Improving cold chain technologies through the use of phase change material

Gemstone Team FRESHVaccine-preventable diseases are responsible for about 25% of the 10 million deaths occurring annually for children under five years of age. The World Health Organization's Expanded Programmes on Immunization succeed in providing standardized guidelines for vaccine storage and distribution, but often fail to accommodate the unique infrastructure between and within countries. In order to better regulate the temperature of vaccines as they travel through countries, we have selected and characterized an appropriate phase change material (PCM) that will resist temperature fluctuations outside of a range of 2-8 °C, based on appropriate thermophysical properties. Additionally, we have integrated the selected PCM within a geometrically and thermally optimized cold box, maintaining long-term stabilization of temperatures within a range of 2-8 °C. In meeting these objectives, we have demonstrated the feasibility of a technological solution that may be readily implemented in the existing vaccine distribution supply chain, or that holds potential to be the centerpiece for new, more efficient vaccine distribution strategies

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Third grade students collaborate and construct meaning using new literacies

The purpose of this research was to study how students collaborate and construct learning using new literacies to understand literature. Specifically, this study investigated how responding to literature digitally shapes students\u27 responses and what students perceive to be effective forms of collaboration. Surveys, interviews, students\u27 constructed responses, anecdotal notes, and a teacher research journal were all analyzed and coded for emerging themes. The findings show that responding to literature digitally can increase classroom efficiency, student engagement, and student motivation. Online discussions also provided opportunities for students to effectively communicate and increased their ability to collaborate. As the study progressed, it was evident that students used new literacies to create a deeper meaning of their learning. Digital tools also caused a shift in traditional teacher and student roles as students used digital tools to redefine literary responses. Overall, the findings from this study support previous research which suggests that the Internet and other forms of information and communication technologies (ICTs) enhance and redefine literacy instruction and learning

Management of hepatic encephalopathy: focus on antibiotic therapy

Altered gut microecology is considered a key pathogenetic factor in the development of both inteststinal (irritable bowel disease, inflammatory bowel disease, ecc.)and systemic (hepatic encephalophaty, steatohepatitis, ecc.) diseases. Hepatic encephalopathy (HE) is a major neuropsychiatric complication of both acute and chronic liver failure. Symptoms of HE include attention deficits, alterations of sleep patterns and muscular incoordination progressing to stupor and coma. The pathogenesis of HE is still unknown, although ammonia-induced alterations of cerebral neurotransmitter balance, especially at the astrocyte-neurone interface, may play a major role. Treatment of HE is therefore directed at reducing the production and absorption of gut-derived neurotoxic substances, especially ammonia. The non-absorbable disaccharides lactulose and lactitol were long considered as a first-line pharmacological treatment of HE, but a recent systematic review questioned their efficacy, pointing out that there is insufficient high-quality evidence to support their use. Oral antibiotics are regarded as a suitable therapeutic alternative. However, the prolonged use of antimicrobials is precluded by the possible occurrence of adverse events. Rifaximin, a synthetic antibiotic structurally related to rifamycin, displays a wide spectrum of antibacterial activity against Gram-negative and Grampositive bacteria, both aerobic and anaerobic, and a very low rate of systemic absorption. Available evidence suggests that rifaximin - thanks to its efficacy and remarkable safety - has the highest benefit-risk ratio in the overall treatment of HE

Efficacy of long term cyclic administration of the poorly absorbed Rifaximin in symptomatic, uncomplicted colonic diverticular disease

Aim: To comparatively ate the long term efficacy of Rifaximin and dietary fibers in reducing symptoms and/or complication frequency in symptomatic, uncomplicated diverticular disease. Methods: 307 patients (118 males, 189 females, age range: 40-80 years) were enrolled in the study and randomly assigned to: Rifaximin (400 mg bid for 7 d every month) plus dietary fiber supplementation (at least 20 gr/d) or dietary fiber supplementation alone. The study duration was 24 mo; both clinical examination and symptoms' questionnaire were performed every two months. Results: Both treatments reduced symptom frequency, but Rifaximin at a greater extent, when compared to basal values. Symptomatic score declined during both treatments, but a greater reduction was evident in the Rifaximin group (6.4 \uc2\ub1 2.8 and 6.2 \uc2\ub1 2.6 at enrollment, P = NS, 1.0 \uc2\ub1 0.7 and 2.4 \uc2\ub1 1.7 after 24 mo, P < 0.001, respectively). Probability of symptom reduction was higher and complication frequency lower (Kaplan-Meyer method) in the Rifaximin group (P < 0.0001 and 0.028, respectively). Conclusion: In patients with symptomatic, uncomplicated diverticular disease, cyclic administration of Rifaximin plus dietary fiber supplementation is more effective in reducing both symptom and complication frequency than simple dietary fiber supplementation. Long term administration of the poorly absorbed antibiotic Rifaximin is safe and well tolerated by the patients, confirming the usefulness of this therapeutic strategy in the overall management of diverticular disease. \uc2\ua9 2007 The WJG Press. All rights reserved

Efficacy of long term cyclic administration of the poorly absorbed Rifaximin in symptomatic, uncomplicted colonic diverticular disease

Aim: To comparatively ate the long term efficacy of Rifaximin and dietary fibers in reducing symptoms and/or complication frequency in symptomatic, uncomplicated diverticular disease. Methods: 307 patients (118 males, 189 females, age range: 40-80 years) were enrolled in the study and randomly assigned to: Rifaximin (400 mg bid for 7 d every month) plus dietary fiber supplementation (at least 20 gr/d) or dietary fiber supplementation alone. The study duration was 24 mo; both clinical examination and symptoms' questionnaire were performed every two months. Results: Both treatments reduced symptom frequency, but Rifaximin at a greater extent, when compared to basal values. Symptomatic score declined during both treatments, but a greater reduction was evident in the Rifaximin group (6.4 \uc2\ub1 2.8 and 6.2 \uc2\ub1 2.6 at enrollment, P = NS, 1.0 \uc2\ub1 0.7 and 2.4 \uc2\ub1 1.7 after 24 mo, P < 0.001, respectively). Probability of symptom reduction was higher and complication frequency lower (Kaplan-Meyer method) in the Rifaximin group (P < 0.0001 and 0.028, respectively). Conclusion: In patients with symptomatic, uncomplicated diverticular disease, cyclic administration of Rifaximin plus dietary fiber supplementation is more effective in reducing both symptom and complication frequency than simple dietary fiber supplementation. Long term administration of the poorly absorbed antibiotic Rifaximin is safe and well tolerated by the patients, confirming the usefulness of this therapeutic strategy in the overall management of diverticular disease. \uc2\ua9 2007 The WJG Press. All rights reserved

Measurement of hepatic functional mass by means of 13C-methacetin and 13C-phenylalanine breath tests in chronic liver disease: comparison with Child-Pugh score and serum bile acid levels

AIM: To evaluate and compare the clinical usefulness of 13C-phenylalanine and 13C-methacetin breath tests in quantitating functional hepatic mass in patients with chronic liver disease and to further compare these results with those of conventional tests, Child-Pugh score and serum bile acid levels. METHODS: One hundred and forty patients (50 HCV-related chronic hepatitis, 90 liver cirrhosis patients) and 40 matched healthy controls were studied. Both breath test and routine liver test, serum levels of cholic and chenodeoxycholic acid conjugates were evaluated. RESULTS: Methacetin breath test, expressed as 60 min cumulative percent of oxidation, discriminated the hepatic functional capacity not only between controls and liver disease patients, but also between different categories of chronic liver disease patients. Methacetin breath test was correlated with liver function tests and serum bile acids. Furthermore, methacetin breath test, as well as serum bile acids, were highly predictive of Child-Pugh scores. The diagnostic power of phenylalanine breath test was always less than that of methacetin breath test. CONCLUSION: Methacetin breath test represents a safe and accurate diagnostic tool in the evaluation of hepatic functional mass in chronic liver disease patients