Plate driven extension and convergence along the East Gondwana active margin: Late Silurian–Middle Devonian tectonics of the Lachlan Fold Belt, southeastern Australia

The Lachlan Fold Belt of southeastern Australia developed along the Panthalassan margin of East Gondwana. Major silicic igneous activity and active tectonics with extensional, strike-slip and contractional deformation have been related to a continental backarc setting with a convergent margin to the east. In the Early Silurian (Benambran Orogeny), tectonic development was controlled by one or more subduction zones involved in collision and accretion of the Ordovician Macquarie Arc. Thermal instability in the Late Silurian to Middle Devonian interval was promoted by the presence of one or more shallow subducted slabs in the upper mantle and resulted in widespread silicic igneous activity. Extension dominated the Late Silurian in New South Wales and parts of eastern Victoria and led to formation of several sedimentary basins. Alternating episodes of contraction and extension, along with dispersed strike-slip faulting particularly in eastern Victoria, occurred in the Early Devonian culminating in the Middle Devonian contractional Tabberabberan Orogeny. Contractional deformation in modern systems, such as the central Andes, is driven by advance of the overriding plate, with highest strain developed at locations distant from plate edges. In the Ordovician to Early Devonian, it is inferred that East Gondwana was advancing towards Panthalassa. Extensional activity in the Lachlan backarc, although minor in comparison to backarc basins in the western Pacific Ocean, was driven by limited but continuous rollback of the subduction hinge. Alternation of contraction and extension reflects the delicate balance between plate motions with rollback being overtaken by advance of the upper plate intermittently in the Early to Middle Devonian resulting in contractional deformation in an otherwise dominantly extensional regime. A modern system that shows comparable behaviour is East Asia where rollback is considered responsible for widespread sedimentary basin development and basin inversion reflects advance of blocks driven by compression related to the Indian collision

Tectonic evolution of the Ordovician Macquarie Arc, central New South Wales: arguments for subduction polarity and anticlockwise rotation

The Ordovician Macquarie Arc is most widely exposed in the Lachlan Fold Belt of central New South Wales. Complex relationships between the arc and the Ordovician turbidite mega-fan are partly explained by anticlockwise rotation of the arc during the Ordovician. Thus, initially two lobes of the mega-fan formed to the north and south of the east-west trending arc, using present-day coordinates. The arc consists of the western Goonumbla-Trangie Volcanic Belt, replacing the inappropriate term Junee-Narromine Volcanic Belt, and an eastern composite of the Molong, Rockley-Gulgong and Kiandra Volcanic Belts. These two major segments of the arc are separated by Ordovician quartz turbidites of the Kirribilli Formation and it is probable that the arc has been duplicated by a sinistral strike-slip fault. Eastonian palaeogeographic reconstruction of the eastern segment of the arc highlights a prominent limestone platform in the western Molong Volcanic Belt that grades eastwards into a realm of mainly deep-marine sedimentation and volcanic activity. By analogy with Guam in the western Pacific Ocean, the limestone platform is equated to a frontal arc ridge. This implies that the associated subduction zone was along the western side of the arc and not to the east, as in previous reconstructions. A wide zone of deformed Ordovician quartz turbidites, making up the Girilambone and Wagga-Omeo Zones west of the Macquarie Arc, is interpreted as a subduction complex that formed rapidly in the Late Ordovician. Flipping of the subduction zone was a relatively long event, inferred to have occurred during the latest Ordovician to early Silurian Benambran Orogeny. This was driven by collision of the subduction complex with northern continuations of the Stawell and Bendigo Zones, with a new west-dipping subduction zone forming to the east

Late Neoproterozoic passive margin of East Gondwana: geochemical constraints from the Anakie Inlier, central Queensland, Australia

Development of the East Gondwana passive margin and when it occurred are constrained by the composition of low grade mafic schists and U-Pb ages of detrital zircons in psammitic schists from the Bathampton Metamorphics in the Anakie Inlier of central Queensland. These rocks show considerable variation in light lithophile elements due to post-magmatic processes. They have flat heavy rare earth element patterns, low-TiO2 (\u3c2 wt%) contents and their immobile element Ti, V, Y, La, Nb, Th and Zr values, indicate that they have an NMORB- like magmatic affinity. However, they differ from N-MORB in that they show light rare earth depleted patterns and lower incompatible trace element contents. Their relative low abundance and association with metasediments suggest they formed in a magma-poor rifted margin setting. They are associated with psammitic rocks with detrital zircon ages indicating probable deposition in the late Neoproterozoic at ca 600 Ma. A magma-poor rifted margin in northeastern Australia differs from the volcanic passive setting that occurred in southeastern Australia at this time. These findings support development of the East Gondwana margin at 600 Ma that may have been related to rifting of a microcontinent off East Gondwana well after the breakup of Rodinia at ca 750 Ma

A 15-Year Analysis of Early and Late Autologous Hematopoietic Stem Cell Transplant in Relapsed, Aggressive, Transformed, and Nontransformed Follicular Lymphoma

AbstractAutologous stem cell transplant (ASCT) has been shown to be an effective treatment for follicular lymphoma (FL). We explored our experience in ASCT for FL among all patients treated over a 15-year period from diagnosis through their entire treatment history including relapse post ASCT. All patients who underwent an unpurged ASCT for relapsed, advanced FL between June 1990 and December 2000 were analyzed. After salvage therapy they received melphalan/etoposide/total body irradiation, BCNU, etoposide, cytarabine, melphalan (BEAM), or cyclophosphamide BCNU etoposide (CBV) as conditioning for the ASCT. One hundred thirty-eight patients with a median age of 48 years and a median follow-up of 7.6 years were analyzed. The majority were of the subtype grade 1, nontransformed (FL-NT), having had 1 prior chemotherapy. The progression-free (PFS) and overall survival (OS) of the FL-NT at 10 years were 46% and 57%, respectively, and at 5 years for the transformed (FL-T) were 25% and 56%, respectively, of which only the PFS was significantly different (P = .007). The median OS from diagnosis was 16 years for the FL-NT. ASCT positively altered the trend of shorter remissions with subsequent chemotherapies, and there was no difference in OS between those who had 1, 2, or >2 chemotherapies prior to ASCT. Salvage therapy for relapse post ASCT was effective (OS >1 year) in a third of patients. Unpurged ASCT is an effective tool in the treatment of relapsed, aggressive FL-NT and FL-T, is superior to retreatment with standard chemotherapy, is effective at various stages of treatment, is likely to have a beneficial influence on the natural history of this disease, and the disease is amenable to salvage therapy post-ASCT relapse

Methods for conducting systematic reviews of risk factors in low- and middle-income countries.

BACKGROUND: Rates of youth violence are disproportionately high in many low- and middle-income countries [LMICs] but existing reviews of risk factors focus almost exclusively on high-income countries. Different search strategies, including non-English language searches, might be required to identify relevant evidence in LMICs. This paper discusses methodological issues in systematic reviews aiming to include evidence from LMICs, using the example of a recent review of risk factors for child conduct problems and youth violence in LMICs. METHODS: We searched the main international databases, such as PsycINFO, Medline and EMBASE in English, as well as 12 regional databases in Arabic, Chinese, English, French, Spanish, Portuguese and Russian. In addition, we used internet search engines and Google Scholar, and contacted over 200 researchers and organizations to identify potentially eligible studies in LMICs. RESULTS: The majority of relevant studies were identified in the mainstream databases, but additional studies were also found through regional databases, such as CNKI, Wangfang, LILACS and SciELO. Overall, 85% of eligible studies were in English, and 15% were reported in Chinese, Spanish, Portuguese, Russian or French. Among eligible studies in languages other than English, two-thirds were identified only by regional databases and one-third was also indexed in the main international databases. CONCLUSIONS: There are many studies on child conduct problems and youth violence in LMICs which have not been included in prior reviews. Most research on these subjects in LMICs has been produced in the last two-three decades and mostly in middle-income countries, such as China, Brazil, Turkey, South Africa and Russia. Based on our findings, it appears that many studies of child conduct problems and youth violence in LMICs are reported in English, Chinese, Spanish and Portuguese, but few such studies are published in French, Arabic or Russian. If non-English language searches and screening had not been conducted in the current review, 15% of eligible studies would have been missed. Although there are benefits to non-English language searches and the inclusion of non-English studies in meta-analyses, systematic reviewers also need to consider the resources required to incorporate multi-lingual research.We are grateful to the Wellcome Trust [089963/Z/09/Z] and Bernard van Leer Foundation for financial support for the research

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Effect of Convalescent Plasma on Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial

Importance: The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive. Objective: To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19. Design, Setting, and Participants: The ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021. Interventions: The immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916). Main Outcomes and Measures: The primary ordinal end point was organ support-free days (days alive and free of intensive care unit-based organ support) up to day 21 (range, -1 to 21 days; patients who died were assigned -1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support-free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support-free days; cardiovascular support-free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events. Results: Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support-free days was 0 (IQR, -1 to 16) in the convalescent plasma group and 3 (IQR, -1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (O