An examination of the intersection of public discourses on sexualities with recent political, economic, and social shifts in the national context of Mexico and the Mexican diaspora in the United ...States.
Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. The majority of GISTs harbor gain of function mutations in either KIT or PDGFRα. ...Determination of the GIST molecular subtype upon diagnosis is important because this information informs therapeutic decisions in both the adjuvant and metastatic setting. The management of GIST was revolutionized by the introduction of imatinib, a KIT inhibitor, which has become the standard first line treatment for metastatic GIST. However, despite a clinical benefit rate of 80%, the majority of patients with GIST experience disease progression after 2-3 years of imatinib therapy. Second and third line options include sunitinib and regorafenib, respectively, and yield low response rates and limited clinical benefit. There have been recent FDA approvals for GIST including ripretinib in the fourth-line setting and avapritinib for PDGFRA exon 18-mutant GIST. This article aims to review the optimal treatment approach for the management of patients with advanced GIST. It examines the standard treatment options available but also explores the novel treatment approaches in the setting of imatinib refractory GIST.
Policía beyond the police Gutiérrez, Laura; Neocleous, Mark
Theoretical criminology,
08/2023, Volume:
27, Issue:
3
Journal Article
Peer reviewed
Open access
This article develops and extends the critical theory of police power by applying it to Colombia. Scholarship on police in Colombia has been undermined by a focus on the kind of creation myth that ...one finds in most histories of police: that policing only properly begins in a key foundational year. In Colombia, that year is 1891. This approach overlooks or downplays the importance of the concept of policía. This is the original and far more expansive police concept through which social order in Colombia was fabricated. By paying attention to the continued importance of policía, this article drastically transforms our understanding of police power and state formation in Colombia, and extends the critical theory of police power.
The Max Planck Institute Grand Ensemble (MPI‐GE) is the largest ensemble of a single comprehensive climate model currently available, with 100 members for the historical simulations (1850–2005) and ...four forcing scenarios. It is currently the only large ensemble available that includes scenario representative concentration pathway (RCP) 2.6 and a 1% CO2 scenario. These advantages make MPI‐GE a powerful tool. We present an overview of MPI‐GE, its components, and detail the experiments completed. We demonstrate how to separate the forced response from internal variability in a large ensemble. This separation allows the quantification of both the forced signal under climate change and the internal variability to unprecedented precision. We then demonstrate multiple ways to evaluate MPI‐GE and put observations in the context of a large ensemble, including a novel approach for comparing model internal variability with estimated observed variability. Finally, we present four novel analyses, which can only be completed using a large ensemble. First, we address whether temperature and precipitation have a pathway dependence using the forcing scenarios. Second, the forced signal of the highly noisy atmospheric circulation is computed, and different drivers are identified to be important for the North Pacific and North Atlantic regions. Third, we use the ensemble dimension to investigate the time dependency of Atlantic Meridional Overturning Circulation variability changes under global warming. Last, sea level pressure is used as an example to demonstrate how MPI‐GE can be utilized to estimate the ensemble size needed for a given scientific problem and provide insights for future ensemble projects.
Key Points
The 100‐member MPI‐GE is currently the largest publicly available ensemble of a comprehensive climate model
MPI‐GE currently has the most forcing scenarios of all large ensemble projects: RCP2.6, RCP4.5, RCP8.5, and 1% CO2
The power of MPI‐GE is to estimate the forced response and internal variability, including changing variability, to unprecedented precision
Objective
This open‐label 12‐week study was conducted to evaluate the efficacy and safety of tofacitinib, a JAK inhibitor, in treatment‐refractory active dermatomyositis (DM).
Methods
Tofacitinib in ...extended‐release doses of 11 mg was administered daily to 10 subjects with DM. Prior to treatment, a complete washout of all steroid‐sparing agents was performed. The primary outcome measure was assessment of disease activity improvement based on the International Myositis Assessment and Clinical Studies group definition of improvement. Response rate was measured as the total improvement score according to the 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) myositis response criteria. Secondary outcome measures included Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) scores, chemokine levels, immunohistochemical analysis of STAT1 expression in the skin, RNA sequencing analysis, and safety.
Results
At 12 weeks, the primary outcome was met in all 10 subjects. Five (50%) of 10 subjects experienced moderate improvement in disease activity, and the other 50% experienced minimal improvement according to the 2016 ACR/EULAR myositis response criteria. The secondary outcome of the mean change in the CDASI activity score over 12 weeks was statistically significant (mean ± SD 28 ± 15.4 at baseline versus 9.5 ± 8.5 at 12 weeks) (P = 0.0005). Serum chemokine levels of CXCL9/CXCL10 showed a statistically significant change from baseline. A marked decrease in STAT1 signaling in association with suppression of interferon target gene expression was demonstrated in 3 of 9 skin biopsy samples from subjects with dermatomyositis. The mean ± SD level of creatine kinase in the 10 subjects at baseline was 82 ± 34.8 IU/liter, highlighting that disease activity was predominantly located in the skin.
Conclusion
This is the first prospective, open‐label clinical trial of tofacitinib in DM that demonstrates strong clinical efficacy of a pan‐JAK inhibitor, as measured by validated myositis response criteria. Future randomized controlled trials using JAK inhibitors should be considered for treating DM.
In patients with bicuspid valve (BAV), ascending aorta (AAo) dilatation may be caused by altered flow patterns and wall shear stress (WSS). These differences may explain different aortic dilatation ...morphotypes. Using 4D-flow cardiovascular magnetic resonance (CMR), we aimed to analyze differences in flow patterns and regional axial and circumferential WSS maps between BAV phenotypes and their correlation with ascending aorta dilatation morphotype.
One hundred and one BAV patients (aortic diameter ≤ 45 mm, no severe valvular disease) and 20 healthy subjects were studied by 4D-flow CMR. Peak velocity, flow jet angle, flow displacement, in-plane rotational flow (IRF) and systolic flow reversal ratio (SFRR) were assessed at different levels of the AAo. Peak-systolic axial and circumferential regional WSS maps were also estimated. Unadjusted and multivariable adjusted linear regression analyses were used to identify independent correlates of aortic root or ascending dilatation. Age, sex, valve morphotype, body surface area, flow derived variables and WSS components were included in the multivariable models.
The AAo was non-dilated in 24 BAV patients and dilated in 77 (root morphotype in 11 and ascending in 66). BAV phenotype was right-left (RL-) in 78 patients and right-non-coronary (RN-) in 23. Both BAV phenotypes presented different outflow jet direction and velocity profiles that matched the location of maximum systolic axial WSS. RL-BAV velocity profiles and maximum axial WSS were homogeneously distributed right-anteriorly, however, RN-BAV showed higher variable profiles with a main proximal-posterior distribution shifting anteriorly at mid-distal AAo. Compared to controls, BAV patients presented similar WSS magnitude at proximal, mid and distal AAo (p = 0.764, 0.516 and 0.053, respectively) but lower axial and higher circumferential WSS components (p < 0.001 for both, at all aortic levels). Among BAV patients, RN-BAV presented higher IRF at all levels (p = 0.024 proximal, 0.046 mid and 0.002 distal AAo) and higher circumferential WSS at mid and distal AAo (p = 0.038 and 0.046, respectively) than RL-BAV. However, axial WSS was higher in RL-BAV compared to RN-BAV at proximal and mid AAo (p = 0.046, 0.019, respectively). Displacement and axial WSS were independently associated with the root-morphotype, and circumferential WSS and SFRR with the ascending-morphotype.
Different BAV-phenotypes present different flow patterns with an anterior distribution in RL-BAV, whereas, RN-BAV patients present a predominant posterior outflow jet at the sinotubular junction that shifts to anterior or right anterior in mid and distal AAo. Thus, RL-BAV patients present a higher axial WSS at the aortic root while RN-BAV present a higher circumferential WSS in mid and distal AAo. These results may explain different AAo dilatation morphotypes in the BAV population.
Chitosan (CS) and sodium alginate (SA)-based biocomposites (CSA) were prepared with the in-situ generation of Calcium Carbonate (CSAX_Ca) through a simple, straightforward, economical, and ...eco-friendly procedure. Different drying conditions (X) were tested to achieve suitable structural and surface characteristics to enhance adsorption capacity: freeze-dried (L), vacuum-dried with methanol (M), and freeze-dried + vacuum-dried with methanol (LM). Temperature and adsorbent dosage effects on the adsorption capacity of Cu2+ or Pb2+ were examined. Results showed that the higher-yielding biocomposite (CSALM_Ca) exhibited rapid adsorption and good diffusion properties, achieving removal above 90 % within contaminant initial concentration ranges of 10–100 mg/L. At 35 °C, a pseudo-second-order kinetic and the Langmuir model effectively described kinetics and isotherms, revealing maximum adsorption (qe, max) of 429 mgCu2+/L and 1742 mgPb2+/g. Characterization through FTIR, XRD, and SEM of the as-prepared adsorbents confirmed the presence of CaCO3 in vaterite and calcite forms and the influence of drying conditions on the material morphology. Post-adsorption material characterization, in combination with adsorption findings, revealed chemisorption processes involving Ca2+ ion exchange for Cu2+ or Pb2+, resulting in surface-insoluble compounds. The best-performing material showed that after three reuse cycles, the removal of Cu2+ and Pb2+ decreased to 75 % and 62 %, respectively.
•Eco-friendly chitosan/alginate/CaCO3 adsorbents for Cu and Pb water remotion.•Vacuum drying with methanol led to calcite formation, hindering heavy metal removal.•Freeze-drying and methanol-water replacement increased vaterite and calcite generation.•In-situ CaCO3 generation on chitosan/alginate composites for Cu and Pb high removal•CaCO3 enhances copper and lead adsorption in chitosan/alginate bio-composites.•Remarkable removal capacity of chitosan/alginate/calcium carbonate bio-adsorbents.•Drying methods impact material structure; lyophilization improves diffusion.
Humid heat presents a major societal challenge through its impacts on human health, energy demand, and economic productivity, underlined by the projected emergence of conditions beyond human ...tolerance. However, systematic assessment of what drives the most extreme humid heat worldwide has been lacking. Here, we investigate factors determining the location and magnitude of humid‐heat extremes, framing our analysis around the four regions with the highest values: the southern Persian Gulf, north‐central Pakistan, eastern South Asia, and the western Amazon. We find that strong boundary‐layer moisture fluxes, together with stability that inhibits moist convection, explain well the timing and location of near‐surface humid‐heat extremes. These favorable conditions are achieved through regionally distinct factors, including shallow sea breezes in the Persian Gulf and large‐scale subsidence in eastern South Asia. Our results demonstrate some of the principal controls on the most intense humid heat, both globally and for particular regions and heat events.
Plain Language Summary
Combinations of high temperatures and high humidity are a primary threat of climate change because they can be not only uncomfortable but deadly, and are growing rapidly in frequency and intensity. In this study, we present a general theory for where the most extreme such events occur and describe the precise meteorological conditions that favor them. We are therefore able to state with new confidence the reasons why extreme humid heat events take place where they do, and why. Our results also highlight the regional distinctions in the factors (such as winds or ocean temperatures) that contribute to these events, increasing the strength of the evidence that some regions are much more sensitive to certain factors than others—information that can be used to guide better forecasts as well as climate‐change projections.
Key Points
A systematic assessment of humid‐heat hotspots reveals the dual importance of vertical stability and low‐level moisture sources
These two conditions are achieved through markedly different meteorological processes and in markedly different geographical contexts
Understanding the most extreme humid heat requires applying global principles to detailed regional analyses across space and time scales
We explore the extent to which internal variability can reconcile discrepancies between observed and simulated warming in the upper tropical troposphere. We compare all extant radiosonde‐based ...estimates for the period 1958–2014 to simulations from the Coupled Model Intercomparison Project phase 5 multimodel ensemble and the 100 realization Max Planck Institute large ensemble. We consider annual mean temperatures and all available 30‐and 15‐year trends. Most observed trends fall within the ensemble spread for most of the record, and trends calculated over 15‐year periods show better agreement than 30‐year trends, with generally larger discrepancies for the older observational products. The simulated amplification of surface warming aloft in the troposphere is consistent with observations, and the linear correlation between surface and simultaneous tropospheric warming trends decreases with trend length. We conclude that trend differences between observations and simulations of tropical tropospheric temperatures are dominated by observational uncertainty and chaotic internal variability rather than by systematic errors in model performance.
Key Points
Radiosonde observations show good agreement with a single‐model 100 member ensemble of simulations for the majority of observational record
Largest trend differences for amplification of tropospheric over surface warming aloft for 30‐year trends occur in second half of the record
Differences in observed and simulated tropical tropospheric temperature trends arise from observational uncertainty and internal variability
This brief and personal essay discusses Ester Hernández's and Astrid Hadad's artistic relationship, which includes a beautiful friendship that spans time and space. In particular, and from an ...intimate vantage point, I read two of Hernández's images that feature Hadad, which the Mexican artist has displayed in her home in Mexico City, to ponder a larger question regarding contemporary cross-border feminist and genderqueer esthetics and relations. The queer kinship between these two artists, I humbly posit, extends to the fans that come out to support Hadad's shows when she performs in cities in the U.S. with large Latinx demographics, particularly in California.
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