Cost-effective Design of Automotive Framing Systems Using Flexibility and Reconfigurability Principles

Manufacturing enterprises are entering an era of new challenges where manufacturing needs to compete in a global economy with open and unpredicted market changes. Manufacturing facilities need to possess a high degree of flexibility, enabling mass customization of production. Reconfigurable Manufacturing Systems (RMS) is a relatively new concept, which if adopted properly, will become a design foundation for the next generation of world-class production systems. They will help automotive companies achieve rapid response and cost-effective product delivery aligned with the current market demand. This research introduces new systematic methods dealing with a complete end-to-end design process to production systems, where the uncertainty of product variety is mapped to product attributes and manufacturing processes, then mapped into a production line using product decomposition into systems, sub-systems, and modular assembly. Graph network (NW), change propagation index (CPI) and hybrid design structure matrix (HDSM) were introduced. Design structures matrix (DSM) and hybrid design structure matrix (HDSM) were used along with axiomatic design (AD) to ensure customer needs are translated into action. A hierarchal structure has been developed for a body-in-white (BIW) framing system. Implementation for best practice and coordination between processes in all design stages is a prerequisite for other function requirements. Knowing systems level interaction early in the product developments process is critical for design concept selection, and systems architectures decisions. However, existing methods that address the system\u27s interaction, such as the design structure matrix (DSM), are good to analyze the systems but cannot be used during conceptual synthesis when most important designs are made. Systems level knowledge is critical to the success of the design of large systems and needs to be captured at the early stage of the design. Results of using the proposed methodology on a real case study shows that the proper implementation of flexibility and reconfigurability in the production system increase the capability and shows significant improvements in throughputs of production systems. Real production data was used to redesign the assembly line of production systems using digital manufacturing (DM) and production simulation. Simulation model of the state of practice was developed using DELMIA\u27s Digital Manufacturing solution (IGRIP)

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Evaluation of management effectiveness of a marine protected area: a case study for Socotra Island, Yemen

Establishing Marine Protected Areas (MPAs) can bring multiple benefits to people and communities, such as increased income from tourism development, and associated benefits from protecting the marine environment. However, the ability of MPAs to conserve marine biodiversity can be constrained, especially when they are poorly planned and the consequences of establishing these areas are not well considered. The establishment of MPAs may have inadvertent consequences such as increased poverty, social tension, conflicts and power struggles in managing these areas when posing new restrictions on resource use. Therefore, it is important to understand whether establishing an MPA has negative consequences or positive benefits to the marine biodiversity and communities living adjacent to the protected area. More importantly, there is a need to improve MPA management because many are not meeting their objectives, including marine biodiversity protection objectives. There is international interest in understanding why MPAs do and don't work and therefore improving their ability to protect natural and cultural diversity. Assessing the success of MPAs requires developing indicators and undertaking evaluative approaches.\ud \ud A series of indicators, linked to specific criteria, are generally used to assess the management effectiveness of Protected Areas (PAs), including MPAs. The International Union for Conservation of Nature (IUCN)-World Commission on Protected Areas (WCPA) developed an evaluation framework for assessing management effectiveness of these areas. This framework includes multiple criteria which relate to six management elements (Context, Planning, Inputs, Process, Outputs and Outcomes). Many methods, including the World Bank (WB) Scorecard Tool, have been developed to assess management effectiveness of MPAs using indicators against criteria in relation to these elements. However, there is no internationally accepted method for such assessment. Researchers have recommended developing and combining several developed approaches as a comprehensive method to assess the effectiveness of MPAs. Developing approaches for such an assessment is still in the early stages. Consequently, there is a need to design a mixed-approach method if researchers are to progress with assessing the management effectiveness evaluation of MPAs.\ud \ud My PhD study aimed to design a comprehensive method for evaluating MPA effectiveness, including a broader community survey than has been typically conducted, to assess MPAs and to test this method on the Socotra Island MPA in Yemen. Meeting this overarching aim necessitated different approaches, including: (1) adapting indicators and modifying the scoring system that were used in the WB Scorecard Tool, (2) adapting criteria in relation to the six elements addressed in the IUCN-WCPA Evaluation Framework, and (3) developing indicators in relation to an additional element (Priorities). Community awareness and stakeholder satisfactions are two broad criteria used in the WB Scorecard Tool to help assess management effectiveness of an MPA. This tool used one indicator in relation to each of these two broad criteria. In contrast, I used several indicators in relation to the community awareness and stakeholder satisfaction to help assess the management effectiveness of the MPA. In addition, the WB Scorecard Tool does not include community preferences, as a criterion, to help assess the management effectiveness of an MPA. To date, this criterion is not identified as a measure to assess management effectiveness of MPAs in the literature. Aligning community preferences for improving MPA management with a government's priorities was used as a new approach I developed in relation to the element 'Priorities' to assess the management effectiveness of the MPA.\ud \ud In this thesis I used two broad approaches to assess the management effectiveness of the MPA. These two approaches were a literature review and a survey of community members. The literature review involved collecting qualitative and quantitative information from available governmental documents, including plans, project progress reports and published papers relating to the MPA management. I also visited the office of the Environmental Protection Authority (EPA) on Socotra Island, which is the Management Authority (MA) for the MPA, to collect secondary data by approaching the senior staff of the MA to update what I found in the literature in relation to the MPA. Socotra Island has an area of 3625 km² with two towns only and about 60 coastal villages. The community survey on this island included Socotrans (n=414) and Yemeni Non-Socotrans (n= 66) living on Socotra Island. The survey was based on a structured questionnaire. Respondents were identified as fitting within 1 of 23 community subgroups, which included Local Council Officials, Fishers and Housewives, at the beginning of each interview and then grouped within 4 key stakeholder groups (Socotran Decision Maker Group, Socotran Primary User Group, Socotran Secondary User Group and Yemeni Non-Socotran Secondary User Group) for analysis purposes. The community survey was conducted in April– May 2011 at 30 coastal locations (2 towns and 28 villages), including remote areas, along most of the coastline of Socotra Island.\ud \ud Seventy-two indicators were used to assess the management effectiveness of the Socotra Island MPA via a literature review and comprehensive community survey in relation to the seven elements mentioned above. These indicators were represented as questions (For example: 'Does the MPA have a legal status?' and 'Are the local community satisfied with the current zoning plan of the MPA?'). Forty-three indicators were used to measure activities conducted by the MA for the MPA management. Twenty-nine indicators were used to explore the community's awareness of several management criteria; participation in management-related activities; satisfaction with many management criteria; and preferences for improving the MPA management.\ud \ud My results showed statistically significant differences in some responses within and between the four key stakeholder groups. For example, more respondents from the Socotran Decision Maker Group participated in MPA management-related activities than those from the other three key stakeholder groups. More respondents from the Socotran User Group were satisfied with the overall management of the MPA than those from the Yemeni Non-Socotran Secondary User Group. More respondents from the Socotran Primary User Group preferred services available for the locals/fishers than those from the other stakeholder groups.\ud \ud I found that the managers of the Socotra Island MPA faced five major difficulties for managing the MPA effectively. First, the MA lacked a sufficient budget and did not have a management plan. Second, the MA did not have strong enforcement power with regard to managing increased threats on natural resources. Third, the MPA was not providing obvious flow on benefits to the local communities. Fourth, the majority of the local community was not satisfied with the MPA management. Fifth, the local community's preferences for improving this management were not aligned with the Yemeni government's priorities.\ud \ud My PhD study showed some differences between results obtained via the literature review and those via the community survey. My study revealed that the MA conducted a large awareness-raising program and involved a wide array of stakeholders in management-related activities prior to the establishment of the MPA. Despite this, I found that the local community's awareness of the MPA was low and stakeholders' participation in these activities was limited.\ud \ud My assessment results also varied when they were assessed in terms of the different approaches I used in this PhD study. I assessed the effectiveness of management of the MPA as 'Moderate' in terms of the activities conducted by the MA and community's satisfaction with the MPA management. In contrast, effectiveness was assessed as 'Low' in terms of the community's awareness of the MPA, their participation in management-related activities and aligning their preferences for improving MPA management with the Yemeni government's priorities. Overall, the effectiveness of the MPA management was assessed as 'Moderate', meaning it was inadequate.\ud \ud The results from my thesis indicate that the ability of the MPA to meet the ecological and socioeconomic objectives addressed in its conservation zoning plan is weak, though the Yemeni government played a significant role in developing the legal status of this area. Based on the findings, I propose multiple recommendations, such as allocating and securing a sufficient operational budget, in this PhD thesis to improve management of the MPA and achieve these objectives. Considering the results and recommendations in this thesis could increase the management effectiveness of the MPA.\ud \ud The mixed-approach method I designed in this PhD thesis considering and combining several approaches was a valuable evaluation strategy because it provided a thorough understanding of how effectively the MPA was managed. Although this method was costly and time consuming, the final outcome was considered worthwhile, contributing to progress in the evaluation of management effectiveness of MPAs globally. My thesis provides a step towards understanding how a comprehensive community survey can be complementary to the activities conducted by a MA in assessing management effectiveness of an MPA, by providing approaches which are recommended to be adapted for this assessment. The future quality of these approaches could be improved by considering the areas of research, including investigation of correlations between community attitudes and education levels, addressed in this thesis

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

BackgroundTranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding.MethodsWe did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124.FindingsBetween July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98).InterpretationWe found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial.</div