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Tax time IT problems strike again at Australian Taxation Office

Slow internet is causing headaches during a busy time at the Tax Office.




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Cyber security threat: Is Australia's power grid safe from hackers?

Cyber attacks have labelled the number one threat to power and utility companies worldwide, a new EY report has found.




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Schnyder corneal dystrophy-associated UBIAD1 is defective in MK-4 synthesis and resists autophagy-mediated degradation

Dong-Jae Jun
May 1, 2020; 61:746-757
Research Articles




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Episode 42 - The Internet of Chinese Boogie Men (IoCBM) Black Friday, Facebook and Autumn Statement

Matt Egan is in the presenter chair this week as he chats about Black Friday and the changing face of online retail with acting editor at Macworld UK, David Price. Then online editor at Techworld.com Scott Carey talks Facebook and its recent issues with fake news and Chinese censorship (12:00). Finally, online editor at Computerworld UK Tamlin Magee brings us up to date with the Government's Autumn Statement and what it means for the technology sector (26:00).  


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




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Episode 55 - The Internet of Leaking Everything (IoLE) New iPads, Vault 7 and Nintendo Switch woes

The big story of the week is Wikileaks' CIA data dump, and we sandwich that topic between Apple's upcoming event and Nintendo Switch hardware issues. Lewis Painter kicks things off with Apple's (fingers crossed) late March event where we hope to see iPads, iMacs and get our six monthly fix of Jony Ive product videos. Then (13 minutes) Tamlin Magee tackles Vault 7 and the CIA's apparent ability to take control of iPhones and TVs, bypassing encryption. Will continuous leaks change anything? Finally (26 minutes) Dom Preston talks about his time over the last few weeks playing Zelda on the Nintendo Switch and why we should be a bit concerned about dodgy controllers.  


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




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Episode 61 - The Internet of automated selfies (IoAS) Amazon Echo Look and job automation

Join host Henry Burrell in conversation with two editors, Karen Khan of Macworld UK in her debut pod along with pod regular Charlotte Jee of Techworld. We tackle the issues of privacy and self esteem, particularly in the young people that we are not, and ask who this product is for (because surely it will sell). Tech obviously plays a big part in the selfie phenomenon/epidemic. Second we discuss automation and how it is affecting the job market. Can a robot make an iPhone? Is Trump right about bringin' it all back home? What should politicians be doing to understand the technology involved? Thanks for listening, listener.  


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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Detection of multiple autoantibodies in patients with ankylosing spondylitis using nucleic acid programmable protein arrays [11. Microarrays/Combinatorics/Display Technology]

Ankylosing Spondylitis (AS) is a common, inflammatory rheumatic disease, which primarily affects the axial skeleton and is associated with sacroiliitis, uveitis and enthesitis. Unlike other autoimmune rheumatic diseases, such as rheumatoid arthritis or systemic lupus erythematosus, autoantibodies have not yet been reported to be a feature of AS. We therefore wished to determine if plasma from patients with AS contained autoantibodies and if so, characterize and quantify this response in comparison to patients with Rheumatoid Arthritis (RA) and healthy controls. Two high-density nucleic acid programmable protein arrays expressing a total of 3498 proteins were screened with plasma from 25 patients with AS, 17 with RA and 25 healthy controls. Autoantigens identified were subjected to Ingenuity Pathway Analysis in order to determine patterns of signalling cascades or tissue origin. 44% of patients with Ankylosing Spondylitis demonstrated a broad autoantibody response, as compared to 33% of patients with RA and only 8% of healthy controls. Individuals with AS demonstrated autoantibody responses to shared autoantigens, and 60% of autoantigens identified in the AS cohort were restricted to that group. The AS patients autoantibody responses were targeted towards connective, skeletal and muscular tissue, unlike those of RA patients or healthy controls. Thus, patients with AS show evidence of systemic humoral autoimmunity and multispecific autoantibody production. Nucleic Acid Programmable Protein Arrays constitute a powerful tool to study autoimmune diseases.




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The Beauty of Proteomics [Invited]

Cover art by Julie Newdoll for MCP April issue.




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Dysregulation of Exosome Cargo by Mutant Tau Expressed in Human-Induced Pluripotent Stem Cell (iPSC) Neurons Revealed by Proteomics Analyses [Research]

Accumulation and propagation of hyperphosphorylated tau (p-tau) is a common neuropathological hallmark associated with neurodegeneration of Alzheimer's disease (AD), frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), and related tauopathies. Extracellular vesicles, specifically exosomes, have recently been demonstrated to participate in mediating tau propagation in brain. Exosomes produced by human induced pluripotent stem cell (iPSC)-derived neurons expressing mutant Tau (mTau), containing the P301L and V337M Tau mutations of FTDP-17, possess the ability to propagate p-tau pathology after injection into mouse brain.  To gain an understanding of the mTau exosome cargo involved in tau pathogenesis, these pathogenic exosomes were analyzed by proteomics and bioinformatics. The data showed that mTau expression dysregulates the exosome proteome to result in (1) proteins uniquely present only in mTau, and not control exosomes, (2) the absence of proteins in mTau exosomes, uniquely present in control exosomes, and (3) shared proteins which were significantly up-regulated or down-regulated in mTau compared to control exosomes. Notably, mTau exosomes (not control exosomes) contain ANP32A (also known as I1PP2A), an endogenous inhibitor of the PP2A phosphatase which regulates the phosphorylation state of p-tau.  Several of the mTau exosome-specific proteins have been shown to participate in AD mechanisms involving lysosomes, inflammation, secretases, and related processes.  Furthermore, the mTau exosomes lacked a substantial portion of proteins present in control exosomes involved in pathways of localization, vesicle transport, and protein binding functions. The shared proteins present in both mTau and control exosomes represented exosome functions of vesicle-mediated transport, exocytosis, and secretion processes. These data illustrate mTau as a dynamic regulator of the biogenesis of exosomes to result in acquisition, deletion, and up- or down-regulation of protein cargo to result in pathogenic mTau exosomes capable of in vivo propagation of p-tau neuropathology in mouse brain. 




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Economic Crisis and the Delayed Arrival of a New President: Transition Trauma

1 November 2008 , Number 1

The new American president will not be inaugurated until January 20. He will certainly face the most difficult economic conditions since Franklin Roosevelt entered the White House in March 1933. The politics of presidential transition – in this year, as seventy-six years ago – seem likely only to exacerbate the global crisis.

John Dumbrell

Professor of Government, Durham University




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Soundscapes of war: the audio-visual performance of war by Shi'a militias in Iraq and Syria

7 May 2020 , Volume 96, Number 3

Helle Malmvig

This article sets out to bring sound and music to the field of visual studies in International Relations. It argues that IR largely has approached the visual field as if it was without sound; neglecting how audial landscapes frame and direct our interpretation of moving imagery. Sound and music contribute to making imagery intelligible to us, we ‘hear the pictures’ often without noticing. The audial can for instance articulate a visual absence, or blast visual signs, bring out certain emotional stages or subjects’ inner life. Audial frames steer us in distinct directions, they can mute the cries of the wounded in war, or amplify the sounds of joy of soldiers shooting in the air. To bring the audial and the visual analytically and empirically together, the article therefore proposes four key analytical themes: 1) the audial–visual frame, 2) point of view/point of audition, 3) modes of audio-visual synchronization and 4) aesthetics moods. These are applied to a study of ‘war music videos’ in Iraq and Syria made and circulated by Shi'a militias currently fighting there. Such war music videos, it is suggested, are not just artefacts of popular culture, but have become integral parts of how warfare is practiced today, and one that is shared by soldiers in the US and Europe. War music videos are performing war, just as they shape how war is known by spectators and participants alike.




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Three Challenges for UK Peacebuilding Policy in the South Caucasus After Brexit

21 January 2020

Laurence Broers

Associate Fellow, Russia and Eurasia Programme
Building on the legacies of a long-term British investment in a peace strategy for the South Caucasus is a realistic and attainable goal.

2020-01-21-NK.jpg

A building in Nagorny Karabakh flies the flag of the self-proclaimed republic. 'Abkhazia, South Ossetia and Nagorny Karabakh have evolved into examples of what scholars call "de facto states" that, to differing degrees, control territory, provide governance and exercise internal sovereignty,' writes Laurence Broers. Photo: Getty Images.

What does Britain’s departure from the EU mean for the country’s policy towards the South Caucasus, a small region on the periphery of Europe, fractured by conflict? Although Britain is not directly involved in any of the region’s peace processes (except in the case of the Geneva International Discussions on conflicts involving Georgia, as an EU member state), it has been a significant stakeholder in South Caucasian stability since the mid-1990s.

Most obviously, Britain has been the single largest foreign investor in Caspian oil and gas. Yet beyond pipelines, Britain also has been a significant investor in long-term civil society-led strategies to build peace in the South Caucasus.

Through what was then the Global Conflict Prevention Pool, in the early 2000s the Department for International Development (DfID) pioneered large-scale peacebuilding interventions, such as the Consortium Initiative, addressing Armenian-Azerbaijani conflict, in 2003-09. These built civic networks in the South Caucasus and partnerships with British-based NGOs.

This experience left a strong intellectual legacy. British expertise on the South Caucasus, including specific expertise on its conflicts, is highly regarded in the region and across the world.

There is also a strong tradition of British scholarship on the Caucasus, and several British universities offer Caucasus-related courses. Through schemes such as the John Smith Fellowship Trust, the Robert Bosch Stiftung Academy Fellowship at Chatham House and Chevening Scholarships, significant numbers of young leaders from the South Caucasus have spent time in British institutions and built effective relationships within them.

Three challenges

This niche as a champion of long-term, strategic peacebuilding and repository of area-specific knowledge should not be lost as Britain’s relationship with the EU and regional actors evolves. This can be ensured through awareness of three challenges confronting a post-Brexit Caucasus policy.

The first challenge for London is to avoid framing a regional policy in the South Caucasus as an extension of a wider ‘Russia policy’. Deteriorating Russian-British relations in recent years strengthen a tendency to view policies in the European neighbourhood through the traditional prisms of Cold War and Russian-Western rivalries.

Yet an overwhelming focus on Russia fails to capture other important aspects of political developments in South Caucasus conflicts. Although often referred to as ‘breakaway’ or ‘occupied’ territories, Abkhazia, South Ossetia and Nagorny Karabakh are not ungoverned spaces. They have evolved into examples of what scholars call ‘de facto states’ that, to differing degrees, control territory, provide governance and exercise internal sovereignty.

Few disagree that these entities would not survive without external patronage. But neither does that patronage explain their sustainability on its own. Russia-centricity diminishes Britain’s latitude to engage on the full range of local drivers sustaining these entities, contributing instead to less effective policies predicated on competition and containment.

A second and related challenge is to maintain and develop Britain’s position on the issue of engaging populations in these entities. De facto states appear to stand outside of the international rules-based system. Yet in many cases, their civil societies are peopled by skilled and motivated activists who want their leaders to be held accountable according to international rules.

Strategies of isolation ignore these voices and contribute instead to fearful and demoralized communities less likely to engage in a transformation of adversarial relationships. Making this case with the wider international community, and facilitating the funding of local civil societies in contested territories, would be important steps in sustaining an effective British policy on the resolution of conflicts.    

The third challenge for Britain is to maintain a long-term approach to the conflicts of the South Caucasus alongside potential short-term imperatives in other policy fields, as relationships shift post-Brexit.

In this fluid international environment, the Foreign and Commonwealth Office has a role to play both as an internal champion of a long-term peacebuilding strategy and a coordinator of British efforts with those of multilateral actors engaged in the South Caucasus. These include the United Nations, the EU’s Special Representative for the South Caucasus and the Crisis in Georgia and OSCE’s Special Representative for the OSCE Chairperson-in-Office for the South Caucasus, all of which have built relationships with relevant actors on the ground.

Recommendations

Britain’s niche as a champion and advocate of a strategic approach to peaceful change can be secured post-Brexit in the following ways.  

First, in-house expertise is crucial to effective peacebuilding programming. The Foreign Office’s research analysts play a vital role in generating independent internal advice and liaising with academic and NGO communities. Their role could be supplemented by the reinstatement of a regional conflict adviser post, based in Tbilisi, tasked with strengthening Britain’s regional presence on conflict issues and coordinating policy at a regional level.

This post, with a remit to cover conflicts and build up area knowledge and relationships can contribute significantly to working closely with local civil societies, where so much expertise and knowledge resides, as well as other stakeholders.

Second, programming should build in conflict sensitivity by dissociating eligibility from contested political status. This can encourage local populations to take advantage of opportunities for funding, study, comparative learning and professional development irrespective of the status of the entity where they reside.

The Chevening Scholarships are an excellent example, whereby applicants can select ‘South Caucasus’ as their affiliated identity from a drop-down menu. This enables citizens from across the region to apply irrespective of the status of the territory in which they live.   

Finally, a holistic understanding of peace is crucial. Programming in unrecognized or partially-recognized entities should acknowledge that effective peacebuilding needs to embrace political dynamics and processes beyond cross-conflict contact and confidence building. Local actors in such entities may find peacebuilding funding streams defined exclusively in terms of cross-conflict contact more politically risky and ineffective in addressing domestic blockages to peace.

While cross-conflict dynamics remain critical, ‘single-community’ programming framed in terms of civic participation, inclusion, civil society capacity-building, minority and human rights in contested territories, and building the confidence from within to engage in constructive dialogue, are no less important.

The ’global Britain’ promised by Brexit remains a fanciful idea. Quiet, painstaking work to build on the legacies of a long-term British investment in a peace strategy for the South Caucasus, on the other hand, is a realistic and attainable goal.




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Hepatic PLIN5 signals via SIRT1 to promote autophagy and prevent inflammation during fasting [Research Articles]

Lipid droplets (LDs) are energy-storage organelles that are coated with hundreds of proteins, including members of the perilipin (PLIN) family. PLIN5 is highly expressed in oxidative tissues, including the liver, and is thought to play a key role in uncoupling LD accumulation from lipotoxicity; however, the mechanisms behind this action are incompletely defined. We investigated the role of hepatic PLIN5 in inflammation and lipotoxicity in a murine model under both fasting and refeeding conditions and in hepatocyte cultures. PLIN5 ablation with antisense oligonucleotides triggered a pro-inflammatory response in livers from mice only under fasting conditions. Similarly, PLIN5 mitigated lipopolysaccharide- or palmitic acid-induced inflammatory responses in hepatocytes. During fasting, PLIN5 was also required for the induction of autophagy, which contributed to its anti-inflammatory effects. The ability of PLIN5 to promote autophagy and prevent inflammation were dependent upon signaling through sirtuin 1 (SIRT1), which is known to be activated in response to nuclear PLIN5 under fasting conditions. Taken together, these data show that PLIN5 signals via SIRT1 to promote autophagy and prevent FA-induced inflammation as a means to maintain hepatocyte homeostasis during periods of fasting and FA mobilization.




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Schnyder corneal dystrophy-associated UBIAD1 is defective in MK-4 synthesis and resists autophagy-mediated degradation [Research Articles]

The autosomal dominant disorder Schnyder corneal dystrophy (SCD) is caused by mutations in UbiA prenyltransferase domain-containing protein-1 (UBIAD1), which uses geranylgeranyl pyrophosphate (GGpp) to synthesize the vitamin K2 subtype menaquinone-4 (MK-4). SCD is characterized by opacification of the cornea, owing to aberrant build-up of cholesterol in the tissue. We previously discovered that sterols stimulate association of UBIAD1 with ER-localized HMG-CoA reductase, which catalyzes a rate-limiting step in the synthesis of cholesterol and nonsterol isoprenoids, including GGpp. Binding to UBIAD1 inhibits sterol-accelerated ER-associated degradation (ERAD) of reductase and permits continued synthesis of GGpp in cholesterol-replete cells. GGpp disrupts UBIAD1-reductase binding and thereby allows for maximal ERAD of reductase as well as ER-to-Golgi translocation of UBIAD1. SCD-associated UBIAD1 is refractory to GGpp-mediated dissociation from reductase and remains sequestered in the ER to inhibit ERAD. Here, we report development of a biochemical assay for UBIAD1-mediated synthesis of MK-4 in isolated membranes and intact cells. Using this assay, we compared enzymatic activity of WT UBIAD1 with that of SCD-associated variants. Our studies revealed that SCD-associated UBIAD1 exhibited reduced MK-4 synthetic activity, which may result from its reduced affinity for GGpp. Sequestration in the ER protects SCD-associated UBIAD1 from autophagy and allows intracellular accumulation of the mutant protein, which amplifies the inhibitory effect on reductase ERAD. These findings have important implications not only for the understanding of SCD etiology but also for the efficacy of cholesterol-lowering statin therapy, which becomes limited, in part, because of UBIAD1-mediated inhibition of reductase ERAD.




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Problem Notes for SAS®9 - 34294: A missing discrete dependent variable in the selection model together with a OUTPUT statement might cause an Access Violation error

If the following conditions are met in PROC QLIM: the SELECT option and DISCRETE option are specified in the same MODEL statement or ENDOGENOUS statement the same dependent variable with S




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Problem Notes for SAS®9 - 65682: Running FedSQL with an Oracle table is slow, even when you use a LIMIT clause

When you query an Oracle table and use the LIMIT clause using either SAS  Federation Server or FedSQL, a row limit is not passed to the database. In this scenario, a Full Article



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Problem Notes for SAS®9 - 65597: An SQL procedure query with a WHERE clause that contains multiple subselects might return incorrect results

An issue occurs when code contains a complex SQL procedure query with a WHERE clause that contains multiple subselects. Incorrect results might be returned. Click the Hot Fix tab in this note to




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Linking risk factors and outcomes in autism spectrum disorder: is there evidence for resilience?




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Autoimmune complications of immunotherapy: pathophysiology and management




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ER stress increases store-operated Ca2+ entry (SOCE) and augments basal insulin secretion in pancreatic beta cells [Molecular Bases of Disease]

Type 2 diabetes mellitus (T2DM) is characterized by impaired glucose-stimulated insulin secretion and increased peripheral insulin resistance. Unremitting endoplasmic reticulum (ER) stress can lead to beta-cell apoptosis and has been linked to type 2 diabetes. Although many studies have attempted to link ER stress and T2DM, the specific effects of ER stress on beta-cell function remain incompletely understood. To determine the interrelationship between ER stress and beta-cell function, here we treated insulin-secreting INS-1(832/13) cells or isolated mouse islets with the ER stress–inducer tunicamycin (TM). TM induced ER stress as expected, as evidenced by activation of the unfolded protein response. Beta cells treated with TM also exhibited concomitant alterations in their electrical activity and cytosolic free Ca2+ oscillations. As ER stress is known to reduce ER Ca2+ levels, we tested the hypothesis that the observed increase in Ca2+ oscillations occurred because of reduced ER Ca2+ levels and, in turn, increased store-operated Ca2+ entry. TM-induced cytosolic Ca2+ and membrane electrical oscillations were acutely inhibited by YM58483, which blocks store-operated Ca2+ channels. Significantly, TM-treated cells secreted increased insulin under conditions normally associated with only minimal release, e.g. 5 mm glucose, and YM58483 blocked this secretion. Taken together, these results support a critical role for ER Ca2+ depletion–activated Ca2+ current in mediating Ca2+-induced insulin secretion in response to ER stress.




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Overexpression of GPR40 in Pancreatic {beta}-Cells Augments Glucose Stimulated Insulin Secretion and Improves Glucose Tolerance in Normal and Diabetic Mice

Objective:

GPR40 is a G protein-coupled receptor regulating free fatty acid-induced insulin secretion. We have generated transgenic mice overexpressing the human GPR40 gene (hGPR40-Tg) under control of the mouse insulin II promoter and have used them to examine the role of GPR40 in the regulation of insulin secretion and glucose homeostasis.

Research Design and Methods:

Normal (C57BL/6J) and diabetic (KK) mice overexpressing the human GPR40 gene under control of the insulin II promoter were generated, and their glucose metabolism and islet function were analyzed.

Results:

In comparison with nontransgenic littermates, hGPR40-Tg mice exhibited improved oral glucose tolerance with an increase in insulin secretion. Although islet morphological analysis showed no obvious differences between hGPR40-Tg and nontransgenic (NonTg) mice, isolated islets from hGPR40-Tg mice enhanced insulin secretion in response to high glucose (16 mM) than those from NonTg mice with unchanged low glucose (3 mM)-stimulated insulin secretion. In addition, hGPR40-Tg islets significantly increased insulin secretion against a naturally occurring agonist palmitate in the presence of 11 mM glucose. hGPR40-Tg mice were also found to be resistant to high fat diet-induced glucose intolerance, and hGPR40-Tg harboring KK mice showed augmented insulin secretion and improved oral glucose tolerance compared to nontransgenic littermates.

Conclusions:

Our results suggest that GPR40 may have a role in regulating glucose-stimulated insulin secretion and plasma glucose levels in vivo, and that pharmacological activation of GPR40 may provide a novel insulin secretagogue beneficial for the treatment of type 2 diabetes.




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A Peripheral Blood DNA Methylation Signature of Hepatic Fat Reveals a Potential Causal Pathway for Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is a risk factor for type 2 diabetes (T2D). We aimed to identify the peripheral blood DNA methylation signature of hepatic fat. We conducted epigenome-wide association studies of hepatic fat in 3,400 European ancestry (EA) participants and in 401 Hispanic ancestry and 724 African ancestry participants from four population-based cohort studies. Hepatic fat was measured using computed tomography or ultrasound imaging and DNA methylation was assessed at >400,000 cytosine-guanine dinucleotides (CpGs) in whole blood or CD14+ monocytes using a commercial array. We identified 22 CpGs associated with hepatic fat in EA participants at a false discovery rate <0.05 (corresponding P = 6.9 x 10–6) with replication at Bonferroni-corrected P < 8.6 x 10–4. Mendelian randomization analyses supported the association of hypomethylation of cg08309687 (LINC00649) with NAFLD (P = 2.5 x 10–4). Hypomethylation of the same CpG was also associated with risk for new-onset T2D (P = 0.005). Our study demonstrates that a peripheral blood–derived DNA methylation signature is robustly associated with hepatic fat accumulation. The hepatic fat–associated CpGs may represent attractive biomarkers for T2D. Future studies are warranted to explore mechanisms and to examine DNA methylation signatures of NAFLD across racial/ethnic groups.




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Genetic Causes of Severe Childhood Obesity: A Remarkably High Prevalence (>=49%) in an Inbred Population of Pakistan

Monogenic forms of obesity have been identified in ≤10% of severely obese European patients. However, the overall spectrum of deleterious variants (point mutations and structural variants) responsible for childhood severe obesity remains elusive. In this study, we genetically screened 225 severely obese children from consanguineous Pakistani families through a combination of techniques including an in-house developed augmented whole-exome sequencing (CoDE-seq) enabling simultaneous detection of whole exome copy number variations (CNVs) and of point mutations in coding regions. We identified 110 probands (49%) carrying 55 different pathogenic point mutations and CNVs in 13 genes/loci responsible for non-syndromic and syndromic monofactorial obesity. CoDE-seq also identified 28 rare or novel CNVs associated with intellectual disability in 22 additional obese subjects (10%). Additionally, we highlight variants in candidate genes for obesity warranting further investigation. Altogether, 59% of the studied cohort are likely to have a discrete genetic cause with 13% of these due to CNVs demonstrating a remarkably higher prevalence of monofactorial obesity than hitherto reported and a plausible over lapping of obesity and intellectual disabilities in several cases. Finally, inbred populations with high prevalence of obesity, provide a unique genetically enriched material in quest of new genes/variants influencing energy balance.




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Is Type 2 Diabetes Mellitus Causally Associated with Cancer Risk? Evidence From a Two-Sample Mendelian Randomisation Study

We conducted a two-sample Mendelian randomisation study to investigate the causal associations of type 2 diabetes mellitus (T2DM) with risk of overall cancer and 22 site-specific cancers. Summary-level data for cancer were extracted from the Breast Cancer Association Consortium and UK Biobank. Genetic predisposition to T2DM was associated with higher odds of pancreatic, kidney, uterine and cervical cancer, lower odds of oesophageal cancer and melanoma, but not associated with 16 other site-specific cancers or overall cancer. The odds ratios (95% confidence interval) were 1.13 (1.04, 1.22), 1.08 (1.00, 1.17), 1.08 (1.01, 1.15), 1.07 (1.01, 1.15), 0.89 (0.81, 0.98), and 0.93 (0.89, 0.97) for pancreatic, kidney, uterine, cervical, and oesophageal cancer and melanoma, respectively. The association between T2DM and pancreatic cancer was also observed in a meta-analysis of this and a previous Mendelian randomisation study (odds ratio 1.08; 1.02, 1.14; p=0.009). There was limited evidence supporting causal associations between fasting glucose and cancer. Genetically predicted fasting insulin levels were positively associated with cancers of the uterus, kidney, pancreas and lung. The present study found causal detrimental effects of T2DM on several cancers. We suggested to reinforce the cancers screening in T2DM patients to enable the early detection of cancer.




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Dextran Sulfate Protects Pancreatic {beta}-Cells, Reduces Autoimmunity and Ameliorates Type 1 Diabetes

A failure in self-tolerance leads to autoimmune destruction of pancreatic β-cells and type 1 diabetes (T1D). Low molecular weight dextran sulfate (DS) is a sulfated semi-synthetic polysaccharide with demonstrated cytoprotective and immunomodulatory properties in vitro. However, whether DS can protect pancreatic β-cells, reduce autoimmunity and ameliorate T1D is unknown. Here we report that DS, but not dextran, protects human β-cells against cytokine-mediated cytotoxicity in vitro. DS also protects mitochondrial function and glucose-stimulated insulin secretion and reduces chemokine expression in human islets in a pro-inflammatory environment. Interestingly, daily treatment with DS significantly reduces diabetes incidence in pre-diabetic non-obese diabetic (NOD) mice, and most importantly, reverses diabetes in early-onset diabetic NOD mice. DS decreases β-cell death, enhances islet heparan sulfate (HS)/heparan sulfate proteoglycan (HSPG) expression and preserves β-cell mass and plasma insulin in these mice. DS administration also increases the expression of the inhibitory co-stimulatory molecule programmed death-1 (PD-1) in T-cells, reduces interferon-+ CD4+ and CD8+ T-cells and enhances the number of FoxP3+ cells. Collectively, these studies demonstrate that the action of one single molecule, DS, on β-cell protection, extracellular matrix preservation and immunomodulation can reverse diabetes in NOD mice highlighting its therapeutic potential for the treatment of T1D.




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Circulating Protein Signatures and Causal Candidates for Type 2 Diabetes

The increasing prevalence of type 2 diabetes poses a major challenge to societies worldwide. Blood-based factors like serum proteins are in contact with every organ in the body to mediate global homeostasis and may thus directly regulate complex processes such as aging and the development of common chronic diseases. We applied a data-driven proteomics approach, measuring serum levels of 4,137 proteins in 5,438 elderly Icelanders and identified 536 proteins associated with prevalent and/or incident type 2 diabetes. We validated a subset of the observed associations in an independent case-control study of type 2 diabetes. These protein associations provide novel biological insights into the molecular mechanisms that are dysregulated prior to and following the onset of type 2 diabetes and can be detected in serum. A bi-directional two-sample Mendelian randomization analysis indicated that serum changes of at least 23 proteins are downstream of the disease or its genetic liability, while 15 proteins were supported as having a causal role in type 2 diabetes.




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Catabolic degradation of endothelial VEGFA via autophagy [Glycobiology and Extracellular Matrices]

Extracellular matrix-evoked angiostasis and autophagy within the tumor microenvironment represent two critical, but unconnected, functions of the small leucine-rich proteoglycan, decorin. Acting as a partial agonist of vascular endothelial growth factor 2 (VEGFR2), soluble decorin signals via the energy sensing protein, AMP-activated protein kinase (AMPK), in the autophagic degradation of intracellular vascular endothelial growth factor A (VEGFA). Here, we discovered that soluble decorin evokes intracellular catabolism of endothelial VEGFA that is mechanistically independent of mTOR, but requires an autophagic regulator, paternally expressed gene 3 (PEG3). We found that administration of autophagic inhibitors such as chloroquine or bafilomycin A1, or depletion of autophagy-related 5 (ATG5), results in accumulation of intracellular VEGFA, indicating that VEGFA is a basal autophagic substrate. Mechanistically, decorin increased the VEGFA clearance rate by augmenting autophagic flux, a process that required RAB24 member RAS oncogene family (RAB24), a small GTPase that facilitates the disposal of autophagic compartments. We validated these findings by demonstrating the physiological relevance of this process in vivo. Mice starved for 48 h exhibited a sharp decrease in overall cardiac and aortic VEGFA that could be blocked by systemic chloroquine treatment. Thus, our findings reveal a unified mechanism for the metabolic control of endothelial VEGFA for autophagic clearance in response to decorin and canonical pro-autophagic stimuli. We posit that the VEGFR2/AMPK/PEG3 axis integrates the anti-angiogenic and pro-autophagic bioactivities of decorin as the molecular basis for tumorigenic suppression. These results support future therapeutic use of decorin as a next-generation protein therapy to combat cancer.




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Zinc promotes liquid-liquid phase separation of tau protein [Protein Structure and Folding]

Tau is a microtubule-associated protein that plays a major role in Alzheimer's disease (AD) and other tauopathies. Recent reports indicate that, in the presence of crowding agents, tau can undergo liquid–liquid phase separation (LLPS), forming highly dynamic liquid droplets. Here, using recombinantly expressed proteins, turbidimetry, fluorescence microscopy imaging, and fluorescence recovery after photobleaching (FRAP) assays, we show that the divalent transition metal zinc strongly promotes this process, shifting the equilibrium phase boundary to lower protein or crowding agent concentrations. We observed no tau LLPS-promoting effect for any other divalent transition metal ions tested, including Mn2+, Fe2+, Co2+, Ni2+, and Cu2+. We also demonstrate that multiple zinc-binding sites on tau are involved in the LLPS-promoting effect and provide insights into the mechanism of this process. Zinc concentration is highly elevated in AD brains, and this metal ion is believed to be an important player in the pathogenesis of this disease. Thus, the present findings bring a new dimension to understanding the relationship between zinc homeostasis and the pathogenic process in AD and related neurodegenerative disorders.




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Risk Factors for Diabetic Peripheral Neuropathy and Cardiovascular Autonomic Neuropathy in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study

Barbara H. Braffett
May 1, 2020; 69:1000-1010
Complications




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Pancreas Pathology of Latent Autoimmune Diabetes in Adults (LADA) in Patients and in a LADA Rat Model Compared With Type 1 Diabetes

Anne Jörns
Apr 1, 2020; 69:624-633
Islet Studies




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Evidence Against an Important Role of Plasma Insulin and Glucagon Concentrations in the Increase in EGP Caused by SGLT2 Inhibitors

Mariam Alatrach
Apr 1, 2020; 69:681-688
Pathophysiology




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Autoantibodies in Diabetes

Catherine Pihoker
Dec 1, 2005; 54:S52-S61
Section II: Type 1-Related Forms of Diabetes




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Latent Autoimmune Diabetes in Adults: Definition, Prevalence, {beta}-Cell Function, and Treatment

Gunnar Stenström
Dec 1, 2005; 54:S68-S72
Section II: Type 1-Related Forms of Diabetes




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Doctors face manslaughter charge for failing to raise alarm over killer nurse




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Iran Crisis: How Far Does Trump’s Authority Go?

10 January 2020

Dr Leslie Vinjamuri

Dean, Queen Elizabeth II Academy for Leadership in International Affairs; Director, US and the Americas Programme
The legal and political boundaries of presidential power are being redefined, but the president may still be attentive to some constraints.

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Donald Trump arrives for a rally in Toledo, Ohio on 9 January. Photo: Getty Images.

On Thursday, the US House of Representatives passed a resolution affirming its authority under the War Powers Resolution Act, and reminding the president, the American people and the world that when it comes to the use of military force, Congress must be taken into account. 

President Donald Trump replied by retweeting John Bolton, his former national security advisor, who tweeted that the War Powers Act was ‘unconstitutional’, effectively dismissing Congressional efforts to rein in the president.

This round of legal Twitter diplomacy came days after the president tweeted that ‘legal notice (to Congress) is not required, but it is given nevertheless’ and that ‘should Iran strike any US person or target, the United States will quickly and fully strike back, and perhaps in a disproportionate manner.’ 

President Trump’s overt attacks on Congressional authority and disregard for the law are not normal for a US president, but legal constraints over the president’s authority to use military force have been eroding for several years.

In 1973, Congress passed the War Powers Act, requiring the president to report to Congress and acquire Congressional approval for continued overseas troop deployments. But Congressional authority over the use of military force has continued to diminish, especially since the 9/11 attacks. 

Now, Congress is pushing back – a resolution similar to that passed by the House is likely to be voted on by the Senate soon. Given the intense frustration of some senators over the president’s handling of the current conflict, this resolution may pass, though the president is still likely to veto. 

The bigger problem, of which this is one part, is the expansion of executive authority, and it predates this presidency. Many argue that executive power is greatest on matters of foreign policy, and that in this domain the US president is unconstrained. As partisanship has increased and the demands on Congress have made it harder for its members to cultivate foreign policy expertise, the power of the president has grown.

So the fact that Congress is taking active steps to check the president’s power not only on the question of impeachment, but also on foreign policy, is significant, even if the law is not likely to restrain President Trump. But Congress is also playing a long game. And its growing determination to assert its authority matters not only for this presidency, but also for the future.

Political constraints

In the short term, other constraints matter more. Even if President Trump rejects legal restraints – and shuns diplomatic pressure that might have mattered to other presidents – he is not impervious to political restraint.

Already there are signs that Trump listens to his key Republican allies in Congress. When Senator Lindsay Graham pushed back against the president’s threat to attack cultural heritage sites in Iran, and the Pentagon failed to shore up the president’s threat, the president changed his position. The threats also provoked an overwhelming response in Europe, and across the Middle East, but the president has shown that he is willing to disregard international admonishment. Not so for domestic allies.

Nor is this the first time that Senator Graham’s views have mattered. When the president announced his decision to pull troops from northeast Syria, effectively abandoning the Kurds, a key partner to the US in its fight against ISIS, Senator Graham and Senator Mitch McConnell pushed back and it mattered. 

Public opinion also matters to the president, especially Republican public opinion, and this is likely to affect the president’s next steps. Recent polls suggest that Americans feel less safe as a result of the killing of General Qassem Soleimani by a considerable margin of 55% to 24%.

But the same survey also shows that a majority of Americans support the decision to kill Soleimani. Already Vice President Mike Pence has spoken at a rally in Ohio designed to bolster support for this Presidential action.  

So what might change public opinion and will this alter the president’s future steps?

Americans are very reluctant to support further deployments of troops overseas. President Trump knows this and he has consistently stated that he seeks to pull US troops out of the Middle East.

In fact, the opposite has happened. And once again, the decision to kill General Soleimani is pulling the US further into the Middle East and putting into stark light the inconsistency of Trump’s foreign policy ambitions. In recent days, the United States has committed to sending thousands of troops to the region.

Continued US troop deployments may not play well with Trump’s base, though they currently support his Iran policy. But absent an obvious justification, this could change, so it is not surprising that this has become a rallying point for Vice President Pence.

An even greater political risk, and one that will matter to the president, is the risk to US military personnel and civilians overseas. Public support for the killing of Soleimani and increased US presence in the region is bound to dissipate if Americans are killed.

But it isn’t clear how the president will respond, and already the death of one American in the militia attack on 27 December seems to have been a critical factor in Trump’s decision to authorize the assassination of General Soleimani.  

So far, Iran’s response appears to be calibrated to avoid this kind of public backlash, and keep the door open to some sort of managed resolution of the current crisis.

But the considerable risk of miscalculation and mistakes has already been born out. A week after the killing of Soleimani, the world is tuning in to the tragic news that a civilian airliner departing Iran for Ukraine appears to have been accidentally shot down by an Iranian missile, resulting in the deaths of all 176 people on board, including 82 Iranians and 63 Canadians.

Whether the US president is constrained is a critical question for Americans, for US democracy and for the rest of the world. Trump is different, but he is not unconstrained. Steps taken by Congress along with diplomatic and political pressure mean he is still operating within boundaries. But it is clear that these boundaries are being redefined.




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The UK, US and Mauritius: Decolonization, Security, Chagos and the ICJ

Invitation Only Research Event

30 January 2020 - 8:15am to 9:15am

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

Event participants

Professor Philippe Sands QC, Professor of Law, UCL 
Richard Burt, Managing Partner, McLarty Associates
Chair: Dr Leslie Vinjamuri, Director, US and Americas Programme; Dean, Queen Elizabeth II Academy, Chatham House

The Chagos archipelago in the Indian Ocean has garnered media attention recently after the UK failed to abide by a UN deadline to return the islands to Mauritius. The US has landed in the middle of the dispute as a 1965 agreement with the UK has allowed the US to establish a military base on one of the islands, Diego Garcia, which has since become instrumental in US missions in the Asia-Pacific and the Middle East. 

In February 2019, an Advisory Opinion of the International Court of Justice (ICJ) found that the Chagos archipelago was unlawfully dismembered from Mauritius, in violation of the right to self-determination and that the United Kingdom is under an obligation to end its administration of the Chagos archipelago ‘as rapidly as possible’. The UN General Assembly subsequently voted overwhelmingly in favour of the UK leaving the islands by the end of November 2019 and the right of the former residents who were removed by the UK to return. The UK does not accept the ICJ and UN rulings and argues that the islands are needed to protect Britain from security threats while Mauritius has made clear the base can remain.

Professor Philippe Sands QC, professor of law at University College London and lead counsel for Mauritius on the ICJ case on Legal Consequences of the Separation of the Chagos archipelago from Mauritius in 1965, will be joining Ambassador Richard Burt, US chief negotiator in the Strategic Arms Reduction Talks with the former Soviet Union for a discussion on the fate of the archipelago including the future of the military base and the right of return of former residents.  

Attendance at this event is by invitation only. 

Event attributes

Chatham House Rule

Department/project

US and Americas Programme




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Diabetes Core Update – August 2019

Diabetes Core Update is a monthly podcast that presents and discusses the latest clinically relevant articles from the American Diabetes Association’s four science and medical journals – Diabetes, Diabetes Care, Clinical Diabetes, and Diabetes Spectrum. Each episode is approximately 20 minutes long and presents 5-6 recently published articles from ADA journals.

Intended for practicing physicians and health care professionals, Diabetes Core Update discusses how the latest research and information published in journals of the American Diabetes Association are relevant to clinical practice and can be applied in a treatment setting.

This month we review articles on:

  1. Dapagliflozin Plus Saxagliptin Add-on Therapy Compared with Insulin
  2. Dulaglutide and Cardiovascular Outcomes in Type 2 Diabetes (REWIND)
  3. Mediterranean Diet and the Need for Glucose- Lowering Medications
  4. Oral Semaglutide versus Subcutaneous Liraglutide and Placebo
  5. Vitamin E and Pioglitazone for Nonalcoholic Steatohepatitis in Patients with Type 2 Diabetes
  6. Durability of Insulin Degludec plus Liraglutide versus Insulin Glargine U100

For more information about each of ADA’s science and medical journals, please visit www.diabetesjournals.org.

Presented by:

Neil Skolnik, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Associate Director, Family Medicine Residency Program, Abington Jefferson Health

John J. Russell, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Director, Family Medicine Residency Program, Abington Jefferson Health




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US$10,000 gofundme launched to support animals at Hope Zoo

A gofundme account has been launched with the hope of keeping animals feed and to preserve endangered wildlife at the Hope Zoo in St Andrew. Curator, Joey Brown, organiser of the fundraiser, indicated that as a non-profit organisation,...




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Three Challenges for UK Peacebuilding Policy in the South Caucasus After Brexit

21 January 2020

Laurence Broers

Associate Fellow, Russia and Eurasia Programme
Building on the legacies of a long-term British investment in a peace strategy for the South Caucasus is a realistic and attainable goal.

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A building in Nagorny Karabakh flies the flag of the self-proclaimed republic. 'Abkhazia, South Ossetia and Nagorny Karabakh have evolved into examples of what scholars call "de facto states" that, to differing degrees, control territory, provide governance and exercise internal sovereignty,' writes Laurence Broers. Photo: Getty Images.

What does Britain’s departure from the EU mean for the country’s policy towards the South Caucasus, a small region on the periphery of Europe, fractured by conflict? Although Britain is not directly involved in any of the region’s peace processes (except in the case of the Geneva International Discussions on conflicts involving Georgia, as an EU member state), it has been a significant stakeholder in South Caucasian stability since the mid-1990s.

Most obviously, Britain has been the single largest foreign investor in Caspian oil and gas. Yet beyond pipelines, Britain also has been a significant investor in long-term civil society-led strategies to build peace in the South Caucasus.

Through what was then the Global Conflict Prevention Pool, in the early 2000s the Department for International Development (DfID) pioneered large-scale peacebuilding interventions, such as the Consortium Initiative, addressing Armenian-Azerbaijani conflict, in 2003-09. These built civic networks in the South Caucasus and partnerships with British-based NGOs.

This experience left a strong intellectual legacy. British expertise on the South Caucasus, including specific expertise on its conflicts, is highly regarded in the region and across the world.

There is also a strong tradition of British scholarship on the Caucasus, and several British universities offer Caucasus-related courses. Through schemes such as the John Smith Fellowship Trust, the Robert Bosch Stiftung Academy Fellowship at Chatham House and Chevening Scholarships, significant numbers of young leaders from the South Caucasus have spent time in British institutions and built effective relationships within them.

Three challenges

This niche as a champion of long-term, strategic peacebuilding and repository of area-specific knowledge should not be lost as Britain’s relationship with the EU and regional actors evolves. This can be ensured through awareness of three challenges confronting a post-Brexit Caucasus policy.

The first challenge for London is to avoid framing a regional policy in the South Caucasus as an extension of a wider ‘Russia policy’. Deteriorating Russian-British relations in recent years strengthen a tendency to view policies in the European neighbourhood through the traditional prisms of Cold War and Russian-Western rivalries.

Yet an overwhelming focus on Russia fails to capture other important aspects of political developments in South Caucasus conflicts. Although often referred to as ‘breakaway’ or ‘occupied’ territories, Abkhazia, South Ossetia and Nagorny Karabakh are not ungoverned spaces. They have evolved into examples of what scholars call ‘de facto states’ that, to differing degrees, control territory, provide governance and exercise internal sovereignty.

Few disagree that these entities would not survive without external patronage. But neither does that patronage explain their sustainability on its own. Russia-centricity diminishes Britain’s latitude to engage on the full range of local drivers sustaining these entities, contributing instead to less effective policies predicated on competition and containment.

A second and related challenge is to maintain and develop Britain’s position on the issue of engaging populations in these entities. De facto states appear to stand outside of the international rules-based system. Yet in many cases, their civil societies are peopled by skilled and motivated activists who want their leaders to be held accountable according to international rules.

Strategies of isolation ignore these voices and contribute instead to fearful and demoralized communities less likely to engage in a transformation of adversarial relationships. Making this case with the wider international community, and facilitating the funding of local civil societies in contested territories, would be important steps in sustaining an effective British policy on the resolution of conflicts.    

The third challenge for Britain is to maintain a long-term approach to the conflicts of the South Caucasus alongside potential short-term imperatives in other policy fields, as relationships shift post-Brexit.

In this fluid international environment, the Foreign and Commonwealth Office has a role to play both as an internal champion of a long-term peacebuilding strategy and a coordinator of British efforts with those of multilateral actors engaged in the South Caucasus. These include the United Nations, the EU’s Special Representative for the South Caucasus and the Crisis in Georgia and OSCE’s Special Representative for the OSCE Chairperson-in-Office for the South Caucasus, all of which have built relationships with relevant actors on the ground.

Recommendations

Britain’s niche as a champion and advocate of a strategic approach to peaceful change can be secured post-Brexit in the following ways.  

First, in-house expertise is crucial to effective peacebuilding programming. The Foreign Office’s research analysts play a vital role in generating independent internal advice and liaising with academic and NGO communities. Their role could be supplemented by the reinstatement of a regional conflict adviser post, based in Tbilisi, tasked with strengthening Britain’s regional presence on conflict issues and coordinating policy at a regional level.

This post, with a remit to cover conflicts and build up area knowledge and relationships can contribute significantly to working closely with local civil societies, where so much expertise and knowledge resides, as well as other stakeholders.

Second, programming should build in conflict sensitivity by dissociating eligibility from contested political status. This can encourage local populations to take advantage of opportunities for funding, study, comparative learning and professional development irrespective of the status of the entity where they reside.

The Chevening Scholarships are an excellent example, whereby applicants can select ‘South Caucasus’ as their affiliated identity from a drop-down menu. This enables citizens from across the region to apply irrespective of the status of the territory in which they live.   

Finally, a holistic understanding of peace is crucial. Programming in unrecognized or partially-recognized entities should acknowledge that effective peacebuilding needs to embrace political dynamics and processes beyond cross-conflict contact and confidence building. Local actors in such entities may find peacebuilding funding streams defined exclusively in terms of cross-conflict contact more politically risky and ineffective in addressing domestic blockages to peace.

While cross-conflict dynamics remain critical, ‘single-community’ programming framed in terms of civic participation, inclusion, civil society capacity-building, minority and human rights in contested territories, and building the confidence from within to engage in constructive dialogue, are no less important.

The ’global Britain’ promised by Brexit remains a fanciful idea. Quiet, painstaking work to build on the legacies of a long-term British investment in a peace strategy for the South Caucasus, on the other hand, is a realistic and attainable goal.




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Chữa đau nhức chân với bồn ngâm massage chân

Chữa đau nhức chân với bồn ngâm massage chân là một phương pháp được đánh giá rất cao hiện nay. Tuy nhiên thông tin về phương pháp này không phải ai cũng...




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Trudeau Election Marks New Start for Canada

22 October 2015

Cleo Paskal

Associate Fellow, Energy, Environment and Resources Programme and Asia-Pacific Programme
Canada's partners are about to see a sea change in policy from the new Liberal government on a range of issues, especially relating to energy and the environment.

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Canadian Liberal Party leader Justin Trudeau arrives to give a press conference in Ottawa on 20 October 2015. Photo by Getty Images.

The Liberal Party likes to think of itself as ‘Canada’s natural governing party’. Though they have been out of power for 10 years, and newly elected prime minister Justin Trudeau is relatively inexperienced, the party has deep and old networks across the country. The backroom is full of experienced old hands, including former prime ministers who have known Trudeau since he was a toddler. With a number of bold shifts promised in Canadian foreign policy, and a willingness to be fiscally expansive (Trudeau has said he is willing to run deficits for three years to implement their policies), the change is likely to be dramatic, fast and unrelenting.

International engagement

The Liberals’ proposed new Canada has a hint of nostalgia for a time when Canadians thought of themselves as a force for good in the world. There is likely to be a large-scale reengagement with the international community, especially the United Nations, not only on climate policy, but also peacekeeping and disaster response. Canada’s French-speaking experts make it well placed to engage in crisis-hit French-speaking countries while carrying somewhat less colonial baggage. Meanwhile, the Liberals have promised to withdraw Canadian forces from the combat mission against ISIS in Iraq, pledging instead to reorient their focus towards aid.

Science-based policies

Trudeau has the backing of a very deep bench of experienced parliamentarians, some of whom have been waiting a long time to get back in the governing game. They include Stéphane Dion, the former environment minister who gained respect for his chairing of the 2005 UN climate change conference in Montreal, and Marc Garneau, former astronaut and president of the Canadian Space Agency. This will be a government that understands and values (and has promised to restore funding for) scientific research.

This means more investment in climate resilience, renewables and other forward planning policies, but also a reexamination of some of Canada’s long-standing strengths, including Canada’s fisheries. Under the previous government, over half-a-dozen critical fisheries research libraries were shut down, in some cases with large-scale loss of data. A more science-based fisheries policy, combined with the promised funding to the Royal Canadian Navy, may result in a reinvigorated and coordinated Canadian fisheries policy. This would become particularly important in a time of global food constraints.

‘Nation-to-nation’

Trudeau’s stated goal of establishing ‘nation-to-nation’ relations with Canada’s indigenous peoples has potentially global implications.

Through treaties, Canada’s First Nations can stake a claim to about a third of Canada’s landmass, including resource rich areas. They own or control access to land that contains oil, gas, uranium, gold, diamonds and much more. China, for one, realized the potential power of First Nations as far back as 2008, when Beijing invited over two dozen indigenous leaders to China to talk business. During that trip, Peguis Chief Glenn Hudson explained that the trip was ‘an important step for us in moving forward. Our future is not only in Canada, but partnering with other countries.’

Trudeau’s ‘nation-to-nation’ statement acknowledges the strengthening role of First Nations in Canada’s resource policy. Indigenous communities have been among the most adversely affected by oil sands development and, in other parts of Canada, have successfully blocked resources extraction or transit. For example, in May, the Lax Kw'alaams Band refused to allow a proposed multi-million dollar Petronas LNG project to be developed on their land over concerns it would affect their economically and culturally important salmon runs.

Real First Nations engagement with resource management has the potential substantially change Canada’s energy, environment and resources profile. First Nations in eastern Canada have already blocked hydro development that could power much of the northeastern United States and, in a time of pipeline expansion, First Nations might become instrumental in deciding if more pipelines will run north-to-south, towards the border with the United States, or east-to-west, towards the Pacific and the markets in Asia.

Energy sector

At the same time, while Trudeau said he was against the Northern Gateway pipeline, in large part because of how it would affect the people of the Pacific coast, he backed Keystone XL. However, he is unlikely to push for it in the face of a veto by President Obama. Also, low fossil fuel prices contributed to the election in May of a left-leaning provincial government in the badly hit oil heartland of Alberta. If prices stay low, that could very well combine with Liberal campaign promises to put a coordinated national price on carbon and to phase out fossil fuel subsidies, additionally reshaping Canada’s energy landscape..

Agriculture and the Trans-Pacific Partnership

The Liberals also have a stated goal of investing in a more innovative and safe agricultural sector, while defending the interests of Canadian farmers. This dovetails with their promise to openly examine and discuss the Trans-Pacific Partnership (TPP) before ratification. Canadian dairy farmers in particular were concerned about some of the TPP provisions but, without access to the details of the text, it was difficult to estimate how the sector would be affected.

One proposed agricultural policy that may have widespread economic implications is the legalization, regulation and taxation of marijuana. As some states in the United States have found, this has the potential to be economically beneficial and, for Canada, a possible major boon to cross-border tourism.

In a myriad of small ways, and a few big ones, the new Liberal government plans to change Canada’s international role and domestic landscape. This is one to watch.

To comment on this article, please contact Chatham House Feedback 




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Marvia Providence ‘Anointed’ for ministry - Offers ‘Bible pull up and come again’ entertainment to gospel audiences

Just the mention of the name Marvia Providence sends a tingle to the toes and, immediately, feet start tapping and bodies begin swaying. Before you know it, all the ‘warriors’ – prayer and otherwise – are in full flight. That’s the effect of the...




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Inner Circle gives thanks for Jacob Miller on his birthday - Singer would have caused ‘problem’ at King’s House, says ­former bandmate

Long before the existence of the Internet and going viral was a thing, reggae singer Jacob Miller, back in the ‘70s, coined a term that went viral – under heavy manners. Ian Lewis of Inner Circle band, the Bad Boys of Reggae, recalled that his...




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JCDC weighs options amid COVID-19 pause - 230 entries received for Festival Song Competition

By the month of May in any given year, the many and varied events and competitions staged by the Jamaica Cultural Development Commission (JCDC) islandwide would have been in high gear. Each year the JCDC rolls out its much-anticipated menu board...




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‘Laugh Online’ with Ity and Fancy Cat

Widely considered the ‘kings of comedy’ in Jamaica, Ity and Fancy Cat have been serving up laughter to audiences for years. Their comedy series, The Ity and Fancy Cat Show, ended in 2017 but the duo continued to deliver high-quality entertainment...




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Mark Wignall | Dunces, COVID-19 and the long haul

Chupski dons her mask once she ventures out in public. To the bank, the supermarket, the ­pharmacy, the ATM. So far I have never even tried on the one I have. Maybe I should have worn it last Thursday mid-­morning as I stood at the entrance to the...




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Antoinette Davis: The Beauty Behind Ettenio

Everyone these days is so focused on the beauty behind hair and skincare lines that they neglect to really explore the science behind them. Creating revolutionary products that are not only innovative but eco-friendly is entrepreneur Antoinette...




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Women with endometriosis have significantly higher rates of depression than women in the general population. That’s according to psychiatrist Dr Kristen Robinson-Barrett. It’s the end of endometriosis month, so Flair spoke to the expert to explore...




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Pancreas Pathology of Latent Autoimmune Diabetes in Adults (LADA) in Patients and in a LADA Rat Model Compared With Type 1 Diabetes

Approximately 10% of patients with type 2 diabetes suffer from latent autoimmune diabetes in adults (LADA). This study provides a systematic assessment of the pathology of the endocrine pancreas of patients with LADA and for comparison in a first rat model mimicking the characteristics of patients with LADA. Islets in human and rat pancreases were analyzed by immunohistochemistry for immune cell infiltrate composition, by in situ RT-PCR and quantitative real-time PCR of laser microdissected islets for gene expression of proinflammatory cytokines, the proliferation marker proliferating cell nuclear antigen (PCNA), the anti-inflammatory cytokine interleukin (IL) 10, and the apoptosis markers caspase 3 and TUNEL as well as insulin. Human and rat LADA pancreases showed differences in areas of the pancreas with respect to immune cell infiltration and a changed ratio between the number of macrophages and CD8 T cells toward macrophages in the islet infiltrate. Gene expression analyses revealed a changed ratio due to an increase of IL-1β and a decrease of tumor necrosis factor-α. IL-10, PCNA, and insulin expression were increased in the LADA situation, whereas caspase 3 gene expression was reduced. The analyses into the underlying pathology in human as well as rat LADA pancreases provided identical results, allowing the conclusion that LADA is a milder form of autoimmune diabetes in patients of an advanced age.