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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]

There is currently an over-emphasis on the economic aims of higher education at the expense of the aims of personal and social transformation. This article proposes a specific approach to integrating educational aims. It draws on the works of Jurgen Habermas and Martha Nussbaum to conceptualise integrative learning as a simultaneous focus on self, others and society. A small-scale case study of five lecturers from different disciplines is employed to explore the value of the conceptual framework by illustrating variation in how integrative learning is understood and practised in contemporary pedagogical conditions. [ABSTRACT FROM AUTHOR]

On the morning of 4 March 1999 Ronald Barnett (Professor of Higher Education and Dean of Professional Development at the Institute of Education, University of London), Jon Nixon, Stephen Rowland and Melanie Walker (members of the Editorial Board of Teaching in Higher Education) met in Scotland at the University of Stirling to discuss Ronald Barnett's last major work, Higher Education: A Critical Business (SRHE/Open University Press, 1997) and to anticipate his forthcoming book Realizing the University (SRHE/Open University Press, 1999). [ABSTRACT FROM AUTHOR]

Mitochondria are complex organelles that play a critical role within the cell; mitochondrial dysfunction can result in significant cell damage or death. Previous studies have demonstrated the promising therapeutic effects of autologous mitochondria transplantation into ischemic cardiac tissue; however, few studies have examined the in vivo effects of mitochondria infusion into the brain. The aim of this study is to report a procedure for carotid infusion of autologous mitochondria into porcine brains. By using this infusion technique, we propose that a selective and minimally invasive administration is feasible and may provide benefits in the treatment of various central nervous system disorders. [ABSTRACT FROM AUTHOR]

In rare cases, individuals with a history of long‐term injecting drug use remain seronegative and aviraemic, despite prolonged and likely repeated exposure to Hepatitis C virus (HCV) through high‐risk behaviour. We describe anti‐HCV Envelope (E) antibody responses in a prospective cohort of carefully defined highly exposed but uninfected subjects (HESN) and comparison subjects who were also high risk and uninfected, but rapidly became HCV infected (Incident). Longitudinally collected samples from HESN cases (n = 22) were compared to Incident controls (n = 22). IgG, IgM and IgA from sera were tested by ELISA to genotype 1a and 3a E glycoproteins, and recombinant genotype 1a E2 antigen. IgG subclass isotyping was performed for those positive for IgG. Virus‐neutralizing activity was assessed on HCV pseudoparticles, and HCV E–specific B cells analysed using flow cytometry. A significant minority of HESN cases (n = 10; 45%) had anti‐E, predominantly in the IgG2 subclass, which was not found in the pre‐infection time point of the Incident cases (n = 1; 5%). A subset of the HESN subjects also had neutralizing activity and HCV‐specific B cells detected significantly more than Incident cases pre‐infection. In conclusion, the HESN phenotype is associated with IgG2 anti‐E antibodies, neutralization activity and HCV E–specific memory B cells. These findings suggest that HESN subjects may be resistant to HCV infection through humoral immune‐mediated mechanisms. [ABSTRACT FROM AUTHOR]

Neutralising antibodies (NAbs) play a key role in clearance of HCV. NAbs have been isolated and mapped to several domains on the HCV envelope proteins. However, the immunodominance of these epitopes in HCV infection remains unknown, hindering efforts to elicit optimal epitope-specific responses. Furthermore, it remains unclear which epitope-specific responses are associated with broad NAb (bNAb) activity in primary HCV infection. The aim of this study was to define B cell immunodominance in primary HCV, and its implications on neutralisation breadth and clearance. Using samples from 168 patients with primary HCV infection, the antibody responses targeted 2 immunodominant domains, termed domains B and C. Genotype 1 and 3 infections were associated with responses targeted towards different bNAb domains. No epitopes were uniquely targeted by clearers compared to those who developed chronic infection. Samples with bNAb activity were enriched for multi-specific responses directed towards the epitopes antigenic region 3, antigenic region 4, and domain D, and did not target non-neutralising domains. This study outlines for the first time a clear NAb immunodominance profile in primary HCV infection, and indicates that it is influenced by the infecting virus. It also highlights the need for a vaccination strategy to induce multi-specific responses that do not target non-neutralising domains. Neutralising antibodies will likely form a key component of a protective hepatitis C virus vaccine. In this work we characterise the predominant neutralising and non-neutralising antibody (epitope) targets in acute hepatitis C virus infection. We have defined the natural hierarchy of epitope immunodominance, and demonstrated that viral genotype can impact on this hierarchy. Our findings highlight key epitopes that are associated with broadly neutralising antibodies, and the deleterious impact of mounting a response towards some of these domains on neutralising breadth. These findings should guide future efforts to design immunogens aimed at generating neutralising antibodies with a vaccine candidate. • Neutralising antibodies will likely form a key component of an HCV vaccine. • We characterise the immunodominance of neutralising and non-neutralising epitopes in primary HCV infection. • We identify that virus genotype might influence the epitopes targeted. • We also identify that certain epitope target combinations are associated with greater breadth. [ABSTRACT FROM AUTHOR]

Undernutrition in children remains a major global health issue and the prevalence of undernutrition in children under age five in the Democratic Republic of the Congo (DRC) is among the highest in the world. Both biological and socioeconomic factors contribute to undernutrition, and the literature reports an association between women's empowerment and lower rates of child undernutrition in sub-Saharan Africa. However, the relationship between women's decision-making power and child undernutrition is less understood. The objective of this study was to evaluate the association between women's decision-making power and stunting/wasting in their children under age five in the DRC. This study used cross-sectional data from the 2013–2014 DRC Demographic and Health Survey, from which a sample of 3,721 woman-child pairs were identified. Women were classified as having decision-making power in five decision-making dimensions if they participated in the decision either alone or jointly with their husband or partner or someone else. Child height-for-age and weight-for-height Z-scores were used to determine stunting and wasting, respectively, according to the World Health Organization Child Growth Standards. Multivariate regression analyses demonstrated that none of the five dimensions of decision-making power were associated with stunting or wasting in children. Further research that evaluates women's decision-making power with more detailed, relevant and context-specific measures is warranted to more accurately investigate women's decision-making power and undernutrition in children. [ABSTRACT FROM AUTHOR]

Hepatitis C (HCV) is a rapidly mutating RNA virus, with a strong propensity to cause chronic infection and progressive liver disease. Recent evidence has shown that early appearance of neutralizing antibodies in primary infection is associated with clearance. Little is known about the characteristics of HCV-specific B cells and their correlation with outcomes in primary infection, as there is a lack of sensitive tools for HCV-specific B cells which are present at very low frequency. We describe the development and optimisation of tetramer staining for flow cytometric detection of HCV-specific B cells using a cocktail of two recombinant HCV Envelope-2 (rE2) glycoproteins (from genotype 1a and 3a; Gt1a and Gt3a) and streptavidin dyes. The optimal weight to weight (w /w) ratio of streptavidin-phycoerythrin (PE) and rE2 proteins were determined for sensitive detection using HCV E2-specific hybridoma cell lines and peripheral blood mononuclear cells (PBMC) from HCV-infected individuals. In a cross-sectional set of PBMC samples collected from 33 subjects with either chronic infection or previous clearance, HCV E2-specific B cells (CD19+CD20+CD10−IgD−tetramer+) were detected in 29 subjects (87.8%), with a mean frequency of 0.45% (0.012–2.20%). To validate the specificity of tetramer staining, 367 HCV E2-specific B cells were single cell sorted from 9 PBMC samples before monoclonal antibodies (mAbs) were synthesised, with 87.5% being reactive to E2 via ELISA. Of these mAbs, 284 and 246 clones were reactive to either Gt1a or Gt3a E2 proteins, respectively. This is a sensitive and robust method for future studies investigating B cell responses against the HCV Envelope protein. [ABSTRACT FROM AUTHOR]

The ability to monitor changes in the expression and localization of integrins is essential for understanding their contribution to development, tissue homeostasis and disease. Here, we pioneered the use of Crispr/Cas9 genome editing to tag an allele of the β4 subunit of the α6β4 integrin. A tdTomato tag was inserted with a linker at the C-terminus of integrin β4 in mouse mammary epithelial cells. Cells harboring this tagged allele were similar to wild-type cells with respect to integrin β4 surface expression, association with the α6 subunit, adhesion to laminin and consequent signaling. These integrin β4 reporter cells were transformed with YAP (also known as YAP1), which enabled us to obtain novel insight into integrin β4 dynamics in response to a migratory stimulus (scratch wound) by livecell video microscopy. An increase in integrin β4 expression in cells proximal to the wound edge was evident, and a population of integrin β4-expressing cells that exhibited unusually rapid migration was identified. These findings could shed insight into integrin β4 dynamics during invasion and metastasis. Moreover, these integrin β4 reporter cells should facilitate studies on the contribution of this integrin to mammary gland biology and cancer. [ABSTRACT FROM AUTHOR]

The ability to monitor changes in the expression and localization of integrins is essential for understanding their contribution to development, tissue homeostasis and disease. Here, we pioneered the use of Crispr/Cas9 genome editing to tag an allele of the β4 subunit of the α6β4 integrin. A tdTomato tag was inserted with a linker at the COOH-terminus of β4 in mouse mammary epithelial cells. Cells harboring this tagged allele were similar to wild-type cells with respect to β4 surface expression, association with the α6 subunit, adhesion to laminin and consequent signaling. These β4 reporter cells were transformed with YAP, which enabled us to obtain novel insight into β4 dynamics in response to a migratory stimulus (scratch wound) by livecell video microscopy. An increase in β4 expression in cells proximal to the wound edge was evident and a population of β4 expressing cells that exhibited unusually rapid migration was identified. These findings could shed insight into β4 dynamics during invasion and metastasis. Moreover, these β4 reporter cells should facilitate studies on the contribution of this integrin to mammary gland biology and cancer. [ABSTRACT FROM AUTHOR]

Cumulative evidence supports a role for neutralizing antibodies contributing to spontaneous viral clearance during acute hepatitis C virus (HCV) infection. Information on the timing and specificity of the B cell response associated with clearance is crucial to inform vaccine design. From an individual who cleared three sequential HCV infections with genotypes 1b, 1a and 3a strains, respectively, we employed peripheral B cells to isolate and characterize neutralizing human monoclonal antibodies (HMAbs) to HCV after the genotype 1 infections. The majority of isolated antibodies, designated as HMAbs 212, target conformational epitopes on the envelope glycoprotein E2 and bound broadly to genotype 1–6 E1E2 proteins. Further, some of these antibodies showed neutralization potential against cultured genotype 1–6 viruses. Competition studies with defined broadly neutralizing HCV HMAbs to epitopes in distinct clusters, designated antigenic domains B, C, D and E, revealed that the selected HMAbs compete with B, C and D HMAbs, previously isolated from subjects with chronic HCV infections. Epitope mapping studies revealed domain B and C specificity of these HMAbs 212. Sequential serum samples from the studied subject inhibited the binding of HMAbs 212 to autologous E2 and blocked a representative domain D HMAb. The specificity of this antibody response appears similar to that observed during chronic infection, suggesting that the timing and affinity maturation of the antibody response are the critical determinants in successful and repeated viral clearance. While additional studies should be performed for individuals with clearance or persistence of HCV, our results define epitope determinants for antibody E2 targeting with important implications for the development of a B cell vaccine. [ABSTRACT FROM AUTHOR]

To examine practice patterns for breast cancer patients with limited sentinel node ( SN) disease in light of the ACOSOG Z0011 results. Retrospective analysis of patients with T1-2 breast cancer and positive sentinel lymph node biopsy ( SLNB) admitted between January 2009 and December 2012. Patient demographics, tumor characteristics, and treatments were recorded. Eight hundred positive SLNBs were identified. A total of 452 (56.5%) proceeded to completion axillary lymph node dissection ( cALND). cALND rate decreased from 65.1% to 49.7% from 2009-2010 to 2011-2012. cALND was performed for micrometastasis or isolated tumor cells in 39.3% in 2009-2010 and 22.2% in 2011-2012, whereas for macrometastases the rates were 83.1% and 68.6%, respectively. cALND rates diminished for both Z0011-eligible and -ineligible patients. The ACOSOG Z0011 trial presentation and publication coincided with a reduction in cALND for breast cancer with limited nodal disease. There appears equipoise regarding management of macrometastatic SN disease. [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]

Background: Hepatitis C virus (HCV) is a rapidly evolving RNA virus that has been classified into seven genotypes. All HCV genotypes cause chronic hepatitis, which ultimately leads to liver diseases such as cirrhosis. The genotypes are unevenly distributed across the globe, with genotypes 1 and 3 being the most prevalent. Until recently, molecular epidemiological studies of HCV evolution within the host and at the population level have been limited to the analyses of partial viral genome segments, as it has been technically challenging to amplify and sequence the full-length of the 9.6 kb HCV genome. Although recent improvements have been made in full genome sequencing methodologies, these protocols are still either limited to a specific genotype or cost-inefficient. Results: In this study we describe a genotype-specific protocol for the amplification and sequencing of the near-full length genome of all six major HCV genotypes. We applied this protocol to 122 HCV positive clinical samples, and had a successful genome amplification rate of 90 %, when the viral load was greater than 15,000 IU/ml. The assay was shown to have a detection limit of 1-3 cDNA copies per reaction. The method was tested with both Illumina and PacBio single molecule, real-time (SMRT) sequencing technologies. Illumina sequencing resulted in deep coverage and allowed detection of rare variants as well as HCV co-infection with multiple genotypes. The application of the method with PacBio RS resulted in sequence reads greater than 9 kb that covered the near full-length HCV amplicon in a single read and enabled analysis of the near full-length quasispecies. Conclusions: The protocol described herein can be utilised for rapid amplification and sequencing of the near-full length HCV genome in a cost efficient manner suitable for a wide range of applications. [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]

The interaction between hepatitis C virus (HCV) and cellular immune responses during very early infection is critical for disease outcome. To date, the impact of antigen-specific cellular immune responses on the evolution of the viral population establishing infection and on potential escape has not been studied. Understanding these early host-virus dynamics is important for the development of a preventative vaccine. Three subjects who were followed longitudinally from the detection of viremia preseroconversion until disease outcome were analyzed. The evolution of transmitted/founder (T/F) viruses was undertaken using deep sequencing. CD8+ T cell responses were measured via enzyme-linked immunosorbent spot (ELISpot) assay using HLA class I-restricted T/F epitopes. T/F viruses were rapidly extinguished in all subjects associated with either viral clearance (n=1) or replacement with viral variants leading to establishment of chronic infection (n 2). CD8+ T cell responses against 11 T/F epitopes were detectable by 33 to 44 days postinfection, and 5 of these epitopes had not previously been reported. These responses declined rapidly in those who became chronically infected and were maintained in the subject who cleared infection. Higher-magnitude CD8+ T cell responses were associated with rapid development of immune escape variants at a rate of up to 0.1 per day. Rapid escape from CD8+ T cell responses has been quantified for the first time in the early phase of primaryHCVinfection. These rapid escape dynamics were associated with higher-magnitude CD8+ T cell responses. These findings raise questions regarding optimal selection of immunogens forHCVvaccine development and suggest that detailed analysis of individual epitopes may be required. [ABSTRACT FROM AUTHOR]

1. The honeybee Apis mellifera is currently in decline worldwide because of the combined impacts of Colony Collapse Disorder and the Varroa destructor mite. In order to gain a balanced perspective of the importance of both wild and managed pollination services, it is essential to compare these services directly, a priori, within a cropping landscape. This process will determine the capacity of other flower visitors to act as honeybee replacements. 2. In a highly modified New Zealand agricultural landscape, we compared the pollination services provided by managed honeybees to unmanaged pollinator taxa (including flies) within a Brassica rapa var. chinensis mass flowering crop. 3. We evaluate overall pollinator effectiveness by separating the pollination service into two components: efficiency (i.e. per visit pollen deposition) and visit rate (i.e. pollinator abundance per available flower and the number of flower visits per minute). 4. We observed 31 species attending flowers of B. rapa. In addition to A. mellifera, seven insect species visited flowers frequently. These were three other bees ( Lasioglossum sordidum, Bombus terrestris and Leioproctus sp .) and four flies ( Dilophus nigrostigma, Melanostoma fasciatum, Melangyna novae-zelandiae and Eristalis tenax). 5. Two bee species, Bombus terrestris and Leioproctus sp . and one fly, Eristalis tenax were as efficient as the honeybee and as effective (in terms of rate of flower visitation). A higher honeybee abundance, however, resulted in it being the more effective pollinator overall. 6. Synthesis and applications. Alternative land management practices that increase the population sizes of unmanaged pollinator taxa to levels resulting in visitation frequencies as high as A. mellifera, have the potential to replace services provided by the honeybee. This will require a thorough investigation of each taxon’s intrinsic biology and a change in land management practices to ensure year round refuge, feeding, nesting and other resource requirements of pollinator taxa are met. [ABSTRACT FROM AUTHOR]

Purpose: Based on our demonstration of a circadian rhythm in the human oral mucosa cell cycle, with most cells in the G1 phase in the morning and M phase at night, we hypothesized that morning radiotherapy (RT) would lead to less oral mucositis than afternoon RT. Methods and Materials: A total of 216 patients were randomized to morning (8–10 AM) vs. afternoon (4–6 PM) RT and stratified by radiation dose, smoking status, and center. Patients receiving primary or postoperative RT alone were eligible. Oral mucositis was scored using the Radiation Therapy Oncology Group (RTOG) criteria and a validated scoring system. Results: Of 205 evaluable patients, 52.9% vs. 62.4% developed RTOG Grade 3 or greater mucositis after morning vs. afternoon RT, respectively (p = 0.17). Morning RT was also associated with significantly less weight loss after 5 months (p = 0.024). In a subgroup of 111 patients treated to a dose of 66–70 Gy in 33–35 fractions, exploratory analyses revealed a significant reduction in Grade 3 or greater mucositis with morning RT (44.6% vs. 67.3%, p = 0.022) and a longer interval to the development of Grade 3 or greater mucositis (median, >7.9 vs. 5.6 weeks, p = 0.033). In 53 patients, who smoked during therapy, a significant reduction was found in Grade 3 or greater mucositis with morning RT (42.9% vs. 76%, p = 0.025). Conclusion: In this proof of principle study, morning RT was associated with significantly less weight loss after 5 months and an apparent reduction in oral mucositis in a subset of patients receiving ≥66 Gy and in patients who smoked during therapy. [Copyright &y& Elsevier]

The purpose of this paper is to stimulate debate on developments within higher education. It is concerned primarily with the hopeful working out of a new kind of professional ethic. It explores the extent to which and ways in which academic staff working within the context of higher education might be seen as professionals with a shared set of values and expectations. It argues that the changing conditions of higher education have made it extremely difficult to speak of academic workers as a unified 'profession'. Moreover, the stratification of higher education has led to increased and deepening divisions of labour, within which academic workers have become increasingly isolated, while also becoming increasingly accountable. The only way out of this impasse, it is argued, is for academics to re-define their professionalism in terms of their underlying commitments and purposes. That task of re-definition is discussed in terms of a distinction between two competing notions of academic freedom: the traditional notion of academic freedom as freedom for academics, and an emergent notion of academic freedom as freedom for others. It is with reference to that emergent notion that this article speculates upon the possibility of a new professionalism for higher education, while recognising that a new professionalism of this kind would be deeply at odds with the prevailing managerialism of higher education as manifest in its quality-control mechanisms, accountability procedures, and planned systems of professional accreditation. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to stimulate debate on developments within higher education. It is concerned primarily with the hopeful working out of a new kind of professional ethic. It explores the extent to which and ways in which academic staff working within the context of higher education might be seen as professionals with a shared set of values and expectations. It argues that the changing conditions of higher education have made it extremely difficult to speak of academic workers as a unified 'profession'. Moreover, the stratification of higher education has led to increased and deepening divisions of labour, within which academic workers have become increasingly isolated, while also becoming increasingly accountable. The only way out of this impasse, it is argued, is for academics to re-define their professionalism in terms of their underlying commitments and purposes. That task of re-definition is discussed in terms of a distinction between two competing notions of academic freedom: the traditional notion of academic freedom as freedom for academics, and an emergent notion of academic freedom as freedom for others. It is with reference to that emergent notion that this article speculates upon the possibility of a new professionalism for higher education, while recognising that a new professionalism of this kind would be deeply at odds with the prevailing managerialism of higher education as manifest in its quality-control mechanisms, accountability procedures, and planned systems of professional accreditation. [ABSTRACT FROM AUTHOR]

Reprints a paragraph from a call for papers issued by the journal 'Teaching in Higher Education.' Search for papers in which the authors would address some aspect of their practice as teachers in higher education.