Network Analysis of Host-Virus Communities in Bats and Rodents Reveals Determinants of Cross-Species Transmission

Bats are natural reservoirs of several important emerging viruses. Cross-species transmission appears to be quite common among bats, which may contribute to their unique reservoir potential. Therefore, understanding the importance of bats as reservoirs requires examining them in a community context rather than concentrating on individual species. Here, we use a network approach to identify ecological and biological correlates of cross-species virus transmission in bats and rodents, another important host group. We show that given our current knowledge the bat viral sharing network is more connected than the rodent network, suggesting viruses may pass more easily between bat species. We identify host traits associated with important reservoir species: gregarious bats are more likely to share more viruses and bats which migrate regionally are important for spreading viruses through the network. We identify multiple communities of viral sharing within bats and rodents and highlight potential species traits that can help guide studies of novel pathogen emergence

Prospective Investigation of Markers of Elevated Delirium Risk (PRIMED Risk) study protocol: a prospective, observational cohort study investigating blood and cerebrospinal fluid biomarkers for delirium and cognitive dysfunction in older patients [version 1; peer review: awaiting peer review]

BACKGROUND: Delirium is a common post-operative complication, particularly in older adults undergoing major or emergency procedures. It is associated with increased length of intensive care and hospital stay, post-operative mortality and subsequent dementia risk. Current methods of predicting delirium incidence, duration and severity have limitations. Investigation of blood and cerebrospinal fluid (CSF) biomarkers linked to delirium may improve understanding of the underlying pathophysiology, particularly with regard to the extent this is shared or distinct with underlying dementia. Together, these have the potential for development of better risk stratification tools and perioperative interventions. / METHODS: 200 patients over the age of 70 scheduled for surgery with routine spinal anaesthetic will be recruited from UK hospitals. Their cognitive and functional baseline status will be assessed pre-operatively by telephone. Time-matched CSF and blood samples will be taken at the time of surgery and analysed for known biomarkers of neurodegeneration and neuroinflammation. Patients will be assessed daily for delirium until hospital discharge and will have regular cognitive follow-up for two years. Primary outcomes will be change in modified Telephone Interview for Cognitive Status (TICS-m) score at 12 months and rate of change of TICS-m score. Delirium severity, duration and biomarker levels will be treated as exposures in a random effects linear regression models. PRIMED Risk has received regulatory approvals from Health Research Authority and London – South East Research Ethics Committee. / DISCUSSION: The main anticipated output from this study will be the quantification of biomarkers of acute and chronic contributors to cognitive impairment after surgery. In addition, we aim to develop better risk prediction models for adverse cognitive outcomes

Estimation of proteinuria as a predictor of complications of pre-eclampsia: a systematic review

Background Proteinuria is one of the essential criteria for the clinical diagnosis of pre-eclampsia. Increasing levels of proteinuria is considered to be associated with adverse maternal and fetal outcomes. We aim to determine the accuracy with which the amount of proteinuria predicts maternal and fetal complications in women with pre-eclampsia by systematic quantitative review of test accuracy studies. Methods We conducted electronic searches in MEDLINE (1951 to 2007), EMBASE (1980 to 2007), the Cochrane Library (2007) and the MEDION database to identify relevant articles and hand-search of selected specialist journals and reference lists of articles. There were no language restrictions for any of these searches. Two reviewers independently selected those articles in which the accuracy of proteinuria estimate was evaluated to predict maternal and fetal complications of pre-eclampsia. Data were extracted on study characteristics, quality and accuracy to construct 2 × 2 tables with maternal and fetal complications as reference standards. Results Sixteen primary articles with a total of 6749 women met the selection criteria with levels of proteinuria estimated by urine dipstick, 24-hour urine proteinuria or urine protein:creatinine ratio as a predictor of complications of pre-eclampsia. All 10 studies predicting maternal outcomes showed that proteinuria is a poor predictor of maternal complications in women with pre-eclampsia. Seventeen studies used laboratory analysis and eight studies bedside analysis to assess the accuracy of proteinuria in predicting fetal and neonatal complications. Summary likelihood ratios of positive and negative tests for the threshold level of 5 g/24 h were 2.0 (95% CI 1.5, 2.7) and 0.53 (95% CI 0.27, 1) for stillbirths, 1.5 (95% CI 0.94, 2.4) and 0.73 (95% CI 0.39, 1.4) for neonatal deaths and 1.5 (95% 1, 2) and 0.78 (95% 0.64, 0.95) for Neonatal Intensive Care Unit admission. Conclusion Measure of proteinuria is a poor predictor of either maternal or fetal complications in women with pre-eclampsia

Cerebrospinal fluid levels of opioid peptides in fibromyalgia and chronic low back pain

BACKGROUND: The mechanism(s) of nociceptive dysfunction and potential roles of opioid neurotransmitters are unresolved in the chronic pain syndromes of fibromyalgia and chronic low back pain. METHODS: History and physical examinations, tender point examinations, and questionnaires were used to identify 14 fibromyalgia, 10 chronic low back pain and 6 normal control subjects. Lumbar punctures were performed. Met-enkephalin-Arg(6)-Phe(7 )(MEAP) and nociceptin immunoreactive materials were measured in the cerebrospinal fluid by radioimmunoassays. RESULTS: Fibromyalgia (117.6 pg/ml; 85.9 to 149.4; mean, 95% C.I.; p = 0.009) and low back pain (92.3 pg/ml; 56.9 to 127.7; p = 0.049) groups had significantly higher MEAP than the normal control group (35.7 pg/ml; 15.0 to 56.5). MEAP was inversely correlated to systemic pain thresholds. Nociceptin was not different between groups. Systemic Complaints questionnaire responses were significantly ranked as fibromyalgia > back pain > normal. SF-36 domains demonstrated severe disability for the low back pain group, intermediate results in fibromyalgia, and high function in the normal group. CONCLUSIONS: Fibromyalgia was distinguished by higher cerebrospinal fluid MEAP, systemic complaints, and manual tender points; intermediate SF-36 scores; and lower pain thresholds compared to the low back pain and normal groups. MEAP and systemic pain thresholds were inversely correlated in low back pain subjects. Central nervous system opioid dysfunction may contribute to pain in fibromyalgia

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

Yb- and Er-doped fiber laser Q-switched with an optically uniform, broadband WS2 saturable absorber.

We demonstrate a ytterbium (Yb) and an erbium (Er)-doped fiber laser Q-switched by a solution processed, optically uniform, few-layer tungsten disulfide saturable absorber (WS2-SA). Nonlinear optical absorption of the WS2-SA in the sub-bandgap region, attributed to the edge-induced states, is characterized by 3.1% and 4.9% modulation depths with 1.38 and 3.83 MW/cm(2) saturation intensities at 1030 and 1558 nm, respectively. By integrating the optically uniform WS2-SA in the Yb- and Er-doped laser cavities, we obtain self-starting Q-switched pulses with microsecond duration and kilohertz repetition rates at 1030 and 1558 nm. Our work demonstrates broadband sub-bandgap saturable absorption of a single, solution processed WS2-SA, providing new potential efficacy for WS2 in ultrafast photonic applications.The authors thank E. J. R. Kelleher for valuable discussions. MZ acknowledges support from Beihang University, China, through a Zhuoyue Bairen Program and TH from the Royal Academy of Engineering through a fellowship (Graphlex). This work at Beihang University was supported by 973 Program (2012CB315601), NSFC (61221061/61435002) and the Fundamental Research Funds for the Central Universities.This is the final version of the article. It was first available from NPG via http://dx.doi.org/10.1038/srep1748

Approach to the Immunosuppressed Patient with Pulmonary Infiltrates

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65614/1/j.1365-4362.1980.tb00811.x.pd

Testing Evolutionary and Dispersion Scenarios for the Settlement of the New World

Background: Discussion surrounding the settlement of the New World has recently gained momentum with advances in molecular biology, archaeology and bioanthropology. Recent evidence from these diverse fields is found to support different colonization scenarios. The currently available genetic evidence suggests a ""single migration'' model, in which both early and later Native American groups derive from one expansion event into the continent. In contrast, the pronounced anatomical differences between early and late Native American populations have led others to propose more complex scenarios, involving separate colonization events of the New World and a distinct origin for these groups. Methodology/Principal Findings: Using large samples of Early American crania, we: 1) calculated the rate of morphological differentiation between Early and Late American samples under three different time divergence assumptions, and compared our findings to the predicted morphological differentiation under neutral conditions in each case; and 2) further tested three dispersal scenarios for the colonization of the New World by comparing the morphological distances among early and late Amerindians, East Asians, Australo-Melanesians and early modern humans from Asia to geographical distances associated with each dispersion model. Results indicate that the assumption of a last shared common ancestor outside the continent better explains the observed morphological differences between early and late American groups. This result is corroborated by our finding that a model comprising two Asian waves of migration coming through Bering into the Americas fits the cranial anatomical evidence best, especially when the effects of diversifying selection to climate are taken into account. Conclusions: We conclude that the morphological diversity documented through time in the New World is best accounted for by a model postulating two waves of human expansion into the continent originating in East Asia and entering through Beringia.Fondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT)[11070091]Fundacao de Amparo a Ciencia do Estado de Sao Paulo (FAPESP)[04/01253-0]Conselho Nacional de Pesquisa (CNPq)[301126-04.6]Max Planck GesellschaftEVAN Marie Curie Research Training Network[MRTN-CT-019564