We study the severity of conflict-related violence in Colombia at an unprecedented granular scale in space and across time. Splitting the data into different geographical regions and different ...historically-relevant periods, we uncover variations in the patterns of conflict severity which we then explain in terms of local conflict actors' different collective behaviors and/or conditions using a simple mathematical model of conflict actors' grouping dynamics (coalescence and fragmentation). Specifically, variations in the approximate scaling values of the distributions of event lethalities can be explained by the changing strength ratio of the local conflict actors for distinct conflict eras and organizational regions. In this way, our findings open the door to a new granular spectroscopy of human conflicts in terms of local conflict actor strength ratios for any armed conflict.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
23.
Shockwavelike Behavior across Social Media Manrique, Pedro D; Huo, Frank Yingjie; El Oud, Sara ...
Physical review letters,
06/2023, Volume:
130, Issue:
23
Journal Article
Peer reviewed
Online communities featuring "anti-X" hate and extremism, somehow thrive online despite moderator pressure. We present a first-principles theory of their dynamics, which accounts for the fact that ...the online population comprises diverse individuals and evolves in time. The resulting equation represents a novel generalization of nonlinear fluid physics and explains the observed behavior across scales. Its shockwavelike solutions explain how, why, and when such activity rises from "out-of-nowhere," and show how it can be delayed, reshaped, and even prevented by adjusting the online collective chemistry. This theory and findings should also be applicable to anti-X activity in next-generation ecosystems featuring blockchain platforms and Metaverses.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
We introduce a generalized form of gelation theory that incorporates individual heterogeneity and show that it can explain the asynchronous, sudden appearance and growth of online extremist groups ...supporting ISIS (so-called Islamic State) that emerged globally post-2014. The theory predicts how heterogeneity impacts their onset times and growth profiles and suggests that online extremist groups present a broad distribution of heterogeneity-dependent aggregation mechanisms centered around homophily. The good agreement between the theory and empirical data suggests that existing strategies aiming to defeat online extremism under the assumption that it is driven by a few "bad apples" are misguided. More generally, this generalized theory should apply to a range of real-world systems featuring aggregation among heterogeneous objects.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
Intranasal delivery has been shown to noninvasively deliver drugs from the nose to the brain in minutes along the olfactory and trigeminal nerve pathways, bypassing the blood−brain barrier. However, ...no one has investigated whether nasally applied drugs target orofacial structures, despite high concentrations observed in the trigeminal nerve innervating these tissues. Following intranasal administration of lidocaine to rats, trigeminally innervated structures (teeth, temporomandibular joint (TMJ), and masseter muscle) were found to have up to 20-fold higher tissue concentrations of lidocaine than the brain and blood as measured by ELISA. This concentration difference could allow intranasally administered therapeutics to treat disorders of orofacial structures (i.e., teeth, TMJ, and masseter muscle) without causing unwanted side effects in the brain and the rest of the body. In this study, an intranasally administered infrared dye reached the brain within 10 minutes. Distribution of dye is consistent with dye entering the trigeminal nerve after intranasal administration through three regions with high drug concentrations in the nasal cavity: the middle concha, the maxillary sinus, and the choana. In humans the trigeminal nerve passes through the maxillary sinus to innervate the maxillary teeth. Delivering lidocaine intranasally may provide an effective anesthetic technique for a noninvasive maxillary nerve block. Intranasal delivery could be used to target vaccinations and treat disorders with fewer side effects such as tooth pain, TMJ disorder, trigeminal neuralgia, headache, and brain diseases.
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IJS, KILJ, NUK, PNG, UL, UM
Although poly(ADP-ribose) polymerase (PARP) inhibitors are active in homologous recombination (HR)-deficient cancers, their utility is limited by acquired resistance after restoration of HR. Here, we ...report that dinaciclib, an inhibitor of cyclin-dependent kinases (CDKs) 1, 2, 5, and 9, additionally has potent activity against CDK12, a transcriptional regulator of HR. In BRCA-mutated triple-negative breast cancer (TNBC) cells and patient-derived xenografts (PDXs), dinaciclib ablates restored HR and reverses PARP inhibitor resistance. Additionally, we show that de novo resistance to PARP inhibition in BRCA1-mutated cell lines and a PDX derived from a PARP-inhibitor-naive BRCA1 carrier is mediated by residual HR and is reversed by CDK12 inhibition. Finally, dinaciclib augments the degree of response in a PARP-inhibitor-sensitive model, converting tumor growth inhibition to durable regression. These results highlight the significance of HR disruption as a therapeutic strategy and support the broad use of combined CDK12 and PARP inhibition in TNBC.
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•Dinaciclib is a potent inhibitor of CDK12 and disrupts homologous recombination•Residual HR is a cause of de novo PARP inhibitor resistance in BRCA-mutated cancer•Dinaciclib sensitizes resistant BRCA-mutated breast cancer models to PARP inhibition•In HR-deficient cancer, dinaciclib augments the response afforded by PARP inhibition
Johnson et al. show that CDK12 inhibition, mediated by the small molecule dinaciclib, disrupts residual or restored homologous recombination (HR) in BRCA-associated breast cancer, sensitizing to PARP inhibition. CDK12 inhibition also augments the degree of PARP inhibitor response in HR-deficient breast cancer. Combined CDK12-PARP inhibition is well tolerated in preclinical models.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
IMPORTANCE: Acupuncture is widely used by women undergoing in vitro fertilization (IVF), although the evidence for efficacy is conflicting. OBJECTIVE: To determine the efficacy of acupuncture ...compared with a sham acupuncture control performed during IVF on live births. DESIGN, SETTING, AND PARTICIPANTS: A single-blind, parallel-group randomized clinical trial including 848 women undergoing a fresh IVF cycle was conducted at 16 IVF centers in Australia and New Zealand between June 29, 2011, and October 23, 2015, with 10 months of pregnancy follow-up until August 2016. INTERVENTIONS: Women received either acupuncture (n = 424) or a sham acupuncture control (n = 424). The first treatment was administered between days 6 to 8 of follicle stimulation, and 2 treatments were administered prior to and following embryo transfer. The sham control used a noninvasive needle placed away from the true acupuncture points. MAIN OUTCOMES AND MEASURES: The primary outcome was live birth, defined as the delivery of 1 or more living infants at greater than 20 weeks’ gestation or birth weight of at least 400 g. RESULTS: Among 848 randomized women, 24 withdrew consent, 824 were included in the study (mean SD age, 35.4 4.3 years); 371 45.0% had undergone more than 2 previous IVF cycles), 607 proceeded to an embryo transfer, and 809 (98.2%) had data available on live birth outcomes. Live births occurred among 74 of 405 women (18.3%) receiving acupuncture compared with 72 of 404 women (17.8%) receiving sham control (risk difference, 0.5% 95% CI, −4.9% to 5.8%; relative risk, 1.02 95% CI, 0.76 to 1.38). CONCLUSIONS AND RELEVANCE: Among women undergoing IVF, administration of acupuncture vs sham acupuncture at the time of ovarian stimulation and embryo transfer resulted in no significant difference in live birth rates. These findings do not support the use of acupuncture to improve the rate of live births among women undergoing IVF. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12611000226909
We consider the looming threat of bad actors using artificial intelligence (AI)/Generative Pretrained Transformer to generate harms across social media globally. Guided by our detailed mapping of the ...online multiplatform battlefield, we offer answers to the key questions of what bad-actor-AI activity will likely dominate, where, when-and what might be done to control it at scale. Applying a dynamical Red Queen analysis from prior studies of cyber and automated algorithm attacks, predicts an escalation to daily bad-actor-AI activity by mid-2024-just ahead of United States and other global elections. We then use an exactly solvable mathematical model of the observed bad-actor community clustering dynamics, to build a Policy Matrix which quantifies the outcomes and trade-offs between two potentially desirable outcomes: containment of future bad-actor-AI activity vs. its complete removal. We also give explicit plug-and-play formulae for associated risk measures.
Zika virus transmission dynamics in urban environments follow a complex spatiotemporal pattern that appears unpredictable and barely related to high mosquito density areas. In this context, human ...activity patterns likely have a major role in Zika transmission dynamics. This paper examines the effect of host variability in the amount of time spent outdoors on Zika epidemiology in an urban environment.
First, we performed a survey on time spent outdoors by residents of Miami-Dade County, Florida. Second, we analyzed both the survey and previously published national data on outdoors time in the U.S. to provide estimates of the distribution of the time spent outdoors. Third, we performed a computational modeling evaluation of Zika transmission dynamics, based on the time spent outdoors by each person. Our analysis reveals a strong heterogeneity of the host population in terms of time spent outdoors-data are well captured by skewed gamma distributions. Our model-based evaluation shows that in a heterogeneous population, Zika would cause a lower number of infections than in a more homogenous host population (up to 4-fold differences), but, at the same time, the epidemic would spread much faster. We estimated that in highly heterogeneous host populations the timing of the implementation of vector control measures is the major factor for limiting the number of Zika infections.
Our findings highlight the need of considering host variability in exposure time for managing mosquito-borne infections and call for the revision of the triggers for vector control strategies, which should integrate mosquito density data and human outdoor activity patterns in specific areas.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
STUDY QUESTION
Is there a global consensus on the management of endometriosis that considers the views of women with endometriosis?
SUMMARY ANSWER
It was possible to produce an international ...consensus statement on the current management of endometriosis through engagement of representatives of national and international, medical and non-medical societies with an interest in endometriosis.
WHAT IS KNOWN ALREADY
Management of endometriosis anywhere in the world has been based partially on evidence-based practices and partially on unsubstantiated therapies and approaches. Several guidelines have been developed by a number of national and international bodies, yet areas of controversy and uncertainty remain, not least due to a paucity of firm evidence.
STUDY DESIGN, SIZE, DURATION
A consensus meeting, in conjunction with a pre- and post-meeting process, was undertaken.
PARTICIPANTS/MATERIALS, SETTING, METHODS
A consensus meeting was held on 8 September 2011, in conjunction with the 11th World Congress on Endometriosis in Montpellier, France. A rigorous pre- and post-meeting process, involving 56 representatives of 34 national and international, medical and non-medical organizations from a range of disciplines, led to this consensus statement.
MAIN RESULTS AND THE ROLE OF CHANCE
A total of 69 consensus statements were developed. Seven statements had unanimous consensus; however, none of the statements were made without expression of a caveat about the strength of the statement or the statement itself. Only two statements failed to achieve majority consensus. The statements covered global considerations, the role of endometriosis organizations, support groups, centres or networks of expertise, the impact of endometriosis throughout a woman's life course, and a full range of treatment options for pain, infertility and other symptoms related to endometriosis.
LIMITATIONS, REASONS FOR CAUTION
This consensus process differed from that of formal guideline development. A different group of international experts from those participating in this process would likely have yielded subtly different consensus statements.
WIDER IMPLICATIONS OF THE FINDINGS
This is the first time that a large, global, consortium, representing 34 major stake-holding organizations from five continents, has convened to systematically evaluate the best available current evidence on the management of endometriosis, and to reach consensus. In addition to 18 international medical organizations, representatives from 16 national endometriosis organizations were involved, including lay support groups, thus generating input from women who suffer from endometriosis.
STUDY FUNDING/COMPETING INTEREST(S)
The World Endometriosis Society commissioned and hosted the consensus meeting. Financial support for participants to attend the meeting was provided by the organizations that they represented. There was no other specific funding for this consensus process. Full disclosures of all participants are presented herein.
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