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A Novel Approach to Adolescents With Type 1 Diabetes: The Team Clinic Model

Jennifer K. Raymond
Feb 1, 2015; 28:68-71
Care Innovations




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Diabetes Self-Management Education for Older Adults: General Principles and Practical Application

Emmy Suhl
Oct 1, 2006; 19:234-240
Articles




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The Diabetes Attitudes, Wishes, and Needs (DAWN) Program: A New Approach to Improving Outcomes of Diabetes Care

Soren E. Skovlund
Jul 1, 2005; 18:136-142
Lifestyle and Behavior




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Happy Family: Investing for the Future

What strategic and operational challenges lie ahead for innovative start-up Happy Family, a leading producer of organic baby foods?




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It felt like prison - Cruise ship worker happy to be home

"It felt like prison." Those are the exact words of Jermaine who returned to the island yesterday after he was stranded on a cruise ship for 56 days in South Hampton, United Kingdom. "Bwoy we are out of prison ... it was rough mentally. They...




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State Cyber Interventions Below the Threshold of the Use of Force: Challenges in the Application of International Law

Invitation Only Research Event

30 April 2019 - 10:00am to 4:00pm

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

Event participants

Chair: Elizabeth Wilmshurst, Distinguished Fellow, International Law Programme, Chatham House

Under what circumstances will a state-sponsored cyberattack on another state that falls below the threshold of the use of force be a breach of international law – for example, hacking into another state’s electoral databases, usurping inherently governmental functions such as parliamentary processes or an attack on another state’s financial system? In the dynamic field of state cyber operations, persistent, low-level cyberattacks are increasing, as are multilateral attempts to attribute the attacks to the states responsible. There is general agreement that international law applies to cyberspace but the question is how it applies and with what consequences.     
   
This meeting will bring together a small group of academics and practitioners to explore the application of international law to states’ cyber operations that interfere in the internal affairs of another state and which fall below the threshold of the use of force. What is the law on non-intervention in international law and how does it apply to states’ cyber activities? Does the Nicaragua case represent the best expression of the law in this area including the requirement of coercion? And are there any other principles of international law that are relevant? The meeting will also consider processes and procedures for agreeing on the law and best practices.
 
The purpose of the meeting will be to inform a research paper by Chatham House.
 
Attendance at this event is by invitation only.

Event attributes

Chatham House Rule

Department/project




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Cyber Interference in Elections: Applying a Human Rights Framework

Invitation Only Research Event

7 May 2019 - 10:00am to 4:15pm

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

The use of social media, including algorithms, bots and micro-targeted advertising, has developed rapidly while there has been a policy lag in identifying and addressing the challenges posed to democracy by the manipulation of voters through cyber activity. 
 
What role should international human rights law play in developing a normative framework to address potential harms caused by such cyber activity including the closing down of democratic space, the spread of disinformation and hate speech?
 
This meeting will bring together a small group of academics and practitioners to explore the implications of applying a human rights framework to both the activities of social media companies and the activities of governments and international organizations in seeking to regulate their activity. The purpose of the meeting will be to inform a report that will provide an overview of the applicable law and recommendations for how that law might inform future policy and regulation. 
 
Attendance at this event is by invitation only.

Event attributes

Chatham House Rule




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Tackling Cyber Disinformation in Elections: Applying International Human Rights Law

Research Event

6 November 2019 - 5:30pm to 7:00pm

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

Susie Alegre, Barrister and Associate Tenant, Doughty Street Chambers
Evelyn Aswad, Professor of Law and the Herman G. Kaiser Chair in International Law, University of Oklahoma
Barbora Bukovská, Senior Director for Law and Policy, Article 19
Kate Jones, Director, Diplomatic Studies Programme, University of Oxford
Chair: Harriet Moynihan, Associate Fellow, International Law Programme, Chatham House

Cyber operations are increasingly used by political parties, their supporters and foreign states to influence electorates – from algorithms promoting specific messages to micro-targeting based on personal data and the creation of filter bubbles.
 
The risks of digital tools spreading disinformation and polarizing debate, as opposed to deepening democratic engagement, have been highlighted by concerns over cyber interference in the UK’s Brexit referendum, the 2016 US presidential elections and in Ukraine. 
 
While some governments are adopting legislation in an attempt to address some of these issues, for example Germany’s ‘NetzDG’ law and France’s ‘Law against the manipulation of information’, other countries have proposed an independent regulator as in the case of the UK’s Online Harms white paper. Meanwhile, the digital platforms, as the curators of content, are under increasing pressure to take their own measures to address data mining and manipulation in the context of elections. 

How do international human rights standards, for example on freedom of thought, expression and privacy, guide the use of digital technology in the electoral context? What practical steps can governments and technology actors take to ensure policies, laws and practices are in line with these fundamental standards? And with a general election looming in the UK, will these steps come soon enough?
 
This event brings together a wide range of stakeholders including civil society, the tech sector, legal experts and government, coincides with the publication of a Chatham House research paper on disinformation, elections and the human rights framework

Jacqueline Rowe

Programme Assistant, International Law Programme
020 7389 3287




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Sovereignty and Non-Intervention: The Application of International Law to State Cyberattacks

Research Event

4 December 2019 - 5:30pm to 7:00pm

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

Event participants

Douglas, Legal Director, GCHQ
Zhixiong Huang, Luojia Chair of International Law, Wuhan University
Nemanja Malisevic, Director of Digital Diplomacy, Microsoft
Harriet Moynihan, Associate Fellow, International Law Programme, Chatham House
Chair: Elizabeth Wilmshurst, Distinguished Fellow, International Law Programme, Chatham House

International law applies to cyber operations – but views differ on exactly how. Does state-sponsored interference in another state's affairs using cyber means – for example,  disinformation campaigns in elections, disabling government websites, or disrupting transport systems – breach international law? If so, on what basis and how are the principles of sovereignty and non-intervention relevant? States are increasingly attributing cyber operations to other states and engaging in the debate on how international law applies, including circumstances that would justify countermeasures.

As states meet to debate these issues at the UN, the panel will explore how international law regulates cyberoperations by states, consider the prospects of progress at the UN, and assess the value of other initiatives.

This event coincides with the launch of a Chatham House research paper which analyses how the principles of sovereignty and intervention apply in the context of cyberoperations, and considers a way forward for agreeing a common understanding of cyber norms.

This event will bring together a broad group of actors, including policymakers, the private sector, legal experts and civil society, and will be followed by a drinks reception.

 

Jacqueline Rowe

Programme Assistant, International Law Programme
020 7389 3287




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Online Disinformation and Political Discourse: Applying a Human Rights Framework

6 November 2019

Although some digital platforms now have an impact on more people’s lives than does any one state authority, the international community has been slow to hold to account these platforms’ activities by reference to human rights law. This paper examines how human rights frameworks should guide digital technology.

Kate Jones

Associate Fellow, International Law Programme

2019-11-05-Disinformation.jpg

A man votes in Manhattan, New York City, during the US elections on 8 November 2016. Photo: Getty Images.

Summary

  • Online political campaigning techniques are distorting our democratic political processes. These techniques include the creation of disinformation and divisive content; exploiting digital platforms’ algorithms, and using bots, cyborgs and fake accounts to distribute this content; maximizing influence through harnessing emotional responses such as anger and disgust; and micro-targeting on the basis of collated personal data and sophisticated psychological profiling techniques. Some state authorities distort political debate by restricting, filtering, shutting down or censoring online networks.
  • Such techniques have outpaced regulatory initiatives and, save in egregious cases such as shutdown of networks, there is no international consensus on how they should be tackled. Digital platforms, driven by their commercial impetus to encourage users to spend as long as possible on them and to attract advertisers, may provide an environment conducive to manipulative techniques.
  • International human rights law, with its careful calibrations designed to protect individuals from abuse of power by authority, provides a normative framework that should underpin responses to online disinformation and distortion of political debate. Contrary to popular view, it does not entail that there should be no control of the online environment; rather, controls should balance the interests at stake appropriately.
  • The rights to freedom of thought and opinion are critical to delimiting the appropriate boundary between legitimate influence and illegitimate manipulation. When digital platforms exploit decision-making biases in prioritizing bad news and divisive, emotion-arousing information, they may be breaching these rights. States and digital platforms should consider structural changes to digital platforms to ensure that methods of online political discourse respect personal agency and prevent the use of sophisticated manipulative techniques.
  • The right to privacy includes a right to choose not to divulge your personal information, and a right to opt out of trading in and profiling on the basis of your personal data. Current practices in collecting, trading and using extensive personal data to ‘micro-target’ voters without their knowledge are not consistent with this right. Significant changes are needed.
  • Data protection laws should be implemented robustly, and should not legitimate extensive harvesting of personal data on the basis of either notional ‘consent’ or the data handler’s commercial interests. The right to privacy should be embedded in technological design (such as by allowing the user to access all information held on them at the click of a button); and political parties should be transparent in their collection and use of personal data, and in their targeting of messages. Arguably, the value of personal data should be shared with the individuals from whom it derives.
  • The rules on the boundaries of permissible content online should be set by states, and should be consistent with the right to freedom of expression. Digital platforms have had to rapidly develop policies on retention or removal of content, but those policies do not necessarily reflect the right to freedom of expression, and platforms are currently not well placed to take account of the public interest. Platforms should be far more transparent in their content regulation policies and decision-making, and should develop frameworks enabling efficient, fair, consistent internal complaints and content monitoring processes. Expertise on international human rights law should be integral to their systems.
  • The right to participate in public affairs and to vote includes the right to engage in public debate. States and digital platforms should ensure an environment in which all can participate in debate online and are not discouraged from standing for election, from participating or from voting by online threats or abuse.




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The Application of International Law to State Cyberattacks: Sovereignty and Non-Intervention

2 December 2019

Hostile cyber operations by one state against another state are increasingly common. This paper analyzes the application of the sovereignty and non-intervention principles in relation to states’ cyber operations in another state below the threshold of the use of force. 

Harriet Moynihan

Senior Research Fellow, International Law Programme

2019-11-29-Intl-Law-Cyberattacks.jpg

A computer hacked by a virus known as Petya. The Petya ransomware cyberattack hit computers of Russian and Ukrainian companies on 27 June 2017. Photo: Getty Images.

Summary

  • The vast majority of state-to-state cyberattacks consist of persistent, low-level intrusions that take place below the threshold of use of force. International law, including the principle of non-intervention in another state’s internal affairs and the principle of sovereignty, applies to these cyber operations.
  • It is not clear whether any unauthorized cyber intrusion would violate the target state’s sovereignty, or whether there is a threshold in operation. While some would like to set limits by reference to effects of the cyber activity, at this time such limits are not reflected in customary international law. The assessment of whether sovereignty has been violated therefore has to be made on a case by case basis, if no other more specific rules of international law apply.
  • In due course, further state practice and opinio iuris may give rise to an emerging cyber-specific understanding of sovereignty, just as specific rules deriving from the sovereignty principle have crystallized in other areas of international law.
  • Before a principle of due diligence can be invoked in the cyber context, further work is needed by states to agree upon rules as to what might be expected of a state in this context.
  • The principle of non-intervention applies to a state’s cyber operations as it does to other state activities. It consists of coercive behaviour by one state that deprives the target state of its free will in relation to the exercise of its sovereign functions in order to compel an outcome in, or conduct with respect to, a matter reserved to the target state.
  • In practice, activities that contravene the non-intervention principle and activities that violates sovereignty will often overlap.
  • In order to reach agreement on how international law applies to states’ cyber operations below the level of use of force, states should put their views on record, where possible giving examples of when they consider that an obligation may be breached, as states such as the UK, Australia, France and the Netherlands have done.
  • Further discussion between states should focus on how the rules apply to practical examples of state-sponsored cyber operations. There is likely to be more commonality about specific applications of the law than there is about abstract principles.
  • The prospects of a general treaty in this area are still far off. In due course, there may be benefit in considering limited rules, for example on due diligence and a prohibition on attacking critical infrastructure, before tackling broad principles.




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Tandem Mass Tag Approach Utilizing Pervanadate BOOST Channels Delivers Deeper Quantitative Characterization of the Tyrosine Phosphoproteome

Xien Yu Chua
Apr 1, 2020; 19:730-743
Technological Innovation and Resources




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Developments and Applications of Functional Protein Microarrays

Guan-Da Syu
Apr 17, 2020; 0:R120.001936v1-mcp.R120.001936
Review




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A cross-linking mass spectrometry approach defines protein interactions in yeast mitochondria

Andreas Linden
Apr 24, 2020; 0:RA120.002028v1-mcp.RA120.002028
Research




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Proximity Dependent Biotinylation: Key Enzymes and Adaptation to Proteomics Approaches

Payman Samavarchi-Tehrani
May 1, 2020; 19:757-773
Review




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Transparency and Accountability for Drone Use: European Approaches

Invitation Only Research Event

11 March 2019 - 9:30am to 12 March 2019 - 12:30pm

Chatham House

With increased use of military drones in recent years there have also been many calls for greater transparency and accountability with regards to drone operations.

This would allow for greater public understanding, particularly as the complex nature of military operations today intensifies difficulties in sustaining perceptions of the legitimate use of force.

For example, in Europe, leading states rely on the US for drone platforms and for the infrastructure - such as military communication networks - that enable those operations, while the US also relies on airbases in European states to operate its drone programme.

In addition, with reports that the US is loosening the rules on the use of drones, it is important to understand how European approaches to transparency and accountability may be affected by these developments.

This workshop focuses on how European states can facilitate transparency to ensure accountability for drone use, as well as what the limits might be, considering both the complexity of military operations today and the need for achieving operational goals.

With the US easing restrictions on export controls, the discussion also considers the role of regulation in ensuring accountability and prospects for developing common standards.

Attendance at this event is by invitation only.

Nilza Amaral

Project Manager, International Security Programme




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European Approaches to Remote Warfare

Research Event

15 May 2019 - 9:00am to 6:00pm

Brussels, Belgium

With continuing instability at Europe's borders, along with uncertainty on future US support for NATO, many European countries are increasing their allocations to defence budgets and to collective European strategic defence. In addition, with non-state armed groups creating instability and threatening civilian lives and livelihoods in proximity to the EU’s borders, various operations have been carried out in conflict theatres in the Middle East, North Africa and the Sahel under the auspices of NATO, the UN, the EU or by single EU member states.

Although European military personnel have been deployed in many regions, with countries becoming more reluctant to deploy ‘boots on the ground’, warfare has been increasingly conducted through remote means. This has led to criticism on the limited transparency and accountability mechanisms at work in these operations, while some have questioned the military effectiveness of such tactics or the capacity and willingness of states to ensure that targets are struck accurately and without impact on civilian populations.

Against this background, the EU has started allocating resources to military research and development projects with a focus on unmanned systems and related technologies. Under the auspices of the European Defence Fund such funding is set to increase, while potential bilateral programmes between some states have also been explored. Despite concerns raised by the European Parliament, the development of these policies and technologies has taken place without significant consideration of what the legal, ethical and military-strategic impact of these instruments might be.    

This event will bring together a range of experts, policymakers and civil society organizations to discuss the technology horizon of European defence investments and policy developments around remote warfare. Participants will discuss the implications of the new EU defence fund, legal, ethical, and transparency issues in military research and development and the position of the EU as a global actor. 

This event is being organized in partnership with PAX Netherlands.

THIS EVENT IS NOW FULL AND REGISTRATION HAS CLOSED.

Nilza Amaral

Project Manager, International Security Programme




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The Smart Peace Initiative: An Integrated and Adaptive Approach to Building Peace

Invitation Only Research Event

12 May 2020 - 10:00am to 11:30am
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Smart Peace brings together global expertise in conflict analysis and research, peacebuilding and mediation programming, and behavioural science and evaluation. Together, Smart Peace partners are developing integrated and adaptive peace initiatives, working with local partners to prevent and resolve complex and intractable conflicts in Central African Republic, Myanmar and northern Nigeria.
 
This roundtable is an opportunity for Smart Peace partners to share the Smart Peace concept, approach and objectives, and experiences of the first phases of programme implementation. Roundtable discussions among participants from policy, practice and research communities will inform future priorities and planning for Smart Peace learning, advocacy and communication.
 
Smart Peace partners include Conciliation Resources, Behavioural Insights Team, The Centre for Humanitarian Dialogue, Chatham House, ETH Zurich, International Crisis Group and The Asia Foundation.

Nilza Amaral

Project Manager, International Security Programme




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Nuclear Weapons: Innovative Approaches for the Complex International Security Environment

This programme of work addresses the conundrum of nuclear weapons as a wicked problem in a complex adaptive system.

Understanding the complexity and the wickedness of the situation allows analysts and strategic planners to approach these complex and intractable issues in new and transformative ways – with a better chance of coping or succeeding and reducing the divisions between experts.

Using complexity theory, a complex adaptive system representing the international system and its interaction with the environment can be represented through an interactive visualization tool that will aid thought processes and policy decision-making. 

Until recently, analysts did not have the tools to be able to create models that could represent the complexity of the international system and the role that nuclear weapons play. Now that these tools are available, analysts should use them to enable decision-makers to gain insights into the range of possible outcomes from a set of possible actions.

This programme builds on work by Chatham House on cyber security and artificial intelligence (AI) in the nuclear/strategic realms.

In order to approach nuclear weapons as wicked problems in a complex adaptive system from different and sometimes competing perspectives, the programme of work involves the wider community of specialists who do not agree on what constitutes the problems of nuclear weapons nor on what are the desired solutions.

Different theories of deterrence, restraint and disarmament are tested. The initiative is international and inclusive, paying attention to gender, age and other aspects of diversity, and the network of MacArthur Grantees are given the opportunity to participate in the research, including in the writing of research papers, so that the complexity modelling can be tested against a wide range of approaches and hypotheses.

In addition, a Senior Reference Group will work alongside the programme, challenging its outcome and findings, and evaluating and guiding the direction of the research.

This project is supported by the MacArthur Foundation.




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Mapping prostate cancer lesions pre/post unsuccessful salvage lymph node dissection using repeat PSMA-PET

Introduction: The aim of this study was to analyze patterns of persistent versus recurrent or new PET lesions in a selected patient cohort with PSA persistence following salvage lymph node dissection (SLND) and pre/post procedure prostate-specific membrane antigen ligand positron emission tomography (PSMA-PET). Material and Methods: 16 patients were included in this multicenter study. Inclusion criteria were: a) PSMA-PET performed for biochemical recurrence before SLND (pre-SLND PET) and b) repeat PSMA-PET performed for persistently elevated PSA level (≥0.1 ng/mL) ≥6 weeks after SLND (post-SLND PET). Image analysis was performed by three independent nuclear medicine physicians applying the molecular imaging TNM system PROMISE. Lesions were confirmed by histopathology, presence on correlative CT/MRI/bone scan or PSA response after focal therapy. Results: post-SLND PET identified PCa-lesions in 88% (14/16) of patients with PSA persistence after SLND. Median PSA was 1.2 ng/mL (IQR, 0.6-2.8 ng/mL). Disease was confined to the pelvis in 56% of patients (9/16) and most of these men had common iliac (6/16, 38%) and internal iliac lymph node metastases (6/16, 38%). Extrapelvic disease was detected in 31% of patients (5/16). In pre- and post-SLND PET comparison, 10/16 had at least one lesion already detected at baseline (63% PET persistence); 4/16 had new lesions only (25% PET recurrence); 2 had no disease on post-SLND PET. All validated regions (11 regions in 9 patients) were true positive. 9/14 (64%) patients underwent repeat local therapies after SLND (7/14 radiotherapy, 2/14 surgery). Conclusion: SLND of pelvic nodal metastases was often not complete according to PSMA-PET. About two thirds of patients had PET positive nodal disease after SLND already seen on pre-SLND PSMA-PET. Notably, about one quarter of patients had new lesions, not detected by pre-surgical PSMA-PET.




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Positron lymphography via intracervical 18F-FDG injection for pre-surgical lymphatic mapping in cervical and endometrial malignancies

Rationale: The presence of metastasis in local lymph nodes (LNs) is a key factor influencing choice of therapy and prognosis in cervical and endometrial cancers; therefore, the exploration of sentinel LNs (SLNs) is highly important. Currently, however, SLN mapping requires LN biopsy for pathologic evaluation, since there are no clinical imaging approaches that can identify tumor-positive LNs in early stages. Staging lymphadenectomy poses risks, such as leg lymphedema or lymphocyst formation. Furthermore, in 80% to 90% of patients, the explored LNs are ultimately tumor free, meaning the vast majority of patients are unnecessarily subjected to lymphadenectomy. Methods: Current lymphoscintigraphy methods only identify the anatomic location of the SLNs but do not provide information on their tumor status. There are no non-invasive methods to reliably identify metastases in LNs before surgery. We have developed positron lymphography (PLG), a method to detect tumor-positive LNs, where 18F-fluoro-2-deoxy-D-glucose (18F-FDG) is injected interstitially into the uterine cervix the day of surgery, and its rapid transport through the lymphatic vessels to the SLN is then visualized with dynamic positron emission tomography/computed tomography (PET/CT). We previously showed that PLG was able to identify metastatic LNs in animal models. Here, we present the first results from our pilot clinical trial (clinical trials identifier NCT02285192) in 23 patients with uterine or cervical cancer. On the morning of surgery, 18F-FDG was injected into the cervix, followed by an immediate dynamic PET/CT scan of the pelvis and a delayed 1-h whole body scan. Results: There were 3 (15%) node-positive cases on final pathologic analysis, and all LNs (including one with a focus of only 80 tumor cells) were identified by PLG except one node with an 11-mm micrometastasis. There were 2 (10%) false-positive cases with PLG, in which final pathology of the corresponding SLNs was negative for tumor. Methods: Current lymphoscintigraphy methods only identify the anatomic location of the SLNs but do not provide information on their tumor status. There are no non-invasive methods to reliably identify metastases in LNs before surgery. We have developed positron lymphography (PLG), a method to detect tumor-positive LNs, where 18F-fluoro-2-deoxy-D-glucose (18F-FDG) is injected interstitially into the uterine cervix the day of surgery, and its rapid transport through the lymphatic vessels to the SLN is then visualized with dynamic positron emission tomography/computed tomography (PET/CT). We previously showed that PLG was able to identify metastatic LNs in animal models. Here, we present the first results from our pilot clinical trial (clinical trials identifier NCT02285192) in 23 patients with uterine or cervical cancer. On the morning of surgery, 18F-FDG was injected into the cervix, followed by an immediate dynamic PET/CT scan of the pelvis and a delayed 1-h whole body scan. Results: There were 3 (15%) node-positive cases on final pathologic analysis, and all LNs (including one with a focus of only 80 tumor cells) were identified by PLG, except for one node with an 11-mm micrometastasis. There were 2 (10%) false-positive cases with PLG, in which final pathology of the corresponding SLNs was negative for tumor. Conclusion: This first-in-human study of PLG in women with uterine and cervical cancer demonstrates its feasibility and its ability to identify patients with nodal metastases, and warrants further evaluation in additional studies.




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11C-(+)-PHNO Trapping Reversibility for Quantitative PET Imaging of Beta-Cell-Mass in Patients with Type-1 Diabetes




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Individual mapping of innate immune cell activation is a candidate marker of patient-specific trajectories of disability worsening in Multiple Sclerosis

Objective: To develop a novel approach to generate individual maps of white matter (WM) innate immune cell activation using 18F-DPA-714 translocator protein (TSPO) positron emission tomography (PET), and to explore the relationship between these maps and individual trajectories of disability worsening in patients with multiple sclerosis (MS). Methods: Patients with MS (n = 37), whose trajectories of disability worsening over the 2 years preceding study entry were calculated, and healthy controls (n = 19) underwent magnetic resonance magnetic and 18F-DPA-714 PET. A threshold of significant activation of 18F-DPA-714 binding was calculated with a voxel-wise randomized permutation-based comparison between patients and controls, and used to classify each WM voxel in patients as characterized by a significant activation of innate immune cells (DPA+) or not. Individual maps of innate immune cell activation in the WM were employed to calculate the extent of activation in WM regions-of-interests and to classify each WM lesion as "DPA-active", "DPA-inactive" or "unclassified". Results: Compared with the WM of healthy controls, patients with MS had a significantly higher percentage of DPA+ voxels in the normal-appearing WM, (NAWM in patients=24.9±9.7%; WM in controls=14.0±7.8%, p<0.001). In patients with MS, the percentage of DPA+ voxels showed a significant increase from NAWM, to perilesional areas, T2 hyperintense lesions and T1 hypointense lesions (38.1±13.5%, 45.0±17.9%, and 51.9±22.9%, respectively, p<0.001). Among the 1379 T2 lesions identified, 512 were defined as DPA-active and 258 as DPA-inactive. A higher number of lesions classified as DPA-active (OR=1.13, P = 0.009), a higher percentage of DPA+ voxels in the NAWM (OR=1.16, P = 0.009) and in T1-spin-echo lesions (OR=1.06, P = 0.036), were significantly associated with a retrospective more severe clinical trajectory in patients with MS. Conclusion: A more severe trajectory of disability worsening in MS is associated with an innate immune cells activation inside and around WM lesions. 18F-DPA-714 PET may provide a promising biomarker to identify patients at risk of severe clinical trajectory.




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Kinetic modeling and test-retest reproducibility of 11C-EKAP and 11C-FEKAP, novel agonist radiotracers for PET imaging of the kappa opioid receptor in humans

The kappa opioid receptor (KOR) is implicated in various neuropsychiatric disorders. We previously evaluated an agonist tracer, 11C-GR103545, for PET imaging of KOR in humans. Although 11C-GR103545 showed high brain uptake, good binding specificity, and selectivity to KOR, it displayed slow kinetics and relatively large test-retest variability (TRV) of distribution volume (VT) estimates (15%). Therefore we set out to develop two novel KOR agonist radiotracers, 11C-EKAP and 11C-FEKAP, and in nonhuman primates, both tracers exhibited faster kinetics and comparable binding parameters to 11C-GR103545. The aim of this study was to assess their kinetic and binding properties in humans. Methods: Six healthy subjects underwent 120-min test-retest PET scans with both 11C-EKAP and 11C-FEKAP. Metabolite-corrected arterial input functions were measured. Regional time-activity curves (TACs) were generated for 14 regions of interest. One- and two-tissue compartment models (1TC, 2TC) and the multilinear analysis-1 (MA1) method were applied to the regional TACs to calculate VT. Time-stability of VT values and test-retest reproducibility were evaluated. Levels of specific binding, as measured by the non-displaceable binding potential (BPND) for the three tracers (11C-EKAP, 11C-FEKAP and 11C-GR103545), were compared using a graphical method. Results: For both tracers, regional TACs were fitted well with the 2TC model and MA1 method (t*=20min), but not with the 1TC model. Given unreliably estimated parameters in several fits with the 2TC model and a good match between VT values from MA1 and 2TC, MA1 was chosen as the appropriate model for both tracers. Mean MA1 VT values were highest for 11C-GR103545, followed by 11C-EKAP, then 11C-FEKAP. Minimum scan time for stable VT measurement was 90 and 110min for 11C-EKAP and 11C-FEKAP, respectively, compared with 140min for 11C-GR103545. The mean absolute TRV in MA1 VT estimates was 7% and 18% for 11C-EKAP and 11C-FEKAP, respectively. BPND levels were similar for 11C-FEKAP and 11C-GR103545, but ~25% lower for 11C-EKAP. Conclusion: The two novel KOR agonist tracers showed faster tissue kinetics than 11C-GR103545. Even with slightly lower BPND, 11C-EKAP is judged to be a better tracer for imaging and quantification of KOR in humans, based on the shorter minimum scan time and excellent test-retest.




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Africa’s Long-standing Leaders Are Disappearing

3 January 2020

Dr Alex Vines OBE

Managing Director, Ethics, Risk & Resilience; Director, Africa Programme
Leaders who cling to power are being pushed out across the continent, and the trend looks set to continue in 2020.

2020-01-03-Zim.jpg

A man holds a portrait of Robert Mugabe during his official funeral ceremony. Photo: Getty Images.

Africa’s dinosaur leaders are members of an increasingly small and unstable club. Popular protests last year forced Algeria’s president, Abdelaziz Bouteflika, out of office after almost 20 years in power, as well as Sudan’s president, Omar al-Bashir, who ruled for 30 years. In 2017, Robert Mugabe was deposed in a military coup (although this was denied) after 40 years. 
And in 2011, mass protests led to the downfall of Tunisia’s president, Zine el-Abidine Ben Ali, after he had been in power for 23 years.

Somewhat smoother are the political transitions in Angola and the Democratic Republic of the Congo (DRC). José Eduardo dos Santos, after almost 38 years in power, stepped down from office in 2017 as his term ended. So did his younger neighbour, Joseph Kabila, in January 2019, after 18 years in the presidency.

What the six former leaders had in common was that they wanted to remain heads of state and considered succession planning or stepping down only as a last resort. This year will be crucial for the six countries in political transition particularly as the reform-window period is short.

From A to Z 

Algeria: Tens of thousands of protesters have rallied in the capital Algiers and other cities against the December 2019 elections, rejecting what they see as sham transitional politics. A soft landing for Algeria in 2020 is unlikely, and what happens in the year has significant regional implications.

Angola: A transition is under way, led by President João Lourenço. This shift is smoother than many others, but 2020 will be the watershed year. The country has been in economic recession for four years but is predicted to see gross domestic product growth in 2020. Investment and job creation will determine the pace of change. The honeymoon period has ended and there are signs of increasing frustration among the urban youth and the middle class.

DRC: Despite his constitutionally mandated term expiring in December 2016, Joseph Kabila continued his presidency by continuously postponing elections until 30 December 2018. This election saw a three-way contest between the Union for Democracy and Social Progress (UDSP), the Engagement for Citizenship and Development party and the People’s Party for Reconstruction and Democracy (PPRD). Fèlix Tshisekedi of the UDSP was declared the winner by the Independent National Electoral Commission on January 10 last year with 38.6% votes. He was followed by Martin Fayulu of the Engagement for Citizenship and Development party, with 34.8%. He denounced the election results. In third place was Emmanuel Ramazani Shadary, of the PPRD, a key ally of Kabila.

Although this was the first peaceful transition of power in DRC, there were widespread electoral inconsistencies and some observers believed that Fayulu was the legitimate winner. In 2020 it will become clearer whether a genuine transition from Kabila’s influence is taking place.

Sudan: More promising than the DRC or Algeria, a 39-month transitional administration led by a technocratic prime minister, Abdalla Hamdok, has been established and enjoys domestic and international goodwill. This honeymoon is likely to be short, and the transitional administration needs to show results. The United States can help by removing Sudan from its terror list, thereby lifting the de facto ban on Sudan’s access to the dollar-based international financial system.

Tunisia: A low-profile, conservative law professor beat a charismatic media magnate released from prison in the presidential election runoff in October 2019. Kais Saied won 70% of the vote and his victory and the putting together of a new governing coalition is another step forward in an open-ended democratic transition that started in 2011 after Ben Ali fell.

Zimbabwe: This is a deeply troubled transition with an acute foreign exchange liquidity crisis, a deteriorating economy, hyperinflation and underperforming government. The state’s clinics and hospitals are closed or turn away patients as medical supplies run out and the doctors’ strike over decimated wages continues. There are power outages and almost half of the people face hunger and starvation as a result of drought and the economic crisis.

Zimbabwe’s 2020 looks bleak, a far cry from the euphoria of two years ago when a “military assisted transition” removed Mugabe and replaced him with Emmerson Mnangagwa.

More changes coming

So what do these political developments in 2019 tell us more broadly?

Long-standing leaders have been persistent in Africa, despite the end of single-party rule in favour of a multiparty system. About a fifth of all African heads of state since independence can be classed as long-standing leaders — in power for more than a decade — and only five countries have never experienced one. But the trend is in decline.

It remains most resilient in central Africa and in the Great Lakes regions. Cracks are appearing in their citadels in Malabo and Kampala, but in 2019 Equatorial Guinea’s President Teodoro Obiang Mbasogo celebrated 40 years in power and Uganda’s Yoweri Museveni 33 years.

Will there be any more departures from the dinosaurs club in 2020?

One of the shortest serving members of this club, President Pierre Nkurunziza (14 years in power) has said he will not stand for the 2020 elections in Burundi, although this is uncertain given that a 2018 constitutional referendum could allow him to stay in power until 2034. Togo’s Faure Gnassingbé (14 years in power) will stand for re-election to the presidency again after Parliament in 2019 approved a constitutional change permitting him to potentially stay in office until 2030.

Amending constitutions to change term limits so that incumbent leaders can run for office is a favoured tactic. Rwanda’s Paul Kagame (19 years in office) and the Republic of Congo’s Denis Sassou Nguesso (25 years in power) have done this. But Eritrea’s Isaias Afwerki has never held an election during his 16 years in power.

Attempts at dynasties have been less successful, such as with Grace Mugabe in Zimbabwe or Gamal Mubarak in Egypt, but Obiang is grooming his playboy son Teodorin to succeed him and Gabon’s Ali Bongo and Togo’s Gnassingbé both succeeded their fathers.

The year is a reminder that more of these long-standing leaders will, in 2020 and beyond, step down or die. Most long-standing leaders in Africa are over the age of 70, with Paul Biya, aged 86, having served 37 years as Cameroon’s president.

Some former leaders capitulated under internal pressure: in Algeria, Sudan, Tunisia and Zimbabwe. Only in Angola and the DRC was a transition process organized as part of an elite bargain.

What the political transitions have in common is that honeymoons are short and that, whether they are led by interim administrations or elected leaders, they need to deliver political and socioeconomic improvements to succeed, but have inherited shambolic economies. Their success depends on accountable political leadership and domestic and international support.

This article was originally published by the Mail & Guardian.




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Phosphoproteomic Approaches to Discover Novel Substrates of Mycobacterial Ser/Thr Protein Kinases [Reviews]

Mycobacterial Ser/Thr protein kinases (STPKs) play a critical role in signal transduction pathways that ultimately determine mycobacterial growth and metabolic adaptation. Identification of key physiological substrates of these protein kinases is, therefore, crucial to better understand how Ser/Thr phosphorylation contributes to mycobacterial environmental adaptation, including response to stress, cell division, and host-pathogen interactions. Various substrate detection methods have been employed with limited success, with direct targets of STPKs remaining elusive. Recently developed mass spectrometry (MS)-based phosphoproteomic approaches have expanded the list of potential STPK substrate identifications, yet further investigation is required to define the most functionally significant phosphosites and their physiological importance. Prior to the application of MS workflows, for instance, GarA was the only known and validated physiological substrate for protein kinase G (PknG) from pathogenic mycobacteria. A subsequent list of at least 28 candidate PknG substrates has since been reported with the use of MS-based analyses. Herein, we integrate and critically review MS-generated datasets available on novel STPK substrates and report new functional and subcellular localization enrichment analyses on novel candidate protein kinase A (PknA), protein kinase B (PknB) and PknG substrates to deduce the possible physiological roles of these kinases. In addition, we assess substrate specificity patterns across different mycobacterial STPKs by analyzing reported sets of phosphopeptides, in order to determine whether novel motifs or consensus regions exist for mycobacterial Ser/Thr phosphorylation sites. This review focuses on MS-based techniques employed for STPK substrate identification in mycobacteria, while highlighting the advantages and challenges of the various applications.




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Tandem Mass Tag Approach Utilizing Pervanadate BOOST Channels Delivers Deeper Quantitative Characterization of the Tyrosine Phosphoproteome [Technological Innovation and Resources]

Dynamic tyrosine phosphorylation is fundamental to a myriad of cellular processes. However, the inherently low abundance of tyrosine phosphorylation in the proteome and the inefficient enrichment of phosphotyrosine(pTyr)-containing peptides has led to poor pTyr peptide identification and quantitation, critically hindering researchers' ability to elucidate signaling pathways regulated by tyrosine phosphorylation in systems where cellular material is limited. The most popular approaches to wide-scale characterization of the tyrosine phosphoproteome use pTyr enrichment with pan-specific, anti-pTyr antibodies from a large amount of starting material. Methods that decrease the amount of starting material and increase the characterization depth of the tyrosine phosphoproteome while maintaining quantitative accuracy and precision would enable the discovery of tyrosine phosphorylation networks in rarer cell populations. To achieve these goals, the BOOST (Broad-spectrum Optimization Of Selective Triggering) method leveraging the multiplexing capability of tandem mass tags (TMT) and the use of pervanadate (PV) boost channels (cells treated with the broad-spectrum tyrosine phosphatase inhibitor PV) selectively increased the relative abundance of pTyr-containing peptides. After PV boost channels facilitated selective fragmentation of pTyr-containing peptides, TMT reporter ions delivered accurate quantitation of each peptide for the experimental samples while the quantitation from PV boost channels was ignored. This method yielded up to 6.3-fold boost in pTyr quantification depth of statistically significant data derived from contrived ratios, compared with TMT without PV boost channels or intensity-based label-free (LF) quantitation while maintaining quantitative accuracy and precision, allowing quantitation of over 2300 unique pTyr peptides from only 1 mg of T cell receptor-stimulated Jurkat T cells. The BOOST strategy can potentially be applied in analyses of other post-translational modifications where treatments that broadly elevate the levels of those modifications across the proteome are available.




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Proximity Dependent Biotinylation: Key Enzymes and Adaptation to Proteomics Approaches [Reviews]

The study of protein subcellular distribution, their assembly into complexes and the set of proteins with which they interact with is essential to our understanding of fundamental biological processes. Complementary to traditional assays, proximity-dependent biotinylation (PDB) approaches coupled with mass spectrometry (such as BioID or APEX) have emerged as powerful techniques to study proximal protein interactions and the subcellular proteome in the context of living cells and organisms. Since their introduction in 2012, PDB approaches have been used in an increasing number of studies and the enzymes themselves have been subjected to intensive optimization. How these enzymes have been optimized and considerations for their use in proteomics experiments are important questions. Here, we review the structural diversity and mechanisms of the two main classes of PDB enzymes: the biotin protein ligases (BioID) and the peroxidases (APEX). We describe the engineering of these enzymes for PDB and review emerging applications, including the development of PDB for coincidence detection (split-PDB). Lastly, we briefly review enzyme selection and experimental design guidelines and reflect on the labeling chemistries and their implication for data interpretation.




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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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Centrelink blocks 60,000 calls a day, blames smartphone apps

Centrelink blocked 22m phone calls last year, with smartphone apps blamed for inflating the figures.




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From AFL star to Big Apple start-up, Swift's Joel MacDonald is kicking goals

Two years ago Joel MacDonald was in Melbourne playing in the AFL; now he's kicking goals in New York.




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Apple v FBI: what the fight is about and why you should care

Apple is in the middle of a legal fight with the FBI over creating a 'back door' to unlock a terrorist's iPhone.




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Slack's secret sauce: how it became the fastest growing business app ever

Slack has launched its Asia-Pacific headquarters in Melbourne. We caught up with Ali Rayl, head of customer experience.




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ACT human rights commission 'concerned' about new app for ACT police

Canberrans' privacy rights could be threatened by the new app.




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The great Chinese surprise: the rupture with the United States is real and is happening

4 March 2020 , Volume 96, Number 2

Xiangfeng Yang

Ample evidence exists that China was caught off guard by the Trump administration's onslaught of punishing acts—the trade war being a prime, but far from the only, example. This article, in addition to contextualizing their earlier optimism about the relations with the United States under President Trump, examines why Chinese leaders and analysts were surprised by the turn of events. It argues that three main factors contributed to the lapse of judgment. First, Chinese officials and analysts grossly misunderstood Donald Trump the individual. By overemphasizing his pragmatism while downplaying his unpredictability, they ended up underprepared for the policies he unleashed. Second, some ingrained Chinese beliefs, manifested in the analogies of the pendulum swing and the ‘bickering couple’, as well as the narrative of the ‘ballast’, lulled officials and scholars into undue optimism about the stability of the broader relationship. Third, analytical and methodological problems as well as political considerations prevented them from fully grasping the strategic shift against China in the US.




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UK Tech Weekly Podcast - Episode Seven: The Internet of Fruit (IoF) Apple, BlackBerry & Raspberry Pi

In this week's UK Tech Weekly Podcast host Matt Egan is joined by acting editor at Macworld.co.uk David Price to discuss this week's Apple event announcements, from the iPhone SE to the iPad Pro and iOS 9.3. Then first time podder and staff writer at Macworld.co.uk Henry Burrell wades in to discuss Facebook dropping its support for Blackberry and the future of the under-fire mobile phone maker (19:45). Finally, online editor at Techworld.com Scott Carey chats coding in schools following the BBC micro:bit news and how it differs from the Raspberry Pi (27:40).  


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Episode Eight: The Internet of Genocidal Chatbots (IoGC) Tay, Microsoft Build and Apple vs FBI

In this week's UK Tech Weekly Podcast host Matt Egan is joined by online editor at Techworld.com Scott Carey to discuss all of the news coming out of Microsoft's Build 2016 developer conference, before being joined by producer Chris to talk about the company's genocidal AI chatbot Tay's public meltdown (13:00). Then, acting editor at Macworld.co.uk David Price jumps in to discuss the apparent resolution to the Apple vs FBI fight (29:00).  


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Episode Nine - The Internet of Li-Fi in Dubai-Fi (IoLFiDF) Huawei, Whatsapp, Panama Papers and Li-Fi

This week host Matt Egan kicks things off by chatting to staff writer Lewis Painter about the (genuinely) impressive Huawei P9 phone release. Then, acting editor at Macworld.co.uk David Price jumps in to discuss Whatsapp encryption (12:30) and the Panama Papers. Finally, Christina Mercer, online editor at Techworld.com, introduces you to the wonderful world of Li-Fi (24:30).  


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Episode 11 - The Internet of Dating Apps (IoDA): Apple Macbook news, Google antitrust & dating apps

This week host Matt Egan is rejoined by Macworld.co.uk acting editor David Price to chat about Apple's latest Macbook announcements. Then online editor at ComputerworldUK Christina Mercer jumps in to give a break down of Google's fight with the EU over antitrust infringements (13:00). Finally, ex-dating app user Scott Carey, online editor at Techworld.com gives a state of the union on dating apps, from Tinder to Bumble to Happn, if they are good for society and which one is set to corner the market (27:00).  


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Episode 12 - The Internet of Voodoo Streaming Services (IoVSS) Apple & Facebook results, Nintendo NX

This week host Matt Egan is joined by regular podder David Price, acting editor of Macworld.co.uk, to discuss Apple's not so awesome results and stalling iPhone sales. Then online editor Scott Carey jumps in to discuss Facebook's far better results and how it has come to dominate the mobile advertising market (15:00) Finally, producer Chris comes out from behind the glass to discuss Nintendo's secretive NX console and having to wait for the new Zelda game (28:00).  


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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).  


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Episode 25 - The Internet of Bread (IoB) Windows 10, Verizon buys Yahoo! & Apple results

Hosting duties fall to Henry Burrell this week as he discusses the deadline for the free Microsoft Windows 10 update with Chris Minasians, staff writer at PC Advisor. Scott Carey, online editor at Techworld.com jumps in to talk about why the Verizon deal for Yahoo is ridiculous and charts the missteps that got the company to this point (15:00). Finally, regular guest David Price discusses Apple's less than stellar financial results and if the iPhone is plateauing (26:00).  


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Episode 30 - The Internet of Unlimited Play-Doh (IoUPD): Amazon Dash, Apple tax and headphone sexism

This week Ashleigh Allsopp is simultaneously fascinated and worried by the UK launch of Amazon's Dash buttons, and discusses the many wonderful and not-so-wonderful things they enable you to buy on a drunken whim. Then David Price takes his turn to shine a spotlight on Apple's mysterious tax affairs (12:20) and tries to explain why the Irish government doesn't want to be given 13 billion euros. Finally a surprisingly riled-up Neil Bennett explains why women wearing headphones are not fair game for dimwitted pick-up artists (25:00), and ponders the social conventions surrounding the place of technology in each of our lives.  


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Episode 31 - The Internet of David's Heroes (IoDH): Apple, Apple, Apple, and the things Apple didn't do (IFA)

In this week's inexplicably klaxon-heavy and fish-themed APPLE SPECIAL episode, David Price praises Apple for rescuing us from the tyranny of wired headphones, and reveals a hitherto unsuspected penchant for former Everton strikers. Chris Martin (22:41) dazzles us with his knowledge of the Apple Watch Series Two, and display some unusual headphone usage, and Henry Burell (32:51) reveals that Berlin is big, and sheds some light on the tiny corner of tech that *isn't* Apple flavoured. Join us.  


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Episode 48 - The Internet of the International Ruling Class (IotIRC) Nintendo Switch, Davos and app prices

Host Matt Egan clips us round the ear and tells us to listen up as we chat yet more tech and then some other stuff about tech. Consumer tech editor at PC Advisor Chris Martin lays down his definitive opinion after he went hands on with the Nintendo Switch this week, and why the company really should have had their star plumber ready in time for launch. Tamlin Magee, Online Editor at Computerworld UK then takes us through the odd goings on at Davos, and whether or not the elite can identify with what tech actually means to real working people. To round us up, Acting Macworld UK Editor David Price explains why app prices are going up in the UK for iOS users, and why it might - might - not be UKIP's fault. Sort of.  


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Episode 51 - The Internet of Sick Burns (IoSB) Snapchat IPO, Android Wear 2.0 and Apple in India

Techworld Editor Charlotte Jee conducts the tech orchestra this week, trying to get a tune out of this cold, creaking week. Online Editor at Computerworld UK Scott Carey lets us know all about Snapchat's upcoming IPO, billions of dollars, and the gang comes to the realisation they'll perhaps never understand what it's for. Then Senior Staff Writer at PC Advisor Henry Burrell recaps on Google and LG's launch of Android Wear 2.0 and ask - frankly - is it a big deal? Finally Acting Editor at Macworld UK David Price discusses Apple's rumoured plans to move manufacturing to India, which inevitably moves us on to Tech Trumps.  


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Episode 52 - The Internet of Nostalgia (IoN) Nokia 3310, drone taxis and Apple on the telly

Matt Egan takes us where no other pod has dared gone before (September 2000) and asks Digital Arts Editor Neil Bennett if anyone cares that Nokia is rereleasing the famous 3310. Is it cool to rock one now? Then Techworld Audience Development Editor Christina Mercer lets us know that the future is already here with self driving drone taxis. Would you hitch a lift round Dubai on a massive quadcopter? Finally Deputy Editor at Macworld David Price ruminates on Apple's forecast foray into the world of snackable media content - will it challenge Netflix or try to buy it?  


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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?  


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Episode 57 - The Internet of Apple press releases (IoAPR) iPads, red iPhones, black OnePlus phones and Android O

Gather round as three men spend 30 minutes talking about tech. Wait, what do you mean 'no thanks'?! Matt Egan shares the mic with David Price and Henry Burrell to thrash out why Apple deemed a press release adequate to announce the successor to 2014's iPad Air 2. There's also a slick new red iPhone, and a black OnePlus 3T. What's with the limited editions, eh? Or are they even limited? The gang also chat about the developer preview of Android O, out now while Android N is barely months old. Is it too early to say if it'll kick ass, and why do Google and Apple need such long public lead time with new OS builds?  


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Episode 64 - The Internet of Hype (IoH) Apple Special, again!

June means WWDC, and boy did Apple deliver this year. HomePod! iPad! Software! It's all here. Join the Macworld massive David Price, Ashleigh Macro, Dom Preston and Henry Burrell as they rifle through 40 minutes of on-the-nose critiques of Apple's latest announcements. With the new iMac Pro, iPad 10.5in and HomePod, the company introduced hardware for the first time since 2013, while the introduction of iOS 11 sets us up for the iPhone 8 in September. To the orchard!  


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