Fostamatinib effectiveness and safety for immune thrombocytopenia in clinical practice.

Fostamatinib, a recently approved syk inhibitor used in adult primary immune thrombocytopenia (ITP), has been shown to be safe and effective in this disorder. However, clinical trial results may not be similarly reproduced in clinical practice. Here 138 ITP patients (both primary and secondary) from 42 Spanish centers who had been treated with fostamatinib were evaluated prospectively and retrospectively. The median age of our cohort (55.8% women) was 66 years (interquartile range, IQR, 56-80 years). The median time since ITP diagnosis at fostamatinib initiation was 51 months (IQR, 10-166 months). The median number of therapies prior to fostamatinib initiation was 4 (IQR, 2-5), including eltrombopag (76.1%), romiplostim (57.2%) and intravenous immunoglobulins (IVIG) (44.2%). Fifty-eight patients (42.0%) had signs/symptoms of bleeding in the month prior to treatment initiation. 79.0% of patients responded to fostamatinib with 53.6% complete responses (platelet count > 100 x 109 /L). Eighty-three patients (60.1%) received fostamatinib monotherapy achieving a high response rate (85.4%). The proportion of time in response during the 27-month period examined was 83.3%. The median time to platelet response was 11 days (IQR, 7-21 days). Sixty-seven patients (48.5%) experienced adverse events, mainly grade 1-2, the commonest of which were diarrhea (n = 28) and hypertension (n = 21). One patient had deep venous thrombosis and one patient developed acute myocardial infarction. Fostamatinib was shown to be effective with good safety profile in patients with primary and secondary ITP across a wide age spectrum in this real-world study.

Estradiol and Estrone Have Different Biological Functions to Induce NF-κB-Driven Inflammation, EMT and Stemness in ER+ Cancer Cells.

In general, the risk of being diagnosed with cancer increases with age; however, the development of estrogen-receptor-positive (ER+) cancer types in women are more closely related to menopausal status than age. In fact, the general risk factors for cancer development, such as obesity-induced inflammation, show differences in their association with ER+ cancer risk in pre- and postmenopausal women. Here, we tested the role of the principal estrogens in the bloodstream before and after menopause, estradiol (E2) and estrone (E1), respectively, on inflammation, epithelial-to-mesenchymal transition (EMT) and cancer stem cell enrichment in the human ER+ cervical cancer cell line HeLa. Our results demonstrate that E1, contrary to E2, is pro-inflammatory, increases embryonic stem-transcription factors (ES-TFs) expression and induces EMT in ER+ HeLa cells. Moreover, we observed that high intratumoural expression levels of 17ß-Hydroxysteroid dehydrogenase (HSD17B) isoforms involved in E1 synthesis is a poor prognosis factor, while overexpression of E2-synthetizing HSD17B isoforms is associated with a better outcome, for patients diagnosed with ER+ ovarian and uterine corpus carcinomas. This work demonstrates that E1 and E2 have different biological functions in ER+ gynaecologic cancers. These results open a new line of research in the study of ER+ cancer subtypes, highlighting the potential key oncogenic role of E1 and HSD17B E1-synthesizing enzymes in the development and progression of these diseases.

First record of partial albinism in the critically endangered Angelshark (Squatina squatina) (Linnaeus, 1758).

We report the first case of partial albinism in the Critically Endangered angelshark, Squatina squatina. The encounter with this specimen took place while SCUBA diving on the beach of Tufia, located on the east coast of the island of Gran Canaria on 2 April 2021. This is also the first confirmed finding of an albino elasmobranch specimen in the Canary Island archipelago.

Genetic diversity and drug susceptibility of Mycobacterium tuberculosis in a city with a high prevalence of drug resistant tuberculosis from Southeast of Mexico.

BACKGROUND: Mexico is on the top five countries with the highest number of TB cases in America continent, nevertheless, information about genotypes circulating is practically unknown. Considering the above this study aims to characterize the genetic diversity of TB in the city of Veracruz, México. METHODS: A cross-sectional study was conducted among positive smear samples from patients living in Veracruz City, samples were cultured, and first-line drug profiles determined. Genotyping was made by spoligotyping and MIRU-VNTR 24 loci. Associations of lineages, clusters, and variables were also analyzed. RESULTS: Among the 202 isolates analyzed resistance to at least one drug was observed in 60 (30%) isolates and 41(20%) were multidrug-resistant. Three major lineages were identified: L4/Euro-American (88%), L1/Indo-Oceanic (9%), and L2/East Asian (3%). The Euro-American lineage included more than six sublineages, the most abundant were: H (32%), T (23%), LAM (18%), and X (12%). 140 isolates (70%) were placed in 42 SITs patterns. CONCLUSIONS: These results provide the first baseline data on the genetic structure of TB in the city of Veracruz. Sublineages H, X and LAM were predominant; however, it was founded an important diversity of genotypes that could contribute to the dispersion of TB and explain the high prevalence. This information might be useful for the development of further interventions to reduce impact of TB.

Realizing the right to health in Latin America, equitably.

This special issue "Realizing the Right to Health in Latin America and the Caribbean" provides an overview of one of the most challenging objectives of health systems: equity and the realization of the right to health. In particular, it concentrates on the issues associated with such a challenge in countries suffering of deep inequity. The experience in Latin America and the Caribbean demonstrates that the efforts of health systems to achieve Universal Health Coverage are necessary but not sufficient to achieve an equitable realization of the right to health for all. The inequitable realization of all other human rights also determines the realization of the right to health.

Understanding inequities in health and health systems in Latin America and the Caribbean: a thematic series.

Latin America, with its culturally and ethnically diverse populations, its burgeoning economies, high levels of violence, growing political instability, and its striking levels of inequality, is a region that is difficult to define and to understand. The region's health systems are deeply fragmented and segmented, which poses great challenges related to the provision of quality of care and overall equity levels in health and in Latin American society at large. Market, social, and political forces continue to push towards the poorly regulated privatization of public health care in many countries within the region, in detriment of public healthcare services where management capacities are limited.In this first collection of papers, we showcase how the region has tackled, with different levels of success, the incorporation of innovative health system reforms aimed at strengthening governance, participation, and the response to the growing epidemiological and demographic demands of its diverse population. We are delighted that this Special Collection will remain open to house future papers from Latin America and the Caribbean. The region has important experiences and lessons to share with the world. We look forward to learning more about how researchers and practitioners continue to experiment and innovate in their struggle to reach equity in health for all. This thematic series is a platform where the region's lessons and approaches can be shared with the global community of Health Policy and Systems Researchers.

Cesarean delivery rates, hospital readiness and quality of clinical management in Ethiopia: national results from two cross-sectional emergency obstetric and newborn care assessments.

BACKGROUND: Cesarean delivery (CD) rates have reached epidemic levels in many high and middle income countries while increasingly, low income countries are challenged both by high urban CD rates and high unmet need in rural areas. The managing authority of health care institutions often plays a role in these disparities. This paper shows changes between 2008 and 2016 in Ethiopian CD rates, readiness of hospitals to provide CD and quality of clinical care, while highlighting the role of hospital management authority. METHODS: This secondary data analysis draws from two national cross-sectional studies to assess emergency obstetric and newborn care. The sample includes 111 hospitals in 2008 and 316 hospitals in 2016, and 275 women whose CD chart was reviewed in 2008 and 568 in 2016. Descriptive statistics are used to describe our primary outcome measures: population- and institutional-based CD rates; hospital readiness to perform CD; quality of clinical management, including the relative size of Robson classification groups. RESULTS: The national population CD rate increased from 2008 to 2016 (< 1 to 2.7%) as did all regional rates. Rates in 2016 ranged from 24% in urban settings to less than 1% in several rural regions. The institutional rate was 54% in private for-profit hospitals in 2016, up from 46% in 2008. Hospital readiness to perform CDs increased in public and private for-profit hospitals. Only half of the women whose charts were reviewed received uterotonics after delivery of the baby, but use of prophylactic antibiotics was high. Partograph use increased from 9 to 42% in public hospitals, but was negligible or declined elsewhere. In 2016, 40% of chart reviews from public hospitals were among low-risk nulliparous women (Robson groups 1&2). CONCLUSIONS: Between 2008 and 2016, government increased the availability of CD services, improved public hospital readiness and some aspects of clinical quality. Strategies tailored to further reduce the high unmet need for CD and what appears to be an increasing number of unnecessary cesareans are discussed. Adherence to best practices and universal coverage of water and electricity will improve the quality of hospital services while the use of the Robson classification system may serve as a useful quality improvement tool.

Preliminary assessment of the impact of Covid-19 Pandemic in the small-scale and recreational fisheries of the Canary Islands.

Covid-19 pandemic has affected worldwide in many different ways. Fisheries around the world are not an exception due to the long-term isolation and the non-activities period suffered. To do an evaluation of its impact on the fishing sectors in the Canary Islands, 87 online and phone questionnaires were carried out between July and September 2020, conducting the interviews to artisanal fishermen, fishmongers, recreational charter boats fishermen and tackle shops along the archipelago. Both, the artisanal and recreational fishing sectors have been affected by this pandemic, but in an unequal manner. The drop of the demand of fresh fishing products in the islands markets due to the closure of hotels, restaurants and other services, and the highly significant decreasing in the number of tourists, provoked an estimated income loss for the artisanal fishermen about the 40% on average, but the majority of vessels continued their activities during the pandemic, with very limited effects on direct employment. However, the fishmonger's activity apparently was not affected and increased their monthly income in relation to the previous year. Likewise, the infeasibility of fishing charter companies due to the great reduction in the number of tourists contrasted with the significant increase in the number of recreational fishing licenses immediately after the confinement ended. Even though that fishing tackle shops increased sales by over 60% in relation to the similar period of the year before, only 4.4% of these shops declared not to have had economic losses.

Axes of alienation: applying an intersectional lens on the social contract during the pandemic response to protect sexual and reproductive rights and health.

While economic inequalities have been a key focus of attention through the COVID 19 pandemic, gendered relations of power at every level have undermined health rights of women, girls and gender diverse individuals. Sexual and reproductive health rights (SRHR) have always been sites of power contestations within families, societies, cultures, and politics; these struggles are exacerbated by economic, racial, religious, caste, citizenship status, and other social inequities, especially in times of crisis such as these. Policy responses to the COVID pandemic such as lockdown, quarantine, contact tracing and similar measures are premised on the existence of a social contract between the government and the people and among people, with the health sector playing a key role in preventive and curative care.We propose the use of an intersectional lens to explore the impact of the COVID-19 pandemic on the social contract, drawing on our field experiences from different continents particularly as related to SRHR. Along with documenting the ways in which the pandemic hinders access to services, we note that it is essential to interrogate state-society relations in the context of vulnerable and marginalized groups, in order to understand implications for SRHR. Intersectional analysis takes on greater importance now than in non-pandemic times as the state exercises more police or other powers and deploys myriad ways of 'othering'.We conclude that an intersectional analysis should not limit itself to the cumulative disadvantages and injustices posed by the pandemic for specific social groups, but also examine the historical inequalities, structural drivers, and damaged social contract that underlie state-society relationships. At the same time, the pandemic has questioned the status quo and in doing so it has provided opportunities for disruption; for re-imagining a social contract that reaches across sectors, and builds community resilience and solidarities while upholding human rights and gender justice. This must find place in future organizing and advocacy around SRHR.

Health equity and COVID-19: global perspectives.

The COVID-19 is disproportionally affecting the poor, minorities and a broad range of vulnerable populations, due to its inequitable spread in areas of dense population and limited mitigation capacity due to high prevalence of chronic conditions or poor access to high quality public health and medical care. Moreover, the collateral effects of the pandemic due to the global economic downturn, and social isolation and movement restriction measures, are unequally affecting those in the lowest power strata of societies. To address the challenges to health equity and describe some of the approaches taken by governments and local organizations, we have compiled 13 country case studies from various regions around the world: China, Brazil, Thailand, Sub Saharan Africa, Nicaragua, Armenia, India, Guatemala, United States of America (USA), Israel, Australia, Colombia, and Belgium. This compilation is by no-means representative or all inclusive, and we encourage researchers to continue advancing global knowledge on COVID-19 health equity related issues, through rigorous research and generation of a strong evidence base of new empirical studies in this field.

Triangulating data sources for further learning from and about the MDSR in Ethiopia: a cross-sectional review of facility based maternal death data from EmONC assessment and MDSR system.

BACKGROUND: Triangulating findings from MDSR with other sources can better inform maternal health programs. A national Emergency Obstetric and Newborn Care (EmONC) assessment and the Maternal Death Surveillance and Response (MDSR) system provided data to determine the coverage of MDSR implementation in health facilities, the leading causes and contributing factors to death, and the extent to which life-saving interventions were provided to deceased women. METHODS: This paper is based on triangulation of findings from a descriptive analysis of secondary data extracted from the 2016 EmONC assessment and the MDSR system databases. EmONC assessment was conducted in 3804 health facilities. Data from interview of each facility leader on MDSR implementation, review of 1305 registered maternal deaths and 679 chart reviews of maternal deaths that happened form May 16, 2015 to December 15, 2016 were included from the EmONC assessment. Case summary reports of 601 reviewed maternal deaths were included from the MDSR system. RESULTS: A maternal death review committee was established in 64% of health facilities. 5.5% of facilities had submitted at least one maternal death summary report to the national MDSR database. Postpartum hemorrhage (10-27%) and severe preeclampsia/eclampsia (10-24.1%) were the leading primary causes of maternal death. In MDSR, delay-1 factors contributed to 7-33% of maternal deaths. Delay-2, related to reaching a facility, contributed to 32% & 40% of maternal deaths in the EmONC assessment and MDSR, respectively. Similarly, delay-3 factor due to delayed transfer of mothers to appropriate level of care contributed for 29 and 22% of maternal deaths. From the EmONC data, 72% of the women who died due to severe pre-eclampsia or eclampsia were given anticonvulsants while 48% of those dying of postpartum haemorrhage received uterotonics. CONCLUSION: The facility level implementation coverage of MDSR was sub-optimal. Obstetric hemorrhage and severe preeclampsia or eclampsia were the leading causes of maternal death. Delayed arrival to facility (Delay 2) was the predominant contributing factor to facility-based maternal deaths. The limited EmONC provision should be the focus of quality improvement in health facilities.

Experiential avoidance and excessive smartphone use: a Bayesian approach. / Evitación experiencial y uso abusivo del smartphone: un enfoque bayesiano.

The smartphone is a common tool in our everyday lives. However, recent research suggests that using the smartphone has both positive and negative consequences. Although there is no agreement on the concept or the term to label it, researchers and clinical practitioners are worried about the negative consequences derived from excessive smartphone usage. This study aims to analyse the relationship between smartphone addiction and experiential avoidance. A sample of 1176 participants (828 women) with ages ranging from 16 to 82 (M = 30.97; SD = 12.05) was used. The SAS-SV scale was used to measure smartphone addiction and the AAQ-II to assess experiential avoidance. To model the relationship between variables, Bayesian inference and Bayesian networks were used. The results show that experiential avoidance and social networks usage are directly related to smartphone addiction. Additionally, the data suggests that sex is playing a mediating role in the observed relationship between these variables. These results are useful for understanding healthy and pathological interaction with smartphones and could be helpful in orienting or planning future psychological interventions to treat smartphone addiction.

El uso del teléfono móvil se ha convertido en una actividad cotidiana en nuestro entorno más cercano. Dicho uso, según investigaciones recientes, tiene tanto aspectos positivos como negativos. Aunque hay controversia en cuanto a la denominación del fenómeno, se aprecia cierta preocupación por las consecuencias negativas que tiene el uso excesivo del teléfono móvil. Este estudio analiza la relación que se establece entre el uso abusivo del teléfono móvil y la evitación experiencial. Se utilizó una muestra compuesta por 1176 participantes (828 fueron mujeres) con edades comprendidas entre los 16 y los 82 años (M = 30.97; DT = 12.05). Se empleó la escala SAS-SV para valorar el uso problemático del móvil y el AAQ-II para la evitación experiencial. Para modelar la relación que se establece entre las variables se hizo uso de inferencia bayesiana y redes bayesianas. Los resultados muestran una relación directa entre el uso abusivo, la evitación experiencial y las redes sociales. Además, los datos sugieren que el sexo juega un papel mediador entre estas variables. Estos resultados son útiles para entender el uso saludable y patológico del teléfono móvil así como para orientar el tratamiento de los trastornos que pueden surgir de un mal uso de estos dispositivos.

Readiness to treat and factors associated with survival of newborns with breathing difficulties in Ethiopia.

BACKGROUND: Ethiopia is one of five countries that account for half of the world's 2.6 million newborn deaths. A quarter of neonatal deaths in Ethiopia are caused by birth asphyxia. Understanding different dimensions of the quality of care for newborns with breathing difficulties can lead to improving service provision environments and practice. We describe facility readiness to treat newborns with breathing difficulties, the extent to which newborn resuscitation is provided, and by modeling the survival of newborns with difficulties breathing, we identify key factors that suggest how mortality from asphyxia can be reduced. METHODS: We carried out a secondary analysis of the 2016 Ethiopia Emergency Obstetric and Newborn Care Assessment that included 3804 facilities providing childbirth services and 2433 chart reviews of babies born with difficulties breathing. We used descriptive statistics to assess health facilities' readiness to treat these newborns and a binary logistic regression to identify factors associated with survival. RESULTS: Over one-quarter of facilities did not have small-sized masks (size 0 or 1) to complete the resuscitation kits. Among the 2190 cases with known survival status, 49% died before discharge, and among 1035 cases with better data quality, 29% died. The odds of surviving birth asphyxia after resuscitation increased eightfold compared to newborns not resuscitated. Other predictors for survival were the availability of a newborn corner, born at term or post-term, normal birth weight (≥2500 g) and delivered by cesarean or assisted vaginal delivery. CONCLUSION: The survival status of newborns with birth asphyxia was low, particularly in the primary care facilities that lacked the required resuscitation pack. Newborns born in a facility with better data quality were more likely to survive than those born in facilities with poor data quality. Equipping health centers/clinics with resuscitation packs and reducing the incidence of preterm and low birth weight babies should improve survival rates.

Healthcare workers' clinical knowledge on maternal and newborn care in Ethiopia: findings from 2016 national EmONC assessment.

BACKGROUND: Improving maternal and newborn health indicators are key if Ethiopia is to achieve the Sustainable Development Goals. To do so, women need access to skilled attendance at birth and emergency obstetric and newborn care. To maximize their impact, understanding gaps in workers' knowledge is required to remedy the weakness. This assessment determines knowledge levels of clinical management of maternal and newborn healthcare and factors that influence knowledge. METHODS: This study used data from the National Emergency Obstetric and Neonatal Care assessment conducted in 2016. Provider knowledge for MNH was assessed by interviewing providers. Respondents were scored on each question by calculating the number of correct responses provided out of the total possible answers, and standardizing this to a scale of 100. Mixed linear regression was used to determine individual and contextual factors associated with the score. RESULTS: A total of 3800 interviews with complete data were included in this study. Most respondents were diploma midwives (73%), BSc midwives (11%) and diploma nurses (10%). On average, midwives scored 60 out of 100 on the question regarding the primary aspects of focused antenatal care and elements of a birth plan. Half of the midwives and health officers, and one-third of nurses knew to provide a loading dose of magnesium sulphate. Midwives scored 90% on the steps of active management of third stage of labor. In the mixed linear regression, working in a private for profit facility, health center/clinic, rural area, or in a facility with a protocol on referral/counter referral predicted lower knowledge scores. More positive scores were associated with work environments that had a computer, internet, and protocols on safe abortion care, management of selected obstetric topics, integrated management of pregnancy, childbirth, postnatal, and newborn, care for low birth weight including kangaroo mother care, and treatment of infection in young infants. CONCLUSION: With regard to most knowledge related questions, health officers and midwives scored similarly. Providers scored substantially better on routine intrapartum and newborn care than on aspects related to care for complications. A substantial proportion of providers indicated that they would never give a loading dose of magnesium sulphate.

Showcasing the contribution of social sciences to health policy and systems research.

BACKGROUND: This Special Issue represents a critical response to the frequent silencing of qualitative social science research approaches in mainstream public health journals, particularly in those that inform the field of health policy and systems research (HPSR), and the study of equity in health. METHODS: This collection of articles is presented by SHAPES, the thematic working group of Health Systems Global focused on social science approaches to research and engagement in health policy and systems. The issue aims to showcase how qualitative and theory-driven approaches can contribute to better promoting equity in health within the field of HPSR. RESULTS: This issue builds on growing recognition of the complex social nature of health systems. The articles in this collection underscore the importance of employing methods that can uncover and help explain health system complexities by exploring the dynamic relationships and decision-making processes of the human actors within. Articles seek to highlight the contribution that qualitative, interpretivist, critical, emancipatory, and other relational methods have made to understanding health systems, health policies and health interventions from the perspective of those involved. By foregrounding actor perspectives, these methods allow us to explore the impact of vital but difficult-to-measure concepts such as power, culture and norms. CONCLUSION: This special issue aims to highlight the critical contribution of social science approaches. Through the application of qualitative methods and, in some cases, development of theory, the articles presented here build broader and deeper understanding of the way health systems function, and simultaneously inform a more people-centred approach to collective efforts to build and strengthen those systems.

Community health workers and accountability: reflections from an international "think-in".

Community health workers (CHWs) are frequently put forward as a remedy for lack of health system capacity, including challenges associated with health service coverage and with low community engagement in the health system, and expected to enhance or embody health system accountability. During a 'think in', held in June of 2017, a diverse group of practitioners and researchers discussed the topic of CHWs and their possible roles in a larger "accountability ecosystem." This jointly authored commentary resulted from our deliberations. While CHWs are often conceptualized as cogs in a mechanistic health delivery system, at the end of the day, CHWs are people embedded in families, communities, and the health system. CHWs' social position and professional role influence how they are treated and trusted by the health sector and by community members, as well as when, where, and how they can exercise agency and promote accountability. To that end, we put forward several propositions for further conceptual development and research related to the question of CHWs and accountability.

Oral medicine acceptance in infants and toddlers: measurement properties of the caregiver-administered Children's acceptance tool (CareCAT).

BACKGROUND: Developing age-appropriate medications remains a challenge in particular for the population of infants and toddlers, as they are not able to reliably self-report if they would accept and consequently take an oral medicine. Therefore, it is common to use caregivers as proxies when assessing medicine acceptance. The outcome measures used in this research field differ and most importantly lack validation, implying a persisting gap in knowledge and controversy in the field. The newly developed Caregiver-administered Children's Acceptance Tool (CareCAT) is based on a 5-point nominal scale, with descriptors of medication acceptance behavior. This cross-sectional study assessed the measurement properties of the tool with regards to the user's understanding and its intra- and inter-rater reliability. METHODS: Participating caregivers were enrolled at a primary healthcare facility where their children (median age 6 months) had been prescribed oral antibiotics. Caregivers, trained observers and the tool developer observed and scored on the CareCAT tool what behavior children exhibited when receiving the medicine (n = 104). The video-records of this process served as replicate observations (n = 69). After using the tool caregivers were asked to explain their observations and the tool descriptors in their own words. The tool's reliability was assessed by percentage agreement and Cohen's unweighted kappa coefficients of agreement for nominal scales. RESULTS: The study found that caregivers using CareCAT had a satisfactory understanding of the tool's descriptors. Using its dichotomized scores the tool reliably was strong for acceptance behavior (agreement inter-rater 84-88%, kappa 0.66-0.76; intra-rater 87-89%, kappa 0.68-0.72) and completeness of medicine ingestion (agreement inter-rater 82-86%, kappa 0.59-0.67; intra-rater 85-93%, kappa 0.50-0.70). CONCLUSIONS: The CareCAT is a low-cost, easy-to-use and reliable instrument, which is relevant to assess acceptance behavior and completeness of medicine ingestion, both of which are of significant importance for developing age-appropriate medications in infants and toddlers.

From Binding-Induced Dynamic Effects in SH3 Structures to Evolutionary Conserved Sectors.

Src Homology 3 domains are ubiquitous small interaction modules known to act as docking sites and regulatory elements in a wide range of proteins. Prior experimental NMR work on the SH3 domain of Src showed that ligand binding induces long-range dynamic changes consistent with an induced fit mechanism. The identification of the residues that participate in this mechanism produces a chart that allows for the exploration of the regulatory role of such domains in the activity of the encompassing protein. Here we show that a computational approach focusing on the changes in side chain dynamics through ligand binding identifies equivalent long-range effects in the Src SH3 domain. Mutation of a subset of the predicted residues elicits long-range effects on the binding energetics, emphasizing the relevance of these positions in the definition of intramolecular cooperative networks of signal transduction in this domain. We find further support for this mechanism through the analysis of seven other publically available SH3 domain structures of which the sequences represent diverse SH3 classes. By comparing the eight predictions, we find that, in addition to a dynamic pathway that is relatively conserved throughout all SH3 domains, there are dynamic aspects specific to each domain and homologous subgroups. Our work shows for the first time from a structural perspective, which transduction mechanisms are common between a subset of closely related and distal SH3 domains, while at the same time highlighting the differences in signal transduction that make each family member unique. These results resolve the missing link between structural predictions of dynamic changes and the domain sectors recently identified for SH3 domains through sequence analysis.