Analysis of the Bronze Age Heslington Brain by FTIR Imaging and Hierarchical Cluster Analysis

Analysis of the Bronze Age Heslington Brain by FTIR Imaging and Hierarchical Cluster AnalysisFTIR has over the past years proven to be a technique capable of discriminating between different tissue structures. Herein we report the preliminary analysis of Heslington brain tissue by FTIR imaging and Hierarchical Cluster Analysis (HCA). Analysis of the average spectra for the different clusters showed bands that are characteristic of proteins and lipids, indicating that these were still present in the tissue. Comparison with spectra obtained by Kraft et al.1 for normal brain tissue that had been snap frozen in liquid nitrogen immediately after post-mortem resection, showed the absence of the C=O lipid stretching band in the spectra from the Heslington brain and a broad spread of absorbance in the region between 1000 to 1350cm-1, which might be due to the degradation of the tissue.Four different areas of tissue were identified from the Hierarchical Cluster Analysis. However, analysis of the average spectra for those areas showed that there was little difference between three of them. The fourth area, related to three small areas at the edge of the tissue analysed, varied significantly from the other three areas, in that it had lower absorbance in the amide bands and in the 1140 to 1430 cm-1 region and it exhibited much higher absorbance in the 1000 to 1140 cm-1 region with maxima at 1120 and 1038 cm-1. Absorption bands around 1120 cm-1 have been associated with RNA2 and bands around 1044 cm-1 have been attributed to the phosphate monoester asymmetric P-O stretch.3 The region between 1000 and 1140 cm-1 is also associated with glycogen and collagen. However, it is not possible to say which type of molecules these observed bands can be attributed to without further analysis. 1 C. Krafft, L. Shapoval, S. B. Sobottka, K. D. Geiger, G. Schackert and R. Salzer, Biochimica et Biophysica Acta - Biomembranes, 2006, 1758, 883-891.2 E. Gazi, J. Dwyer, P. Gardner, A. Ghanbari-Siahkali, A. P. Wade, J. Miyan, N. P. Lockyer, J. C. Vickerman, N. W. Clarke, J. H. Shanks, L. J. Scott, C. A. Hart and M. Brown, Journal of Pathology, 2003, 201, 99-108.3 P. S. Bromberg, K. M. Gough, M. Ogg, M. R. Del Bigio and R. Julian (1999) in Proceedings of SPIE - The International Society for Optical Engineering, Vol. 3775, pp. 118-126

Rethinking professional practice: the logic of competition and the crisis of identity in housing practice

The relationship between professionalism, education and housing practice has become increasingly strained following the introduction of austerity measures and welfare reforms across a range of countries. Focusing on the development of UK housing practice, this article considers how notions of professionalism are being reshaped within the context of welfare retrenchment and how emerging tensions have both affected the identity of housing professionals and impacted on the delivery of training and education programmes. The article analyses the changing knowledge and skills valued in contemporary housing practice and considers how the sector has responded to the challenges of austerity. The central argument is that a dominant logic of competition has culminated in a crisis of identity for the sector. Although the focus of the article is on UK housing practice, the processes identified have a wider relevance for the analysis of housing and welfare delivery in developed economies

Creating a proof-of-concept climate service to assess future renewable energy mixes in Europe: an overview of the C3S ECEM project

The EU Copernicus Climate Change Service (C3S) European Climatic Energy Mixes (ECEM) has produced, in close collaboration with prospective users, a proof-of-concept climate service, or Demonstrator, designed to enable the energy industry and policy makers assess how well different energy supply mixes in Europe will meet demand, over different time horizons (from seasonal to long-term decadal planning), focusing on the role climate has on the mixes. The concept of C3S ECEM, its methodology and some results are presented here. The first part focuses on the construction of reference data sets for climate variables based on the ERA-Interim reanalysis. Subsequently, energy variables were created by transforming the bias-adjusted climate variables using a combination of statistical and physically-based models. A comprehensive set of measured energy supply and demand data was also collected, in order to assess the robustness of the conversion to energy variables. Climate and energy data have been produced both for the historical period (1979–2016) and for future projections (from 1981 to 2100, to also include a past reference period, but focusing on the 30 year period 2035–2065). The skill of current seasonal forecast systems for climate and energy variables has also been assessed. The C3S ECEM project was designed to provide ample opportunities for stakeholders to convey their needs and expectations, and assist in the development of a suitable Demonstrator. This is the tool that collects the output produced by C3S ECEM and presents it in a user-friendly and interactive format, and it therefore constitutes the essence of the C3S ECEM proof-of-concept climate service

Satellite data for the offshore renewable energy sector: Synergies and innovation opportunities

Can satellite data be used to address challenges currently faced by the Offshore Renewable Energy (ORE) sector? What benefit can satellite observations bring to resource assessment and maintenance of ORE farms? Can satellite observations be used to assess the environmental impact of offshore renewables leading towards a more sustainable ORE sector? This review paper faces these questions presenting a holistic view of the current interactions between satellite and ORE sectors, and future needs to make this partnership grow. The aim of the work is to start the conversation between these sectors by establishing a common ground. We present offshore needs and satellite technology limitations, as well as potential opportunities and areas of growth. To better understand this, the reader is guided through the history, current developments, challenges and future of offshore wind, tidal and wave energy technologies. Then, an overview on satellite observations for ocean applications is given, covering types of instruments and how they are used to provide different metocean variables, satellite performance, and data processing and integration. Past, present and future satellite missions are also discussed. Finally, the paper focuses on innovation opportunities and the potential of synergies between the ORE and satellite sectors. Specifically, we pay attention to improvements that satellite observations could bring to standard measurement techniques: assessing uncertainty, wind, tidal and wave conditions forecast, as well as environmental monitoring from space. Satellite–enabled measurement of ocean physical processes and applications for fisheries, mammals and birds, and habitat change, are also discussed in depth

B lymphocytes contribute to indirect pathway T cell sensitisation via acquisition of extracellular vesicles

B cells have been implicated in transplant rejection via antibody‐mediated mechanisms and more recently by presenting donor‐antigens to T cells. We have shown in patients with chronic antibody‐mediated rejection that B cells control the indirect T cell alloresponses. To understand more about the role of B cells as antigen presenting cells for CD4⁺ T cell with indirect allospecificity, B cells were depleted in C57BL/6 mice, using an anti‐CD20 antibody, prior to receiving MHC‐class I‐mismatched (Kᵈ) skin. The absence of B cells at the time of transplantation prolonged skin graft survival. To study the mechanisms behind this observation, T cells with indirect allospecificity were transferred in mice receiving a Kᵈ skin transplant. T cell proliferation was markedly inhibited in the absence of recipient B cells, suggesting that B cells contribute to indirect pathway sensitisation. Furthermore, we have shown that a possible way in which B cells present alloantigens is via acquisition of MHC‐peptide complexes. Finally, we demonstrate that the addition of B cell depletion to the transfer of Tregs with indirect alloresponse further prolonged skin graft survival. This study supports an important role for B cells in indirect T cell priming and further emphasises the advantage of combination therapies in prolonging transplant survival

Implementing two-stage consent pathway in neonatal trials

Perinatal trials sometimes require rapid recruitment processes to facilitate inclusion of participants when interventions are time-critical. A two-stage consent pathway has been used in some trials and is supported by national guidance. This pathway includes seeking oral assent for participation during the time-critical period followed by informed written consent later. This approach is being used in the fluids exclusively enteral from day one (FEED1) trial where participants need to be randomised within 3 hours of birth. There is some apprehension about approaching parents for participation via the oral assent pathway. The main reasons for this are consistent with previous research: lack of a written record, lack of standardised information and unfamiliarity with the process. Here, we describe how the pathway has been implemented in the FEED1 trial and the steps the trial team have taken to support sites. We provide recommendations for future trials to consider if they are considering implementing a similar pathway. Trial registration number: ISRCTN89654042

Enteral lactoferrin supplementation for very preterm infants: a randomised placebo-controlled trial

Background Infections acquired in hospital are an important cause of morbidity and mortality in very preterm infants. Several small trials have suggested that supplementing the enteral diet of very preterm infants with lactoferrin, an antimicrobial protein processed from cow's milk, prevents infections and associated complications. The aim of this large randomised controlled trial was to collect data to enhance the validity and applicability of the evidence from previous trials to inform practice. Methods In this randomised placebo-controlled trial, we recruited very preterm infants born before 32 weeks' gestation in 37 UK hospitals and younger than 72 h at randomisation. Exclusion criteria were presence of a severe congenital anomaly, anticipated enteral fasting for longer than 14 days, or no realistic prospect of survival. Eligible infants were randomly assigned (1:1) to receive either enteral bovine lactoferrin (150 mg/kg per day; maximum 300 mg/day; lactoferrin group) or sucrose (same dose; control group) once daily until 34 weeks' postmenstrual age. Web-based randomisation minimised for recruitment site, gestation (completed weeks), sex, and single versus multifetal pregnancy. Parents, caregivers, and outcome assessors were unaware of group assignment. The primary outcome was microbiologically confirmed or clinically suspected late-onset infection (occurring >72 h after birth), which was assessed in all participants for whom primary outcome data was available by calculating the relative risk ratio with 95% CI between the two groups. The trial is registered with the International Standard Randomised Controlled Trial Number 88261002. Findings We recruited 2203 participants between May 7, 2014, and Sept 28, 2017, of whom 1099 were assigned to the lactoferrin group and 1104 to the control group. Four infants had consent withdrawn or unconfirmed, leaving 1098 infants in the lactoferrin group and 1101 in the sucrose group. Primary outcome data for 2182 infants (1093 [99·5%] of 1098 in the lactoferrin group and 1089 [99·0] of 1101 in the control group) were available for inclusion in the modified intention-to-treat analyses. 316 (29%) of 1093 infants in the intervention group acquired a late-onset infection versus 334 (31%) of 1089 in the control group. The risk ratio adjusted for minimisation factors was 0·95 (95% CI 0·86–1·04; p=0·233). During the trial there were 16 serious adverse events for infants in the lactoferrin group and 10 for infants in the control group. Two events in the lactoferrin group (one case of blood in stool and one death after intestinal perforation) were assessed as being possibly related to the trial intervention. Interpretation Enteral supplementation with bovine lactoferrin does not reduce the risk of late-onset infection in very preterm infants. These data do not support its routine use to prevent late-onset infection and associated morbidity or mortality in very preterm infants. Funding UK National Institute for Health Research Health Technology Assessment programme (10/57/49)

Enteral lactoferrin supplementation for very preterm infants: a randomised placebo-controlled trial

Background Infections acquired in hospital are an important cause of morbidity and mortality in very preterm infants. Several small trials have suggested that supplementing the enteral diet of very preterm infants with lactoferrin, an antimicrobial protein processed from cow's milk, prevents infections and associated complications. The aim of this large randomised controlled trial was to collect data to enhance the validity and applicability of the evidence from previous trials to inform practice. Methods In this randomised placebo-controlled trial, we recruited very preterm infants born before 32 weeks' gestation in 37 UK hospitals and younger than 72 h at randomisation. Exclusion criteria were presence of a severe congenital anomaly, anticipated enteral fasting for longer than 14 days, or no realistic prospect of survival. Eligible infants were randomly assigned (1:1) to receive either enteral bovine lactoferrin (150 mg/kg per day; maximum 300 mg/day; lactoferrin group) or sucrose (same dose; control group) once daily until 34 weeks' postmenstrual age. Web-based randomisation minimised for recruitment site, gestation (completed weeks), sex, and single versus multifetal pregnancy. Parents, caregivers, and outcome assessors were unaware of group assignment. The primary outcome was microbiologically confirmed or clinically suspected late-onset infection (occurring >72 h after birth), which was assessed in all participants for whom primary outcome data was available by calculating the relative risk ratio with 95% CI between the two groups. The trial is registered with the International Standard Randomised Controlled Trial Number 88261002. Findings We recruited 2203 participants between May 7, 2014, and Sept 28, 2017, of whom 1099 were assigned to the lactoferrin group and 1104 to the control group. Four infants had consent withdrawn or unconfirmed, leaving 1098 infants in the lactoferrin group and 1101 in the sucrose group. Primary outcome data for 2182 infants (1093 [99·5%] of 1098 in the lactoferrin group and 1089 [99·0] of 1101 in the control group) were available for inclusion in the modified intention-to-treat analyses. 316 (29%) of 1093 infants in the intervention group acquired a late-onset infection versus 334 (31%) of 1089 in the control group. The risk ratio adjusted for minimisation factors was 0·95 (95% CI 0·86–1·04; p=0·233). During the trial there were 16 serious adverse events for infants in the lactoferrin group and 10 for infants in the control group. Two events in the lactoferrin group (one case of blood in stool and one death after intestinal perforation) were assessed as being possibly related to the trial intervention. Interpretation Enteral supplementation with bovine lactoferrin does not reduce the risk of late-onset infection in very preterm infants. These data do not support its routine use to prevent late-onset infection and associated morbidity or mortality in very preterm infants. Funding UK National Institute for Health Research Health Technology Assessment programme (10/57/49)

Ursodeoxycholic acid to reduce adverse perinatal outcomes for intrahepatic cholestasis of pregnancy: the PITCHES RCT

Background: Intrahepatic cholestasis of pregnancy, characterised by maternal pruritus and raised serum bile acid concentrations, is associated with increased rates of stillbirth, preterm birth and neonatal unit admission. Ursodeoxycholic acid is widely used as a treatment, but without an adequate evidence base. / Objective: We aimed to evaluate whether or not ursodeoxycholic acid reduces adverse perinatal outcomes in affected women. / Design: Multicentre, masked, randomised, placebo-controlled, two-arm, parallel-group trial. / Setting: Thirty-three UK maternity units. / Participants: Women with intrahepatic cholestasis of pregnancy aged ≥ 18 years, between 20+0 and 40+6 weeks’ gestation with a singleton or twin pregnancy and no known lethal fetal anomaly. / Interventions: Women were randomly assigned (1 : 1 allocation ratio) to take ursodeoxycholic acid tablets or matched placebo tablets, at an equivalent dose of 1000 mg daily, titrated as needed. / Main outcome measures: The primary outcome was a composite of perinatal death (in utero fetal death after randomisation or known neonatal death up to 7 days) or preterm delivery (< 37 weeks’ gestation) or neonatal unit admission for at least 4 hours (from birth until hospital discharge). Each infant was counted once within this composite. Analyses were by intention to treat. / Results: Between 23 December 2015 and 7 August 2018, 605 women were randomised, with 305 women allocated to the ursodeoxycholic acid arm and 300 women to the placebo arm. There was no evidence of a significant difference in the incidence of the primary outcome between the groups: 23.0% (74 out of 322 infants) in the ursodeoxycholic acid group compared with 26.7% (85 out of 318 infants) in the placebo group; adjusted risk ratio 0.85 (95% confidence interval 0.62 to 1.15). There was no evidence of a significant difference in total costs (maternal, infant and the cost of ursodeoxycholic acid) between the two trial groups. There were two serious adverse events in the ursodeoxycholic acid group and six in the placebo group. / Limitations: Limitations include a primary outcome event rate in the control group that was lower than that estimated for the sample size calculation, but the lack of evidence of effect in all analyses suggests that it is unlikely that the trial had insufficient power. / Conclusions: In this clinical trial of ursodeoxycholic acid in women with intrahepatic cholestasis of pregnancy, there is no evidence that it is effective in reducing a composite of adverse perinatal outcomes. / Future work: Future research should aim to elucidate the aetiology and pathophysiology of adverse perinatal outcomes, particularly stillbirth, in women with intrahepatic cholestasis of pregnancy to assist the development of an effective preventative treatment. Further exploratory analyses may identify groups of women who might respond to ursodeoxycholic acid treatment. / Trial registration: Current Controlled Trials ISRCTN91918806. / Funding: This project was funded by the Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 7, No. 9. See the NIHR Journals Library website for further project information