GRADEing the quality of evidence on safety: an adapted GRADE approach for preparing lists of potentially inappropriate medication for older adults

BackgroundSystematic reviews that synthesize safety outcomes pose challenges (e.g. rare events), which poses questions for grading the strength of the body of evidence. In this contribution, we suggest adaption of the GRADE system for grading the quality of evidence on safety outcomes for developing a potentially inappropriate medication list (PRISCUS).MethodsWe systematically assessed each of the five GRADE domains for rating-down (study limitations, imprecision, inconsistency, indirectness, publication bias) and the criteria for rating-up, considering if special considerations or revisions of the original approach were indicated. The result was gathered in a written document and discussed in a group-meeting. Subsequently, we performed a proof-of-concept application using a convenience sample of systematic reviews. Results We adapted aspects of the criteria study limitations, imprecision, publication bias and rating-up for large effect. In addition, we suggest a new criterion to account for data from subgroup-analyses. The proof-of-concept application did not reveal a need for further revision and thus we used the approach for the systematic reviews that were prepared for the PRISCUS-list. We assessed 51 outcomes for 19 clinical questions. Each of the proposed adaptions was applied. There were neither an excessive number of low and very low ratings, nor an excessive number of high ratings, but the different methodological quality of the safety outcomes appeared to be well reflected.ConclusionThe adaptions appear to have the potential to overcome some of the challenges when grading the methodological quality of harms and thus may be helpful for producers of evidence syntheses considering safety.

Maintenance of quiescent oocytes by noradrenergic signals

All females adopt an evolutionary conserved reproduction strategy; under unfavorable conditions such as scarcity of food or mates, oocytes remain quiescent. However, the signals to maintain oocyte quiescence are largely unknown. Here, we report that in four different species – Caenorhabditis elegans, Caenorhabditis remanei, Drosophila melanogaster, and Danio rerio – octopamine and norepinephrine play an essential role in maintaining oocyte quiescence. In the absence of mates, the oocytes of Caenorhabditis mutants lacking octopamine signaling fail to remain quiescent, but continue to divide and become polyploid. Upon starvation, the egg chambers of D. melanogaster mutants lacking octopamine signaling fail to remain at the previtellogenic stage, but grow to full-grown egg chambers. Upon starvation, D. rerio lacking norepinephrine fails to maintain a quiescent primordial follicle and activates an excessive number of primordial follicles. Our study reveals an evolutionarily conserved function of the noradrenergic signal in maintaining quiescent oocytes.

Revisión de la Metodología para la Mejora de la Enseñanza Universitaria = Review of the Methodology for the Improvement of University Teaching

El presente trabajo pretende indagar qué aspectos de la metodología del aprendizaje basado en retos resultan mejor valorados por parte de los alumnos y qué aspectos son susceptibles de mejora. Para ello se realiza una encuesta abierta. Se detecta que valoran especialmente la cercanía del planteamiento de la asignatura con la realidad profesional y el acompañamiento de los alumnos a lo largo del proceso de aprendizaje. La mitad considera que la carga de trabajo es adecuada, mientras que la otra mitad la considera excesiva. El resto de los aspectos mejor valorados son el enfoque de la asignatura y la innovación educativa. Las características y habilidades de los profesores reciben una valoración media; son peor valorados la coordinación con otras asignaturas, los recursos facilitados, las cuestiones organizativas y el excesivo número de alumnos en clase. Se concluye que la opinión de los alumnos es una ayuda inestimable para evaluar la metodología utilizadaAbstractThe present work aims to investigate which aspects of the challenge-based learning methodology are best valued by students and which aspects are susceptible to improvement. For this, an open survey is carried out. It is detected that they especially value the closeness of the approach to the subject with the professional reality and the accompaniment of the students throughout the learning process. Half consider the workload adequate, while the other half consider it excessive. The rest of the best valued aspects are the focus of the subject and educational innovation. The characteristics and abilities of the teachers receive an average evaluation; Coordination with other subjects, the resources provided, organizational issues and the excessive number of students in class are less valued. It is concluded that the opinion of the students is an invaluable help to evaluate the methodology used.

A Selective Neutraligand for CXCL12/SDF-1α With Beneficial Regulatory Functions in MRL/Lpr Lupus Prone Mice

Dysregulation of CXCL12/SDF-1-CXCR4/CD184 signaling is associated with inflammatory diseases and notably with systemic lupus erythematosus. Issued from the lead molecule chalcone-4, the first neutraligand of the CXCL12 chemokine, LIT-927 was recently described as a potent analogue with improved solubility and stability. We aimed to investigate the capacity of LIT-927 to correct immune alterations in lupus-prone MRL/lpr mice and to explore the mechanism of action implemented by this small molecule in this model. We found that in contrast to AMD3100, an antagonist of CXCR4 and agonist of CXCR7, LIT-927 reduces the excessive number of several B/T lymphocyte subsets occurring in the blood of sick MRL/lpr mice (including CD3+/CD4-/CD8-/B220+ double negative T cells). In vitro, LIT-927 downregulated the overexpression of several activation markers on splenic MRL/lpr lymphocytes. It exerted effects on the CXCR4 pathway in MRL/lpr CD4+ T spleen cells. The results underline the importance of the CXCL12/CXCR4 axis in lupus pathophysiology. They indicate that neutralizing CXCL12 by the neutraligand LIT-927 can attenuate hyperactive lymphocytes in lupus. This mode of intervention might represent a novel strategy to control a common pathophysiological mechanism occurring in inflammatory diseases.

Review on Air Pollution on Health and Its Prevention

Air pollution is the major environmental pollution that contains different types of gases, dust particles, small molecules, etc. Smoke and other hazardous gases, such as carbon, sulfur, and nitrogen oxides, are the primary causes of air pollution. Otherwise, air pollution is the contaminated air that poisonous effect on people's health. Most air pollution is affected by auto-rickshaw drivers. Auto drivers doing very stressful works which have been associated with environmental interaction factors. So the auto drivers are working within the environment, auto drivers are exposed to climate changes and poor road conditions. So the drivers are exposed to air pollution, dust, droplets, job insecurity, noise and vibration, business demands, damage to equipment, an excessive number of stops, schedule-related pressure, among others. Drivers’ social role is also reflected in the responsibility of passengers and pedestrians ‘lives and other vehicles.

THE EFFECT OF BITCOIN ON THE GLOBAL ECONOMY IN THE CONTEXT OF THE EVOLUTION OF CONCEPTS RELATED TO DIGITAL DEVELOPMENT

This study intends to sort out what will be the normal choices of the customary financial frameworks and how the world economy will draw in and manage those normal other options. Since technological improvement is profoundly quick and momentous, it is imperative to comprehend the discernments, practices, correspondence, and the possibility of selection of those other options. Advanced monetary standards and cryptographic forms of money are non-customary financial monetary forms that depend on something referred to as blockchain innovation. There is an excessive number of advanced digital forms of money these days, all of them having their own attributes and specificities. A portion of those advanced digital currencies will be studied in this research. It is imperative to mention here that only one out of every odd nation acknowledges the progress in this area, and such nations arrangement are often influenced by their World Bank rank — low, lower-middle, upper-middle, and high-income countries. More, this research looks at the social side of bitcoin and blockchain development in these nations. Bitcoin is tremendously influencing the economy overall. That’s why it quickly became of interest for many financially trained professionals and academicians. Unfortunately, this type of money has been increasingly used for criminal activities too. This research discusses all these sides as well as the important impacts bitcoin has on the population.

Numerical Investigation on a Axial Slot Casing Treatment of a Large Circumferential Interval and Small Opening Area

Axial slot casing treatment is a common method to extend the stall margin of a compressor. Based on the mechanism of unsteady flow control, this paper redesigns axial slots with large circumferential interval and small opening area. To test the effect of this axial slot structure, unsteady numerical simulations were carried out with different slot areas and circumferential intervals. The results show that this novel axial slot casing treatment can significantly improve compressor stall margin. Meanwhile, compared with the traditional axial slot, the efficiency loss is greatly reduced. The flow field analysis shows that the new axial slot structure proposed in this paper can suppress the development of tip leakage vortex and unsteadiness in the tip region at the near stall condition through decreasing the tip loading periodically. Moreover, we find that the slot area is proportional to the improvement of stability margin. Under the same slot area, an excessive number of slots is not conducive to the improvement of the stability margin.

Enshrining Terror for the Nation: Affect and Nationalism at the National September 11 Memorial and Museum

The National September 11 Memorial and Museum (9/11 MM) employs affective rhetoric to enshrine the trauma of September 11 in support of U.S. nationalism. Applying Brian Massumi's understanding of affect as intensity, I examine how the site's rhetoric amplifies affect. The memorial pools and many signifiers of destruction magnify affective intensity through scale and repetition. The 9/11 MM continues its affective onslaught through an excessive number of shocking visuals and narrative details in its historical exhibition. The site’s affective intensity culminates in a non-linear and non-narrative memorial space of seemingly infinite individualized mourning. The article discusses the site's political and social impact by considering Nigel Thrift's idea of affect in the built environment as imbedded thought and Georg Böhme's theory of atmosphere, understood as the reciprocal relationship between affective urban space and its impact on people.

Factors of slowing down the economic growth of modern Russia

The study of the influence of the Federal laws adopted in Russia on the rate of economic growth made it possible to establish that since 2005, lawmaking has hindered the growth of the Russian economy. In the work, a model of the dependence of the rates of economic growth on the number of employees of state authorities and local self-government obtained. The model shows that the number of employees of state authorities and local self-government determines the rate of economic growth by one third, and the increase in their number causes a decrease in the rate of economic growth. Excessive number of employees of state authorities and local self-government, enforcing these laws, inhibits economic growth. To assess the possibility of increasing human capital due to the functioning of the education system, the value of the «education premium» estimated. The obtained results of the assessment of the «premium for education» indicate that the education system in modern Russia is losing its role as a means of forming human capital. In the period from 2009 to 2019, premiums for secondary vocational, secondary (complete) general and basic general education were completely lost. The premium for higher education has more than halved; by 2027, the premium for higher education for employed workers will also be completely lost. The loss by the institution of education of the role of a means of forming human capital is due to continuous ineffective reforms in education.

Rationalizing Mongolia’s Hospital Services: Experiences, Lessons Learned, and Future Directions

Before the 1990s, Mongolia had a health care system that largely depended on hospital-based services. The country’s hospital sector was characterized by the extensive use of an excessive number of acute beds, a large number of medically unjustified admissions, and lengthy hospital stays. In the early 1990s, the Government of Mongolia started socioeconomic reforms as part of the transition to a market economy. It requested the Asian Development Bank (ADB) to support health sector reforms in the country. This paper describes the hospital sector in Mongolia along with the reforms and results achieved, challenges that remain, and ongoing and future directions for ADB support to better respond to the needs of the people.