evol 2019 04 11;3(4):528-538. Epub 2019 Mar 11.

Finnish Museum of Natural History, University of Helsinki, Helsinki, Finland.

The 'Cambrian Explosion' describes the rapid increase in animal diversity and abundance, as manifest in the fossil record, between ~540 and 520 million years ago (Ma). This event, however, is nested within a far more ancient record of macrofossils extending at least into the late Ediacaran at ~571 Ma. The evolutionary events documented during the Ediacaran-Cambrian interval coincide with geochemical evidence for the modernisation of Earth's biogeochemical cycles. Holistic integration of fossil and geochemical records leads us to challenge the notion that the Ediacaran and Cambrian worlds were markedly distinct, and places biotic and environmental change within a longer-term narrative. We propose that the evolution of metazoans may have been facilitated by a series of dynamic and global changes in redox conditions and nutrient supply, which, potentially together with biotic feedbacks, enabled turnover events that sustained multiple phases of radiation. We argue that early metazoan diversification should be recast as a series of successive, transitional radiations that extended from the late Ediacaran and continued through the early Palaeozoic. We conclude that while the Cambrian Explosion represents a radiation of crown-group bilaterians, it was simply one phase amongst several metazoan radiations, some older and some younger.
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http://dx.doi.org/10.1038/s41559-019-0821-6DOI Listing
April 2019

Postoperative Opioid Consumption After Scheduled Compared With Unscheduled Cesarean Delivery.

Obstet Gynecol 2019 02;133(2):354-363

Department of Obstetrics and Gynecology, Women and Infants Hospital, Providence, Rhode Island; and the Department of Obstetrics and Gynecology and the Deborah Kelly Center for Outcomes Research, Massachusetts General Hospital, the Department of Anesthesiology, Perioperative and Pain Medicine and the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, and the Department of Obstetrics & Gynecology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

Objective: To identify characteristics associated with high inpatient daily opioid consumption after cesarean delivery.

Methods: This is a retrospective cohort study of all cesarean deliveries performed under neuraxial anesthesia with neuraxial morphine, at a single institution from January 1, 2015, to December 31, 2015. Women with preoperative opioid use disorder or chronic opioid use were excluded. Sociodemographic data, medical comorbidities, use of anxiolytics or antidepressants, smoking history, nonopioid substance use, intrapartum and cesarean delivery characteristics, and opioid consumption data (converted to morphine milligram equivalents) were abstracted. We defined high opioid use as a mean daily opioid consumption, standardized to the postoperative length of stay (excluding the first 24 postoperative hours to account for neuraxial morphine), greater than the 75th percentile of all opioid consumption. We used multivariable Poisson regression, stratified by whether or not cesarean delivery was scheduled, to identify characteristics associated with high opioid consumption.

Results: Among 949 women who underwent cesarean delivery, the mean (SD) and median (interquartile range) daily opioid consumption was 48.6 (22.8) and 44.6 (36.6-66.6) morphine milligram equivalents, respectively. Among those women with high opioid consumption, the mean (SD) and median (interquartile range) daily opioid consumption was 78.8 (8.5) and 78.3 (72.9-83.5) morphine milligram equivalents, respectively. Daily opioid consumption among those with high consumption was similar among women with scheduled compared with unscheduled cesarean delivery. Sociodemographic characteristics were similar among women with and without high opioid consumption. No sociodemographic, antepartum, or intrapartum characteristics were associated with high opioid consumption for either women having unscheduled or scheduled cesarean deliveries.

Conclusion: For a quarter of women undergoing cesarean delivery, daily consumption of opioids is equivalent to 10 tablets of oxycodone 5 mg daily. No characteristics were associated with high opioid use for women having a scheduled or unscheduled cesarean delivery. Understanding opioid consumption after cesarean delivery is critical to managing women's postoperative pain while decreasing opioid exposure and risks of long-term opioid use disorder.
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http://dx.doi.org/10.1097/AOG.0000000000003087DOI Listing
February 2019

Effects of Intermittent Versus Continuous Energy Intakes on Insulin Sensitivity and Metabolic Risk in Women with Overweight.

Obesity (Silver Spring) 2019 01;27(1):50-58

Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.

Objective: This study aimed to compare intermittent fasting (IF) versus continuous energy intakes at 100% or 70% of calculated energy requirements on insulin sensitivity, cardiometabolic risk, body weight, and composition.

Methods: Women with overweight (n = 88; 50 ± 1 years, BMI 32.3 ± 0.5 kg/m ) were randomized to one of four diets (IF70, IF100, dietary restriction [DR70], or control) in a 2:2:2:1 ratio for 8 weeks. IF groups fasted for 24 hours after breakfast on three nonconsecutive days per week. All foods were provided and diets matched for macronutrient composition (35% fat, 15% protein, 50% carbohydrate). Insulin sensitivity by hyperinsulinemic-euglycemic clamp, weight, body composition, and plasma markers were assessed following a "fed" day (12-hour fast) and a 24-hour fast (IF only).

Results: IF70 displayed greater reductions in weight, fat mass, total- and low-density lipoprotein cholesterol, and nonesterified fatty acids compared with DR70 and IF100 (all P ≤ 0.05). IF100 lost more weight and fat than control. However, fasting insulin was increased. There were no group differences in insulin sensitivity by clamp; however, a 24-hour fast transiently reduced insulin sensitivity.

Conclusions: When prescribed at matched energy restriction, IF reduced weight and fat mass and improved total and low-density lipoprotein cholesterol more than DR. IF prescribed in energy balance did not improve health compared with other groups, despite modest weight loss.
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http://dx.doi.org/10.1002/oby.22345DOI Listing
January 2019

Noninvasive Detection of Tuberculosis by Oral Swab Analysis.

J Clin Microbiol 2019 03 27;57(3). Epub 2019 Feb 27.

Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, Washington, USA

Diagnostic tests for tuberculosis (TB) usually require collection of sputum, a viscous material derived from human airways. Sputum can be difficult and hazardous to collect and challenging to process in the laboratory. Oral swabs have been proposed as alternative sample types that are noninvasive and easy to collect. This study evaluated the biological feasibility of oral swab analysis (OSA) for the diagnosis of TB. Swabs were tested from South African adult subjects, including sputum GeneXpert MTB/RIF (GeneXpert)-confirmed TB patients ( = 138), sputum GeneXpert-negative but culture-positive TB patients ( = 10), ill non-TB patients ( = 37), and QuantiFERON-negative controls ( = 34). Swabs were analyzed by using a manual, nonnested quantitative PCR (qPCR) targeting IS Two swab brands and three sites within the oral cavity were compared. Tongue swabbing yielded significantly stronger signals than cheek or gum swabbing. A flocked swab performed better than a more expensive paper swab. In a two-phase study, tongue swabs (two per subject) exhibited a combined sensitivity of 92.8% relative to sputum GeneXpert. Relative to all laboratory-diagnosed TB, the diagnostic yields of sputum GeneXpert (1 sample per subject) and OSA (2 samples per subject) were identical at 49/59 (83.1%) each. The specificity of the OSA was 91.5%. An analysis of "air swabs" suggested that most false-positive results were due to contamination of manual PCRs. With the development of appropriate automated methods, oral swabs could facilitate TB diagnosis in clinical settings and patient populations that are limited by the physical or logistical challenges of sputum collection.
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http://dx.doi.org/10.1128/JCM.01847-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425180PMC
March 2019

The two phases of the Cambrian Explosion.

Sci Rep 2018 11 9;8(1):16656. Epub 2018 Nov 9.

School of GeoSciences, University of Edinburgh, King's Buildings, James Hutton Road, Edinburgh, EH9 3FE, UK.

The dynamics of how metazoan phyla appeared and evolved - known as the Cambrian Explosion - remains elusive. We present a quantitative analysis of the temporal distribution (based on occurrence data of fossil species sampled in each time interval) of lophotrochozoan skeletal species (n = 430) from the terminal Ediacaran to Cambrian Stage 5 (~545 - ~505 Million years ago (Ma)) of the Siberian Platform, Russia. We use morphological traits to distinguish between stem and crown groups. Possible skeletal stem group lophophorates, brachiopods, and molluscs (n = 354) appear in the terminal Ediacaran (~542 Ma) and diversify during the early Cambrian Terreneuvian and again in Stage 2, but were devastated during the early Cambrian Stage 4 Sinsk extinction event (~513 Ma) never to recover previous diversity. Inferred crown group brachiopod and mollusc species (n = 76) do not appear until the Fortunian, ~537 Ma, radiate in the early Cambrian Stage 3 (~522 Ma), and with minimal loss of diversity at the Sinsk Event, continued to diversify into the Ordovician. The Sinsk Event also removed other probable stem groups, such as archaeocyath sponges. Notably, this diversification starts before, and extends across the Ediacaran/Cambrian boundary and the Basal Cambrian Carbon Isotope Excursion (BACE) interval (~541 to ~540 Ma), ascribed to a possible global perturbation of the carbon cycle. We therefore propose two phases of the Cambrian Explosion separated by the Sinsk extinction event, the first dominated by stem groups of phyla from the late Ediacaran, ~542 Ma, to early Cambrian stage 4, ~513 Ma, and the second marked by radiating bilaterian crown group species of phyla from ~513 Ma and extending to the Ordovician Radiation.
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http://dx.doi.org/10.1038/s41598-018-34962-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6226464PMC
November 2018

Wintertime stress, nursing, and lead exposure in Neanderthal children.

Sci Adv 2018 10 31;4(10):eaau9483. Epub 2018 Oct 31.

The Senator Frank R. Lautenberg Environmental Health Sciences Laboratory, Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Scholars endeavor to understand the relationship between human evolution and climate change. This is particularly germane for Neanderthals, who survived extreme Eurasian environmental variation and glaciations, mysteriously going extinct during a cool interglacial stage. Here, we integrate weekly records of climate, tooth growth, and metal exposure in two Neanderthals and one modern human from southeastern France. The Neanderthals inhabited cooler and more seasonal periods than the modern human, evincing childhood developmental stress during wintertime. In one instance, this stress may have included skeletal mobilization of elemental stores and weight loss; this individual was born in the spring and appears to have weaned 2.5 years later. Both Neanderthals were exposed to lead at least twice during the deep winter and/or early spring. This multidisciplinary approach elucidates direct relationships between ancient environments and hominin paleobiology.
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http://dx.doi.org/10.1126/sciadv.aau9483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209393PMC
October 2018

Exploring the drivers of early biomineralization.

Authors:
Rachel Wood

Emerg Top Life Sci 2018 Sep;2(2):201-212

School of GeoSciences, University of Edinburgh, James Hutton Road, Edinburgh EH9 3FE, U.K.

The first biomineralized hard parts are known from ∼810 Million years ago (Ma), consisting of phosphatic plates of probable protists formed under active biological control. Large skeletons in diverse taxa, probably including total-group poriferans and total-group cnidarians, first appear in the terminal Ediacaran, ∼550 Ma. This is followed by a substantial increase in abundance, diversity and mineralogy during the early Cambrian. The biological relationship of Ediacaran to early Cambrian skeletal biota is unclear, but tubular skeletal fossils such as Cloudina and Anabarites straddle the transition. Many Ediacaran skeletal biota are found exclusively in carbonate settings, and present skeletons whose form infers an organic scaffold which provided the framework for interactions between extracellular matrix and mineral ions. Several taxa have close soft-bodied counterparts hosted in contemporary clastic rocks. This supports the assertion that the calcification was an independent and derived feature that appeared in diverse groups, which was initially acquired with minimal biological control in the highly saturated, high-alkalinity carbonate settings of the Ediacaran, where the carbonate polymorph was further controlled by seawater chemistry. The trigger for Ediacaran-Cambrian biomineralization is far from clear, but may have been either changing seawater Mg/Ca ratios that facilitated widespread aragonite and high-Mg calcite precipitation, and/or increasing or stabilizing oxygen levels. By the Early Cambrian, the diversity of biomineralization styles may have been an escalating defensive response to increasing predation pressure, with skeletal hard parts first appearing in abundance in clastic settings by the Fortunian. This marks full independence from ambient seawater chemistry and significant biological control of biomineralization.
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http://dx.doi.org/10.1042/ETLS20170164DOI Listing
September 2018

A reassessment of the early archaeological record at Leang Burung 2, a Late Pleistocene rock-shelter site on the Indonesian island of Sulawesi.

PLoS One 2018 11;13(4):e0193025. Epub 2018 Apr 11.

Centre for Archaeological Science, School of Earth & Environmental Sciences, University of Wollongong, Wollongong, New South Wales, Australia.

This paper presents a reassessment of the archaeological record at Leang Burung 2, a key early human occupation site in the Late Pleistocene of Southeast Asia. Excavated originally by Ian Glover in 1975, this limestone rock-shelter in the Maros karsts of Sulawesi, Indonesia, has long held significance in our understanding of early human dispersals into 'Wallacea', the vast zone of oceanic islands between continental Asia and Australia. We present new stratigraphic information and dating evidence from Leang Burung 2 collected during the course of our excavations at this site in 2007 and 2011-13. Our findings suggest that the classic Late Pleistocene modern human occupation sequence identified previously at Leang Burung 2, and proposed to span around 31,000 to 19,000 conventional 14C years BP (~35-24 ka cal BP), may actually represent an amalgam of reworked archaeological materials. Sources for cultural materials of mixed ages comprise breccias from the rear wall of the rock-shelter-remnants of older, eroded deposits dated to 35-23 ka cal BP-and cultural remains of early Holocene antiquity. Below the upper levels affected by the mass loss of Late Pleistocene deposits, our deep-trench excavations uncovered evidence for an earlier hominin presence at the site. These findings include fossils of now-extinct proboscideans and other 'megafauna' in stratified context, as well as a cobble-based stone artifact technology comparable to that produced by late Middle Pleistocene hominins elsewhere on Sulawesi.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0193025PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5894965PMC
July 2018

The therapeutic effect of anti-CD52 treatment in murine experimental autoimmune encephalomyelitis is associated with altered IL-33 and ST2 expression levels.

J Neuroimmunol 2018 05 24;318:87-96. Epub 2018 Feb 24.

Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK. Electronic address:

Experimental autoimmune encephalomyelitis (EAE) mice were administered with murine anti-CD52 antibody to investigate its therapeutic effect and whether the treatment modulates IL-33 and ST2 expression. EAE severity and central nervous system (CNS) inflammation were reduced following the treatment, which was accompanied by peripheral T and B lymphocyte depletion and reduced production of various cytokines including IL-33, while sST2 was increased. In spinal cords of EAE mice, while the number of IL-33 cells remained unchanged, the extracellular level of IL-33 protein was significantly reduced in anti-CD52 antibody treated mice compared with controls. Furthermore the number of ST2 cells in the spinal cord of treated EAE mice was downregulated due to decreased inflammation and immune cell infiltration in the CNS. These results suggest that treatment with anti-CD52 antibody differentially alters expression of IL-33 and ST2, both systemically and within the CNS, which may indicate IL-33/ST2 axis is involved in the action of the antibody in inhibiting EAE.
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http://dx.doi.org/10.1016/j.jneuroim.2018.02.012DOI Listing
May 2018

Conflicting evidence for the role of JNK as a target in breast cancer cell proliferation: Comparisons between pharmacological inhibition and selective shRNA knockdown approaches.

Pharmacol Res Perspect 2018 02;6(1)

Strathclyde Institute for Pharmacy and Biomedical Sciences (SIPBS), University of Strathclyde, Glasgow, UK.

As a target, the JNK pathway has been implicated in roles including cell death, proliferation, and inflammation in variety of contexts which span cardiovascular disease, neurodegenerative pathologies, and cancer. JNK1 and JNK2 have recently been demonstrated to function independently, highlighting a new parameter in the study of the JNK pathway. In order for JNK1 and JNK2-specific roles to be defined, better tools need to be employed. Previous studies have relied upon the broad spectrum JNK inhibitor, SP600125, to characterize the role of JNK signaling in a number of cell lines, including the breast cancer cell line MCF-7. In line with previous literature, our study has demonstrated that SP600125 treatment inhibited c-Jun and JNK phosphorylation and MCF-7 proliferation. However, in addition to targeting JNK1, JNK2, and JNK3, SP600125 has been previously demonstrated to suppress the activity of a number of other serine/threonine kinases, making SP600125 an inadequate tool for JNK isoform-specific roles to be determined. In this study, lentiviral shRNA was employed to selectively knockdown JNK1, JNK2, and JNK1/2 in MCF-7 cells. Using this approach, JNK phosphorylation was fully inhibited following stable knockdown of respective JNK isoforms. Interestingly, despite suppression of JNK phosphorylation, MCF-7 cell proliferation, cell cycle progression, or cell death remained unaffected. These findings raise the question of whether JNK phosphorylation really is pivotal in MCF-7 cell growth and death or if suppression of these events is a result of one of the many off-targets cited for SP600125.
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http://dx.doi.org/10.1002/prp2.376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5817830PMC
February 2018

Substrate growth dynamics and biomineralization of an Ediacaran encrusting poriferan.

Proc Biol Sci 2018 01;285(1870)

School of GeoSciences, University of Edinburgh, James Hutton Road, Edinburgh EH9 3FE, UK.

The ability to encrust in order to secure and maintain growth on a substrate is a key competitive innovation in benthic metazoans. Here we describe the substrate growth dynamics, mode of biomineralization and possible affinity of , a large (up to 1 m), robustly skeletal, and modular Ediacaran metazoan which encrusted the walls of synsedimentary fissures within microbial-metazoan reefs. formed laminar or domal morphologies with an internal structure of open tubules and transverse elements, and had a very plastic, non-deterministic growth form which could encrust both fully lithified surfaces as well as living microbial substrates, the latter via modified skeletal holdfasts. shows complex growth interactions and substrate competition with contemporary living microbialites and thrombolites, including the production of plate-like dissepiments in response to microbial overgrowth which served to elevate soft tissue above the microbial surface. could also recover from partial mortality due to microbial fouling. We infer initial skeletal growth to have propagated via the rapid formation of an organic scaffold via a basal pinacoderm prior to calcification. This is likely an ancient mode of biomineralization with similarities to the living calcified demosponge also shows inferred skeletal growth banding which, combined with its large size, implies notable individual longevity. In sum, was a large, relatively long-lived Ediacaran clonal skeletal metazoan that propagated via an organic scaffold prior to calcification, enabling rapid, effective and dynamic substrate occupation and competition in cryptic reef settings. The open tubular internal structure, highly flexible, non-deterministic skeletal organization, and inferred style of biomineralization of places probable affinity within total-group poriferans.
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http://dx.doi.org/10.1098/rspb.2017.1938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5784191PMC
January 2018

Innovation not recovery: dynamic redox promotes metazoan radiations.

Biol Rev Camb Philos Soc 2018 05 16;93(2):863-873. Epub 2017 Oct 16.

Department of Paleobiology, Smithsonian Institution, Washington, DC 20013-7012, U.S.A.

Environmental fluctuations in redox may reinforce rather than hinder evolutionary transitions, such that variability in near-surface oceanic oxygenation can promote morphological evolution and novelty. Modern, low-oxygen regions are heterogeneous and dynamic habitats that support low diversity and are inhabited by opportunistic and non-skeletal metazoans. We note that several major radiation episodes follow protracted or repeating intervals (>1 million years) of persistent and dynamic shallow marine redox (oceanic anoxic events). These are also often associated with short-lived mass-extinction events (<0.5 million years) where skeletal benthic incumbents are removed, and surviving or newly evolved benthos initially inhabit transient oxic habitats. We argue that such intervals create critical opportunities for the generation of evolutionary novelty, followed by innovation and diversification. We develop a general model for redox controls on the distribution and structure of the shallow marine benthos in a dominantly anoxic world, and compile data from the terminal Ediacaran-mid-Cambrian (∼560-509 Ma), late Cambrian-Ordovician (∼500-445 Ma), and Permo-Triassic (∼255-205 Ma) to test these predictions. Assembly of phylogenetic data shows that prolonged and widespread anoxic intervals indeed promoted morphological novelty in soft-bodied benthos, providing the ancestral stock for subsequently skeletonized lineages to appear as innovations once oxic conditions became widespread and stable, in turn promoting major evolutionary diversification. As a result, we propose that so-called 'recovery' intervals after mass extinctions might be better considered as 'innovation' intervals.
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http://dx.doi.org/10.1111/brv.12375DOI Listing
May 2018

Can the Apgar Score be Used for International Comparisons of Newborn Health?

Paediatr Perinat Epidemiol 2017 07 16;31(4):338-345. Epub 2017 Jun 16.

INSERM UMR 1153, Obstetrical, Perinatal and Pediatric Epidemiology Research Team, Center for Epidemiology and Biostatistics, Paris-Descartes University, Paris, France.

Background: The Apgar score has been shown to be predictive of neonatal mortality in clinical and population studies, but has not been used for international comparisons. We examined population-level distributions in Apgar scores and associations with neonatal mortality in Europe.

Methods: Aggregate data on the 5 minute Apgar score for live births and neonatal mortality rates from countries participating in the Euro-Peristat project in 2004 and 2010 were analysed. Country level associations between the Apgar score and neonatal mortality were assessed using the Spearman rank correlation coefficient.

Results: Twenty-three countries or regions provided data on Apgar at 5 minutes, covering 2 183 472 live births. Scores <7 ranged from 0.3% to 2.4% across countries in 2004 and 2010 and were correlated over time (ρ = 0.88, P < 0.01). There were large differences in healthy baby scores: scores of 10 ranged from 8.8% to 92.7% whereas scores of 9 or 10 ranged from 72.9% to 96.8%. Countries more likely to score 10 s, as opposed to 9 s, for healthy babies had lower proportions of Apgar <7 (ρ = -0.43, P = 0.04). Neonatal mortality rates were weakly correlated with Apgar score <7 (ρ = -0.06, P = 0.61), but differences over time in these two indicators were correlated (ρ =0.56, P = 0.02).

Conclusions: Large variations in the distribution of Apgar scores likely due to national scoring practices make the Apgar score an unsuitable indicator for benchmarking newborn health across countries. However, country-level trends over time in the Apgar score may reflect real changes and merit further investigation.
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http://dx.doi.org/10.1111/ppe.12368DOI Listing
July 2017

First macrobiota biomineralization was environmentally triggered.

Proc Biol Sci 2017 Mar;284(1851)

Department of Biological Evolution, Faculty of Biology, Lomonosov Moscow State University, Leninskie gory 1(12), Moscow 119234, Russia.

Why large and diverse skeletons first appeared 550 Ma is not well understood. Many Ediacaran skeletal biota show evidence of flexibility, and bear notably thin skeletal walls with simple, non-hierarchical microstructures of either aragonite or high-Mg calcite. We present evidence that the earliest skeletal macrobiota, found only in carbonate rocks, had close soft-bodied counterparts hosted in contemporary clastic rocks. This includes the calcareous discoidal fossil similar to holdfasts of Ediacaran biota taxa previously known only as casts and moulds, as well as tubular and vase-shaped fossils. In sum, these probably represent taxa of diverse affinity including unicellular eukaryotes, total group cnidarians and problematica. Our findings support the assertion that the calcification was an independent and derived feature that appeared in diverse groups where an organic scaffold was the primitive character, which provided the framework for interactions between the extracellular matrix and mineral ions. We conclude that such skeletons may have been acquired with relative ease in the highly saturated, high alkalinity carbonate settings of the Ediacaran, where carbonate polymorph was further controlled by seawater chemistry. The trigger for Ediacaran biomineralization may have been either changing seawater Mg/Ca and/or increasing oxygen levels. By the Early Cambrian, however, biomineralization styles and the range of biominerals had significantly diversified, perhaps as an escalating defensive response to increasing predation pressure. Indeed skeletal hardparts had appeared in clastic settings by Cambrian Stage 1, suggesting independence from ambient seawater chemistry where genetic and molecular mechanisms controlled biomineralization and mineralogy had become evolutionarily constrained.
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http://dx.doi.org/10.1098/rspb.2017.0059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378091PMC
March 2017