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Showing papers by "University of the Witwatersrand published in 2014"


Journal ArticleDOI
TL;DR: Evidence for associations between parental disorders and offspring outcomes from fetal development to adolescence in high-income, middle- income, and low-income countries is summarized and the need for early identification of those parents at high risk and for more early interventions and prevention research is underlined.

1,427 citations


Reference EntryDOI
TL;DR: The average risk of high blood pressure was reduced with calcium supplementation compared with placebo and the composite outcome maternal death or serious morbidity was reduced, but there was an anomalous increase in the risk of HELLP.
Abstract: Background Pre-eclampsia and eclampsia are common causes of serious morbidity and death. Calcium supplementation may reduce the risk of pre-eclampsia, and may help to prevent preterm birth. Objectives To assess the effects of calcium supplementation during pregnancy on hypertensive disorders of pregnancy and related maternal and child outcomes. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 March 2013) and contacted study authors for more data where possible. We updated the search in May 2014 and added the results to the 'Awaiting Classification' section of the review. Selection criteria Randomised controlled trials (RCTs) comparing high-dose (at least 1 g daily of calcium) or low-dose calcium supplementation during pregnancy with placebo or no calcium. Data collection and analysis We assessed eligibility and trial quality, extracted and double-entered data. Main results High-dose calcium supplementation (≥1 g/day) We included 14 studies in the review, however one study contributed no data. We included 13 high-quality studies in our meta-analyses (15,730 women). The average risk of high blood pressure (BP) was reduced with calcium supplementation compared with placebo (12 trials, 15,470 women: risk ratio (RR) 0.65, 95% confidence interval (CI) 0.53 to 0.81; I² = 74%). There was also a significant reduction in the risk of pre-eclampsia associated with calcium supplementation (13 trials, 15,730 women: RR 0.45, 95% CI 0.31 to 0.65; I² = 70%). The effect was greatest for women with low calcium diets (eight trials, 10,678 women: average RR 0.36, 95% CI 0.20 to 0.65; I² = 76%) and women at high risk of pre-eclampsia (five trials, 587 women: average RR 0.22, 95% CI 0.12 to 0.42; I² = 0%). These data should be interpreted with caution because of the possibility of small-study effect or publication bias. The composite outcome maternal death or serious morbidity was reduced (four trials, 9732 women; RR 0.80, 95% CI 0.65 to 0.97; I² = 0%). Maternal deaths were not significantly different (one trial of 8312 women: calcium group one death versus placebo group six deaths). There was an anomalous increase in the risk of HELLP (haemolysis, elevated liver enzymes and low platelets) syndrome (two trials, 12,901 women: RR 2.67, 95% CI 1.05 to 6.82; I² = 0%) in the calcium group, however, the absolute number of events was low (16 versus six). The average risk of preterm birth was reduced in the calcium group (11 trials, 15,275 women: RR 0.76, 95% CI 0.60 to 0.97; I² = 60%) and amongst women at high risk of developing pre-eclampsia (four trials, 568 women: average RR 0.45, 95% CI 0.24 to 0.83; I² = 60%), but no significant reduction in neonatal high care admission. There was no overall effect on the risk of stillbirth or infant death before discharge from hospital (11 trials 15,665 babies: RR 0.90, 95% CI 0.74 to 1.09; I² = 0%). One study showed a reduction in childhood systolic BP greater than 95th percentile among children exposed to calcium supplementation in utero (514 children: RR 0.59, 95% CI 0.39 to 0.91). In a subset of these children, dental caries at 12 years old was also reduced (195 children, RR 0.73, 95% CI 0.62 to 0.87). Low-dose calcium supplementation (< 1 g/day) We included 10 trials (2234 women) that evaluated low-dose supplementation with calcium alone (4) or in association with vitamin D (3), linoleic acid (2), or antioxidants (1). Most studies recruited women at high risk for pre-eclampsia, and were at high risk of bias, thus the results should be interpreted with caution. Supplementation with low doses of calcium significantly reduced the risk of pre-eclampsia (RR 0.38, 95% CI 0.28 to 0.52; I² = 0%). There was also a reduction in hypertension, low birthweight and neonatal intensive care unit admission. Authors' conclusions Calcium supplementation (≥ 1 g/day) is associated with a significant reduction in the risk of pre-eclampsia, particularly for women with low calcium diets. The treatment effect may be overestimated due to small-study effects or publication bias. It also reduces preterm birth and the occurrence of the composite outcome 'maternal death or serious morbidity'. We considered these benefits to outweigh the increased risk of HELLP syndrome, which was small in absolute numbers. The World Health Organization recommends calcium 1.5 g to 2 g daily for pregnant women with low dietary calcium intake. The limited evidence on low-dose calcium supplementation suggests a reduction in pre-eclampsia, but needs to be confirmed by larger, high-quality trials. Pending such results, in settings of low dietary calcium where high-dose supplementation is not feasible, the option of lower-dose supplements (500 to 600 mg/day) might be considered in preference to no supplementation.

997 citations


Journal ArticleDOI
TL;DR: It is time to ease the strain on healthcare systems through clear policy initiatives that prioritize heart failure prevention and champion equity of care for all.
Abstract: Heart failure is a life-threatening disease and addressing it should be considered a global health priority. At present, approximately 26 million people worldwide are living with heart failure. The outlook for such patients is poor, with survival rates worse than those for bowel, breast or prostate cancer. Furthermore, heart failure places great stresses on patients, caregivers and healthcare systems. Demands on healthcare services, in particular, are predicted to increase dramatically over the next decade as patient numbers rise owing to ageing populations, detrimental lifestyle changes and improved survival of those who go on to develop heart failure as the final stage of another disease. It is time to ease the strain on healthcare systems through clear policy initiatives that prioritize heart failure prevention and champion equity of care for all. Despite the burdens that heart failure imposes on society, awareness of the disease is poor. As a result, many premature deaths occur. This is in spite of the fact that most types of heart failure are preventable and that a healthy lifestyle can reduce risk. Even after heart failure has developed, premature deaths could be prevented if people were taught to recognize the symptoms and seek immediate medical attention. Public awareness campaigns focusing on these messages have great potential to improve outcomes for patients with heart failure and ultimately to save lives. Compliance with clinical practice guidelines is also associated with improved outcomes for patients with heart failure. However, in many countries, there is considerable variation in how closely physicians follow guideline recommendations. To promote equity of care, improvements should be encouraged through the use of hospital performance measures and incentives appropriate to the locality. To this end, policies should promote the research required to establish an evidence base for performance measures that reflect improved outcomes for patients. Continuing research is essential if we are to address unmet needs in caring for patients with heart failure. New therapies are required for patients with types of heart failure for which current treatments relieve symptoms but do not address the disease. More affordable therapies are desperately needed in the economically developing world. International collaborative research focusing on the causes and treatment of heart failure worldwide has the potential to benefit tens of millions of people. Change at the policy level has the power to drive improvements in prevention and care that will save lives. It is time to make a difference across the globe by confronting the problem of heart failure. A call to action: policy recommendations We urge policymakers at local, national and international levels to collaborate and act on the following recommendations. Promote heart failure prevention Support the development and implementation of public awareness programmes about heart failure. These should define heart failure in simple and accessible language, explain how to recognize the symptoms and emphasize that most types of heart failure are preventable. Highlight the need for healthcare professionals across all clinical disciplines to identify patients with illnesses that increase the risk of heart failure and to prescribe preventive medications. Prioritize the elimination of infectious diseases in parts of the world where they still cause heart failure. Improve heart failure awareness amongst healthcare professionals Encourage the development and use of heart failure education programmes for all appropriate healthcare professionals. These should aim to improve the prevention, diagnosis, treatment and long-term management of heart failure and raise awareness of clinical practice guidelines. Ensure equity of care for all patients with heart failure Provide a healthcare system that delivers timely access to diagnostic services and treatment of heart failure, as well as a seamless transition to long-term management. Ensure that the best available and most appropriate care is consistently provided to all patients with heart failure through efficient use of resources. Support and empower patients and their caregivers Provide resources for the education and practical support of patients with heart failure and their families or other caregivers, empowering them to engage proactively in long-term care. Promote heart failure research Fund and encourage international collaborative research to improve understanding of the patterns, causes and effects of modern day heart failure and how the disease can be prevented across the globe. Fund and encourage research into new and more affordable therapies and medical devices for all types of heart failure. Fund and encourage research into evidence-based healthcare performance measures that reflect improved clinical outcomes for patients with heart failure.

944 citations


Journal ArticleDOI
TL;DR: In this article, the authors summarized the evidence about epidemiology, risk factors, identification, and interventions for non-psychotic mental disorders for perinatal mental disorders, including depression during pregnancy and breastfeeding.

806 citations


Journal ArticleDOI
TL;DR: This paper explored a broader conceptualisation of adaptation pathways that draws on path-thinking in the sustainable development domain to consider the implications of path dependency, interactions between adaptation plans, vested interests and global change, and situations where values, interests or institutions constrain societal responses to change.
Abstract: The need to adapt to climate change is now widely recognised as evidence of its impacts on social and natural systems grows and greenhouse gas emissions continue unabated. Yet efforts to adapt to climate change, as reported in the literature over the last decade and in selected case studies, have not led to substantial rates of implementation of adaptation actions despite substantial investments in adaptation science. Moreover, implemented actions have been mostly incremental and focused on proximate causes; there are far fewer reports of more systemic or transformative actions. We found that the nature and effectiveness of responses was strongly influenced by framing. Recent decision-oriented approaches that aim to overcome this situation are framed within a “pathways” metaphor to emphasise the need for robust decision making within adaptive processes in the face of uncertainty and inter-temporal complexity. However, to date, such “adaptation pathways” approaches have mostly focused on contexts with clearly identified decision-makers and unambiguous goals; as a result, they generally assume prevailing governance regimes are conducive for adaptation and hence constrain responses to proximate causes of vulnerability. In this paper, we explore a broader conceptualisation of “adaptation pathways” that draws on ‘pathways thinking’ in the sustainable development domain to consider the implications of path dependency, interactions between adaptation plans, vested interests and global change, and situations where values, interests, or institutions constrain societal responses to change. This re-conceptualisation of adaptation pathways aims to inform decision makers about integrating incremental actions on proximate causes with the transformative aspects of societal change. Case studies illustrate what this might entail. The paper ends with a call for further exploration of theory, methods and procedures to operationalise this broader conceptualisation of adaptation.

801 citations


Journal ArticleDOI
31 Jan 2014-Science
TL;DR: Using data from 2154 sites in savannas across Africa, Australia, and South America, it is found that increasing moisture availability drives increases in fire and tree basal area, whereas fire reduces tree basal Area.
Abstract: Ecologists have long sought to understand the factors controlling the structure of savanna vegetation. Using data from 2154 sites in savannas across Africa, Australia, and South America, we found that increasing moisture availability drives increases in fire and tree basal area, whereas fire reduces tree basal area. However, among continents, the magnitude of these effects varied substantially, so that a single model cannot adequately represent savanna woody biomass across these regions. Historical and environmental differences drive the regional variation in the functional relationships between woody vegetation, fire, and climate. These same differences will determine the regional responses of vegetation to future climates, with implications for global carbon stocks.

500 citations



Journal ArticleDOI
TL;DR: In severe hypertriglyceridaemia, intervention can be indicated to prevent cardiovascular disease, dependent on triglyceride concentration, concomitant lipoprotein disturbances, and overall cardiovascular risk; in mild-to-moderate hypertrIGlyceridaemic states, intervention is indicated to Prevent cardiovascular disease and treatment includes management of lifestyle and secondary factors, and pharmacotherapy.

444 citations


Journal ArticleDOI
TL;DR: The clinical benefits recorded, combined with the striking reduction in HIV-1 transmission risk previously reported, provides strong support for earlier initiation of antiretroviral treatment.
Abstract: Summary Background Use of antiretroviral treatment for HIV-1 infection has decreased AIDS-related morbidity and mortality and prevents sexual transmission of HIV-1. H owever, the best time to initiate antiretroviral treatment to reduce progression of HIV-1 infection or non-AIDS clinical events is unknown. We reported previously that early antiretroviral treatment reduced HIV-1 transmission by 96%. We aimed to compare the eff ects of early and delayed initiation of antiretroviral treatment on clinical outcomes. Methods The HPTN 052 trial is a randomised controlled trial done at 13 sites in nine countries. We enrolled HIV-1-serodiscordant couples to the study and randomly allocated them to either early or delayed antiretroviral treatment by use of permuted block randomisation, stratifi ed by site. Random assignment was unblinded. The HIV-1-infected member of every couple initiated antiretroviral treatment either on entry into the study (early treatment group) or after a decline in CD4 count or with onset of an AIDS-related illness (delayed treatment group). Primary events were AIDS clinical events (WHO stage 4 HIV-1 disease, tuberculosis, and severe bacterial infections) and the following serious medical conditions unrelated to AIDS: serious cardiovascular or vascular disease, serious liver disease, end-stage renal disease, new-onset diabetes mellitus, and non-AIDS malignant disease. Analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00074581. Findings 1763 people with HIV-1 infection and a serodiscordant partner were enrolled in the study; 886 were assigned early antiretroviral treatment and 877 to the delayed treatment group (two individuals were excluded from this group af ter randomisation). Median CD4 counts at randomisation were 442 (IQR 373–522) cells per μL in patients assigned to the early treatment group and 428 (357–522) cells per μL in those allocated delayed antiretroviral treatment. In the delayed group, antiretroviral treatment was initiated at a median CD4 count of 230 (IQR 197–249) cells per μL. Primary clinical events were reported in 57 individuals assigned to early treatment initiation versus 77 people allocated to delayed antiretroviral treatment (hazard ratio 0·73, 95% CI 0·52–1·03; p=0·074). New-onset AIDS events were recorded in 40 participants assigned to early antiretroviral treatment versus 61 allocated delayed initiation (0·64, 0·43–0·96; p=0·031), tuberculosis developed in 17 versus 34 patients, respectively (0·49, 0·28–0·89, p=0·018), and primary nonAIDS events were rare (12 in the early group vs nine with delayed treatment). In total, 498 primary and secondary outcomes occurred in the early treatment group (incidence 24·9 per 100 person-years, 95% CI 22·5–27·5) versus 585 in the delayed treatment group (29·2 per 100 person-years, 26·5–32·1; p=0·025). 26 people died, 11 who were allocated to early antiretroviral treatment and 15 who were assigned to the delayed treatment group.

441 citations


Journal ArticleDOI
TL;DR: A review of the state-of-the-art of acid mine drainage can be found in this article, where the authors critically analyze the work performed in recent years on its occurrence, effects (on human health, plant life and aquatic species), and summarizes the remediation approaches taken so far to overcome the problem of AMD.
Abstract: Acid mine drainage (AMD) or acid rock drainage (ARD) is considered as one of the main pollutants of water in many countries that have historic or current mining activities. Its generation, release, mobility, and attenuation involves complex processes governed by a combination of physical, chemical, and biological factors. In general, AMD is produced by the oxidative dissolution of sulphide minerals. This paper reviews the current state-of-the-art of AMD. It critically analyses the work performed in recent years on its occurrence, effects (on human health, plant life and aquatic species), and summarizes the remediation approaches taken so far to overcome the problem of AMD. The challenges faced in tackling the remediation of AMD have also been considered. Commercially developed projects that are either in operation, being piloted or under evaluation have also been discussed. Finally, the paper speculates on future directions or opportunities that deserve exploration.

437 citations


Journal ArticleDOI
TL;DR: Influenza vaccine was immunogenic in HIV-uninfected and HIV-infected pregnant women and provided partial protection against confirmed influenza in both groups of women and in infants who were not exposed to HIV.
Abstract: Background There are limited data on the efficacy of vaccination against confirmed influenza in pregnant women with and those without human immunodeficiency virus (HIV) infection and protection of their infants. Methods We conducted two double-blind, randomized, placebo-controlled trials of trivalent inactivated influenza vaccine (IIV3) in South Africa during 2011 in pregnant women infected with HIV and during 2011 and 2012 in pregnant women who were not infected. The immunogenicity, safety, and efficacy of IIV3 in pregnant women and their infants were evaluated until 24 weeks after birth. Immune responses were measured with a hemagglutination inhibition (HAI) assay, and influenza was diagnosed by means of reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assays of respiratory samples. Results The study cohorts included 2116 pregnant women who were not infected with HIV and 194 pregnant women who were infected with HIV. At 1 month after vaccination, seroconversion rates and the proportion of partic...

Journal ArticleDOI
TL;DR: For the first time, evidence-based clinical recommendations comprehensively address this branch of point-of-care ultrasound, providing a framework for FoCUS to standardize its application in different clinical settings around the world.
Abstract: Background Focused cardiac ultrasound (FoCUS) is a simplified, clinician-performed application of echocardiography that is rapidly expanding in use, especially in emergency and critical care medicine. Performed by appropriately trained clinicians, typically not cardiologists, FoCUS ascertains the essential information needed in critical scenarios for time-sensitive clinical decision making. A need exists for quality evidence-based review and clinical recommendations on its use. Methods The World Interactive Network Focused on Critical UltraSound conducted an international, multispecialty, evidence-based, methodologically rigorous consensus process on FoCUS. Thirty-three experts from 16 countries were involved. A systematic multiple-database, double-track literature search (January 1980 to September 2013) was performed. The Grading of Recommendation, Assessment, Development and Evaluation method was used to determine the quality of available evidence and subsequent development of the recommendations. Evidence-based panel judgment and consensus was collected and analyzed by means of the RAND appropriateness method. Results During four conferences (in New Delhi, Milan, Boston, and Barcelona), 108 statements were elaborated and discussed. Face-to-face debates were held in two rounds using the modified Delphi technique. Disagreement occurred for 10 statements. Weak or conditional recommendations were made for two statements and strong or very strong recommendations for 96. These recommendations delineate the nature, applications, technique, potential benefits, clinical integration, education, and certification principles for FoCUS, both for adults and pediatric patients. Conclusions This document presents the results of the first International Conference on FoCUS. For the first time, evidence-based clinical recommendations comprehensively address this branch of point-of-care ultrasound, providing a framework for FoCUS to standardize its application in different clinical settings around the world.

Journal ArticleDOI
TL;DR: A systematic review and meta-analysis examining the epidemiology of chronic kidney disease in sub-Saharan Africa found poor data quality limits inferences and draws attention to the need for more information and validated measures of kidney function especially in the context of the growing burden of non-communicable diseases.

Journal ArticleDOI
TL;DR: The 6-month regimen that included weekly administration of high-dose rifapentine and moxifloxacin was as effective as the control regimen and the 4- month regimen was not noninferior to thecontrol regimen.
Abstract: BACKGROUND Tuberculosis regimens that are shorter and simpler than the current 6-month daily regimen are needed. METHODS We randomly assigned patients with newly diagnosed, smear-positive, drug-sensitive tuberculosis to one of three regimens: a control regimen that included 2 months of ethambutol, isoniazid, rifampicin, and pyrazinamide administered daily followed by 4 months of daily isoniazid and rifampicin; a 4-month regimen in which the isoniazid in the control regimen was replaced by moxifloxacin administered daily for 2 months followed by moxifloxacin and 900 mg of rifapentine administered twice weekly for 2 months; or a 6-month regimen in which isoniazid was replaced by daily moxifloxacin for 2 months followed by one weekly dose of both moxifloxacin and 1200 mg of rifapentine for 4 months. Sputum specimens were examined on microscopy and after culture at regular intervals. The primary end point was a composite treatment failure and relapse, with noninferiority based on a margin of 6 percentage points and 90% confidence intervals. RESULTS We enrolled a total of 827 patients from South Africa, Zimbabwe, Botswana, and Zambia; 28% of patients were coinfected with the human immunodefiency virus. In the per-protocol analysis, the proportion of patients with an unfavorable response was 4.9% in the control group, 3.2% in the 6-month group (adjusted difference from control, −1.8 percentage points; 90% confidence interval [CI], −6.1 to 2.4), and 18.2% in the 4-month group (adjusted difference from control, 13.6 percentage points; 90% CI, 8.1 to 19.1). In the modified intention-to-treat analysis these proportions were 14.4% in the control group, 13.7% in the 6-month group (adjusted difference from control, 0.4 percentage points; 90% CI, −4.7 to 5.6), and 26.9% in the 4-month group (adjusted difference from control, 13.1 percentage points; 90% CI, 6.8 to 19.4). CONCLUSIONS The 6-month regimen that included weekly administration of high-dose rifapentine and moxifloxacin was as effective as the control regimen. The 4-month regimen was not noninferior to the control regimen. (Funded by the European and Developing Countries Clinical Trials Partnership and the Wellcome Trust; RIFAQUIN Current Controlled Trials number, ISRCTN44153044.)

Journal ArticleDOI
Charles N. Rotimi1, Akin Abayomi2, Alash'le Abimiku3, Victoria Adabayeri4  +242 moreInstitutions (82)
20 Jun 2014-Science
TL;DR: If the dearth of genomics research involving Africans persists, the potential health and economic benefits emanating from genomic science may elude an entire continent.
Abstract: H3Africa is developing capacity for health-related genomics research in Africa Our understanding of genome biology, genomics, and disease, and even human history, has advanced tremendously with the completion of the Human Genome Project. Technological advances coupled with significant cost reductions in genomic research have yielded novel insights into disease etiology, diagnosis, and therapy for some of the world's most intractable and devastating diseases—including malaria, HIV/AIDS, tuberculosis, cancer, and diabetes. Yet, despite the burden of infectious diseases and, more recently, noncommunicable diseases (NCDs) in Africa, Africans have only participated minimally in genomics research. Of the thousands of genome-wide association studies (GWASs) that have been conducted globally, only seven (for HIV susceptibility, malaria, tuberculosis, and podoconiosis) have been conducted exclusively on African participants; four others (for prostate cancer, obsessive compulsive disorder, and anthropometry) included some African participants (www.genome.gov/gwastudies/). As discussed in 2011 (www.h3africa.org), if the dearth of genomics research involving Africans persists, the potential health and economic benefits emanating from genomic science may elude an entire continent.

Journal ArticleDOI
TL;DR: HBV genotypes/subgenotypes and genetic variability of HBV are useful in epidemiological and transmission studies, tracing human migrations, and in predicting the risk for the development of severe liver disease and response to antiviral therapy.
Abstract: Sequence heterogeneity is a feature of hepatitis B virus (HBV), the prototype member of the family Hepadnaviridae. Based on an intergroup divergence of greater than 7.5% across the

Journal ArticleDOI
Georges Aad1, Brad Abbott2, Jalal Abdallah3, S. Abdel Khalek4  +2911 moreInstitutions (209)
TL;DR: In this paper, a measurement of the Z/gamma* boson transverse momentum spectrum using ATLAS proton-proton collision data at a centre-of-mass energy of root s = 7TeV at the LHC is described.
Abstract: This paper describes a measurement of the Z/gamma* boson transverse momentum spectrum using ATLAS proton-proton collision data at a centre-of-mass energy of root s = 7TeV at the LHC. The measurement is performed in the Z/gamma* -> e(+)e(-) and Z/gamma* -> mu(+)mu(-) channels, using data corresponding to an integrated luminosity of 4.7 fb(-1). Normalized differential cross sections as a function of the Z/gamma* boson transverse momentum are measured for transverse momenta up to 800 GeV. The measurement is performed inclusively for Z/gamma* rapidities up to 2.4, as well as in three rapidity bins. The channel results are combined, compared to perturbative and resummed QCD calculations and used to constrain the parton shower parameters of Monte Carlo generators.

Journal ArticleDOI
TL;DR: It is shown that panitumumab is non-inferior to cetuximab and that these agents provide similar overall survival benefit in this population of patients, and small but meaningful differences in the rate of grade 3-4 infusion reactions and differences in dose scheduling can guide physician choice of anti-EGFR treatment.
Abstract: Summary Background The anti-EGFR monoclonal antibodies panitumumab and cetuximab are effective in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer. We assessed the efficacy and toxicity of panitumumab versus cetuximab in these patients. Methods For this randomised, open-label, phase 3 head-to-head study, we enrolled patients (from centres in North America, South America, Europe, Asia, Africa, and Australia) aged 18 years or older with chemotherapy-refractory metastatic colorectal cancer, an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less, and wild-type KRAS exon 2 status. Using a computer-generated randomisation sequence, we assigned patients (1:1; stratified by geographical region and ECOG performance status, with a permuted block method) to receive panitumumab (6 mg/kg once every 2 weeks) or cetuximab (initial dose 400 mg/m 2 ; 250 mg/m 2 once a week thereafter). The primary endpoint was overall survival assessed for non-inferiority (retention of ≥50% of the cetuximab treatment effect; historical hazard ratio [HR] for cetuximab plus best supportive care vs best supportive care alone of 0·55). The primary analysis included patients who received one or more dose of panitumumab or cetuximab, analysed per allocated treatment. Recruitment for this trial is closed. The trial is registered with ClinicalTrials.gov, number NCT01001377. Findings Between Feb 2, 2010, and July 19, 2012, we enrolled and randomly allocated 1010 patients, 999 of whom began study treatment: 499 received panitumumab and 500 received cetuximab. For the primary analysis of overall survival, panitumumab was non-inferior to cetuximab ( Z score −3·19; p=0·0007). Median overall survival was 10·4 months (95% CI 9·4–11·6) with panitumumab and 10·0 months (9·3–11·0) with cetuximab (HR 0·97; 95% CI 0·84–1·11). Panitumumab retained 105·7% (81·9–129·5) of the effect of cetuximab on overall survival seen in this study. The incidence of adverse events of any grade and grade 3–4 was similar across treatment groups. Grade 3–4 skin toxicity occurred in 62 (13%) patients given panitumumab and 48 (10%) patients given cetuximab. The occurrence of grade 3–4 infusion reactions was lower with panitumumab than with cetuximab (one [ vs nine [2%] patients), and the occurrence of grade 3–4 hypomagnesaemia was higher in the panitumumab group (35 [7%] vs 13 [3%]). We recorded one treatment-related fatal adverse event: a lung infection in a patient given cetuximab. Interpretation Our findings show that panitumumab is non-inferior to cetuximab and that these agents provide similar overall survival benefit in this population of patients. Both agents had toxicity profiles that were to be expected. In view of the consistency in efficacy and toxicity seen, small but meaningful differences in the rate of grade 3–4 infusion reactions and differences in dose scheduling can guide physician choice of anti-EGFR treatment. Funding Amgen Inc.


Journal ArticleDOI
Georges Aad1, Brad Abbott2, Jalal Abdallah3, S. Abdel Khalek4  +2916 moreInstitutions (211)
TL;DR: In this article, a search for squarks and gluinos in final states containing high-p T jets, missing transverse momentum and no electrons or muons is presented.
Abstract: A search for squarks and gluinos in final states containing high-p T jets, missing transverse momentum and no electrons or muons is presented. The data were recorded in 2012 by the ATLAS experiment in s√=8 TeV proton-proton collisions at the Large Hadron Collider, with a total integrated luminosity of 20.3 fb−1. Results are interpreted in a variety of simplified and specific supersymmetry-breaking models assuming that R-parity is conserved and that the lightest neutralino is the lightest supersymmetric particle. An exclusion limit at the 95% confidence level on the mass of the gluino is set at 1330 GeV for a simplified model incorporating only a gluino and the lightest neutralino. For a simplified model involving the strong production of first- and second-generation squarks, squark masses below 850 GeV (440 GeV) are excluded for a massless lightest neutralino, assuming mass degenerate (single light-flavour) squarks. In mSUGRA/CMSSM models with tan β = 30, A 0 = −2m 0 and μ > 0, squarks and gluinos of equal mass are excluded for masses below 1700 GeV. Additional limits are set for non-universal Higgs mass models with gaugino mediation and for simplified models involving the pair production of gluinos, each decaying to a top squark and a top quark, with the top squark decaying to a charm quark and a neutralino. These limits extend the region of supersymmetric parameter space excluded by previous searches with the ATLAS detector.

Journal ArticleDOI
TL;DR: Inhibition of PCSK9 with evolocumab resulted in significant dose-related reductions in lipoprotein (a), and the mean percentage of reduction was significantly greater in those patients with baseline Lp(a) of ≤125 nmol/l, the absolute reduction was substantially larger in those with levels >125 nml/l.

Journal ArticleDOI
TL;DR: In this article, the authors show that the long gamma-ray burst (GRB) 100621A, at the time the brightest X-ray transient ever detected by Swift-XRT in the 0.3-10 keV range, has been observed with the HESS.
Abstract: The long gamma-ray burst (GRB) 100621A, at the time the brightest X-ray transient ever detected by Swift-XRT in the 0.3-10 keV range, has been observed with the H.E.S.S. imaging air Cherenkov telescope array, sensitive to gamma radiation in the very-high-energy (VHE, >100 GeV) regime. Due to its relatively small redshift of z similar to 0.5, the favourable position in the southern sky and the relatively short follow-up time (<700 s after the satellite trigger) of the H.E.S.S. observations, this GRB could be within the sensitivity reach of the HESS. instrument. The analysis of the HESS. data shows no indication of emission and yields an integral flux upper limit above similar to 380 GeV of 4.2 x 10(-12) cm(-2) s(-1) s (95% confidence level), assuming a simple Band function extension model. A comparison to a spectral-temporal model, normalised to the prompt flux at sub-MeV energies, constraints the existence of a temporally extended and strong additional hard power law, as has been observed in the other bright X-ray GRB 130427A. A comparison between the HESS. upper limit and the contemporaneous energy output in X-rays constrains the ratio between the X-ray and VHE gamma-ray fluxes to be greater than 0.4. This value is an important quantity for modelling the afterglow and can constrain leptonic emission scenarios, where leptons are responsible for the X-ray emission and might produce VHE gamma rays.

Journal ArticleDOI
Georges Aad1, Brad Abbott2, Jalal Abdallah3, S. Abdel Khalek4  +2870 moreInstitutions (169)
TL;DR: The performance of the ATLAS muon reconstruction during the LHC run withpp collisions at s=7–8 TeV in 2011–2012 is presented, focusing mainly on data collected in 2012.
Abstract: This paper presents the performance of the ATLAS muon reconstruction during the LHC run with pp collisions at root s = 7-8 TeV in 2011-2012, focusing mainly on data collected in 2012. Measurements ...

Journal ArticleDOI
Georges Aad1, T. Abajyan2, Brad Abbott3, Jalal Abdallah4  +2885 moreInstitutions (169)
TL;DR: In this article, the electron reconstruction and identification efficiencies of the ATLAS detector at the LHC have been evaluated using proton-proton collision data collected in 2011 at TeV and corresponding to an integrated luminosity of 4.7 fb.
Abstract: Many of the interesting physics processes to be measured at the LHC have a signature involving one or more isolated electrons. The electron reconstruction and identification efficiencies of the ATLAS detector at the LHC have been evaluated using proton-proton collision data collected in 2011 at TeV and corresponding to an integrated luminosity of 4.7 fb. Tag-and-probe methods using events with leptonic decays of and bosons and mesons are employed to benchmark these performance parameters. The combination of all measurements results in identification efficiencies determined with an accuracy at the few per mil level for electron transverse energy greater than 30 GeV.

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TL;DR: In this article, the authors review current approaches and recent advances in research on climate impacts and adaptation in South Africa, focusing on cross-sectoral linkages in adaptation responses at a national level.
Abstract: In this paper we review current approaches and recent advances in research on climate impacts and adaptation in South Africa. South Africa has a well-developed earth system science research program that underpins the climate change scenarios developed for the southern African region. Established research on the biophysical impacts of climate change on key sectors (water, agriculture, and biodiversity) integrates the climate change scenarios but further research is needed in a number of areas, such as the climate impacts on cities and the built environment. National government has developed a National Climate Change Response White Paper, but this has yet to translate into policy that mainstreams adaptation in everyday practice and longer-term planning in all spheres and levels of government. A national process to scope long-term adaptation scenarios is underway, focusing on cross-sectoral linkages in adaptation responses at a national level. Adaptation responses are emerging in certain sectors. Some notable city-scale and project-based adaptation responses have been implemented, but institutional challenges persist. In addition, a number of knowledge gaps remain in relation to the biophysical and socio-economic impacts of climate change. A particular need is to develop South Africa's capacity to undertake integrated assessments of climate change that can support climate-resilient development planning. WIREs Clim Change 2014, 5:605–620. doi: 10.1002/wcc.295 For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article.

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TL;DR: An evaluation of different RapidEye bands using the two classifiers showed that incorporation of the red-edge band has a significant effect on the overall classification accuracy in vegetation cover types, indicating pursuit of high classification accuracy using high-spatial resolution imagery on complex landscapes remains paramount.
Abstract: Mapping of patterns and spatial distribution of land-use/cover (LULC) has long been based on remotely sensed data. In the recent past, efforts to improve the reliability of LULC maps have seen a proliferation of image classification techniques. Despite these efforts, derived LULC maps are still often judged to be of insufficient quality for operational applications, due to disagreement between generated maps and reference data. In this study we sought to pursue two objectives: first, to test the new-generation multispectral RapidEye imagery classification output using machine-learning random forest (RF) and support vector machines (SVM) classifiers in a heterogeneous coastal landscape; and second, to determine the importance of different RapidEye bands on classification output. Accuracy of the derived thematic maps was assessed by computing confusion matrices of the classifiers’ cover maps with respective independent validation data sets. An overall classification accuracy of 93.07% with a kappa value of ...

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TL;DR: A concerted effort has been made within this review to highlight the current advances of microneedles, and to provide an update of pharmaceutical research in the field ofmicroneedle-assisted transdermal drug delivery systems.

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Georges Aad1, Brad Abbott2, Jalal Abdallah3, S. Abdel Khalek4  +2868 moreInstitutions (187)
TL;DR: In this paper, an improved measurement of the mass of the Higgs boson is derived from a combined fit to the reconstructed invariant mass spectra of the decay channels H -> gamma gamma and H -> ZZ* -> 4l.
Abstract: An improved measurement of the mass of the Higgs boson is derived from a combined fit to the reconstructed invariant mass spectra of the decay channels H -> gamma gamma and H -> ZZ* -> 4l. The analysis uses the pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at center-of-mass energies of 7 TeV and 8 TeV, corresponding to an integrated luminosity of 25 fb(-1). The measured value of the Higgs boson mass is m(H) = 125.36 +/- 0.37(stat) +/- 0.18 (syst) GeV. This result is based on improved energy-scale calibrations for photons, electrons, and muons as well as other analysis improvements, and supersedes the previous result from ATLAS. Upper limits on the total width of the Higgs boson are derived from fits to the invariant mass spectra of the H -> gamma gamma and H -> ZZ* -> 4l decay channels.

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Georges Aad1, Brad Abbott2, Jalal Abdallah3, S. Abdel Khalek4  +2916 moreInstitutions (196)
TL;DR: In this paper, a measurement of the production processes of the recently discovered Higgs boson is performed in the two-photon final state using 4.5 fb(-1) of proton-proton collisions data at root s = 7 TeV and 20.4 GeV.
Abstract: A measurement of the production processes of the recently discovered Higgs boson is performed in the two-photon final state using 4.5 fb(-1) of proton-proton collisions data at root s = 7 TeV and 20.3 fb(-1) at root s = 8 TeV collected by the ATLAS detector at the Large Hadron Collider. The number of observed Higgs boson decays to diphotons divided by the corresponding Standard Model prediction, called the signal strength, is found to be mu = 1.17 +/- 0.27 at the value of the Higgs boson mass measured by ATLAS, m(H) = 125.4 GeV. The analysis is optimized to measure the signal strengths for individual Higgs boson production processes at this value of m(H). They are found to be mu(ggF) = 1.32 +/- 0.38, mu(VBF) = 0.8 +/- 0.7, mu(WH) = 1.0 +/- 1.6, mu(ZH) = 0.1(-0.1)(+3.7), and mu t (t) over barH = 1.6(-1.8)(+2.7), for Higgs boson production through gluon fusion, vector-boson fusion, and in association with a W or Z boson or a top-quark pair, respectively. Compared with the previously published ATLAS analysis, the results reported here also benefit from a new energy calibration procedure for photons and the subsequent reduction of the systematic uncertainty on the diphoton mass resolution. No significant deviations from the predictions of the Standard Model are found.

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TL;DR: In this paper, the effects of magnetic interaction number, slip factor and relative temperature difference on velocity and temperature profiles as well as entropy generation in magnetohydrodynamic (MHD) flow of a fluid with variable properties over a rotating disk are investigated using numerical methods.