Plans for the northern section of Haltom City sound great, but the declining south and central areas need attention now.

Research Highlights: Heart disease, Type 2 diabetes, high blood pressure and obesity were more common and linked to reduced access to healthy food among people who lived in neighborhoods previously subjected to structural racism-based policies that ...

How does an urban environment influence its rainfall? This is what a recent study published in the Proceedings of the National Academy of Sciences hopes to

How does an urban environment influence its rainfall? This is what a recent study published in the Proceedings of the National Academy of Sciences hopes to

Global crisis: 1.7 billion people in urban and peri-urban areas face food insecurity

New UN report highlights urgent need to strengthen urban and peri-urban food systems for global food security and nutrition.

The post Global crisis: 1.7 billion people in urban and peri-urban areas face food insecurity appeared first on IFPRI.

The fourth in a series of five OSCE-supported training seminars for women entrepreneurs working in the field of green technology started on 29 July 2016 in Arnasai village, Central Kazakhstan.

The training seminar, organized by the OSCE Programme Office in Astana in close co-operation with the Coalition for Green Economy and G-Global Development brought together some 20 participants from rural areas of the Central Kazakhstan region to raise their awareness on the use of modern green technologies in effective horticulture, such as energy and water-saving methods, drip irrigation, solar greenhouses and vermicultivation.

“We believe that the role of women in promoting green businesses in the rural areas is crucial and enormous. This is due to the fact that most of them are involved in agriculture and household management activities, which nowadays remain one of the few opportunities to support the family and community in remote regions,” said György Szabó, Head of the OSCE Programme Office in Astana. “Thus, the Office stands ready to provide its continuous expert support to such initiatives aiming at better information- and technology-sharing.”

The event is part of the Office’s multi-year efforts to promote green growth, environmental security and women’s empowerment in economic activities.

Related Stories

• OSCE supports water co-operation in southern Kazakhstan
• OSCE launches series of anti-trafficking seminars for law-enforcement officers and social workers across Kazakhstan
• OSCE Programme Office concludes series of training seminars on National Preventive Mechanism Implementation in Kazakhstan

SLOVIANSK, Ukraine, 7 April 2016 – The OSCE Project Co-ordinator in Ukraine, at a ceremony in Sloviansk, Donetsk region today, presented representatives of the Infrastructure Ministry’s State Special Transport Service with 15 sets of protective equipment, including vests and helmets, which are to be delivered to local deminers working along transport routes in the east of the country.

The State Special Transport Service is responsible for ensuring the safety of the transport network and for restoring railways and bridges destroyed by hostilities. This often involves clearing mines and unexploded ordnance that threaten civilian transportation routes. 

“Safety of communications is extremely important in the context of sustainable post-conflict recovery, future peace and security in the region,” said Vaidotas Verba, the OSCE Project Co-ordinator in Ukraine. “I hope that with our help the Service will be in better position to swiftly and efficiently ensure safer conditions for the movement of people and goods in the conflict-affected areas.”

Since July 2014 the Service has cleared over 300 kilometres of railways in government-controlled areas of Donbas and disposed of more than 4,500 unexploded ordnance, mines and booby traps. This is among the more than 100,000 such dangerous items discovered and destroyed by all organizations working in the region, which are involved in dealing with these remnants of conflict.

To help Ukraine address this new challenge, the OSCE Project Co-ordinator is also training the country's humanitarian deminers on international mine action standards, helping to introduce a modern information management system to improve operations and the inter-agency co-ordination of efforts, and assisting in developing relevant legislation and standards.

Related Stories

• Spot Report by OSCE Special Monitoring Mission to Ukraine (SMM):“DPR” members threaten SMM at gunpoint near Lukove
• OSCE-trained Ukrainian cyber-police officers begin fulfilling their mission
• OSCE Project Co-ordinator to assist Ukraine in strengthening democratic control of defence and security sectors

The fourth in a series of five OSCE-supported training seminars for women entrepreneurs working in the field of green technology started on 29 July 2016 in Arnasai village, Central Kazakhstan.

The training seminar, organized by the OSCE Programme Office in Astana in close co-operation with the Coalition for Green Economy and G-Global Development brought together some 20 participants from rural areas of the Central Kazakhstan region to raise their awareness on the use of modern green technologies in effective horticulture, such as energy and water-saving methods, drip irrigation, solar greenhouses and vermicultivation.

“We believe that the role of women in promoting green businesses in the rural areas is crucial and enormous. This is due to the fact that most of them are involved in agriculture and household management activities, which nowadays remain one of the few opportunities to support the family and community in remote regions,” said György Szabó, Head of the OSCE Programme Office in Astana. “Thus, the Office stands ready to provide its continuous expert support to such initiatives aiming at better information- and technology-sharing.”

The event is part of the Office’s multi-year efforts to promote green growth, environmental security and women’s empowerment in economic activities.

Related Stories

• OSCE Programme Office trains notaries and advocates on countering money laundering and financing of terrorism
• OSCE concludes series of training seminars on implementing the National Preventive Mechanism in Kazakhstan
• OSCE supports water co-operation in southern Kazakhstan

PineappleNet has a Black Friday special for home internet - $49 for 150Mbps symmetrical speeds. Certainly a lot better prices, speed and service than NBN.

PineappleNet is a reseller of the DGTek fibre network, who operate only in buildings in very limited areas near Melbourne CBD and some South Eastern suburbs. And not in every building, so check your address to see if they're available.

I've been a customer for over 2 years and very happy to recommend.

Referral solicitation removed — Mod.

Note: This is not NBN FTTP.

I checked postage for all of capital cities and it seems only NSW is eligible for postage.

Next cheapest would be $6867 @ The Good Guys via the price beat button

Specs: https://www.tcl.com/au/en/tvs/98c855

Prices may come down further on Black Friday, but I can't be sure as my crystal ball is broken. Please feel free to speculate below.

DoD's Transition Assistance Program aims to prepare service members for life outside the military. But for members whose final duty station is small or rural, the benefits of TAP are fairly limited.

The post Service members in remote areas missing out on transition benefits first appeared on Federal News Network.

No Comment: Aid on the ground slow to arrive in flood-hit areas

Part 3 of a three-part series summarizing the findings of a new and unsettling report on climate change.

Location: Electronic Resource- 

En este episodio, La Luciérnaga se enciende para analizar la carta de presentación del Embajador de Colombia en Venezuela, Armando Benedetti También, ya casi acaba el primer mes del nuevo gobierno y ¿ya tiene tareas pendientes? Además, le contamos sobre una nueva ola de estafas piramidales.La Luciérnaga, un espacio de humor, análisis y opinión de Caracol Radio que acompaña desde hace 30 años a sus oyentes en el regreso a casa.

El documental narra durante 18 años, la vida de cuatro hermanos de una familia que no goza de oportunidades para salir adelante.

Carlos Carrillo, director de la Unidad de Gestión de Riesgo de Desastre, compartió en 6AM las medidas que adoptará para evitar que se presenten casos como la reconstrucción de Mocoa o los albergues del Galeras

NPR's Ayesha Rascoe talks with A.B. Stoddard, columnist at The Bulwark, about the election results and if it means there has been a durable political realignment.

“This winter has been a difficult one for many fishermen as windy conditions have limited the number of fishing days,” said the Minister of Home Affairs, Walter Roban, following detailed discussions with technical experts in the department and a review of information on local fisheries, particularly the Hind Grounds, “As such, to assist the fishermen, […]

The Ministry of Home Affairs is reminding commercial and recreational fishers that fishing in the Seasonally Protected Areas, also known as the “Hind Grounds” and “Grouper Grounds”, will be prohibited from 15 April through 14 August 2024 in order to protect spawning Red Hinds and Black Groupers. According to yesterday’s official notices, “The Ministry of […]

China Paves Its Way in New Areas of International Law Expert comment sysadmin 31 March 2017

China is looking to increase its capacity and influence in international legal matters – and it is particularly in frontier areas of the law that China is likely to take a proactive stance.

Foreign Minister Wang Yi called China a staunch defender and builder of the international rule of law in his speech to the UN General Assembly in October 2014. He promised that as China grew stronger, it would make a greater contribution to the maintenance and promotion of international rule of law, and would work with other countries to build a fairer and more reasonable international political and economic order.

For many in China, that time has now come: there is a sense that China deserves a much stronger and more respected voice in discussions surrounding the future of the international system. The recent speeches of Xi Jinping in Davos and Geneva in January 2017 suggest that China is now seizing the initiative and fighting for a voice and influence commensurate with its status and power as the number two economy in the world.

But there is an interesting divide in the areas in which China chooses to assert itself. In traditional areas of international law – such as the law of the sea and international human rights law – China continues to harbour reservations about the fairness of the existing international order. Its misgivings are fuelled by a perception that it did not play a significant part in the creation of the post-Second World War international order, and that those rules operate mainly in the interests of Western powers.

There is also a sense that traditional areas of international law do not offer a level playing field for China, since Western states have far more experience at operating in those. We know from Chinese experts that in the South China Sea case, one background issue that played into China’s refusal to engage in litigation with the Philippines and other interested states (which were represented by leading Western international lawyers) was a lack of experience before international courts and tribunals.

Contrast this with newer areas of international law– such as the regimes governing cyber, space, climate change and deep sea mining issues. In these areas, the rules are still in the process of being developed and tested, and the influence of the existing powers is not so firmly established or accepted, so there is more opportunity for China’s voice to be heard and heeded.

On climate change, China has become a champion of the Paris Agreement, which it worked hard with the Obama administration to secure. China is also active in some of the processes related to cyber rule-making, both as a member of the UN Group of Governmental Experts on cyber issues and through bilateral dialogues with a number of states. China has taken a keen interest in the regime applicable to the mining of the international seabed, making submissions to the International Tribunal on the Law of the Sea about the procedure for settling disputes. In international economic law, another relatively new area, China has been assiduously cultivating expertise, and is a major player in the negotiation of the ‘mega regional’ trade deal, the Regional Comprehensive Economic Partnership.

In time, the development of China’s much heralded Belt and Road Initiative may provide an opportunity for China to be further involved in international norm-setting, through the creation of a system of economic and political interaction that is built and run more along Chinese determined lines. The emergence of the Asian Infrastructure Investment Bank may offer an early indicator of China’s attempts to shape global governance, although in this context China has so far scrupulously observed international standards and has made no open attempt to challenge them.

So far, China’s practical input to international norm-setting has been limited. While China is prone to making wide-ranging statements of principle, it finds it more challenging to engage in the nitty gritty of specific rule making. But as is clear from its membership of the WTO, China can adapt quickly. While initially it was a reluctant adherent to the WTO dispute settlement mechanism, China is now adept at making active and effective use of its rules to promote China’s interests, including launching a legal challenge regarding the contested issue of its non-market economy status. Overall, there is strong leadership backing for a more activist approach to its engagement with the international legal system.

China sees international law as an important instrument in the “toolbox” of international diplomacy. It will increasingly be seeking to leverage international law to promote its own interests, particularly in newer areas, as it seeks to strengthen its wider soft power and influence.

In SAS Retail Space Management, it should be possible to click on any location object, then Show Properties, and change the location fill color. This can be done on the gray-filled objects. However, w

Deaths from cardiovascular disease have surged among adults ages 25 to 64 living in rural areas, a new study shows.

Matthew F. Glasser
Aug 10, 2011; 31:11597-11616
BehavioralSystemsCognitive

The Manitoba government made a "political compromise" in its decision to issue a reduced number of moose hunting licences to non-Indigenous hunters in northern parts of the province earlier this year, a lawyer representing a First Nation in the area has argued in court.

Here’s how Hamilton and other cities in the area are marking Remembrance Day this year.

DNREC and DDA have determined that trail cameras for recreational use are no longer to be permitted on state wildlife areas, state parks, or state forests.

AI is no longer a futuristic concept – it’s a mainstay in our daily lives, both personally and professionally. In the business world, AI is revolutionizing workflows, driving efficiency and speeding up processes. However, as organizations rush to benefit from this modern technology, they must prioritize the ethical and transparent [...]

Critical areas for productivity gains with data and AI was published on SAS Voices by Manisha Khanna

Remember the first time you held a smartphone in your hand? It wasn’t just a fancy phone – it was the beginning of a revolution. Before smartphones, we used separate calls, cameras, emails, and navigation devices. But almost overnight, this gadget transformed everything: how we communicate, consume media, work and [...]

Productivity revolution: 4 strategic areas generative AI can transform organizations was published on SAS Voices by Marinela Profi

Rejoice Muzamani is studying in preparation for her next paper during the end-of-term examinations at Mwenje Primary School in Chiredzi, southeast Zimbabwe. The 13-year-old girl, who is in Grade 7 or final year of primary school, is not worried about leaving school early to make the 7-kilometer journey back home before dusk, risking attacks from […]

ADB sought to understand what improving transport meant for the community. Prior to project design, consultations were conducted with residents in Ulaanbaatar’s ger areas. Design decisions were tested back to ensure that mobility pain points were addressed.

ATP-binding cassette transporter subfamily G member 2 (ABCG2) is a membrane-bound transporter responsible for the efflux of various xenobiotics and endobiotics, including protoporphyrin IX (PPIX), an intermediate in the heme biosynthesis pathway. Certain genetic mutations and chemicals impair the conversion of PPIX to heme and/or increase PPIX production, leading to PPIX accumulation and toxicity. In mice, deficiency of ABCG2 protects against PPIX-mediated phototoxicity and hepatotoxicity by modulating PPIX distribution. In addition, in vitro studies revealed that ABCG2 inhibition increases the efficacy of PPIX-based photodynamic therapy by retaining PPIX inside target cells. In this review, we discuss the roles of ABCG2 in modulating the tissue distribution of PPIX, PPIX-mediated toxicity, and PPIX-based photodynamic therapy.

The regulation of drug-metabolizing enzymes and transporters by cytokines has been extensively studied in vitro and in clinic. Cytokine-mediated suppression of cytochrome P450 (CYP) or drug transporters may increase or decrease the systemic clearance of drug substrates that are primarily cleared via these pathways; neutralization of cytokines by therapeutic proteins may thereby alter systemic exposures of such drug substrates. The Food and Drug Administration recommends evaluating such clinical drug interactions during clinical development and has provided labeling recommendations for therapeutic proteins. To determine the clinical relevance of these drug interactions to dose adjustments, trends in steady-state exposures of CYP-sensitive substrates coadministered with cytokine modulators as reported in the University of Washington Drug Interaction Database were extracted and examined for each of the CYPs. Coadministration of cytochrome P450 family 3 subfamily A (CYP3A) (midazolam/simvastatin), cytochrome P450 subfamily 2C19 (omeprazole), or cytochrome P450 subfamily 1A2 (caffeine/tizanidine) substrates with anti-interleukin-6 and with anti-interleukin-23 therapeutics led to changes in systemic exposures of CYP substrates ranging from ~ –58% to ~35%; no significant trends were observed for cytochrome P450 subfamily 2D6 (dextromethorphan) and cytochrome P450 subfamily 2C9 (warfarin) substrates. Although none of these changes in systemic exposures have been reported as clinically meaningful, dose adjustment of midazolam for optimal sedation in acute care settings has been reported. Simulated concentration-time profiles of midazolam under conditions of elevated cytokine levels when coadministered with tocilizumab, suggest a ~six- to sevenfold increase in midazolam clearance, suggesting potential implications of cytokine–CYP drug interactions on dose adjustments of sensitive CYP3A substrates in acute care settings. Additionally, this article also provides a brief overview of nonclinical and clinical assessments of cytokine–CYP drug interactions in drug discovery and development.

The precision medicine initiative has driven a substantial change in the way scientists and health care practitioners think about diagnosing and treating disease. While it has long been recognized that drug response is determined by the intersection of genetic, environmental, and disease factors, improvements in technology have afforded precision medicine guided dosing of drugs to improve efficacy and reduce toxicity. Pharmacometabolomics aims to evaluate small molecule metabolites in plasma and/or urine to help evaluate mechanisms that predict and/or reflect drug efficacy and toxicity. In this mini review, we provide an overview of pharmacometabolomic approaches and methodologies. Relevant examples where metabolomic techniques have been used to better understand drug efficacy and toxicity in major depressive disorder and cancer chemotherapy are discussed. In addition, the utility of metabolomics in drug development and understanding drug metabolism, transport, and pharmacokinetics is reviewed. Pharmacometabolomic approaches can help describe factors mediating drug disposition, efficacy, and toxicity. While important advancements in this area have been made, there remain several challenges that must be overcome before this approach can be fully implemented into clinical drug therapy.

A STING (stimulator of interferon genes) agonist GSK3996915 under investigation in early discovery for hepatitis B was orally dosed to a mouse model for understanding the parent drug distribution in liver, the target organ. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) was used to quantify the distribution of GSK3996915 in liver collected from mice administered a single oral dose at 90 mg/kg. GSK3996915 was detected with a zonal distribution localized in the portal triad and highly concentrated in the main bile ducts, indicating clearance through biliary excretion. High spatial resolution imaging showed the distribution of the parent drug localized to the cellular populations in the sinusoids, including the Kupffer cells. Additionally, a series of drug-related metabolites were observed to be localized in the central zones of the liver. These results exemplify the potential of utilizing MALDI IMS for measuring not only quantitative drug distribution and target exposure but also drug metabolism and elimination in a single suite of experiments.

Drug–drug interaction (DDI) assessment of therapeutic peptides is an evolving area. The industry generally follows DDI guidelines for small molecules, but the translation of data generated with commonly used in vitro systems to in vivo is sparse. In the current study, we investigated the ability of advanced human hepatocyte in vitro systems, namely HepatoPac, spheroids, and Liver-on-a-chip, to assess potential changes in regulation of CYP1A2, CYP2B6, CYP3A4, SLCO1B1, and ABCC2 in the presence of selected therapeutic peptides, proteins, and small molecules. The peptide NN1177, a glucagon and GLP-1 receptor co-agonist, did not suppress mRNA expression or activity of CYP1A2, CYP2B6, and CYP3A4 in HepatoPac, spheroids, or Liver-on-a-chip; these findings were in contrast to the data obtained in sandwich cultured hepatocytes. No effect of NN1177 on SLCO1B1 and ABCC2 mRNA was observed in any of the complex systems. The induction magnitude differed across the systems (e.g., rifampicin induction of CYP3A4 mRNA ranged from 2.8-fold in spheroids to 81.2-fold in Liver-on-a-chip). Small molecules, obeticholic acid and abemaciclib, showed varying responses in HepatoPac, spheroids, and Liver-on-a-chip, indicating a need for EC₅₀ determinations to fully assess translatability data. HepatoPac, the most extensively investigated in this study (3 donors), showed high potential to investigate DDIs associated with CYP regulation by therapeutic peptides. Spheroids and Liver-on-a-chip were only assessed in one hepatocyte donor and further evaluations are required to confirm their potential. This study establishes an excellent foundation toward the establishment of more clinically-relevant in vitro tools for evaluation of potential DDIs with therapeutic peptides.

Pregnane X receptor (PXR) belongs to the nuclear receptor superfamily that plays a crucial role in hepatic physiologic and pathologic conditions. Phase separation is a process in which biomacromolecules aggregate and condense into a dense phase as liquid condensates and coexist with a dilute phase, contributing to various cellular and biologic functions. Until now, whether PXR could undergo phase separation remains unclear. This study aimed to investigate whether PXR undergoes phase separation. Analysis of the intrinsically disordered regions (IDRs) using algorithm tools indicated a low propensity of PXR to undergo phase separation. Experimental assays such as hyperosmotic stress, agonist treatment, and optoDroplets assay demonstrated the absence of phase separation for PXR. OptoDroplets assay revealed the inability of the fusion protein of Cry2 with PXR to form condensates upon blue light stimulation. Moreover, phase separation of PXR did not occur even though the mRNA and protein expression levels of PXR target, cytochrome P450 3A4, changed after sorbitol treatment. In conclusion, for the first time, these findings suggested that exogenous PXR does not undergo phase separation following activation or under hyperosmotic stress in nucleus of cells.

Protein abundance data of drug-metabolizing enzymes and transporters (DMETs) are useful for scaling in vitro and animal data to humans for accurate prediction and interpretation of drug clearance and toxicity. Targeted DMET proteomics that relies on synthetic stable isotope-labeled surrogate peptides as calibrators is routinely used for the quantification of selected proteins; however, the technique is limited to the quantification of a small number of proteins. Although the global proteomics-based total protein approach (TPA) is emerging as a better alternative for large-scale protein quantification, the conventional TPA does not consider differential sequence coverage by identifying unique peptides across proteins. Here, we optimized the TPA approach by correcting protein abundance data by the sequence coverage, which was applied to quantify 54 DMETs for characterization of 1) differential tissue DMET abundance in the human liver, kidney, and intestine, and 2) interindividual variability of DMET proteins in individual intestinal samples (n = 13). Uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7), microsomal glutathione S-transferases (MGST1, MGST2, and MGST3) carboxylesterase 2 (CES2), and multidrug resistance-associated protein 2 (MRP2) were expressed in all three tissues, whereas, as expected, four cytochrome P450s (CYP3A4, CYP3A5, CYP2C9, and CYP4F2), UGT1A1, UGT2B17, CES1, flavin-containing monooxygenase 5, MRP3, and P-glycoprotein were present in the liver and intestine. The top three DMET proteins in individual tissues were: CES1>CYP2E1>UGT2B7 (liver), CES2>UGT2B17>CYP3A4 (intestine), and MGST1>UGT1A6>MGST2 (kidney). CYP3A4, CYP3A5, UGT2B17, CES2, and MGST2 showed high interindividual variability in the intestine. These data are relevant for enhancing in vitro to in vivo extrapolation of drug absorption and disposition and can be used to enhance the accuracy of physiologically based pharmacokinetic prediction of systemic and tissue concentration of drugs.

Hydrolases represent an essential class of enzymes indispensable for the metabolism of various clinically essential medications. Individuals exhibit marked differences in the expression and activation of hydrolases, resulting in significant variability in the pharmacokinetics (PK) and pharmacodynamics (PD) of drugs metabolized by these enzymes. The regulation of hydrolase expression and activity involves both genetic polymorphisms and nongenetic factors. This review examines the current understanding of genetic and nongenetic regulators of six clinically significant hydrolases, including carboxylesterase (CES)-1 CES2, arylacetamide deacetylase (AADAC), paraoxonase (PON)-1 PON3, and cathepsin A (CTSA). We explore genetic variants linked to the expression and activity of the hydrolases and their effects on the PK and PD of their substrate drugs. Regarding nongenetic regulators, we focus on the inhibitors and inducers of these enzymes. Additionally, we examine the developmental expression patterns and gender differences in the hydrolases when pertinent information was available. Many genetic and nongenetic regulators were found to be associated with the expression and activity of the hydrolases and PK and PD. However, hydrolases remain generally understudied compared with other drug-metabolizing enzymes, such as cytochrome P450s. The clinical significance of genetic and nongenetic regulators has not yet been firmly established for the majority of hydrolases. Comprehending the mechanisms that underpin the regulation of these enzymes holds the potential to refine therapeutic regimens, thereby enhancing the efficacy and safety of drugs metabolized by the hydrolases.

WIDESPREAD rain fell across NSW at the weekend.

Mental health experts are hopeful about the de-stigmatization of behavioral health, the promise of AI and other areas, they shared at a recent conference.

The post 4 Areas Within Mental Health Care that Give Executives Hope appeared first on MedCity News.