UW Neurological Surgery Recent PubMed Publications

Effects of intrastriatal dopamine D1 or D2 antagonists on methamphetamine-induced egocentric and allocentric learning and memory deficits in Sprague-Dawley rats.

Psychopharmacology (Berl). 2019 Jul;236(7):2243-2258

Authors: Gutierrez A, Regan SL, Hoover CS, Williams MT, Vorhees CV

Abstract
RATIONALE: Methamphetamine (MA) is an abused psychostimulant that causes cognitive deficits after chronic use. Neostriatal dopamine receptors play a role in MA monoamine neurotoxicity. Blocking dopamine receptors prior to MA exposure in adult rats attenuates monoamine reductions and reactive gliosis.
OBJECTIVES: We tested whether blocking dopamine receptors protects against cognitive deficits.
METHODS: First, we determined the effects of MA alone versus MA in combination with the dopamine receptor D1 antagonist SCH-23390 or the dopamine receptor D2 antagonist sulpiride on cFos expression and monoamines at the age when rats in the cognitive experiment were to begin testing and monoamines in rats after cognitive testing.
RESULTS: SCH-23390 infused into the neostriatum prior to systemic administration of MA attenuated MA-induced cFos activation while sulpiride induced cFos activation. Two weeks after MA, rats had dopamine and serotonin reductions that were attenuated by each antagonist. Other rats treated the same way, were tested for egocentric learning and memory in the Cincinnati water maze, for navigational strategy in a star water maze, and spatial learning and memory in a Morris water maze. Pre-treatment with SCH-23390 or sulpiride attenuated the effects of MA on egocentric and spatial learning and memory. MA-treated rats showed a shift from an egocentric to a disorganized strategy in the star maze that was less disorganized in groups receiving MA and an antagonist. Post-behavior monoamine reductions remained but were attenuated by the antagonists but not identically to what was seen in rats not behaviorally tested.
CONCLUSIONS: The results show for the first time that dopamine receptors are mediators of MA-induced cognitive deficits.

PMID: 30919007 [PubMed - indexed for MEDLINE]

High level of capture of coronary intervention and associated acute coronary syndromes in the all New Zealand acute coronary syndrome quality improvement cardiac registry and excellent agreement with national administrative datasets (ANZACS-QI 25).

N Z Med J. 2019 03 29;132(1492):19-29

Authors: Kerr AJ, Lee M, Jiang Y, Grey C, Wells S, Williams M, Jackson R, Poppe K

Abstract
BACKGROUND: The All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) registry was designed to collect data on all coronary angiograms and percutaneous coronary interventions (PCI) in New Zealand, and all acute coronary syndromes (ACS) associated with these procedures. This study compares the completeness of capture in ANZACS-QI of coronary procedures and ACS admissions with those recorded in the National Hospitalisation Dataset and evaluates data quality by assessing agreement in ACS diagnoses and coronary procedures between datasets.
METHODS: The national dataset, which included all New Zealand public hospital admissions in 2015 (n=962,700 episodes), was anonymously linked with the ANZACS-QI CathPCI (n=14,649 coronary angiogram episodes) and ACS cohorts (n=8,141 episodes) for 2015. Total numbers of coronary angiogram, PCI and ACS admissions were used as denominators and calculated by combining unique episodes from both data sources.
RESULTS: Of all coronary angiogram episodes (n=15,377) and all PCI episodes (n=5,711), 92% were captured in both datasets, 5% in the national dataset only and 3% in ANZACS-QI only. Overall, 95% of coronary angiogram and PCI episodes were captured in ANZACS-QI. Of ACS episodes with associated coronary angiography (n=8,237), 85% were captured. Overall, 54% of all ACS episodes (n=15,167) were captured, including 71% in <70-year-olds. Seventy-five percent of all ST-elevation myocardial infarctions (STEMI) were captured. Ninety percent of ACS diagnoses in ANZACS-QI had a matching diagnosis in the national dataset. There was excellent agreement in recorded gender, date of birth and ethnicity (>99%). Sub-type of ACS was also highly concordant for STEMI and non-STEMI diagnoses (92% and 89% agreement, respectively).
CONCLUSIONS: Consistent with its aim, the ANZACS-QI registry captured almost all New Zealand public hospital coronary angiography and PCI procedures including those associated with an ACS diagnosis. The high level of agreement between the registry and national dataset supports the use of both datasets for ongoing quality improvement reporting and research.

PMID: 30921308 [PubMed - indexed for MEDLINE]

Malaria Parasite Density in Individuals with Different Rapid Diagnostic Test Results and Concentrations of HRP2 Antigen.

Am J Trop Med Hyg. 2019 05;100(5):1202-1203

Authors: Plucinski MM, Dimbu PR, Fortes F, Murphy SC, Smith NT, Cruz KR, Seilie AM, Halsey ES, Aidoo M, Rogier E

Abstract
Low-density malaria infections are a source of human morbidity in endemic settings and potentially contribute to ongoing malaria transmission. Conventional rapid diagnostic tests (RDTs) were designed to detect clinically relevant parasite and antigen levels, but it is largely unknown what proportion of parasite (and antigen positive) infections are missed by conventional RDTs. Furthermore, RDTs can also provide false positives from lingering histidine-rich protein 2 (HRP2) antigenemia from a past infection. We analyzed 207 samples from Angolan outpatients with a bead-based HRP2 antigen assay and by qRT-PCR for the presence of parasite nucleic acids. Among patients HRP2 positive but negative by conventional RDT, the rate of quantitative reverse transcription-PCR (qRT-PCR) positivity was 45% (95% CI: 35-56%), with a median parasitemia of 3.4 parasites/µL (interquartile range: 0.14-4.8). Only 15% (7-26%) of HRP2-negative samples were found to have parasite nucleic acids. A substantial proportion of persons with blood HRP2 antigen concentrations not detected by the conventional RDT were found to have evidence of active infection, but at low parasite density levels.

PMID: 30915959 [PubMed - indexed for MEDLINE]

Divergent 6-Month Functional Recovery Trajectories and Predictors after Traumatic Brain Injury: Novel Insights from the COBRIT Study.

J Neurotrauma. 2019 Mar 26;:

Authors: Gardner RC, Cheng J, Ferguson AR, Boylan R, Boscardin WJ, Zafonte RD, Manley GT, Bagiella E, Ansel BM, Novack TA, Friedewald WT, Hesdorffer DC, Timmons S, Jallo J, Eisenberg H, Hart T, Ricker JH, Diaz-Arrastia R, Merchant R, Temkin NR, Melton S, Dikmen S, Okonkwo DO

Abstract
Cross-sectional approaches to outcome assessment may not adequately capture heterogeneity in recovery after traumatic brain injury (TBI). Using latent class mixed models (LCMM), a data-driven analytic that identifies groups of patients with similar trajectories, we identified distinct 6-month functional recovery trajectories in a large cohort (n=1,046) of adults age 18-70 years with complicated mild to severe TBI who participated in the Citicoline Brain Injury Treatment Trial (COBRIT). We used multinomial logistic fixed effect models and backward elimination, forward selection, and forward stepwise selection with several stopping rules to explore baseline predictors of functional recovery trajectory. Based on statistical and clinical considerations, the 7-class model was deemed superior. Visualization of these 7 functional recovery trajectories revealed that each trajectory class started at one of 3 recovery levels at 1-month, which, for ease of reference we labeled groups A-C: Group A. good recovery (2 classes; A1 and A2), Group B. moderate disability (2 classes; B1 and B2), Group C. severe disability (3 classes; C1, C2, and C3). By 6-months, these 3 groups experienced dramatically divergent trajectories: A experienced stable good recovery (A1, n=115) or dramatic decline (A2, n=4); B, rapid complete recovery (B1, n=71) or gradual recovery (B2, n=742); C, dramatic rapid recovery (C1, n=12), no recovery (C2, n=91), or death (C3, n=11). Trajectory class membership was not predicted by citicoline treatment (p=0.57). The models identified demographic, pre-injury, and injury-related predictors of functional recovery trajectory, including: age, race, education, pre-injury employment, pre-injury diabetes, pre-injury psychiatric disorder, site, Glasgow Coma Scale (GCS), post-traumatic amnesia, TBI mechanism, major extracranial injury, hemoglobin, and acute CT findings. GCS was the most consistently selected predictor across all models. All models also selected at least one demographic or pre-injury medical predictor. LCMM successfully identified dramatically divergent, clinically meaningful 6-month recovery trajectories with utility to inform clinical trial design.

PMID: 30909795 [PubMed - as supplied by publisher]

Brief and cost-effective tool for assessing verbal learning in multiple sclerosis: Comparison of the Rey Auditory Verbal Learning Test (RAVLT) to the California Verbal Learning Test - II (CVLT-II).

J Neurol Sci. 2019 May 15;400:104-109

Authors: Beier M, Hughes AJ, Williams MW, Gromisch ES

Abstract
BACKGROUND: The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) is a common cognitive screening tool. However, administration and scoring can be time-consuming, and its use of proprietary subtests like the California Verbal Learning Test - II (CVLT-II) is financially limiting. Use of the non-proprietary Rey Auditory Verbal Learning Test (RAVLT) may be provide a valid alternative.
OBJECTIVES: To compare the RAVLT and CVLT-II in terms of diagnostic accuracy for detecting cognitive impairment, and to determine optimal cut-scores for the RAVLT.
METHODS: 100 participants with MS completed the five learning trials from the RAVLT and CVLT-II. Receiver operating characteristic analyses were used to compare the measures' sensitivities, specificities, positive predictive values (PPV) and negative predictive values (NPV), and to identify optimal cut-scores.
RESULTS: Using a criterion of 1.5 SD below the normative sample mean, the RAVLT showed fair to good (κs = 0.21-0.41) agreement with the CVLT-II. A cut-score of 12 on Trials 1 + 2 of the RAVLT showed fair sensitivity (75%) and specificity (76%) and did not differ significantly from the CVLT-II (p > .05).
CONCLUSIONS: Performance on initial learning trials of the RAVLT may provide a brief, valid, and cost-effective alternative to the CVLT-II for screening verbal learning impairments in MS.

PMID: 30913522 [PubMed - indexed for MEDLINE]

Evidence that Human Skin Microbiome Dysbiosis Promotes Atopic Dermatitis.

J Invest Dermatol. 2017 12;137(12):2460-2461

Authors: Williams MR, Gallo RL

Abstract
Patients with atopic dermatitis are frequently colonized by Staphylococcus aureus. If S. aureus is present, then the subject tends to have more severe disease. However, it is unclear if S. aureus is a cause of atopic dermatitis or a consequence of the abnormal epithelial environment. In this issue of the Journal of Investigative Dermatology, Meylan et al. present evidence from a prospective clinical trial that shows that S. aureus colonization precedes onset of atopic dermatitis in children. These observations suggest that S. aureus may cause atopic dermatitis in some individuals.

PMID: 29169458 [PubMed - indexed for MEDLINE]

Pilocytic astrocytoma with leptomeningeal spread in a patient with incontinentia pigmenti presenting with unilateral nystagmus.

Pediatr Blood Cancer. 2018 03;65(3):

Authors: Bayart CB, Ishak GE, Finn LS, Lee A, Baran F, Sun A, Gupta D, Vitanza NA

Abstract
Incontinentia pigmenti (IP) is a genetic disorder caused by mutations in IKBKG, leading to functional loss of nuclear factor kappa B (NF-ĸB). We report the case of a 6-month-old female child with IP who presented with unilateral nystagmus and was found to have a pilocytic astrocytoma with leptomeningeal spread. Enhanced understanding of the relationship between NF-ĸB, along with its upstream regulators, and tumorigenesis may shed light on whether a subset of patients with IP may be at increased risk for neoplasia.

PMID: 29171168 [PubMed - indexed for MEDLINE]

Diagnosing the GOSE: Structural and Psychometric Properties Using Item Response Theory, a TRACK-TBI Pilot Study.

J Neurotrauma. 2019 09 01;36(17):2493-2505

Authors: Ranson J, Magnus BE, Temkin N, Dikmen S, Giacino JT, Okonkwo DO, Valadka AB, Manley GT, Nelson LD, TRACK-TBI Investigators

Abstract
The Glasgow Outcome Scale-Extended (GOSE) was designed to assess global outcome after traumatic brain injury (TBI). Since its introduction, several empirically founded criticisms of the GOSE have been raised, including poor reliability; an insensitivity to small, but potentially meaningful, changes; a tendency to produce ceiling effects; inconsistent associations with neurocognitive, psychological, and quality-of-life measures; and an inability to assess the multi-dimensional nature of TBI outcome. The current project took a diagnostic approach to identifying the underlying causes of reported limitations by exploring the internal construct validity of the GOSE at 3 and 6 months post-injury using item response theory (IRT) techniques. Data were from the TRACK-TBI Pilot Study, a large (N = 586), prospective, multi-site project that included TBI cases of all injury severity levels. To assess the level of latent functional "impairment" captured by GOSE items independent of the assigned outcome category or GOSE total score, items were modified so that higher scores reflected greater impairment. Results showed that although the GOSE's items capture varying levels of impairment across a broad disability spectrum at 3 and 6 months, there was also evidence at each time point of item redundancy (multiple items capturing similar levels of impairment), item deficiency (lack of items capturing lower levels of impairment), and item inefficiency (items only capturing minimal impairment information). The findings illustrate the value of IRT to illuminate strengths and weaknesses of clinical outcome assessment measures and provide a framework for future measure refinement.

PMID: 30907261 [PubMed - indexed for MEDLINE]

Modeling breathing rhythms.

Elife. 2019 03 25;8:

Authors: Ramirez JM, Baertsch NA

Abstract
Computational models are helping researchers to understand how certain properties of neurons contribute to respiratory rhythms.

PMID: 30907725 [PubMed - indexed for MEDLINE]

Intense Focused Ultrasound Preferentially Stimulates Transected Nerves Within Residual Limbs: Pilot Study.

Pain Med. 2018 03 01;19(3):541-549

Authors: Mourad PD, Friedly JL, McClintic AM, Olmstead TA, Loeser JD

Abstract
Objective: Identifying pain generators in tissue deep in the skin can require uncomfortable, complicated, and invasive tests. We describe pilot studies testing the hypothesis that ultrasound image-guided, intense focused ultrasound (ig-iFU) can noninvasively and differentially stimulate the end of transected nerves in the residual limbs of amputee patients.
Design: We applied iFU to the transected nerve ending as individual pulses with a length of 0.1 seconds using a carrier frequency of 2.0 MHz. After targeting, we gradually increased the iFU intensity to reach consistent patient-reported stimulation of the transected nerve ending. We also stimulated the proximal nerve, tissue near the nerve ending, and the intact contralateral nerve. We described the resulting sensations and correlated the results of the study participant's pre-iFU study responses to phantom and residual limb pain questionnaires.
Results: iFU spatial and temporal average intensity values between 16 W/cm2 and 433 W/cm2 that were applied to the transected nerve ending and proximal nerve elicited sensations, including phantom limb sensations, while the same intensity applied to control tissue centimeters away from the nerve ending, or to the intact nerve on the contralateral limb, did not. Two out of 11 study participants reported only mild and transient pain created by iFU stimulation. Successful iFU intensity values correlated with neither phantom nor residual limb pain scores.
Conclusions: Transected nerves had greater sensitivity to iFU stimulation than ipsilateral and contralateral control tissue, including intact nerve. These results support the view that ig-iFU may one day help physicians identify deep, tender tissue in patients who report experiencing pain.

PMID: 29025106 [PubMed - indexed for MEDLINE]

All-Cause Mortality Following an Acute Coronary Syndrome: 12-Year Follow-Up of the Comprehensive 2002 New Zealand Acute Coronary Syndrome Audit.

Heart Lung Circ. 2019 Feb;28(2):245-256

Authors: Ellis CJ, Gamble GD, Williams MJA, Matsis P, Elliott JM, Devlin G, Mann S, French JK, White HD, Regional Cardiac Society NZ ACS Audit Group

Abstract
BACKGROUND: To describe the long-term mortality of a complete national cohort of acute coronary syndrome (ACS) patients enrolled in 2002, to compare this with a national age, sex and Māori ethnicity matched population, and to assess the influence of baseline factors on the 12-year mortality.
METHODS: We reviewed 721 patients with a discharge diagnosis of an ACS who were enrolled in the first New Zealand ACS audit group cohort over 14days in May 2002. We matched the cohort to the national mortality database using each patient's unique national identity number.
RESULTS: Over a median follow-up of 12.7 years of 721 patients discharged with an ACS, overall mortality was 52%: ST-elevation myocardial infarction (STEMI) (58%), non-ST-elevation myocardial infarction (NSTEMI) (61%) and unstable angina pectoris (UAP) (42%) patients, p<0.0001. In an age-adjusted survival model, males had a 29% increased mortality rate compared to females with a hazard ratio of 1.29 (95% CI 1.04, 1.61, p=0.019). Over 12 years there were 339 (47%) deaths, compared to 284 (39%) deaths observed in the matched population. The standardised mortality ratio for patients admitted with an ACS in New Zealand is 1.3 (95% CI 1.2, 1.5) with eight patients per 100 not surviving to 12 years compared to this matched population.
CONCLUSIONS: The high mortality rate in this ACS cohort is a stark reminder of the prognostic implications of a presentation with an ACS. It emphasises the on-going need for optimal management of these patients throughout every stage of their initial treatment and subsequent on-going care.

PMID: 29150157 [PubMed - indexed for MEDLINE]

Isoalantolactone induces apoptosis through ROS-mediated ER stress and inhibition of STAT3 in prostate cancer cells.

J Exp Clin Cancer Res. 2018 Dec 12;37(1):309

Authors: Chen W, Li P, Liu Y, Yang Y, Ye X, Zhang F, Huang H

Abstract
BACKGROUND: Prostate cancer is one of the most commonly diagnosed cancers in men worldwide. Currently available therapies for metastatic prostate cancer are only marginally effective. Therefore, new therapeutic agents are urgently needed to improve patient outcome. Isoalantolactone (IATL), an active sesquiterpene naturally present in many vegetables and medicinal plants, is known to induce cell death and apoptosis in various cancer cell lines. Nevertheless, antitumor mechanisms initiated by IATL in cancer cells have not been fully defined.
METHODS: Cell apoptosis and cellular ROS levels were analyzed by flow cytometry. Western blot and qRT-PCR were used to analyze the protein and mRNA levels of indicated molecules, respectively. Nude mice xenograft model was used to test the effects of IATL on prostate cancer cell growth in vivo.
RESULTS: In this study, we found that IATL dose-dependently inhibited cancer cell growth and induced apoptosis in PC-3 and DU145 cells. Mechanistically, our data found that IATL induced reactive oxygen species (ROS) production, resulting in the activation of endoplasmic reticulum stress pathway and eventually cell apoptosis in prostate cancer cells. IATL also decreased the protein expression levels of p-STAT3 and STAT3, and the effects of IATL were reversed by pretreatment with N-acetyl-L-cysteine (NAC). In vivo, we found that IATL inhibited the growth of prostate cancer xenografts without exhibiting toxicity. Treatment of mice bearing human prostate cancer xenografts with IATL was also associated with induction of ER stress and inhibtion of STAT3.
CONCLUSION: In summary, our results unveil a previously unrecognized mechanism underlying the biological activity of IATL, and provide a novel anti-cancer candidate for the treatment of prostate cancer.

PMID: 30541589 [PubMed - indexed for MEDLINE]

Discussion: Craniometric Analysis of Endoscopic Suturectomy for Bilateral Coronal Craniosynostosis.

Plast Reconstr Surg. 2019 01;143(1):199-201

Authors: Hopper RA, Lee A

PMID: 30589794 [PubMed - indexed for MEDLINE]

Misclassification of Myocardial Injury as Myocardial Infarction: Implications for Assessing Outcomes in Value-Based Programs.

JAMA Cardiol. 2019 05 01;4(5):460-464

Authors: McCarthy C, Murphy S, Cohen JA, Rehman S, Jones-O'Connor M, Olshan DS, Singh A, Vaduganathan M, Januzzi JL, Wasfy JH

Abstract
Importance: Similar to other patients with acute myocardial infarction, patients with type 2 myocardial infarction (T2MI) are included in several value-based programs, including the Hospital Readmissions Reduction Program and the Hospital Value-Based Purchasing Program. To our knowledge, whether nonischemic myocardial injury is being misclassified as T2MI is unknown and may have implications for these programs.
Objective: To determine whether patients with nonischemic myocardial injury are being miscoded as having T2MI and if this has implications for 30-day readmission and mortality rates.
Design, Settings, and Participants: Using the new International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code, we identified patients who were coded as having T2MI between October 2017 and May 2018 at Massachusetts General Hospital. Strict adjudication using the fourth universal definition of MI was then applied.
Main outcome and Measures: Clinical adjudication of T2MI and 30-day readmission and mortality rates as a function of T2MI or nonischemic myocardial injury.
Results: Of 633 patients, 369 (58.3%) were men and 514 (81.2%) were white. After strict adjudication, 359 (56.7%) had T2MI, 265 (41.9%) had myocardial injury, 6 (0.9%) had type 1 MI, and 3 (0.5%) had unstable angina. Patients with T2MI had a higher prevalence of cardiovascular comorbidities than those with myocardial injury. Patients with T2MI and myocardial injury had high in-hospital mortality rates (10.6% and 8.7%, respectively; P = .50). Of those discharged alive (563 [88.9%]), 30-day readmission rates (22.7% vs 21.1%; P = .68) and mortality rates (4.4% vs 7.4%; P = .14) were comparable among patients with T2MI and myocardial injury.
Conclusions and Relevance: A substantial percentage of patients coded as having T2MI actually have myocardial injury. Both conditions have high 30-day readmission and mortality rates. Including patients with high-risk myocardial injury may have substantial implications for value-based programs.

PMID: 30879022 [PubMed - indexed for MEDLINE]

Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform.

Sci Rep. 2017 08 18;7(1):8837

Authors: Skardal A, Murphy SV, Devarasetty M, Mead I, Kang HW, Seol YJ, Shrike Zhang Y, Shin SR, Zhao L, Aleman J, Hall AR, Shupe TD, Kleensang A, Dokmeci MR, Jin Lee S, Jackson JD, Yoo JJ, Hartung T, Khademhosseini A, Soker S, Bishop CE, Atala A

Abstract
Many drugs have progressed through preclinical and clinical trials and have been available - for years in some cases - before being recalled by the FDA for unanticipated toxicity in humans. One reason for such poor translation from drug candidate to successful use is a lack of model systems that accurately recapitulate normal tissue function of human organs and their response to drug compounds. Moreover, tissues in the body do not exist in isolation, but reside in a highly integrated and dynamically interactive environment, in which actions in one tissue can affect other downstream tissues. Few engineered model systems, including the growing variety of organoid and organ-on-a-chip platforms, have so far reflected the interactive nature of the human body. To address this challenge, we have developed an assortment of bioengineered tissue organoids and tissue constructs that are integrated in a closed circulatory perfusion system, facilitating inter-organ responses. We describe a three-tissue organ-on-a-chip system, comprised of liver, heart, and lung, and highlight examples of inter-organ responses to drug administration. We observe drug responses that depend on inter-tissue interaction, illustrating the value of multiple tissue integration for in vitro study of both the efficacy of and side effects associated with candidate drugs.

PMID: 28821762 [PubMed - indexed for MEDLINE]

Aspirin for the Primary Prevention of Cardiovascular Disease: Weighing Up the Evidence.

Am J Med. 2019 09;132(9):1007-1008

Authors: Murphy S, McCarthy CP, McEvoy JW

PMID: 30871925 [PubMed - indexed for MEDLINE]

Improving estimation of puma (Puma concolor) population density: clustered camera-trapping, telemetry data, and generalized spatial mark-resight models.

Sci Rep. 2019 03 14;9(1):4590

Authors: Murphy SM, Wilckens DT, Augustine BC, Peyton MA, Harper GC

Abstract
Obtaining reliable population density estimates for pumas (Puma concolor) and other cryptic, wide-ranging large carnivores is challenging. Recent advancements in spatially explicit capture-recapture models have facilitated development of novel survey approaches, such as clustered sampling designs, which can provide reliable density estimation for expansive areas with reduced effort. We applied clustered sampling to camera-traps to detect marked (collared) and unmarked pumas, and used generalized spatial mark-resight (SMR) models to estimate puma population density across 15,314 km2 in the southwestern USA. Generalized SMR models outperformed conventional SMR models. Integrating telemetry data from collars on marked pumas with detection data from camera-traps substantially improved density estimates by informing cryptic activity (home range) center transiency and improving estimation of the SMR home range parameter. Modeling sex of unmarked pumas as a partially identifying categorical covariate further improved estimates. Our density estimates (0.84-1.65 puma/100 km2) were generally more precise (CV = 0.24-0.31) than spatially explicit estimates produced from other puma sampling methods, including biopsy darting, scat detection dogs, and regular camera-trapping. This study provides an illustrative example of the effectiveness and flexibility of our combined sampling and analytical approach for reliably estimating density of pumas and other wildlife across geographically expansive areas.

PMID: 30872785 [PubMed - indexed for MEDLINE]

Climate-Altered Wetlands Challenge Waterbird Use and Migratory Connectivity in Arid Landscapes.

Sci Rep. 2019 Mar 15;9(1):4666

Authors: Haig SM, Murphy SP, Matthews JH, Arismendi I, Safeeq M

Abstract
Wetlands in arid landscapes provide critical habitat for millions of migratory waterbirds across the world and throughout their annual cycle. The scope and scale of understanding avian use of these wetlands in conjunction with changes in climate are daunting yet critical to address lest we lose continent-wide migratory pathways. Here, we assess changes in waterbird use of North America's Pacific Flyway in the Great Basin by examining water availability and climate trends over the past 100 years. We found recent (1980-2015) climate warming has significantly reduced the amount and shifted seasonality of water flowing into wetlands. Further, we found remarkable changes in waterbird species composition over time. We propose that a reduced hydroperiod and lower water quality from reduction in water level and flow limits sites used by waterbirds. These factors reduce chick survivorship as they cannot metabolize saline water, which makes suitable freshwater conditions a limiting resource. Collectively, climate-induced changes in Great Basin wetlands suggest a major shift in freshwater ecosystems, resulting in degradation of a continental migratory route. This work illustrates the importance of examining multi-scale changes in critical regional resources to understand their impact across a hemispheric flyway and provides a model to examine other flyways.

PMID: 30874622 [PubMed - in process]

Clot Analysis in Acute Ischemic Stroke.

Stroke. 2019 04;50(4):e106-e109

Authors: Walker M, Levitt MR, Gibbons EF, Horne DJ, Corcorran MA

PMID: 30869564 [PubMed - indexed for MEDLINE]

Dynamic molecular changes during the first week of human life follow a robust developmental trajectory.

Nat Commun. 2019 03 12;10(1):1092

Authors: Lee AH, Shannon CP, Amenyogbe N, Bennike TB, Diray-Arce J, Idoko OT, Gill EE, Ben-Othman R, Pomat WS, van Haren SD, Cao KL, Cox M, Darboe A, Falsafi R, Ferrari D, Harbeson DJ, He D, Bing C, Hinshaw SJ, Ndure J, Njie-Jobe J, Pettengill MA, Richmond PC, Ford R, Saleu G, Masiria G, Matlam JP, Kirarock W, Roberts E, Malek M, Sanchez-Schmitz G, Singh A, Angelidou A, Smolen KK, EPIC Consortium, Brinkman RR, Ozonoff A, Hancock REW, van den Biggelaar AHJ, Steen H, Tebbutt SJ, Kampmann B, Levy O, Kollmann TR

Abstract
Systems biology can unravel complex biology but has not been extensively applied to human newborns, a group highly vulnerable to a wide range of diseases. We optimized methods to extract transcriptomic, proteomic, metabolomic, cytokine/chemokine, and single cell immune phenotyping data from <1 ml of blood, a volume readily obtained from newborns. Indexing to baseline and applying innovative integrative computational methods reveals dramatic changes along a remarkably stable developmental trajectory over the first week of life. This is most evident in changes of interferon and complement pathways, as well as neutrophil-associated signaling. Validated across two independent cohorts of newborns from West Africa and Australasia, a robust and common trajectory emerges, suggesting a purposeful rather than random developmental path. Systems biology and innovative data integration can provide fresh insights into the molecular ontogeny of the first week of life, a dynamic developmental phase that is key for health and disease.

PMID: 30862783 [PubMed - indexed for MEDLINE]