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The pathogenesis of malaria is associated with blood-stage infection and there is strong evidence that antibodies specific to parasite blood-stage antigens can control parasitemia. This provides a strong rational for applying blood-stage antigen components in a multivalent vaccine, as the induced antibodies in combination can enhance protection. The Plasmodium falciparum rhoptry-associated membrane antigen (PfRAMA) is a promising vaccine target, due to its fundamental role in merozoite invasion and low level of polymorphism. Polyclonal antibodies against PfRAMA are able to inhibit P. falciparum growth and interact synergistically when combined with antibodies against P. falciparum reticulocyte-binding protein 5 (PfRh5) or cysteine-rich protective antigen (PfCyRPA). In this study, we identified a novel PfRAMA-specific mAb with neutralizing activity, which in combination with PfRh5- or PfCyRPA-specific mAbs potentiated the neutralizing effect. By applying phage display technology, we mapped the protective epitope to be in the C-terminal region of PfRAMA. Our results confirmed previous finding of synergy between PfRAMA-, PfRh5- and PfCyRPA-specific antibodies, thereby paving the way of testing these antigens (or fragments of these antigens) in combination to improve the efficacy of blood-stage malaria vaccines. The results emphasize the importance of directing antibody responses towards protective epitopes, as the majority of anti-PfRAMA mAbs were unable to inhibit merozoite invasion of erythrocytes. [ABSTRACT FROM AUTHOR]

The focus is on the micro-possibilities of student capabilities formation as the end of public-good higher education, rather than on a systems or organizations approach more commonly found in discussions of the public good and higher education. This does not discount other valuable public-good ends. Using South Africa as a global South context, a capability-based approach to the public good of higher education is proposed for its humanizing ethic, attention to fair opportunities, and participation in terms of what students are able to do and to be in and through higher education. A capability frame is complemented by thinking about decoloniality and epistemic justice to help identify central higher education capabilities. The three proposed intersecting capability dimensions are as follows: personhood self-formation, epistemic contribution, and sufficiency of economic resources, intended to guide university practices and policy interventions in the direction of the public good. By populating the space of the public good with capabilities, a shift is made away from micro-economics which see the public good as a reductionist space of commodities and human capital development. Higher education is rather understood as having both instrumental and intrinsic value, generating an alternative logic to that of neo-liberalism, and an individualist ontology of competition and untrammeled markets. The pressures of the global context are acknowledged so that the public good is understood as both “ideal-aspirational” but also “practical-feasible” in the light of local South African conditions. An expanded capability-based framing would contribute to reducing higher education inequalities as a public-good and public-accountable contribution by universities. [ABSTRACT FROM AUTHOR]

The paper explores a conceptual approach to the question of what it means to provide a university education that addresses equity, and encourages the formation of STEM graduates oriented to public-good values and with commitments to making professional contributions to society which will advance human well-being. It considers and rejects resource-based and utilitarian approaches to well-being and opts for Amartya Sen and Martha Nussbaum's capabilities approach which involves developing graduates' capabilities and functionings to be and do in ways which they have reason to value. The capabilities approach argues for educational and social development as the expansion of such freedoms. The approach is sensitive also to diversity through the focus on the choice of a plurality of functionings and a wide informational basis for policy, practice and social justice evaluations. It allows an analysis of how different individuals can convert available resources into functionings through attending to conversion factors: personal (internal) conversion factors, social conversion factors and environmental (external) conversion factors. All make a difference to how an individual converts her resources into functionings and makes advantage and disadvantage visible. There is a further education-specific issue, that of selecting core valuable capabilities because not any form of science and engineering education will do. Educators need to deliberate and agree which capabilities and corresponding functionings are valuable and so should be supported in policy and practice. In a capabilities-friendly education, education would aim to secure and distribute valuable education capabilities to diverse students (women and men, black and white, rural and urban and so on) paying attention to the social arrangements in education (pedagogies, institutional culture and education policy) and to conversion factors and barriers that might impede the development of opportunities and valued outcomes. [ABSTRACT FROM AUTHOR]

The genome sequence of tomato ringspot virus (ToRSV, a subgroup C nepovirus) is currently available for one raspberry isolate. In this study, we describe the complete genome sequence of three additional isolates from raspberry (Rasp1-2014), grapevine (GYV-2014) and prunus (13C280). The degree of nucleotide sequence identity shared between RNA1 and RNA2 in the 5′-terminal 900 nucleotides and 3′ untranslated region varied from 98-99 % (13C280, GYV-2014) to 80 % (Rasp1-2014). Phylogenetic studies revealed distinct origins for Rasp1-2014 RNA1 and RNA2, suggesting reassortment. Two recombination events were also identified in the 3′ UTR and 5′-terminal region of RNA1. [ABSTRACT FROM AUTHOR]

Introduction: Delayed posthypoxic demyelination may rarely complicate an episode of severe hypoxia, with or without exposure to carbon monoxide. Following recovery from initial coma, progressive neurologic deterioration ensues with outcomes ranging from death to full recovery. Delayed posthypoxic demyelination is hypothesized to be immunemediated, with support coming from recent animal experiments.Methods: We report a 46-year-old man who developed progressive cognitive deficits with abulia approximately 3 weeks after recovering from coma related to alcohol and morphine intoxication.Results: Despite treatment with high-dose steroids and plasmapheresis, he continued to deteriorate and remained in a vegetative state until his death under hospice care more than 2 months after his initial hypoxic insult. Serial brain imaging and postmortem examination showed bilateral necrosis of the globi pallidi and extensive demyelination in the centrum semiovale and corona radiata.Conclusions: Based on an immune-mediated model of disease and given a lack of effective treatments, future use of immunomodulatory therapy may still be worth considering early in the course of this rare and potentially devastating condition. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is one of very few viruses that are either naturally cleared, or alternatively persist to cause chronic disease. Viral diversity and escape, as well as host adaptive immune factors, are believed to control the outcome. To date, there is limited understanding of the critical, early host-pathogen interactions. The asymptomatic nature of early HCV infection generally prevents identification of the transmitted/founder (T/F) virus, and thus the study of host responses directed against the autologous T/F strain. In this study, 14 rare subjects identified from very early in infection (4–45 days) with varied disease outcomes (n = 7 clearers) were examined in regard to the timing, breadth, and magnitude of the neutralizing antibody (nAb) response, as well as evolution of the T/F strain. Clearance was associated with earlier onset and more potent nAb responses appearing at a mean of 71 days post-infection (DPI), but these responses were narrowly directed against the autologous T/F virus or closely related variants. In contrast, a delayed onset of nAbs (mean 425 DPI) was observed in chronic progressors that appear to have targeted longitudinal variants rather than the T/F strain. The nAb responses in the chronic progressors mapped to known CD81 binding epitopes, and were associated with rapid emergence of new viral variants with reduced CD81 binding. We propose that the prolonged period of viremia in the absence of nAbs in these subjects was associated with an increase in viral diversity, affording the virus greater options to escape nAb pressure once it emerged. These findings indicate that timing of the nAb response is essential for clearance. Further investigation of the specificities of the early nAbs and the factors regulating early induction of protective nAbs is needed. [ABSTRACT FROM AUTHOR]

Clinical immunity to malaria develops slowly after repeated episodes of infection and antibodies are essential in naturally acquired immunity against malaria. However, chronic exposure to malaria has been linked to perturbation in B-cell homeostasis with the accumulation of atypical memory B cells. It is unclear how perturbations in B cell subsets influence antibody breadth, avidity, and function in individuals naturally exposed to malaria. We show that individuals living in high malaria transmission regions in Ghana have higher Plasmodium falciparum merozoite antigen-specific antibodies and an increased antibody breadth score but lower antibody avidities relative to low transmission regions. The frequency of circulating atypical memory B cells is positively associated with an individual's antibody breadth. In vitro growth inhibition is independent of the ability to bind to free merozoites but associated with the breadth of antibody reactivity in an individual. Taken together, our data shows that repeated malaria episodes hamper the development of high avid antibodies which is compensated for by an increase in antibody breadth. Our results provide evidence to reinforce the idea that in regions with high malaria prevalence, repeated malaria infections lead to the broadening of antibody diversity and the continued presence of atypical memory B cell populations. [ABSTRACT FROM AUTHOR]

Stroke is the leading cause of disability and one of the most common causes of death worldwide. Outside the setting of acute management, secondary prevention and stroke rehabilitation, little has been written to address the ongoing symptomatic and palliative needs of these patients and their families. In this literature review, we look beyond secondary prevention with the aim of providing evidence-informed management guidelines for the myriad and often under-recognized symptomatic and palliative care needs of stroke survivors. Some of the most common and disabling post-stroke symptoms that are reviewed here include central post-stroke pain, hemiplegic shoulder pain, painful spasticity, fatigue, incontinence, post-stroke seizures, sexual dysfunction, sleep-disordered breathing, depression and emotionalism. We review the role of caregivers and explore ways to support them and, lastly, remind the reader to be perceptive to the patient's spiritual needs. The literature is most robust, including controlled trials, for central post-stroke pain and depression. Synthesis and discussion outside these areas are frequently limited to smaller studies, case reports and expert opinion. While some data exists to guide informed decision-making, there is an urgent need to document best practice and identify appropriate clinical standards for the full spectrum of symptoms experienced by stroke survivors. We present the current and established data to aid health care providers in symptomatic and palliative management of stroke survivors. [ABSTRACT FROM AUTHOR]

In this study, we report the genome sequence of five isolates of strawberry mottle virus (family Secoviridae, order Picornavirales) from strawberry field samples with decline symptoms collected in Eastern Canada. The Canadian isolates differed from the previously characterized European isolate 1134 in that they had a longer RNA2, resulting in a 239-amino-acid extension of the C-terminal region of the polyprotein. Sequence analysis suggests that reassortment and recombination occurred among the isolates. Phylogenetic analysis revealed that the Canadian isolates are diverse, grouping in two separate branches along with isolates from Europe and the Americas. [ABSTRACT FROM AUTHOR]

A correction to the article "Symptomatic and Palliative Care for Stroke Survivors" by Claire J. Creutzfeldt, Robert G. Holloway, and Melanie Walker is presented.

Purpose: Although health-related quality of life (HRQL) is increasingly assessed in randomized controlled trials (RCTs), HRQL findings are not always incorporated into clinical decision making. We examined the current perspectives of oncologists on the use of HRQL findings from RCTs, and variation of these perspectives between countries and specialties. Methods: A cross-sectional e-survey of oncologist members of the NCIC Clinical Trials Group, the United Kingdom National Cancer Research Institute Clinical Studies Groups, and the Australia/New Zealand cancer clinical trials network was conducted. Respondents reported their perceptions of the usefulness of RCT HRQL outcomes for informing practice, their use of HRQL findings in practice, barriers/facilitators to this use, and preferences for HRQL data presentation in RCT publications. Chi-square tests compared responses between countries and specialties. Results: A total of 396 oncologists participated (estimated response rate: 30 %). The most frequently reported specialties were medical (46 %) and radiation (37 %) oncology. HRQL findings from RCTs were reported as useful (73 %), but were infrequently used to guide clinical decisions with patients. Perceived barriers were lack of time (67 %) and understanding (57 %), and concerns about generalizability of results (68 %). Identified facilitators included joint publication of HRQL/clinical outcomes (96 %) and summary of clinical implications of HRQL findings in RCT publications (76 %). Use of HRQL findings, perceived barriers/facilitators, and presentation preferences did not differ by country or specialty. Conclusions: Oncologists support HRQL findings from RCTs, but perceive important barriers to their use in clinical decision making, regardless of country or specialty. Combined, clear reporting of HRQL/clinical data may facilitate their clinical application. [ABSTRACT FROM AUTHOR]