The LDL receptor-related protein-1 (LRP1) is highly expressed in numerous cell types, and its impairment is associated with obesity, diabetes, and fatty liver disease. However, the mechanisms linking LRP1 to metabolic disease are not completely understood. Here, we compared the metabolic phenotype of C57BL/6J wild type and LRP1 knock-in mice carrying an inactivating mutation in the distal NPxY motif after feeding a low fat (LF) diet or high fat diets with (HFHC) or without (HF) cholesterol supplementation. In response to HF feeding, both groups developed hyperglycemia, hyperinsulinemia, and hyperlipidemia, as well as increased adiposity with adipose tissue inflammation and liver steatosis. However, when animals were fed the HF diet supplemented with cholesterol, the LRP1 NPxY mutation prevents hypercholesterolemia, reduces adipose tissue and brain inflammation, and limits liver progression to steatohepatitis. Nevertheless, insulin signaling is impaired in LRP1 NPxY mutant hepatocytes and this mutation does not protect against HFHC-induced insulin resistance. The selective metabolic improvement observed in HFHC-fed LRP1 NPxY mutant mice is due to an apparent increase of hepatic LDL receptor levels, leading to an elevated rate of plasma lipoprotein clearance and lowering of plasma and hepatic cholesterol levels. The unique metabolic phenotypes displayed by LRP1 NPxY mutant mice in response to HF or HFHC diet feeding indicate an LRP1-cholesterol axis in modulating tissue inflammation. The LRP1 NPxY mutant mouse phenotype differs from phenotypes observed in mice with tissue-specific LRP1 inactivation, thus highlighting the importance of an integrative approach to evaluate how global LRP1 dysfunction contributes to metabolic disease development.

Genome-wide association studies (GWAS) have implicated ~380 genetic loci for plasma lipid regulation. However, these loci only explain 17-27% of the trait variance and a comprehensive understanding of the molecular mechanisms has not been achieved. In this study, we utilized an integrative genomics approach leveraging diverse genomic data from human populations to investigate whether genetic variants associated with various plasma lipid traits, namely total cholesterol (TC), high and low density lipoprotein cholesterol (HDL and LDL), and triglycerides (TG), from GWAS were concentrated on specific parts of tissue-specific gene regulatory networks. In addition to the expected lipid metabolism pathways, gene subnetworks involved in ‘interferon signaling’, ‘autoimmune/immune activation’, ‘visual transduction’, and ‘protein catabolism’ were significantly associated with all lipid traits. Additionally, we detected trait-specific subnetworks, including cadherin-associated subnetworks for LDL, glutathione metabolism for HDL, valine, leucine and isoleucine biosynthesis for TC, and insulin signaling and complement pathways for TG. Finally, utilizing gene-gene relations revealed by tissue-specific gene regulatory networks, we detected both known (e.g. APOH, APOA4, and ABCA1) and novel (e.g. F2 in adipose tissue) key regulator genes in these lipid-associated subnetworks. Knockdown of the F2 gene (Coagulation Factor II, Thrombin) in 3T3-L1 and C3H10T1/2 adipocytes reduced gene expression of Abcb11, Apoa5, Apof, Fabp1, Lipc, and Cd36, reduced intracellular adipocyte lipid content, and increased extracellular lipid content, supporting a link between adipose thrombin and lipid regulation. Our results shed light on the complex mechanisms underlying lipid metabolism and highlight potential novel targets for lipid regulation and lipid-associated diseases.

Bile acids (BAs) have been established as ubiquitous regulatory molecules implicated in a large variety of healthy and pathological processes. However, the scope of BA heterogeneity is often underrepresented in current literature. This is due in part to inadequate detection methods, which fail to distinguish the individual constituents of the BA pool. Thus, the primary aim of this study was to develop a method that would allow the simultaneous analysis of specific C24 BA species, and to apply that method to biological systems of interest. Herein, we describe the generation and validation of an LC-MS/MS assay for quantification of numerous BAs in a variety of cell systems and relevant biofluids and tissue. These studies included the first baseline level assessment for planar BAs, including allocholic acid, in cell lines, biofluids, and tissue in a nonhuman primate (NHP) laboratory animal, Macaca mulatta, in healthy conditions. These results indicate that immortalized cell lines make poor models for the study of BA synthesis and metabolism, whereas human primary hepatocytes represent a promising alternative model system. We also characterized the BA pool of M. mulatta in detail. Our results support the use of NHP models for the study of BA metabolism and pathology in lieu of murine models. Moreover, the method developed here can be applied to the study of common and planar C24 BA species in other systems.

Adaptive thermogenesis is highly dependent on uncoupling protein 1 (UCP1), a protein expressed by thermogenic adipocytes present in brown adipose tissue (BAT) and white adipose tissue (WAT). Thermogenic capacity of human and mouse BAT can be measured by positron emission tomography-computed tomography quantifying the uptake of ¹⁸F-fluodeoxyglucose or lipid tracers. BAT activation is typically studied in response to cold exposure or treatment with β-3-adrenergic receptor agonists such as CL316,243 (CL). Currently, it is unknown whether cold-stimulated uptake of glucose or lipid tracers is a good surrogate marker of UCP1-mediated thermogenesis. In metabolic studies using radiolabeled tracers, we found that glucose uptake is increased in mildly cold-activated BAT of Ucp1^–/– versus WT mice kept at subthermoneutral temperature. Conversely, lower glucose disposal was detected after full thermogenic activation achieved by sustained cold exposure or CL treatment. In contrast, uptake of lipoprotein-derived fatty acids into chronically activated thermogenic adipose tissues was substantially increased in UCP1-deficient mice. This effect is linked to higher sympathetic tone in adipose tissues of Ucp1^–/– mice, as indicated by elevated levels of thermogenic genes in BAT and WAT. Thus, glucose and lipoprotein handling does not necessarily reflect UCP1-dependent thermogenic activity, but especially lipid uptake rather mirrors sympathetic activation of adipose tissues.

Beiging of white adipose tissue (WAT) has beneficial effects on metabolism. Although it is known that beige adipocytes are active in lipid catabolism and thermogenesis, how they are regulated deserves more explorations. In this study, we demonstrate that stearoyl-CoA desaturase 1 (SCD1) in subcutaneous WAT (scWAT) responded to cold stimulation and was able to promote mobilization of triacylglycerol [TAG (triglyceride)]. In vitro studies showed that SCD1 promoted lipolysis in C3H10T1/2 white adipocytes. The lipolytic effect was contributed by one of SCD1’s products, oleic acid (OA). OA upregulated adipose TAG lipase and hormone-sensitive lipase expression. When SCD1 was overexpressed in the scWAT of mice, lipolysis was enhanced, and oxygen consumption and heat generation were increased. These effects were also demonstrated by the SCD1 knockdown experiments in mice. In conclusion, our study suggests that SCD1, known as an enzyme for lipid synthesis, plays a role in upregulating lipid mobilization through its desaturation product, OA.

The dominant role of CaV2 voltage-gated calcium channels for driving neurotransmitter release is broadly conserved. Given the overlapping functional properties of CaV2 and CaV1 channels, and less so CaV3 channels, it is unclear why there have not been major shifts toward dependence on other CaV channels for synaptic transmission. Here, we provide a structural and functional profile of the CaV2 channel cloned from the early-diverging animal Trichoplax adhaerens, which lacks a nervous system but possesses single gene homologues for CaV1–CaV3 channels. Remarkably, the highly divergent channel possesses similar features as human CaV2.1 and other CaV2 channels, including high voltage–activated currents that are larger in external Ba2+ than in Ca2+; voltage-dependent kinetics of activation, inactivation, and deactivation; and bimodal recovery from inactivation. Altogether, the functional profile of Trichoplax CaV2 suggests that the core features of presynaptic CaV2 channels were established early during animal evolution, after CaV1 and CaV2 channels emerged via proposed gene duplication from an ancestral CaV1/2 type channel. The Trichoplax channel was relatively insensitive to mammalian CaV2 channel blockers ω-agatoxin-IVA and ω-conotoxin-GVIA and to metal cation blockers Cd2+ and Ni2+. Also absent was the capacity for voltage-dependent G-protein inhibition by co-expressed Trichoplax Gβγ subunits, which nevertheless inhibited the human CaV2.1 channel, suggesting that this modulatory capacity evolved via changes in channel sequence/structure, and not G proteins. Last, the Trichoplax channel was immunolocalized in cells that express an endomorphin-like peptide implicated in cell signaling and locomotive behavior and other likely secretory cells, suggesting contributions to regulated exocytosis.

Influenza A virus (IAV) mutates rapidly, resulting in antigenic drift and poor year-to-year vaccine effectiveness. One challenge in designing effective vaccines is that genetic mutations frequently cause amino acid variations in IAV envelope protein hemagglutinin (HA) that create new N-glycosylation sequons; resulting N-glycans cause antigenic shielding, allowing viral escape from adaptive immune responses. Vaccine candidate strain selection currently involves correlating antigenicity with HA protein sequence among circulating strains, but quantitative comparison of site-specific glycosylation information may likely improve the ability to design vaccines with broader effectiveness against evolving strains. However, there is poor understanding of the influence of glycosylation on immunodominance, antigenicity, and immunogenicity of HA, and there are no well-tested methods for comparing glycosylation similarity among virus samples. Here, we present a method for statistically rigorous quantification of similarity between two related virus strains that considers the presence and abundance of glycopeptide glycoforms. We demonstrate the strength of our approach by determining that there was a quantifiable difference in glycosylation at the protein level between WT IAV HA from A/Switzerland/9715293/2013 (SWZ13) and a mutant strain of SWZ13, even though no N-glycosylation sequons were changed. We determined site-specifically that WT and mutant HA have varying similarity at the glycosylation sites of the head domain, reflecting competing pressures to evade host immune response while retaining viral fitness. To our knowledge, our results are the first to quantify changes in glycosylation state that occur in related proteins of considerable glycan heterogeneity. Our results provide a method for understanding how changes in glycosylation state are correlated with variations in protein sequence, which is necessary for improving IAV vaccine strain selection. Understanding glycosylation will be especially important as we find new expression vectors for vaccine production, as glycosylation state depends greatly on the host species.

Extracellular vesicles (EVs) secreted by the epididymal epithelium transfer to spermatozoa key proteins that are essential in promoting motility and subsequent fertilization success. Using the domestic cat model, the objectives were to (1) characterize and compare protein content of EVs between segments of the epididymis, and (2) compare EV protein compositions between normo- and teratospermic individuals (producing >60% of abnormal spermatozoa). Epididymal EVs from adult cats were isolated and assessed via liquid chromatography tandem MS. Both male types shared 3008 proteins in total, with 98 and 20 EV proteins unique to normospermic and teratospermic males, respectively. Expression levels of several proteins changed between epididymal segments in both male types. Several proteins in both groups were related to sperm motility (e.g. hexokinase 1, adenylate kinase isoenzyme) and zona pellucida or oolemma binding (e.g. disintegrin and metalloproteinase domain proteins, zona binding proteins 1 and 2). Interestingly, seven cauda-derived EV proteins trended downward in teratospermic compared with normospermic males, which may relate to poor sperm quality. Collective results revealed, for the first time, EV proteins related to sequential sperm maturation with differences observed between normospermic and teratospermic individuals.

Les médicaments utilisés pour le traitement des troubles mentaux peuvent avoir des effets secondaires plus ou moins graves sur la santé des patients. C’est le cas de seroplex, un médicament largement utilisé comme traitement dans le domaine de la santé mentale. Mais en réalité, quelle est la composition de ce médicament et quels sont ses […]

L’article Quels sont les effets secondaires de seroplex ? est apparu en premier sur Ortho Doc France.

En France, environ 2 à 4 % de la population, souvent des femmes, est touchée par la fibromyalgie. Mais en réalité, qu’est-ce que la fibromyalgie ? Quelles sont les astuces naturelles permettant de soulager les patients qui présentent des symptômes de cette maladie ? Quels sont les symptômes de la fibromyalgie ? La fibromyalgie, ou syndrome fibromyalgique, […]

L’article Quelques remèdes de grand-mère pour soulager les symptômes de la fibromyalgie est apparu en premier sur Ortho Doc France.

Contrairement à ce qu’on pourrait croire, bien plus de femmes se préoccupent de leurs poids et y font attention. Pour ces femmes, comprendre ce qu’est un indice de masse corporelle (IMC) normal peut permettre de maintenir une bonne santé et savoir quand faire appel à un médecin pour leurs poids. C’est quoi l’IMC ou indice de masse […]

L’article Quel est l’IMC normal pour une femme ? est apparu en premier sur Ortho Doc France.

Pour beaucoup de personnes, la perte de poids rime obligatoirement avec une période de privation. Mais contrairement à ces idées reçues, il est bien possible d’observer un régime pour perdre du poids tout en vous faisant plaisir. Découvrez notre recette minceur de biscuits croquants sans beurre aux flocons d’avoine qui raviront vos papilles sans pour autant vous apporter […]

L’article Quelle est la meilleure recette minceur à base de biscuits aux flocons d’avoine ? est apparu en premier sur Ortho Doc France.

Le ventre est l’une des parties du corps où il est plus difficile de perdre de la graisse. Souvent, la meilleure solution pour arriver à perdre de la graisse à cet endroit précis du corps consiste à manger sainement et équilibré. Cependant, quels sont les aliments qui brûlent les graisses du ventre sans danger pour la […]

L’article Quels sont les aliments qui brûlent rapidement les graisses du ventre ? est apparu en premier sur Ortho Doc France.

Les troubles gastro-intestinaux peuvent avoir un impact significatif sur la qualité de vie des patients. Ils engendrent en effet des symptômes variés et inconfortables allant de douleurs abdominales et nausées à des troubles plus graves comme les maladies inflammatoires chroniques de l’intestin. Quelles sont les principales pathologies rencontrées dans cette spécialité de la médecine ? À quel […]

L’article Quelles sont les principales pathologies en gastroentérologie ? est apparu en premier sur Ortho Doc France.

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.

Paramphistomosis, caused by the rumen fluke, Calicophoron daubneyi, is a parasitic infection of ruminant livestock which has seen a rapid rise in prevalence throughout Western Europe in recent years. Following ingestion of metacercariae (parasite cysts) by the mammalian host, newly-excysted juveniles (NEJs) emerge and invade the duodenal submucosa which causes significant pathology in heavy infections. The immature larvae then migrate upwards, along the gastrointestinal tract, and enter the rumen where they mature and begin to produce eggs. Despite their emergence, and sporadic outbreaks of acute disease, we know little about the molecular mechanisms used by C. daubneyi to establish infection, acquire nutrients and to avoid the host immune response. Here, transcriptome analysis of four intra-mammalian life-cycle stages, integrated with secretome analysis of the NEJ and adult parasites (responsible for acute and chronic disease respectively), revealed how the expression and secretion of selected families of virulence factors and immunomodulators are regulated in accordance with fluke development and migration. Our data show that whilst a family of cathepsins B with varying S2 sub-site residues (indicating distinct substrate specificities) are differentially secreted by NEJs and adult flukes, cathepsins L and F are secreted in low abundance by NEJs only. We found that C. daubneyi has an expanded family of aspartic peptidases, which is up-regulated in adult worms, although they are underrepresented in the secretome. The most abundant proteins in adult fluke secretions were helminth defence molecules (HDMs) that likely establish an immune environment permissive to fluke survival and/or neutralise pathogen-associated molecular patterns (PAMPs) such as bacterial lipopolysaccharide in the microbiome-rich rumen. The distinct collection of molecules secreted by C. daubneyi allowed the development of the first coproantigen-based ELISA for paramphistomosis which, importantly, did not recognise antigens from other helminths commonly found as co-infections with rumen fluke.

The complexity and dynamics of the immensely heterogeneous glycoproteome of the prostate cancer (PCa) tumour micro-environment remain incompletely mapped, a knowledge gap that impedes our molecular-level understanding of the disease. To this end, we have used sensitive glycomics and glycoproteomics to map the protein-, cell- and tumour grade-specific N- and O-glycosylation in surgically-removed PCa tissues spanning five histological grades (n = 10/grade) and tissues from patients with benign prostatic hyperplasia (n = 5). Quantitative glycomics revealed PCa grade-specific alterations of the oligomannosidic-, paucimannosidic- and branched sialylated complex-type N-glycans, and dynamic remodelling of the sialylated core 1- and core 2-type O-glycome. Deep quantitative glycoproteomics identified ~7,400 unique N-glycopeptides from 500 N-glycoproteins and ~500 unique O-glycopeptides from nearly 200 O-glycoproteins. With reference to a recent Tissue and Blood Atlas, our data indicate that paucimannosidic glycans of the PCa tissues arise mainly from immune cell-derived glycoproteins. Further, the grade-specific PCa glycosylation arises primarily from dynamics in the cellular makeup of the PCa tumour microenvironment across grades involving increased oligomannosylation of prostate-derived glycoproteins and decreased bisecting GlcNAcylation of N-glycans carried by the extracellular matrix proteins. Further, elevated expression of several oligosaccharyltransferase subunits and enhanced N-glycoprotein site occupancy were observed associated with PCa progression. Finally, correlations between the protein-specific glycosylation and PCa progression were observed including increased site-specific core 2-type O-glycosylation of collagen VI. In conclusion, integrated glycomics and glycoproteomics have enabled new insight into the complexity and dynamics of the tissue glycoproteome associated with PCa progression generating an important resource to explore the underpinning disease mechanisms.

The early detection of pancreatic ductal adenocarcinoma is a complex clinical obstacle yet is key to improving the overall likelihood of patient survival. Current and prospective carbohydrate biomarkers CA19-9 and sTRA are sufficient for surveilling disease progression yet are not approved for delineating PDAC from other abdominal cancers and non-cancerous pancreatic pathologies. To further understand these glycan epitopes, an imaging mass spectrometry approach was utilized to assess the N-glycome of the human pancreas and pancreatic cancer in a cohort of PDAC patients represented by tissue microarrays and whole tissue sections. Orthogonally, these same tissues were characterized by multi-round immunofluorescence which defined expression of CA19-9 and sTRA as well as other lectins towards carbohydrate epitopes with the potential to improve PDAC diagnosis. These analyses revealed distinct differences not only in N-glycan spatial localization across both healthy and diseased tissues but importantly between different biomarker-categorized tissue samples. Unique sulfated bi-antennary N-glycans were detected specifically in normal pancreatic islets. N-glycans from CA19-9 expressing tissues tended to be bi-, tri- and tetra-antennary structures with both core and terminal fucose residues and bisecting N-acetylglucosamines. These N-glycans were detected in less abundance in sTRA-expressing tumor tissues, which favored tri- and tetra-antennary structures with polylactosamine extensions. Increased sialylation of N-glycans was detected in all tumor tissues. A candidate new biomarker derived from IMS was further explored by fluorescence staining with selected lectins on the same tissues. The lectins confirmed the expression of the epitopes in cancer cells and revealed different tumor-associated staining patterns between glycans with bisecting GlcNAc and those with terminal GlcNAc. Thus, the combination of lectin-IHC and IMS techniques produces more complete information for tumor classification than the individual analyses alone. These findings potentiate the development of early assessment technologies to rapidly and specifically identify PDAC in the clinic that may directly impact patient outcomes.

Exploring Public International Law Issues with Chinese Scholars – Part Four Other resource sysadmin 30 October 2018

As part of a roundtable series, Chatham House and the China University of Political Science and Law (CUPL) held a two-day roundtable in Beijing on emerging issues of public international law.

The specific objectives were to:

• create a platform for Chinese international law academics working on international human rights law issues to present their thinking and exchange ideas with counterparts from outside China;
• build stronger understanding within the wider international law community of intellectual debates taking place in China about the international human rights system and China’s role within it;
• support networking between Chinese and non-Chinese academics working on international human rights and related areas of international law.

The roundtable forms part of a wider Chatham House project exploring China’s impact on the international human rights system and was inspired by early discussions with a burgeoning community of Chinese academics thinking, writing (mainly in Chinese) and teaching about international human rights law.

For CUPL, one of the largest and most prestigious law schools in China and perhaps the only university in the world with an entire faculty of international law, the initiative is part of a drive to forge partnerships beyond China in the international law field.

The meeting was co-hosted with CUPL and involved 28 participants, consisting of 19 Chinese participants (from six leading research institutions in Beijing and Shanghai) and nine nonChinese participants (from eight leading research institutions in Australia, the Netherlands, the UK, Switzerland, Canada and Singapore).

To ensure continuity while also expanding the expert network being built, the fifth meeting included a mix of participants from the previous meetings and some new participants.

All discussions were held in English under the Chatham House Rule.

The Costs of Fuelling Humanitarian Aid Research paper sysadmin 7 December 2018

As humanitarian crises become more protracted and aid budgets face unprecedented scrutiny, agencies could save millions by switching from diesel and oil fuels to cleaner energy sources.

Download the accompanying toolkit

Most refugee and internal displacement camps are in remote locations, so humanitarian agencies consume large amounts of fuel on the transport of staff, equipment, and goods such as food and water.

Operations tend to rely on on-site electricity generation to power reception centres, clinics, schools, food storage, water-pumping and street lighting. Despite the essential role of energy in humanitarian action, and the UN’s stated commitment to carbon neutrality by 2020, there is no concerted effort to move away from fossil fuel to date.

Summary points

• Agencies are paying too much for the energy they consume. They are overwhelmingly dependent on oil fuel for electricity generation, even though renewable energy solutions are reducing costs for those deploying them in similar conditions. Well-below-optimum standards of efficiency in buildings, generator use and fleet management are also the norm.
• Agencies typically have few incentives to do things better. There is rarely motivation to conserve fuel, nor performance indicators for energy or fuel use. In addition, energy spending and use lacks transparency.
• Few agencies collect and report on energy use. Where numbers are available, they are usually partial and unverified. Energy costs are rarely transparent in budgets; and donors do not know how much is being spent.
• We estimate that around 5 per cent of humanitarian agencies’ expenditure goes on diesel, petrol and associated costs such as fixing generators. That would mean that the sector spent some $1.2 billion on polluting fuel in 2017.
• Based on current best-practice, the sector could save at least 10 per cent of fuel costs on ground transport, 37 per cent through behaviour change and more efficient technologies, and 60 per cent on generation – all using currently available, affordable and proven practice and technology changes.
• At current prices, this could mean operational savings of over $517 million a year for the humanitarian sector, roughly equal to 5 per cent of UNHCR’s funding gap for 2017.
• In Kenya, annual spending on diesel and petrol for the seven agencies surveyed was $6.7 million in 2017. Replacing gensets with solar systems could create significant savings due the costs of diesel, the likelihood of protracted camp situations, and the opportunities that off-grid solar would offer for extending electricity access to refugees and local populations in Garissa and Turkana counties.
• In Jordan, solar energy now powers the majority of camp facilities and many households. However, the use of grid electricity by humanitarian agencies’ large head offices in Amman remains high and expensive. Improving the energy efficiency of buildings is a priority for savings.
• In Burkina Faso’s Goudoubo camp, NGO offices are desperately short of power – they have no computers or air-conditioning. Investment in renewable forms of energy for this and other camp services such as street lighting and water pumping would enable better service provision, and could drive increased rural energy access among host populations across this area of the Sahel.

Toolkit

An accompanying toolkit, Powering Ahead: Improving How We Use and Account for Energy in Humanitarian Operations, provides practical guidance for humanitarian agencies that want to make energy cost savings and reduce their carbon and emissions footprint.

Cooking in Displacement Settings: Engaging the Private Sector in Non-wood-based Fuel Supply Research paper sysadmin 22 January 2019

In displacement settings, providing cooking solutions that reduce negative impacts on the environment and health remains a challenge for local governments, humanitarian agencies, businesses and refugees.

Summary

• Providing adequate cooking fuel and clean-burning, fuel-efficient stoves in displacement settings has long been a major challenge for local authorities, humanitarian agencies, non-governmental organizations, local communities and refugees themselves. Refugees generally have limited access to modern cooking solutions. Most either depend on insufficient humanitarian agency handouts of ‘in-kind’ firewood or have to travel long distances to collect firewood.
• There is significant potential for private-sector engagement in this context – which, though largely overlooked to date, could result in win-win scenarios for all stakeholders. Refugee camps and other displacement settings present opportunities for private-sector cooking fuel companies to expand their customer bases, with the added advantage for vendors of offering concentrated demand and scope for economies of scale.
• For the Kakuma refugee camp complex in Kenya, the Moving Energy Initiative (MEI) decided to engage with the private sector directly. The MEI requested expressions of interest from local private-sector companies for expanding sales and distribution of fuels in the complex through the concession. The winning company – National Oil Corporation of Kenya – is to receive a prize of $50,000 for its proposed concession to supply liquefied petroleum gas both to refugees in the Kakuma complex and to the surrounding host community.
• The MEI also conducted interviews with various stakeholders in other contexts and countries who are engaged in efforts to develop market-based approaches to providing clean, fuel-efficient cooking solutions to refugees.
• Based on the interviews and the concession process, the MEI recommends greater donor investment and longer-term guaranteed funding for cooking interventions. This is needed to allow sufficient time to build sustainable markets and secure the requisite engagement and investments from the private sector.
• Larger, longer-term investments by the private sector – supported through partnerships with donors and humanitarian agencies – in infrastructure and demand creation (both in and outside the refugee community) can reduce the price of alternative solutions and support a gradual transition away from subsidies.

The Phillies continued to bolster their infield depth on Friday by signing versatile veteran Sean Rodriguez to a Minor League contract with an invite to big league Spring Training, MLB.com has learned.

Phillies president Andy MacPhail opened a 28-minute press conference on Friday afternoon at Spectrum Field with facts and figures about investments the organization made the past few seasons as the team wallowed at the bottom of the National League. Then MacPhail talked a lot about Bryce Harper and Manny Machado as well as manager Gabe Kapler.

Our weekly series previewing each of baseball's six divisions begins with the American League West. Let's take a team-by-team look at the biggest questions this season.

The Angels announced their Minor League coaching staffs on Saturday, including former Major League catcher Lou Marson being named the new manager of Triple-A Salt Lake and former big leaguer David Newhan as the new skipper at Double-A Birmingham.

How Influential Is China in Zimbabwe? Expert comment sysadmin 20 November 2017

A trip to Beijing by Zimbabwe’s military chief was a ‘normal military exchange’, China’s foreign ministry said after the army seized power in Harare. Alex Vines examines the extent of China’s influence in Zimbabwe.

The news that General Constantino Chiwenga had visited China only a few days before the military takeover in Zimbabwe was a coincidence that did not go unnoticed. There was also speculation after China said it was closely watching developments, but stopped short of condemning President Robert Mugabe’s apparent removal from power.

China is Zimbabwe’s fourth-largest trading partner and its largest source of investment - with stakes worth many billions of pounds in everything from agriculture to construction. Zimbabwe is the dependent partner - with China providing the largest market for its exports and much needed support to its fragile economy.

China’s relations with Zimbabwe are deep, starting during the Rhodesian Bush War. Robert Mugabe failed in 1979 to get Soviet backing, so turned to China, which provided his guerrilla fighters with weapons and training. Both countries formally established diplomatic relations at Zimbabwean independence in 1980 and Mugabe visited Beijing as prime minister the following year. He has been a regular visitor since.

For years, Zimbabwe’s officials have tried to play off China against the West, advocating the country’s ‘Look East’ strategy, particularly following the introduction of EU sanctions in 2002. Indeed, a decade ago, Mugabe told a packed rally at the Chinese-built national sports stadium in Harare: ‘We have turned east, where the sun rises, and given our back to the west, where the sun sets.’

China’s military engagement also deepened during Zimbabwe’s ‘Look East’ era. Significant purchases were made, including Hongdu JL-8 jet aircraft, JF-17 Thunder fighter aircraft, vehicles, radar and weapons. However, following a controversy about a shipment of arms in 2008, Beijing decided to list Zimbabwe for ‘limited level’ military trading.

Despite Zimbabwe’s efforts, the ‘Look East’ strategy did not bring the investment flood hoped for and a decade later, in August 2015, Mugabe openly asked for Western re-engagement in his ‘state of the nation’ address.

Now, the reality is that increasingly Chinese and Western interests - particularly those of the UK - have become aligned. Not far from each other in the outer suburbs of Harare, two of the biggest embassies in Zimbabwe are the British and the Chinese. As other embassies scaled down or closed, Beijing’s expanded. Whereas British diplomats were well connected with business, civil society and opposition figures, the Chinese invested in ‘technical support’ of the party of government Zanu-PF, including state security and the presidency. When it came to Zanu-PF politics and factionalism, Chinese diplomats were well connected and insightful and, like their Western colleagues, concerned about stability, a better investment climate and adherence to the rule of law.

President Xi Jinping visited Zimbabwe in 2015 and President Mugabe visited Beijing in January 2017. In public, the Chinese leader said his country is willing to encourage capable companies to invest in Zimbabwe. But in private, the message was that there would be no more loans until Zimbabwe stabilized its economy.

In 2016 trade between the two countries amounted to $1.1 billion, with China the biggest buyer of Zimbabwean tobacco and also importing cotton and various minerals. In return Zimbabwe imported electronics, clothing and other finished products. Chinese state construction firms have also been active, building infrastructure including Zimbabwe’s $100 million National Defence College. And last year China agreed to finance a new 650-seat parliament in Harare.

But Chinese diplomats and many businesses are waiting for better days in Zimbabwe. Some companies have found the investment climate challenging - being burned on diamonds, for example - and have looked for alternative markets. A couple of weeks ago I was in China, attending a meeting on China-Africa relations and Zimbabwe was not mentioned once. Unlike Ethiopia, Sudan, or Angola that are strategic partners, or big markets like Nigeria, Kenya and South Africa, Zimbabwe is far from being Beijing’s new priority.

So, Beijing’s interest is in a better investment climate in Zimbabwe. A clear transitional arrangement resulting in elections for a legitimate government in Harare is as much in Beijing’s interest as London’s.

The ‘Look East’ and the ‘Re-engagement with the West’ strategies have not brought about the confidence and investment that Zimbabwe needs. What Zimbabwe requires is stable and accountable government - then investors from Asia, America and Europe will seriously consider that Zimbabwe has an investment future. This was the message that Mugabe received in Beijing in January. And the one which Zimbabwe’s military chief also was given last week.

This article was originally published by BBC News.

Afonso Dhlakama’s Death Changes the Calculation for Peace Prospects in Mozambique Expert comment sysadmin 4 May 2018

If politicians continue to act in good faith, the death of the opposition leader may be a significant opportunity to finally draw a line under Mozambique’s long war.

The unexpected death of opposition and ex-rebel leader Afonso Dhlakama on 3 May is a game changer for Mozambique’s politics and an almost-completed peace process. The 65-year old Dhlakama, who died of a heart attack, had led Renamo for 38 years and had totally dominated his party. Dhlakama regularly boasted that he was Mozambique’s ‘father of democracy’, despite not allowing competition within his own party, and he leaves a legacy of more than 30 years of struggle, through both armed action and peaceful politics.

A long war

Originally Renamo had been a tool for the white minority regimes of Rhodesia and apartheid South Africa to challenge the socialist Frelimo political party that took power in Mozambique in 1975. But under Dhlakama’s command, by the late 1980s Renamo had become increasingly independent and rooted in Mozambique. After Renamo’s long war with Frelimo ground to a hurting stalemate, a transition led to Mozambique’s first multiparty elections in 1994, and the creation of a new joint army. A ‘pay and scatter’ programme successfully dispersed and reintegrated many thousands of ex-combatants.

But early post-election gains did not translate to lasting peace. Disarmament was a time-limited, technical process, and devoted declining resources and attention to clusters of ex-combatants that failed to disperse. In addition, Dhlakama was allowed to maintain an armed militia under the guise of a presidential guard.

Mounting economic inequality, notably in opposition strongholds such as central Mozambique, saw Renamo made political gains and Dhlakama nearly won the 1999 presidential elections. (Some believe he did.) The result focused Frelimo’s attention on the threat that Renamo posed and, ultimately, a strategy of pursuing total Frelimo domination across the country, culminating in a crushing Frelimo victory at the 2009 elections.

This humiliated and marginalized former Renamo rebels, resulting in Dhlakama ordering their return to targeted armed violence in 2013. Frelimo’s new leader, President Filipe Nyusi, took power in 2015 and sought direct dialogue with Dhlakama. Five rounds of internationally mediated peace talks took place from July to December. Finally, in late December 2016, Dhlakama announced a unilateral truce, which was extended twice and subsequently made indefinite.

New peace talks also started and, in August 2017 and February 2018, President Nyusi and Dhlakama showed the courage to meet in person, near Renamo’s base in central Mozambique, to build up mutual trust and discuss the details of the emerging peace deal – including the demobilization or integration into government security forces for Renamo’s now mostly middle-aged gunmen.

Dhlakama the ‘Big Man’

Dhlakama’s sudden death has fundamentally changed the negotiation dynamics. He never allowed for any serious succession planning, and ensured all key decisions were his and his alone. Renamo had already decided that he would be its presidential candidate for the 2019 national elections.

His party is significantly weakened by his death and unlikely able to fully recover – but needs to try and reach consensus quickly on a successor, as it will also compete in municipal elections in October and was expecting significant gains. There will be a number of contenders to succeed him including from the parliamentary wing, led by his niece Ivone Soares, its secretary general, Manuel Bissopo, and a few others.

But Renamo’s key leverage for now remains some 1,000 middle-aged gunmen in central Mozambique who have been stoically loyal to Dhlakama since the 1980s and who have little respect for the younger generation of professional politicians based in Maputo. Some may be bought off by government offers, others integrated into localised organized crime groups and others into internal Renamo sectarianism. The risk of fragmentation is real.

Renamo’s weakness could also embolden Frelimo hardliners to seek a return to unilateral domination of Mozambique’s political landscape, and to undermine the peace process. That would be a serious tactical mistake by Frelimo, as a lasting deal is close and the death of Dhlakama could actually assist in making this settlement lasting. Dhlakama was quixotic and prone to changing his mind, often influenced by the last person he spoke to – his death potentially introduces greater predictability in negotiations and in any post-deal implementation.

President Nyusi is clearly aware of this as he hailed on state television TVM that Dhlakama was ‘a citizen who has always worked for Mozambique’ and said he was distraught at the news of his death. He stated, ‘I hope that we as Mozambicans can continue to do everything so things do not go down.’ He also addressed Renamo’s support base by saying that ‘[Dhlakama] did everything so that there would be peace. The last time he spoke to me, he said he was not going to miss out anything in peace negotiations.’

Renamo’s gunmen are fatigued and want to retire with dignity but are vulnerable to manipulation and political miscalculation by Mozambican’s positioning politicians. International partners and investors can engage, by emphasizing that sustainable peace is the only pathway to poverty reduction and inclusive economic development.

This includes assisting development and reconciliation projects in areas impacted by the renewed conflict since 2013. Long-term investment for development in Renamo’s key constituencies could help avoid fragmentation at a critical time – faith groups and NGOs may also have a key role to play.

If Mozambique’s politicians continue to act in good faith, the death of Dhlakama may constitute a significant opportunity to finally draw a line under Mozambique’s long war.

Hope, Peace and Reconciliation: Pope Francis in Mozambique Expert comment sysadmin 4 September 2019

A papal visit will highlight the importance of the recently signed peace agreement between the government and opposition.

Pope Francis’ visit to Mozambique on 4–6 September comes at a critical political moment. The theme for the papal Africa trip (which also includes Madagascar and Mauritius) is ‘pilgrim of hope, peace and reconciliation’. This is especially relevant for Mozambique, as this is the first week of the official campaign for Mozambique’s sixth national elections on 15 October.

It is also the one-month anniversary of the Maputo Accords for Peace and Reconciliation between the government and the armed opposition, RENAMO (and the fifth anniversary of the previous such agreement in 2014).

What is unusual is that the pope accepted to visit Mozambique just after a peace accord and in the run-up to national elections. Something similar has happened only once, when Pope John Paul II visited Angola in June 1992 (following the Bicesse Accords) prior to the country’s first ever national elections in September. Unfortunately Pope John Paul’s preaching of reconciliation and pluralism failed and civil war resumed some months later, following rejection of the preliminary election results. Angola’s civil war only finally ended a decade later in 2002.

The last papal visit to Mozambique was also by Pope John Paul II in 1988, when civil war was still ongoing, and the country was still a single party state. Despite the war, massive congregations attended and RENAMO reached local ceasefires and agreements to maintain electricity supply to honour the visit. Some of the seeds for the Rome peace process were laid during this trip – especially as it also represented a formal reconciliation of FRELIMO, the ruling party, with the Catholic Church.

This papal visit to Mozambique is equally anticipated, as was highlighted several times during speeches at the 6 August peace agreement signing in Maputo. When I was in Maputo last month, sales of papal-pictured capulanas (a Mozambican sarong) were brisk and Mozambican television carried countdown clocks on many programmes for the touchdown of Pope Francis on national soil.

The Catholic Church has played an instrumental role in promoting peace in Mozambique over the years. The 1977–92 civil war ended through negotiations hosted at the Sant’ Egidio lay community in Rome, and the current Archbishop of Bologna, Dom Matteo Zuppi (who led the Sant’ Egido negotiations in 1992 and is soon to be made a cardinal) was an official witness to 6 August accords signing.

When targeted armed conflict resumed in 2013, faith groups once more re-engaged and in 2016 Sant’ Egidio once more co-led mediation efforts, less successfully than in 1991–92. Sant’ Egidio (including during a presidential visit to Rome in July) contributed to convincing the Vatican that this papal visit should occur before the October elections.

President Filipe Nyusi anxiously wanted this visit to occur before the elections. He is seeking re-election for his second and final term and a papal visit should help win some votes. His party, FRELIMO, is also worried about securing a majority in the national assembly, as it has been weakened by patchy delivery of services and ongoing high-level corruption scandals.

This year, President Nyusi’s priorities have been to show that he can attract international investment (such as Andarko’s recently announced final investment decision on its gas project), a peace agreement with RENAMO (the August agreements) and a papal visit, so a successful trip would complete his goals.

The pope’s ‘hope, peace and reconciliation’ message of his visit is important. Twice previously, the FRELIMO-led government and RENAMO have reached definitive agreements, in Rome (1992) and Maputo (2014), but failed to fully end bloodshed. This new August 2019 agreement is the third attempt, and if it is to last, it will require political goodwill, compromise and an acceptance of more inclusive national politics by both parties.

There are two immediate threats to this agreement. The first is the forthcoming 15 October elections and their conduct could make or break it. Accepting reconciliation and greater pluralism underpins this agreement, but RENAMO expects to increase its share of the parliamentary vote and win a majority in some provinces (and therefore indirectly elect their choice for governor).

A second threat is the ‘Military Junta’, a RENAMO splinter group that claims to be 500 strong, but probably accounts for 80 armed persons. It rejects the 6 August agreement and warns that it could disrupt the elections. This group has asked for mediation, and hopefully can be accommodated in a side deal to the main one agreed in August, which already provides for the reintegration of over 5,000 RENAMO supporters and combatants.

A recent Chatham House research paper on elite bargains in Mozambique concluded that the October elections will be the first immediate test of the August agreement. If the elections pass without significant electoral manipulation or violence and this August deal sticks on the third attempt, the domestic focus should then move onto poverty reduction, combating inequality, education and solving the new security crisis with Islamic militants in Cabo Delgado province.

Mozambique’s Peace and National Reconciliation Agreement: One Year On 6 August 2020 — 2:30PM TO 4:30PM Anonymous (not verified) 29 July 2020 Online

August 6, 2020 marks one year since the Peace and National Reconciliation Agreement was signed in Maputo. The agreement, signed by the President of Mozambique Filipe Nyusi and RENAMO leader Ossufo Momade, and witnessed by regional and international political and religious leaders, ended the return to conflict that started in 2013.

It also paved the way for Mozambique’s national elections in October 2019. Since the agreement, the Mozambique Liberation Front (FRELIMO) won a landslide victory in the elections, weakening RENAMO, and a splinter group has conducted targeted armed violence in Manica and Sofala provinces. Yet, the disarmament, demobilization, and reintegration (DDR) process has made progress.

At this event, senior figures reflect on the peace agreement and the key factors of its success. The event also draws upon insights from the authors of recent publications on the latest peace agreement in the context of longer term trends of democratization and peace-building in Mozambique.

A Chatham House Africa Programme research paper published in August 2019, Prospects for a Sustainable Elite Bargain in Mozambique: Third Time Lucky?, examined how the deal was achieved. The Portuguese version includes the full text of the peace accord. Read the research paper in Portuguese or English here.

Inclusion, agency and influence: The role of women in Zimbabwe’s economy 8 July 2021 — 3:00PM TO 4:30PM Anonymous (not verified) 2 July 2021 Online

Speakers discuss the changing role of women in Zimbabwe’s economic structures and the priorities for promoting greater economic inclusion, agency and influence of women.

Zimbabwe’s National Development Strategy of 2021-2025 highlights the importance of gender sensitivity in policymaking and of women’s economic participation in attaining the government’s Vision 2030.

However, women have been among the worst affected groups by the devastating effects that COVID-19 has had on Zimbabwe’s already floundering economy, which has exacerbated the challenges they face in economic life, such as access to credit, financial services and social security.

Leveraging existing structures such as women’s groups, micro-finance facilities, education and training, and national gender mechanisms, as well as supporting wider financial and digital inclusion in Zimbabwe, is central for the country’s sustained economic recovery.

This event also focuses on the differing impacts of COVID-19 on women’s economic activities across various sectors, as well as along rural-urban and formal-informal economy lines.

Read a meeting summary

This webinar is part of a series of events in partnership with the Konrad Adenauer Stiftung on Zimbabwe’s economic recovery and reform.

This event will also be broadcast live on the Africa Programme Facebook page.

At a recent clinical meeting, I heard that GPs local to me are about to lose the ability to request magnetic resonance imaging (MRI) scans for patients presenting with musculoskeletal symptoms. We’re instead advised to refer our patients to a musculoskeletal clinical assessment and triage service (CATS)—staffed largely by musculoskeletal advanced practitioners, who will assess our patients and determine whether imaging is warranted.The hope is that fewer patients will have unnecessary imaging and that this will reduce the potential harms of overdiagnosis. Radiologists rarely report musculoskeletal MRI scans as entirely normal, and it can be hard to know what to do with abnormal findings on an MRI. More often than not, patients with abnormal scans are referred to orthopaedic teams, even though there may not necessarily be a surgical target.At a population level, this is problematic on two fronts. Firstly, MRI scans are expensive and need to be used judiciously....

Issues to watch in 2023 The World Today mhiggins.drupal 29 November 2022

From nuclear proliferation to African debt, here are the issues six of our expert contributors expect to make the news in the year ahead.

Europe’s energy outlook

Mike Bradshaw, Professor of Global Energy, Warwick Business School

There is cautious optimism that Europe will endure this winter without an energy crisis. Gas prices have fallen, storage is 95 per cent full, and the autumn was mild. High summer gas prices cut industrial demand but domestic heating demand will be critical over the winter. Already, France’s problematic nuclear fleet and lower hydroelectric output mean Europe is using more gas to generate power. 

Russian pipeline gas supply to southern Europe has fallen by 55 per cent. While Asian demand has fallen, Europe has still paid record prices to secure additional liquefied natural gas (LNG), largely from America but also Russia. European demand for LNG this winter will push prices up, and these will rise even higher if China relaxes its Zero-Covid policy and demand recovers. However, with luck, Europe will avoid power cuts in early 2023. The problem is next winter. With less Russian pipeline gas and a tight LNG market, 90 per cent winter gas storage levels will be much harder to achieve. 

NATO’s resurgence

Alice Billon-Galland, Research Fellow, Europe Programme, Chatham House and one of 14 NATO Young Leaders

In response to Russia’s invasion of Ukraine, NATO adopted a new strategic concept. Member states will reinforce NATO battlegroups and bolster higher readiness forces from 40,000 troops to more than 300,000, while striving to avoid escalation with Russia. Turkey’s attempts to block Sweden and Finland’s NATO membership will preoccupy Jens Stoltenberg, the Secretary-General, until he leaves his post next autumn.

Expect arguments on defence spending in the run-up to the July summit in Vilnius. Although only nine of its 30 members are expected to meet the 2 per cent spending target, the debate is moving towards 3 per cent, in part to reduce dependency on American assets and hedge against the uncertainty of the 2024 US presidential election. Infrastructure vulnerabilities, such as the Nord Stream pipeline sabotage in the Baltic, will also be a focus. Otherwise, NATO ’s eyes will be on China: from its relations with Russia to the threat of cyberattacks.

Universal health reforms

Robert Yates, Executive Director, Centre for Universal Health, Chatham House

In response to the perma-crisis experienced by many populations this past year, some leaders are launching or extending universal health reforms. New left-wing leaders in Chile, Colombia and Brazil have promised to rebuild their publicly financed universal health systems. In Brazil, newly elected president Lula da Silva has pledged to increase public health spending and improve access to medicines. It is hoped Malaysia’s new coalition will carry forward its predecessor’s pledge to raise health spending to 5 per cent of GDP by 2027 to provide a universal package of free health services.

In September, world leaders will discuss universal health coverage at the UN General Assembly. There, Chatham House will publish its Commission for Universal Health report, identifying countries in which crises may trigger new national health programmes. Might this be when a US presidential candidate announces a platform to create a publicly financed health system?

Weapons of mass destruction

Patricia Lewis, Director of the International Security Programme, Chatham House

Since its illegal invasion of Ukraine, Russia has attacked civil nuclear power stations, falsely accused Ukraine of possessing bioweapons and radiological bombs, and threatened to use nuclear weapons. In contrast, NATO has instead demonstrated that deterrence can be highly effective with conventional weaponry. In the coming year, the Kremlin’s nuclear brinkmanship will still be a focus. Washington will try to restart bilateral nuclear negotiations with Moscow and similarly try to engage Beijing.

Following the failure of the nuclear Non-Proliferation Treaty Review Conference to reach consensus in August, the next review cycle will start by looking at strengthening the process. Iran’s nuclear capabilities remain a concern, and North Korea’s nuclear weapons programme is a growing threat. So, we are left with a question: will 2023 be the year of  nuclear conflict or the year when states get busy again on non-proliferation and disarmament?  

Africa’s mounting debt

Joseph Asunka, Chief Executive Officer, Afrobarometer

Inflation is at historic highs in several African economies. Meanwhile, many African countries including Nigeria, Zimbabwe and Democratic Republic of Congo will hold  elections in 2023, driving up public spending, increasing inflationary pressures and exacerbating poverty. According to Afrobarometer data, the proportion of Africans experiencing high levels of poverty has increased from 19 per cent in 2014/2015 to  26 per cent in 2021/2022.

Worse still, many of those countries holding elections are either, like Zimbabwe, in debt distress – that is unable to honour their obligations to creditors – or at high risk of debt distress, like Nigeria. This makes the elections in Zimbabwe and Nigeria critical. The expiration of the World Bank/IMF-backed debt service suspension initiative in 2021 has only amplified this risk. What are viable policy options to tackle this dire economic predicament? A debt service moratorium, debt cancellation and serious attention to fiscal discipline.

Feminist foreign policy

Daniela Philipson García, Co-founder of Internacional Feminista, and a PhD candidate, Monash University

Feminist Foreign Policy (FFP) is under threat. The war in Ukraine led to strengthened military budgets and alliances at odds with FFP’s human security and peace-centred approaches. Sweden’s new right-wing government reversed its FFP. In Mexico, the first Global South country to adopt an FFP, Congress has voted to expand the military’s role to curb cartel-related violence, in contradiction of its FFP. The second anniversary of the US withdrawal from Afghanistan will be a moment to assess how foreign policy, diplomacy and women’s and girls’ rights have been affected globally. 

There is hope. Germany, whose coalition government adopted an FFP in 2021, is to publish more guidelines in the spring. The governments of Colombia and Chile have announced their own FFPs. Colombia’s first National Action Plan on Women, Peace and Security, to be announced at the UN General Assembly in September, is expected to set a standard for a region submerged in violence. 

The peptide hormone ghrelin is produced in cardiomyocytes and acts through the myocardial growth hormone secretagogue receptor (GHSR) to promote cardiomyocyte survival. Administration of ghrelin may have therapeutic effects on post–myocardial infarction (MI) outcomes. Therefore, there is a need to develop molecular imaging probes that can track the dynamics of GHSR in health and disease to better predict the effectiveness of ghrelin-based therapeutics. We designed a high-affinity GHSR ligand labeled with ¹⁸F for imaging by PET and characterized its in vivo properties in a canine model of MI. Methods: We rationally designed and radiolabeled with ¹⁸F a quinazolinone derivative ([¹⁸F]LCE470) with subnanomolar binding affinity to GHSR. We determined the sensitivity and in vivo and ex vivo specificity of [¹⁸F]LCE470 in a canine model of surgically induced MI using PET/MRI, which allowed for anatomic localization of tracer uptake and simultaneous determination of global cardiac function. Uptake of [¹⁸F]LCE470 was determined by time–activity curve and SUV analysis in 3 regions of the left ventricle—area of infarct, territory served by the left circumflex coronary artery, and remote myocardium—over a period of 1.5 y. Changes in cardiac perfusion were tracked by [¹³N]NH₃ PET. Results: The receptor binding affinity of LCE470 was measured at 0.33 nM, the highest known receptor binding affinity for a radiolabeled GHSR ligand. In vivo blocking studies in healthy hounds and ex vivo blocking studies in myocardial tissue showed the specificity of [¹⁸F]LCE470, and sensitivity was demonstrated by a positive correlation between tracer uptake and GHSR abundance. Post-MI changes in [¹⁸F]LCE470 uptake occurred independently of perfusion tracer distributions and changes in global cardiac function. We found that the regional distribution of [¹⁸F]LCE470 within the left ventricle diverged significantly within 1 d after MI and remained that way throughout the 1.5-y duration of the study. Conclusion: [¹⁸F]LCE470 is a high-affinity PET tracer that can detect changes in the regional distribution of myocardial GHSR after MI. In vivo PET molecular imaging of the global dynamics of GHSR may lead to improved GHSR-based therapeutics in the treatment of post-MI remodeling.

This analysis aimed to identify clinical factors associated with positivity on repeat ⁶⁸Ga-PSMA-11 PET/CT after a negative scan in patients with recurrent prostate cancer (PCa) under observation. Methods: This single-center, retrospective analysis included patients who underwent at least 2 ⁶⁸Ga-PSMA-11 PET/CT scans (PET1 and PET2) at UCLA between October 2016 and June 2021 for recurrent PCa with negative PET1 and no PCa-related treatments between the 2 scans. Using Prostate Cancer Molecular Imaging Standardized Evaluation criteria to define negative and positive scans, the final cohort was divided into PET2-negative (PET2-Neg) and PET2-positive (PET2-Pos). The same PET1 was used twice in the more than 2 PET cases with inclusion criteria fulfilled. Patient characteristics and clinical parameters were compared between the 2 cohorts using Mann–Whitney U test and Fisher exact test. Areas under the curve (AUCs) of the receiver operating characteristic and the Youden index were computed to determine the discrimination ability of statistically significant factors and specific cut points that maximized sensitivity and specificity, respectively. Results: The final analysis included 83 sets of 2 PET/CT scans from 70 patients. Thirty-nine of 83 (47%) sets were PET2-Neg, and 44 of 83 (53%) sets were PET2-Pos. Prostate-specific antigen (PSA) increased from PET1 to PET2 for all 83 (100%) sets of scans. Median PSA at PET1 was 0.4 ng/mL (interquartile range, 0.2–1.0) and at PET2 was 1.6 ng/mL (interquartile range, 0.9–3.8). We found higher serum PSA at PET2 (median, 1.8 vs. 1.1 ng/mL; P = 0.015), absolute PSA difference (median, 1.4 vs. 0.7 ng/mL; P = 0.006), percentage of PSA change (median, +270.4% vs. +150.0%: P = 0.031), and median PSA velocity (0.044 vs. 0.017 ng/mL/wk, P = 0.002) and shorter PSA doubling time (DT; median, 5.1 vs. 8.3 mo; P = 0.006) in the PET2-Pos cohort than in the PET2-Neg cohort. Receiver operating characteristic curves showed cutoffs for PSA at PET2 of 4.80 ng/mL (sensitivity, 34%; specificity, 92%; AUC, 0.66), absolute PSA difference of 0.95 ng/mL (sensitivity, 62%; specificity, 71%; AUC, 0.68), percentage of PSA change of a positive 289.50% (sensitivity, 48%; specificity, 82%; AUC, 0.64), PSA velocity of 0.033 ng/mL/wk (sensitivity, 57%; specificity, 80%; AUC, 0.70), and PSA DT of 7.91 mo (sensitivity, 71%; specificity, 62%; AUC, 0.67). Conclusion: Patients with recurrent PCa under observation after a negative ⁶⁸Ga-PSMA-11 PET/CT scan with markedly elevated serum PSA levels and shorter PSA DT are more likely to have positive findings on repeat ⁶⁸Ga-PSMA-11 PET/CT.

A Credit-fuelled Economic Recovery Stores Up Trouble for Turkey Expert comment sysadmin 17 February 2020

Turkey is repeating the mistakes that led to the 2018 lira crisis and another freefall for the currency may not be far off.

Since the 2018 economic crisis, when the value of the lira plummeted and borrowing costs soared, Turkey’s economy has achieved a miraculous ‘V-shaped’ economic recovery from a recession lasting three quarters to a return back to quarterly growth above 1 per cent in the first three months of 2019.

But this quick turnaround has been built on vast amounts of cheap credit used to re-stimulate a consumption and construction boom. This so-called ‘triple C’ economy generated a rapid growth spurt akin to a modestly able professional sprinter injected with steroids.

This has made the currency vulnerable. The lira has steadily depreciated by 11 per cent against the US dollar since the beginning of 2019 and crossed the rate of 6 lira versus the US dollar on 7 February. And there are further warning signs on the horizon.

Credit bonanza

Statistics reveal that Turkish domestic credit grew by around 13 per cent on average throughout 2019. The credit bonanza is still ongoing. Mortgage-backed home sales jumped by a record high of 600 per cent last December alone and the 2019 budget deficit catapulted by 70 per cent due to higher government spending.

Turkey’s central bank fuelled this credit expansion by cutting interest rates aggressively to below inflation and, since the start of this year, purchasing lira-denominated bonds equivalent to around one-third of total acquisitions last year to push yields lower.

Equally, it has linked bank lending to reserve requirements – the money that banks have to keep at the central bank – to boost borrowings via state and private banks. Banks with a ‘real’ loan growth (including inflation) of between 5 and 15 per cent enjoy a 2 per cent reserve ratio on most lira deposits, which authorities adjusted from an earlier band of 10-20 per cent that did not consider double-digit inflation.

Cumulatively, bond purchases (effectively quantitative easing) and reserve management policies have also contributed to eased credit conditions.

Commercial banks have also reduced deposit rates on lira accounts to less than inflation to encourage consumption over saving. Together with low lending rates, the boost to the economy has flowed via mortgages, credit card loans, vehicle leasing transactions and general business borrowings.

Accordingly, stimulus is at the forefront of the government’s economic approach, as it was in 2017 and 2018. It does not seem to be implementing structural change to re-orient growth away from consumption towards productivity.

In addition, governance is, again, a central issue. President Recep Tayyip Erdogan’s near total monopolization of policymaking means he guides all domestic and external policies. He forced out the previous central bank governor, Murat Cetinkaya, in July 2019 because he did not share the president’s desire for an accelerated pace of interest rate reductions.

New challenges

Despite the similarities, the expected future financial turbulence will be materially different from its 2018 predecessor in four crucial respects.

Firstly, foreign investors will only be marginally involved. Turkey has shut out foreign investors since 2018 from lira-denominated assets by restricting lira swap arrangements. Unsurprisingly, the non-resident holdings of lira bonds has plummeted from 20 per cent in 2018 to less than 10 per cent today.

Secondly, the Turkish government has recently introduced indirect domestic capital controls by constraining most commercial transactions to the lira rather than to the US dollar or euro to reduce foreign currency demand in light of short-term external debt obligations of $191 billion.

Thirdly, the Turkish state banks are intervening quite regularly to soften Lira volatility, thereby transitioning from a ‘free float’ to a ‘managed float’. So far, they have spent over $37 billion over the last two years in a futile effort to buttress the lira. This level of involvement in currency markets cannot be maintained.

Fourthly, the Turkish state is being far more interventionist in the Turkish stock exchange and bond markets to keep asset prices elevated. Government-controlled local funds have participated in the Borsa Istanbul and state banks in sovereign debt to sustain rallies or reverse a bear market.

All these measures have one running idea: exclude foreign investors and no crisis will recur. Yet, when the credit boom heads to a downturn sooner or later, Turks will probably escalate lira conversions to US dollars; 51 per cent of all Turkish bank deposits are already dollar-denominated and the figure is still rising.

If Turkey’s limited foreign reserves cannot satisfy the domestic dollar demand, the government may have to impose comprehensive capital controls and allow for a double digit depreciation in the value of the lira to from its current level, with significant repercussions on Turkey’s political stability and economic climate.

To avoid this scenario, it needs to restore fiscal and monetary prudence, deal the with the foreign debt overhang in the private sector and focus on productivity-improving economic and institutional reforms to gain the confidence of global financial markets and Turks alike.

The Supreme Court appeared skeptical that companies should be required to include past events in their risk disclosure statements during oral arguments for Facebook Inc. vs. Amalgamated Bank on Wednesday.

Oil giant Shell emerged victorious Tuesday from a Dutch court where it was appealing a ruling ordering it to slash its global carbon emissions by 45% by the end of the decade in line with the Paris climate agreement.

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.

Lunchables are being pulled from school menus throughout the United States, after food manufacturer Kraft Heinz announced Tuesday that demand for the meal kits has dropped.

SAN JOSE, Calif., Oct. 16, 2024 — Supermicro, Inc. is launching a new optimized storage system for high performance AI training, inference and HPC workloads. This JBOF (Just a Bunch […]

The post Supermicro Introduces JBOF Storage Platform Powered by NVIDIA BlueField-3 for Scalable AI and HPC appeared first on HPCwire.

Oil giant Shell emerged victorious Tuesday from a Dutch court where it was appealing a ruling ordering it to slash its global carbon emissions by 45% by the end of the decade in line with the Paris climate agreement.

Premier League reference David Coote is suspended indefinitely after videos surfaced that appeared to show him criticizing former Liverpool coach Jurgen Klopp, officials announced Monday.

BOSTON, Oct. 25, 2024 — QuEra Computing, a leader in neutral-atom quantum computing, today announced that on September 6th, it signed a Memorandum of Understanding (MOU) with the National Institute of […]

The post QuEra and AIST Partner on Quantum-HPC Integration for Research and Industry appeared first on HPCwire.

Animal rescuers in Texas came to the assistance of a fox that apparently attempted to scale a wooden fence and ended up dangling by its caught leg.

A baby goat stranded on a Hawaii cliff was rescued by members of the public after four days.

A 77-year-old slice of cake from Queen Elizabeth II's wedding to Prince Philip was auctioned for $2,800.

A coyote that had a plastic jug stuck over its head for at least a week was rescued by members of the public in Illinois and is now recovering at a wildlife rescue.