A transcriptional constraint mechanism limits the homeostatic response to activity deprivation in mammalian neocortex.

Healthy neuronal networks rely on homeostatic plasticity to maintain stable firing rates despite changing synaptic drive. These mechanisms, however, can themselves be destabilizing if activated inappropriately or excessively. For example, prolonged activity deprivation can lead to rebound hyperactivity and seizures. While many forms of homeostasis have been described, whether and how the magnitude of homeostatic plasticity is constrained remains unknown. Here, we uncover negative regulation of cortical network homeostasis by the PARbZIP family of transcription factors. In cortical slice cultures made from knockout mice lacking all three of these factors, the network response to prolonged activity withdrawal measured with calcium imaging is much stronger, while baseline activity is unchanged. Whole-cell recordings reveal an exaggerated increase in the frequency of miniature excitatory synaptic currents reflecting enhanced upregulation of recurrent excitatory synaptic transmission. Genetic analyses reveal that two of the factors, Hlf and Tef, are critical for constraining plasticity and for preventing life-threatening seizures. These data indicate that transcriptional activation is not only required for many forms of homeostatic plasticity but is also involved in restraint of the response to activity deprivation.

The human brain is made up of billions of nerve cells called neurons which receive and send signals to one another. To avoid being over- or under-stimulated, neurons can adjust the strength of the inputs they receive by altering how connected they are to other nerve cells. This process, known as homeostatic plasticity, is thought to be necessary for normal brain activity as it helps keep the outgoing signals of neurons relatively constant. However, homeostatic plasticity can lead to seizures if it becomes too strong and overcompensates for weak input signals. Regulating this process is therefore central to brain health, but scientists do not understand if or how it is controlled. To address this, Valakh et al. analyzed the genes activated in neurons lacking incoming signals to find proteins that regulate homeostatic plasticity. This revealed a class of molecules called transcription factors (which switch genes on or off) that constrain the process. In brain samples from mice without these regulatory proteins, neurons received twice as much input, leading to an increase in brain activity resembling that observed during seizures. Valakh et al. confirmed this finding using live mice, which developed seizures in the absence of these transcription factors. These findings suggest that this type of regulation to keep homeostatic plasticity from becoming too strong may be important. This could be especially vital as the brain develops, when the strength of connections between neurons changes rapidly. The discovery of the transcription factors involved provides a potential target for activating or restraining homeostatic plasticity. This control could help researchers better understand how the process stabilizes brain signaling.

Management of Adverse Events in Early Clinical Trials by Advanced Practice Providers in the Outpatient Setting: The University of Texas MD Anderson Cancer Center Experience.

Background: Advanced practice providers (APPs) play important roles in enrolling, educating, and caring for patients in clinical trials. However, much remains unknown about the role of APPs in managing adverse events (AEs) in early (phase I to II) clinical trials. In this study, we assessed the outpatient management of grade 3 to 4 AEs by APPs in early trials and characterized the workflow of our APP Phase I to II Fast Track (FT) Clinic. Patients and Methods: We retrospectively reviewed records of patients with advanced or metastatic solid tumors enrolled in phase I to II clinical trials who were seen by APPs from September 2017 to August 2018 in the APP phase I to II FT clinic in the Department of Investigational Cancer Therapeutics. Results: A total of 808 patients enrolled in 159 clinical trials were seen in 2,697 visits (median 3 visits per patient; range 1-28) by 10 APPs. Treatment was interrupted in 6.9% of visits, and grade 3 to 4 AEs were seen in 5.4% of visits; however, patients from 1.4% of visits were sent to the emergency center (EC) and/or admitted. Patients referred to the EC and/or admitted were more likely to have baseline hypoalbuminemia, high lactate dehydrogenase, and poor Eastern Cooperative Oncology Group performance status (i.e., ECOG > 1; p < .001). There were no associations between EC referral and gender, APP years of experience, or type of treatment. Conclusions: The APP Phase I to II FT Clinic has an important role in the management of AEs by APPs in early clinical trials in the outpatient setting, potentially avoiding EC visits and admissions.

Measuring Violence Against Women: A Global Index.

Violence against women (VaW) is a widespread crime and violation of the rights of women. It is present in every country without exception and crosses boundaries of culture, class, education, income, and race. Despite the magnitude of the literature and the abundance of publications on this problem, the field lacks a comprehensive and homogeneous way to measure and compare the extent of VaW across countries. Proper quantification of this problem is needed to develop preventive policies and strategies to reduce it. This article develops an index of VaW (VAWI) with global scope and multidimensional approach for 102 countries. It is an original index that calculates the total level of VaW by capturing information from the main VaW types (physical, sexual, psychological, and economic violence) in a single value between 0 and 1, where 0 denotes complete absence of violence and 1 the highest level of violence in a country. The proposed index is easy to compute and is comparable across countries. Our main results show that the nations with the highest levels of global VaW are Yemen, Senegal, Oman, Cameroon, and Uganda. The countries with the lowest levels are the Northern European Countries, Canada, and Malta. This VAWI makes a novel and important contribution to the study of gender issues. It can be used not only to monitor the statistics on VaW data within countries over time but also to make comparisons among countries. Further, it could be useful in designing new policy initiatives to reduce VaW.

Assessment of Ambivalent Sexism in University Students in Colombia and Spain: A Comparative Analysis.

(1) Background: Gender-based violence has no geographical, personal, or social boundaries. It constitutes a serious public health problem that affects the entire society. This research aims to identify and compare the level of ambivalent sexism in Spanish and Colombian university students and its relationship with sociodemographic factors. Ambivalent sexism, developed by Glick and Fiske (1996), is considered a new type of sexism since, for the first time, it combines negative and positive feelings that give rise to hostile and benevolent sexism, maintaining the subordination of women through punishment and rewards. (2) Methods: The methodology consisted of the application of the validated Spanish version of the Ambivalent Sexism Inventory (ASI) to a sample of 374 students in their final academic year of the Law program, of which 21.7% were students at the University of Santander (Bucaramanga, Colombia), 45.5% at the University Rey Juan Carlos (Madrid, Spain), and the remaining 32.9% at the University of Seville (Seville, Spain). (3) Results: A high level of ambivalent sexism is reported in Colombian students nowadays. In the two countries. there are similarities (e.g., the great weight of religion and the variation in attitudes towards sexism in people who identify themselves as women, compared to male or students consulted that prefer not to answer) and differences (e.g., absence in Colombia of gender-specific legislation, low number of students who have received gender education in Spain). (4) Conclusions: These findings may contribute to the construction of laws that take into account the particular problems of women and the development of educational programs on gender that are offered in a transversal and permanent way and that take into account cultural factors and equity between men and women as an essential element in the training of future judges who have the legal responsibility to protect those who report gender violence.

Microfinance and Violence Against Women in Rural Guatemala.

Violence against Women (VaW) has come to be recognized as a serious human rights abuse with important consequences not only for women but for whole societies. Since VaW has several manifestations, it is possible to differentiate among different types of violence. In this article, a broad theoretical framework with different dimensions of gender violence was adapted to a Latin American social and cultural context to measure three out of the five main types of violence: economic violence, emotional psychological violence, and coercive control. The goal of this article is to provide empirical evidence to determine whether access to microfinance services plays a role in reducing VaW. To this end, we designed and performed a cross-sectional study with a treatment and a control group in rural Guatemala. A sample of 883 rural women in the "Altiplano" area of Guatemala (448 women with microfinance services and 435 without) was surveyed from May to November 2012. The results of the bivariate logistic regression showed evidence of association between access to microfinance services and reduction of VaW. After adjusting for covariates, global, economic, and emotional psychological violence maintained a negative and statistically significant association with microfinance, while only coercive control showed no statistical association with microfinance services. Access to microcredits showed a very clear relationship to reducing economic and emotional violence but not coercive control, a factor that may be determined by social and cultural norms. In contrast to Status Inconsistency Theory, which has been tested primarily in Asia, our study of Guatemala showed that increased status and economic independence of women due to their participation in microfinance services reduced VaW.