The Social Impact Score: a Framework for Including Social Benefits in Rural Road Prioritization Investments and Decision Making

Rural roads and transport infrastructure play a crucial role in the larger development picture. These physical assets have non-economic impacts including reaching goals such as reducing poverty, increasing access to health centers and schools, expansion of agricultural and non-farm economic activities, increasing political participation, access to information, and can play a role in reducing the traditional taboos that engender discrimination of women and minority groups. However, there remains a disconnect between these potential benefits and their implementation in policy decisions. The inclusion of social benefits in rural road investment prioritization has not become a routine part of the decision making process of policy makers and infrastructure planners. Several reasons contribute to this, including a focus on economic justification and return on investment, as well as the difficult and often impossible task of fully isolating the impact of indirect and induced impact of road infrastructure on the larger development picture. However, simply ignoring the larger impact of rural road infrastructure because of difficulty in quantifying the impacts fails to fully seize the opportunity to contribute to larger development goals in transport planning. The purpose of this thesis is to create a metric called the Social Impact Score (SIS). Building on three main pillars of research, the SIS seeks to fill the gap between well-established case study literature highlighting the importance of rural roads and the inclusion of these considerations at the national infrastructure policy level. The metric was designed in conjunction with other analysis tools, including a life-cycle analysis on road maintenance and construction under current and future climate scenarios. The information provided by the SIS will serve national level policy makers as an important step in expanding the criteria and justification used to allocate investments in rural road infrastructure, based upon a sustainable life-cycle perspective and more holistic development impact. The `further research' section discusses the use of the SIS as a tool that can highlight areas where further research may be needed or desired at a sub-national level

Infrastructure and climate change: a study of impacts and adaptations in Malawi, Mozambique, and Zambia

The African Development Bank has called for $40 Billion USD per year over the coming decades to be provided to African countries to address development issues directly related to climate change. The current study addresses a key component of these issues, the effect of climate change on the road infrastructure of Malawi, Mozambique, and Zambia. The study incorporates a stressor-response approach to estimate the effects of projected precipitation, temperature, and flooding changes on the paved and unpaved road infrastructure of these countries. The paper highlights the result of running 425 climate scenarios for each road type and policy option from 2010 to 2050. Based on this broad analysis, it is estimated that the three southern African countries are facing a potential$596 million price tag based on median climate scenarios to maintain and repair roads as a result of damages directly related to temperature and precipitation changes from potential climate change through 2050. The challenge for policy makers is to determine the potential risk that a country is facing based on the uncertainties associated with the multiple aspects of climate change modeling. This article is part of a Special Issue on “Climate Change and the Zambezi River Valley” edited by Finn Tarp, James Juana, and Philip Ward

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Road Infrastructure and Climate Change in Vietnam

Climate change is a potential threat to Vietnam’s development as current and future infrastructure will be vulnerable to climate change impacts. This paper focuses on the physical asset of road infrastructure in Vietnam by evaluating the potential impact of changes from stressors, including: sea level rise, precipitation, temperature and flooding. Across 56 climate scenarios, the mean additional cost of maintaining the same road network through 2050 amount to US$10.5 billion. The potential scale of these impacts establishes climate change adaptation as an important component of planning and policy in the current and near future

Road Infrastructure and Climate Change in Vietnam

Abstract Climate change is a potential threat to Vietnam's development as current and future infrastructure will be vulnerable to climate change impacts. This paper focuses on the physical asset of road infrastructure in Vietnam by evaluating the potential impact of changes from stressors, including: sea level rise, precipitation, temperature and flooding. Across 56 climate scenarios, the mean additional cost of maintaining the same road network through 2050 amount to US$10.5 billion. The potential scale of these impacts establishes climate change adaptation as an important component of planning and policy in the current and near future

Interactions between human osteoblasts and prostate cancer cells in a novel 3D in vitro model

Cell-cell and cell-matrix interactions play a major role in tumor morphogenesis and cancer metastasis. Therefore, it is crucial to create a model with a biomimetic microenvironment that allows such interactions to fully represent the pathophysiology of a disease for an in vitro study. This is achievable by using three-dimensional (3D) models instead of conventional two-dimensional (2D) cultures with the aid of tissue engineering technology. We are now able to better address the complex intercellular interactions underlying prostate cancer (CaP) bone metastasis through such models. In this study, we assessed the interaction of CaP cells and human osteoblasts (hOBs) within a tissue engineered bone (TEB) construct. Consistent with other in vivo studies, our findings show that intercellular and CaP cell-bone matrix interactions lead to elevated levels of matrix metalloproteinases, steroidogenic enzymes and the CaP biomarker, prostate specific antigen (PSA); all associated with CaP metastasis. Hence, it highlights the physiological relevance of this model. We believe that this model will provide new insights for understanding of the previously poorly understood molecular mechanisms of bone metastasis, which will foster further translational studies, and ultimately offer a potential tool for drug screening