A local projection stabilization/continuous Galerkin--Petrov method for incompressible flow problems

The local projection stabilization (LPS) method in space is consid-ered to approximate the evolutionary Oseen equations. Optimal error bounds independent of the viscosity parameter are obtained in the continuous-in-time case for the approximations of both velocity and pressure. In addition, the fully discrete case in combination with higher order continuous Galerkin--Petrov (cGP) methods is studied. Error estimates of order k + 1 are proved, where k denotes the polynomial degree in time, assuming that the convective term is time-independent. Numerical results show that the predicted order is also achieved in the general case of time-dependent convective terms

Medical Audit of Diabetes Mellitus in Primary Care Setting in Bosnia and Herzegovina

Aim To assess the quality of diabetes care provided by family medicine teams in primary health centers in Bosnia and Herzegovina (BH) through a medical audit, addressing the extent to which clinical practice complied with pre-determined explicit criteria of long-term management. Method Retrospective analysis included randomly selected medical records of patients with type 1 or 2 diabetes mellitus treated by 18 family medicine teams at 5 locations in BH, included in the Canadian International Development Agency/World Health Organization project “Strengthening health care system in BH with focus on primary health care/family medicine model.” Audit record form contained 24 questions on sex, age, diabetes type, body mass index (BMI), hypertension, family anamnesis, annual xaminations (HbA1C, BMI, lipid profile or total cholesterol, blood creatinin, neurological examination, urinanalysis for albuminuria, foot care, and examination of ocular fundus), smoking habits, alcohol consumption, patient education, prescribed insulin and other drugs, and patient’s health care-seeking behavior. Standardized and record forms were returned anonymously with 99.3% response rate. Results Records of 536 patients with diabetes were analyzed (64% women and 87% patients with diabetes mellitus type 2). Family medicine teams showed poor compliance with established criteria for diabetes control. Metabolic control (69.5%) was acceptable, but the level of monitoring complications of diabetes (foot and ocular fundus examined in 53.4% and 53% of patients, respectively) was low. There were also considerable variations in diabetes management between different centers as well as between the teams in the same center. Conclusion The audit revealed deficiencies in the quality of diabetes care and variations in care provision between primary care teams. Clinical guidelines and continuing education about acceptable diabetes care should be developed and implemented in BH

Project finance as a driver of economic growth in low-income countries

This study investigates the role of project finance as a driver of economic growth. We hypothesize that project finance is beneficial to the least developed economies as it is able to compensate for a lack of domestic financial development. The contractual structure unique to project finance leads to better investment management and governance. Investigating 90 countries from 1991 to 2005, we find support for our hypothesis. Results show that project finance fosters economic growth and that its effect is strongest in low-income countries, where financial development and governance is weakest

The pluripotency factor Nanog regulates pericentromeric heterochromatin organization in mouse embryonic stem cells.

An open and decondensed chromatin organization is a defining property of pluripotency. Several epigenetic regulators have been implicated in maintaining an open chromatin organization, but how these processes are connected to the pluripotency network is unknown. Here, we identified a new role for the transcription factor NANOG as a key regulator connecting the pluripotency network with constitutive heterochromatin organization in mouse embryonic stem cells. Deletion of Nanog leads to chromatin compaction and the remodeling of heterochromatin domains. Forced expression of NANOG in epiblast stem cells is sufficient to decompact chromatin. NANOG associates with satellite repeats within heterochromatin domains, contributing to an architecture characterized by highly dispersed chromatin fibers, low levels of H3K9me3, and high major satellite transcription, and the strong transactivation domain of NANOG is required for this organization. The heterochromatin-associated protein SALL1 is a direct cofactor for NANOG, and loss of Sall1 recapitulates the Nanog-null phenotype, but the loss of Sall1 can be circumvented through direct recruitment of the NANOG transactivation domain to major satellites. These results establish a direct connection between the pluripotency network and chromatin organization and emphasize that maintaining an open heterochromatin architecture is a highly regulated process in embryonic stem cells.We thank Ludovic Vallier for constitutive Nanog-EpiSC, Gabrielle Brons for 129S2 EpiSC, Prim Singh for H3K9me3 antibody, Maria Elena Torres Padilla for TALE-mClover and luciferase plasmids, Wellcome Trust Sanger Institute for pCyL43 plasmid and Andras Nagy for PB-TET and rtTA plasmids. We are grateful to David Oxley and Judith Webster Novo et al. for mass spectrometry support, Simon Walker for imaging support and Anne Segonds- Pichon for statistical advice. We thank Wolf Reik and Jon Houseley for comments on the manuscript and members of Wolf Reik’s group for helpful discussions. P.J.R.-G. is supported by the Wellcome Trust [WT093736], BBSRC [M022285] and the European Commission Network of Excellence EpiGeneSys [HEALTH-F4-2010-257082]. The work was also supported with funds from the Canadian Institutes of Health Research to J.E. [Team Grant EPS-129129] and D.P.B.-J. D.P.B-J. holds the Canada Research Chair in Molecular and Cellular Imaging. I.C. is supported by the MRC

INTEGRIRANA SKRB U MOSTARU: PRIORITET ZA ZDRAVSTVENI SUSTAV

Introduction: Integrated care could be defi ned differently and that is why the following terms can be found in the literature: integrated health, coordinated care, comprehensive care, seamless care, or trans-mural care. It has become a worldwide trend in health care reforms and new organizational arrangements focusing on more coordination between professionals and institutions and integrated forms of care or service provision. The Agency for Quality and Accreditation in Health Care in the Federation of Bosnia and Herzegovina (AKAZ) is using accreditation standards as a tool for quality improvement process aiming to increase the capacity of health care institutions in the Federation of Bosnia and Herzegovina in order to provide safe and quality care for the citizens. In the Agency, it is fi rmly believed that a wisely set and well-organized integrated care can help health professionals deliver health care in accordance with patient needs and even expectations. Aim: The aim of the study was to fi nd out how to implement measures for integration of health care, to fi nd out whether there are any gaps in the health care system, and how to bridge to the application of the best solutions of integrated care in the city of Mostar and Herzegovina-Neretva Canton (HNC). Methods: In this paper, we used feedback and results from the workshop held at the Federal Public Health Institute in Mostar as part of lectures for participants of the course within the Integrated Health Care module held in June 2019. The Integrated Health Care module is part of the Continuous Professional Education for Health Managers in the Federation of Bosnia and Herzegovina. Participants were experienced experts in different fi elds of medicine and pharmacists divided into two groups. Results: Participants identifi ed the most common problems for both primary and hospital physicians, such as unclear referral system to specialist examination, inappropriate patient expectations from primary care, lack of communication between primary care and hospital care, and inadequate use of clinical practice guidelines. To solve these problems, both groups stressed the importance of common strategy documents and guidelines, which should provide clear framework for cooperation and integration including levels of competence and service prices. Furthermore, effi cient information system is crucial for the integration or digitalization of, in strategy documents, agreed mechanisms of coordination and integration. Third, the growing proportion of elderly population should be taken in consideration, including the need of hospice and development of geriatric medicine in the Canton. Participants discussed and compared the results with feedback and results from three workshops held several years before. Discussion: The results of our study stressed the importance of better communication among different sectors, institutions and levels of health care involved in the treatment of patients, pointed to some measures for integration including standardized models of communication, training and education and highlighted priorities for integration. Analysis indicated the necessity for the following: regular analysis of unnecessary or inappropriate referrals and evaluation of such practices, as well as of any duplication of tests and prescriptions (failure to control costs); joint planning of preventive treatments (including the ministry and public health authorities); and clear responsibilities regarding screening programs and patient path analysis. Conclusions: Strong commitment of health care authorities and vision of integrated care and collaborative networks, as well as good communication and leadership were highlighted as key integrated care facilitators. Health care institutions at all levels of care have to organize multidisciplinary teams to work more on better and effective communication and to exchange information among key stakeholders in the system.Uvod: Integrirana skrb može se različito defi nirati i to je razlog zbog kojeg se u literaturi mogu naći sljedeći pojmovi: integrirano zdravlje, koordinirana njega, sveobuhvatna njega, besprijekorna njega ili transmuralna njega. Postala je svjetski trend u reformama zdravstva i novim organizacijskim aranžmanima koji su usredotočeni na veću koordinaciju između stručnjaka, institucija i pružatelja usluga. Agencija za kvalitet i akreditaciju u zdravstvu u Federaciji Bosne i Hercegovine koristi akreditacijske standarde kao alat za poboljšanje kvalitete s ciljem povećanja kapaciteta zdravstvenih ustanova u Federaciji Bosne i Hercegovine za pružanje sigurne i kvalitetne skrbi za građane. U Agenciji čvrsto vjeruju da mudro postavljena i dobro organizirana integrirana skrb može pomoći zdravstvenim radnicima da pruže zdravstvenu skrb u skladu s potrebama, pa čak i očekivanjima pacijenta. Cilj: Otkriti i analizirati kako se provode mjere za integraciju zdravstvene zaštite, postoje li nedostatci u zdravstvenom sustavu i kako ih premostiti za primjenu najboljih rješenja integrirane skrbi u gradu Mostaru i Hercegovačko-neretvanskoj županiji. Metode: U ovom smo radu koristili povratne informacije i rezultate radionice Federalnog zavoda za javno zdravstvo u Mostaru u sklopu predavanja za polaznike tečaja u okviru modula Integrirana zdravstvena zaštita održanog u lipnju 2019. Integrirani modul zdravstvene zaštite je dio kontinuiranog stručnog usavršavanja za zdravstvene menadžere u Federaciji Bosne i Hercegovine. Sudionici radionice bili su iskusni liječnici specijalisti različitih specijalnosti i farmaceuti podijeljeni u dvije skupine. Rezultati: Sudionici su odredili najčešće poteškoće za uspostavljanje integrirane zdravstvene zaštite kako za primarne, tako i za bolničke liječnike, a to su: nejasan sustav upućivanja na specijalistički pregled, neprimjereno očekivanje pacijenta od liječnika primarne zdravstvene zaštite, nedostatak komunikacijskog kanala između primarne i tercijarne bolničke skrbi i nedosljedna uporaba smjernica za kliničku praksu. Za rješavanje ovih problema obje skupine ističu važnost zajedničkih strateških dokumenata i smjernica koje bi trebale dati jasan okvir za suradnju i integraciju uključujući razinu stručnosti i cijene usluga. Nadalje, učinkovit informacijski sustav ključan je za integraciju ili digitalizaciju, u strateškim dokumentima, dogovorenih mehanizama koordinacije i integracije. Treće, potrebno je uzeti u obzir starenje populacije, nužne potrebe za hospicijima i razvoj gerijatrijske medicine u Županiji. Sudionici su raspravljali i uspoređivali svoje rezultate s povratnim informacijama i rezultatima ostalih triju istovjetnih radionica održanih ranijih godina. Rasprava: Rezultati naše studije istaknuli su važnost bolje komunikacije između različitih sektora, institucija i razina zdravstvene zaštite uključenih u liječenje pacijenata te istaknuli određene mjere integracije uključujući standardizirane modele komunikacije, obuke i obrazovanja te istaknute prioritete integracije. Analiza je ukazala na potrebu za sljedećim: redovitim analizama nepotrebnih ili neprikladnih uputnica i procjenom takve prakse, kao i podvostručenja testova i recepata (propust u kontroli troškova); zajedničko planiranje preventivnih tretmana i jasne odgovornosti u vezi s programima probira i analizom puta pacijenta. Zaključci: Snažna predanost zdravstvenih vlasti, vizija integrirane skrbi i suradničke mreže, kao i dobra komunikacija i vodstvo istaknuti su kao ključni pokretači integrirane skrbi. Zdravstvene ustanove sa svih razina skrbi moraju organizirati multidisciplinske timove koji će raditi na boljoj i učinkovitijoj komunikaciji i razmjeni informacija između ključnih dionika u sustavu

Consistent patterns of common species across tropical tree communities

Trees structure the Earth’s most biodiverse ecosystem, tropical forests. The vast number of tree species presents a formidable challenge to understanding these forests, including their response to environmental change, as very little is known about most tropical tree species. A focus on the common species may circumvent this challenge. Here we investigate abundance patterns of common tree species using inventory data on 1,003,805 trees with trunk diameters of at least 10 cm across 1,568 locations1,2,3,4,5,6 in closed-canopy, structurally intact old-growth tropical forests in Africa, Amazonia and Southeast Asia. We estimate that 2.2%, 2.2% and 2.3% of species comprise 50% of the tropical trees in these regions, respectively. Extrapolating across all closed-canopy tropical forests, we estimate that just 1,053 species comprise half of Earth’s 800 billion tropical trees with trunk diameters of at least 10 cm. Despite differing biogeographic, climatic and anthropogenic histories7, we find notably consistent patterns of common species and species abundance distributions across the continents. This suggests that fundamental mechanisms of tree community assembly may apply to all tropical forests. Resampling analyses show that the most common species are likely to belong to a manageable list of known species, enabling targeted efforts to understand their ecology. Although they do not detract from the importance of rare species, our results open new opportunities to understand the world’s most diverse forests, including modelling their response to environmental change, by focusing on the common species that constitute the majority of their trees.Publisher PDFPeer reviewe

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Food Legumes and Rising Temperatures: Effects, Adaptive Functional Mechanisms Specific to Reproductive Growth Stage and Strategies to Improve Heat Tolerance

Ambient temperatures are predicted to rise in the future owing to several reasons associated with global climate changes. These temperature increases can result in heat stress- a severe threat to crop production in most countries. Legumes are well-known for their impact on agricultural sustainability as well as their nutritional and health benefits. Heat stress imposes challenges for legume crops and has deleterious effects on the morphology, physiology, and reproductive growth of plants. High-temperature stress at the time of the reproductive stage is becoming a severe limitation for production of grain legumes as their cultivation expands to warmer environments and temperature variability increases due to climate change. The reproductive period is vital in the life cycle of all plants and is susceptible to high-temperature stress as various metabolic processes are adversely impacted during this phase, which reduces crop yield. Food legumes exposed to high-temperature stress during reproduction show flower abortion, pollen and ovule infertility, impaired fertilization, and reduced seed filling, leading to smaller seeds and poor yields. Through various breeding techniques, heat tolerance in major legumes can be enhanced to improve performance in the field. Omics approaches unravel different mechanisms underlying thermotolerance, which is imperative to understand the processes of molecular responses toward high-temperature stress