• Bacteria and bioburden and healing in complex wounds: A prognostic systematic review

      Norman, Gill; orcid: 0000-0002-3972-5733; email: gill.norman@manchester.ac.uk; Shi, Chunhu; Westby, Maggie J.; orcid: 0000-0003-4273-3942; Price, Bianca L.; McBain, Andrew J.; Dumville, Jo C.; Cullum, Nicky (John Wiley & Sons, Inc., 2021-02-16)
      Abstract: The wound microbiome may play an important role in the wound healing process. We conducted the first systematic prognosis review investigating whether aspects of the wound microbiome are independent prognostic factors for the healing of complex wounds. We searched Medline, Embase, CINAHL and the Cochrane Library to February 2019. We included longitudinal studies which assessed the independent association of aspects of wound microbiome with healing of complex wounds while controlling for confounding factors. Two reviewers extracted data and assessed risk of bias and certainty of evidence using the GRADE approach. We synthesised studies narratively due to the clinical and methodological heterogeneity of included studies and sparse data. We identified 28 cohorts from 21 studies with a total of 38,604 participants, including people with diabetes and foot ulcers, open surgical wounds, venous leg ulcers and pressure ulcers. Risk of bias varied from low (2 cohorts) to high (17 cohorts); the great majority of participants were in cohorts at high risk of bias. Most evidence related to the association of baseline clinical wound infection with healing. Clinical infection at baseline may be associated with less likelihood of wound healing in foot ulcers in diabetes (HR from cohort with moderate risk of bias 0.53, 95% CI 0.33 to 0.83) or slower healing in open surgical wounds (HR 0.65, 95% CI 0.51 to 0.83); evidence in other wounds is more limited. Most other associations assessed showed no clear relationship with wound healing; evidence was limited and often sparse; and we documented gaps in the evidence. There is low certainty evidence that a diagnosis of wound infection may be prognostic of poorer healing in foot ulcers in diabetes, and some moderate certainty evidence for this in open surgical wounds. Low certainty evidence means that more research could change these findings.
    • Bad law or implementation flaws? Lessons from the implementation of the new law on epidemics during the response to the first wave of COVID-19 in Switzerland.

      Francetic, Igor; email: igor.francetic@manchester.ac.uk (2021-08-15)
      After the 2009-2010 H1N1 pandemic, Switzerland overhauled its 1970 law on epidemics. The reform aimed at improving early detection, surveillance, and preparedness for future outbreaks of infectious diseases. Notably, the law introduced stronger coordination between Federal and Cantonal authorities, better management tools and international cooperation. The new law entered into force in 2016 after a long legislative process. During the process, the law survived a referendum fuelled by concerns about vaccine safety and pharmaceutical industry interference. The law was first applied during the COVID-19 pandemic in early 2020. The epicentre of the outbreak in Europe was in Lombardy, a large Italian region adjacent to Switzerland and with strong economic ties with its southern region of Ticino. The first months of pandemic response highlighted two major weaknesses. Firstly, the mechanisms introduced by the new law did not ease the tension between Cantonal autonomy and central coordination of the pandemic response. Central and Cantonal authorities will need to put in place new rules and arrangements to avoid dangerous delayed responses to foreseeable problems related to the spread of infectious diseases. Secondly, relevant stakeholders excluded from the policymaking process (trade unions, firms, large industries) should be involved to allow the introduction of harsh restrictions when needed, both internally and in relation to cross-border workers. [Abstract copyright: Copyright © 2021. Published by Elsevier B.V.]
    • Bafilomycin A1 enhances NLRP3 inflammasome activation in human monocytes independent of lysosomal acidification

      Yu, Shi; Green, Jack; orcid: 0000-0003-1108-3422; Wellens, Rose; Lopez‐Castejon, Gloria; orcid: 0000-0002-8585-3381; Brough, David; orcid: 0000-0002-2250-2381; email: david.brough@manchester.ac.uk (2020-11-21)
      The release of interleukin (IL)‐1β from primary human monocytes in response to extracellular LPS occurs through the NACHT, LRR and PYD domains‐containing protein 3 (NLRP3) inflammasome. In primary monocytes, in response to LPS, NLRP3 inflammasome activation is characterized by an independence of K+ efflux and ASC speck formation and has been termed the ‘alternative’ pathway. Here, we report that pharmacological inhibition of V‐ATPase with bafilomycin A1 exacerbated LPS‐induced NLRP3 inflammasome activation in primary human monocytes. Inhibition of V‐ATPase in the presence of extracellular LPS led to NLRP3‐dependent, K+ efflux‐independent, ASC oligomerization and caspase‐1 activation. Although V‐ATPases are required for lysosomal acidification, we found that acidic lysosomal pH and protease activity were dispensable for this altered response, suggesting that V‐ATPase inhibition triggered alternative signalling events. Therefore, V‐ATPases may serve additional roles during NLRP3 inflammasome activation in primary human monocytes.
    • Balancing exploration and exploitation in public management: Proposal for an organizational model

      Palmi, Pamela; Corallo, Angelo; Prete, M. Irene; orcid: 0000-0001-9360-0475; harris, Phil (Wiley, 2020-08-05)
    • Balancing exploration and exploitation in public management: Proposal for an organizational model

      Palmi, Pamela; Corallo, Angelo; Prete, M. Irene; orcid: 0000-0001-9360-0475; Harris, Phil (Wiley, 2020-08-05)
    • ‘Banks 1 – Portugal 0’? Financial player entanglements in the Eurozone crisis

      Stadheim, Victoria B-G; orcid: 0000-0001-5801-0146; email: victoria.stadheim@winchester.ac.uk (SAGE Publications, 2020-11-01)
      The euro has been at the heart of the debate about the crisis in the Eurozone. For some, it represents a fixed exchange rate regime, which hampered peripheral countries’ competitiveness, and for others, the European Monetary Union has a ‘flawed institutional design’ and an insufficient degree of integration that engendered the crisis. The present article analyses monetary integration from a materialist perspective. It draws attention to political agency, power and crisis management. The article focuses on the case of Portugal and poses the question of how the country's authorities were compelled to request a rescue package from the International Monetary Fund, the European Central Bank and the European Commission in 2011. It shows that this decision was triggered by the political agency of a series of players within the world of finance, most notably Portugal’s domestic banks, the independent Bank of Portugal and the European Central Bank. Reflecting their material interconnection through the European monetary system, their agency was highly coordinated. The strategies for crisis management that came to deepen the recession were not the result of insufficient European integration – they rather reflected Portugal’s form of integration within the European Monetary Union at the specific moment of crisis.
    • Baseline Behavioral Data and Behavioral Correlates of Disturbance for the Lake Oku Clawed Frog ( Xenopus longipes )

      Dias, Jemma E.; email: jemmaedias@gmail.com; Ellis, Charlotte; email: charlotte.ellis@zsl.org; Smith, Tessa E.; email: tessa.smith@chester.ac.uk; Hosie, Charlotte A.; orcid: 0000-0002-3869-2108; email: l.hosie@chester.ac.uk; Tapley, Benjamin; email: ben.tapley@zsl.org; Michaels, Christopher J.; orcid: 0000-0002-4733-8397; email: christopher.michaels@zsl.org (MDPI, 2022-04-19)
      Animal behavior and welfare science can form the basis of zoo animal management. However, even basic behavioral data are lacking for the majority of amphibian species, and species-specific research is required to inform management. Our goal was to develop the first ethogram for the critically endangered frog Xenopus longipes through observation of a captive population of 24 frogs. The ethogram was applied to produce a diurnal activity budget and to measure the behavioral impact of a routine health check where frogs were restrained. In the activity budget, frogs spent the vast majority of time swimming, resting in small amounts of time devoted to feeding, foraging, breathing, and (in males) amplexus. Using linear mixed models, we found no effect of time of day or sex on baseline behavior, other than for breathing, which had a greater duration in females. Linear mixed models indicated significant effects of the health check on duration of swimming, resting, foraging, feeding, and breathing behaviors for all frogs. This indicates a welfare trade-off associated with veterinary monitoring and highlights the importance of non-invasive monitoring where possible, as well as providing candidates for behavioral monitoring of acute stress. This investigation has provided the first behavioral data for this species which can be applied to future research regarding husbandry and management practices.
    • Basil Lythgoe. 18 August 1913—18 April 2009

      Jones, J. C. (The Royal Society, 2021-03-03)
      Basil Lythgoe was distinguished as an organic chemist. He began his career at the University of Manchester, where he had studied for his undergraduate and PhD degrees, before moving to University of Cambridge. During this period he collaborated with Alexander Todd on the structural elucidation and total synthesis of the natural nucleosides, and was also noted for his investigation of the structure of the natural substance macrozamin. In 1953 he moved to the chair of organic chemistry at the University of Leeds, running a research group from which several graduate students went on to academic careers of the highest distinction. At Leeds he worked on the structure of the alkaloid taxine 1 and calciferol, among other natural substances. Lythgoe's work was characterized by a combination of insight and high experimental skill.
    • Basil Lythgoe. 18 August 1913—18 April 2009

      Jones, J. C. (The Royal Society, 2021-03-03)
      Basil Lythgoe was distinguished as an organic chemist. He began his career at the University of Manchester, where he had studied for his undergraduate and PhD degrees, before moving to University of Cambridge. During this period he collaborated with Alexander Todd on the structural elucidation and total synthesis of the natural nucleosides, and was also noted for his investigation of the structure of the natural substance macrozamin. In 1953 he moved to the chair of organic chemistry at the University of Leeds, running a research group from which several graduate students went on to academic careers of the highest distinction. At Leeds he worked on the structure of the alkaloid taxine 1 and calciferol, among other natural substances. Lythgoe's work was characterized by a combination of insight and high experimental skill.
    • Bayesian Reference Analysis for the Generalized Normal Linear Regression Model

      Tomazella, Vera Lucia Damasceno; orcid: 0000-0002-6780-2089; email: vera@ufscar.br; Jesus, Sandra Rêgo; email: sandrarj@ufba.br; Gazon, Amanda Buosi; orcid: 0000-0001-8140-5496; email: amandagazon@alumni.usp.br; Louzada, Francisco; orcid: 0000-0001-7815-9554; email: louzada@icmc.usp.br; Nadarajah, Saralees; email: saralees.nadarajah@manchester.ac.uk; Nascimento, Diego Carvalho; orcid: 0000-0002-3406-4518; email: diego.nascimento@uda.cl; Rodrigues, Francisco Aparecido; email: francisco@icmc.usp.br; Ramos, Pedro Luiz; orcid: 0000-0002-5387-2457; email: pedrolramos@usp.br (MDPI, 2021-05-12)
      This article proposes the use of the Bayesian reference analysis to estimate the parameters of the generalized normal linear regression model. It is shown that the reference prior led to a proper posterior distribution, while the Jeffreys prior returned an improper one. The inferential purposes were obtained via Markov Chain Monte Carlo (MCMC). Furthermore, diagnostic techniques based on the Kullback–Leibler divergence were used. The proposed method was illustrated using artificial data and real data on the height and diameter of Eucalyptus clones from Brazil.
    • Bearing Bad News: The Impact of Delivering and Receiving News of Sudden Bereavement

      Sweeney, Susan; orcid: 0000-0003-0165-3065 (SAGE Publications, 2021-12-06)
      First responders and care professionals are often required to convey the deeply distressing news to relatives of the sudden death of a loved one. Witnessing the extreme anguish and grief of those receiving such news can have a detrimental effect on the bearers, leading to peritraumatic distress and feelings of inadequacy and burnout. For the recipients of such news, how it is delivered will impact on their understanding, acceptance, and processing of the sudden loss and may be a precursor for complicated grief or mental health issues such as anxiety or depression. Through writing about her own experience, the author aims to illustrate how interaction with professionals supported or impacted adversely on her grief and is intended to maintain professionals’ awareness of the impact of their delivery on recipients. Ancillary professionals also have an important role in how they interact with the bereaved and in ameliorating their deep distress.
    • Bedtime Oral Hygiene Behaviours, Dietary Habits and Children’s Dental Health

      Kitsaras, George; orcid: 0000-0002-1631-1730; email: georgios.kitsaras@manchester.ac.uk; Goodwin, Michaela; orcid: 0000-0002-0375-3118; email: michaela.goodwin@manchester.ac.uk; Kelly, Michael P.; orcid: 0000-0002-2029-5841; email: mk744@medschl.cam.ac.uk; Pretty, Iain A.; email: iain.a.pretty@manchester.ac.uk (MDPI, 2021-05-19)
      Background: Oral hygiene behaviours as well as dietary habits before bed can affect children’s dental health resulting in higher prevalence of dental disease. Dental disease can affect children’s health, development and even school performance. If left untreated, dental disease can progress and it can lead to extractions under general anaesthetic causing further distress for children and families. Consistent and appropriate oral hygiene behaviours and dietary habits can prevent dental diseases from occurring in the first place. Objective: This cross-sectional study examines the relationship between oral hygiene behaviours, dietary habits around bedtime and children’s dental health. Methods: A total of 185 parents with children between the ages of 3 and 7 years from deprived areas participated in the study. Data on bedtime routine activities were collected using an automated text-survey system. Children’s dental health status was established through examination of dental charts and dmft (decayed, missed, filled teeth) scores. Results: In total, 52.4% of parents reported that their children’s teeth were brushed every night. The majority of children (58.9%) had dmft scores over zero. In total, 51 (46.7% of children with dmft score over 0 and 27.5% of all children) children had active decay. The mean dmft score for those experiencing decay was 2.96 (SD = 2.22) with an overall mean dmft score of 1.75 (SD = 2.24). There were significant correlations between frequency of tooth brushing, frequency of snacks/drinks before bed and dmft scores (r = −0.584, p 0.001 and r = 0.547, p = 0.001 respectively). Finally, higher brushing frequency was associated with a lower likelihood of a dmft score greater than 0 (Exp(B) = 0.9). Conclusions: Despite families implementing oral hygiene behaviours as part of their bedtime routines those behaviours varied in their consistency. Results of this study highlight the need for additional studies that consider bedtime routine-related activities and especially the combined effects of oral hygiene practices and dietary habits due to their potentially important relationship with children’s dental health.
    • Benefits and harms of Risperidone and Paliperidone for treatment of patients with schizophrenia or bipolar disorder: a meta-analysis involving individual participant data and clinical study reports

      Hodkinson, Alexander; orcid: 0000-0003-2063-0977; email: alexander.hodkinson@manchester.ac.uk; Heneghan, Carl; Mahtani, Kamal R.; Kontopantelis, Evangelos; Panagioti, Maria (BioMed Central, 2021-08-25)
      Abstract: Background: Schizophrenia and bipolar disorder are severe mental illnesses which are highly prevalent worldwide. Risperidone and Paliperidone are treatments for either illnesses, but their efficacy compared to other antipsychotics and growing reports of hormonal imbalances continue to raise concerns. As existing evidence on both antipsychotics are solely based on aggregate data, we aimed to assess the benefits and harms of Risperidone and Paliperidone in the treatment of patients with schizophrenia or bipolar disorder, using individual participant data (IPD), clinical study reports (CSRs) and publicly available sources (journal publications and trial registries). Methods: We searched MEDLINE, Central, EMBASE and PsycINFO until December 2020 for randomised placebo-controlled trials of Risperidone, Paliperidone or Paliperidone palmitate in patients with schizophrenia or bipolar disorder. We obtained IPD and CSRs from the Yale University Open Data Access project. The primary outcome Positive and Negative Syndrome Scale (PANSS) score was analysed using one-stage IPD meta-analysis. Random-effect meta-analysis of harm outcomes involved methods for coping with rare events. Effect-sizes were compared across all available data sources using the ratio of means or relative risk. We registered our review on PROSPERO, CRD42019140556. Results: Of the 35 studies, IPD meta-analysis involving 22 (63%) studies showed a significant clinical reduction in the PANSS in patients receiving Risperidone (mean difference − 5.83, 95% CI − 10.79 to − 0.87, I2 = 8.5%, n = 4 studies, 1131 participants), Paliperidone (− 6.01, 95% CI − 8.7 to − 3.32, I2 = 4.3%, n = 13, 3821) and Paliperidone palmitate (− 7.89, 95% CI − 12.1 to − 3.69, I2 = 2.9%, n = 5, 2209). CSRs reported nearly two times more adverse events (4434 vs. 2296 publication, relative difference (RD) = 1.93, 95% CI 1.86 to 2.00) and almost 8 times more serious adverse events (650 vs. 82; RD = 7.93, 95% CI 6.32 to 9.95) than the journal publications. Meta-analyses of individual harms from CSRs revealed a significant increased risk among several outcomes including extrapyramidal disorder, tardive dyskinesia and increased weight. But the ratio of relative risk between the different data sources was not significant. Three treatment-related gynecomastia events occurred, and these were considered mild to moderate in severity. Conclusion: IPD meta-analysis conclude that Risperidone and Paliperidone antipsychotics had a small beneficial effect on reducing PANSS score over 9 weeks, which is more conservative than estimates from reviews based on journal publications. CSRs also contained significantly more data on harms that were unavailable in journal publications or trial registries. Sharing of IPD and CSRs are necessary when performing meta-analysis on the efficacy and safety of antipsychotics.
    • Benefits and harms of Risperidone and Paliperidone for treatment of patients with schizophrenia or bipolar disorder: a meta-analysis involving individual participant data and clinical study reports.

      Hodkinson, Alexander; orcid: 0000-0003-2063-0977; email: alexander.hodkinson@manchester.ac.uk; Heneghan, Carl; Mahtani, Kamal R; Kontopantelis, Evangelos; Panagioti, Maria (2021-08-25)
      <h4>Background</h4>Schizophrenia and bipolar disorder are severe mental illnesses which are highly prevalent worldwide. Risperidone and Paliperidone are treatments for either illnesses, but their efficacy compared to other antipsychotics and growing reports of hormonal imbalances continue to raise concerns. As existing evidence on both antipsychotics are solely based on aggregate data, we aimed to assess the benefits and harms of Risperidone and Paliperidone in the treatment of patients with schizophrenia or bipolar disorder, using individual participant data (IPD), clinical study reports (CSRs) and publicly available sources (journal publications and trial registries).<h4>Methods</h4>We searched MEDLINE, Central, EMBASE and PsycINFO until December 2020 for randomised placebo-controlled trials of Risperidone, Paliperidone or Paliperidone palmitate in patients with schizophrenia or bipolar disorder. We obtained IPD and CSRs from the Yale University Open Data Access project. The primary outcome Positive and Negative Syndrome Scale (PANSS) score was analysed using one-stage IPD meta-analysis. Random-effect meta-analysis of harm outcomes involved methods for coping with rare events. Effect-sizes were compared across all available data sources using the ratio of means or relative risk. We registered our review on PROSPERO, CRD42019140556.<h4>Results</h4>Of the 35 studies, IPD meta-analysis involving 22 (63%) studies showed a significant clinical reduction in the PANSS in patients receiving Risperidone (mean difference - 5.83, 95% CI - 10.79 to - 0.87, I<sup>2</sup> = 8.5%, n = 4 studies, 1131 participants), Paliperidone (- 6.01, 95% CI - 8.7 to - 3.32, I<sup>2</sup> = 4.3%, n = 13, 3821) and Paliperidone palmitate (- 7.89, 95% CI - 12.1 to - 3.69, I<sup>2</sup> = 2.9%, n = 5, 2209). CSRs reported nearly two times more adverse events (4434 vs. 2296 publication, relative difference (RD) = 1.93, 95% CI 1.86 to 2.00) and almost 8 times more serious adverse events (650 vs. 82; RD = 7.93, 95% CI 6.32 to 9.95) than the journal publications. Meta-analyses of individual harms from CSRs revealed a significant increased risk among several outcomes including extrapyramidal disorder, tardive dyskinesia and increased weight. But the ratio of relative risk between the different data sources was not significant. Three treatment-related gynecomastia events occurred, and these were considered mild to moderate in severity.<h4>Conclusion</h4>IPD meta-analysis conclude that Risperidone and Paliperidone antipsychotics had a small beneficial effect on reducing PANSS score over 9 weeks, which is more conservative than estimates from reviews based on journal publications. CSRs also contained significantly more data on harms that were unavailable in journal publications or trial registries. Sharing of IPD and CSRs are necessary when performing meta-analysis on the efficacy and safety of antipsychotics.
    • Bettina Hitzer, Krebs Fühlen: Eine Emotionsgeschichte des 20. Jahrhunderts

      Timmermann, Carsten; email: carsten.timmermann@manchester.ac.uk (Brill, 2021-11-26)
    • Beyond factor H: The impact of genetic-risk variants for age-related macular degeneration on circulating factor-H-like 1 and factor-H-related protein concentrations.

      Cipriani, Valentina; email: v.cipriani@qmul.ac.uk; Tierney, Anna; Griffiths, John R; Zuber, Verena; Sergouniotis, Panagiotis I; Yates, John R W; Moore, Anthony T; Bishop, Paul N; Clark, Simon J; Unwin, Richard D; email: r.unwin@manchester.ac.uk (2021-07-12)
      Age-related macular degeneration (AMD) is a leading cause of vision loss; there is strong genetic susceptibility at the complement factor H (CFH) locus. This locus encodes a series of complement regulators: factor H (FH), a splice variant factor-H-like 1 (FHL-1), and five factor-H-related proteins (FHR-1 to FHR-5), all involved in the regulation of complement factor C3b turnover. Little is known about how AMD-associated variants at this locus might influence FHL-1 and FHR protein concentrations. We have used a bespoke targeted mass-spectrometry assay to measure the circulating concentrations of all seven complement regulators and demonstrated elevated concentrations in 352 advanced AMD-affected individuals for all FHR proteins (FHR-1, p = 2.4 × 10 ; FHR-2, p = 6.0 × 10 ; FHR-3, p = 1.5 × 10 ; FHR-4, p = 1.3 × 10 ; FHR-5, p = 1.9 × 10 ) and FHL-1 (p = 4.9 × 10 ) when these individuals were compared to 252 controls, whereas no difference was seen for FH (p = 0.94). Genome-wide association analyses in controls revealed genome-wide-significant signals at the CFH locus for all five FHR proteins, and univariate Mendelian-randomization analyses strongly supported the association of FHR-1, FHR-2, FHR-4, and FHR-5 with AMD susceptibility. These findings provide a strong biochemical explanation for how genetically driven alterations in circulating FHR proteins could be major drivers of AMD and highlight the need for research into FHR protein modulation as a viable therapeutic avenue for AMD. [Abstract copyright: Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.]
    • Beyond relational continuity.

      Burch, Patrick Bm; email: patrick.burch@manchester.ac.uk (2021-07-29)