Microclimates at the Sixth Facade

Elevating buildings above grade is an increasingly- common design approach to address risks of costal and riverine flooding. While elevating buildings improves resistance to flood waters and potentially debris damage, other implications are less well-understood, including the influence of unique thermal and moisture conditions in the space between the ground and the underside of the elevated building—the so-called sixth facade. Unlike conventional basements, crawlspaces, or slabs-on-grade that respond to soil moisture through the installation of a vapor barrier, exposed, elevated floors contend with unique hygrothermal conditions, linked-to but distinct- from both the soil and the ambient air. Uncontrolled moisture has significant energy consequences, can foster mold and fungi growth, and contributes to deterioration of building materials through rot and corrosion. To better understand conditions at the sixth facade, this study compares the conditions of the sixth facade to those of the interior and exterior ambient air of the same elevated building during the condensation-risk period of a year. Temperature and relative humidity were recorded inside, under, and adjacent-to the building at sub-hourly intervals for eleven months, to enable calculations of condensation risk. While extensive prior literature considers condensation in wall and roof assemblies and vented versus unvented crawlspaces; little data or guidance is available about the frequency of condensation risk on the underside of elevated buildings. The growing awareness and effort to improve building resilience at the residential scale demands a greater understanding of conditions at the sixth façade to guide design

The Youngest Victims of the Opioid Epidemic

When babies are born to opioid-addicted mothers, they often develop Neonatal Abstinence Syndrome (NAS). NAS is characterized by symptoms associated with abrupt opioid withdrawal (“Neonatal Abstinence”, 2015). By preventing NAS in babies before they are born and properly caring for a baby with NAS after birth, we will aim to decrease the incidence of this condition and as its harmful effects in the lives of babies. In Ohio, there are many neonates suffering from NAS. The rates for babies born with NAS have quadrupled since 2011 when 2.2 out of every 1000 babies had NAS to 2015, where 12.3 out of 1000 babies suffer from NAS (“Number”, nd). NAS not only affects the baby immediately after birth, but also throughout the course of their lives. Babies with NAS are more likely to experience things like chronic stress, inconsistent caregiving, out-of-home placements, and long-term health issues. (“Long-Term Outcomes”, nd). To counter the problem of NAS, we would like to propose a two-part solution. This solution consists of medical care that first focuses on preventing NAS, and secondly treating its effects. Two treatments that show great promise in the prevention of NAS include the use of Ondansetron while the baby is in utero (“Ondansetron Pharmacokinetics”, 2014), and vaccination against opioids (“Novel pharmacotherapeutic”, 2012). The second part of the solution is used if these preventative treatments are not possible. In this case, the goal of treatment becomes to mitigate the effects of NAS. In this situation, promising interventions include stabilizing the baby in the NICU and admitting the baby to a facility specializing in NAS. In order to solve the ongoing health effects of NAS, we have two recommendations. The first is that specialized facilities enroll parents in counseling and parenting classes, reducing the chance that the child will experience out of home placement (“Assessment of”, 2014). Secondly, we propose that specialized facilities expand their scope of care to treat babies with NAS until age 18 with the goal of decreasing the incidence of common NAS-related health issues by providing more consistency in healthcare

Understanding direct and indirect driver vision in heavy goods vehicles

The research described in this report has been performed by Loughborough Design School (LDS) under the CLOCS programme funded by TfL. The project was specified to allow an understanding of the variability of blind spots in direct vision through windows and indirect vision through mirrors for the top selling HGVs in the UK. The impetus for the research was the increasing number of accidents between Vulnerable Road Users (VRUs) and HGVs in London. The aim was to compare the manufacturers’ most sold vehicle specifications to determine which vehicle design variables can affect the size of blind spots, and to explore issues that have been raised in previous research including the potential for construction HGVs to be involved in more accidents with VRUs than distribution variants of HGV designs. The LDS team have utilised a virtual modelling technique to explore this issue. This virtual approach allows multiple accident scenarios to be modelled and simulated. In order to allow the analysis of vehicle blind spots 19 vehicle models have been created by digitally scanning the real world vehicles. The vehicles that have been modelled include construction, distribution and long haul HGV designs, as well as ‘high vision’ low entry cab designs. These models have been used in combination with simulations of cyclist and pedestrian VRUs in a manner which recreates critical accident scenarios that have been defined through the analysis of accident data. This involves placing the simulated VRUs in a number of defined locations adjacent to the vehicle. Subsequently the simulated VRUs are moved away from the vehicle into a position where they ‘just can’t be seen’ by the driver of the vehicle, i.e. moving them further away would allow them to be partially visible. The distance that the VRU is away from the side or front of the vehicle cab determines the size of the direct vision blind spot. In this way vehicle designs and configurations can be compared. In addition to this further testing was performed to determine if the VRUs located in the direct vision blind spots could be viewed by the driver through the use of mirrors. A further analysis technique utilised a method which projects the volume of space that can be seen by a driver through the windows and mirrors on to the surface of sphere. This provides a field of view value which can be used to compare the glazed area of HGVs and provides a method to distinguish between vehicles that perform at the same level in the VRU simulation. The results of the work highlight the follow key issues. 1. All standard vehicle configurations have blind spots which can hide VRUs from the driver’s direct vision 2. The height of the cab above the ground is the key vehicle factor which affects the size of direct vision and indirect vision blind spots 3. The design of window apertures and the driver location in relation to these window apertures can reduce the size of the identified blind spots. i.e. two different vehicle designs with the same cab height can have different results for blind spot size due to window design and driver seat location 4. Low entry cab designs, which are the lowest of the 19 vehicles tested, demonstrated real benefits in terms of reducing direct vision blind spots when compared to standard vehicle designs 5. The construction vehicles assessed in the project are on average 32% higher than the same cab design in the distribution configuration 6. For construction vehicles the distance away that a pedestrian in front of the vehicle can be hidden from the driver’s view is on average nearly three times greater than the distribution vehicles 7. For the construction vehicles the distance away that a cyclist to the passenger side of the vehicle can be hidden is on average more than two times greater than the distribution vehicles 8. The work has highlighted the need for a new standard which defines what should be visible through direct vision from the vehicle. Such a standard does not currently exist, and is seen as a key mechanism for improving future vehicle design

Monthly hemostatic factor variability in women and men

Hormonal status influences hemostatic factors including fibrinogen, factor VII and plasminogen activator inhibitor (PAI-1), and concentrations differ among men, premenopausal and postmenopausal women. This study examines how phases of the menstrual cycle influence variability of fibrinogen, factor VII and PAI-1

3,3′-Diindolylmethane Induces G1 Arrest and Apoptosis in Human Acute T-Cell Lymphoblastic Leukemia Cells

Certain bioactive food components, including indole-3-carbinol (I3C) and 3,3′-diindolylmethane (DIM) from cruciferous vegetables, have been shown to target cellular pathways regulating carcinogenesis. Previously, our laboratory showed that dietary I3C is an effective transplacental chemopreventive agent in a dibenzo[def,p]chrysene (DBC)-dependent model of murine T-cell lymphoblastic lymphoma. The primary objective of the present study was to extend our chemoprevention studies in mice to an analogous human neoplasm in cell culture. Therefore, we tested the hypothesis that I3C or DIM may be chemotherapeutic in human T-cell acute lymphoblastic leukemia (T-ALL) cells. Treatment of the T-ALL cell lines CCRF-CEM, CCRF-HSB2, SUP-T1 and Jurkat with DIM in vitro significantly reduced cell proliferation and viability at concentrations 8- to 25-fold lower than the parent compound I3C. DIM (7.5 µM) arrested CEM and HSB2 cells at the G1 phase of the cell cycle and 15 µM DIM significantly increased the percentage of apoptotic cells in all T-ALL lines. In CEM cells, DIM reduced protein expression of cyclin dependent kinases 4 and 6 (CDK4, CDK6) and D-type cyclin 3 (CCND3); DIM also significantly altered expression of eight transcripts related to human apoptosis (BCL2L10, CD40LG, HRK, TNF, TNFRSF1A, TNFRSF25, TNFSF8, TRAF4). Similar anticancer effects of DIM were observed in vivo. Dietary exposure to 100 ppm DIM significantly decreased the rate of growth of human CEM xenografts in immunodeficient SCID mice, reduced final tumor size by 44% and increased the apoptotic index compared to control-fed mice. Taken together, our results demonstrate a potential for therapeutic application of DIM in T-ALL

Policymakers\u27 experience of a capacity-building intervention designed to increase their use of research: A realist process evaluation

Background: An intervention’s success depends on how participants interact with it in local settings. Process evaluation examines these interactions, indicating why an intervention was or was not effective, and how it (and similar interventions) can be improved for better contextual fit. This is particularly important for innovative trials like Supporting Policy In health with Research: an Intervention Trial (SPIRIT), where causal mechanisms are poorly understood. SPIRIT was testing a multi-component intervention designed to increase the capacity of health policymakers to use research. Methods: Our mixed-methods process evaluation sought to explain variation in observed process effects across the six agencies that participated in SPIRIT. Data collection included observations of intervention workshops (n = 59), purposively sampled interviews (n = 76) and participant feedback forms (n = 553). Using a realist approach, data was coded for context-mechanism-process effect configurations (retroductive analysis) by two authors. Results: Intervention workshops were very well received. There was greater variation of views regarding other aspects of SPIRIT such as data collection, communication and the intervention’s overall value. We identified nine inter-related mechanisms that were crucial for engaging participants in these policy settings: (1) Accepting the premise (agreeing with the study’s assumptions); (2) Self-determination (participative choice); (3) The Value Proposition (seeing potential gain); (4) ‘Getting good stuff’ (identifying useful ideas, resources or connections); (5) Self-efficacy (believing ‘we can do this!’); (6) Respect (feeling that SPIRIT understands and values one’s work); (7) Confidence (believing in the study’s integrity and validity); (8) Persuasive leadership (authentic and compelling advocacy from leaders); and (9) Strategic insider facilitation (local translation and mediation). These findings were used to develop tentative explanatory propositions and to revise the programme theory. Conclusion: This paper describes how SPIRIT functioned in six policy agencies, including why strategies that worked well in one site were less effective in others. Findings indicate a complex interaction between participants’ perception of the intervention, shifting contextual factors, and the form that the intervention took in each site. Our propositions provide transferable lessons about contextualised areas of strength and weakness that may be useful in the development and implementation of similar studies

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

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

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden