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Now that the global eradication of wild poliovirus is almost within sight, planning for the post-certification era is becoming a priority issue. It is agreed that a stockpile of appropriate polio vaccines will need to be established, and a surveillance and response capacity will need to be maintained, in order to protect the world against any possible future outbreaks attributable either to the persistence of wild poliovirus or vaccine-derived polioviruses (VDPVs) or to the unintentional or intentional release of poliovirus from a laboratory or vaccine store. Although it has been suggested that the stockpile should consist of monovalent oral poliovirus vaccine (mOPV), many questions remain concerning its nature, financing, management, and use - in particular, because of uncertainties over future national vaccination policies, and over the availability of different vaccines, after the certification of wild poliovirus eradication. There are further uncertainties concerning the possible role and efficacy of inactivated poliovirus vaccine (IPV) used either routinely or in outbreak control in low-hygiene settings, the potential for rapid geographical spread of polioviruses should an outbreak occur after certification, and the risks inherent in introducing additional oral polio vaccine (OPV) viruses into populations in which the vaccine coverage and prevalence of immunity have declined, and which may thus favour the spread of VDPVs. Given these important gaps in knowledge, no country should discontinue polio vaccination until a coordinated policy for the post-certification era has been developed and the recommended measures have been put in place.

OBJECTIVE: To estimate the impact of cotrimoxazole prophylaxis on the survival of human immunodeficiency virus (HIV)-positive tuberculosis (TB) patients. METHODS: A cohort study with a historical comparison group was conducted. End-of-treatment outcomes and 18-month survival were compared between TB patients registered in 1999 and patients registered in 2000 in Karonga District, Malawi. Case ascertainment, treatment and outpatient follow-up were identical in the two years except that in 2000 cotrimoxazole prophylaxis was offered to HIV-positive patients in addition to routine care. The prophylaxis was provided from the time a patient was identified as HIV-positive until 12 months after registration. Analyses were carried out on an intention-to-treat basis for all TB patients, and also separately by HIV status, TB type and certainty of diagnosis. FINDINGS: 355 and 362 TB patients were registered in 1999 and 2000, respectively; 70% were HIV-positive. The overall case fatality rate fell from 37% to 29%, i.e. for every 12.5 TB patients treated, one death was averted. Case fatality rates were unchanged between the two years in HIV-negative patients, but fell in HIV-positive patients from 43% to 24%. The improved survival became apparent after the first 2 months and was maintained beyond the end of treatment. The improvement was most marked in patients with smear-positive TB and others with confirmed TB diagnoses. CONCLUSION: Survival of HIV-positive TB patients improved dramatically with the addition of cotrimoxazole prophylaxis to the treatment regimen. The improvement can be attributed to cotrimoxazole because other factors were unchanged and the survival of HIV-negative patients was not improved. Cotrimoxazole prophylaxis should therefore be added to the routine care of HIV-positive TB patients.

Abstract Background The addition of Rituximab (R) to standard chemotherapy (C) has been reported to improve the end of treatment outcome in patients affected by CD-20 positive malignant lymphomas (CD20+ ML). Nevertheless, given the profound and prolonged immunosuppression produced by R there are concerns that severe infections may arise. A systematic review and meta-analysis were performed to determine whether or not the addition of R to C may increase the risk of severe infections in adults undergoing induction therapy for CD20+ ML. Methods Only randomised controlled trials comparing R-C to C standard alone in adult patients with CD20+ ML were included. Meta-analysis was performed on overall incidence of severe infection, risk of dying as the consequence of infection, risk of febrile neutropenia, risk of severe leucopenia, risk of severe granulocytopenia and overall response assuming a fixed effect model. Heterogeneity was investigated, if present and I2 >20%, according to several predefined baseline characteristics of the study populations. Results Several relevant results have emerged. First, the addition of R to standard C does not increase the overall risk of severe infections (RR = 1.00; 95% CI 0.87 to 1.14) nor does it increase the risk of dying as a consequence of infection (RR = 1.60; 95% CI 0.68 to 3.75). Second, we confirmed that the addition of R to standard C increases the proportion of overall response (RR = 1.12; 95% CI 1.09 to 1.15), but it also increases the risk of severe leucopenia (RR = 1.24; 95% CI 1.12 to 1.37) and granulocytopenia (RR = 1.07; 95% CI 1.02 to 1.12). Conclusions R-C is superior to standard C in terms of overall response and it does not increase the overall incidence of severe infection. However, data on special groups of patients (for example, HIV positive subjects and HBV carriers) are lacking. In our opinion more studies are needed to explore the potential effect of R on silent and chronic viral infections.

Abstract Background Routine ART programme statistics generally only provide information about individuals who start treatment. We aimed to investigate the outcome of those who are eligible but do not start ART in the Malawi programme, factors associated with this dropout, and reasons for not starting treatment, in a prospective cohort study. Methods Individuals having a first screening visit at the ART clinic at Karonga District Hospital, northern Malawi, between September 2005 and July 2006 were interviewed. Study follow-up to identify treatment outcomes was conducted at the clinic and in the community. Logistic regression models were used to identify factors associated with dropout before ART initiation among participants identified as clinically eligible for ART. Results 88 participants eligible for ART at their first screening visit (out of 633, 13.9%) defaulted before starting ART. Participants with less education, difficulties in dressing, a more delayed ART initiation appointment, and mid-upper arm circumference (MUAC) < 22 cm were significantly less likely to have visited the clinic subsequently. Thirty-five (58%) of the 60 participants who defaulted and were tracked at home had died, 21 before their ART initiation appointment. Conclusions MUAC and reported difficulties in dressing may provide useful screening indicators to identify sicker ART-eligible individuals at high risk of dropping out of the programme who might benefit from being brought back quickly or admitted to hospital for observation. Individuals with less education may need adapted health information at screening. Deaths of ART-eligible individuals occurring prior to ART initiation are not included in routine programme statistics. Considering all those who are eligible for ART as a denominator for programme indicators would help to highlight this vulnerable group, in order to identify new opportunities for further improving ART programmes.

Abstract Background Differences in degree of environmental exposure to antigens in early life have been hypothesized to lead to differences in immune status in individuals from different populations, which may have implications for immune responses in later years. Methods Venous blood from HIV-negative adolescents and blood from the umbilical cords of babies, born to HIV-negative women, post-delivery was collected and analysed using flow cytometry. T cell phenotype was determined from peripheral blood lymphocytes and cytomegalovirus (CMV) seropositivity was assessed by ELISA in adolescents. Results HIV-negative Malawian adolescents were shown to have a lower percentage of naïve T cells (CD45RO-CD62Lhi CD11alo), a higher proportion of memory T cells and a higher percentage of CD28- memory (CD28-CD45RO+) T cells compared to age-matched UK adolescents. Malawian adolescents also had a lower percentage of central memory (CD45RA-CCR7+) T cells and a higher percentage of stable memory (CD45RA+CCR7-) T cells than UK adolescents. All of the adolescents tested in Malawi were seropositive for CMV (59/59), compared to 21/58 (36%) of UK adolescents. CMV seropositivity in the UK was associated with a reduced percentage of naïve T cells and an increased percentage of CD28- memory T cells in the periphery. No differences in the proportions of naïve and memory T cell populations were observed in cord blood samples from the two sites. Conclusion It is likely that these differences between Malawian and UK adolescents reflect a greater natural exposure to various infections, including CMV, in the African environment and may imply differences in the ability of these populations to induce and maintain immunological memory to vaccines and natural infections.

Abstract Background Although BCG vaccination is recommended in most countries of the world, little is known of the persistence of BCG-induced immune responses. As novel TB vaccines may be given to boost the immunity induced by neonatal BCG vaccination, evidence concerning the persistence of the BCG vaccine-induced response would help inform decisions about when such boosting would be most effective. Methods A randomised control study of UK adolescents was carried out to investigate persistence of BCG immune responses. Adolescents were tested for interferon-gamma (IFN-γ) response to Mycobacterium tuberculosis purified protein derivative (M.tb PPD) in a whole blood assay before, 3 months, 12 months (n = 148) and 3 years (n = 19) after receiving teenage BCG vaccination or 14 years after receiving infant BCG vaccination (n = 16). Results A gradual reduction in magnitude of response was evident from 3 months to 1 year and from 1 year to 3 years following teenage vaccination, but responses 3 years after vaccination were still on average 6 times higher than before vaccination among vaccinees. Some individuals (11/86; 13%) failed to make a detectable antigen-specific response three months after vaccination, or lost the response after 1 (11/86; 13%) or 3 (3/19; 16%) years. IFN-γ response to Ag85 was measured in a subgroup of adolescents and appeared to be better maintained with no decline from 3 to 12 months. A smaller group of adolescents were tested 14 years after receiving infant BCG vaccination and 13/16 (81%) made a detectable IFN-γ response to M.tb PPD 14 years after infant vaccination as compared to 6/16 (38%) matched unvaccinated controls (p = 0.012); teenagers vaccinated in infancy were 19 times more likely to make an IFN-γ response of > 500 pg/ml than unvaccinated teenagers. Conclusion BCG vaccination in infancy and adolescence induces immunological memory to mycobacterial antigens that is still present and measurable for at least 14 years in the majority of vaccinees, although the magnitude of the peripheral blood response wanes from 3 months to 12 months and from 12 months to 3 years post vaccination. The data presented here suggest that because of such waning in the response there may be scope for boosting anti-tuberculous immunity in BCG vaccinated children anytime from 3 months post-vaccination. This supports the prime boost strategies being employed for some new TB vaccines currently under development.

Social distancing policies have been implemented around the world to reduce the spread of coronavirus disease 2019 (COVID-19). These measures have included temporary restrictions on mass gatherings and the closure of public facilities, limiting the pursuit of leisure activities such as travel while allowing more time for at-home pursuits, including creative activities such as gardening and painting. Previous research has demonstrated the benefits of physical activity for psychological well-being during COVID-19, but less attention has been given to the potential benefits of creative pursuits, such as arts and music. The present study investigated changes in the pursuit of creative, non-creative, and physical leisure activities and the relationship between engaging in leisure, the motivations for and barriers to pursuing these activities, and psychological well-being during COVID-19. A total of 3,827 participants from 74 countries completed an online leisure activities questionnaire and the World Health Organization Five Well-Being Index. Logistic regression indicated that gender, age, social distancing adherence, and employment status significantly predicted leisure engagement during COVID-19. Compared to sports and outdoor pursuits, participation in creative activities was generally more likely to increase during this period, while participation in non-creative activities was less likely to increase. Multiple linear regression indicated that maintaining or increasing time on leisure activities significantly predicted well-being during COVID-19, with increased time spent on home crafts and artisanship, fine arts, musical and performing arts engagement, sports and outdoor pursuits, niche and IT interests, and language activities each predicting higher well-being outcomes. Motivations such as seeking creative expression and mental stimulation, keeping fit, and maintaining social connections also predicted higher well-being. These findings suggest that participation in both physical and creative leisure activities may offer protective benefits for well-being during COVID-19, and that strategies to promote engagement in creative activities should also be considered in future guidance for mental health during periods of lockdown or isolation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Morse, Fine and Friedlander.)

A new protocol for eliciting insight ("Aha!"/Eureka) moments is proposed, involving the solving of British-style cryptic crosswords. The mechanics of cryptic crossword clues are briefly explained, and the process is set into the insight literature, with parallels being drawn between several different types of cryptic crossword clues and other insight-triggering problems such as magic, jokes, anagrams, rebus, and remote association puzzles (RAT), as well as "classic" thematic or spatial challenges. We have evidence from a previous survey of cryptic crossword solvers that the "Aha!" moment is the most important driver of continued participation in this hobby, suggesting that the positive emotional "payback" has an energizing effect on a participant's motivation to continue solving. Given the success with which a good quality cryptic crossword elicits "Aha!" moments, cryptics should prove highly valuable in exploring insight under lab conditions. We argue that the crossword paradigm overcomes many of the issues which beset other insight problems: for example, solution rates of cryptic crossword clues are high; new material can easily be commissioned, leading to a limitless pool of test items; and each puzzle contains clues resembling a wide variety of insight problem types, permitting a comparison of heterogeneous solving mechanisms within the same medium. Uniquely among insight problems, considerations of expertise also come into play, allowing us to explore how crossword solving experts handle the deliberate misdirection of the cryptic clue more effectively than non-expert, but equally experienced, peers. Many have debated whether there is such a thing as an "insight problem" per se : typically, problems can be solved with or without insight, depending on the context. We argue that the same is true for cryptic crosswords, and that the key to the successful triggering of insight may lie in both the difficulty of the challenge and the degree to which misdirection has been used. Future research is outlined which explores the specific mechanisms of clue difficulty. This opens the way to an exploration of potential links between solving constraints and the experiencing of the "Aha!" moment, which may shed light on the cognitive processes involved in insight solution.

Study Design: Qualitative, semi-structured interviews., Objectives: Neuropathic pain (NP) can be psychologically and physically debilitating, and is present in approximately half of the spinal cord injured (SCI) population. However, under half of those with NP are adherent to pain medication. Understanding the impact of NP during rehabilitation is required to reduce long-term impact and to promote adherence to medication and psychoeducation recommendations., Setting: United Kingdom., Methods: Five males and three females with SCI and chronic NP, resident in rehabilitation wards at a specialist SCI center in the United Kingdom, took part. Semi-structured interviews were conducted with participants less than 15 months post-SCI (mean = 8.4 months). Verbatim transcripts were subject to interpretative phenomenological analysis (IPA)., Results: Three super-ordinate themes were identified, mediating pain and adherence: (1) the dichotomy of safety perceptions; (2) adherence despite adversity; and (3) fighting the future. Analyses suggest that experience of the rehabilitation setting and responsiveness of care shapes early distress. Attitudes to medication and psychosocial adjustment are relevant to developing expectations about pain management., Conclusions: Enhancing self-efficacy, feelings of safety in hospital, and encouraging the adoption of adaptive coping strategies may enhance psychosocial and pain-related outcomes, and improve adherence to medication. Encouraging adaptive responses to, and interpretation of, pain, through the use of interventions such as coping effectiveness training, targeted cognitive behavioral pain management, and acceptance-based interventions such as mindfulness, is recommended in order to reduce long-term reliance on medication., Competing Interests: Compliance with ethical standardsThe authors declare that they have no competing interests.

Objectives: Metaphorical expressions of persistent pain play an influential role in the modulation of pain. This may be particularly distressing for those with physical disabilities such as spinal cord injury (SCI). Neuropathic pain (NP) after SCI is often described using metaphorical expressions such as burning and electricity. This study explored the use of metaphors by those with NP after SCI., Design: A qualitative, semi-structured interview design was employed., Methods: Data were analysed using content analysis (CA) and interpretative phenomenological analysis to explore prevalence of metaphor use and its meaning. Sixteen individuals aged between 23 and 82 years, with chronic NP (persisting for 3 months or longer), arising from SCI were interviewed in their homes or on hospital wards (M = 10, F = 6). Interviews lasted between 40 and 120 min., Results: The results capture a range of metaphorical expressions embedded in participants' accounts. Three themes emerged: (1) pain as a personal attack, (2) the desire to be understood, and (3) conveying distress without adequate terminology. CA revealed that younger age, female gender, and outpatient status were associated with increased metaphor use., Conclusions: This study highlights the power of metaphor in eliciting understanding of NP after SCI from others, whilst demonstrating the challenge of communicating NP. Cognitive treatment that incorporates image-based techniques with acceptance and mindfulness-based therapies may encourage adaptive responses to, and interpretation of, pain. This may subsequently reduce pain-related distress and catastrophizing. Statement of contribution What is already known on this subject? Neuropathic pain is often described with metaphorical language such as burning and crushing. For those with physical limitations, metaphor use may induce or exacerbate psychological distress. However, for those with spinal cord injuries, metaphor use has received little attention. What does this study add? Metaphor use is common in those with spinal cord injury, with differences across gender and age. Core metaphors used conceptualized pain as an attacker or likened pain to heat and burning. Such language may have benefits in terms of improved understanding and increased empathy, but may be reflective of catastrophic thinking., (© 2016 The British Psychological Society.)

This paper presents a relatively unexplored area of expertise research which focuses on the solving of British-style cryptic crossword puzzles. Unlike its American "straight-definition" counterparts, which are primarily semantically-cued retrieval tasks, the British cryptic crossword is an exercise in code-cracking detection work. Solvers learn to ignore the superficial "surface reading" of the clue, which is phrased to be deliberately misleading, and look instead for a grammatical set of coded instructions which, if executed precisely, will lead to the correct (and only) answer. Sample clues are set out to illustrate the task requirements and demands. Hypothesized aptitudes for the field might include high fluid intelligence, skill at quasi-algebraic puzzles, pattern matching, visuospatial manipulation, divergent thinking and breaking frame abilities. These skills are additional to the crystallized knowledge and word-retrieval demands which are also a feature of American crossword puzzles. The authors present results from an exploratory survey intended to identify the characteristics of the cryptic crossword solving population, and outline the impact of these results on the direction of their subsequent research. Survey results were strongly supportive of a number of hypothesized skill-sets and guided the selection of appropriate test content and research paradigms which formed the basis of an extensive research program to be reported elsewhere. The paper concludes by arguing the case for a more grounded approach to expertise studies, termed the Grounded Expertise Components Approach. In this, the design and scope of the empirical program flows from a detailed and objectively-based characterization of the research population at the very onset of the program.

Singing is universal, and understanding sung words is thought to be important for many listeners' enjoyment of vocal and choral music. However, this is not a trivial task, and sung text intelligibility is probably affected by many factors. A survey of musicians was undertaken to identify the factors believed to have most impact on intelligibility, and to assess the importance of understanding sung words in familiar and unfamiliar languages. A total of 143 professional and amateur musicians, including singers, singing teachers, and regular listeners to vocal music, provided 394 statements yielding 851 references to one or more of 43 discrete factors in four categories: performer-related, listener-related, environment-related and words/music-related. The factors mentioned most frequently in each of the four categories were, respectively: diction; hearing ability; acoustic; and genre. In more than a third of references, the extent to which sung text is intelligible was attributed to the performer. Over 60% of respondents rated the ability to understand words in familiar languages as "very important," but only 17% when the text was in an unfamiliar language. Professional musicians (47% of the sample) rated the importance of understanding in both familiar and unfamiliar languages significantly higher than amateurs but listed fewer factors overall and fewer listener-related factors. The more important the respondents rated understanding, the more performer-related and environment-related factors they tended to list. There were no significant differences between the responses of those who teach singing and those who do not. Enhancing sung text intelligibility is thus perceived to be within the singer's control, at least to some extent, but there are also many factors outside their control. Empirical research is needed to explore some of these factors in greater depth, and has the potential to inform pedagogy for singers, composers, and choral directors.