Inhibitory synapses dampen neuronal activity through postsynaptic hyperpolarization.The composition of the inhibitory postsynapse and the mechanistic basis of its regulation, however, remain poorly ...understood. We used an in vivo chemico-genetic proximity-labeling approach to discover inhibitory postsynaptic proteins. Quantitative mass spectrometry not only recapitulated known inhibitory postsynaptic proteins but also revealed a large network of new proteins, many of which are either implicated in neurodevelopmental disorders or are of unknown function. Clustered regularly interspaced short palindromic repeats (CRISPR) depletion of one of these previously uncharacterized proteins, InSyn1, led to decreased postsynaptic inhibitory sites, reduced the frequency of miniature inhibitory currents, and increased excitability in the hippocampus. Our findings uncover a rich and functionally diverse assemblage of previously unknown proteins that regulate postsynaptic inhibition and might contribute to developmental brain disorders.
Push notifications offer a promising strategy for enhancing engagement with smartphone-based health interventions. Intelligent sensor-driven machine learning models may improve the timeliness of ...notifications by adapting delivery to a user's current context (e.g. location). This exploratory mixed-methods study examined the potential impact of timing and frequency on notification response and usage of Healthy Mind, a smartphone-based stress management intervention. 77 participants were randomised to use one of three versions of Healthy Mind that provided: intelligent notifications; daily notifications within pre-defined time frames; or occasional notifications within pre-defined time frames. Notification response and Healthy Mind usage were automatically recorded. Telephone interviews explored participants' experiences of using Healthy Mind. Participants in the intelligent and daily conditions viewed (d = .47, .44 respectively) and actioned (d = .50, .43 respectively) more notifications compared to the occasional group. Notification group had no meaningful effects on percentage of notifications viewed or usage of Healthy Mind. No meaningful differences were indicated between the intelligent and non-intelligent groups. Our findings suggest that frequent notifications may encourage greater exposure to intervention content without deterring engagement, but adaptive tailoring of notification timing does not always enhance their use. Hypotheses generated from this study require testing in future work.
ISRCTN67177737.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The European Union's position on “one China” has stood since the establishment of diplomatic relations with the People's Republic of China (PRC) in 1975. As a union of distinct member states, the ...nature of the European Union's (EU) foreign policymaking complicates efforts to maintain coherent common positions. Its effective “one China policy” (and those of its member states) is no exception. In recent years, the edges of the bloc's long-standing policy have started to fray as the EU–PRC relationship has become more fraught and many member states have sought to deepen their effective, if “unofficial,” engagement with Taiwan. I explore these changes to the EU's effective “one China policy” by employing a subsystems framework, starting from the position that the EU has foreign policies (rather than a singular policy) created through three subsystems. Through the Normative Power Europe lens, I explore the extent to which the actors pulling at these “threads” at the edges of the EU's policy are motivated by normative concerns. I argue that the “fraying” of the EU's “one China policy” is not the result of a conscious decision by the EU as a collective normative actor but stems from shifting preferences within the national and supranational subsystems.
In this study involving nearly 3400 patients with venous thromboembolism, both prophylactic and therapeutic doses of rivaroxaban were superior to aspirin in reducing the risk of recurrent ...thromboembolism with a similar risk of bleeding.
Venous thromboembolism, which includes deep-vein thrombosis and pulmonary embolism, is the third most common cause of vascular death after myocardial infarction and stroke.
1
–
3
The mainstay of treatment is anticoagulation,
4
and in patients without active cancer, guidelines suggest the use of direct oral anticoagulant agents such as rivaroxaban over vitamin K antagonists such as warfarin.
4
Anticoagulation therapy is administered for 3 months or longer, depending on the balance between the risk of recurrent venous thromboembolism and the risk of bleeding.
4
In patients without reversible risk factors, the risk of recurrent venous thromboembolism is as much as 10% in the first . . .
Response assessment in the context of immunomodulatory treatments represents a major challenge for the medical imaging community and requires a multidisciplinary approach with involvement of ...oncologists, radiologists, and nuclear medicine specialists. There is evolving evidence that
FFDG PET/CT is a useful diagnostic modality for this purpose. The clinical indications for, and the principal aspects of its standardization in this context have been detailed in the recently published "Joint EANM/SNMMI/ANZSNM practice guidelines/procedure standards on recommended use of
FFDG PET/CT imaging during immunomodulatory treatments in patients with solid tumors version 1.0". These recommendations arose from a fruitful collaboration between international nuclear medicine societies and experts in cancer treatment. In this perspective, the key elements of the initiative are reported, summarizing the core aspects of the guidelines for radiologists and nuclear medicine physicians. Beyond the previous guidelines, this perspective adds further commentary on how this technology can advance development of novel therapeutic approaches and guide management of individual patients.
Purpose
The goal of this guideline/procedure standard is to assist nuclear medicine physicians, other nuclear medicine professionals, oncologists or other medical specialists for recommended use of
...18
FFDG PET/CT in oncological patients undergoing immunotherapy, with special focus on response assessment in solid tumors.
Methods
In a cooperative effort between the EANM, the SNMMI and the ANZSNM, clinical indications, recommended imaging procedures and reporting standards have been agreed upon and summarized in this joint guideline/procedure standard.
Conclusions
The field of immuno-oncology is rapidly evolving, and this guideline/procedure standard should not be seen as definitive, but rather as a guidance document standardizing the use and interpretation of
18
FFDG PET/CT during immunotherapy. Local variations to this guideline should be taken into consideration.
Preamble
The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association founded in 1985 to facilitate worldwide communication among individuals pursuing clinical and academic excellence in nuclear medicine. The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote science, technology and practical application of nuclear medicine. The Australian and New Zealand Society of Nuclear Medicine (ANZSNM), founded in 1969, represents the major professional society fostering the technical and professional development of nuclear medicine practice across Australia and New Zealand. It promotes excellence in the nuclear medicine profession through education, research and a commitment to the highest professional standards. EANM, SNMMI and ANZSNM members are physicians, technologists, physicists and scientists specialized in the research and clinical practice of nuclear medicine. All three societies will periodically put forth new standards/guidelines for nuclear medicine practice to help advance the science of nuclear medicine and improve service to patients. Existing standards/guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated. Each standard/guideline, representing a policy statement by the EANM/SNMMI/ANZSNM, has undergone a thorough consensus process, entailing extensive review. These societies recognize that the safe and effective use of diagnostic nuclear medicine imaging requires particular training and skills, as described in each document. These standards/guidelines are educational tools designed to assist practitioners in providing appropriate and effective nuclear medicine care for patients. These guidelines are consensus documents based on current knowledge. They are not intended to be inflexible rules or requirements of practice, nor should they be used to establish a legal standard of care. For these reasons and those set forth below, the EANM, SNMMI and ANZSNM caution against the use of these standards/guidelines in litigation in which the clinical decisions of a practitioner are called into question. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by medical professionals considering the unique circumstances of each case. Thus, there is no implication that an action differing from what is laid out in the guidelines/procedure standards, standing alone, is below standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the standards/guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources or advances in knowledge or technology subsequent to publication of the guidelines/procedure standards. The practice of medicine involves not only the science, but also the art of dealing with the prevention, diagnosis, alleviation and treatment of disease. The variety and complexity of human conditions make it impossible for general guidelines to consistently allow for an accurate diagnosis to be reached or a particular treatment response to be predicted. Therefore, it should be recognized that adherence to these standards/ guidelines will not ensure a successful outcome. All that should be expected is that practitioners follow a reasonable course of action, based on their level of training, current knowledge, clinical practice guidelines, available resources and the needs/context of the patient being treated. The sole purpose of these guidelines is to assist practitioners in achieving this objective. The present guideline/procedure standard was developed collaboratively by the EANM, the SNMMI and the ANZSNM, with the support of international experts in the field. They summarize also the views of the Oncology and Theranostics and the Inflammation and Infection Committees of the EANM, as well as the procedure standards committee of the SNMMI, and reflect recommendations for which the EANM and SNMMI cannot be held responsible. The recommendations should be taken into the context of good practice of nuclear medicine and do not substitute for national and international legal or regulatory provisions.
Does the reproductive potential of embryos change when blastocyst development takes longer than the traditionally accepted 5 days when accounting for aneuploidy and endometrial-embryo asynchrony?
...Aneuploidy increases with increasing duration of blastulation, but if blastocyst morphologic quality and endometrial-embryo asynchrony are controlled for, euploid Day 7 embryos have similar sustained implantation as compared to Days 5 and 6 euploid blastocysts.
The relative contributions of diminished embryo quality versus endometrial and embryo asynchrony to poor outcomes associated with embryos cultured past Day 6 are not clear. Asynchrony can be eliminated by embryo vitrification with transfer in a subsequent month after retrieval.
Retrospective cohort study of patients from a single center attempting conception through ICSI and utilizing preimplantation genetic testing for aneuploidy screening (PGT-A) from January 2017 to September 2018. Cycles were excluded if they utilized surgical sperm or preimplantation genetic testing for monogenetic/single gene defects. ICSI cycle outcomes from 2586 patients were evaluated for ploidy status of embryos.
Only patients undergoing single, euploid frozen embryo transfer were included when analyzing cycle outcomes by day of blastocyst expansion of the transferred embryo (n = 2130). Ploidy rates by the day upon which an embryo was considered to be usable (denoted, 'usable blastulation day') were determined so as to assess the contribution of aneuploidy to slow embryo development. Outcomes of euploid frozen single embryo transfers (SET) of Day 7 embryos were evaluated to assess the reproductive potential associated with embryos that were slowly developing for reasons other than aneuploidy. Analyses were adjusted by maternal age and blastocyst morphology.
Overall, 67.7% (n = 3508) of usable Day 5 blastocysts were euploid, 52.1% (n = 5560) of usable Day 6 blastocysts were euploid and 43.1% (n = 229) of usable Day 7 embryos were euploid (Day 5 versus Day 6: odds ratio (OR) 0.7 (95% CI, 0.64-0.76), P < 0.001; Day 5 versus Day 7: OR 0.56 (95% CI, 0.46-0.69), P < 0.001; Day 6 versus Day 7: OR 0.81 (95% CI, 0.67-0.99), P = 0.036). Stratified by Society for Assisted Reproductive Technology maternal age groups, a reduction in the prevalence of euploidy by increasing time to embryo blastulation was still seen. The sustained implantation rate (SIR) was similar after euploid SET of Days 5 and 6 embryos (overall, 68.9% (95% CI, 66.0-71.6) and 66.8% (95% CI, 63.8-69.7), respectively; P = 0.81). SIR after euploid Day 7 SET appeared slightly lower than that of Days 5 and 6 embryos (52.6% (95% CI, 35.8-69.0); (Day 5 versus Day 7: OR, 0.67 (95% CI, 0.32-1.41), P = 0.29; Day 6 versus Day 7: OR 0.58 (95% CI, 0.28-1.2), P = 0.14)) but did not achieve statistical significance.
The primary limitation is the low number of Day 7 blastocyst transfers that limits statistical power. Additionally, the retrospective nature of this study may prevent full elucidation of potential biases with respect to culture, morphologic assessment and selection of Day 7 embryos for transfer.
Routine culture through Day 7 may successfully increase the pool of transferrable embryos for patients who would otherwise have no usable embryos if culture terminated on Day 6. This is particularly true for older patients (i.e. greater than 35 years of age), whose embryos take longer to blastulate and, therefore, are more susceptible to cycle cancelation. Additionally, as evidenced by an adequate overall SIR of 52.6% after euploid SET of Day 7 blastocysts, embryos developing to a usable blastocyst on Day 7 are likely within the 'window of blastulation.'
None.
Background
Prior studies show that ADHD prevalence rates vary by race-ethnicity, but these studies do not include a full range of racial-ethnic minority groups.
Objective
This study aimed to ...understand differences in ADHD prevalence among children across a wider range of racial-ethnic groups, overall and stratified by biological sex.
Method
Data on children aged 5 to 17 from the 2004 to 2018 National Health Interview Survey Sample Child Files were used in analyses (N = 120,129).
Results
Compared to Non-Hispanic White children, ADHD prevalence was lower among Hispanic and Non-Hispanic Asian children. This difference was present for both males and females. Across all racial-ethnic groups, males had higher ADHD prevalence than females.
Conclusion
Results from this study provide further evidence that racial-ethnic disparities in ADHD prevalence rates persist across sex and provide initial evidence of substantially lower ADHD prevalence among Non-Hispanic Asians. Implications, limitations, and future research directions derived from the results are discussed.
People with intellectual and developmental disabilities (IDD) appear to be at greater risk for severe outcomes from COVID-19. The roles of congregate living and skilled nursing care needs in this ...disparity are unclear.
To determine the impact of residential setting and level of skilled nursing care on COVID-19 outcomes for people receiving IDD services, compared to those not receiving IDD services.
Utilizing publicly available California data on COVID-19 outcomes for people receiving IDD services (early May through October 2, 2020), we report outcomes based on seven types of residence, differentiated by number of residents and level of skilled nursing care provided. We compared these results to the larger California published outcomes.
Compared to Californians not receiving IDD services, in general, those receiving IDD services had a 60% lower case rate, but 2.8 times higher case-fatality rate. COVID-19 outcomes varied significantly among Californians receiving IDD services by type of residence and skilled nursing care needs: higher rates of diagnosis in settings with larger number of residents, higher case-fatality and mortality rates in settings that provided 24-h skilled nursing care.
Diagnosis with COVID-19 among Californians receiving IDD services appears to be related to the number of individuals within the residence, while adverse COVID-19 outcomes were associated with level of skilled nursing care. When data is available, future research should examine whether these relationships persist even when controlling for age and pre-existing conditions.
Abstract
Summary
ScaffoldGraph (SG) is an open-source Python library and command-line tool for the generation and analysis of molecular scaffold networks and trees, with the capability of processing ...large sets of input molecules. With the increase in high-throughput screening data, scaffold graphs have proven useful for the navigation and analysis of chemical space, being used for visualization, clustering, scaffold-diversity analysis and active-series identification. Built on RDKit and NetworkX, SG integrates scaffold graph analysis into the growing scientific/cheminformatics Python stack, increasing the flexibility and extendibility of the tool compared to existing software.
Availability and implementation
SG is freely available and released under the MIT licence at https://github.com/UCLCheminformatics/ScaffoldGraph.
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