Complement deficiencies limit CD20 monoclonal antibody treatment efficacy in CLL

Monoclonal antibodies (MAbs) form a central part of chronic lymphocytic leukaemia (CLL) treatment. We therefore evaluated whether complement defects in CLL patients reduced the induction of complement-dependent cytotoxicity (CDC) by using anti-CD20 MAbs rituximab (RTX) and ofatumumab (OFA). Ofatumumab elicited higher CDC levels than RTX in all CLL samples examined, particularly in poor prognosis cohorts (11q− and 17p−). Serum sample analyses revealed that 38.1% of patients were deficient in one or more complement components, correlating with reduced CDC responses. Although a proportion of patients with deficient complement levels initially induced high levels of CDC, on secondary challenge CDC activity in sera was significantly reduced, compared with that in normal human serum (NHS; P<0.01; n=52). In addition, a high CLL cell number contributed to rapid complement exhaustion. Supplementing CLL serum with NHS or individual complement components, particularly C2, restored CDC on secondary challenge to NHS levels (P<0.0001; n=9). In vivo studies revealed that complement components were exhausted in CLL patient sera post RTX treatment, correlating with an inability to elicit CDC. Supplementing MAb treatment with fresh-frozen plasma may therefore maintain CDC levels in CLL patients with a complement deficiency or high white blood cell count. This study has important implications for CLL patients receiving anti-CD20 MAb therapy

Nitrogen footprints: Past, present and future

The human alteration of the nitrogen cycle has evolved from minimal in the mid-19th century to extensive in the present time. The consequences to human and environmental health are significant. While much attention has been given to the extent and impacts of the alteration, little attention has been given to those entities (i.e., consumers, institutions) that use the resources that result in extensive reactive nitrogen (Nr) creation. One strategy for assessment is the use of nitrogen footprint tools. A nitrogen footprint is generally defined as the total amount of Nr released to the environment as a result of an entity's consumption patterns. This paper reviews a number of nitrogen footprint tools (N-Calculator, N-Institution, N-Label, N-Neutrality, N-Indicator) that are designed to provide that attention. It reviews N-footprint tools for consumers as a function of the country that they live in (N-Calculator, N-Indicator) and the products they buy (N-Label), for the institutions that people work in and are educated in (N-Institution), and for events and decision-making regarding offsets (N-Neutrality). N footprint tools provide a framework for people to make decisions about their resource use and show them how offsets can be coupled with behavior change to decrease consumer/institution contributions to N-related problems

Anisotropic Bose-Einstein condensates and completely integrable dynamical systems

A Gaussian ansatz for the wave function of two-dimensional harmonically trapped anisotropic Bose-Einstein condensates is shown to lead, via a variational procedure, to a coupled system of two second-order, nonlinear ordinary differential equations. This dynamical system is shown to be in the general class of Ermakov systems. Complete integrability of the resulting Ermakov system is proven. Using the exact solution, collapse of the condensate is analyzed in detail. Time-dependence of the trapping potential is allowed

Bounds and optimisation of orbital angular momentum bandwidths within parametric down-conversion systems

The measurement of high-dimensional entangled states of orbital angular momentum prepared by spontaneous parametric down-conversion can be considered in two separate stages: a generation stage and a detection stage. Given a certain number of generated modes, the number of measured modes is determined by the measurement apparatus. We derive a simple relationship between the generation and detection parameters and the number of measured entangled modes.Comment: 6 pages, 4 figure

Nitrogen : too much of a vital resource : Science Brief

It is now clear that the nitrogen problem is one of the most pressing environmental issues that we face. But in spite of the enormity of our influence on the N cycle and consequent implications for the environment and for human well-being, there is surprisingly little attention paid to the issue. While biodiversity loss and climate change have spawned huge budgets to create national and multidisciplinary programs, global organizations, political and media attention, the N challenge remains much less apparent in our thinking and actions. This is because we are educated with the important role that N plays with regard to food security. This paper aims to contribute to the understanding of the N challenge, and to provide options for decreasing the negative impacts of excess N

Small Scale Structure Formation in Chameleon Cosmology

Chameleon fields are scalar fields whose mass depends on the ambient matter density. We investigate the effects of these fields on the growth of density perturbations on sub-galactic scales and the formation of the first dark matter halos. Density perturbations on comoving scales $R < 1 {\rm pc}$ go non--linear and collapse to form structure much earlier than in standard $\Lambda$CDM cosmology. The resulting mini-halos are hence more dense and resilient to disruption. We therefore expect (provided that the density perturbations on these scales have not been erased by damping processes) that the dark matter distribution on small scales would be more clumpy in chameleon cosmology than in the $\Lambda$CDM model.Comment: 13 pages, 4 figure

A Millennium Learning Goal for education post‐2015: a question of outcomes or processes

As the target year for the current Millennium Development Goal of universal completion of primary education approaches, three World Bank economists have proposed its replacement with a Millennium Learning Goal. This is part of a trend of increased privileging of learning outcomes. The proposal is assessed from the perspective of human rights-based and social justice conceptualisations of education quality. A Millennium Learning Goal may enhance information on inclusion, conceived as equal opportunity to achieve learning outcomes. However, there is a danger that it would be misused to generate high stakes tests that can be detrimental to the achievement of goals that are not readily measurable and hence to the relevance of education. It is argued that a process goal with qualitative targets for the assessment of learning, for the monitoring of educational processes and for the processes by which learning goals are determined would be more appropriate for the international level.As the target year for the current Millennium Development Goal of universal completion of primary education approaches, three World Bank economists have proposed its replacement with a Millennium Learning Goal. This is part of a trend of increased privileging of learning outcomes. The proposal is assessed from the perspective of human rights-based and social justice conceptualisations of education quality. A Millennium Learning Goal may enhance information on inclusion, conceived as equal opportunity to achieve learning outcomes. However, there is a danger that it would be misused to generate high stakes tests that can be detrimental to the achievement of goals that are not readily measurable and hence to the relevance of education. It is argued that a process goal with qualitative targets for the assessment of learning, for the monitoring of educational processes and for the processes by which learning goals are determined would be more appropriate for the international level

Protecting the environment through insect farming as a means to produce protein for use as livestock, poultry, and aquaculture feed

Securing protein for the approximate 10 billion humans expected to inhabit our planet by 2050 is a major priority for the global community. Evidence has accrued over the past 30 years that strongly supports and justifies the sustainable use of insects as a means to produce protein products as feed for pets, livestock, poultry, and aquacultured species. Researchers and entrepreneurs affiliated with universities and industries, respectively, from 18 nations distributed across North and South America, Europe, Asia, Africa and Australia contributed to the development of this article, which is an indication of the global interest on this topic. A brief overview of insects as feed for the aquaculture industry along with a review of the black soldier fly, Hermetia illucens (Diptera: Stratiomyidae), as a model for such systems is provided