A validation of the Oswestry Spinal Risk Index

Purpose The purpose of this study was to validate the Oswestry Spinal Risk Index (OSRI) in an external population. The OSRI predicts survival in patients with metastatic spinal cord compression (MSCC). Methods We analysed the data of 100 patients undergoing surgical intervention for MSCC at a tertiary spinal unit and recorded the primary tumour pathology and Karnofsky performance status to calculate the OSRI. Logistic regression models and survival plots were applied to the data in accordance with the original paper. Results Lower OSRI scores predicted longer survival. The OSRI score predicted survival accurately in 74% of cases (p = 0.004). Conclusions Our study has found that the OSRI is a significant predictor of survival at levels similar to those of the original authors and is a useful and simple tool in aiding complex decision making in patients presenting with MSC

Safety and Pharmacokinetics of Motesanib in Combination with Panitumumab and Gemcitabine-Cisplatin in Patients with Advanced Cancer

Purpose. The aim of this study was to assess the safety and tolerability of motesanib (an orally administered small-molecule antagonist of vascular endothelial growth factor receptors 1, 2, and 3, platelet-derived growth factor receptor, and Kit) when administered in combination with panitumumab, gemcitabine, and cisplatin. Methods. This was an open-label, multicenter phase 1b study in patients with advanced solid tumors with an ECOG performance status ≤1 and for whom a gemcitabine/cisplatin regimen was indicated. Patients received motesanib (0 mg [control], 50 mg once daily [QD], 75 mg QD, 100 mg QD, 125 mg QD, or 75 mg twice daily [BID]) with panitumumab (9 mg/kg), gemcitabine (1250 mg/m2) and cisplatin (75 mg/m2) in 21-day cycles. The primary endpoint was the incidence of dose-limiting toxicities (DLTs). Results. Forty-one patients were enrolled and received treatment (including 8 control patients). One of eight patients in the 50 mg QD cohort and 5/11 patients in the 125 mg QD cohort experienced DLTs. The maximum tolerated dose was established as 100 mg QD. Among patients who received motesanib (n = 33), 29 had motesanib-related adverse events. Fourteen patients had serious motesanib-related events. Ten patients had motesanib-related venous thromboembolic events and three had motesanib-related arterial thromboembolic events, two of which were considered serious. One patient had a complete response and nine had partial responses as their best objective response. Conclusions. The combination of motesanib, panitumumab, and gemcitabine/cisplatin could not be administered consistently and, at the described doses and schedule, may be intolerable. However, encouraging antitumor activity was noted in some cases

The Floor of Yellowstone Lake is Anything but Quiet—New Discoveries from High-Resolution Sonar Imaging, Seismic- Reflection Profiling, and Submersible Studies

Discoveries from multibeam sonar mapping and seis-mic-reflection surveys of Yellowstone Lake provide new insight into the recent geologic forces that have shaped a large lake at the active front of the Yellowstone hot spot, a region strongly affected by young (\u3c2 \u3em.y.), large-volume (\u3e100–1,000s km3) silicic volcanism, active tectonism, and accompanying uplift. Specifically, our mapping has identified the extent of postcaldera-collapse volcanism and active hydrothermal processes occurring above a large magma chamber beneath the lake floor. Multiple advances and recessions of thick glacial ice have overlapped volcanic and hydrothermal activity leaving a lake basin that has been shaped predominantly by fire and ice. Yellowstone Lake has an irregular bottom covered with dozens of features directly related to hydrothermal, tectonic, volcanic,and sedimentary processes. Detailed bathymetric, seismic-reflection, and magnetic evidence reveals that rhyolitic lava flows underlie much of Yellowstone Lake and exert fundamental control on lake morphology and localization of hydrothermal activity in the northern, West Thumb, and central basins. Many previously unknown features have been identified and include more than 660 hydrothermal vents, several very large (\u3e500-m diameter) hydrothermal-explosion craters, many small hydrothermal-vent craters (~1-to 200-m diameter), domed lacustrine sediments related to hydrothermal activity, elongate fissures cutting postglacial sediments, siliceous hydrothermal-spire structures, sublacustrine landslide deposits, submerged former shorelines, large glacial melting features, incipient faulting along the trace of the Eagle Bay fault zone, and a recently active graben. Sampling and observations with a submersible remotely operated vehicle confirm and extend our understanding of the identified features. Faults, fissures, hydrothermally inflated domal structures, hydrothermal-explosion craters, and sublacustrine landslides constitute potentially significant geologic hazards. Toxic elements derived from hydrothermal processes also may significantly affect the Yellowstone ecosystem

The Floor of Yellowstone Lake is Anything but Quiet—New Discoveries from High-Resolution Sonar Imaging, Seismic- Reflection Profiling, and Submersible Studies

Discoveries from multibeam sonar mapping and seis-mic-reflection surveys of Yellowstone Lake provide new insight into the recent geologic forces that have shaped a large lake at the active front of the Yellowstone hot spot, a region strongly affected by young (\u3c2 \u3em.y.), large-volume (\u3e100–1,000s km3) silicic volcanism, active tectonism, and accompanying uplift. Specifically, our mapping has identified the extent of postcaldera-collapse volcanism and active hydrothermal processes occurring above a large magma chamber beneath the lake floor. Multiple advances and recessions of thick glacial ice have overlapped volcanic and hydrothermal activity leaving a lake basin that has been shaped predominantly by fire and ice. Yellowstone Lake has an irregular bottom covered with dozens of features directly related to hydrothermal, tectonic, volcanic,and sedimentary processes. Detailed bathymetric, seismic-reflection, and magnetic evidence reveals that rhyolitic lava flows underlie much of Yellowstone Lake and exert fundamental control on lake morphology and localization of hydrothermal activity in the northern, West Thumb, and central basins. Many previously unknown features have been identified and include more than 660 hydrothermal vents, several very large (\u3e500-m diameter) hydrothermal-explosion craters, many small hydrothermal-vent craters (~1-to 200-m diameter), domed lacustrine sediments related to hydrothermal activity, elongate fissures cutting postglacial sediments, siliceous hydrothermal-spire structures, sublacustrine landslide deposits, submerged former shorelines, large glacial melting features, incipient faulting along the trace of the Eagle Bay fault zone, and a recently active graben. Sampling and observations with a submersible remotely operated vehicle confirm and extend our understanding of the identified features. Faults, fissures, hydrothermally inflated domal structures, hydrothermal-explosion craters, and sublacustrine landslides constitute potentially significant geologic hazards. Toxic elements derived from hydrothermal processes also may significantly affect the Yellowstone ecosystem

Effectiveness of guided self-help in decreasing expressed emotion in family caregivers of people diagnosed with depression in Thailand: a randomised controlled trial

Background: High expressed emotion (EE) can extend the duration of illness and precipitate relapse; however, little evidence-based information is available to assist family caregivers of individuals with depression. In the present exploratory study, we examined the effectiveness of a cognitive behaviour therapy (CBT) based guided self-help (GSH) manual in decreasing EE in caregivers of people with depression, in Thailand. Method: A parallel group randomised controlled trial was conducted, following CONSORT guidelines, with 54 caregivers who were allocated equally to GSH or control group (standard outpatient department support). In addition, both groups were contacted weekly by telephone. EE was assessed, using the Family Questionnaire (FQ), at baseline, post-test (Week 8) and follow-up (Week 12). Results: FQ scores at baseline indicated that both groups had similar, though moderately high level of EE. However, between baseline and post-test EE scores decreased markedly in the intervention group, but in contrast, they increased slightly in the control group. Between post-test and follow-up, little change took place in the EE scores of either group. Overall, the intervention group recipients of GSH showed a significant decrease in EE whereas the control group recipients of standard outpatient department support reported a slight increase in EE. Conclusion: These findings provide preliminary evidence that GSH is beneficial in reducing EE in caregivers, which is advantageous to family members with depression and caregivers. The approach may be used as an adjunct to the limited outpatient department support given to caregivers by mental health professionals and, perhaps, to caregivers who do not attend these departments

Managing lifestyle change to reduce coronary risk: a synthesis of qualitative research on peoples’ experiences

Background Coronary heart disease is an incurable condition. The only approach known to slow its progression is healthy lifestyle change and concordance with cardio-protective medicines. Few people fully succeed in these daily activities so potential health improvements are not fully realised. Little is known about peoples’ experiences of managing lifestyle change. The aim of this study was to synthesise qualitative research to explain how participants make lifestyle change after a cardiac event and explore this within the wider illness experience. Methods A qualitative synthesis was conducted drawing upon the principles of meta-ethnography. Qualitative studies were identified through a systematic search of 7 databases using explicit criteria. Key concepts were identified and translated across studies. Findings were discussed and diagrammed during a series of audiotaped meetings. Results The final synthesis is grounded in findings from 27 studies, with over 500 participants (56% male) across 8 countries. All participants experienced a change in their self-identity from what was ‘familiar’ to ‘unfamiliar’. The transition process involved ‘finding new limits and a life worth living’ , ‘finding support for self’ and ‘finding a new normal’. Analyses of these concepts led to the generation of a third order construct, namely an ongoing process of ‘reassessing past, present and future lives’ as participants considered their changed identity. Participants experienced a strong urge to get back to ‘normal’. Support from family and friends could enable or constrain life change and lifestyle changes. Lifestyle change was but one small part of a wider ‘life’ change that occurred. Conclusions The final synthesis presents an interpretation, not evident in the primary studies, of a person-centred model to explain how lifestyle change is situated within ‘wider’ life changes. The magnitude of individual responses to a changed health status varied. Participants experienced distress as their notion of self identity shifted and emotions that reflected the various stages of the grief process were evident in participants’ accounts. The process of self-managing lifestyle took place through experiential learning; the level of engagement with lifestyle change reflected an individual’s unique view of the balance needed to manage ‘realistic change’ whilst leading to a life that was perceived as ‘worth living’. Findings highlight the importance of providing person centred care that aligns with both psychological and physical dimensions of recovery which are inextricably linked

A strategy for the next decade to address data deficiency in neglected biodiversity

Measuring progress toward international biodiversity targets requires robust information on the conservation status of species, which the International Union for Conservation of Nature (IUCN) Red List of Threatened Species provides. However, data and capacity are lacking for most hyperdiverse groups, such as invertebrates, plants, and fungi, particularly in megadiverse or high-endemism regions. Conservation policies and biodiversity strategies aimed at halting biodiversity loss by 2020 need to be adapted to tackle these information shortfalls after 2020. We devised an 8-point strategy to close existing data gaps by reviving explorative field research on the distribution, abundance, and ecology of species; linking taxonomic research more closely with conservation; improving global biodiversity databases by making the submission of spatially explicit data mandatory for scientific publications; developing a global spatial database on threats to biodiversity to facilitate IUCN Red List assessments; automating preassessments by integrating distribution data and spatial threat data; building capacity in taxonomy, ecology, and biodiversity monitoring in countries with high species richness or endemism; creating species monitoring programs for lesser-known taxa; and developing sufficient funding mechanisms to reduce reliance on voluntary efforts. Implementing these strategies in the post-2020 biodiversity framework will help to overcome the lack of capacity and data regarding the conservation status of biodiversity. This will require a collaborative effort among scientists, policy makers, and conservation practitioners.Peer reviewe

Canvass: a crowd-sourced, natural-product screening library for exploring biological space

NCATS thanks Dingyin Tao for assistance with compound characterization. This research was supported by the Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health (NIH). R.B.A. acknowledges support from NSF (CHE-1665145) and NIH (GM126221). M.K.B. acknowledges support from NIH (5R01GM110131). N.Z.B. thanks support from NIGMS, NIH (R01GM114061). J.K.C. acknowledges support from NSF (CHE-1665331). J.C. acknowledges support from the Fogarty International Center, NIH (TW009872). P.A.C. acknowledges support from the National Cancer Institute (NCI), NIH (R01 CA158275), and the NIH/National Institute of Aging (P01 AG012411). N.K.G. acknowledges support from NSF (CHE-1464898). B.C.G. thanks the support of NSF (RUI: 213569), the Camille and Henry Dreyfus Foundation, and the Arnold and Mabel Beckman Foundation. C.C.H. thanks the start-up funds from the Scripps Institution of Oceanography for support. J.N.J. acknowledges support from NIH (GM 063557, GM 084333). A.D.K. thanks the support from NCI, NIH (P01CA125066). D.G.I.K. acknowledges support from the National Center for Complementary and Integrative Health (1 R01 AT008088) and the Fogarty International Center, NIH (U01 TW00313), and gratefully acknowledges courtesies extended by the Government of Madagascar (Ministere des Eaux et Forets). O.K. thanks NIH (R01GM071779) for financial support. T.J.M. acknowledges support from NIH (GM116952). S.M. acknowledges support from NIH (DA045884-01, DA046487-01, AA026949-01), the Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program (W81XWH-17-1-0256), and NCI, NIH, through a Cancer Center Support Grant (P30 CA008748). K.N.M. thanks the California Department of Food and Agriculture Pierce's Disease and Glassy Winged Sharpshooter Board for support. B.T.M. thanks Michael Mullowney for his contribution in the isolation, elucidation, and submission of the compounds in this work. P.N. acknowledges support from NIH (R01 GM111476). L.E.O. acknowledges support from NIH (R01-HL25854, R01-GM30859, R0-1-NS-12389). L.E.B., J.K.S., and J.A.P. thank the NIH (R35 GM-118173, R24 GM-111625) for research support. F.R. thanks the American Lebanese Syrian Associated Charities (ALSAC) for financial support. I.S. thanks the University of Oklahoma Startup funds for support. J.T.S. acknowledges support from ACS PRF (53767-ND1) and NSF (CHE-1414298), and thanks Drs. Kellan N. Lamb and Michael J. Di Maso for their synthetic contribution. B.S. acknowledges support from NIH (CA78747, CA106150, GM114353, GM115575). W.S. acknowledges support from NIGMS, NIH (R15GM116032, P30 GM103450), and thanks the University of Arkansas for startup funds and the Arkansas Biosciences Institute (ABI) for seed money. C.R.J.S. acknowledges support from NIH (R01GM121656). D.S.T. thanks the support of NIH (T32 CA062948-Gudas) and PhRMA Foundation to A.L.V., NIH (P41 GM076267) to D.S.T., and CCSG NIH (P30 CA008748) to C.B. Thompson. R.E.T. acknowledges support from NIGMS, NIH (GM129465). R.J.T. thanks the American Cancer Society (RSG-12-253-01-CDD) and NSF (CHE1361173) for support. D.A.V. thanks the Camille and Henry Dreyfus Foundation, the National Science Foundation (CHE-0353662, CHE-1005253, and CHE-1725142), the Beckman Foundation, the Sherman Fairchild Foundation, the John Stauffer Charitable Trust, and the Christian Scholars Foundation for support. J.W. acknowledges support from the American Cancer Society through the Research Scholar Grant (RSG-13-011-01-CDD). W.M.W.acknowledges support from NIGMS, NIH (GM119426), and NSF (CHE1755698). A.Z. acknowledges support from NSF (CHE-1463819). (Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health (NIH); CHE-1665145 - NSF; CHE-1665331 - NSF; CHE-1464898 - NSF; RUI: 213569 - NSF; CHE-1414298 - NSF; CHE1361173 - NSF; CHE1755698 - NSF; CHE-1463819 - NSF; GM126221 - NIH; 5R01GM110131 - NIH; GM 063557 - NIH; GM 084333 - NIH; R01GM071779 - NIH; GM116952 - NIH; DA045884-01 - NIH; DA046487-01 - NIH; AA026949-01 - NIH; R01 GM111476 - NIH; R01-HL25854 - NIH; R01-GM30859 - NIH; R0-1-NS-12389 - NIH; R35 GM-118173 - NIH; R24 GM-111625 - NIH; CA78747 - NIH; CA106150 - NIH; GM114353 - NIH; GM115575 - NIH; R01GM121656 - NIH; T32 CA062948-Gudas - NIH; P41 GM076267 - NIH; R01GM114061 - NIGMS, NIH; R15GM116032 - NIGMS, NIH; P30 GM103450 - NIGMS, NIH; GM129465 - NIGMS, NIH; GM119426 - NIGMS, NIH; TW009872 - Fogarty International Center, NIH; U01 TW00313 - Fogarty International Center, NIH; R01 CA158275 - National Cancer Institute (NCI), NIH; P01 AG012411 - NIH/National Institute of Aging; Camille and Henry Dreyfus Foundation; Arnold and Mabel Beckman Foundation; Scripps Institution of Oceanography; P01CA125066 - NCI, NIH; 1 R01 AT008088 - National Center for Complementary and Integrative Health; W81XWH-17-1-0256 - Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program; P30 CA008748 - NCI, NIH, through a Cancer Center Support Grant; California Department of Food and Agriculture Pierce's Disease and Glassy Winged Sharpshooter Board; American Lebanese Syrian Associated Charities (ALSAC); University of Oklahoma Startup funds; 53767-ND1 - ACS PRF; PhRMA Foundation; P30 CA008748 - CCSG NIH; RSG-12-253-01-CDD - American Cancer Society; RSG-13-011-01-CDD - American Cancer Society; CHE-0353662 - National Science Foundation; CHE-1005253 - National Science Foundation; CHE-1725142 - National Science Foundation; Beckman Foundation; Sherman Fairchild Foundation; John Stauffer Charitable Trust; Christian Scholars Foundation)Published versionSupporting documentatio

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes