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The counter intuitive effect of open label placebo

Ted Kaptchuk, professor of medicine at Harvard Medical school - and leading placebo researcher, has just published an analysis on bmj.com describing the effect of open label placebo - placebos that patient's know are placebos, but still seem to have some clinical effect. Ted joins us to speculate about what's going on in the body, what this means...




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Talk Evidence - Devices and facebook vaccines

In the second of our EBM round-ups, Carl Heneghan, Helen Macdonald and Duncan Jarvies are joined by Deborah Cohen, investigative journalist and scourge of device manufacturers. We're giving our verdict on the sensitivity and specificity of ketone testing for hyperemesis, and the advice to drinking more water to prevent recurrent UTIs in...




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Working as a team, and combating stress, in space

Nicole Stott is an engineer, aquanaut and one of the 220 astronauts to have lived and worked on the International Space Station. In a confined space, under huge pressure, with no way out, it's important that teams maintain healthy dynamics, and individuals can manage their stress adequately, and in this podcast Nicole explains a little about...




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Born equal - the launch of The BMJ special issue on race in medicine

Last week the BMJ published it’s first special edition into Racism in Medicine. The issues tacked ranged from differential attainment in medical school, to the physiological effects that experiencing everyday discrimination has. The issue was guest edited by Victor Adebowale, the Chief Executive of the social care enterprise Turning Point, and...




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Talk Evidence covid-19 update - hydroxy/chloroquinine, prognostic models and facemaskss

For the next few months Talk Evidence is going to focus on the new corona virus pandemic. There is an enormous amount of uncertainty about the disease, what the symptoms are, fatality rate, treatment options, things we shouldn't be doing. We're going to try to get away from the headlines and talk about what we need to know - to hopefully give...




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Interplay of Placental DNA Methylation and Maternal Insulin Sensitivity in Pregnancy

The placenta participates in maternal insulin sensitivity changes during pregnancy; however, mechanisms remain unclear. We investigated associations between maternal insulin sensitivity and placental DNA methylation markers across the genome. We analyzed data from 430 mother-offspring dyads in the Gen3G cohort. All women underwent 75-g oral glucose tolerance tests at ~26 weeks of gestation; we used glucose and insulin measures to estimate insulin sensitivity (Matsuda index). At delivery, we collected samples from placenta (fetal side) and measured DNA methylation using Illumina EPIC arrays. Using linear regression models to quantify associations at 720,077 cytosine-guanine dinucleotides (CpGs), with adjustment for maternal age, gravidity, smoking, BMI, child sex, and gestational age at delivery, we identified 188 CpG sites where placental DNA methylation was associated with Matsuda index (P < 6.94 x 10–8). Among genes annotated to these 188 CpGs, we found enrichment in targets for miRNAs, in histone modifications, and in parent-of-origin DNA methylation including the H19/MIR675 locus (paternally imprinted). We identified 12 known placenta imprinted genes, including KCNQ1. Mendelian randomization analyses revealed five loci where placenta DNA methylation may causally influence maternal insulin sensitivity, including the maternally imprinted gene DLGAP2. Our results suggest that placental DNA methylation is fundamentally linked to the regulation of maternal insulin sensitivity in pregnancy.




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Bread-and-butter issues surface under St Mary community restrictions

DOVER, St Mary: Residents of Epsom and Dover in St Mary are on edge, but have accepted quarantine measures imposed by the Government to curtail the spread of the dreaded coronavirus in that parish. Security checkpoints at both ends of the parish...




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Disco embraces fresh start after tough end to '18

Reds starting pitcher Anthony DeSclafani hated how his 2018 season ended and didn't need any motivation to make improvements over the winter.




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George Headley Primary creates Peace Garden

A ‘Peace of Paradise’ garden has been created in George Headley Primary School, which is positively affecting behavioural change in students. The garden was created by students, teachers, and members of the community for the 2019 Trees for Peace...




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The roots to peace in the Democratic Republic of Congo: conservation as a platform for green development

2 July 2014 , Volume 90, Number 4

Richard Milburn




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Resource Development in Fragile and Conflict-Affected States: Can it Promote Peace?

Research Event

30 September 2014 - 1:30pm to 4:45pm

Chatham House, London

The discovery of valuable natural resources such as hydrocarbons or minerals in conflict-affected states or disputed regions can be a double-edged sword. While economic growth may help overcome conflict and consolidate peace, much of the academic literature links the economic, social and environmental impacts of resource development with an increased risk of violent conflict between or within fragile states. 

Recently however, the role of business in advancing peace has emerged as a topic of increasing discussion in academia and in forums such as the UN Global Compact. Resource development has also become a key objective for donor development strategies in fragile states such as Afghanistan, Somalia and Myanmar, on the assumption that extractive sector development can contribute to stability and security. 

This event will gather key stakeholders from business and policy to investigate if and where natural resource development has contributed to peace-building, built cooperation among stakeholders or helped to resolve, rather than exacerbate, tensions. If so, it will endeavour to draw out common, replicable lessons of what made these developments successful from a peace-building perspective.

The event will be held under the Chatham House Rule.

Event attributes

Chatham House Rule




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Diagnostic Accuracy of PET Tracers for the Differentiation of Tumor Progression from Treatment-Related Changes in High-Grade Glioma: A Systematic Review and Metaanalysis

Posttreatment high-grade gliomas are usually monitored with contrast-enhanced MRI, but its diagnostic accuracy is limited as it cannot adequately distinguish between true tumor progression and treatment-related changes. According to recent Response Assessment in Neuro-Oncology recommendations, PET overcomes this limitation. However, it is currently unknown which tracer yields the best results. Therefore, a systematic review and metaanalysis were performed to compare the diagnostic accuracy of the different PET tracers in differentiating tumor progression from treatment-related changes in high-grade glioma patients. Methods: PubMed, Web of Science, and Embase were searched systematically. Study selection, data extraction, and quality assessment were performed independently by 2 authors. Metaanalysis was performed using a bivariate random-effects model when at least 5 studies were included. Results: The systematic review included 39 studies (11 tracers). 18F-FDG (12 studies, 171 lesions) showed a pooled sensitivity and specificity of 84% (95% confidence interval, 72%–92%) and 84% (95% confidence interval, 69%–93%), respectively. O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) (7 studies, 172 lesions) demonstrated a sensitivity of 90% (95% confidence interval, 81%–95%) and specificity of 85% (95% confidence interval, 71%–93%). For S-11C-methyl)-l-methionine (11C-MET) (8 studies, 151 lesions), sensitivity was 93% (95% confidence interval, 80%–98%) and specificity was 82% (95% confidence interval, 68%–91%). The numbers of included studies for the other tracers were too low to combine, but sensitivity and specificity ranged between 93%–100% and 0%–100%, respectively, for 18F-FLT; 85%–100% and 72%–100%, respectively, for 3,4-dihydroxy-6-18F-fluoro-l-phenylalanine (18F-FDOPA); and 100% and 70%–88%, respectively, for 11C-choline. Conclusion: 18F-FET and 11C-MET, both amino-acid tracers, showed a comparably higher sensitivity than 18F-FDG in the differentiation between tumor progression and treatment-related changes in high-grade glioma patients. The evidence for other tracers is limited; thus, 18F-FET and 11C-MET are preferred when available. Our results support the incorporation of amino-acid PET tracers for the treatment evaluation of high-grade gliomas.




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Another CDU Leadership Race Begins in Merkel’s Shadow

28 February 2020

Quentin Peel

Associate Fellow, Europe Programme
The election of a new leader of the chancellor’s party will be another contest over her legacy.

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German Chancellor Angela Merkel is depicted on a float in the Rosenmontag parade in Mainz on 24 February. Photo: Getty Images.

Perhaps it will be second time lucky. At the end of April, Germany’s Christian Democratic Union (CDU) will elect a new party leader to follow in the footsteps of Angela Merkel. An emergency party congress has been summoned to do that after the surprise resignation of Annegret Kramp-Karrenbauer, Merkel’s chosen successor.

The plan is to leave the decision on who will be the CDU candidate for chancellor at the next election until after Germany’s EU presidency concludes in December. So Merkel will keep her job until 2021, and the new leader will have to learn to live with her.

The three leading candidates are Armin Laschet, Friedrich Merz and Norbert Röttgen, all from the state of North Rhine-Westphalia. Two of the three – Merz and Röttgen – were sacked by Merkel from their former jobs. They have not forgotten. Only Armin Laschet, currently CDU leader in North Rhine-Westphalia and state premier, can be described as a Merkel loyalist, true to her centrist mantra.

He is the man to beat, having teamed up with Jens Spahn, the 39-year-old health minister, who is popular with party conservatives. Spahn will run as his deputy, so the team straddles the left-right divide in the party. But the contest still seems set to be a bitter battle between pro- and anti-Merkel factions that could leave the party badly split.

After nearly 15 years as chancellor, and 18 years as CDU leader, Merkel remains the most popular politician in Germany. In spite of criticism that she lacks vision, her caution and predictability appear to be just what most German voters like.

But her term in office has also seen the steady shrinking of the centre ground in German politics, with the rise of the environmentalist Green party and the far-right Alternative for Germany (AfD) at the expense of the centre-right CDU and the centre-left Social Democratic Party (SPD).

The battle for the soul of the CDU is between those who think Merkel has been too left-wing, and want a more conservative leader to win back AfD voters, and those who believe that the CDU must stay in the centre, and prepare for a future coalition with the Greens. Merz is seen as the former, Laschet and Röttgen the latter.

Unless Laschet emerges as the clear winner in April, the leadership contest is likely to leave Germany sorely distracted by domestic politics just as it takes over the EU presidency in the second half of the year. Instead of Merkel having a triumphant international swansong on the EU stage, she could be battling to protect her inheritance at home.

The one area on which all three leadership candidates seem to agree is foreign policy: they all want Germany to take more leadership and responsibility, and for the European Union to play a bigger role in security, defence and international affairs. They are all Atlanticists, but critical of Donald Trump’s ‘America First’ stance. All are on the record criticizing the chancellor – at least tacitly – for not having a more vigorous foreign policy.

There the similarity ends.

On the right, the 64-year-old Merz is both the most conservative and the most popular with the party grassroots. He fell out with the chancellor when she took over his job as CDU leader in parliament in 2002. He quit politics to become a corporate lawyer (and a millionaire), but never lost his political ambition. He is an economic liberal but socially conservative, a strong critic of Merkel’s migration policy and her lack of clear leadership. Critics say he is a man of the past, and not a team player.

On the EU, he believes Germany is ‘leaving too much to the French’. If France and Germany cannot agree on financial matters, he said at the London School of Economics in February, they should instead forge a stronger EU industrial policy focused on creating more ‘European champions’.

Laschet, the Merkel loyalist, is four years younger, and from the left of the party. Like Merz, he is a former member of the European parliament. In 2015, he defended Merkel’s open border policy to accept refugees stranded in the Balkans. On Russia, however, he is more critical, calling for a new effort to re-engage with Vladimir Putin. Most recently, at the Munich Security Conference, he called for stronger Franco-German relations, and more support for the eurozone reforms proposed by Emmanuel Macron.

As CDU leader in North Rhine-Westphalia, Laschet has the strongest power base. He earned his political spurs there by winning the last state election in 2017, in contrast to Röttgen, who lost to the SPD and Greens five years earlier.

Röttgen, chairman of the Bundestag foreign affairs committee, is the surprise candidate. Once a Merkel favourite, they fell out when she sacked him as environment minister after he lost the North Rhine-Westphalia election. By throwing his hat in the ring, he has forced it to become an open contest. He is independent-minded and outspoken, but not as bitterly hostile to the chancellor as Merz, so he could be a compromise candidate.

Laschet is clearly the man Merkel would find it easiest to live with. The decision will be taken by a party congress, not a grassroots ballot, which gives him a better chance. But Merz is the most eloquent orator and seen as the best campaigner. The challenge for party members is whether they believe it is better to swing right and squeeze the AfD, or stick to the centre to hold onto voters tempted by the Greens, who have replaced the SPD as the second-most popular party in Germany.

The race is wide open. So is the future of the CDU. The only prediction one can make with much certainty is that as long as Merkel remains chancellor, any successor will struggle to get out of her shadow.




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Energy and Displacement in Eight Objects: Insights from Sub-Saharan Africa

5 November 2019

This ethnographic study is the first of its kind to analyse energy access and resilience strategies deployed in two refugee camps in Kenya and Burkina Faso. It highlights the need for new methodological approaches to expand the evidence base for humanitarian energy interventions and policies.

Owen Grafham

Manager, Energy, Environment and Resources Programme

Glada Lahn

Senior Research Fellow, Energy, Environment and Resources Programme

Jamie Cross

Senior Lecturer in Social Anthropology, University of Edinburgh

Megan Douglas

PhD Candidate in International Development, University of Edinburgh

Craig Martin

Reader in Design, University of Edinburgh.

Charlotte Ray

Research Associate, University of Loughborough

Arno Verhoeven

Lecturer in Design, University of Edinburgh

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Portable battery connected to a solar PV and used to recharge mobile phones and power a radio in Goudoubo Refugee camp (Burkina Faso). Photo: Edoardo Santangelo

In recent years, clean energy access for refugees and internally displaced people has emerged as a potential method of improving humanitarian outcomes and enabling self-reliance. While recent research emphasizes the need for more quantitative data to inform energy access interventions, better qualitative understanding would also improve innovation in this area.

This ethnographic study is the first of its kind to analyse energy access and resilience strategies deployed in two refugee camps, Kakuma in Kenya and Goudoubo in Burkina Faso. The stories of residents in these camps demonstrate the importance of considering everyday experiences of displaced people in developing sustainable humanitarian energy interventions.

This paper highlights the need for new methodological approaches to expand the evidence base for humanitarian energy interventions and policies. Future research could usefully inform humanitarian energy projects by examining the technical knowledge and existing practices of refugees in the design of energy technologies, systems and business models. Uptake and sustained use of new systems may be more likely where interventions build on or work in harmony with these factors.




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The histone H4 basic patch regulates SAGA-mediated H2B deubiquitination and histone acetylation [DNA and Chromosomes]

Histone H2B monoubiquitylation (H2Bub1) has central functions in multiple DNA-templated processes, including gene transcription, DNA repair, and replication. H2Bub1 also is required for the trans-histone regulation of H3K4 and H3K79 methylation. Although previous studies have elucidated the basic mechanisms that establish and remove H2Bub1, we have only an incomplete understanding of how H2Bub1 is regulated. We report here that the histone H4 basic patch regulates H2Bub1. Yeast cells with arginine-to-alanine mutations in the H4 basic patch (H42RA) exhibited a significant loss of global H2Bub1. H42RA mutant yeast strains also displayed chemotoxin sensitivities similar to, but less severe than, strains containing a complete loss of H2Bub1. We found that the H4 basic patch regulates H2Bub1 levels independently of interactions with chromatin remodelers and separately from its regulation of H3K79 methylation. To measure H2B ubiquitylation and deubiquitination kinetics in vivo, we used a rapid and reversible optogenetic tool, the light-inducible nuclear exporter, to control the subcellular location of the H2Bub1 E3 ligase, Bre1. The ability of Bre1 to ubiquitylate H2B was unaffected in the H42RA mutant. In contrast, H2Bub1 deubiquitination by SAGA-associated Ubp8, but not by Ubp10, increased in the H42RA mutant. Consistent with a function for the H4 basic patch in regulating SAGA deubiquitinase activity, we also detected increased SAGA-mediated histone acetylation in H4 basic patch mutants. Our findings uncover that the H4 basic patch has a regulatory function in SAGA-mediated histone modifications.




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The Changing Face of Emigration: Harnessing the Potential of the New Greek Diaspora

Large outflows of educated young people escaping high levels of unemployment, in tandem with inflows of unauthorized migrants, pose a fresh set of challenges for Greek policymakers. This Transatlantic Council on Migration report examines Greek emigration, and its economic implications, before exploring policy directions to minimize the costs and maximize the benefits of this mobility.




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Afghanistan: Displacement Challenges in a Country on the Move

Nearly 6 million Afghans fled after violence erupted in the late 1970s, primarily to Iran and Pakistan. While millions returned after the collapse of the Taliban in 2001, the security situation has since deteriorated and the government struggles to meet the needs of vulnerable populations, particularly the internally displaced. This country profile explores Afghanistan’s complex migration and displacement history as well as ongoing challenges.




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Years After Crimea’s Annexation, Integration of Ukraine’s Internally Displaced Population Remains Uneven

With nearly 1.4 million internally displaced persons (IDPs), Ukraine is home to one of the largest IDP populations in the world. Five years after Russia's annexation of Crimea, displaced Ukrainians continue to face challenges related to national identity, social cohesion, and political participation. While the Ukrainian government has had some success integrating IDPs, the conflict’s end remains uncertain, and many are unlikely to return to their communities of origin no matter the outcome.




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Climate Change and Natural Disasters Displace Millions, Affect Migration Flows

From earthquakes to drought, natural disasters and climate change played a key role in migration flows in 2015. Climate-induced migration surfaced as a concern at the United Nations Climate Change Conference (known as COP21) as international organizations and policymakers have begun to recognize the growing challenges, and potential protection obligations, of such movement.




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With Millions Displaced by Climate Change or Extreme Weather, Is There a Role for Labor Migration Pathways?

Climate-related displacement is not hypothetical: An average of 21.5 million people per year have been displaced since 2008 by natural disasters, and thousands more have fled slow-onset environmental hazards. While migration can serve as a safety valve to adapt to changing conditions, few orderly, legal channels exist for climate migrants (also known as environmental migrants), as this article explores.




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Superior Long-term Survival for Simultaneous Pancreas-Kidney Transplantation as Renal Replacement Therapy: 30-Year Follow-up of a Nationwide Cohort

OBJECTIVE

In patients with type 1 diabetes and end-stage renal disease, it is controversial whether a simultaneous pancreas-kidney (SPK) transplantation improves survival compared with kidney transplantation alone. We compared long-term survival in SPK and living- or deceased-donor kidney transplant recipients.

RESEARCH DESIGN AND METHODS

We included all 2,796 patients with type 1 diabetes in the Netherlands who started renal replacement therapy between 1986 and 2016. We used multivariable Cox regression analyses adjusted for recipient age and sex, dialysis modality and vintage, transplantation era, and donor age to compare all-cause mortality between deceased- or living-donor kidney and SPK transplant recipients. Separately, we analyzed mortality between regions where SPK transplant was the preferred intervention (80% SPK) versus regions where a kidney transplant alone was favored (30% SPK).

RESULTS

Of 996 transplanted patients, 42%, 16%, and 42% received a deceased- or living-donor kidney or SPK transplant, respectively. Mean (SD) age at transplantation was 50 (11), 48 (11), and 42 (8) years, respectively. Median (95% CI) survival time was 7.3 (6.2; 8.3), 10.5 (7.2; 13.7), and 16.5 (15.1; 17.9) years, respectively. SPK recipients with a functioning pancreas graft at 1 year (91%) had the highest survival (median 17.4 years). Compared with deceased-donor kidney transplant recipients, adjusted hazard ratios (95% CI) for 10- and 20-year all-cause mortality were 0.79 (0.49; 1.29) and 0.98 (0.69; 1.39) for living-donor kidney and 0.67 (0.46; 0.98) and 0.79 (0.60; 1.05) for SPK recipients, respectively. A treatment strategy favoring SPK over kidney transplantation alone showed 10- and 20-year mortality hazard ratios of 0.56 (0.40; 0.78) and 0.69 (0.52; 0.90), respectively.

CONCLUSIONS

Compared with living- or deceased-donor kidney transplantation, SPK transplant was associated with improved patient survival, especially in recipients with a long-term functioning pancreatic graft, and resulted in an almost twofold lower 10-year mortality rate.




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Targeting CXCR1/2 Does Not Improve Insulin Secretion After Pancreatic Islet Transplantation: A Phase 3, Double-Blind, Randomized, Placebo-Controlled Trial in Type 1 Diabetes

OBJECTIVE

Reparixin is an inhibitor of CXCR1/2 chemokine receptor shown to be an effective anti-inflammatory adjuvant in a pilot clinical trial in allotransplant recipients.

RESEARCH DESIGN AND METHODS

A phase 3, multicenter, randomized, double-blind, parallel-assignment study (NCT01817959) was conducted in recipients of islet allotransplants randomized (2:1) to reparixin or placebo in addition to immunosuppression. Primary outcome was the area under the curve (AUC) for C-peptide during the mixed-meal tolerance test at day 75 ± 5 after the first and day 365 ± 14 after the last transplant. Secondary end points included insulin independence and standard measures of glycemic control.

RESULTS

The intention-to-treat analysis did not show a significant difference in C-peptide AUC at both day 75 (27 on reparixin vs. 18 on placebo, P = 0.99) and day 365 (24 on reparixin vs. 15 on placebo, P = 0.71). There was no statistically significant difference between treatment groups at any time point for any secondary variable. Analysis of patient subsets showed a trend for a higher percentage of subjects retaining insulin independence for 1 year after a single islet infusion in patients receiving reparixin as compared with patients receiving placebo (26.7% vs. 0%, P = 0.09) when antithymocyte globulin was used as induction immunosuppression.

CONCLUSIONS

In this first double-blind randomized trial, islet transplantation data obtained with reparixin do not support a role of CXCR1/2 inhibition in preventing islet inflammation-mediated damage.




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Despite Flurry of Actions, Trump Administration Faces Constraints in Achieving Its Immigration Agenda

Though it has achieved success in some areas, the Trump administration’s many efforts to stiffen immigration enforcement in the U.S. interior and at the Southwest border are being consistently stymied by court injunctions, existing laws and settlements, state and local resistance, congressional pushback, and migration pressures that are beyond the government’s ability to swiftly address, as this article explores.




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After Deportation, Some Congolese Returnees Face Detention and Extortion

This article explores post-deportation dynamics and challenges returnees face in the Democratic Republic of the Congo (DRC). Even as European countries focus on increasing returns of migrants deemed not to have a right to stay, little attention has been given to conditions at return—even to a country such as the DRC where allegations of serious human-rights violations against returned migrants have been reported for years.




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Exploring the Potential of the SGLT2 Inhibitor Dapagliflozin in Type 1 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Pilot Study

Robert R. Henry
Mar 1, 2015; 38:412-419
Evolving Tactics With Inhibition of Sodium-Glucose Cotransporters




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Empagliflozin as Add-On to Metformin in Patients With Type 2 Diabetes: A 24-Week, Randomized, Double-Blind, Placebo-Controlled Trial

Hans-Ulrich Häring
Jun 1, 2014; 37:1650-1659
Emerging Technologies and Therapeutics




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Efficacy and Safety of Cannabidiol and Tetrahydrocannabivarin on Glycemic and Lipid Parameters in Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Pilot Study

Khalid A. Jadoon
Oct 1, 2016; 39:1777-1786
Emerging Technologies and Therapeutics




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PIONEER 1: Randomized Clinical Trial of the Efficacy and Safety of Oral Semaglutide Monotherapy in Comparison With Placebo in Patients With Type 2 Diabetes

Vanita R. Aroda
Sep 1, 2019; 42:1724-1732
Emerging Therapies: Drugs and Regimens




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A Multinational, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Trial to Evaluate the Efficacy of Cyclical Topical Wound Oxygen (TWO2) Therapy in the Treatment of Chronic Diabetic Foot Ulcers: The TWO2 Study

OBJECTIVE

Topical oxygen has been used for the treatment of chronic wounds for more than 50 years. Its effectiveness remains disputed due to the limited number of robust high-quality investigations. The aim of this study was to assess the efficacy of multimodality cyclical pressure Topical Wound Oxygen (TWO2) home care therapy in healing refractory diabetic foot ulcers (DFUs) that had failed to heal with standard of care (SOC) alone.

RESEARCH DESIGN AND METHODS

Patients with diabetes and chronic DFUs were randomized (double-blind) to either active TWO2 therapy or sham control therapy—both in addition to optimal SOC. The primary outcome was the percentage of ulcers in each group achieving 100% healing at 12 weeks. A group sequential design was used for the study with three predetermined analyses and hard stopping rules once 73, 146, and ultimately 220 patients completed the 12-week treatment phase.

RESULTS

At the first analysis point, the active TWO2 arm was found to be superior to the sham arm, with a closure rate of 41.7% compared with 13.5%. This difference in outcome produced an odds ratio (OR) of 4.57 (97.8% CI 1.19, 17.57), P = 0.010. After adjustment for University of Texas Classification (UTC) ulcer grade, the OR increased to 6.00 (97.8% CI 1.44, 24.93), P = 0.004. Cox proportional hazards modeling, also after adjustment for UTC grade, demonstrated >4.5 times the likelihood to heal DFUs over 12 weeks compared with the sham arm with a hazard ratio of 4.66 (97.8% CI 1.36, 15.98), P = 0.004. At 12 months postenrollment, 56% of active arm ulcers were closed compared with 27% of the sham arm ulcers (P = 0.013).

CONCLUSIONS

This sham-controlled, double-blind randomized controlled trial demonstrates that, at both 12 weeks and 12 months, adjunctive cyclical pressurized TWO2 therapy was superior in healing chronic DFUs compared with optimal SOC alone.




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ACE and Type 2 Diabetes Risk: A Mendelian Randomization Study

OBJECTIVE

To determine whether ACE inhibitors reduce the risk of type 2 diabetes using a Mendelian randomization (MR) approach.

RESEARCH DESIGN AND METHODS

A two-sample MR analysis included 17 independent genetic variants associated with ACE serum concentration in 4,147 participants from the Outcome Reduction with Initial Glargine INtervention (ORIGIN) (clinical trial reg. no. NCT00069784) trial, and their effects on type 2 diabetes risk were estimated from 18 studies of the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium. A genetic risk score (GRS) underpinning lower ACE concentration was then tested for association with type 2 diabetes prevalence in 341,872 participants, including 16,320 with type 2 diabetes, from the UK Biobank. MR estimates were compared after standardization for blood pressure change, with the estimate obtained from a randomized controlled trial (RCT) meta-analysis of ACE inhibitors versus placebo (n = 31,200).

RESULTS

Genetically lower ACE concentrations were associated with a lower risk of type 2 diabetes (odds ratio [OR] per SD 0.92 [95% CI 0.89–0.95]; P = 1.79 x 10–7). This result was replicated in the UK Biobank (OR per SD 0.97 [0.96–0.99]; P = 8.73 x 10–4). After standardization, the ACE GRS was associated with a larger decrease in type 2 diabetes risk per 2.4-mmHg lower mean arterial pressure (MAP) compared with that obtained from an RCT meta-analysis (OR per 2.4-mmHg lower MAP 0.19 [0.07–0.51] vs. 0.76 [0.60–0.97], respectively; P = 0.007 for difference).

CONCLUSIONS

These results support the causal protective effect of ACE inhibitors on type 2 diabetes risk and may guide therapeutic decision making in clinical practice.




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Amid an Unfolding Humanitarian Crisis in Syria, the European Union Faces the Perils of Devolving Migration Management to Turkey

The high-stakes gambit taken by Turkish President Recep Tayyip Erdoğan to allow tens of thousands of asylum seekers and migrants free movement to the Greek border demonstrated the fragility of the EU-Turkey deal and the European Union's broader approach to outsource migration management to third countries. This article examines the causes for the tensions, the EU approach to external partnerships, and a hardening European attitude towards unwanted arrivals.




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As the United States Resettles Fewer Refugees, Some Countries and Religions Face Bigger Hits than Others

Even as refugee admissions have dropped sharply during the Trump administration, some countries and religions have been significantly more affected than others, as this commentary explores. In fiscal year 2019, 79 percent of refugees were Christian and 16 percent Muslim—as compared to 44 percent Christian and 46 percent Muslim in fiscal year 2016, which was the last full year of the Obama administration.




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“Cubicle Activism”: Companies Face Growing Demands from Workers to Cut Ties with ICE and Others in Immigration Arena

From online petitions to organized walkouts, corporate America is facing increasing employee activism over its business involvement with agencies implementing the federal government's immigration policies. This "cubicle activism," seen at companies ranging from Amazon and Google to Bank of America and Wayfair, has garnered mixed success to date, forcing divestiture from private prison contractors but fewer results in other contexts, as this article explores.




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FDA approves combination ibuprofen-acetaminophen drug for U.S.

The Food and Drug Administration has approved the first over-the-counter ibuprofen and acetaminophen combination drug for the U.S.




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Wisconsin faces wave of anti-fluoridation efforts

The ADA and the Wisconsin Dental Association are partnering up with other fluoridated water proponents to address February anti-fluoridation movements in three Wisconsin municipalities: Lake Delton, Berlin and Hayward.




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JADA’s new CSA Corner highlights ACE Panel survey results on HPV vaccine

Dentists’ comfort levels and perceived roles in discussing and administering the human papillomavirus vaccine appear to vary, according to the results of an American Dental Association Clinical Evaluators Panel survey published in The Journal of the American Dental Association.




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Study: ACE inhibitors, ARBs don't increase risk for COVID-19

Certain high blood pressure medications may be linked with more serious illness from COVID-19, but they don't increase a person's risk for getting the disease, a new study published Tuesday by JAMA Cardiology reports.




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Face-aging app increases sunscreen use among teens by 50%, study finds

A face-aging app could encourage young people to protect their skin from harmful UV rays and lessen their risk for skin cancer, a study published Wednesday by JAMA Dermatology has found.




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Dapagliflozin Versus Placebo on Left Ventricular Remodeling in Patients With Diabetes and Heart Failure: The REFORM Trial

OBJECTIVE

To determine the effects of dapagliflozin in patients with heart failure (HF) and type 2 diabetes mellitus (T2DM) on left ventricular (LV) remodeling using cardiac MRI.

RESEARCH DESIGN AND METHODS

We randomized 56 patients with T2DM and HF with LV systolic dysfunction to dapagliflozin 10 mg daily or placebo for 1 year, on top of usual therapy. The primary end point was difference in LV end-systolic volume (LVESV) using cardiac MRI. Key secondary end points included other measures of LV remodeling and clinical and biochemical parameters.

RESULTS

In our cohort, dapagliflozin had no effect on LVESV or any other parameter of LV remodeling. However, it reduced diastolic blood pressure and loop diuretic requirements while increasing hemoglobin, hematocrit, and ketone bodies. There was a trend toward lower weight.

CONCLUSIONS

We were unable to determine with certainty whether dapagliflozin in patients with T2DM and HF had any effect on LV remodeling. Whether the benefits of dapagliflozin in HF are due to remodeling or other mechanisms remains unknown.




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Stay connected with School Psychologist Files by joining the School Psychologist Files Facebook Page.  You can be one of the first to know about new articles on the School Psychologist Files website such as the brand new FAQ Parents ask about the IEP that I finished this weekend. 




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Honey bees face chronic paralysis pandemic in Britain

The virus responsible for chronic bee paralysis is spreading rapidly among honey bee colonies in Britain, according to a new study.




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NASA lengthens SpaceX's first crewed mission to International Space Station

The duration of SpaceX's first mission with astronauts on board -- planned for launch at 4:32 p.m. EDT on May 27 from Florida -- has been extended from a few days to potentially weeks aboard the space station.




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Facebook site unveils a new look

Facebook launched its new site Friday, offering users a less cluttered desktop appearance, darker colors and lower brightness.




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'RuPaul's Drag Race' announces 'All Stars 5' cast

'RuPaul's Drag Race' announced the 10 competitors from previous seasons who will get another chance in the fifth 'All Stars' season, premiering June 5 on VH1.




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Famous birthdays for May 9: Ghostface Killah, Noah Centineo

Rapper Ghostface Killah turns 50 and actor Noah Centineo 24, among the famous birthdays for May 9.




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[ Politics ] Open Question : Why hasn't there ever been a great Democrat presidents' face on Mount Rushmore?

Maybe because there's never been a great Democrat president?  And never will be.  They're all horrible.




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A Race Against the Clock: Meeting Seasonal Labor Needs in the Age of COVID-19

As governments have reacted to the coronavirus pandemic by closing borders, seasonal workers have been kept out, raising a pressing question: who is going to produce the food amid agricultural labor shortages? Policymakers in the Asia Pacific, Europe, and North America have responded by seeking to recruit residents, lengthen stays for already present seasonal workers, and find ways to continue admitting foreign seasonal labor, as this commentary explores.




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Embrace the Ultimate Unknown

 The best way to have a good death is to live a good life

-- Read more on ScientificAmerican.com




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In Today's Rat Race, the Most Overworked Win

For years, economists have taught their students a simple maxim: As employers hunt for workers, they want to get the best talent at the lowest price.




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Why Torture Keeps Pace With Enlightenment

In the year 65, the Roman emperor Nero discovered that a group of nobles had hatched a conspiracy to kill him. The tyrant captured the suspects one by one and threatened them with torture; most confessed and implicated others. One of the conspirators, Epicharis, was publicly tortured -- her bones...