Clearance of human IgG1-sensitised red blood cells in vivo in humans relates to the in vitro properties of antibodies from alternative cell lines.

We previously produced a recombinant version of the human anti-RhD antibody Fog-1 in the rat myeloma cell line, YB2/0. When human, autologous RhD-positive red blood cells (RBC) were sensitised with this IgG1 antibody and re-injected, they were cleared much more rapidly from the circulation than had been seen earlier with the original human-mouse heterohybridoma-produced Fog-1. Since the IgG have the same amino acid sequence, this disparity is likely to be due to alternative glycosylation that results from the rat and mouse cell lines. By comparing the in vitro properties of YB2/0-produced Fog-1 IgG1 and the same antibody produced in the mouse myeloma cell line NS0, we now have a unique opportunity to pinpoint the cause of the difference in ability to clear RBC in vivo. Using transfected cell lines that express single human FcγR, we showed that IgG1 made in YB2/0 and NS0 cell lines bound equally well to receptors of the FcγRI and FcγRII classes but that the YB2/0 antibody was superior in FcγRIII binding. When measuring complexed IgG binding, the difference was 45-fold for FcγRIIIa 158F, 20-fold for FcγRIIIa 158V and approximately 40-fold for FcγRIIIb. The dissimilarity was greater at 100-fold in monomeric IgG binding assays with FcγRIIIa. When used to sensitise RBC, the YB2/0 IgG1 generated 100-fold greater human NK cell antibody-dependent cell-mediated cytotoxicity and had a 103-fold advantage over the NS0 antibody in activating NK cells, as detected by CD54 levels. In assays of monocyte activation and macrophage adherence/phagocytosis, where FcγRI plays major roles, RBC sensitised with the two antibodies produced much more similar results. Thus, the alternative glycosylation profiles of the Fog-1 antibodies affect only FcγRIII binding and FcγRIII-mediated functions. Relating this to the in vivo studies confirms the importance of FcγRIII in RBC clearance.The work was supported by funding from the Department of Pathology, University of Cambridge through income that was derived from commercial exploitation of patented antibodies. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final published version. It first appeared at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0109463

Planar laser-induced fluorescence (PLIF) investigation of hypersonic flowfields in a Mach 10 wind tunnel

Planar laser-induced fluorescence (PLIF) of nitric oxide (NO) was used to visualize four different hypersonic flowfields in the NASA Langley Research Center 31-Inch Mach 10 Air wind tunnel. The four configurations were: (1) the wake flowfield of a fuselage-only X-33 lifting body, (2) flow over a flat plate containing a rectangular cavity, (3) flow over a 70deg blunted cone with a cylindrical afterbody, formerly studied by an AGARD working group, and (4) an Apollo-geometry entry capsule - relevant to the Crew Exploration Vehicle currently being developed by NASA. In all cases, NO was seeded into the flowfield through tubes inside or attached to the model sting and strut. PLIF was used to visualize the NO in the flowfield. In some cases pure NO was seeded into the flow while in other cases a 5% NO, 95% N2 mix was injected. Several parameters were varied including seeding method and location, seeding mass flow rate, model angle of attack and tunnel stagnation pressure, which varies the unit Reynolds number. The location of the laser sheet was as also varied to provide three dimensional flow information. Virtual Diagnostics Interface (ViDI) technology developed at NASA Langley was used to visualize the data sets in post processing. The measurements demonstrate some of the capabilities of the PLIF method for studying hypersonic flows

The reporting of statistics in medical educational studies: an observational study

<p>Abstract</p> <p>Background</p> <p>There is confusion in the medical literature as to whether statistics should be reported in survey studies that query an entire population, as is often done in educational studies. Our objective was to determine how often statistical tests have been reported in such articles in two prominent journals that publish these types of studies.</p> <p>Methods</p> <p>For this observational study, we used electronic searching to identify all survey studies published in <it>Academic Medicine </it>and the <it>Journal of General Internal Medicine </it>in which an entire population was studied. We tallied whether inferential statistics were used and whether p-values were reported.</p> <p>Results</p> <p>Eighty-four articles were found: 62 in <it>Academic Medicine </it>and 22 in the <it>Journal of General Internal Medicine</it>. Overall, 38 (45%) of the articles reported or stated that they calculated statistics: 35% in <it>Academic Medicine </it>and 73% in the <it>Journal of General Internal Medicine</it>.</p> <p>Conclusion</p> <p>Educational enumeration surveys frequently report statistical tests. Until a better case can be made for doing so, a simple rule can be proffered to researchers. When studying an entire population (e.g., all program directors, all deans, and all medical schools) for factual information, do not perform statistical tests. Reporting percentages is sufficient and proper.</p

Eating Paradise: Food as Coloniality and Leisure

Sandals Resorts’ Gourmet Discovery Dining programme continues the company’s practice of marketing difference by combining tourism with the commodification of food from non-Western cultures (Dodman and Rhiney 2008). The article draws on bell hooks’ (1992) concept of ‘eating the other’ and the analysis undertakes an interdisciplinary approach that combines visual analysis with Anibal Quijano’s (2007) concept of modernity/coloniality. The discussion explores the trends of global multiculturalism that have been adopted by Sandals in a hybridized cut and mix approach to selling a packaged ideal of the Caribbean. The visual techniques devised to create a culinary holiday package are overlaid onto a manufactured and homogenised or McDonaldized (Ritzer and Liska 1997) Caribbean that provides insight into the way in which global neoliberal multiculturalism is framed by ongoing colonial relations after formal colonial rule has ended in the Caribbean region

A Study of B0 -> J/psi K(*)0 pi+ pi- Decays with the Collider Detector at Fermilab

We report a study of the decays B0 -> J/psi K(*)0 pi+ pi-, which involve the creation of a u u-bar or d d-bar quark pair in addition to a b-bar -> c-bar(c s-bar) decay. The data sample consists of 110 1/pb of p p-bar collisions at sqrt{s} = 1.8 TeV collected by the CDF detector at the Fermilab Tevatron collider during 1992-1995. We measure the branching ratios to be BR(B0 -> J/psi K*0 pi+ pi-) = (8.0 +- 2.2 +- 1.5) * 10^{-4} and BR(B0 -> J/psi K0 pi+ pi-) = (1.1 +- 0.4 +- 0.2) * 10^{-3}. Contributions to these decays are seen from psi(2S) K(*)0, J/psi K0 rho0, J/psi K*+ pi-, and J/psi K1(1270)

Is speed of healing a good predictor of eventual healing of pyoderma gangrenosum?

Background: Pyoderma gangrenosum is a rare inflammatory skin condition. The STOPGAP studies compared treatments for pyoderma gangrenosum using a primary outcome of healing speed at 6 weeks. Objective: Using data from both studies we assessed the predictive value of three early predictors for healing at 6 months - speed of healing, Investigator Global Assessment and resolution of inflammation, recorded at 2 and 6 weeks. Methods: Logistic regression models were applied and the effectiveness of the three measures was assessed through estimating the positive (PPV) and negative predictive values (NPV) and the area under the receiver operating characteristic curve (AUC). Results: The PPV and NPV at 6 weeks were 63.5% (95% CI:52.4%, 73.7%) and 74.6% (95% CI:62.5%, 84.5%) respectively for speed of healing; 80% (95% CI:68.7%, 88.6%) and 74.2% (95% CI:64.1%, 2.7%) for IGA; and 72.1% (95% CI:59.9%, 82.3%) and 68.1% (95% CI:57.7%, 77.3%) for resolution of inflammation. Investigator Global Assessment had the best combined PPV, NPV and AUC at 2 and 6 weeks. Limitations: We were limited by data available from the STOP GAP trial and cohort study. Conclusion: Speed of healing, Investigator Global Assessment and resolution of inflammation were all shown to be good predictors of eventual healing

Measurement, reporting and verification of climate-smart agriculture: Change of perspective, change of possibilities?

The World Agroforestry Centre (ICRAF), Unique Forestry and Land Use and Vuna have been working with stakeholders in four countries in eastern and southern Africa (Tanzania, Malawi, Zambia and Zimbabwe) to assess the current state of national CSA M&E and to set out country-specific roadmaps for developing systems for monitoring and reporting on CSA. The project took a country-driven approach to documenting stakeholders’ information needs, exploring how to build on and align with existing M&E systems and international reporting frameworks, and encouraging cross-country comparisons. Though the research was grounded in southern Africa, these lessons are applicable to CSA and other topic-driven initiatives (such as land restoration and the Bonn Challenge) across similar environments and social contexts on the continent and around the world. Here we detail three key findings from the assessment

Mesure, notification et vérification de l’agriculture intelligente face au climat: changement de perspective, changement de possibilités ? Conclusions de l’auto-évaluation nationale des besoins, systèmes et opportunités

Depuis 2009, des milliards de dollars ont été investis dans des programmes d’AIC dans le but d’aider les petits exploitants à augmenter leur productivité tout en s’adaptant aux changements climatiques et en contribuant à les atténuer. Cependant, l’AIC a récemment dépassé les cercles de l’aide au développement et de la société civile, et les pays se sont mis à adopter des stratégies d’AIC dans le cadre de leurs politiques et stratégies de riposte aux changements climatiques et de développement agricole, notamment leurs Contributions déterminées au niveau national (CDN)

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Effect of ready-to-use supplementary food on mortality in severely immunocompromised HIV-infected individuals in Africa initiating antiretroviral therapy (REALITY): an open-label, parallel-group, randomised controlled trial.

BACKGROUND: In sub-Saharan Africa, severely immunocompromised HIV-infected individuals have a high risk of mortality during the first few months after starting antiretroviral therapy (ART). We hypothesise that universally providing ready-to-use supplementary food (RUSF) would increase early weight gain, thereby reducing early mortality compared with current guidelines recommending ready-to-use therapeutic food (RUTF) for severely malnourished individuals only. METHODS: We did a 2 × 2 × 2 factorial, open-label, parallel-group trial at inpatient and outpatient facilities in eight urban or periurban regional hospitals in Kenya, Malawi, Uganda, and Zimbabwe. Eligible participants were ART-naive adults and children aged at least 5 years with confirmed HIV infection and a CD4 cell count of fewer than 100 cells per μL, who were initiating ART at the facilities. We randomly assigned participants (1:1) to initiate ART either with (RUSF) or without (no-RUSF) 12 weeks' of peanut-based RUSF containing 1000 kcal per day and micronutrients, given as two 92 g packets per day for adults and one packet (500 kcal per day) for children aged 5-12 years, regardless of nutritional status. In both groups, individuals received supplementation with RUTF only when severely malnourished (ie, body-mass index [BMI] 0·7). Through 48 weeks, adults and adolescents aged 13 years and older in the RUSF group had significantly greater gains in weight, BMI, and MUAC than the no-RUSF group (p=0·004, 0·004, and 0·03, respectively). The most common type of serious adverse event was specific infections, occurring in 90 (10%) of 897 participants assigned RUSF and 87 (10%) of 908 assigned no-RUSF. By week 48, 205 participants had serious adverse events in both groups (p=0·81), and 181 had grade 4 adverse events in the RUSF group compared with 172 in the non-RUSF group (p=0·45). INTERPRETATION: In severely immunocompromised HIV-infected individuals, providing RUSF universally at ART initiation, compared with providing RUTF to severely malnourished individuals only, improved short-term weight gain but not mortality. A change in policy to provide nutritional supplementation to all severely immunocompromised HIV-infected individuals starting ART is therefore not warranted at present. FUNDING: Joint Global Health Trials Scheme (UK Medical Research Council, UK Department for International Development, and Wellcome Trust).This study was funded by the Joint Global Health Trials Scheme (JGHTS) of the UK Department for International Development (DFID), the Wellcome Trust, and the UK Medical Research Council (MRC; G1100693). Additional funding support was provided by the PENTA foundation and core support to the MRC Clinical Trials Unit at University College London (London, UK; MC_UU_12023/23, MC_UU_12023/26). Cipla, Gilead Sciences, ViiV Healthcare/GlaxoSmithKline, and Merck Sharp & Dohme donated drugs for the study and ready-to-use supplementary food was purchased from Valid International. The MRC Clinical Trials Unit has received other funding from Tibotec and Gilead Sciences for data safety monitoring board membership and lectures. The Malawi–Liverpool–Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine (101113/Z/13/Z), and the KEMRI/Wellcome Trust Research Programme, Kilifi (203077/Z/16/Z) are supported by strategic awards from the Wellcome Trust (UK)