are Flare phenomenon in O-(2-[18F]-Fluoroethyl)-L-Tyrosine PET after resection of gliomas By jnm.snmjournals.org Published On :: 2020-01-31T13:36:41-08:00 Purpose: PET using O-(2-[18F]Fluoroethyl)-L-tyrosine (18F-FET) is useful to detect residual tumor tissue after glioma resection. Recent animal experiments detected reactive changes of 18F-FET uptake at the rim of the resection cavity within the first two weeks after resection of gliomas. In the present study, we evaluated pre- and postoperative 18F-FET PET scans of glioma patients with particular emphasis on the identification of reactive changes after surgery. Methods: Forty-three patients with cerebral gliomas (9 low-grade, 34 high-grade; 9 primary tumors, 34 recurrent tumors) who had preoperative (time before surgery, median 23 d, range 6-44 d) and postoperative 18F-FET-PET (time after surgery, median 14, range 5–28 d) were included. PET scans (20-40 min p.i.) were evaluated visually for complete or incomplete resection (CR, IR) and compared with MRI. Changes of 18F-FET-uptake in residual tumor were evaluated by tumor-to-brain ratios (TBRmax) and in the vicinity of the resection cavity by maximum lesion-to-brain ratios (LBRmax). Results: Visual analysis of 18F-FET PET scans revealed CR in 16/43 patients and IR in the remaining patients. PET results were concordant with MRI in 69% of the patients. LBRmax of 18F-FET uptake in the vicinity of the resection cavity was significantly higher compared with preoperative values (1.59 ± 0.36 versus 1.14 ± 0.17; n = 43, p<0.001). In 11 patients (26%) a "flare phenomenon" was observed with a considerable increase of 18F-FET uptake compared with preoperative values in either the residual tumor (n = 5) or in areas remote from tumor in the preoperative PET scan (n = 6) (2.92 ± 1.24 versus 1.62 ± 0.75; p<0.001). Further follow-up in five patients showed decreasing 18F-FET uptake in the flare areas in four and progress in one case. Conclusion: Our study confirms that 18F-FET PET provides valuable information for assessing the success of glioma resection. Postoperative reactive changes at the rim of the resection cavity appear to be mild. However, in 23 % of the patients, a postoperative "flare phenomenon" was observed that warrants further investigation. Full Article
are Performance of digital PET compared to high-resolution conventional PET in patients with cancer By jnm.snmjournals.org Published On :: 2020-02-14T14:01:21-08:00 Recently introduced PET systems using silicon photomultipliers with digital readout (dPET) have an improved timing and spatial resolution, aiming at a better image quality, over conventional PET (cPET) systems. We prospectively evaluated the performance of a dPET system in patients with cancer, as compared to high-resolution (HR) cPET imaging. Methods: After a single FDG-injection, 66 patients underwent dPET (Vereos, Philips Healthcare) and cPET (Ingenuity TF, Philips Healthcare) imaging in a randomized order. We used HR-reconstructions (2x2x2 mm3 voxels) for both scanners and determined SUVmax, SUVmean, lesion-to-background ratio (LBR), metabolic tumor volume (MTV) and lesion diameter in up to 5 FDG-positive lesions per patient. Furthermore, we counted the number of visible and measurable lesions on each PET scan. Two nuclear medicine specialists blindly determined the Tumor Node Metastasis (TNM) score from both image sets in 30 patients referred for initial staging. For all 66 patients, these specialists separately and blindly evaluated image quality (4-point scale) and determined the scan preference. Results: We included 238 lesions that were visible and measurable on both PET scans. We found 37 additional lesions on dPET in 27 patients (41%), which were unmeasurable (n = 14) or invisible (n = 23) on cPET. SUVmean, SUVmax, LBR and MTV on cPET were 5.2±3.9 (mean±SD), 6.9±5.6, 5.0±3.6 and 2991±13251 mm3, respectively. On dPET SUVmean, SUVmax and LBR increased 24%, 23% and 27%, respectively (p<0.001) while MTV decreased 13% (p<0.001) compared to cPET. Visual analysis showed TNM upstaging with dPET in 13% of the patients (4/30). dPET images also scored higher in image quality (P = 0.003) and were visually preferred in the majority of cases (65%). Conclusion: Digital PET improved the detection of small lesions, upstaged the disease and images were visually preferred as compared to high-resolution conventional PET. More studies are necessary to confirm the superior diagnostic performance of digital PET. Full Article
are Defining hyper-progressive disease using tumor growth rate: what are limitations and shortcuts? By jnm.snmjournals.org Published On :: 2020-03-13T14:12:30-07:00 Full Article
are The Changing Face of Nuclear Cardiology: Guiding Cardiovascular Care towards Molecular Medicine By jnm.snmjournals.org Published On :: 2020-04-17T08:32:41-07:00 Radionuclide imaging of myocardial perfusion, function, and viability has been established for decades and remains a robust, evidence-based and broadly available means for clinical workup and therapeutic guidance in ischemic heart disease. Yet, powerful alternative modalities have emerged for this purpose, and their growth has resulted in increasing competition. But the potential of the tracer principle goes beyond the assessment of physiology and function, towards the interrogation of biology and molecular pathways. This is a unique selling point of radionuclide imaging, which has been under-recognized in cardiovascular medicine until recently. Now, molecular imaging methods for the detection of myocardial infiltration, device infection and cardiovascular inflammation are successfully gaining clinical acceptance. This is further strengthened by the symbiotic quest of cardiac imaging and therapy for an increasing implementation of molecular-targeted procedures, where specific therapeutic interventions require specific diagnostic guidance towards the most suitable candidates. This review will summarize the current advent of clinical cardiovascular molecular imaging and highlight its transformative contribution to the evolution of cardiovascular therapy beyond mechanical interventions and broad "blockbuster" medication, towards a future of novel, individualized molecular targeted and molecular imaging-guided therapies. Full Article
are The African Continental Free Trade Area Could Boost African Agency in International Trade By feedproxy.google.com Published On :: Tue, 10 Dec 2019 09:17:12 +0000 10 December 2019 Tighisti Amare Assistant Director, Africa Programme @tighistiamare Treasure Thembisile Maphanga Director, Trade and Industry, African Union Commission (2012–19) The agreement, which entered into force in May, could be a major step for Africa’s role in international trade, if the continent can overcome barriers to implementation. 2019-12-10-Niger.jpg Delegates arrive at the closing ceremony of the African Union summit in Niger in July. Photo: Getty Images. The entry into force of the African Continental Free Trade Area (AfCFTA) on 30 May, after only three years of negotiations, is an economic, political and diplomatic milestone for the African Union (AU) and its member states, crucial for economic growth, job creation, and making Africa a meaningful player in international trade. But the continent will have to work together to ensure that the potential benefits are fully realized.A necessary innovationWith its advances in maintaining peace and security, abundant natural resources, high growth rates, improved linkages to global supply chains and a youthful population, Africa is emerging as a new global centre of economic growth, increasingly sought after as a partner by the world’s biggest economies. Governments from across Africa have been taking a more assertive role in international markets, including through proactive diversification of trading partners, and the continent remains a strong advocate for the multilateral trading system.However, this is not yet reflected in outcomes. The African Union does not have observer status at the World Trade Organization, despite diplomatic efforts in the past decade. Africa has less than a three per cent share of global trade, and the growing trend towards protectionism across the global economy may only increase the vulnerability of a disunited Africa. Its fractured internal market means that trade within Africa is lower than for any other region on the globe, with intra-African trade just 18 per cent of overall exports, as compared to 70 per cent in Europe.The AfCFTA is the continent’s tool to address the disparity between Africa’s growing economic significance and its peripheral place in the global trade system, to build a bridge between present fragmentation and future prosperity. It is an ambitious, comprehensive agreement covering trade in goods, services, investment, intellectual property rights and competition policy. It has been signed by all of Africa’s states with the exception of Eritrea.It is the AU's Agenda 2063 flagship project, brought about by the decisions taken at the January 2012 African Union Summit to boost intra-African trade and to fast track the establishment of the Continental Free Trade Area. It builds upon ambitions enshrined in successive agreements including the Lagos Plan of Action and the Abuja Treaty. Access to new regional markets and reduced non-tariff barriers are intended to help companies scale up, driving job creation and poverty reduction, as well as attracting inward investment to even Africa’s smaller economies.The signing in 2018 of the instruments governing the Single Air Transport Market and the Protocol on Free Movement of Persons, Right of Residence and Right of Establishment provided another step towards the gradual elimination of barriers to the movement of goods, services and people within the continent.Tests to comeHowever, while progress is being made towards the ratification of the AfCFTA, much remains to be done before African countries can fully trade under its terms. The framework for implementation is still under development, and the creation of enabling infrastructure that is critical for connectivity will take time to develop and requires extensive investment. Africa’s Future in a Changing Global Order: Africa’s Economic Diplomacy Treasure Thembisile Maphanga talks about the international implications of the African Continental Free Trade Agreement (AfCFTA). So, the first test for the AfCFTA will be the level to which Africa’s leaders make it a domestic priority, and whether a consensus can be maintained across the AU’s member states as the costs of implementation become clear.There is no guarantee that the gains of free trade will be evenly distributed. They will mainly depend on the extent to which countries embrace industrialization, liberalization of their markets and opening of their borders for free movement of goods and people – policies that some incumbent leaders may be reluctant to implement. Political will to maintain a unified negotiating position with diverse stakeholders, including the private sector, will come under increasing stress. A second challenge is how the AfCFTA relates to already existing trade arrangements, notably with the EU. The AU has long preferred to pursue a continent-to-continent trading arrangement instead of the bilateral Economic Partnership Agreements being sought by the EU under the African, Caribbean and Pacific (ACP) framework to which, with the exception of Algeria, Egypt, Libya, Morocco, Tunisia and South Africa, all African states belong. The signing of the AfCFTA is one important step towards making this possible.But there are currently negotiations under the ACP to replace the Cotonou Accord (the framework governing trade between ACP members and the EU, including Economic Partnership Agreements [EPAs], that is due to expire in 2020). Negotiations on the African pillar of the accord are due to take place after the AfCFTA has entered into force. So African states and the AU will face the challenge of balancing their commitment to the ACP bloc with pursuing their own interests.And though the AfCFTA should supersede any other agreements, the EPAs or their successors, will continue to govern day-to-day trading, in parallel to the new pan-African market. It is not yet clear how these contradictions will be reconciled.A new role for the AU?The AU will need to play an active role as the main interlocutor with Africa´s international trading partners, with the AfCFTA secretariat being the arbiter of internal tensions and trade disputes. The AU´s engagement at continental level has to date revolved mainly around headline political diplomacy, security and peacekeeping. With the continental free market becoming a reality, an effective pivot to economic diplomacy will be critical for growth and development.With the AfCFTA, the AU has endeavoured to address Africa’s unsustainable position in global trade, to stimulate growth, economic diversification and jobs for its growing population. Much will depend on the commitment of African leaders to maintaining a unified negotiating position to implement the agreement and the AU’s capacity to effectively move from political to economic diplomacy. Full Article
are Africa’s Long-standing Leaders Are Disappearing By feedproxy.google.com Published On :: Fri, 03 Jan 2020 16:07:49 +0000 3 January 2020 Dr Alex Vines OBE Managing Director, Ethics, Risk & Resilience; Director, Africa Programme Leaders who cling to power are being pushed out across the continent, and the trend looks set to continue in 2020. 2020-01-03-Zim.jpg A man holds a portrait of Robert Mugabe during his official funeral ceremony. Photo: Getty Images. Africa’s dinosaur leaders are members of an increasingly small and unstable club. Popular protests last year forced Algeria’s president, Abdelaziz Bouteflika, out of office after almost 20 years in power, as well as Sudan’s president, Omar al-Bashir, who ruled for 30 years. In 2017, Robert Mugabe was deposed in a military coup (although this was denied) after 40 years. And in 2011, mass protests led to the downfall of Tunisia’s president, Zine el-Abidine Ben Ali, after he had been in power for 23 years.Somewhat smoother are the political transitions in Angola and the Democratic Republic of the Congo (DRC). José Eduardo dos Santos, after almost 38 years in power, stepped down from office in 2017 as his term ended. So did his younger neighbour, Joseph Kabila, in January 2019, after 18 years in the presidency.What the six former leaders had in common was that they wanted to remain heads of state and considered succession planning or stepping down only as a last resort. This year will be crucial for the six countries in political transition particularly as the reform-window period is short.From A to Z Algeria: Tens of thousands of protesters have rallied in the capital Algiers and other cities against the December 2019 elections, rejecting what they see as sham transitional politics. A soft landing for Algeria in 2020 is unlikely, and what happens in the year has significant regional implications.Angola: A transition is under way, led by President João Lourenço. This shift is smoother than many others, but 2020 will be the watershed year. The country has been in economic recession for four years but is predicted to see gross domestic product growth in 2020. Investment and job creation will determine the pace of change. The honeymoon period has ended and there are signs of increasing frustration among the urban youth and the middle class.DRC: Despite his constitutionally mandated term expiring in December 2016, Joseph Kabila continued his presidency by continuously postponing elections until 30 December 2018. This election saw a three-way contest between the Union for Democracy and Social Progress (UDSP), the Engagement for Citizenship and Development party and the People’s Party for Reconstruction and Democracy (PPRD). Fèlix Tshisekedi of the UDSP was declared the winner by the Independent National Electoral Commission on January 10 last year with 38.6% votes. He was followed by Martin Fayulu of the Engagement for Citizenship and Development party, with 34.8%. He denounced the election results. In third place was Emmanuel Ramazani Shadary, of the PPRD, a key ally of Kabila.Although this was the first peaceful transition of power in DRC, there were widespread electoral inconsistencies and some observers believed that Fayulu was the legitimate winner. In 2020 it will become clearer whether a genuine transition from Kabila’s influence is taking place.Sudan: More promising than the DRC or Algeria, a 39-month transitional administration led by a technocratic prime minister, Abdalla Hamdok, has been established and enjoys domestic and international goodwill. This honeymoon is likely to be short, and the transitional administration needs to show results. The United States can help by removing Sudan from its terror list, thereby lifting the de facto ban on Sudan’s access to the dollar-based international financial system.Tunisia: A low-profile, conservative law professor beat a charismatic media magnate released from prison in the presidential election runoff in October 2019. Kais Saied won 70% of the vote and his victory and the putting together of a new governing coalition is another step forward in an open-ended democratic transition that started in 2011 after Ben Ali fell.Zimbabwe: This is a deeply troubled transition with an acute foreign exchange liquidity crisis, a deteriorating economy, hyperinflation and underperforming government. The state’s clinics and hospitals are closed or turn away patients as medical supplies run out and the doctors’ strike over decimated wages continues. There are power outages and almost half of the people face hunger and starvation as a result of drought and the economic crisis.Zimbabwe’s 2020 looks bleak, a far cry from the euphoria of two years ago when a “military assisted transition” removed Mugabe and replaced him with Emmerson Mnangagwa.More changes comingSo what do these political developments in 2019 tell us more broadly?Long-standing leaders have been persistent in Africa, despite the end of single-party rule in favour of a multiparty system. About a fifth of all African heads of state since independence can be classed as long-standing leaders — in power for more than a decade — and only five countries have never experienced one. But the trend is in decline.It remains most resilient in central Africa and in the Great Lakes regions. Cracks are appearing in their citadels in Malabo and Kampala, but in 2019 Equatorial Guinea’s President Teodoro Obiang Mbasogo celebrated 40 years in power and Uganda’s Yoweri Museveni 33 years.Will there be any more departures from the dinosaurs club in 2020?One of the shortest serving members of this club, President Pierre Nkurunziza (14 years in power) has said he will not stand for the 2020 elections in Burundi, although this is uncertain given that a 2018 constitutional referendum could allow him to stay in power until 2034. Togo’s Faure Gnassingbé (14 years in power) will stand for re-election to the presidency again after Parliament in 2019 approved a constitutional change permitting him to potentially stay in office until 2030.Amending constitutions to change term limits so that incumbent leaders can run for office is a favoured tactic. Rwanda’s Paul Kagame (19 years in office) and the Republic of Congo’s Denis Sassou Nguesso (25 years in power) have done this. But Eritrea’s Isaias Afwerki has never held an election during his 16 years in power.Attempts at dynasties have been less successful, such as with Grace Mugabe in Zimbabwe or Gamal Mubarak in Egypt, but Obiang is grooming his playboy son Teodorin to succeed him and Gabon’s Ali Bongo and Togo’s Gnassingbé both succeeded their fathers.The year is a reminder that more of these long-standing leaders will, in 2020 and beyond, step down or die. Most long-standing leaders in Africa are over the age of 70, with Paul Biya, aged 86, having served 37 years as Cameroon’s president.Some former leaders capitulated under internal pressure: in Algeria, Sudan, Tunisia and Zimbabwe. Only in Angola and the DRC was a transition process organized as part of an elite bargain.What the political transitions have in common is that honeymoons are short and that, whether they are led by interim administrations or elected leaders, they need to deliver political and socioeconomic improvements to succeed, but have inherited shambolic economies. Their success depends on accountable political leadership and domestic and international support.This article was originally published by the Mail & Guardian. Full Article
are Chemical Genetics of AGC-kinases Reveals Shared Targets of Ypk1, Protein Kinase A and Sch9 [Research] By feedproxy.google.com Published On :: 2020-04-01T00:05:32-07:00 Protein phosphorylation cascades play a central role in the regulation of cell growth and protein kinases PKA, Sch9 and Ypk1 take center stage in regulating this process in S. cerevisiae. To understand how these kinases co-ordinately regulate cellular functions we compared the phospho-proteome of exponentially growing cells without and with acute chemical inhibition of PKA, Sch9 and Ypk1. Sites hypo-phosphorylated upon PKA and Sch9 inhibition were preferentially located in RRxS/T-motifs suggesting that many are directly phosphorylated by these enzymes. Interestingly, when inhibiting Ypk1 we not only detected several hypo-phosphorylated sites in the previously reported RxRxxS/T-, but also in an RRxS/T-motif. Validation experiments revealed that neutral trehalase Nth1, a known PKA target, is additionally phosphorylated and activated downstream of Ypk1. Signaling through Ypk1 is therefore more closely related to PKA- and Sch9-signaling than previously appreciated and may perform functions previously only attributed to the latter kinases. Full Article
are The mRNA levels of heat shock factor 1 are regulated by thermogenic signals via the cAMP-dependent transcription factor ATF3 [Metabolism] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 Heat shock factor 1 (HSF1) regulates cellular adaptation to challenges such as heat shock and oxidative and proteotoxic stresses. We have recently reported a previously unappreciated role for HSF1 in the regulation of energy metabolism in fat tissues; however, whether HSF1 is differentially expressed in adipose depots and how its levels are regulated in fat tissues remain unclear. Here, we show that HSF1 levels are higher in brown and subcutaneous fat tissues than in those in the visceral depot and that HSF1 is more abundant in differentiated, thermogenic adipocytes. Gene expression experiments indicated that HSF1 is transcriptionally regulated in fat by agents that modulate cAMP levels, by cold exposure, and by pharmacological stimulation of β-adrenergic signaling. An in silico promoter analysis helped identify a putative response element for activating transcription factor 3 (ATF3) at −258 to −250 base pairs from the HSF1 transcriptional start site, and electrophoretic mobility shift and ChIP assays confirmed ATF3 binding to this sequence. Furthermore, functional assays disclosed that ATF3 is necessary and sufficient for HSF1 regulation. Detailed gene expression analysis revealed that ATF3 is one of the most highly induced ATFs in thermogenic tissues of mice exposed to cold temperatures or treated with the β-adrenergic receptor agonist CL316,243 and that its expression is induced by modulators of cAMP levels in isolated adipocytes. To the best of our knowledge, our results show for the first time that HSF1 is transcriptionally controlled by ATF3 in response to classic stimuli that promote heat generation in thermogenic tissues. Full Article
are AIG1 and ADTRP are endogenous hydrolases of fatty acid esters of hydroxy fatty acids (FAHFAs) in mice [Metabolism] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 Fatty acid esters of hydroxy fatty acids (FAHFAs) are a newly discovered class of signaling lipids with anti-inflammatory and anti-diabetic properties. However, the endogenous regulation of FAHFAs remains a pressing but unanswered question. Here, using MS-based FAHFA hydrolysis assays, LC-MS–based lipidomics analyses, and activity-based protein profiling, we found that androgen-induced gene 1 (AIG1) and androgen-dependent TFPI-regulating protein (ADTRP), two threonine hydrolases, control FAHFA levels in vivo in both genetic and pharmacologic mouse models. Tissues from mice lacking ADTRP (Adtrp-KO), or both AIG1 and ADTRP (DKO) had higher concentrations of FAHFAs particularly isomers with the ester bond at the 9th carbon due to decreased FAHFA hydrolysis activity. The levels of other lipid classes were unaltered indicating that AIG1 and ADTRP specifically hydrolyze FAHFAs. Complementing these genetic studies, we also identified a dual AIG1/ADTRP inhibitor, ABD-110207, which is active in vivo. Acute treatment of WT mice with ABD-110207 resulted in elevated FAHFA levels, further supporting the notion that AIG1 and ADTRP activity control endogenous FAHFA levels. However, loss of AIG1/ADTRP did not mimic the changes associated with pharmacologically administered FAHFAs on extent of upregulation of FAHFA levels, glucose tolerance, or insulin sensitivity in mice, indicating that therapeutic strategies should weigh more on FAHFA administration. Together, these findings identify AIG1 and ADTRP as the first endogenous FAHFA hydrolases identified and provide critical genetic and chemical tools for further characterization of these enzymes and endogenous FAHFAs to unravel their physiological functions and roles in health and disease. Full Article
are Australian Federal Police walk away from $145 million Israeli crime-fighting software deal By www.smh.com.au Published On :: Wed, 19 Aug 2015 06:25:36 GMT Police walk away from deal with contractor, conceding numerous issues have put project beyond rescue. Full Article
are The NBN satellite Malcolm Turnbull never wanted prepares for liftoff By www.smh.com.au Published On :: Fri, 28 Aug 2015 06:31:02 GMT In 34 days and counting down, Australia is set to blast a satellite weighing as much as an elephant one-tenth of the way to the moon. Full Article
are Uber and the ATO's $3.8 million taxi fare By www.smh.com.au Published On :: Sun, 06 Sep 2015 14:15:00 GMT Tax Office could turn to rideshare service to curb $3.8 million taxi fare Full Article
are Australians are avoiding cash-only businesses: survey By www.smh.com.au Published On :: Thu, 24 Sep 2015 03:39:45 GMT As internet banking and tap-and-go cards become ubiquitous, Australians are beginning to reject businesses that operate on a cash only basis. Full Article
are The real reason St George Bank, Bank of Melbourne and BankSA are suffering a long outage By www.smh.com.au Published On :: Mon, 05 Oct 2015 06:44:52 GMT It was meant to be a simple task: turn the computer off and on again while performing scheduled maintenance. Full Article
are Australian public service failing to share information: Public Sector Data Management report By www.smh.com.au Published On :: Tue, 08 Dec 2015 02:59:08 GMT A report has revealed stunning examples of public service inefficiency when it comes to releasing and managing data. Full Article
are Centrelink apologises for web welfare shutdown By www.smh.com.au Published On :: Tue, 15 Dec 2015 22:35:03 GMT Centrelink clients around Australia are furious over missing payments. Full Article
are Why Hollywood animation powerhouses are resisting the cloud By www.smh.com.au Published On :: Thu, 03 Mar 2016 20:14:05 GMT Despite new performance bottlenecks, the digital animation and visual effects industry is very reluctant to move their productions to the cloud, according to Sydney's Animal Logic. Full Article
are Apple v FBI: what the fight is about and why you should care By www.smh.com.au Published On :: Fri, 04 Mar 2016 15:27:05 GMT Apple is in the middle of a legal fight with the FBI over creating a 'back door' to unlock a terrorist's iPhone. Full Article
are Centrelink debt debacle shows government is unprepared for digital revolution By www.smh.com.au Published On :: Mon, 06 Feb 2017 13:15:00 GMT The public service needs to embrace partnerships if it's to harvest big data's massive yields. Full Article
are How federal government departments are protecting Australians' data against cyber hack By www.smh.com.au Published On :: Mon, 15 May 2017 10:09:02 GMT Cyber Security Minister Dan Tehan says the government can't rule out vulnerabilities to cyber threats. Full Article
are Medicare details available on dark web is just tip of data breach iceberg By www.smh.com.au Published On :: Mon, 17 Jul 2017 14:00:00 GMT The next wave of government reform will have to focus on data management. Full Article
are Medical records exposed by flaw in Telstra Health's Argus software By www.smh.com.au Published On :: Wed, 21 Mar 2018 21:21:02 GMT Default static password allowed medical practitioners' computers and servers to be accessed remotely by hackers. Full Article
are The African Continental Free Trade Area Could Boost African Agency in International Trade By feedproxy.google.com Published On :: Tue, 10 Dec 2019 09:17:12 +0000 10 December 2019 Tighisti Amare Assistant Director, Africa Programme @tighistiamare Treasure Thembisile Maphanga Director, Trade and Industry, African Union Commission (2012–19) The agreement, which entered into force in May, could be a major step for Africa’s role in international trade, if the continent can overcome barriers to implementation. 2019-12-10-Niger.jpg Delegates arrive at the closing ceremony of the African Union summit in Niger in July. Photo: Getty Images. The entry into force of the African Continental Free Trade Area (AfCFTA) on 30 May, after only three years of negotiations, is an economic, political and diplomatic milestone for the African Union (AU) and its member states, crucial for economic growth, job creation, and making Africa a meaningful player in international trade. But the continent will have to work together to ensure that the potential benefits are fully realized.A necessary innovationWith its advances in maintaining peace and security, abundant natural resources, high growth rates, improved linkages to global supply chains and a youthful population, Africa is emerging as a new global centre of economic growth, increasingly sought after as a partner by the world’s biggest economies. Governments from across Africa have been taking a more assertive role in international markets, including through proactive diversification of trading partners, and the continent remains a strong advocate for the multilateral trading system.However, this is not yet reflected in outcomes. The African Union does not have observer status at the World Trade Organization, despite diplomatic efforts in the past decade. Africa has less than a three per cent share of global trade, and the growing trend towards protectionism across the global economy may only increase the vulnerability of a disunited Africa. Its fractured internal market means that trade within Africa is lower than for any other region on the globe, with intra-African trade just 18 per cent of overall exports, as compared to 70 per cent in Europe.The AfCFTA is the continent’s tool to address the disparity between Africa’s growing economic significance and its peripheral place in the global trade system, to build a bridge between present fragmentation and future prosperity. It is an ambitious, comprehensive agreement covering trade in goods, services, investment, intellectual property rights and competition policy. It has been signed by all of Africa’s states with the exception of Eritrea.It is the AU's Agenda 2063 flagship project, brought about by the decisions taken at the January 2012 African Union Summit to boost intra-African trade and to fast track the establishment of the Continental Free Trade Area. It builds upon ambitions enshrined in successive agreements including the Lagos Plan of Action and the Abuja Treaty. Access to new regional markets and reduced non-tariff barriers are intended to help companies scale up, driving job creation and poverty reduction, as well as attracting inward investment to even Africa’s smaller economies.The signing in 2018 of the instruments governing the Single Air Transport Market and the Protocol on Free Movement of Persons, Right of Residence and Right of Establishment provided another step towards the gradual elimination of barriers to the movement of goods, services and people within the continent.Tests to comeHowever, while progress is being made towards the ratification of the AfCFTA, much remains to be done before African countries can fully trade under its terms. The framework for implementation is still under development, and the creation of enabling infrastructure that is critical for connectivity will take time to develop and requires extensive investment. Africa’s Future in a Changing Global Order: Africa’s Economic Diplomacy Treasure Thembisile Maphanga talks about the international implications of the African Continental Free Trade Agreement (AfCFTA). So, the first test for the AfCFTA will be the level to which Africa’s leaders make it a domestic priority, and whether a consensus can be maintained across the AU’s member states as the costs of implementation become clear.There is no guarantee that the gains of free trade will be evenly distributed. They will mainly depend on the extent to which countries embrace industrialization, liberalization of their markets and opening of their borders for free movement of goods and people – policies that some incumbent leaders may be reluctant to implement. Political will to maintain a unified negotiating position with diverse stakeholders, including the private sector, will come under increasing stress. A second challenge is how the AfCFTA relates to already existing trade arrangements, notably with the EU. The AU has long preferred to pursue a continent-to-continent trading arrangement instead of the bilateral Economic Partnership Agreements being sought by the EU under the African, Caribbean and Pacific (ACP) framework to which, with the exception of Algeria, Egypt, Libya, Morocco, Tunisia and South Africa, all African states belong. The signing of the AfCFTA is one important step towards making this possible.But there are currently negotiations under the ACP to replace the Cotonou Accord (the framework governing trade between ACP members and the EU, including Economic Partnership Agreements [EPAs], that is due to expire in 2020). Negotiations on the African pillar of the accord are due to take place after the AfCFTA has entered into force. So African states and the AU will face the challenge of balancing their commitment to the ACP bloc with pursuing their own interests.And though the AfCFTA should supersede any other agreements, the EPAs or their successors, will continue to govern day-to-day trading, in parallel to the new pan-African market. It is not yet clear how these contradictions will be reconciled.A new role for the AU?The AU will need to play an active role as the main interlocutor with Africa´s international trading partners, with the AfCFTA secretariat being the arbiter of internal tensions and trade disputes. The AU´s engagement at continental level has to date revolved mainly around headline political diplomacy, security and peacekeeping. With the continental free market becoming a reality, an effective pivot to economic diplomacy will be critical for growth and development.With the AfCFTA, the AU has endeavoured to address Africa’s unsustainable position in global trade, to stimulate growth, economic diversification and jobs for its growing population. Much will depend on the commitment of African leaders to maintaining a unified negotiating position to implement the agreement and the AU’s capacity to effectively move from political to economic diplomacy. Full Article
are Parenteral lipids shape gut bile acid pools and microbiota profiles in the prevention of cholestasis in preterm pigs By feedproxy.google.com Published On :: 2020-04-29 Lee CallApr 29, 2020; 0:jlr.RA120000652v1-jlr.RA120000652Research Articles Full Article
are The fatty acids from LPL-mediated processing of triglyceride-rich lipoproteins are taken up rapidly by cardiomyocytes By feedproxy.google.com Published On :: 2020-04-02 Haibo JiangApr 2, 2020; 0:jlr.ILR120000783v1-jlr.ILR120000783Images in Lipid Research Full Article
are Episode 110 - The Internet of These are a Few of Our Favourite Things (IoTaaFoOFT) Best Tech of 2018 By play.acast.com Published On :: Thu, 13 Dec 2018 14:45:40 GMT Scott Carey is in the hosting chair this week as we have a rotating cast of staffers from across Macworld, Tech Advisor, Techworld and Computerworld to discuss our two favourite techie things of the year, from the best games and films, to our favourite devices and even, microchips.Thank you for listening this year and for your continued support for the UK Tech Weekly Podcast and we will see you in the new year. See acast.com/privacy for privacy and opt-out information. Full Article
are The fatty acids from LPL-mediated processing of triglyceride-rich lipoproteins are taken up rapidly by cardiomyocytes [Images in Lipid Research] By feedproxy.google.com Published On :: 2020-04-02T09:30:25-07:00 Full Article
are Parenteral lipids shape gut bile acid pools and microbiota profiles in the prevention of cholestasis in preterm pigs [Research Articles] By feedproxy.google.com Published On :: 2020-04-29T08:36:37-07:00 Multi-component lipid emulsions, rather than soy-oil emulsions, prevent cholestasis by an unknown mechanism. Here, we quantified liver function, bile acid pools, and gut microbial and metabolite profiles in premature, parenterally fed pigs given a soy-oil lipid emulsion, Intralipid (IL); a multi component lipid emulsion, SMOFlipid (SMOF); a novel emulsion with a modified fatty-acid composition (EXP); or a control enteral diet (ENT) for 22 days. We assayed serum cholestasis markers; measured total bile acid levels in plasma, liver, and gut contents; and analyzed colonic bacterial 16S rRNA gene sequences and metabolomic profiles. Serum cholestasis markers (i.e. bilirubin, bile acids, and g-glutamyl transferase) were highest in IL-fed pigs and normalized in those given SMOF, EXP, or ENT. Gut bile acid pools were lowest in the IL treatment and were increased in the SMOF and EXP treatments and comparable to ENT. Multiple bile acids, especially their conjugated forms, were higher in the colon contents of SMOF and EXP than in IL pigs. Colonic microbial communities of SMOF and EXP pigs had lower relative abundance of several Gram-positive anaerobes, including Clostridrium XIVa, and higher abundance of Enterobacteriaceae than those of IL and ENT pigs. Differences in lipid and microbial-derived compounds were also observed in colon metabolite profiles. These results indicate that multi-component lipid emulsions prevent cholestasis and restore enterohepatic bile flow in association with gut microbial and metabolomic changes. We conclude that sustained bile flow induced by multi-component lipid emulsions likely exerts a dominant effect in reducing bile acid–sensitive, Gram-positive bacteria. Full Article
are 2-Chlorofatty acids are biomarkers of sepsis mortality and mediators of barrier dysfunction in rats [Research Articles] By feedproxy.google.com Published On :: 2020-05-06T11:30:34-07:00 Sepsis is defined as the systemic, dysregulated host immune response to an infection that leads to injury to host organ systems, and, often, death. Complex interactions between pathogens and their hosts elicit microcirculatory dysfunction. Neutrophil myeloperoxidase (MPO) is critical for combating pathogens, but MPO-derived hypochlorous acid (HOCl) can react with host molecular species as well. Plasmalogens are targeted by HOCl, leading to the production of 2-chlorofatty acids (2-CLFAs). 2-CLFAs are associated with human sepsis mortality, decrease in vitroendothelial barrier function, and activate human neutrophil extracellular trap formation. Here, we sought to examine 2-CLFAs in an in vivorat sepsis model. Intraperitoneal cecal slurry sepsis with clinically relevant rescue therapies led to ~73% mortality and evidence of microcirculatory dysfunction. Plasma concentrations of 2-CLFAs assessed 8h after sepsis induction were lower in rats that survived sepsis than in non-survivors. 2-CLFA levels were elevated in kidney, liver, spleen, lung, colon and ileum in septic animals. In vivo, exogenous 2-CLFA treatments increased kidney permeability, and in in vitroexperiments 2-CLFA also increased epithelial surface expression of vascular cell adhesion molecule 1 and decreased epithelial barrier function. Collectively, these studies support a role of free 2-CLFAs as biomarkers of sepsis mortality, potentially mediated, in part, by 2-CLFA-elicited endothelial and epithelial barrier dysfunction. Full Article
are Beware Russian and Chinese Positioning for After the Pandemic By feedproxy.google.com Published On :: Thu, 09 Apr 2020 10:00:11 +0000 9 April 2020 Keir Giles Senior Consulting Fellow, Russia and Eurasia Programme @KeirGiles LinkedIn Google Scholar Authoritarian regimes can use the COVID-19 crisis to improve their international standing, taking advantage of others’ distraction. Their aims are different, but their methods have much in common. 2020-04-09-Russia-Aid-Serbia An airlifter of the Russian Aerospace Forces prepares to fly to Serbia carrying equipment and professionals during the COVID-19 crisis. Photo by Russian Defence MinistryTASS via Getty Images. Both Russia and China have mounted combined charm offensives and disinformation campaigns on the back of the pandemic. Shipments of ‘aid’ – reportedly of questionable utility and quality - have gone hand in hand with a concerted effort to deflect any blame from China for the early spread, and an ongoing drive by Russia to undermine states’ confidence and have sanctions lifted.These concurrent operations have very different objectives, as Russia seeks to subvert international order while China is continuing its bid to demonstrate global leadership - but in both cases, they are seeking long-term gains by exploiting the inattention and distraction of their targets.Both seek to present themselves as globally responsible stakeholders, but for divergent reasons – especially China which needs the rest of the world to recover and return to stability to ensure its own economic recovery. But despite this, the two campaigns appear superficially similar.Fertile ground for disinformationOne reason lies in the unique nature of the current crisis. Unlike political issues that are local or regional in nature, COVID-19 affects everybody worldwide. The perceived lack of reliable information about the virus provides fertile ground for information and disinformation campaigns, especially feeding on fear, uncertainty and doubt. But Russia in particular would not be succeeding in its objectives without mis-steps and inattention by Western governments.Confused reporting on Russia sending medical supplies to the United States showed Moscow taking advantage of a US administration in apparent disarray. Claims Russia was sending ’humanitarian aid’ were only belatedly countered by the US State Department pointing out it had been paid for. Meanwhile the earlier arrival of Russian military equipment in Italy also scored a propaganda victory for Russia, facilitated by curious passivity by the Italian government.In both cases Russia also achieved secondary objectives. With the United States, Russia scored bonus points by shipping equipment produced by a subsidiary of a company under US sanctions. In the case of Italy, Russian state media made good use of misleading or heavily edited video clips to give the impression of widespread Italian acclaim for Russian aid, combined with disdain for the efforts of the EU.Beijing’s external information campaigns have sought to deflect or defuse criticism of its early mishandling and misinformation on coronavirus and counter accusations of secrecy and falsifying data while also pursuing an opportunity to exercise soft power. For Moscow, current efforts boost a long-standing and intensive campaign to induce the lifting of sanctions, demonstrating if nothing else that sanctions are indeed an effective measure. Official and unofficial lobbying has intensified in numerous capital cities, and will inevitably find supporters.But both the aid and the information campaigns are seriously flawed. While appropriate and useful aid for countries that are struggling should of course be welcomed, both Russian and Chinese equipment delivered to Europe has repeatedly been found to be inappropriate or defective. Russian photographs of cardboard boxes stacked loose and unsecured in a transport aircraft bound for the United States sparked alarm and disbelief among military and aviation experts - and there has still been no US statement on what exactly was purchased, and whether it was found to be fit for purpose when it arrived.Reporting from Italy that the Russian equipment delivered there was ‘80% useless’ has not been contradicted by the Italian authorities. In fact, although the Italian sources criticizing Russia remain anonymous it is striking that - President Trump aside - no government has publicly endorsed materials and assistance received from Russia as actually being useful and helpful.Even in Serbia, with its traditionally close ties with Russia, the only information forthcoming on the activities of the Russian Nuclear, Biological and Chemical Protection Troops and their equipment that arrived on April 3 was from Russian press releases.Both countries’ strategic communications efforts are similarly fallible. China’s notoriously heavy-handed approach to its critics is of only limited use in the face of such a severe and immediate threat. One suggestion that the virus originated in the US – an early response to US criticism – has already been walked back by the Chinese diplomat who made it.And Russia continues to be capable of spectacularly misjudging its targets. When investigative journalists looked more closely at the nature of the assistance to Italy, Russia’s official response was rage and personal threats, laying bare the real nature of the campaign and immediately alienating many of those whom Moscow had sought to win over.Errors and deficiencies such as these provide opportunities to mitigate the worst side-effects of the campaigns. And actions by individuals can also mitigate much of the impact. The most effective disinformation plays on deeply emotional issues and triggers visceral rather than rational reactions.Advocates of ’informational distancing’ as well as social distancing suggest a tactical pause to assess information calmly, instead of reacting or spreading it further unthinkingly. This approach would bolster not only calm dispassionate assessment of the real impact of Russian and Chinese actions, but also counter spreading of misinformation on the pandemic as a whole - especially when key sources of disinformation are national leaders seeking to politicize or profit from the crisis.Limitations of Russian and Chinese altruism must be stated clearly and frankly to fill gaps in public understanding. Where help is genuine, it should of course be welcomed: but if it is the case that assistance received from Moscow or Beijing is not appropriate, not useful, or not fit for purpose, this should be acknowledged publicly.Even without central direction or coordination with other Russian strategic communications efforts, the self-perpetuating Russian disinformation ecosystem continues to push narratives designed to undermine confidence in institutions and their ability to deal with the crisis. This too must continue to be monitored closely and countered where it matters.In all cases, miscalculations by Russia or China that expose the true intent of their campaigns – no matter how different their objectives might be - should be watched for closely and highlighted where they occur.Despite the enormity of the present emergency it is not a time for any government to relax its vigilance over longer-term threats. States must not lose sight of manoeuvres seeking to exploit weakness and distraction. If Russia and China emerge from the current crisis with enhanced authority and unjustifiably restored reputations, this will make it still harder to resist their respective challenges to the current rules-based international order in the future. Full Article
are Why an Inclusive Circular Economy is Needed to Prepare for Future Global Crises By feedproxy.google.com Published On :: Wed, 15 Apr 2020 13:23:01 +0000 15 April 2020 Patrick Schröder Senior Research Fellow, Energy, Environment and Resources Programme @patricks_CH Google Scholar The risks associated with existing production and consumption systems have been harshly exposed amid the current global health crisis but an inclusive circular economy could ensure both short-term and long-term resilience for future challenges. 2020-04-15-Waste-Collection-Peru.jpg Lima city employees picking up garbage during lockdown measures in Peru amid the COVID-19 crisis. Photo: Getty Images. The world is currently witnessing how vulnerable existing production and consumption systems are, with the current global health crisis harshly exposing the magnitude of the risks associated with the global economy in its current form, grounded, as it is, in a linear system that uses a ‘take–make–throw away’ approach.These ‘linear risks’ associated with the existing global supply chain system are extremely high for national economies overly dependent on natural resource extraction and exports of commodities like minerals and metals. Equally vulnerable are countries with large manufacturing sectors of ready-made garments and non-repairable consumer goods for western markets. Furthermore, workers and communities working in these sectors are vulnerable to these changes as a result of disruptive technologies and reduced demand.In a recently published Chatham House research paper, ‘Promoting a Just Transition to an Inclusive Circular Economy’, we highlight why a circular economy approach presents the world with a solution to old and new global risks – from marine plastic pollution to climate change and resource scarcity.Taking the long viewSo far, action to transition to a circular economy has been slow compared to the current crisis which has mobilized rapid global action. For proponents of transitioning to a circular economy, this requires taking the long view. The pandemic has shown us that global emergencies can fast-forward processes that otherwise might take years, even decades, to play out or reverse achievements which have taken years to accomplish.In this vein, there are three striking points of convergence between the COVID-19 pandemic and the need to transition to an inclusive circular economy.Firstly, the current crisis is a stark reminder that the circular economy is not only necessary to ensure long-term resource security but also short-term supplies of important materials. In many cities across the US, the UK and Europe, councils have suspended recycling to focus on essential waste collection services. The UK Recycling Association, for example, has warned about carboard shortages due to disrupted recycling operations with possible shortages for food and medicine packaging on the horizon.Similarly, in China, most recycling sites were shut during the country’s lockdown presenting implications for global recycling markets with additional concerns that there will be a fibre shortage across Europe and possibly around the world.Furthermore, worldwide COVID-19 lockdowns are resulting in a resurgence in the use of single-use packaging creating a new wave of plastic waste especially from food deliveries – already seen in China – with illegal waste fly-tipping dramatically increasing in the UK since the lockdown.In this vein, concerns over the current global health crisis is reversing previous positive trends where many cities had established recycling schemes and companies and consumers had switched to reusable alternatives.Secondly, the need to improve the working conditions of the people working in the informal circular economy, such as waste pickers and recyclers, is imperative. Many waste materials and recyclables that are being handled and collected may be contaminated as a result of being mixed with medical waste.Now, more than ever, key workers in waste management, collection and recycling require personal protective equipment and social protection to ensure their safety as well as the continuation of essential waste collection so as not to increase the potential for new risks associated with additional infectious diseases.In India, almost 450 million workers including construction workers, street vendors and landless agricultural labourers, work in the informal sector. In the current climate, the poorest who are unable to work pose a great risk to the Indian economy which could find itself having to shut down.Moreover, many informal workers live in make-shift settlements areas such as Asia’s largest slum, Dharavi in Mumbai, where health authorities are now facing serious challenges to contain the spread of the disease. Lack of access to handwashing and sanitation facilities, however, further increase these risks but circular, decentralized solutions could make important contributions to sustainable sanitation, health and improved community resilience.Thirdly, it is anticipated that in the long term several global supply chains will be radically changed as a result of transformed demand patterns and the increase in circular practices such as urban mining for the recovery and recycling of metals or the reuse and recycling of textile fibres and localized additive manufacturing (e.g. 3D printing).Many of these supply chains and trade flows have now been already severely disrupted due to the COVID-19 pandemic. For example, the global garment industry has been particularly hard-hit due to the closure of outlets amid falling demand for apparel.It is important to note, workers at the bottom of these garment supply chains are among the most vulnerable and most affected by the crisis as global fashion brands, for example, have been cancelling orders – in the order of $6 billion in the case of Bangladesh alone. Only after intense negotiations are some brands assuming financial responsibility in the form of compensation wage funds to help suppliers in Myanmar, Cambodia and Bangladesh to pay workers during the ongoing crisis.In addition, the current pandemic is damaging demand for raw materials thereby affecting mining countries. Demand for Africa’s commodities in China, for example, has declined significantly, with the impact on African economies expected to be serious, with 15 per cent of the world’s copper and 20 per cent of the world’s zinc mines currently going offline. A further threat is expected to come from falling commodity prices as a result of the curtailment of manufacturing activity in China particularly for crude oil, copper, iron ore and other industrial commodities which, in these cases, will have direct impacts on the Australian and Canadian mining sectors.This is all being compounded by an associated decline in consumer demand worldwide. For example, many South African mining companies – leading producers of metals and minerals – have started closing their mining operations following the government’s announcement of a lockdown in order to prevent the transmission of the virus among miners who often work in confined spaces and in close proximity with one another. As workers are laid off due to COVID-19, there are indications that the mining industry will see fast-tracking towards automated mining operations. All of these linear risks that have been exposed through the COVID-19 pandemic reinforce the need for a just transition to a circular economy. But while the reduction in the consumption of resources is necessary to achieve sustainability, the social impacts on low- and middle- income countries and their workers requires international support mechanisms.In addition, the current situation also highlights the need to find a new approach to globalized retail chains and a balance between local and global trade based on international cooperation across global value chains rather than implementation of trade protectionist measures.In this vein, all of the recovery plans from the global COVID-19 pandemic need to be aligned with the principles of an inclusive circular economy in order to ensure both short-term and long-term resilience and preparedness for future challenges and disruptions. Full Article
are Legal Provision for Crisis Preparedness: Foresight not Hindsight By feedproxy.google.com Published On :: Tue, 21 Apr 2020 17:03:31 +0000 21 April 2020 Dr Patricia Lewis Research Director, Conflict, Science & Transformation; Director, International Security Programme @PatriciaMary COVID-19 is proving to be a grave threat to humanity. But this is not a one-off, there will be future crises, and we can be better prepared to mitigate them. 2020-04-21-Nurse-COVID-Test Examining a patient while testing for COVID-19 at the Velocity Urgent Care in Woodbridge, Virginia. Photo by Chip Somodevilla/Getty Images. A controversial debate during COVID-19 is the state of readiness within governments and health systems for a pandemic, with lines of the debate drawn on the issues of testing provision, personal protective equipment (PPE), and the speed of decision-making.President Macron in a speech to the nation admitted French medical workers did not have enough PPE and that mistakes had been made: ‘Were we prepared for this crisis? We have to say that no, we weren’t, but we have to admit our errors … and we will learn from this’.In reality few governments were fully prepared. In years to come, all will ask: ‘how could we have been better prepared, what did we do wrong, and what can we learn?’. But after every crisis, governments ask these same questions.Most countries have put in place national risk assessments and established processes and systems to monitor and stress-test crisis-preparedness. So why have some countries been seemingly better prepared?Comparing different approachesSome have had more time and been able to watch the spread of the disease and learn from those countries that had it first. Others have taken their own routes, and there will be much to learn from comparing these different approaches in the longer run.Governments in Asia have been strongly influenced by the experience of the SARS epidemic in 2002-3 and - South Korea in particular - the MERS-CoV outbreak in 2015 which was the largest outside the Middle East. Several carried out preparatory work in terms of risk assessment, preparedness measures and resilience planning for a wide range of threats.Case Study of Preparedness: South KoreaBy 2007, South Korea had established the Division of Public Health Crisis Response in Korea Centers for Disease Control and Prevention (KCDC) and, in 2016, the KCDC Center for Public Health Emergency Preparedness and Response had established a round-the-clock Emergency Operations Center with rapid response teams.KCDC is responsible for the distribution of antiviral stockpiles to 16 cities and provinces that are required by law to hold and manage antiviral stockpiles.And, at the international level, there are frameworks for preparedness for pandemics. The International Health Regulations (IHR) - adopted at the 2005 World Health Assembly and binding on member states - require countries to report certain disease outbreaks and public health events to the World Health Organization (WHO) and ‘prevent, protect against, control and provide a public health response to the international spread of disease in ways that are commensurate with and restricted to public health risks, and which avoid unnecessary interference with international traffic and trade’.Under IHR, governments committed to a programme of building core capacities including coordination, surveillance, response and preparedness. The UN Sendai Framework for Disaster Risk highlights disaster preparedness for effective response as one of its main purposes and has already incorporated these measures into the Sustainable Development Goals (SDGs) and other Agenda 2030 initiatives. UN Secretary-General António Guterres has said COVID-19 ‘poses a significant threat to the maintenance of international peace and security’ and that ‘a signal of unity and resolve from the Council would count for a lot at this anxious time’.Case Study of Preparedness: United StatesThe National Institutes of Health (NIH) and the Center for Disease Control (CDC) established PERRC – the Preparedness for Emergency Response Research Centers - as a requirement of the 2006 Pandemic and All-Hazards Preparedness Act, which required research to ‘improve federal, state, local, and tribal public health preparedness and response systems’.The 2006 Act has since been supplanted by the 2019 Pandemic and All-Hazards Preparedness and Advancing Innovation Act. This created the post of Assistant Secretary for Preparedness and Response (ASPR) in the Department for Health and Human Services (HHS) and authorised the development and acquisitions of medical countermeasures and a quadrennial National Health Security Strategy.The 2019 Act also set in place a number of measures including the requirement for the US government to re-evaluate several important metrics of the Public Health Emergency Preparedness cooperative agreement and the Hospital Preparedness Program, and a requirement for a report on the states of preparedness and response in US healthcare facilities.This pandemic looks set to continue to be a grave threat to humanity. But there will also be future pandemics – whether another type of coronavirus or a new influenza virus – and our species will be threatened again, we just don’t know when.Other disasters too will befall us – we already see the impacts of climate change arriving on our doorsteps characterised by increased numbers and intensity of floods, hurricanes, fires, crop failure and other manifestations of a warming, increasingly turbulent atmosphere and we will continue to suffer major volcanic eruptions, earthquakes and tsunamis. All high impact, unknown probability events.Preparedness for an unknown future is expensive and requires a great deal of effort for events that may not happen within the preparers’ lifetimes. It is hard to imagine now, but people will forget this crisis, and revert to their imagined projections of the future where crises don’t occur, and progress follows progress. But history shows us otherwise.Preparations for future crises always fall prey to financial cuts and austerity measures in lean times unless there is a mechanism to prevent that. Cost-benefit analyses will understandably tend to prioritise the urgent over the long-term. So governments should put in place legislation – or strengthen existing legislation – now to ensure their countries are as prepared as possible for whatever crisis is coming.Such a legal requirement would require governments to report back to parliament every year on the state of their national preparations detailing such measures as:The exact levels of stocks of essential materials (including medical equipment)The ability of hospitals to cope with large influx of patientsHow many drills, exercises and simulations had been organised – and their findingsWhat was being done to implement lessons learned & improve preparednessIn addition, further actions should be taken:Parliamentary committees such as the UK Joint Committee on the National Security Strategy should scrutinise the government’s readiness for the potential threats outlined in the National Risk register for Civil Emergencies in-depth on an annual basis.Parliamentarians, including ministers, with responsibility for national security and resilience should participate in drills, table-top exercises and simulations to see for themselves the problems inherent with dealing with crises.All governments should have a minister (or equivalent) with the sole responsibility for national crisis preparedness and resilience. The Minister would be empowered to liaise internationally and coordinate local responses such as local resilience groups.There should be ring-fenced budget lines in annual budgets specifically for preparedness and resilience measures, annually reported on and assessed by parliaments as part of the due diligence process.And at the international level:The UN Security Council should establish a Crisis Preparedness Committee to bolster the ability of United Nations Member States to respond to international crisis such as pandemics, within their borders and across regions. The Committee would function in a similar fashion as the Counter Terrorism Committee that was established following the 9/11 terrorist attacks in the United States.States should present reports on their level of preparedness to the UN Security Council. The Crisis Preparedness Committee could establish a group of experts who would conduct expert assessments of each member state’s risks and preparedness and facilitate technical assistance as required.Regional bodies such as the OSCE, ASEAN and ARF, the AU, the OAS, the PIF etc could also request national reports on crisis preparedness for discussion and cooperation at the regional level.COVID-19 has been referred to as the 9/11 of crisis preparedness and response. Just as that shocking terrorist attack shifted the world and created a series of measures to address terrorism, we now recognise our security frameworks need far more emphasis on being prepared and being resilient. Whatever has been done in the past, it is clear that was nowhere near enough and that has to change.Case Study of Preparedness: The UKThe National Risk Register was first published in 2008 as part of the undertakings laid out in the National Security Strategy (the UK also published the Biological Security Strategy in July 2018). Now entitled the National Risk Register for Civil Emergencies it has been updated regularly to analyse the risks of major emergencies that could affect the UK in the next five years and provide resilience advice and guidance.The latest edition - produced in 2017 when the UK had a Minister for Government Resilience and Efficiency - placed the risk of a pandemic influenza in the ‘highly likely and most severe’ category. It stood out from all the other identified risks, whereas an emerging disease (such as COVID-19) was identified as ‘highly likely but with moderate impact’.However, much preparatory work for an influenza pandemic is the same as for COVID-19, particularly in prepositioning large stocks of PPE, readiness within large hospitals, and the creation of new hospitals and facilities.One key issue is that the 2017 NHS Operating Framework for Managing the Response to Pandemic Influenza was dependent on pre-positioned ’just in case’ stockpiles of PPE. But as it became clear the PPE stocks were not adequate for the pandemic, it was reported that recommendations about the stockpile by NERVTAG (the New and Emerging Respiratory Virus Threats Advisory Group which advises the government on the threat posed by new and emerging respiratory viruses) had been subjected to an ‘economic assessment’ and decisions reversed on, for example, eye protection.The UK chief medical officer Dame Sally Davies, when speaking at the World Health Organization about Operation Cygnus – a 2016 three-day exercise on a flu pandemic in the UK – reportedly said the UK was not ready for a severe flu attack and ‘a lot of things need improving’.Aware of the significance of the situation, the UK Parliamentary Joint Committee on the National Security Strategy launched an inquiry in 2019 on ‘Biosecurity and human health: preparing for emerging infectious diseases and bioweapons’ which intended to coordinate a cross-government approach to biosecurity threats. But the inquiry had to postpone its oral hearings scheduled for late October 2019 and, because of the general election in December 2019, the committee was obliged to close the inquiry. Full Article
are The ProteoRed MIAPE web toolkit: A user-friendly framework to connect and share proteomics standards [Technology] By feedproxy.google.com Published On :: 2011-06-19T13:05:33-07:00 The development of the HUPO-PSI's (Proteomics Standards Initiative) standard data formats and MIAPE (Minimum Information About a Proteomics Experiment) guidelines should improve proteomics data sharing within the scientific community. Proteomics journals have encouraged the use of these standards and guidelines to improve the quality of experimental reporting and ease the evaluation and publication of manuscripts. However, there is an evident lack of bioinformatics tools specifically designed to create and edit standard file formats and reports, or embed them within proteomics workflows. In this article, we describe a new web-based software suite (The ProteoRed MIAPE web toolkit) that performs several complementary roles related to proteomic data standards. Firstly, it can verify the reports fulfill the minimum information requirements of the corresponding MIAPE modules, highlighting inconsistencies or missing information. Secondly, the toolkit can convert several XML-based data standards directly into human readable MIAPE reports stored within the ProteoRed MIAPE repository. Finally, it can also perform the reverse operation, allowing users to export from MIAPE reports into XML files for computational processing, data sharing or public database submission. The toolkit is thus the first application capable of automatically linking the PSI's MIAPE modules with the corresponding XML data exchange standards, enabling bidirectional conversions. This toolkit is freely available at http://www.proteored.org/MIAPE/. Full Article
are MaxQuant software for ion mobility enhanced shotgun proteomics [Technological Innovation and Resources] By feedproxy.google.com Published On :: 2020-03-10T07:35:19-07:00 Ion mobility can add a dimension to LC-MS based shotgun proteomics which has the potential to boost proteome coverage, quantification accuracy and dynamic range. Required for this is suitable software that extracts the information contained in the four-dimensional (4D) data space spanned by m/z, retention time, ion mobility and signal intensity. Here we describe the ion mobility enhanced MaxQuant software, which utilizes the added data dimension. It offers an end to end computational workflow for the identification and quantification of peptides and proteins in LC-IMS-MS/MS shotgun proteomics data. We apply it to trapped ion mobility spectrometry (TIMS) coupled to a quadrupole time-of-flight (QTOF) analyzer. A highly parallelizable 4D feature detection algorithm extracts peaks which are assembled to isotope patterns. Masses are recalibrated with a non-linear m/z, retention time, ion mobility and signal intensity dependent model, based on peptides from the sample. A new matching between runs (MBR) algorithm that utilizes collisional cross section (CCS) values of MS1 features in the matching process significantly gains specificity from the extra dimension. Prerequisite for using CCS values in MBR is a relative alignment of the ion mobility values between the runs. The missing value problem in protein quantification over many samples is greatly reduced by CCS aware MBR.MS1 level label-free quantification is also implemented which proves to be highly precise and accurate on a benchmark dataset with known ground truth. MaxQuant for LC-IMS-MS/MS is part of the basic MaxQuant release and can be downloaded from http://maxquant.org. Full Article
are Zelenskyy Finds That There Are No Easy Solutions in Donbas By feedproxy.google.com Published On :: Wed, 23 Oct 2019 14:46:36 +0000 23 October 2019 Duncan Allan Associate Fellow, Russia and Eurasia Programme Leo Litra Senior Research Fellow, New Europe Center The president has attempted to use the so-called Steinmeier Formula to find a compromise on holding elections in the east of Ukraine. But he has run into a stark reality: Moscow and Kyiv’s interests remain irreconcilable. 2019-10-23-Ukraine.jpg A banner reading 'No capitulation!' is unfurled above the entrance to the city hall in Kyiv as part of protests against implementation of the so-called Steinmeier Formula. Photo: Getty Images. In 2016, the then-German foreign minister, Frank-Walter Steinmeier, suggested a way around the impasse in east Ukraine.He proposed that elections in the areas held by Russian-backed insurgents – the ‘Donetsk People’s Republic’ (DNR) and the ‘Luhansk People’s Republic’ (LNR) – could be held under Ukrainian legislation, with Kyiv adopting a temporary law on ‘special status’, the main disagreement between Russia and Ukraine in the Minsk Agreements. This law would become permanent once the Organization for Security and Cooperation in Europe (OSCE) had declared that elections correspond with OSCE standards.The reaction in Ukraine was strongly negative. The so-called Steinmeier Formula contradicted Kyiv’s position that elections in the occupied Donbas should only go ahead in a secure environment – requiring the prior withdrawal of Russian forces and the return of the eastern border to Ukraine’s control. It also did not address the differing views of ‘special status’; Russia demands a much greater devolution of constitutional powers to the DNR and LNR regimes than Ukraine will grant.But on 1 October, Volodymyr Zelenskyy, the new Ukrainian president, announced that he was signing up to the Steinmeier Formula. He also announced a conditional withdrawal of Ukrainian forces from two frontline areas in the east.Quick reversalDuring the 2019 presidential election campaign, Zelenskyy repeatedly promised that, if elected, he would re-energize efforts to end the war. This appealed to many Ukrainians, who understandably want the conflict over, although Zelenskyy’s eventual electoral victory was largely won on domestic issues.But his initiative quickly ran into two problems.First, following a major prisoner swap in September, Russian President Vladimir Putin appeared to judge that Zelenskyy was in a hurry to deliver his election promises and was acting without consulting France and Germany. Russia had earlier demanded that Ukraine formally agree to elections in the Donbas as the precondition for a summit of the ‘Normandy’ powers (the diplomatic format comprising leaders of Ukraine, Russia, Germany and France, which has not met since 2016).Moreover, the US, which is not part of the ‘Normandy’ group, has seemed disengaged because of domestic controversies. Concluding that Zelenskyy was vulnerable, the Kremlin welcomed his announcement about the Steinmeier Formula but declined to assent to a summit, hoping to extract further concessions.Second, Zelenskyy’s action triggered protests in Kyiv and other Ukrainian cities. Critics feared that he intended to make unilateral concessions over ‘special status’. Though he tried to assure Ukrainians that ‘there won't be any elections there if the [Russian] troops are still there’, concerns were fuelled by what many saw as his lack of openness about what the Steinmeier Formula really meant. Ukrainian public opinion wants an end to the war, but apparently not at any price.Zelenskyy duly rowed back. During a marathon 14-hour press conference on 10 October, he emphasized that he would not surrender Ukraine’s vital interests. He also acknowledged that he had been insufficiently open with the Ukrainian public. For the time being at least, he seems to have been given pause.A situation resistant to compromiseInstead, Zelenskyy may now attempt to ‘freeze’ the conflict by ending active operations. This is not Ukraine’s favoured outcome but could be the most realistic one in current conditions. Russia still calculates that time is on its side. It believes that Western support for Ukraine is lukewarm and that Kyiv will eventually have to give it what it wants. Russia clearly felt no pressure to respond positively to Zelenskyy’s overture, which it probably read as a weakness to be exploited. For these reasons, Zelenskyy now appears less optimistic that rapid progress to end the war is possible. A new summit of the ‘Normandy’ powers may happen but looks unlikely in the near future. This may act as an incentive for further bilateral negotiations between Ukraine and Russia, such as those which delivered the prisoner swap. However, a diplomatic process managed by Zelenskyy and Putin alone risks reducing Ukraine’s leverage. Finally, the main obstacles to implementation of the Minsk Agreements – radically different views of elections in, and ‘special status’ for, the DNR and LNR – remain. The Kremlin’s versions of both would gravely limit Ukraine’s sovereignty; Kyiv’s would facilitate the re-establishment of its control over the east. It is hard to see how this gap can be bridged.Tellingly, the Steinmeier Formula offers no answer to this conundrum. Some conflicts, it seems, are resistant to diplomatic compromises that aim to satisfy everyone equally. Full Article
are Beware Russian and Chinese Positioning for After the Pandemic By feedproxy.google.com Published On :: Thu, 09 Apr 2020 10:00:11 +0000 9 April 2020 Keir Giles Senior Consulting Fellow, Russia and Eurasia Programme @KeirGiles LinkedIn Google Scholar Authoritarian regimes can use the COVID-19 crisis to improve their international standing, taking advantage of others’ distraction. Their aims are different, but their methods have much in common. 2020-04-09-Russia-Aid-Serbia An airlifter of the Russian Aerospace Forces prepares to fly to Serbia carrying equipment and professionals during the COVID-19 crisis. Photo by Russian Defence MinistryTASS via Getty Images. Both Russia and China have mounted combined charm offensives and disinformation campaigns on the back of the pandemic. Shipments of ‘aid’ – reportedly of questionable utility and quality - have gone hand in hand with a concerted effort to deflect any blame from China for the early spread, and an ongoing drive by Russia to undermine states’ confidence and have sanctions lifted.These concurrent operations have very different objectives, as Russia seeks to subvert international order while China is continuing its bid to demonstrate global leadership - but in both cases, they are seeking long-term gains by exploiting the inattention and distraction of their targets.Both seek to present themselves as globally responsible stakeholders, but for divergent reasons – especially China which needs the rest of the world to recover and return to stability to ensure its own economic recovery. But despite this, the two campaigns appear superficially similar.Fertile ground for disinformationOne reason lies in the unique nature of the current crisis. Unlike political issues that are local or regional in nature, COVID-19 affects everybody worldwide. The perceived lack of reliable information about the virus provides fertile ground for information and disinformation campaigns, especially feeding on fear, uncertainty and doubt. But Russia in particular would not be succeeding in its objectives without mis-steps and inattention by Western governments.Confused reporting on Russia sending medical supplies to the United States showed Moscow taking advantage of a US administration in apparent disarray. Claims Russia was sending ’humanitarian aid’ were only belatedly countered by the US State Department pointing out it had been paid for. Meanwhile the earlier arrival of Russian military equipment in Italy also scored a propaganda victory for Russia, facilitated by curious passivity by the Italian government.In both cases Russia also achieved secondary objectives. With the United States, Russia scored bonus points by shipping equipment produced by a subsidiary of a company under US sanctions. In the case of Italy, Russian state media made good use of misleading or heavily edited video clips to give the impression of widespread Italian acclaim for Russian aid, combined with disdain for the efforts of the EU.Beijing’s external information campaigns have sought to deflect or defuse criticism of its early mishandling and misinformation on coronavirus and counter accusations of secrecy and falsifying data while also pursuing an opportunity to exercise soft power. For Moscow, current efforts boost a long-standing and intensive campaign to induce the lifting of sanctions, demonstrating if nothing else that sanctions are indeed an effective measure. Official and unofficial lobbying has intensified in numerous capital cities, and will inevitably find supporters.But both the aid and the information campaigns are seriously flawed. While appropriate and useful aid for countries that are struggling should of course be welcomed, both Russian and Chinese equipment delivered to Europe has repeatedly been found to be inappropriate or defective. Russian photographs of cardboard boxes stacked loose and unsecured in a transport aircraft bound for the United States sparked alarm and disbelief among military and aviation experts - and there has still been no US statement on what exactly was purchased, and whether it was found to be fit for purpose when it arrived.Reporting from Italy that the Russian equipment delivered there was ‘80% useless’ has not been contradicted by the Italian authorities. In fact, although the Italian sources criticizing Russia remain anonymous it is striking that - President Trump aside - no government has publicly endorsed materials and assistance received from Russia as actually being useful and helpful.Even in Serbia, with its traditionally close ties with Russia, the only information forthcoming on the activities of the Russian Nuclear, Biological and Chemical Protection Troops and their equipment that arrived on April 3 was from Russian press releases.Both countries’ strategic communications efforts are similarly fallible. China’s notoriously heavy-handed approach to its critics is of only limited use in the face of such a severe and immediate threat. One suggestion that the virus originated in the US – an early response to US criticism – has already been walked back by the Chinese diplomat who made it.And Russia continues to be capable of spectacularly misjudging its targets. When investigative journalists looked more closely at the nature of the assistance to Italy, Russia’s official response was rage and personal threats, laying bare the real nature of the campaign and immediately alienating many of those whom Moscow had sought to win over.Errors and deficiencies such as these provide opportunities to mitigate the worst side-effects of the campaigns. And actions by individuals can also mitigate much of the impact. The most effective disinformation plays on deeply emotional issues and triggers visceral rather than rational reactions.Advocates of ’informational distancing’ as well as social distancing suggest a tactical pause to assess information calmly, instead of reacting or spreading it further unthinkingly. This approach would bolster not only calm dispassionate assessment of the real impact of Russian and Chinese actions, but also counter spreading of misinformation on the pandemic as a whole - especially when key sources of disinformation are national leaders seeking to politicize or profit from the crisis.Limitations of Russian and Chinese altruism must be stated clearly and frankly to fill gaps in public understanding. Where help is genuine, it should of course be welcomed: but if it is the case that assistance received from Moscow or Beijing is not appropriate, not useful, or not fit for purpose, this should be acknowledged publicly.Even without central direction or coordination with other Russian strategic communications efforts, the self-perpetuating Russian disinformation ecosystem continues to push narratives designed to undermine confidence in institutions and their ability to deal with the crisis. This too must continue to be monitored closely and countered where it matters.In all cases, miscalculations by Russia or China that expose the true intent of their campaigns – no matter how different their objectives might be - should be watched for closely and highlighted where they occur.Despite the enormity of the present emergency it is not a time for any government to relax its vigilance over longer-term threats. States must not lose sight of manoeuvres seeking to exploit weakness and distraction. If Russia and China emerge from the current crisis with enhanced authority and unjustifiably restored reputations, this will make it still harder to resist their respective challenges to the current rules-based international order in the future. Full Article
are Problem Notes for SAS®9 - 65852: The PANEL procedure produces incorrect results for certain models when the NOINT and RANONE options are specified By feedproxy.google.com Published On :: Fri, 8 May 2020 13:34:29 EST The estimation results might be incorrect in PROC PANEL when the RANONE and NOINT options are specified in the MODEL statement. Full Article ETS+SAS/ETS
are Problem Notes for SAS®9 - 65031: Grid options set mappings are returned based on which option set is the first in the metadata search chain By feedproxy.google.com Published On :: Tue, 5 May 2020 15:04:46 EST When users are defined in multiple groups associated with grid options set mappings, the first grid option set that is returned by the metadata search chain takes precedence. Only one grid options set mapping is used Full Article GRIDMGR+SAS+Grid+Manager
are Problem Notes for SAS®9 - 65574: Decimal values are rounded after they are inserted into a new Databricks table via SAS/ACCESS Interface to JDBC By feedproxy.google.com Published On :: Fri, 1 May 2020 13:17:00 EST A DATA step and PROC SQL can round numeric values while creating and loading data into a new Databricks table via JDBC. Full Article BASE+Base+SAS
are Problem Notes for SAS®9 - 65893: Custom sorts are sorted incorrectly when they are used in a hierarchy in SAS Visual Analytics Designer By feedproxy.google.com Published On :: Wed, 29 Apr 2020 12:29:05 EST A custom sort might be sorted incorrectly when the data item is used in a custom category, which is then used in a hierarchy. The issue can occur in the following scenario: Full Article VISANLYTBNDL+SAS+Visual+Analytics
are Rays' 2019 mantra: Prepare to win from within By mlb.mlb.com Published On :: Fri, 8 Feb 2019 16:05:02 EDT Over the past couple seasons, the Rays have preached patience as the organization provided time for the top prospects to make it up to the Majors. Now, the focus has been primarily in remaining flexible and keeping positions open for the young talent arriving from the Minors. Full Article
are Here are 10 Rays players to watch this spring By mlb.mlb.com Published On :: Sun, 17 Feb 2019 13:46:36 EDT While most of the attention will fall on the players who are expected to make the Opening Day roster, manager Kevin Cash and the rest of the organization will be keeping a close eye on some of the players that could find their way to the big leagues at some point within the next year. Full Article
are Hybrid Insulin Peptides are Recognized by Human T Cells in the Context of DRB1*04:01 By diabetes.diabetesjournals.org Published On :: 2020-04-24T13:05:31-07:00 T cells isolated from the pancreatic infiltrates of non-obese diabetic mice have been shown to recognize epitopes formed by the covalent cross-linking of proinsulin and secretory granule peptides. Formation of such hybrid insulin peptides (HIPs) was confirmed through mass spectrometry and responses to HIPs were observed among the islet-infiltrating T cells of pancreatic organ donors and in the peripheral blood of individuals with type 1 diabetes (T1D). However, questions remain about the prevalence of HIP-specific T cells in humans, the sequences they recognize, and their role in disease. We identified six novel HIPs that are recognized in the context of DRB1*04:01, discovered by utilizing a library of theoretical HIP sequences derived from insulin fragments covalently linked to one another or to fragments of secretory granule proteins or other islet-derived proteins. We demonstrate that T cells that recognize these HIPs are detectable in the peripheral blood of subjects with T1D and exhibit an effector memory phenotype. HIP-reactive T cell clones produced Th1-associated cytokines and proliferated in response to human islet preparations. These results support the relevance of HIPs in human disease, further establishing a novel post-translational modification that may contribute to the loss of peripheral tolerance in T1D. Full Article
are Secretory Functions of Macrophages in the Human Pancreatic Islet are Regulated by Endogenous Purinergic Signaling By diabetes.diabetesjournals.org Published On :: 2020-04-24T13:05:31-07:00 Endocrine cells of the pancreatic islet interact with their microenvironment to maintain tissue homeostasis. Communication with local macrophages is particularly important in this context, but the homeostatic functions of human islet macrophages are not known. Here we show that the human islet contains macrophages in perivascular regions that are the main local source of the anti-inflammatory cytokine Il-10 and the metalloproteinase MMP9. Macrophage production and secretion of these homeostatic factors is controlled by endogenous purinergic signals. In obese and diabetic states, macrophage expression of purinergic receptors, MMP9, and Il-10 is reduced. We propose that in those states exacerbated beta cell activity due to increased insulin demand and increased cell death produces high levels of ATP that downregulate purinergic receptor expression. Loss of ATP sensing in macrophages may reduce their secretory capacity. Full Article
are The Metabolic Responses to 24-h Fasting and Mild Cold Exposure in Overweight Individuals are Correlated and Accompanied by Changes in FGF21 Concentration By diabetes.diabetesjournals.org Published On :: 2020-04-27T16:35:54-07:00 A greater decrease in 24-h energy expenditure (24EE) during 24h fasting defines a thriftier metabolic phenotype prone to weight gain during overfeeding and resistant to weight loss during caloric restriction. As the thermogenic response to mild cold exposure (COLD) may similarly characterize this human phenotype identified by acute fasting conditions, we analyzed changes in 24EE and sleeping metabolic rate (SLEEP) in a whole-room indirect calorimeter during 24h fasting at thermoneutrality (24°C) and during energy balance both at thermoneutrality (24°C) and mild cold (19°C) in 20 healthy volunteers (80% male, age: 36.6±11.4y, percentage body fat: 34.8±10.5%). Greater decrease in 24EE during fasting (thriftier phenotype) was associated with less increase in 24EE during COLD, i.e. less cold-induced thermogenesis. Greater decreases in plasma fibroblast growth factor 21 (FGF21) after 24h fasting and after COLD were highly correlated and associated with greater decreases in SLEEP in both conditions. We conclude that the metabolic responses to short-term fasting and COLD are associated and mediated by the liver-derived hormone FGF21. Thus, the 24EE response to COLD further identifies the thrifty versus spendthrift phenotype, providing an additional setting to investigate the physiological mechanisms underlying the human metabolic phenotype and characterizing the individual susceptibility to weight change. Full Article
are Certain ortho-hydroxylated brominated ethers are promiscuous kinase inhibitors that impair neuronal signaling and neurodevelopmental processes [Cell Biology] By feedproxy.google.com Published On :: 2020-05-01T00:06:09-07:00 The developing nervous system is remarkably sensitive to environmental signals, including disruptive toxins, such as polybrominated diphenyl ethers (PBDEs). PBDEs are an environmentally pervasive class of brominated flame retardants whose neurodevelopmental toxicity mechanisms remain largely unclear. Using dissociated cortical neurons from embryonic Rattus norvegicus, we found here that chronic exposure to 6-OH–BDE-47, one of the most prevalent hydroxylated PBDE metabolites, suppresses both spontaneous and evoked neuronal electrical activity. On the basis of our previous work on mitogen-activated protein kinase (MAPK)/extracellular signal-related kinase (ERK) (MEK) biology and our observation that 6-OH–BDE-47 is structurally similar to kinase inhibitors, we hypothesized that certain hydroxylated PBDEs mediate neurotoxicity, at least in part, by impairing the MEK–ERK axis of MAPK signal transduction. We tested this hypothesis on three experimental platforms: 1) in silico, where modeling ligand–protein docking suggested that 6-OH–BDE-47 is a promiscuous ATP-competitive kinase inhibitor; 2) in vitro in dissociated neurons, where 6-OH–BDE-47 and another specific hydroxylated BDE metabolite similarly impaired phosphorylation of MEK/ERK1/2 and activity-induced transcription of a neuronal immediate early gene; and 3) in vivo in Drosophila melanogaster, where developmental exposures to 6-OH–BDE-47 and a MAPK inhibitor resulted in offspring displaying similarly increased frequency of mushroom-body β–lobe midline crossing, a metric of axonal guidance. Taken together, our results support that certain ortho-hydroxylated PBDE metabolites are promiscuous kinase inhibitors and can cause disruptions of critical neurodevelopmental processes, including neuronal electrical activity, pre-synaptic functions, MEK–ERK signaling, and axonal guidance. Full Article
are Pancreas Pathology of Latent Autoimmune Diabetes in Adults (LADA) in Patients and in a LADA Rat Model Compared With Type 1 Diabetes By diabetes.diabetesjournals.org Published On :: 2020-04-01 Anne JörnsApr 1, 2020; 69:624-633Islet Studies Full Article
are Inbox: Are Giants waiting to make big splash? By mlb.mlb.com Published On :: Fri, 8 Feb 2019 14:40:47 EDT Do you think the Giants are just waiting around and could go after Bryce Harper for a big splash? Beat reporter Maria Guardado answers this question and more from fans. Full Article
are Duggar, Jones cleared for next step in recovery By mlb.mlb.com Published On :: Fri, 15 Feb 2019 18:10:20 EDT Steven Duggar and Ryder Jones continue to take steps forward in their rehab, as they were both cleared to take batting practice on the field Friday for the first time since their September surgeries. Full Article
are Enhanced Health in Care Homes during Covid19 By feeds.bmj.com Published On :: Friday, May 8, 2020 - 07:47 Full Article