Becaplermin gel in the treatment of pressure ulcers: a phase II randomized, double-blind, placebo-controlled study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72172/1/j.1524-475X.1999.00141.x.pd

REMCARE : pragmatic multi-centre randomised trial of reminiscence groups for people with dementia and their family carers : effectiveness and economic analysis

Background Joint reminiscence groups, involving people with dementia and family carers together, are popular, but the evidence-base is limited. This study aimed to assess the effectiveness and cost-effectiveness of joint reminiscence groups as compared to usual care. Methods This multi-centre, pragmatic randomised controlled trial had two parallel arms: intervention group and usual-care control group. A restricted dynamic method of randomisation was used, with an overall allocation ratio of 1:1, restricted to ensure viable sized intervention groups. Assessments, blind to treatment allocation, were carried out at baseline, three months and ten months (primary end-point), usually in the person's home. Participants were recruited in eight centres, mainly through NHS Memory Clinics and NHS community mental health teams. Included participants were community resident people with mild to moderate dementia (DSM-IV), who had a relative or other care-giver in regular contact, to act as informant and willing and able to participate in intervention. 71% carers were spouses. 488 people with dementia (mean age 77.5) were randomised: 268 intervention, 220 control; 350 dyads completed the study (206 intervention, 144 control). The intervention evaluated was joint reminiscence groups (with up to 12 dyads) weekly for twelve weeks; monthly maintenance sessions for further seven months. Sessions followed a published treatment manual and were held in a variety of community settings. Two trained facilitators in each centre were supported by volunteers. Primary outcome measures were self-reported quality of life for the person with dementia (QoL-AD), psychological distress for the carer (General Health Questionnaire, GHQ-28). Secondary outcome measures included: autobiographical memory and activities of daily living for the person with dementia; carer stress for the carer; mood, relationship quality and service use and costs for both. Results The intention to treat analysis (ANCOVA) identified no differences in outcome between the intervention and control conditions on primary or secondary outcomes (self-reported QoL-AD mean difference 0.07 (-1.21 to 1.35), F = 0.48, p = 0.53). Carers of people with dementia allocated to the reminiscence intervention reported a significant increase in anxiety on a General Health Questionnaire-28 sub-scale at the ten month end-point (mean difference 1.25 (0.25 to 2.26), F = 8.28, p = 0.04). Compliance analyses suggested improved autobiographical memory, quality of life and relationship quality for people with dementia attending more reminiscence sessions, however carers attending more groups showed increased care-giving stress. Economic analyses from a public sector perspective indicated that joint reminiscence groups are unlikely to be cost-effective. There were no significant adverse effects attributed to the intervention. Potential limitations of the study include less than optimal attendance at the group sessions—only 57% of participants attended at least half of the intervention sessions over the 10 month period, and a higher rate of study withdrawal in the control group. Conclusions This trial does not support the clinical effectiveness or cost-effectiveness of joint reminiscence groups. Possible beneficial effects for people with dementia who attend sessions as planned are offset by raised anxiety and stress in their carers. The reasons for these discrepant outcomes need to be explored further, and may necessitate reappraisal of the movement towards joint interventions

Report on the ISIKLE Project: Increasing and Evaluating Student Impact in Knowledge and Learning Exchange (ISIKLE)

This final report on the ISIKLE project which summarises the findings of the mixed-method evaluation of the work of ISIKLE over the two years from June 2020. The project was by funded by Research England and OfS to demonstrate and evaluate effective practices in student engagement in Knowledge Exchange activities to assess their economic and social benefits to individual students and to external partners and communities. The evaluation includes a Systematic Review of the literature on student knowledge exchange; narrative case studies of the innovations introduced on the ISIKLE sub-projects at UCL and University of Manchester; and both quantitative and qualitative evaluations of the impacts of the programmes on students and external partner

Insertion of heterometals into the NifEN-associated iron–molybdenum cofactor precursor

The cofactors of Mo-, V-, Fe-dependent nitrogenases are believed to be highly homologous in structure despite the different types of heterometals (Mo, V, and Fe) they contain. Previously, a precursor form of the FeMo cofactor (FeMoco) was captured on NifEN, a scaffold protein for FeMoco biosynthesis. This all-Fe precursor closely resembles the Fe/S core structure of the FeMoco and, therefore, could reasonably serve as a precursor for all nitrogenase cofactors. Here, we report the heterologous incorporation of V and Fe into the NifEN-associated FeMoco precursor. EPR and activity analyses indicate that V and Fe can be inserted at much reduced efficiencies compared with Mo, and incorporation of both V and Fe is enhanced in the presence of homocitrate. Further, native polyacrylamide gel electrophoresis experiments suggest that NifEN undergoes a significant conformational rearrangement upon metal insertion, which allows the subsequent NifEN–MoFe protein interactions and the transfer of the cofactor between the two proteins. The combined outcome of these in vitro studies leads to the proposal of a selective mechanism that is utilized in vivo to maintain the specificity of heterometals in nitrogenase cofactors, which is likely accomplished through the redox regulation of metal mobilization by different Fe proteins (encoded by nifH, vnfH, and anfH, respectively), as well as the differential interactions between these Fe proteins and their respective scaffold proteins (NifEN and VnfEN) in the Mo-, V-, and Fe-dependent nitrogenase systems

EXPLORE: A Prospective, Multinational, Natural History Study of Patients with Acute Hepatic Porphyria with Recurrent Attacks

Abstract Acute hepatic porphyria comprises a group of rare, genetic diseases caused by mutations in genes involved in heme biosynthesis. Patients can experience acute neurovisceral attacks, debilitating chronic symptoms, and long-term complications. There is a lack of multinational, prospective data characterizing the disease and current treatment practices in severely affected patients. EXPLORE is a prospective, multinational, natural history study characterizing disease activity and clinical management in patients with acute hepatic porphyria who experience recurrent attacks. Eligible patients had a confirmed acute hepatic porphyria diagnosis and had experienced ≥3 attacks in the prior 12 months or were receiving prophylactic treatment. A total of 112 patients were enrolled and followed for at least 6 months. In the 12 months prior to the study, patients reported a median (range) of 6 (0-52) acute attacks, with 52 (46%) patients receiving hemin prophylaxis. Chronic symptoms were reported by 73 (65%) patients, with 52 (46%) patients experiencing these daily. During the study, 98 (88%) patients experienced a total of 483 attacks, 77% of which required treatment at a healthcare facility and/or hemin administration (median [range] annualized attack rate 2.0 [0.0-37.0]). Elevated levels of hepatic δ-aminolevulinic acid synthase 1 messenger ribonucleic acid levels, δ-aminolevulinic acid, and porphobilinogen compared with the upper limit of normal in healthy individuals were observed at baseline and increased further during attacks. Patients had impaired quality of life and increased healthcare utilization. Conclusions: Patients experienced attacks often requiring treatment in a healthcare facility and/or with hemin, as well as chronic symptoms that adversely influence day-to-day functioning. In this patient group, the high disease burden and diminished quality of life highlight the need for novel therapies. This article is protected by copyright. All rights reserved.Peer reviewe

Review of interventions to encourage SMEs to make environmental improvements

Small and medium-sized enterprises (SMEs) are an important part of the world economy but they are thought to be responsible for around 60% of all carbon dioxide emissions and 70% of all pollution. SMEs often have major problems with limited resources, limited knowledge, and limited technical capabilities to deal with their own negative environmental impact. SMEs exhibit widely differing characteristics and commitment where environmental issues are concerned. Yet under these conditions they are all expected to engage in environmental improvement. Interventions that encourage environmental improvement are often polarised between regulation and legislation at one extreme and voluntary environmental agreement at the other. It is clear that a holistic mixture of interventions is necessary to achieve maximum engagement and environmental improvement by all SMEs. In this paper we categorise the different levels of environmental commitment observed in SMEs and develop a selection or &lsquo;toolkit&rsquo; of intervention strategies that might be deployed within each category of SME.<br /

Die Weltgeschichte ist das Weltgericht : Schillers Vers und die deutsche Geschichtsphilosophie des 19. Jahrhunderts

<p><b>A.</b><i>SerpinA3N</i> gene expression in the liver was significantly up-regulated in a HF diet at all times tested 3 days (<i>P</i><0.01), 1 week (<i>P</i><0.001) and 16 weeks (<i>P</i><0.01). <b>B.</b><i>Haptoglobin</i> gene expression was unchanged in HF fed mice liver after 3 days on diet but was increased after 1 week (<i>P</i><0.01) and 16 weeks (<i>P</i><0.01). <b>C.</b><i>SAA</i> gene expression was significantly higher on a HF diet after 3 days (<i>P</i><0.01) and 1 week (<i>P</i><0.001) but was not different after 16 weeks. <b>D.</b><i>ApoA-IV</i> gene expression was significantly down-regulated in the liver of HF fed mice after 3 days (<i>P</i><0.05) and 1 week (<i>P</i><0.01) on diet but was unchanged after 16 weeks on diet. <b>E.</b> In comparison <i>ApoA-IV</i> gene expression was significantly up-regulated in the ileum of HF fed mice after 3 days, 1 week and 16 weeks on diet (<i>P</i><0.05). <b>F.</b><i>SerpinA3N</i> gene expression in the liver was significantly down-regulated with time on a LF diet between 3 days and 16 weeks (<i>P</i><0.001). Units are fold expression changes between experimental groups relative to <i>B2M</i> and calculated from the ΔΔ<i>C</i>_t values (n = 6–8).</p

EXPLORE: A Prospective, Multinational, Natural History Study of Patients with Acute Hepatic Porphyria with Recurrent Attacks

BACKGROUND AND AIMS: Acute hepatic porphyria comprises a group of rare genetic diseases caused by mutations in genes involved in heme biosynthesis. Patients can experience acute neurovisceral attacks, debilitating chronic symptoms, and long-term complications. There is a lack of multinational, prospective data characterizing the disease and current treatment practices in severely affected patients. APPROACH AND RESULTS: EXPLORE is a prospective, multinational, natural history study characterizing disease activity and clinical management in patients with acute hepatic porphyria who experience recurrent attacks. Eligible patients had a confirmed acute hepatic porphyria diagnosis and had experienced ≥3 attacks in the prior 12 months or were receiving prophylactic treatment. A total of 112 patients were enrolled and followed for at least 6 months. In the 12 months before the study, patients reported a median (range) of 6 (0-52) acute attacks, with 52 (46%) patients receiving hemin prophylaxis. Chronic symptoms were reported by 73 (65%) patients, with 52 (46%) patients experiencing these daily. During the study, 98 (88%) patients experienced a total of 483 attacks, 77% of which required treatment at a health care facility and/or hemin administration (median [range] annualized attack rate 2.0 [0.0-37.0]). Elevated levels of hepatic δ-aminolevulinic acid synthase 1 messenger ribonucleic acid levels, δ-aminolevulinic acid, and porphobilinogen compared with the upper limit of normal in healthy individuals were observed at baseline and increased further during attacks. Patients had impaired quality of life and increased health care utilization. CONCLUSIONS: Patients experienced attacks often requiring treatment in a health care facility and/or with hemin, as well as chronic symptoms that adversely influenced day-to-day functioning. In this patient group, the high disease burden and diminished quality of life highlight the need for novel therapies. (Hepatology 2020;71:1546-1558)

EXPLORE: A prospective, multinational natural history study of patients with acute hepatic porphyria with recurrent attacks

BACKGROUND AND AIMS: Acute hepatic porphyria comprises a group of rare genetic diseases caused by mutations in genes involved in heme biosynthesis. Patients can experience acute neurovisceral attacks, debilitating chronic symptoms, and long-term complications. There is a lack of multinational, prospective data characterizing the disease and current treatment practices in severely affected patients. APPROACH AND RESULTS: EXPLORE is a prospective, multinational, natural history study characterizing disease activity and clinical management in patients with acute hepatic porphyria who experience recurrent attacks. Eligible patients had a confirmed acute hepatic porphyria diagnosis and had experienced ≥3 attacks in the prior 12 months or were receiving prophylactic treatment. A total of 112 patients were enrolled and followed for at least 6 months. In the 12 months before the study, patients reported a median (range) of 6 (0-52) acute attacks, with 52 (46%) patients receiving hemin prophylaxis. Chronic symptoms were reported by 73 (65%) patients, with 52 (46%) patients experiencing these daily. During the study, 98 (88%) patients experienced a total of 483 attacks, 77% of which required treatment at a health care facility and/or hemin administration (median [range] annualized attack rate 2.0 [0.0-37.0]). Elevated levels of hepatic δ-aminolevulinic acid synthase 1 messenger ribonucleic acid levels, δ-aminolevulinic acid, and porphobilinogen compared with the upper limit of normal in healthy individuals were observed at baseline and increased further during attacks. Patients had impaired quality of life and increased health care utilization. CONCLUSIONS: Patients experienced attacks often requiring treatment in a health care facility and/or with hemin, as well as chronic symptoms that adversely influenced day-to-day functioning. In this patient group, the high disease burden and diminished quality of life highlight the need for novel therapies. (Hepatology 2020;71:1546-1558)

Network analysis of sea turtle movements and connectivity: A tool for conservation prioritization

Aim: Understanding the spatial ecology of animal movements is a critical element in conserving long-lived, highly mobile marine species. Analyzing networks developed from movements of six sea turtle species reveals marine connectivity and can help prioritize conservation efforts. Location: Global. Methods: We collated telemetry data from 1235 individuals and reviewed the literature to determine our dataset's representativeness. We used the telemetry data to develop spatial networks at different scales to examine areas, connections, and their geographic arrangement. We used graph theory metrics to compare networks across regions and species and to identify the role of important areas and connections. Results: Relevant literature and citations for data used in this study had very little overlap. Network analysis showed that sampling effort influenced network structure, and the arrangement of areas and connections for most networks was complex. However, important areas and connections identified by graph theory metrics can be different than areas of high data density. For the global network, marine regions in the Mediterranean had high closeness, while links with high betweenness among marine regions in the South Atlantic were critical for maintaining connectivity. Comparisons among species-specific networks showed that functional connectivity was related to movement ecology, resulting in networks composed of different areas and links. Main conclusions: Network analysis identified the structure and functional connectivity of the sea turtles in our sample at multiple scales. These network characteristics could help guide the coordination of management strategies for wide-ranging animals throughout their geographic extent. Most networks had complex structures that can contribute to greater robustness but may be more difficult to manage changes when compared to simpler forms. Area-based conservation measures would benefit sea turtle populations when directed toward areas with high closeness dominating network function. Promoting seascape connectivity of links with high betweenness would decrease network vulnerability.Fil: Kot, Connie Y.. University of Duke; Estados UnidosFil: Åkesson, Susanne. Lund University; SueciaFil: Alfaro Shigueto, Joanna. Universidad Cientifica del Sur; Perú. University of Exeter; Reino Unido. Pro Delphinus; PerúFil: Amorocho Llanos, Diego Fernando. Research Center for Environmental Management and Development; ColombiaFil: Antonopoulou, Marina. Emirates Wildlife Society-world Wide Fund For Nature; Emiratos Arabes UnidosFil: Balazs, George H.. Noaa Fisheries Service; Estados UnidosFil: Baverstock, Warren R.. The Aquarium and Dubai Turtle Rehabilitation Project; Emiratos Arabes UnidosFil: Blumenthal, Janice M.. Cayman Islands Government; Islas CaimánFil: Broderick, Annette C.. University of Exeter; Reino UnidoFil: Bruno, Ignacio. Instituto Nacional de Investigaciones y Desarrollo Pesquero; ArgentinaFil: Canbolat, Ali Fuat. Hacettepe Üniversitesi; Turquía. Ecological Research Society; TurquíaFil: Casale, Paolo. Università degli Studi di Pisa; ItaliaFil: Cejudo, Daniel. Universidad de Las Palmas de Gran Canaria; EspañaFil: Coyne, Michael S.. Seaturtle.org; Estados UnidosFil: Curtice, Corrie. University of Duke; Estados UnidosFil: DeLand, Sarah. University of Duke; Estados UnidosFil: DiMatteo, Andrew. CheloniData; Estados UnidosFil: Dodge, Kara. New England Aquarium; Estados UnidosFil: Dunn, Daniel C.. University of Queensland; Australia. The University of Queensland; Australia. University of Duke; Estados UnidosFil: Esteban, Nicole. Swansea University; Reino UnidoFil: Formia, Angela. Wildlife Conservation Society; Estados UnidosFil: Fuentes, Mariana M. P. B.. Florida State University; Estados UnidosFil: Fujioka, Ei. University of Duke; Estados UnidosFil: Garnier, Julie. The Zoological Society of London; Reino UnidoFil: Godfrey, Matthew H.. North Carolina Wildlife Resources Commission; Estados UnidosFil: Godley, Brendan J.. University of Exeter; Reino UnidoFil: González Carman, Victoria. Instituto National de Investigación y Desarrollo Pesquero; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Harrison, Autumn Lynn. Smithsonian Institution; Estados UnidosFil: Hart, Catherine E.. Grupo Tortuguero de las Californias A.C; México. Investigacion, Capacitacion y Soluciones Ambientales y Sociales A.C; MéxicoFil: Hawkes, Lucy A.. University of Exeter; Reino UnidoFil: Hays, Graeme C.. Deakin University; AustraliaFil: Hill, Nicholas. The Zoological Society of London; Reino UnidoFil: Hochscheid, Sandra. Stazione Zoologica Anton Dohrn; ItaliaFil: Kaska, Yakup. Dekamer—Sea Turtle Rescue Center; Turquía. Pamukkale Üniversitesi; TurquíaFil: Levy, Yaniv. University Of Haifa; Israel. Israel Nature And Parks Authority; IsraelFil: Ley Quiñónez, César P.. Instituto Politécnico Nacional; MéxicoFil: Lockhart, Gwen G.. Virginia Aquarium Marine Science Foundation; Estados Unidos. Naval Facilities Engineering Command; Estados UnidosFil: López-Mendilaharsu, Milagros. Projeto TAMAR; BrasilFil: Luschi, Paolo. Università degli Studi di Pisa; ItaliaFil: Mangel, Jeffrey C.. University of Exeter; Reino Unido. Pro Delphinus; PerúFil: Margaritoulis, Dimitris. Archelon; GreciaFil: Maxwell, Sara M.. University of Washington; Estados UnidosFil: McClellan, Catherine M.. University of Duke; Estados UnidosFil: Metcalfe, Kristian. University of Exeter; Reino UnidoFil: Mingozzi, Antonio. Università Della Calabria; ItaliaFil: Moncada, Felix G.. Centro de Investigaciones Pesqueras; CubaFil: Nichols, Wallace J.. California Academy Of Sciences; Estados Unidos. Center For The Blue Economy And International Environmental Policy Program; Estados UnidosFil: Parker, Denise M.. Noaa Fisheries Service; Estados UnidosFil: Patel, Samir H.. Coonamessett Farm Foundation; Estados Unidos. Drexel University; Estados UnidosFil: Pilcher, Nicolas J.. Marine Research Foundation; MalasiaFil: Poulin, Sarah. University of Duke; Estados UnidosFil: Read, Andrew J.. Duke University Marine Laboratory; Estados UnidosFil: Rees, ALan F.. University of Exeter; Reino Unido. Archelon; GreciaFil: Robinson, David P.. The Aquarium and Dubai Turtle Rehabilitation Project; Emiratos Arabes UnidosFil: Robinson, Nathan J.. Fundación Oceanogràfic; EspañaFil: Sandoval-Lugo, Alejandra G.. Instituto Politécnico Nacional; MéxicoFil: Schofield, Gail. Queen Mary University of London; Reino UnidoFil: Seminoff, Jeffrey A.. Noaa National Marine Fisheries Service Southwest Regional Office; Estados UnidosFil: Seney, Erin E.. University Of Central Florida; Estados UnidosFil: Snape, Robin T. E.. University of Exeter; Reino UnidoFil: Sözbilen, Dogan. Dekamer—sea Turtle Rescue Center; Turquía. Pamukkale University; TurquíaFil: Tomás, Jesús. Institut Cavanilles de Biodiversitat I Biologia Evolutiva; EspañaFil: Varo Cruz, Nuria. Universidad de Las Palmas de Gran Canaria; España. Ads Biodiversidad; España. Instituto Canario de Ciencias Marinas; EspañaFil: Wallace, Bryan P.. University of Duke; Estados Unidos. Ecolibrium, Inc.; Estados UnidosFil: Wildermann, Natalie E.. Texas A&M University; Estados UnidosFil: Witt, Matthew J.. University of Exeter; Reino UnidoFil: Zavala Norzagaray, Alan A.. Instituto politecnico nacional; MéxicoFil: Halpin, Patrick N.. University of Duke; Estados Unido