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Improving Diabetes Care in the Hospital Using Guideline-Directed Orders

Stephen F. Quevedo
Oct 1, 2001; 14:
Feature Articles




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Dancers' Paradise: Devon Unruly working hard to expand dance group

He's celebrating 10 years of dancing both competitively and in the street, and the co-founder of Unruly Skankaz, Devon Brown, says he is looking to expand the brand. The once three-member male dance group has grown to five, he told THE WEEKEND...




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Beyond CARES: Economist Glenn Hubbard on Government Response to COVID-19

Hubbard asks: Can we design a more effective plan, in case of a next time?




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China and the International Order

Invitation Only Research Event

21 November 2018 - 12:30pm to 2:00pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Harriet Moynihan, Associate Fellow, International Law Programme, Chatham House
Dr Champa Patel, Head, Asia-Pacific Programme, Chatham House
Chair: Rod Wye, Associate Fellow, Asia-Pacific Programme, Chatham House

In 2014, the Chinese government announced its intention to strengthen China's discourse power and influence in international legal affairs. Since then, the International Law Programme and Asia-Pacific Programmes at Chatham House have been evaluating the increasing emphasis on international law in China's global governance agenda. Our research includes the hosting of roundtables with a global network of international lawyers including leading Chinese academics.

This meeting will discuss insights emerging from two recent roundtables held in Beijing(opens in new window) and New York in 2018. The Beijing roundtable focussed on China’s approach to emerging areas of international law, including the law applicable to cyber operations, the Arctic, dispute settlement and business and human rights. The New York roundtable discussed the international law relating to peace and security including use of force, sanctions, international humanitarian law applicable to peacekeepers, international criminal law including the crime of aggression and human rights, peace and security.

Harriet Moynihan will discuss China's ambitions to play a more influential role in shaping international law drawing on findings from both roundtables. The meeting will also consider how China's ambitions for the international order fit within China's foreign and domestic policy agenda and changes to global governance generally.

Attendance at this event is by invitation only. 

Chanu Peiris

Programme Manager, International Law
+44 (0)20 7314 3686




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Dorothy Gordon

Associate Fellow, International Security Programme and Global Economy and Finance Programme

Biography

Dorothy was the founding director general of the Ghana-India Kofi Annan Centre of Excellence in ICT, a position which she held for over a decade.

She works globally as a policy adviser, evaluator, project manager and organizational management consultant.

Over the course of her 30-year career in international development and technology she has held management positions with the UN and global management consulting firms on four continents.

As a strong advocate of the importance of building robust local innovation ecosystems based on open source technologies, she serves on the board and as a mentor to a number of start-ups and NGOs focused on women in tech.




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Cyber Governance in the Commonwealth: Towards Stability and Responsible State Behaviour in Cyberspace

Invitation Only Research Event

7 October 2019 - 10:30am to 5:30pm

Addis Ababa, Ethiopia

This roundtable is part of a series under the project, 'Implementing the Commonwealth Cybersecurity Agenda', funded by the UK Foreign and Commonwealth Office (FCO). The roundtable aims to provide a multi-stakeholder, pan-Commonwealth platform to discuss how to implement the Commonwealth Cyber Declaration with a focus on its third pillar 'To promote stability in cyberspace through international cooperation'.

In particular, the roundtable focuses on points 3 and 4 of the third pillar which revolve around the commitment to promote frameworks for stability in cyberspace including the applicability of international law, agreed voluntary norms of responsible state behaviour and the development and implementation of confidence-building measures consistent with the 2015 report of the UNGGE. 

The workshop also focuses on the commitment to advance discussions on how existing international law, including the Charter of the United Nations and applicable international humanitarian law, applies in cyberspace.

The roundtable addresses the issue of global cyber governance from a Commonwealth perspective and will also include a discussion around the way forward, the needed capacity of the different Commonwealth countries and the cooperation between its members for better cyber governance.

Participants include UNGGE members from Commonwealth countries in addition to representatives to the UN Open-Ended Working Group from African countries as well as members from academia, civil society and industry.

Calum Inverarity

Research Analyst and Coordinator, International Security Department
+44 (0) 207 957 5751




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The Commonwealth Cyber Declaration: Achievements and Way Forward

Invitation Only Research Event

4 February 2020 - 9:15am to 5:30pm

Chatham House, London

In April 2018, the Commonwealth Heads of Government Meeting (CHOGM), held in London, saw the creation and the adoption of the Commonwealth Cyber Declaration. The declaration outlines the framework for a concerted effort to advance cybersecurity practices to promote a safe and prosperous cyberspace for Commonwealth citizens, businesses and societies. 

The conference will aim to provide an overview on the progress made on cybersecurity in the Commonwealth since the declaration was announced in 2018. In addition, it will examine future challenges and potential solutions going forward.

This conference is part of the International Security Programme's project on Implementing the Commonwealth Cybersecurity Agenda and will convene a range of senior Commonwealth representatives as well as a selection of civil society and industry stakeholders. This project aims to develop a pan-Commonwealth platform to take the Commonwealth Cyber Declaration forward by means of a holistic, inclusive and representative approach.

Please see below meeting summaries from previous events on Cybersecurity in the Commonwealth:  

Attendance at this event is by invitation only. 

Esther Naylor

Research Assistant, International Security Programme
+44 (0)20 7314 3628




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POSTPONED: Working Towards Cyber Resilience in the GCC: Opportunities and Challenges

Invitation Only Research Event

12 March 2020 - 9:00am to 5:00pm

Muscat, Oman

The GCC states have invested significantly in cybersecurity and have made large strides in protecting governments, businesses and individuals from cyber threats, with the aim of delivering on their ambitious national strategies and future visions. However, several challenges to cybersecurity and cyber resilience in the region persist, putting those ambitious plans at risk.

These challenges include the uneven nature of cybersecurity protections, the incomplete implementation of cybersecurity strategies and regulations, and the issues around international cooperation. Such challenges mean that GCC states need to focus on the more difficult task of cyber resilience, in addition to the simpler initial stages of cybersecurity capacity-building, to ensure they harness the true potential of digital technologies and mitigate associated threats.

Set against this background, this workshop will explore opportunities and challenges to cyber resilience in the GCC focusing on four main pillars:

1. Cyber resilience: in concept and in practice
2. Building an effective cybersecurity capacity
3. The potential of regional and international cooperation to cyber resilience
4. Deterrence and disruption: different approaches

This event will be held in collaboration with the Arab Regional Cybersecurity Centre (ARCC) and OMAN CERT.

PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE. 

Event attributes

Chatham House Rule

Esther Naylor

Research Assistant, International Security Programme
+44 (0)20 7314 3628




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Local Pathways Towards De-escalation of Libya's Conflict

Invitation Only Research Event

28 January 2020 - 3:00pm to 4:30pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Usama Otman Essed, Libya Center for Strategic & Future Studies
Chair: Tim Eaton, Middle East and North Africa Programme, Chatham House

A shaky truce remains broadly in place among rival Libyan forces fighting for control of Tripoli. However, a durable ceasefire to bring an end to the current bout of conflict, which was initiated by Khalifa Haftar’s Libyan Arab Armed Forces’ (LAAF) offensive on the capital in April 2019, has not been reached. In recent weeks attention has focused on talks hosted in Moscow and Berlin, with the former aimed at agreeing a ceasefire and the latter seeking to reach agreement among international actors to bring an end to external military support for Libyan warring actors, and to craft a way forward for future intra-Libyan talks. Yet, there has been little emphasis on Libyan actors – beyond Haftar and prime minister Fayez al-Serraj – in this process.
 
This roundtable will bring together experts and policymakers to discuss means of de-escalating the conflict and seeking a lasting resolution through the development of interconnected intra-Libyan social and security negotiation tracks. Mr Usama Otman Essed of the Libya Center for Strategic and Future Studies (LCSFS) will present his research group’s ideas on these issues and discuss their ongoing efforts to promote dialogue among social and security actors.

Attendance at this event is by invitation only. 

Event attributes

Chatham House Rule

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
+44 (0)20 7314 3624




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Prospects for Reforming Libya’s Economic Governance: Ways Forward

Invitation Only Research Event

6 February 2020 - 10:30am to 12:30pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Jason Pack, Non-Resident Fellow, Middle East Institute
Tim Eaton, Senior Research Fellow, Middle East and North Africa Programme, Chatham House
Chair: Elham Saudi, Director, Lawyers for Justice Libya

There is a broad consensus that Libya’s rentier, patronage-based system of governance is a driver, and not only a symptom, of Libya’s continuing conflict. The dysfunction of Libya’s economic system of governance has been exacerbated by the governance split that has prevailed since 2014 whereby rival administrations of state institutions have emerged. Despite these challenges, a system of economic interdependence, whereby forces aligned with Field Marshal Haftar control much of the oil and gas infrastructure and the UN-backed Government of National Accord controls the means of financial distribution, has largely prevailed. Yet, at the time of writing, this is under threat: a damaging oil blockade is being implemented by forces aligned with Haftar and those state institutions that do function on a national basis are finding it increasingly difficult to avoid being dragged into the conflict.

This roundtable will bring together analysts and policymakers to discuss these dynamics and look at possible remedies. Jason Pack, non-resident fellow at the Middle East Institute, will present the findings of his latest paper on the issue which recommends the formation of 'a Libyan-requested and Libyan-led International Financial Commission vested with the requisite authorities to completely restructure the economy.' Tim Eaton, who has been leading Chatham House’s work on Libya’s conflict economy, supporting UNSMIL’s efforts in this field, will act as respondent.

Attendance at this event is by invitation only. 

Event attributes

Chatham House Rule




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Why is it So Hard for Iraq to Form A Government?

25 April 2020

Dr Renad Mansour

Senior Research Fellow, Middle East and North Africa Programme; Project Director, Iraq Initiative
Mustafa al-Kadhimi has emerged as the compromise prime minister designate, but his potential appointment is built on shaky foundations.

2020-04-25-Iraq-Security-COVID

A member of Iraqi security forces stands guard behind a yellow line after the government declared curfew due to coronavirus. Photo by Fariq Faraj Mahmood/Anadolu Agency via Getty Images.

On April 9, Iraqi President Barham Salih gathered the Shia, Kurdish and Sunni political blocs at the presidential palace to task head of intelligence Mustafa al-Kadhimi with forming a government.

Kadhimi is the third prime minister-designate assigned since Prime Minister Adil abd al-Mehdi resigned in November, in the wake of mass protests against government corruption and the country’s ethno-sectarian based political system.

Kadhimi’s two predecessors, Muhammad Tawfiq Allawi and Adnan al-Zurfi, both failed to form a government. This third attempt came as Iraq struggles with repeated crises since October 2019, when the government began responding with deadly force to large-scale mass protests, killing more than 600 and injuring tens of thousands.

In January, the assassination of Qasem Soleimani escalated tensions between the United States and Iran, with Iraq stuck in the middle and becoming the home for regular tit-for-tat attacks. The Islamic State — never completely defeated — took advantage of these crises and increased its attacks in disputed territories.

The outbreak of COVID-19 challenges the country’s fragile public health sector, while the decline in the price of oil will make it harder for leaders to pay the public salaries that keep the system (and patronage) moving.

What does the delay in forming a government amid multiple crises mean for the post-2003 Iraqi political system?

Iraq’s post-2003 political system is designed to withstand crisis. Over the years, political parties reflecting the country’s ethnic and sectarian divides have had a tacit understanding that crises represent a risk to their collective interests. These elite stakeholders have together weathered civil war, insurgency and multiple protests — despite deep conflicts with one another.

For instance, in September 2018 protesters attacked most major political party headquarters and the Iranian consulate in Basra, and authorities killed some 20 protesters.

Since the May election of that year, the fragmented Shia elite had been unable to even declare which side has the largest parliamentary bloc, let alone decide on a government.

But after the September crisis, the previously gridlocked parties swiftly came together to form an “understanding” that pushed through the impasse leading to the Mehdi government. In 2020, however, Iraq’s political parties were slower to come back together despite the multiple crises — far greater than 2018. The system is less able to swiftly fix itself, based primarily on the fragmentation of the elite — and their determination to prevent any challenge to their rule.

Why did the two prior attempts fail?

The two previous prime minister-designates each fell short for different reasons. When I met Allawi in February at the prime minister’s guesthouse in Baghdad, he was very clearly convinced that his mandate was to sideline the parties.

He hoped that simply choosing technocratic ministers outside the elite pact, with the support of Moqtada al-Sadr behind him, would garner support from protesters and the disillusioned public. He failed, however, because his cabinet had to go through parliament and the parties rejected what they saw a threat to the elite pact and the system.

Zurfi similarly failed after being directly appointed in March by Salih after the Shia parties failed to come up with a candidate. From the beginning, then, Zurfi faced challenges because parties were not in agreement. He attempted to directly confront his opposition, and spoke out against Iranian influence in Iraq. As a result, Zurfi was unable to even get to parliament with his proposed cabinet, as the Shia parties got back together to bring him down.

The failure of both strategies — Allawi attempting to work outside the elite party system and Zurfi trying to target certain parties — reveals tensions in Iraq’s political system. This fragmentation strains the parties’ ability to swiftly unite, and the system’s ability to withstand crises.

The endemic problems are a consequence of fragmentation, including the failure following the 2018 elections to declare governing parliamentary bloc. Moreover, after that election, newcomers into the political system (two-thirds of the MPs are serving their first term) are increasingly making their own demands and less willing to blindly toe party lines.

Can Kadhimi overcome the impasse?

Kadhimi’s appointment as prime minister-designate nonetheless is on shaky foundations. His appointment had previously faced a veto from Iran and its allied groups which make up the Fateh bloc. Kataeb Hezbollah, an armed group close to Iran and linked to the Popular Mobilization Units, issued a statement accusing Kadhimi with blood on his hands for the deaths of Soleimani and Abu Mahdi al-Muhandis.

Many Fateh bloc members had for months vetoed Kadhimi’s name due to this allegation. Immediately before Kadhimi addressed the nation for the first time, Iraqi state television broadcast a prerecorded statement by PMU (and Fateh) leader Qais al-Khazali, who had also previously accused Kadhimi of spying for the Americans and being complicit in the two killings.

Khazali, who commands the second-largest party within Fateh, accepted the party line to back Kadhimi but came out with his own conditions on television. However, the concerns about the COVID-19 crisis and the collapse of the price of oil finally brought all sides to compromise — a design of the political system.

Kadhimi has signalled he will play by the old rules with these stakeholders. Because of the magnitude of these simultaneous crises, Iraqi politics is moving back to the post-2003 norm. The ethno-sectarian based political system is geared to weather such existential crises more than it is to handling day-to-day governance. Despite the notion of “post-sectarianism” in Iraq, this system is based on ethno-sectarian political party compromise.

In his television address, Khazali, who had previously attempted to move away from sectarian language, explained that the process of selecting a prime minister is reserved to the Shia, who have the right as the majority, and not to Salih, a Kurd.

Over the years Kadhimi has expressed an admiration of the bravery of the protesters and of the importance of civil society. Many Iraqi civil society activists owe their lives to the work of the former intelligence chief. However, he has also been part of the same system that has violently suppressed protesters.

As the compromise prime minister-designate, he will find it difficult to transform his country as long as he plays by the rules of post-2003 Iraq — an irony not lost on the protesters who immediately rejected the candidacy of a man whom until recently many protesters had supported.

This article was originally published in The Washington Post




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11C-Methionine PET Identifies Astroglia Involvement in Heart-Brain Inflammation Networking after Acute Myocardial Infarction

Acute myocardial infarction (MI) triggers a local and systemic inflammatory response. We recently showed microglia involvement using TSPO imaging. Here, we evaluate whether 11C-methionine provides further insights into heart-brain inflammation networking. Methods: Male Bl6N mice underwent permanent coronary artery ligation followed by 11C-methionine PET at 3 and 7 days (n = 3). In subgroups, leukocyte homing was blocked by integrin antibodies (n = 5). The cellular substrate for PET signal was identified using brain section immunostaining. Results: 11C-methionine uptake peaked in the MI region at d3 (5.9±0.9vs 2.4±0.5 %ID/cc), decreasing to control level by d7 (4.3±0.6 %ID/cc). Brain uptake was proportional to cardiac uptake (r=0.47,p<0.05), peaking also at d3 (2.9±0.4vs 2.4±0.3 %ID/cc) and returning to baseline at d7 (2.3±0.4 %ID/cc). Integrin blockade reduced uptake at every time point. Immunostaining at d3 revealed co-localization of the L-type amino acid transporter with GFAP-positive astrocytes but not CD68-positive microglia. Conclusion: PET imaging with 11C-methionine specifically identifies an astrocyte component, enabling further dissection of the heart-brain axis in post MI inflammation.




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Targeted optical imaging of the glucagon-like peptide 1 receptor using exendin-4-IRDye800CW

Rationale: The treatment of choice for insulinomas and focal lesions in congenital hyperinsulinism (CHI) is surgery. However, intra-operative detection can be challenging. This could be overcome with intra-operative fluorescence imaging, which provides real-time lesion detection with a high spatial resolution. Here, a novel method for targeted near-infrared (NIR) fluorescence imaging of glucagon-like peptide 1 receptor (GLP-1R) positive lesions, using the GLP-1 agonist exendin-4, labeled with IRDye800CW, was examined in vitro and in vivo. Methods: A competitive binding assay was performed using Chinese hamster lung (CHL) cells transfected with the GLP-1R. Tracer biodistribution was determined in BALB/c nude mice bearing subcutaneous CHL-GLP-1R xenografts. In vivo NIR fluorescence imaging of CHL-GLP-1R xenografts was performed. Localization of the tracer in the pancreatic islets of BALB/c nude mice was examined using fluorescence microscopy. Laparoscopic imaging was performed to detect the fluorescent signal of the tracer in the pancreas of mini pigs. Results: Exendin-4-IRDye800CW binds the GLP-1R with an IC50 value of 3.96 nM. The tracer accumulates in CHL-GLP-1R xenografts. Subcutaneous CHL-GLP-1R xenografts were visualized using in vivo NIR fluorescence imaging. The tracer accumulates specifically in the pancreatic islets of mice and a clear fluorescent signal was detected in the pancreas of mini pigs. Conclusion: These date provide the first in vivo evidence of the feasibility of targeted fluorescence imaging of GLP-1R positive lesions. Intra-operative lesion delineation using exendin-4-IRDye800CW could benefit open as well as laparoscopic surgical procedures for removal of insulinomas and focal lesions in CHI.




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Light-induced radiosynthesis of 89ZrDFO-azepin-onartuzumab for imaging the hepatocyte growth factor receptor

Methods that provide rapid access to radiolabeled antibodies are vital in the development of diagnostic and radiotherapeutic agents for positron emission tomography (PET) or radioimmunotherapy. The human hepatocyte growth factor receptor (c-MET) signaling pathway is dysregulated in a number of malignancies including gastric cancer, and is an important biomarker in drug discovery. Here, we used a photoradiochemical approach to produce 89Zr-radiolabeled onartuzumab (a monovalent, anti-human c-MET antibody), starting directly from the fully formulated drug (MetMAb). Methods: Simultaneous 89Zr-radiolabeling and protein conjugation was performed in one-pot reactions containing 89Zr-oxalate, the photoactive chelate DFO-aryl azide (DFO-ArN3) and MetMAb to give 89ZrDFO-azepin-onartuzumab. As a control, 89ZrDFO-Bn-NCS-onartuzumab was prepared via a conventional two-step process using pre-purified onartuzumab and DFO-Bn-NCS. Radiotracers were purified by using size-exclusion methods and evaluated by radiochromatography. Radiochemical stability was studied in human serum and immunoreactivity was determined by cellular binding assays using MKN-45 gastric carcinoma cells. PET imaging at multiple time points (0–72 h) was performed in female athymic nude mice bearing subcutaneous MKN-45 xenografts. Biodistribution experiments were performed after the final image. Tumor specificity of 89ZrDFO-azepin-onartuzumab was assessed by competitive inhibition (blocking) studies. Results: Initial photoradiosynthesis experiments produced 89ZrDFO-azepin-onartuzumab in <15 min. with an isolated decay-corrected radiochemical yield (RCY) of 24.8%, a radiochemical purity (RCP) ~90% and a molar activity (Am) of ~1.5 MBq nmol-1. Reaction optimization improved the radiochemical conversion (RCC) of 89ZrDFO-azepin-onartuzumab to 56.9±4.1% (n = 3), with isolated RCYs of 41.2±10.6% (n = 3), and RCPs >90%. Conventional methods produced 89ZrDFO-Bn-NCS-onartuzumab with isolated RCY >97%, RCP >97% and Am ~14.0 MBq nmol-1. Both radiotracers were immunoreactive and stable in human serum. PET imaging and biodistribution studies showed high tumor uptake for both radiotracers. By 72 h, tumor and liver uptake reached 15.37±5.21 %ID g-1, 6.56±4.03 %ID g-1, respectively for 89ZrDFO-azepin-onartuzumab (n = 4), and 21.38±11.57 %ID g-1 and 18.84±6.03 %ID g-1 for 89ZrDFO-Bn-NCS-onartuzumab (n = 4). Blocking experiments gave a statistically significant reduction in tumor uptake (6.34±0.47 %ID g-1) of 89ZrDFO-azepin-onartuzumab (n = 4). Conclusion: Experiments demonstrate that photoradiosynthesis is a viable alternative approach for producing 89Zr-radiolabeled antibodies direct in protein formulation buffer which reduces protein aggregation and liver uptake.




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Immune checkpoint imaging in oncology - a game changer towards personalized immunotherapy?

Immune checkpoint blockade represents a promising approach in oncology, showing anti-tumor activities in various cancers. However, although being generally far more well-tolerated than classical cytotoxic chemotherapy, this treatment, too, may be accompanied by considerable side effects and not all patients benefit equally. Therefore, careful patient selection and monitoring of the treatment response is mandatory. At present, checkpoint-specific molecular imaging is increasingly investigated as a tool for patient selection and response evaluation. Here, an overview of the current developments in immune checkpoint imaging is provided.




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18F-FDG PET/CT in the Diagnostic and Treatment Evaluation of Pediatric Post-transplant Lymphoproliferative Disorders

We aimed to evaluate the diagnostic performance of 18F-FDG PET/CT for the detection of post-transplantation lymphoproliferative disorder (PTLD) in a pediatric population and explore its feasibility during response assessment. Methods: This retrospective study included 28 pediatric transplant recipients who underwent a total of 32 18F-FDG PET/CT scans due to clinical suspicion of PTLD within an 8-year period. Pathology reports and 2-year follow-up were used as reference standard. Twenty-one response assessment 18F-FDG PET/CT scans were re-evaluated according to the Lugano criteria. Results: The diagnosis of PTLD was established in 14 patients (49%). Sensitivity, specificity, positive predictive value, and negative predictive value of 18F-FDG PET/CT for the detection of PTLD in children with a clinical suspicion of this disease, was 50% (7/14), 100% (18/18), 100% (7/7), and 72% (18/25), respectively. False-negative results occurred in patients with PTLD in the Waldeyer’s ring, cervical lymph nodes or small bowel with either non-destructive or polymorphic PTLD. Two of 5 interim 18F-FDG PET/CT scans and 3 of 9 end-of-treatment 18F-FDG PET/CT scans were false-positive. Conclusion: 18F-FDG PET/CT had good specificity and positive predictive value but low to moderate sensitivity and negative predictive value for the detection of PTLD in a 28 pediatric patient cohort with a clinical suspicion of this disease. False-negative results were confirmed in the Waldeyer’s ring, cervical lymph nodes and small bowel with either non-destructive or polymorphic PTLD subtypes. 18F-FDG PET/CT appears to have a limited role in the response assessment setting of pediatric PTLD, given the observed high proportions of false-positives both at interim and end-of-treatment evaluations.




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PSMA PET/CT and standard plus PET/CT-Ultrasound fusion targeted prostate biopsy can diagnose clinically significant prostate cancer in men with previous negative biopsies

The purpose of this study was to investigate the feasibility and diagnostic efficacy of 68Ga-PSMA positron emission tomography/computed tomography (PET/CT) combined with PET-ultrasound image-guided biopsy in the diagnosis of prostate cancer. Methods: A total of 31 patients with previously negative prostate biopsy, but persistent elevated serum prostate specific antigen (PSA), were imaged with a 68Ga-labeled prostate-specific membrane antigen (PSMA) PET/CT ligand prior to undergoing repeat prostate biopsy. Based on the proposed PROMISE criteria, PSMA PET/CT results were interpreted as negative (miPSMA-ES 0-1) or positive (miPSMA-ES 2-3). All patients underwent standard template systematic biopsy with up to four additional PSMA PET-ultrasound fusion image-guided biopsy cores. The sensitivity, specificity, positive and negative predictive values, and accuracy of PSMA PET/CT were determined. In addition, the correlation between miPSMA-ES and detection rate of prostate cancer was also analyzed. Univariate logistic regression models were established using PSMA PET/CT semi-quantitative analysis parameters to predict the outcome of repeat prostate biopsy. Results: The median age of patients was 65 years (range 53-81), and the median PSA level was 18.0 ng/ml (range 5.48-49.77 ng/ml). Prostate cancer was detected in 15/31 patients (48.4%) and 12/31 patients (38.7%) had clinically significant disease. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 68Ga-PSMA PET/CT in the diagnosis of clinically significant prostate cancer were 100.0%, 68.4%, 66.7%, 100.0% and 80.6%, respectively. The detection rate of prostate cancer increased with the increase of miPSMA-ES score. The detection rate of clinically significant prostate cancer in miPSMA-ES 0-1, 2 and 3 groups were 0%, 54.5% and 85.7% respectively. Semi-quantitative analysis of 68Ga-PSMA PET/CT images showed that predictive models based on maximum standardized uptake value (SUVmax), tumor-to-background normal prostate SUV (SUVT/BGp) and tumor-to-background normal liver SUV (SUVratio) could effectively predict clinically significant prostate cancer; area under the curves were 0.930, 0.877, and 0.956, respectively. Conclusion: This study preliminarily confirmed that 68Ga-PSMA PET/CT imaging combined with PET-ultrasound fusion image-guided prostate biopsy can effectively detect clinically significant prostate cancer. Prebiopsy 68Ga-PSMA PET/CT has predictive value for clinically significant cancer in the studied patient population.




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18F-DCFPyL PET/CT in Patients with Subclinical Recurrence of Prostate Cancer: Effect of Lesion Size, Smooth Filter and Partial Volume Correction on Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) criteria

Purpose: To determine the effect of smooth filter and partial volume correction (PVC) method on measured prostate-specific membrane antigen (PSMA) activity in small metastatic lesions and to determine the impact of these changes on the molecular imaging (mi) PSMA scoring. Materials & Methods: Men with biochemical recurrence of prostate cancer with negative CT and bone scintigraphy were referred for 18F-DCFPyL PET/CT. Examinations were performed on one of 2 PET/CT scanners (GE Discovery 610 or Siemens mCT40). All suspected tumor sites were manually contoured on co-registered CT and PET images, and each was assigned a miPSMA score as per the PROMISE criteria. The PVC factors were calculated for every lesion using the anatomical CT and then applied to the unsmoothed PET images. The miPSMA scores, with and without the corrections, were compared, and a simplified "rule of thumb" (RoT) correction factor (CF) was derived for lesions at various sizes (<4mm, 4-7mm, 7-9mm, 9-12mm). This was then applied to the original dataset and miPSMA scores obtained using the RoT CF were compared to those found using the actual corrections. Results: There were 75 men (median age, 69 years; median serum PSA of 3.69 ug/L) with 232 metastatic nodes < 12 mm in diameter (mean lesion volume of 313.5 ± 309.6 mm3). Mean SUVmax before and after correction was 11.0 ± 9.3 and 28.5 ± 22.8, respectively (p<0.00001). The mean CF for lesions <4mm (n = 22), 4-7mm (n = 140), 7-9mm (n = 50), 9-12 mm (n = 20) was 4 (range: 2.5-6.4), 2.8 (range: 1.6-4.9), 2.3 (range: 1.6-3.3) and 1.8 (range 1.4-2.4), respectively. Overall miPSMA scores were concordant between the corrected dataset and RoT in 205/232 lesions (88.4%). Conclusion: There is a significant effect of smooth filter and partial volume correction on measured PSMA activity in small nodal metastases, impacting the miPSMA score.




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Moving towards multicenter therapeutic trials in ALS: feasibility of data pooling using different TSPO positron emission tomography (PET) radioligands.

Rationale: Neuroinflammation has been implicated in Amyotrophic Lateral Sclerosis (ALS) and can be visualized using translocator protein (TSPO) radioligands. To become a reliable pharmacodynamic biomarker for ALS multicenter trials, some challenges have to be overcome. We aimed to investigate whether multicenter data pooling of different TSPO tracers (11C-PBR28 and 18F-DPA714) is feasible, after validation of an established 11C-PBR28 PET pseudoreference analysis technique for 18F-DPA714. Methods: 7 ALS-Belgium (58.9±6.7 years,5M) and 8 HV-Belgium (52.1±15.2 years,3M); and 7 ALS-US (53.4±9.8 years,5M) and 7 HV-US (54.6±9.6 years,4M) from a previously published study (1) underwent dynamic 18F-DPA714 (Leuven, Belgium) or 11C-PBR28 (Boston, US) PET-MR scans. For 18F-DPA714, volume of distribution (VT) maps were compared to standardized uptake value ratios (SUVR)40-60 calculated using the pseudoreference regions (1)cerebellum, (2)occipital cortex, and (3)whole brain without ventricles (WB-ventricles). Also for 11C-PBR28, SUVR60-90 using WB-ventricles were calculated. Results: In line with previous studies, increased 18F-DPA714 uptake (17.0±5.6%) in primary motor cortices was observed in ALS, as measured by both VT and SUVR40-60 approaches. Highest sensitivity was found for SUVRWB-ventricles (average cluster 21.6±0.1%). 18F-DPA714 VT ratio and SUVR40-60 results were highly correlated (r>0.8, p<0.001). A similar pattern of increased uptake (average cluster 20.5±0.5%) in primary motor cortices was observed in ALS with 11C-PBR28 using the SUVRWB-ventricles. Analysis of the 18F-DPA714 and 11C-PBR28 data together, resulted in a more extensive pattern of significant increased glial activation in the bilateral primary motor cortices. Conclusion: The same pseudoreference region analysis technique for 11C-PBR28 PET imaging can be extended towards 18F-DPA714 PET. Therefore, in ALS, standardized analysis across these two tracers enables pooling of TSPO PET data across multiple centers and increase power of TSPO as biomarker for future therapeutic trials.




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Folate Receptor {beta} Targeted PET Imaging of Macrophages in Autoimmune Myocarditis

Rationale: Currently available imaging techniques have limited specificity for the detection of active myocardial inflammation. Aluminum fluoride-18-labeled 1,4,7-triazacyclononane-N,N',N''-triacetic acid conjugated folate (18F-FOL) is a positron emission tomography (PET) tracer targeting folate receptor β (FR-β) that is expressed on activated macrophages at sites of inflammation. We evaluated 18F-FOL PET for the detection of myocardial inflammation in rats with autoimmune myocarditis and studied expression of FR-β in human cardiac sarcoidosis specimens. Methods: Myocarditis was induced by immunizing rats (n = 18) with porcine cardiac myosin in complete Freund’s adjuvant. Control rats (n = 6) were injected with Freund’s adjuvant alone. 18F-FOL was intravenously injected followed by imaging with a small animal PET/computed tomography (CT) scanner and autoradiography. Contrast-enhanced high-resolution CT or 2-deoxy-2-18F-fluoro-D-glucose (18F-FDG) PET images were used for co-registration. Rat tissue sections and myocardial autopsy samples of 6 patients with cardiac sarcoidosis were studied for macrophages and FR-β. Results: The myocardium of 10 out of 18 immunized rats showed focal macrophage-rich inflammatory lesions with FR-β expression occurring mainly in M1-polarized macrophages. PET images showed focal myocardial 18F-FOL uptake co-localizing with inflammatory lesions (SUVmean, 2.1 ± 1.1), whereas uptake in the remote myocardium of immunized rats and controls was low (SUVmean, 0.4 ± 0.2 and 0.4 ± 0.1, respectively; P < 0.01). Ex vivo autoradiography of tissue sections confirmed uptake of 18F-FOL in myocardial inflammatory lesions. Uptake of 18F-FOL to inflamed myocardium was efficiently blocked by a non-labeled FR-β ligand folate glucosamine in vivo. The myocardium of patients with cardiac sarcoidosis showed many FR-β-positive macrophages in inflammatory lesions. Conclusion: In a rat model of autoimmune myocarditis, 18F-FOL shows specific uptake in inflamed myocardium containing macrophages expressing FR-β, which were also present in human cardiac sarcoid lesions. Imaging of FR-β expression is a potential approach for the detection of active myocardial inflammation.




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PET imaging of phosphodiesterase-4 identifies affected dysplastic bone in McCune-Albright syndrome, a genetic mosaic disorder

McCune-Albright syndrome (MAS) is a mosaic disorder arising from gain-of-function mutations in the GNAS gene, which encodes the 3', 5'-cyclic adenosine monophosphate (cAMP) pathway-associated G-protein, Gsα. Clinical manifestations of MAS in a given individual, including fibrous dysplasia, are determined by the timing and location of the GNAS mutation during embryogenesis, the tissues involved, and the role of Gsα in the affected tissues. The Gsα mutation results in dysregulation of the cAMP signaling cascade, leading to upregulation of phosphodiesterase type 4 (PDE4), which catalyzes the hydrolysis of cAMP. Increased cAMP levels have been found in vitro in both animal models of fibrous dysplasia and in cultured cells from individuals with MAS, but not in humans with fibrous dysplasia. Positron emission tomography (PET) imaging of PDE4 with 11C-(R)-rolipram has been used successfully to study the in vivo activity of the cAMP cascade. To date, it remains unknown whether fibrous dysplasia and other symptoms of MAS, including neuropsychiatric impairments, are associated with increased PDE4 activity in humans. Methods: 11C-(R)-rolipram whole-body and brain PET scans were performed in six individuals with MAS (three for brain scans and six for whole-body scans) and nine healthy controls (seven for brain scans and six for whole-body scans). Results: 11C-(R)-rolipram binding correlated with known locations of fibrous dysplasia in the periphery of individuals with MAS; no uptake was observed in the bones of healthy controls. In peripheral organs and the brain, no difference in 11C-(R)-rolipram uptake was noted between participants with MAS and healthy controls. Conclusion: This study is the first to find evidence for increased cAMP activity in areas of fibrous dysplasia in vivo. No differences in brain uptake between MAS participants and controls were detected, which could be due to several reasons, including the limited anatomic resolution of PET. Nevertheless, the results confirm the usefulness of PET scans with 11C-(R)-rolipram to indirectly measure increased cAMP pathway activation in human disease.




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The Changing Face of Nuclear Cardiology: Guiding Cardiovascular Care towards Molecular Medicine

Radionuclide imaging of myocardial perfusion, function, and viability has been established for decades and remains a robust, evidence-based and broadly available means for clinical workup and therapeutic guidance in ischemic heart disease. Yet, powerful alternative modalities have emerged for this purpose, and their growth has resulted in increasing competition. But the potential of the tracer principle goes beyond the assessment of physiology and function, towards the interrogation of biology and molecular pathways. This is a unique selling point of radionuclide imaging, which has been under-recognized in cardiovascular medicine until recently. Now, molecular imaging methods for the detection of myocardial infiltration, device infection and cardiovascular inflammation are successfully gaining clinical acceptance. This is further strengthened by the symbiotic quest of cardiac imaging and therapy for an increasing implementation of molecular-targeted procedures, where specific therapeutic interventions require specific diagnostic guidance towards the most suitable candidates. This review will summarize the current advent of clinical cardiovascular molecular imaging and highlight its transformative contribution to the evolution of cardiovascular therapy beyond mechanical interventions and broad "blockbuster" medication, towards a future of novel, individualized molecular targeted and molecular imaging-guided therapies.




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Integrity of neurocognitive networks in dementing disorders as measured with simultaneous PET/fMRI

Background: Functional magnetic resonance imaging (fMRI) studies have reported altered integrity of large-scale neurocognitive networks (NCNs) in dementing disorders. However, findings on specificity of these alterations in patients with Alzheimer’s disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are still very limited. Recently, NCNs have been successfully captured using positron emission tomography (PET) with F18-fluordesoxyglucose (FDG). Methods: Network integrity was measured in 72 individuals (38 male) with mild AD, bvFTD, and healthy controls using a simultaneous resting state fMRI and FDG-PET. Indices of network integrity were calculated for each subject, network, and imaging modality. Results: In either modality, independent component analysis revealed four major NCNs: anterior default mode network (DMN), posterior DMN, salience network, and right central executive network (CEN). In fMRI data, integrity of posterior DMN was found to be significantly reduced in both patient groups relative to controls. In the AD group anterior DMN and CEN appeared to be additionally affected. In PET data, only integrity of posterior DMN in patients with AD was reduced, while three remaining networks appeared to be affected only in patients with bvFTD. In a logistic regression analysis, integrity of anterior DMN as measured with PET alone accurately differentiated between the patient groups. A correlation between indices of two imaging modalities was overall low. Conclusion: FMRI and FDG-PET capture partly different aspects of network integrity. A higher disease specificity of NCNs as derived from PET data supports metabolic connectivity imaging as a promising diagnostic tool.




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Confirmation of 123I-FP-CIT-SPECT (ioflupane) quantification methods in dementia with Lewy body and other neurodegenerative disorders

Rationale: To conduct a retrospective study comparing three 123I-FP-CIT-SPECT quantitative methods in patients with neurodegenerative syndromes as referenced to neuropathological findings. Methods: 123I-FP-CIT-SPECT and neuropathological findings among patients with neurodegenerative syndromes from the Mayo Alzheimer's Disease Research Center and Mayo Clinic Study of Aging were examined. Three 123I-FP-CIT-SPECT quantitative assessment Methods: MIMneuro (MIM Software Inc.), DaTQUANT (GE Healthcare), and manual region of interest (ROI) creation on an Advantage Workstation (GE Healthcare) were compared to neuropathological findings describing the presence or absence of Lewy body disease (LBD). Striatum to background ratios (SBRs) generated by DaTQUANT were compared to the calculated SBRs of the manual method and MIMneuro. The left and right SBRs for caudate, putamen and striatum were evaluated with the manual method. For DaTQUANT and MIMneuro the left, right, total and average SBRs and z-scores for whole striatum, caudate, putamen, anterior putamen, and posterior putamen were calculated. Results: The cohort included 24 patients [20 (83%) male, aged 75.4 +/- 10.0 at death]. The antemortem clinical diagnoses were Alzheimer’s disease dementia (ADem, N = 6), probable dementia with Lewy bodies (pDLB, N = 12), mixed ADem/pDLB (N = 1), Parkinson’s disease with mild cognitive impairment (N = 2), corticobasal syndrome (N = 1), idiopathic rapid eye movement sleep behavior disorder (iRBD) (N = 1) and behavioral variant frontotemporal dementia (N = 1). Seventeen (71%) had LBD pathology. All three 123I-FP-CIT-SPECT quantitative methods had area under the receiver operating characteristics (AUROC) values above 0.93 and up to 1.000 (p<0.001) and showed excellent discrimination between LBD and non-LBD patients in each region assessed, p<.001. There was no significant difference between the accuracy of the regions in discriminating the two groups, with good discrimination for both caudate and putamen. Conclusion: All three 123I-FP-CIT-SPECT quantitative methods showed excellent discrimination between LBD and non-LBD patients in each region assessed, using both SBRs and z-scores.




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Decentralization and Cross-border Integration in the Horn of Africa

Research Event

4 February 2020 - 5:00pm to 6:15pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Mohamed Guleid, Chief Executive Officer, Frontier Counties Development Council
Nuradin Dirie, Chair, Puntland Presidential Advisory Council
Aden Abdi, Horn of Africa Programme Director, Conciliation Resources
Chair: Dr Zahbia Yousuf, Senior Research Advisor, Saferworld 

The interdependence of communities across the Horn of Africa results from social, familial, linguistic and cultural ties that cross territorial borders. Such linkages are reinforced by established patterns of movement and trade, often leading to stronger political and social connections between communities on either side of borders, than with their respective national capitals. States in the region are increasingly being challenged by demands for decentralization and more effective local governance. Improved understanding of the complexity of sub-national and cross-border political and economic contexts will be required to meet these demands and support enhanced governance so that challenges such as marginalization, intercommunal conflict and more equitable sharing of resources can be effectively addressed.

At this event, speakers will examine some of the key subnational and cross-border relations in the Horn of Africa. They will also discuss initiatives and stakeholders needed to support common solutions to building peace, furthering development and bolstering inclusive growth and integration. 

THIS EVENT IS NOW FULL AND REGISTRATION HAS CLOSED.

Sahar Eljack

Programme Administrator, Africa Programme
+ 44 (0) 20 7314 3660




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DHS herding people on to an imperfect system in myGov

Over the past few weeks I have been answering calls for the myGov helpdesk.




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How Australian public service's digital reforms will happen, according to the Digital Transformation Office

The millions of customers, the short deadline: how the public service's digital revolution will start.




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Taxpayer records exposed by serious ATO, myGov security flaw

Taxpayer says he was hung up on twice by call centre staff when trying to report the issue.




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Governments should hack less, deliver better online services: Harvard IT expert

Western governments have established the international norm of online hacking and should not be surprised when foreign governments do the same.




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ACT scientist teaches computers to police the border

A Canberra-based scientist is teaching computers to pick up suspicious activity at the border.




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Medical records exposed by flaw in Telstra Health's Argus software

Default static password allowed medical practitioners' computers and servers to be accessed remotely by hackers.




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Webinar: Coordinating the Fight Against Financial Crime

Corporate Members Event Webinar

1 July 2020 - 5:00pm to 6:00pm
Add to Calendar

Che Sidanius, Global Head of Regulation & Industry Affairs, Refinitiv

Patricia Sullivan, Global Co-Head, Financial Crime Compliance, Standard Chartered

Dame Sara Thornton, Independent Anti-Slavery Commissioner, UK

Chair: Tom Keatinge, Director, Centre for Financial Crime and Security Studies, RUSI

 

Illicit finance not only threatens financial stability and inclusion but also provides support for terrorism and is a primary incentive for human trafficking, the illegal wildlife trade and narcotics smuggling. Frequently, actors capitalize on loopholes and inefficiencies resulting from the lack of a coordinated response to financial crime and an underpowered global system for tracking illicit financial flows. Enhanced public-private partnerships, in addition to investment in tackling financial crime from governments, international bodies and private industries, are necessary to develop regulatory frameworks, effective responses and valuable coordination between law enforcement, policymakers, regulators and financial institutions. But how should businesses structure their efforts so that their business interests are protected and the work they do is of use to others fighting financial crime?

This webinar will explore solutions to enable public-private partnerships to work together to combat financial crime. What do successful partnerships need from each side to ensure that the work being done is efficient and effective? How can the industry’s internal effectiveness impact the ‘real-world’ victims? And what barriers impede public-private partnerships operating as a force for good? 

This event is part of a fortnightly series of 'Business in Focus' webinars reflecting on the impact of COVID-19 on areas of particular professional interest for our corporate members and giving circles.

Not a corporate member? Find out more.




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Heritability of 596 lipid species and genetic correlation with cardiovascular traits in the Busselton Family Heart Study

Gemma Cadby
Apr 1, 2020; 61:537-545
Patient-Oriented and Epidemiological Research




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Circulating oxidized LDL increased in patients with acute myocardial infarction is accompanied by heavily modified HDL.

Naoko Sawada
Apr 14, 2020; 0:jlr.RA119000312v1-jlr.RA119000312
Research Articles




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The fatty acids from LPL-mediated processing of triglyceride-rich lipoproteins are taken up rapidly by cardiomyocytes

Haibo Jiang
Apr 2, 2020; 0:jlr.ILR120000783v1-jlr.ILR120000783
Images in Lipid Research




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UK Tech Weekly Podcast - Episode Six: The Internet of Board Games (IoBG) + The Budget & AlphaGo

In this week's UK Tech Weekly Podcast host Matt Egan is joined by first time podder Tamlin Magee (1:50), online editor at ComputerworldUK.com, to discuss the UK tech implications of this year's Budget, including rural broadband and driverless cars. Then Christina Mercer, assistant online editor at Techworld.com, chats AlphaGo (10:00) and board games following the AI's historic win over world Go champion Lee Sedol. Later, resident Virtual Reality (VR) enthusiast and PCAdvisor.co.uk staff writer Lewis Painter discussed "the big three" VR headset release dates, pricing and features from HTC, Sony Playstation and Oculus Rift (19:00). Finally, UKTW Podcast regular David Price, acting editor at Macworld.co.uk chats about Apple's big upcoming event (28:45).  


See acast.com/privacy for privacy and opt-out information.




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Episode 16 - The internet of the Apple iBoards (IoAi) Pebble, death of Hoverboards and Twitter

This week host Matt Egan is joined by producer Chris to talk about the recent batch of new Pebble devices and the smartwatch market. Staff writer at PC Advisor Lewis Painter joins in to talk about the death of the hoverboard (13:00). Finally, regular podder David Price comes on to talk about Appl...oh Twitter, specifically changes to the character limit and the sad loss of the @ (24:00).  


See acast.com/privacy for privacy and opt-out information.




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Episode 24 – The Internet of David’s Rules (IoDR) ARM, graphics cards & Twitter’s crackdown

Macworld UK’s Acting Editor David Price takes the reins for this edition, and is joined by Online Editor of Computerworld UK Scott Carey to chat about billions and billions of pounds and the acquisition of ARM by SoftBank. Second up, Staff Writer at PC Advisor and Macworld UK Christopher Minasians plugs in to the haunting world of graphics cards and makes sense of it all for the rest of us. Digital Arts Staff Writer Mimi Launder then explains why Twitter has slapped a troll right in the face in order to stand up to Internet bullying.  


See acast.com/privacy for privacy and opt-out information.




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Episode 41 - The Internet of Our Overlords (IoOO)

In our post-truth post-Trump world, host Matt Egan leads the gang down the road of soul searching and government confines. Following the passing of the Investigatory Powers Bill, Techworld Editor Charlotte Jee lets us know why we might be concerned. Second (11:40), Macworld UK Acting Editor David Price talks about the Facebook fake news buzz, and whether social media has a responsibility to edit out the blatant lies. Finally (28:14) for a bit of lighter chat, Staff Writer at PC Advisor Henry Burrell discusses the launch of the OnePlus 3T, price hikes on phones and why consumers might be a bit miffed if they shelled out for a OnePlus 3 just 5 months ago.  


See acast.com/privacy for privacy and opt-out information.




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Episode 53 - The Internet of UberEATS Itself (IoUEI) Uber's mess, Apple's orchards and MWC's phones

Allow Matt Egan (and Shed7) to lull you into this week's pod as we tackle the big tech issues of the week. Staff Writer at Digital Arts Miriam Harris explains the latest HR and PR mess over at Uber. How long will consumers use a service when the company are clearly not treating its staff well? Then (16:30) Deputy Editor of Macworld UK David Price gets excited about Apple Park, the so-called 'spaceship campus' that has been under construction for years. May contain orchards. Finally (26:48) Senior Staff Writer at Tech Advisor Henry Burrell previews Mobile World Congress which gets underway on 26th February. Are any of the major handset launches worth your attention?  


See acast.com/privacy for privacy and opt-out information.




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Episode 60 - The Internet of post-Easter nerds (IoPEN) F8, Mac Pro and RIP NES Classic

Back with a bumper edition after the Easter break, as Henry Burrell takes Scott Carey, David Price and Dom Preston on a chat odyssey to discuss Facebook's F8 conference. Will chat bots ever be good and who uses QR codes? The gang then discusses Apple's out of character decision to brief journos on the Mac Pro and even admit they got it wrong. Finally we talk about Nintendo stopping production of the NES Classic and whether there's more affordable retro goodness around the corner.  


See acast.com/privacy for privacy and opt-out information.




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Episode 96 - The Internet of Automation (IoA) IBM and the Third Reich, Facebook slump and MacBook Pro woes

Join host Henry Burrell in hot as hell London town to bring you 40 minutes of air conditioned tech chat.


Tamlin Magee talks us through the murky ways IBM helped the Third Reich in the Thirties and Forties with data collection and asks what responsibility tech companies have today to ensure their work does not contribute to evil.


Charlotte Jee then analyses Facebook's stock price slump, asking why it happened and does it really affect the company? The team muses on Facebook as a whole and the fascinating if polarising Zuckerberg.


Finally Macworld's David Price chats about the new MacBook Pros and how Apple has already fixed the major flaw in the high-end model - but why did they ship this way? Is Apple less concerned with quality control these days?

 

See acast.com/privacy for privacy and opt-out information.




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Episode 111 - The Internet of Not Watching Films (IoNWF) Bird Box, Black Mirror and bent iPads

Happy New Year from the UK Tech Weekly Podcast!


We are back this week to discuss what we have been watching (or not watching) over the festive period, including Scott Carey on the meme-marketed sensation of Bird Box and what this says about Netflix's ability to dominate the cultural conversation. Then Tamlin Magee jumps in to talk about the interactive Black Mirror movie Bandersnatch and why it may have been destined to fail.


Lastly David Price steps out of the hosting chair to talk about bendy iPads and Apple's strange rhetoric.

 

See acast.com/privacy for privacy and opt-out information.




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The fatty acids from LPL-mediated processing of triglyceride-rich lipoproteins are taken up rapidly by cardiomyocytes [Images in Lipid Research]




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Circulating oxidized LDL increased in patients with acute myocardial infarction is accompanied by heavily modified HDL. [Research Articles]

Oxidized low-density lipoprotein (oxLDL) is a known risk factor for atherogenesis. This study aimed to reveal structural features of oxLDL present in human circulation related to atherosclerosis. When LDL was fractionated on an anion-exchange column, in vivo-oxLDL, detected by the anti-oxidized phosphatidylcholine (oxPC) monoclonal antibody, was recovered in flow-through and electronegative LDL (LDL(-)) fractions. The amount of the electronegative in vivo-oxLDL, namely oxLDL in LDL(-) fraction, present in patients with acute myocardial infarction (AMI) was three-fold higher than that observed in healthy subjects. Surprisingly, LDL(-) fraction contained apoA1 in addition to apoB, and HDL-sized particles were observed with transmission electron microscopy. In LDL(-) fractions, acrolein adducts were identified at all lysine residues in apoA1, with only a small number of acrolein-modified residues were identified in apoB. The amount of oxPC adducts of apoB was higher in LDL(-) than in L1 fraction as determined using western blotting. The electronegative in vivo-oxLDL was immunologically purified from the LDL(-) fraction with an anti-oxPC monoclonal antibody. Majority of PC species was not oxidized, whereas oxPC and lysoPC did not accumulate. Here, we propose that there are two types of in vivo-oxLDL in human circulating plasma and the electronegative in vivo-oxLDL accompanies oxidized HDL.




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The Hurdles to Developing a COVID-19 Vaccine: Why International Cooperation is Needed

23 April 2020

Professor David Salisbury CB

Associate Fellow, Global Health Programme

Dr Champa Patel

Director, Asia-Pacific Programme
While the world pins its hopes on vaccines to prevent COVID-19, there are scientific, regulatory and market hurdles to overcome. Furthermore, with geopolitical tensions and nationalistic approaches, there is a high risk that the most vulnerable will not get the life-saving interventions they need.

2020-04-23-Covid-Vaccine.jpg

A biologist works on the virus inactivation process in Belo Horizonte, Brazil on 24 March 2020. The Brazilian Ministry of Health convened The Technological Vaccine Center to conduct research on COVID-19 in order to diagnose, test and develop a vaccine. Photo: Getty Images.

On 10 January 2020, Chinese scientists released the sequence of the COVID-19 genome on the internet. This provided the starting gun for scientists around the world to start developing vaccines or therapies. With at least 80 different vaccines in development, many governments are pinning their hopes on a quick solution. However, there are many hurdles to overcome. 

Vaccine development

Firstly, vaccine development is normally a very long process to ensure vaccines are safe and effective before they are used. 

Safety is not a given: a recent dengue vaccine caused heightened disease in vaccinated children when they later were exposed to dengue, while Respiratory Syncytial Virus vaccine caused the same problem. Nor is effectiveness a given. Candidate vaccines that use novel techniques where minute fragments of the viruses’ genetic code are either injected directly into humans or incorporated into a vaccine (as is being pursued, or could be pursued for COVID-19) have higher risks of failure simply because they haven’t worked before. For some vaccines, we know what levels of immunity post-vaccination are likely to be protective. This is not the case for coronavirus. 

Clinical trials will have to be done for efficacy. This is not optional – regulators will need to know extensive testing has taken place before licencing any vaccine. Even if animal tests are done in parallel with early human tests, the remainder of the process is still lengthy. 

There is also great interest in the use of passive immunization, whereby antibodies to SARS-CoV-2 (collected from people who have recovered from infection or laboratory-created) are given to people who are currently ill. Antivirals may prove to be a quicker route than vaccine development, as the testing requirements would be shorter, manufacturing may be easier and only ill people would need to be treated, as opposed to all at-risk individuals being vaccinated.

Vaccine manufacturing

Developers, especially small biotechs, will have to make partnerships with large vaccine manufacturers in order to bring products to market. One notorious bottleneck in vaccine development is getting from proof-of-principle to commercial development: about 95 per cent of vaccines fail at this step. Another bottleneck is at the end of production. The final stages of vaccine production involve detailed testing to ensure that the vaccine meets the necessary criteria and there are always constraints on access to the technologies necessary to finalize the product. Only large vaccine manufacturers have these capacities. There is a graveyard of failed vaccine candidates that have not managed to pass through this development and manufacturing process.

Another consideration is adverse or unintended consequences. Highly specialized scientists may have to defer their work on other new vaccines to work on COVID-19 products and production of existing products may have to be set aside, raising the possibility of shortages of other essential vaccines. 

Cost is another challenge. Vaccines for industrialized markets can be very lucrative for pharmaceutical companies, but many countries have price caps on vaccines. Important lessons have been learned from the 2009 H1N1 flu pandemic when industrialized countries took all the vaccines first. Supplies were made available to lower-income countries at a lower price but this was much later in the evolution of the pandemic. For the recent Ebola outbreaks, vaccines were made available at low or no cost. 

Geopolitics may also play a role. Should countries that manufacture a vaccine share it widely with other countries or prioritize their own populations first? It has been reported that President Trump attempted to purchase CureVac, a German company with a candidate vaccine.  There are certainly precedents for countries prioritizing their own populations. With H1N1 flu in 2009, the Australian Government required a vaccine company to meet the needs of the Australian population first. 

Vaccine distribution

Global leadership and a coordinated and coherent response will be needed to ensure that any vaccine is distributed equitably. There have been recent calls for a G20 on health, but existing global bodies such as the Coalition for Epidemic Preparedness Innovations (CEPI) and GAVI are working on vaccines and worldwide access to them. Any new bodies should seek to boost funding for these entities so they can ensure products reach the most disadvantaged. 

While countries that cannot afford vaccines may be priced out of markets, access for poor, vulnerable or marginalized peoples, whether in developed or developing countries, is of concern. Developing countries are at particular risk from the impacts of COVID-19. People living in conflict-affected and fragile states – whether they are refugees or asylum seekers, internally displaced or stateless, or in detention facilities – are at especially high risk of devastating impacts. 

Mature economies will also face challenges. Equitable access to COVID-19 vaccine will be challenging where inequalities and unequal access to essential services have been compromised within some political systems. 

The need for global leadership 

There is an urgent need for international coordination on COVID-19 vaccines. While the WHO provides technical support and UNICEF acts as a procurement agency, responding to coronavirus needs clarity of global leadership that arches over national interests and is capable of mobilizing resources at a time when economies are facing painful recessions. We see vaccines as a salvation but remain ill-equipped to accelerate their development.

While everyone hopes for rapid availability of safe, effective and affordable vaccines that will be produced in sufficient quantities to meet everyone’s needs, realistically, we face huge hurdles. 




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Why is it So Hard for Iraq to Form A Government?

25 April 2020

Dr Renad Mansour

Senior Research Fellow, Middle East and North Africa Programme; Project Director, Iraq Initiative
Mustafa al-Kadhimi has emerged as the compromise prime minister designate, but his potential appointment is built on shaky foundations.

2020-04-25-Iraq-Security-COVID

A member of Iraqi security forces stands guard behind a yellow line after the government declared curfew due to coronavirus. Photo by Fariq Faraj Mahmood/Anadolu Agency via Getty Images.

On April 9, Iraqi President Barham Salih gathered the Shia, Kurdish and Sunni political blocs at the presidential palace to task head of intelligence Mustafa al-Kadhimi with forming a government.

Kadhimi is the third prime minister-designate assigned since Prime Minister Adil abd al-Mehdi resigned in November, in the wake of mass protests against government corruption and the country’s ethno-sectarian based political system.

Kadhimi’s two predecessors, Muhammad Tawfiq Allawi and Adnan al-Zurfi, both failed to form a government. This third attempt came as Iraq struggles with repeated crises since October 2019, when the government began responding with deadly force to large-scale mass protests, killing more than 600 and injuring tens of thousands.

In January, the assassination of Qasem Soleimani escalated tensions between the United States and Iran, with Iraq stuck in the middle and becoming the home for regular tit-for-tat attacks. The Islamic State — never completely defeated — took advantage of these crises and increased its attacks in disputed territories.

The outbreak of COVID-19 challenges the country’s fragile public health sector, while the decline in the price of oil will make it harder for leaders to pay the public salaries that keep the system (and patronage) moving.

What does the delay in forming a government amid multiple crises mean for the post-2003 Iraqi political system?

Iraq’s post-2003 political system is designed to withstand crisis. Over the years, political parties reflecting the country’s ethnic and sectarian divides have had a tacit understanding that crises represent a risk to their collective interests. These elite stakeholders have together weathered civil war, insurgency and multiple protests — despite deep conflicts with one another.

For instance, in September 2018 protesters attacked most major political party headquarters and the Iranian consulate in Basra, and authorities killed some 20 protesters.

Since the May election of that year, the fragmented Shia elite had been unable to even declare which side has the largest parliamentary bloc, let alone decide on a government.

But after the September crisis, the previously gridlocked parties swiftly came together to form an “understanding” that pushed through the impasse leading to the Mehdi government. In 2020, however, Iraq’s political parties were slower to come back together despite the multiple crises — far greater than 2018. The system is less able to swiftly fix itself, based primarily on the fragmentation of the elite — and their determination to prevent any challenge to their rule.

Why did the two prior attempts fail?

The two previous prime minister-designates each fell short for different reasons. When I met Allawi in February at the prime minister’s guesthouse in Baghdad, he was very clearly convinced that his mandate was to sideline the parties.

He hoped that simply choosing technocratic ministers outside the elite pact, with the support of Moqtada al-Sadr behind him, would garner support from protesters and the disillusioned public. He failed, however, because his cabinet had to go through parliament and the parties rejected what they saw a threat to the elite pact and the system.

Zurfi similarly failed after being directly appointed in March by Salih after the Shia parties failed to come up with a candidate. From the beginning, then, Zurfi faced challenges because parties were not in agreement. He attempted to directly confront his opposition, and spoke out against Iranian influence in Iraq. As a result, Zurfi was unable to even get to parliament with his proposed cabinet, as the Shia parties got back together to bring him down.

The failure of both strategies — Allawi attempting to work outside the elite party system and Zurfi trying to target certain parties — reveals tensions in Iraq’s political system. This fragmentation strains the parties’ ability to swiftly unite, and the system’s ability to withstand crises.

The endemic problems are a consequence of fragmentation, including the failure following the 2018 elections to declare governing parliamentary bloc. Moreover, after that election, newcomers into the political system (two-thirds of the MPs are serving their first term) are increasingly making their own demands and less willing to blindly toe party lines.

Can Kadhimi overcome the impasse?

Kadhimi’s appointment as prime minister-designate nonetheless is on shaky foundations. His appointment had previously faced a veto from Iran and its allied groups which make up the Fateh bloc. Kataeb Hezbollah, an armed group close to Iran and linked to the Popular Mobilization Units, issued a statement accusing Kadhimi with blood on his hands for the deaths of Soleimani and Abu Mahdi al-Muhandis.

Many Fateh bloc members had for months vetoed Kadhimi’s name due to this allegation. Immediately before Kadhimi addressed the nation for the first time, Iraqi state television broadcast a prerecorded statement by PMU (and Fateh) leader Qais al-Khazali, who had also previously accused Kadhimi of spying for the Americans and being complicit in the two killings.

Khazali, who commands the second-largest party within Fateh, accepted the party line to back Kadhimi but came out with his own conditions on television. However, the concerns about the COVID-19 crisis and the collapse of the price of oil finally brought all sides to compromise — a design of the political system.

Kadhimi has signalled he will play by the old rules with these stakeholders. Because of the magnitude of these simultaneous crises, Iraqi politics is moving back to the post-2003 norm. The ethno-sectarian based political system is geared to weather such existential crises more than it is to handling day-to-day governance. Despite the notion of “post-sectarianism” in Iraq, this system is based on ethno-sectarian political party compromise.

In his television address, Khazali, who had previously attempted to move away from sectarian language, explained that the process of selecting a prime minister is reserved to the Shia, who have the right as the majority, and not to Salih, a Kurd.

Over the years Kadhimi has expressed an admiration of the bravery of the protesters and of the importance of civil society. Many Iraqi civil society activists owe their lives to the work of the former intelligence chief. However, he has also been part of the same system that has violently suppressed protesters.

As the compromise prime minister-designate, he will find it difficult to transform his country as long as he plays by the rules of post-2003 Iraq — an irony not lost on the protesters who immediately rejected the candidacy of a man whom until recently many protesters had supported.

This article was originally published in The Washington Post




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WITHDRAWN: Extraordinary apolipoprotein oxidation in chronic hepatitis C and liver cirrhosis [13. Other]

Withdrawn by Author.




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The ProteoRed MIAPE web toolkit: A user-friendly framework to connect and share proteomics standards [Technology]

The development of the HUPO-PSI's (Proteomics Standards Initiative) standard data formats and MIAPE (Minimum Information About a Proteomics Experiment) guidelines should improve proteomics data sharing within the scientific community. Proteomics journals have encouraged the use of these standards and guidelines to improve the quality of experimental reporting and ease the evaluation and publication of manuscripts. However, there is an evident lack of bioinformatics tools specifically designed to create and edit standard file formats and reports, or embed them within proteomics workflows. In this article, we describe a new web-based software suite (The ProteoRed MIAPE web toolkit) that performs several complementary roles related to proteomic data standards. Firstly, it can verify the reports fulfill the minimum information requirements of the corresponding MIAPE modules, highlighting inconsistencies or missing information. Secondly, the toolkit can convert several XML-based data standards directly into human readable MIAPE reports stored within the ProteoRed MIAPE repository. Finally, it can also perform the reverse operation, allowing users to export from MIAPE reports into XML files for computational processing, data sharing or public database submission. The toolkit is thus the first application capable of automatically linking the PSI's MIAPE modules with the corresponding XML data exchange standards, enabling bidirectional conversions. This toolkit is freely available at http://www.proteored.org/MIAPE/.




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Towards a Low-Carbon Future: China and the European Union

1 October 2007 , Number 7

Chinese goods seem to flood western markets: computers, light bulbs, sweaters, T-shirts and bras. The instinct is to try to protect home producers. A better plan would be to work with Beijing on producing products for the next industrial revolution – the creation of a low-carbon economy. But that would take real vision and political courage.

Bernice Lee OBE

Research Director; Executive Director, Hoffmann Centre for Sustainable Resource Economy

Nick Mabey

Founding director and Chief Executive, E3G