Mallory-Denk-bodies (MDBs) are hepatic protein aggregates associated with inflammation both clinically and in MDB-inducing models. Similar protein aggregation in neurodegenerative diseases also triggers inflammation and NF-B activation. However, the precise mechanism that links protein aggregation to NF-B-activation and inflammatory response remains unclear. Herein we find that treating primary hepatocytes with MDB-inducing agents (N-methylprotoporphyrin (NMPP), protoporphyrin IX (PPIX), or Zinc-protoporphyrin IX (ZnPP)) elicited an IBα-loss with consequent NF-B activation. Four known mechanisms of IBα-loss i.e. the canonical ubiquitin-dependent proteasomal degradation (UPD), autophagic-lysosomal degradation, calpain degradation and translational inhibition, were all probed and excluded. Immunofluorescence analyses of ZnPP-treated cells coupled with 8 M urea/CHAPS-extraction revealed that this IBα-loss was due to its sequestration along with IBβ into insoluble aggregates, thereby releasing NF-B. Through affinity pulldown, proximity biotinylation by antibody recognition, and other proteomic analyses, we verified that NF-B subunit p65, which stably interacts with IBα under normal conditions, no longer binds to it upon ZnPP-treatment. Additionally, we identified 10 proteins that interact with IBα under baseline conditions, aggregate upon ZnPP-treatment, and maintain the interaction with IBα after ZnPP-treatment, either by cosequestering into insoluble aggregates or through a different mechanism. Of these 10 proteins, the nucleoporins Nup153 and Nup358/RanBP2 were identified through RNA-interference, as mediators of IBα-nuclear import. The concurrent aggregation of IBα, NUP153, and RanBP2 upon ZnPP-treatment, synergistically precluded the nuclear entry of IBα and its consequent binding and termination of NF-B activation. This novel mechanism may account for the protein aggregate-induced inflammation observed in liver diseases, thus identifying novel targets for therapeutic intervention. Because of inherent commonalities this MDB cell model is a bona fide protoporphyric model, making these findings equally relevant to the liver inflammation associated with clinical protoporphyria.

Protein tyrosine kinases (PTKs) play key roles in cellular signal transduction, cell cycle regulation, cell division, and cell differentiation. Dysregulation of PTK-activated pathways, often by receptor overexpression, gene amplification, or genetic mutation, is a causal factor underlying numerous cancers. In this study, we have developed a parallel reaction monitoring (PRM)-based assay for quantitative profiling of 83 PTKs. The assay detects 308 proteotypic peptides from 54 receptor tyrosine kinases and 29 nonreceptor tyrosine kinases in a single run. Quantitative comparisons were based on the labeled reference peptide method. We implemented the assay in four cell models: 1) a comparison of proliferating versus epidermal growth factor (EGF)-stimulated A431 cells, 2) a comparison of SW480Null (mutant APC) and SW480APC (APC restored) colon tumor cell lines, and 3) a comparison of 10 colorectal cancer cell lines with different genomic abnormalities, and 4) lung cancer cell lines with either susceptibility (11-18) or acquired resistance (11-18R) to the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib. We observed distinct PTK expression changes that were induced by stimuli, genomic features or drug resistance, which were consistent with previous reports. However, most of the measured expression differences were novel observations. For example, acquired resistance to erlotinib in the 11-18 cell model was associated not only with previously reported upregulation of MET, but also with upregulation of FLK2 and downregulation of LYN and PTK7. Immunoblot analyses and shotgun proteomics data were highly consistent with PRM data. Multiplexed PRM assays provide a targeted, systems-level profiling approach to evaluate cancer-related proteotypes and adaptations. Data are available through Proteome eXchange Accession PXD002706.

This article has been withdrawn by the authors. This article did not comply with the editorial guidelines of MCP. Specifically, single peptide based protein identifications of 9-19% were included in the analysis and discussed in the results and conclusions. We wish to withdraw this article and resubmit a clarified, corrected manuscript for review.

CD4+ T cell responses are crucial for inducing and maintaining effective anti-cancer immunity, and the identification of human leukocyte antigen class II (HLA-II) cancer-specific epitopes is key to the development of potent cancer immunotherapies. In many tumor types, and especially in glioblastoma (GBM), HLA-II complexes are hardly ever naturally expressed. Hence, little is known about immunogenic HLA-II epitopes in GBM. With stable expression of the class II major histocompatibility complex transactivator (CIITA) coupled to a detailed and sensitive mass spectrometry based immunopeptidomics analysis, we here uncovered a remarkable breadth of the HLA-ligandome in HROG02, HROG17 and RA GBM cell lines. The effect of CIITA expression on the induction of the HLA-II presentation machinery was striking in each of the three cell lines, and it was significantly higher compared to interferon gamma (IFN) treatment. In total, we identified 16,123 unique HLA-I peptides and 32,690 unique HLA-II peptides. In order to genuinely define the identified peptides as true HLA ligands, we carefully characterized their association with the different HLA allotypes. In addition, we identified 138 and 279 HLA-I and HLA-II ligands, respectively, most of which are novel in GBM, derived from known GBM-associated tumor-antigens that have been used as source proteins for a variety of GBM vaccines. Our data further indicate that CIITA-expressing GBM cells acquired an antigen presenting cell-like phenotype as we found that they directly present external proteins as HLA-II ligands. Not only that CIITA-expressing GBM cells are attractive models for antigen discovery endeavors, but also such engineered cells have great therapeutic potential through massive presentation of a diverse antigenic repertoire.

Regulation of gene expression is essential for the functioning of all eukaryotic organisms. Understanding gene expression regulation requires determining which proteins interact with regulatory elements in chromatin. Mass spectrometry-based analysis of chromatin has emerged as a powerful tool to identify proteins associated with gene regulation, as it allows studying protein function and protein complex formation in their in vivo chromatin-bound context. Total chromatin isolated from cells can be directly analysed using mass spectrometry or further fractionated into transcriptionally active and inactive chromatin prior to MS-based analysis. Newly formed chromatin that is assembled during DNA replication can also be specifically isolated and analysed. Furthermore, capturing specific chromatin domains facilitates the identification of previously unknown transcription factors interacting with these domains. Finally, in recent years, advances have been made towards identifying proteins that interact with a single genomic locus of interest. In this review, we highlight the power of chromatin proteomics approaches and how these provide complementary alternatives compared to conventional affinity purification methods. Furthermore, we discuss the biochemical challenges that should be addressed to consolidate and expand the role of chromatin proteomics as a key technology in the context of gene expression regulation and epigenetics research in health and disease.

The histopathological subtype of lung adenocarcinoma (LUAD) is closely associated with prognosis. Micropapillary or solid predominant LUAD tends to relapse after surgery at an early stage, whereas lepidic pattern shows a favorable outcome. However, the molecular mechanism underlying this phenomenon remains unknown. Here, we recruited 31 lepidic predominant LUADs (LR: low-risk subtype group) and 28 micropapillary or solid predominant LUADs (HR: high-risk subtype group). Tissues of these cases were obtained and label-free quantitative proteomic and bioinformatic analyses were performed. Additionally, prognostic impact of targeted proteins was validated using The Cancer Genome Atlas databases (n=492) and tissue microarrays composed of early-stage LUADs (n=228). A total of 192 differentially expressed proteins were identified between tumor tissues of LR and HR and three clusters were identified via hierarchical clustering excluding eight proteins. Cluster 1 (65 proteins) showed a sequential decrease in expression from normal tissues to tumor tissues of LR and then to HR and was predominantly enriched in pathways such as tyrosine metabolism and ECM-receptor interaction, and increased matched mRNA expression of 18 proteins from this cluster predicted favorable prognosis. Cluster 2 (70 proteins) demonstrated a sequential increase in expression from normal tissues to tumor tissues of LR and then to HR and was mainly enriched in pathways such as extracellular organization, DNA replication and cell cycle, and high matched mRNA expression of 25 proteins indicated poor prognosis. Cluster 3 (49 proteins) showed high expression only in LR, with high matched mRNA expression of 20 proteins in this cluster indicating favorable prognosis. Furthermore, high expression of ERO1A and FEN1 at protein level predicted poor prognosis in early-stage LUAD, supporting the mRNA results. In conclusion, we discovered key differentially expressed proteins and pathways between low-risk and high-risk subtypes of early-stage LUAD. Some of these proteins could serve as potential biomarkers in prognostic evaluation.

The goal of clinical proteomics is to identify, quantify, and characterize proteins in body fluids or tissue to assist diagnosis, prognosis, and treatment of patients. In this way, it is similar to more mature omics technologies, such as genomics, that are increasingly applied in biomedicine. We argue that, similar to those fields, proteomics also faces ethical issues related to the kinds of information that is inherently obtained through sample measurement, although their acquisition was not the primary purpose. Specifically, we demonstrate the potential to identify individuals both by their characteristic, individual-specific protein levels and by variant peptides reporting on coding single nucleotide polymorphisms. Furthermore, it is in the nature of blood plasma proteomics profiling that it broadly reports on the health status of an individual – beyond the disease under investigation. Finally, we show that private and potentially sensitive information, such as ethnicity and pregnancy status, can increasingly be derived from proteomics data. Although this is potentially valuable not only to the individual, but also for biomedical research, it raises ethical questions similar to the incidental findings obtained through other omics technologies. We here introduce the necessity of - and argue for the desirability for - ethical and human rights-related issues to be discussed within the proteomics community. Those thoughts are more fully developed in our accompanying manuscript. Appreciation and discussion of ethical aspects of proteomic research will allow for deeper, better-informed, more diverse, and, most importantly, wiser guidelines for clinical proteomics.

The origin recognition complex (ORC), composed of six subunits, ORC1–6, binds to origins of replication as a ring-shaped heterohexameric ATPase that is believed to be essential to recruit and load MCM2–7, the minichromosome maintenance protein complex, around DNA and initiate DNA replication. We previously reported the creation of viable cancer cell lines that lacked detectable ORC1 or ORC2 protein without a reduction in the number of origins firing. Here, using CRISPR-Cas9–mediated mutations, we report that human HCT116 colon cancer cells also survive when ORC5 protein expression is abolished via a mutation in the initiator ATG of the ORC5 gene. Even if an internal methionine is used to produce an undetectable, N terminally deleted ORC5, the protein would lack 80% of the AAA+ ATPase domain, including the Walker A motif. The ORC5-depleted cells show normal chromatin binding of MCM2–7 and initiate replication from a similar number of origins as WT cells. In addition, we introduced a second mutation in ORC2 in the ORC5 mutant cells, rendering both ORC5 and ORC2 proteins undetectable in the same cells and destabilizing the ORC1, ORC3, and ORC4 proteins. Yet the double mutant cells grow, recruit MCM2–7 normally to chromatin, and initiate DNA replication with normal number of origins. Thus, in these selected cancer cells, either a crippled ORC lacking ORC2 and ORC5 and present at minimal levels on the chromatin can recruit and load enough MCM2–7 to initiate DNA replication, or human cell lines can sometimes recruit MCM2–7 to origins independent of ORC.

Faithful replication of the mitochondrial genome is carried out by a set of key nuclear-encoded proteins. DNA polymerase γ is a core component of the mtDNA replisome and the only replicative DNA polymerase localized to mitochondria. The asynchronous mechanism of mtDNA replication predicts that the replication machinery encounters dsDNA and unique physical barriers such as structured genes, G-quadruplexes, and other obstacles. In vitro experiments here provide evidence that the polymerase γ heterotrimer is well-adapted to efficiently synthesize DNA, despite the presence of many naturally occurring roadblocks. However, we identified a specific G-quadruplex–forming sequence at the heavy-strand promoter (HSP1) that has the potential to cause significant stalling of mtDNA replication. Furthermore, this structured region of DNA corresponds to the break site for a large (3,895 bp) deletion observed in mitochondrial disease patients. The presence of this deletion in humans correlates with UV exposure, and we have found that efficiency of polymerase γ DNA synthesis is reduced after this quadruplex is exposed to UV in vitro.

All 30 Major League teams will wear special "MLB 150" patches on their uniforms for the entire 2019 season in honor of the 150th anniversary of the 1869 Cincinnati Red Stockings, the first openly all-salaried professional baseball team.

All 30 Major League teams will wear special "MLB 150" patches on their uniforms for the entire 2019 season in honor of the 150th anniversary of the 1869 Cincinnati Red Stockings, the first openly all-salaried professional baseball team.

The Angels have a new closer in Cody Allen and there isn't any manager in baseball who knows him better than Indians skipper Terry Francona.

Mugabe’s Fall Is a Wake-Up Call for Africa’s Leaders Expert comment sysadmin 27 November 2017

The continent’s long-standing leaders will come under increasing pressure to demonstrate their societal value. Some will become more oppressive; others may conclude that their time has expired.

The end of the Mugabe presidency in Zimbabwe – with the swearing in of Emmerson Mnangagwa in Harare on Friday – is being watched closely across Africa, and especially by its long-standing leaders.

Currently, 30 per cent of African countries are ruled by long-standing rulers, defined as heads of state that have ruled for more than 10 years. Africa is not unique in this respect (Central Asia also has its share of ageing leaders), but Africa has a long tradition, and about a fifth of all African heads of state since independence can be classified as long-standing.

A recent study, African Futures: Horizon 2025, by the European Union Institute of Security Studies (and which this writer contributed to), shows that long-standing rulers in Africa are reducing in number. President José Eduardo dos Santos of Angola stepped down voluntarily in September after almost 38 years in office, and Yahya Jammeh of Gambia was forced out after 23 years in office in early 2017. Robert Mugabe was forced out as leader earlier this week after 37 years.

This still leaves a cluster of other ageing leaders: Teodoro Obiang Nguema Mbasogo of Equatorial Guinea (38 years); Paul Biya of Cameroon (35 years); Yoweri Museveni of Uganda (31 years); Omar al-Bashir of Sudan (28 years); and eight others.

Many of them are coming under increased internal pressure. Demonstrations against Togo’s Faure Gnassingbé in Lome over the summer resulted in him agreeing that any future president could stand for only two terms. In the Democratic Republic of the Congo, Joseph Kabila is also under increased pressure to agree to elections, after 16 years in power.

Within all of this, there is a pattern of leaders in west and southern Africa adopting the principle of only serving two terms.

De-facto monarchies

Long-standing rulers still thrive in central Africa and its Great Lakes region. Presidents here have successfully changed constitutions to remain in office. They include Denis Sassou Nguesso of the Republic of the Congo and Yoweri Museveni of Uganda. Zimbabwe will be a warning to them that they should not assume that they will be able to behave as de-facto monarchies, leaving office only after dying of natural causes and handing power over to their family.

Robert Mugabe’s intention to hand power to his wife, Grace, spectacularly backfired. As a couple of Zimbabwe military officials dryly commented: ‘Leadership is not sexually transmitted.’ Former president Hosni Mubarak in Egypt also miscalculated by trying to groom his son, although Ali Bongo Ondimba succeeded his father as president of Gabon after his father died. Equatorial Guinea is still heading for a crisis as President Obiang is grooming his deeply unpopular playboy son, Teodorin, to succeed him.

What Zimbabwe reminds us is that, with the exception of central Africa, there will be more long-standing leaders in Africa disappearing over the coming decade. This is due partly to pressure and partly to their ageing: 13 current long-standing rulers are aged between 65 and 84 years old. This means there will be more transitions taking place such as the one that occurred in Zimbabwe on Friday or the smooth one in Angola in September, when president dos Santos stepped down and handed power to João Lourenço.

This is good news for Africa, which has the most youthful and fastest-growing population in the world. It is the second-largest and second-most populated continent. More than 40 per cent of Africans are under 15, and 20 per cent are between 15 and 24. By 2050, one third of the world’s youth population will live in Africa, up from one fifth in 2012. This means a dramatic disconnect is developing between long-standing leaders and their population.

Generational politics was visible over the past week in Zimbabwe and in the end the older generation prevailed through military intervention. This is transitional politics, and there is likely to be more of it.

Increasing pressure

Other long-serving leaders like Museveni have watched closely. Museveni has already responded to shore up support of his military by giving them a significant pay rise. There is likely to be more investment in the military by Africa’s long-standing leaders in the coming months.

Change in Africa comes in fits and starts. The fall of Mugabe is a reminder that Africa is dynamic and change is occurring all the time. Africa’s long-standing leaders will come under increasing pressure to demonstrate their societal value. Some will become more oppressive; others may conclude that their time has expired and that they should welcome a transition.

This is the key lesson of Angola – where president dos Santos willingly retired after 37 years in power. Mugabe dreamed of dying in office and being succeeded by his wife – and was forced out by the military. I predict both models will be repeated in Africa in coming years.

This article was originally published in the Irish Times.

Zimbabwe Ahead of the Elections: Political and Economic Challenges 8 May 2018 — 10:00AM TO 11:00AM Anonymous (not verified) 3 May 2018 Chatham House, London

The upcoming elections in Zimbabwe will be the first since 2000 in which former president Robert Mugabe and long-time opposition leader Morgan Tsvangirai are not on the ballot paper. A key electoral issue for many voters will be the economy: recent years have been marked by high unemployment rates, chronic cash shortages and mounting public debt. Although this has traditionally been a strong campaigning issue for the opposition, President Emmerson Mnangagwa has fast-tracked comprehensive economic reforms.

At this event, Nelson Chamisa, MDC Alliance presidential candidate, will discuss his efforts to build a united opposition coalition with a strong message, the steps needed to ensure a free and fair election can take place, and the role that international partners can play in Zimbabwe’s democratic process.

Higher Education in South Africa: Demands for Inclusion and the Challenges of Reform 17 October 2018 — 5:00PM TO 6:00PM Anonymous (not verified) 18 September 2018 Chatham House, London

Political Reform in Angola: Challenges and Priorities for Elected Officials 31 October 2018 — 4:00PM TO 5:00PM Anonymous (not verified) 26 October 2018 Chatham House, London

Angola’s reformulated National Assembly has passed a series of legislative reforms since elections in August 2017, in which the ruling MPLA won a majority of 150 seats to the 51 held by the UNITA leading opposition party.

Many of the changes have targeted the revitalization of an underperforming economy and improved governance: in June 2018 parliament approved a new private investment law aimed at diversifying Angola’s fiscal base beyond oil revenues while new legislation in May mandated the return of illicitly exported capital of over $100,000.

As the appetite for measurable progress across all sectors of society remains high, and with newly constituted municipal elections scheduled for 2020, inclusive and accountable political debate will remain critical to Angola’s future.

At the event, a cross-party delegation discuss the role of the National Assembly in affecting political change and the importance of maintaining open dialogue among opposing voices to address the challenges facing Angola.

Can Liberation Movements Really Rid Southern Africa of Corruption? Expert comment sysadmin 16 December 2019

Southern Africa’s national liberation movements have survived ‘end of decade’ elections across the region. Combating corruption has been at the heart of many of the campaigns, but the question is can they succeed?

Swapo’s victory in Namibia two weeks ago was the last in a series of recent ‘end of decade’ elections that have returned dominant parties to power across Southern Africa. However, the “enduring appeal of liberation” is wearing thin.

Experiences across the region show that if governments are to deliver on their electoral promises, they must empower institutions, actively promote a culture of accountability and transparency within their party ranks and pursue economic reforms that untangle the web of party-state-business alliances. Such actions are critical for the survival of national liberation movements as the dominant force in the politics of Southern Africa – but will be difficult to implement.

Avoid political factionalism

South Africa, Botswana, Angola and Zimbabwe all saw new presidents take over just before elections. All used the rhetoric of anti-corruption to distance themselves from the tainted image of their predecessors. But acting on this requires a shift in mind-set in parties that have always preferred to deal with their problems behind closed doors. High profile adversaries from past regimes make tempting targets but could also drive party divisions.

In Angola, the transition of power was safeguarded by an agreement that former president José Eduardo dos Santos would be immune from prosecution. But this week his son faced corruption charges before the country’s supreme court, a high-profile example of a wave of anti-corruption cases across Southern Africa, driven by dominant parties wary of their future.

The allegations against José Filemino De Sousa Dos Santos, nickname ‘Zenu’, include a $500-million fraud involving the country’s central bank. Pressure is also mounting on Zenu’s sister Isabel — once prominent in Angola, she is now absent from public life.

Other leaders have had to tread more carefully. Immunity was a luxury Cyril Ramaphosa was neither willing nor politically able to grant Jacob Zuma in South Africa. Reliant on a few close allies at the top of the party, Ramaphosa lacks foot soldiers at the grassroots level, and his campaign against corruption within the ANC has faced persistent opposition.

Rebuilding institutions and empowering authorities takes time, and with few high-profile cases to point to, people are getting restless. This is also the case in Zimbabwe, where a worsening economic situation has left policy reformers politically isolated.

Party, state, and business

Long term incumbency has blurred the distinction between the party and the state. Liberation movements have created vast party-linked business empires. Political allegiance grants access to economic resources through appointments to lucrative positions in state-owned enterprises, preferential bids for tenders and licenses, and direct access to decision makers.

In Angola, this was fuelled by oil revenues. In South Africa, state capture flourished in an environment where the ANC and its constituent elements had significant power on the panels that chose leaders for state-owned enterprises (SOEs). In Namibia, an Icelandic fishing company paid backhanders to officials for fishing rights in what has become known as the ‘Fishrot’ scandal. Zanu-PF officials’ access to preferential foreign exchange rates present them with lucrative opportunities in Zimbabwe.

Ending this bureaucratic rent seeking goes beyond appointing ‘clean’ officials, which has been central to the anti-corruption campaigns in Angola and South Africa. Governments must also allow scrutiny of the state and empower those institutions designed for that role, such as the National Prosecuting Authority and the Public Protector in South Africa. Zimbabwe’s auditor general has published an in-depth report of the state of corruption in the country’s SOEs.

Companies must also be held to account for their role in aiding, and at worst directly benefitting, from state graft. International businesses have actively sought to benefit from corruption. They are now starting to face the consequences. A former Credit Suisse banker has pleaded guilty in the US over handling alleged kickbacks in Mozambique’s $2-billion “tuna bond” scandal. Global banks and consultancies continue to feel the squeeze for their complicity in state capture in South Africa.

Competition and pluralism

National liberation movements may only have a limited window within which to act. Across the region civil society campaigns and investigative journalists have shed light on some of the worst abuses of power. Anti-corruption campaigns are starting to bite. The state will continue to play a central role in Southern African economies, an important arbiter of economic transformation able to balance the region’s highly unequal and resource-dependent economies.

But opposition, civil society and the media are also critical for the progression towards democratic competition and pluralism in Southern Africa. Parliaments remain vital for holding rulers to account. Long used to unchallenged dominance, liberation movements have significant adjustments to make to rise to the challenge of a new era.

This article was originally published in the Mail and Guardian.

The National Institute for Health and Care Excellence (NICE) has recommended that all women with suspected endometriosis be offered an early transvaginal ultrasound scan, even if the pelvic or abdominal examination is normal.In its updated guideline1 on the diagnosis and management of endometriosis, NICE recommends specialist ultrasound as an alternative to magnetic resonance imaging for investigating suspected cases of the condition in secondary care.The updated guideline follows recent reports from both the National Confidential Enquiry into Patient Outcome and Death2 and Endometriosis UK which highlighted problems with delayed diagnoses, partly owing to a lack of awareness among healthcare professionals of the condition and how it presents. Such delays can result in prolonged suffering, ill health, and risks to fertility, the reports warned.Other new and updated recommendations include asking women with suspected endometriosis if any first degree relatives have a history of the condition, and considering neurodiversity when taking into account...

Memory politics: the challenge of commemoration in post-Soviet Eastern Europe and the Caucasus 5 October 2021 — 1:00PM TO 2:30PM Anonymous (not verified) 21 September 2021 Online

This event explores how to address memory and commemoration in the former Soviet states, considering their role in political processes and violent conflict. 

How the past is remembered and commemorated plays a large role – perhaps too large – in contemporary political debates and in how conflicts are negotiated.

Perceptions of history influence people’s actions and are used to judge or dismiss the actions of others. Nowhere is this more so than in the political, territorial and social debates and disputes across the former Soviet Union.
 
This event examines how to address the problems caused by entrenched memory debates – and proposes a framework for ‘ethical political commemoration’ for use across historical enquiry, political processes, and conflict transformation initiatives.

The speakers explore the topic through the context of Turkey and the Armenian genocide, as well as more broadly through their own experiences in conflict transformation and peace processes.

Ukraine crisis could trigger cascading risks globally Expert comment NCapeling 16 March 2022

The effects on the wider world from the Ukraine invasion go far beyond the waves of shock and horror being felt from this escalating conflict.

Russia and Ukraine rank 11th and 55th respectively in terms of their national economies but, for the global supply of critical resources such as energy, food, and minerals, these two countries together are far bigger hitters – and both the threat and reality of resource flows from them being reduced have already driven up global prices.

The world is already facing a cost-of-living squeeze coming out of the COVID-19 pandemic, so further price spikes or supply constraints have the potential to seriously undermine food and energy security, equitable access to basic goods and services, and social stability around the world – which can then potentially create systemic risks for economies and societies.

The global implications of the Ukraine conflict are only just beginning to be explored fully but the immediate impacts of the crisis on global markets are already well-documented. In the first few days after Russia’s invasion, energy prices spiked, triggering further fertilizer price rises – as fertilizer production is highly energy intensive – which in turn is contributing to food price rises because fertilizer costs are an important factor in food production.

Interruptions to shipping in the region around Ukraine – as well as globally – have impeded the flow of goods which pushed prices up even further, while economic sanctions on cross-border flows of goods and finance are further adding to market pressures. But this is just the start – these impacts will bring ripple effects which propagate far beyond their point of origin, known as ‘cascading risks’.

Risk is a combination of hazard, exposure, and vulnerability – in terms of the Ukraine invasion, the hazard is the conflict and its immediate impacts on the societies and economies of Ukraine and Russia, while exposure relates to the degree to which other countries are likely to be affected depending on how much they are integrated into the global economy or the ‘just in time’ nature of their supply chains.

Vulnerability relates to a society’s capacity to mitigate the harmful impacts of the conflict, such as controlling borders, sourcing alternative goods from suppliers, or protecting against price or supply shocks.

Risk cascades – the second- and third-order impacts of the original hazard and of responses to that hazard – can interact across sectoral boundaries – as with energy and food, for example – and their compound effect can lead to overall systemic risks for society.

Anticipating this potential is essential to understanding the nature and scale of the global ramifications being felt from the Ukraine conflict. Recent work in the UK to assess levels of cascading risks resulting from a changing climate – the UK Climate Change Risk Assessment – provides a valuable framework for thinking about this area.

It examines key pathways for risk to cascade through global systems – when applied to the situation in Ukraine, these pathways and their interactions offer an indication of the scale of crisis that citizens face far beyond Ukraine’s and Russia’s borders.

Interruptions to the flows of goods and energy

In globalized trade networks, localized disruption to supply chains rapidly yields widespread international impacts – of particular concern is the immediate supply of food because most countries rely on lean supply chains and some may only have a few days food within their own borders.

Experience from previous food price crises indicate even small interruptions to trade can result in runs on the market and rapid price inflation. In the case of this conflict, the trade interruption will be far from small because, between them, Russia and Ukraine export around one-quarter of all traded wheat, more than three-quarters of traded sunflower oil, and one-sixth of traded maize.

Energy markets are also a concern because many countries use more energy than they produce and therefore rely on imports of energy or fuel for domestic use. Russia produces around ten per cent of the world’s commercial energy with a concentration of sales in major regions such as the European Union (EU) and China.

As with food, a shortfall in energy provision leads to market runs and rapid inflation as actors compete in a tightening space, while poorly designed policy interventions by nations trying to ensure their own security add further pressure to global supply and worsen price rises. In addition, the closely interconnected nature of energy markets means disruption to one fuel – such as gas in this case – affects global prices for other forms of energy.

The impact of moving people and money

As the last decade richly illustrates, the cross-border flows of people impact those societies absorbing them – for example, contributing to a rise in nationalism – as well as increase the costs of supplying essential resources. Given many people are understandably fleeing this conflict, other countries may struggle to cope as the cost-of-living crisis and urgent efforts to bolster national security infrastructure may squeeze available public funds.

Financial flows are crucial to the functioning of global economies, whether for inward investment or insurance and – as Russian citizens may be about to discover – restricting the global flow of money has a serious impact on households. Beyond Russia, the outflow of money from major financial centres such as London to meet insurance claims or to enable infrastructure reinvestment post-conflict may also have severe knock-on economic impacts.

The impact on governance and health

The global spikes in energy and food prices resulting from these supply chain disruptions will see many countries struggle with rising food and energy insecurity as well as increased inequality. Taken together these conditions create many issues beyond immigration pressures and the associated politics, including increased inequality and civil unrest.

This potentially destabilizes governments which has consequences for the stability of an entire region such as interrupted supply chains, the need to deploy peacekeeping forces, or significant flows of aid – all with global consequences far beyond the countries in question.

Populations may suffer mental health impacts arising from the Ukraine invasion, whether from the trauma of being forced to leave home to escape conflict, anxiety for the wellbeing and safety of families and friends caught up in it, or a more general anxiety arising from the perception of living in an unstable world.

Neoadjuvant therapy in patients with locally advanced rectal cancer (LARC) has achieved good pathologic complete response (pCR) rates, potentially eliminating the need for surgical intervention. This study investigated preoperative methods for predicting pCR after neoadjuvant short-course radiotherapy (SCRT) combined with immunochemotherapy. Methods: Treatment-naïve patients with histologically confirmed LARC were enrolled from February 2023 to July 2023. Before surgery, the patients received neoadjuvant SCRT followed by 2 cycles of capecitabine and oxaliplatin plus camrelizumab. ⁶⁸Ga-labeled fibroblast activation protein inhibitor ([⁶⁸Ga]Ga-FAPI-04) PET/MRI, [¹⁸F]FDG PET/CT, and contrast-enhanced MRI were performed before treatment initiation and before surgery in each patient. PET and MRI features and the size and number of lesions were also collected from each scan. Each parameter’s sensitivity, specificity, and diagnostic cutoff were derived via receiver-operating-characteristic curve analysis. Results: Twenty eligible patients (13 men, 7 women; mean age, 60.2 y) were enrolled and completed the entire trial, and all patients had proficient mismatch repair or microsatellite-stable LARC. A postoperative pCR was achieved in 9 patients (45.0%). In the visual evaluation, both [⁶⁸Ga]Ga-FAPI-04 PET/MRI and [¹⁸F]FDG PET/CT were limited to forecasting pCR. Contrast-enhanced MRI had a low sensitivity of 55.56% to predict pCR. In the quantitative evaluation, [⁶⁸Ga]Ga-FAPI-04 change in SUL_peak percentage, where SUL_peak is SUV_peak standardized by lean body mass, had the largest area under the curve (0.929) with high specificity (sensitivity, 77.78%; specificity, 100.0%; cutoff, 63.92%). Conclusion: [⁶⁸Ga]Ga-FAPI-04 PET/MRI is a promising imaging modality for predicting pCR after SCRT combined with immunochemotherapy. The SUL_peak decrease exceeding 63.92% may provide valuable guidance in selecting patients who can forgo surgery after neoadjuvant therapy.

Webinar: Turkey’s Challenging Post-COVID 19 Outlook 7 May 2020 — 1:00PM TO 2:00PM Anonymous (not verified) 17 April 2020

More than 500,000 space heaters from GoveeLife and GoveeSmart Electric are being recalled because of safety issues, according to the U.S. Consumer Product Safety Commission.

President-elect Donald Trump wants legal authorities to investigate what he said were possibly illegal rumors he is going to sell his majority stock stake in Trump Media. He claims he won't sell.

Costco voluntarily recalled 79,200 pounds of two types of its store-brand butter over the past month because their labels may not have said the products contain milk.

An American woman who was traveling in Hungary was killed in Budapest last week allegedly by a man she met on vacation.

The Dallas Cowboys agreed to trade a fourth-round pick in the 2025 NFL Draft to the Carolina Panthers in exchange for wide receiver Jonathan Mingo and a seventh-round pick, a league source told UPI on Tuesday.

Oregon, Ohio State, Georgia and Miami lead the first edition of the 2024-25 College Football Playoff rankings, the selection committee announced.

Tua Tagovailoa and Daniel Jones are among UPI senior sports writer Alex Butler's five must-start fantasy football quarterbacks for Week 10.

Billy Napier will remain in place as head football coach at Florida, despite the Gators producing another lackluster campaign during his third season, athletic director Scott Stricklin announced Thursday.

Mike Gesicki and Jonnu Smith are among UPI senior sports writer Alex Butler's four must-start fantasy football tight ends for Week 10.

Tyrone Tracy Jr. and Najee Harris are among UPI senior sports writer Alex Butler's four must-start fantasy football running backs for Week 10.

Brian Thomas Jr. and Jameson Williams are among UPI senior sports writer Alex Butler's four must-start wide receivers for Week 10 of the fantasy football campaign.

Gerry Faust, who won five Ohio high school football state titles before taking over as coach at Notre Dame in the early 1980s, has died, his family announced. He was 89.

Veteran quarterback Dak Prescott will undergo season-ending surgery to repair his injured hamstring, Dallas Cowboys owner Jerry Jones announced Tuesday.

Justin Herbert, Russell Wilson and Quentin Johnston lead UPI senior sports writer Alex Butler's fantasy football waiver wire priority list for Week 11 of the 2024 NFL season.

Last week NSF issued a request for the next round of proposals for its Quantum Leap Challenge Institutes (QLCI). First established in 2020, the QLCI program, as directed by National […]

The post NSF Seeks Proposals for Next Round of Quantum Leap Challenge Institutes appeared first on HPCwire.

BEAVERTON, Ore., Sept. 10, 2024 — The Ethernet Alliance, a global consortium dedicated to the continued success and advancement of Ethernet technologies, today announced details of its exhibit at stand #A3 […]

The post Ethernet Alliance to Feature Cross-Industry Collaboration at ECOC 2024 Exhibit appeared first on HPCwire.

Mysterious black balls that washed up on Sydney, Australia, beaches were initially suspected to be tar balls but turned out to be miniature "fatbergs" containing human feces.

A wallaby on the loose in Kentucky was caught on security camera during a nighttime visit to a Perry County family's front yard.