3. Wheat versus maize Civilizing Dietary Strategies and Early Mexican Republicanism

This article explored the role of food in the rise of political modernity in the Atlantic world, toward the end of the 18th century and beginning of the 19th. The three food programs analyzed here—the production of a “patriotic” bread, the program of “public and common” meals, and the regime of “hard digestion” founded upon ideal indigenous food habits—shaped one of the first republican discourses in Mexico. ese discussions about republic, citizenship and food standards, although they reflected varied, eclectic and often contradictory positions, shared one point in common: they resignified some of the basic notions of the colonial political language, including community, territory, patria and “common good”.

Planck Constraints and Gravitational Wave Forecasts for Primordial Black Hole Dark Matter Seeded by Multifield Inflation

We perform a Markov Chain Monte Carlo (MCMC) analysis of a simple yet generic multifield inflation model characterized by two scalar fields coupled to each other and nonminimally coupled to gravity, fit to Planck 2018 cosmic microwave background (CMB) data. In particular, model parameters are constrained by data on the amplitude of the primordial power spectrum of scalar curvature perturbations on CMB scales $A_s$, the spectral index $n_s$, and the ratio of power in tensor to scalar modes $r$, with a prior that the primordial power spectrum should also lead to primordial black hole (PBH) production sufficient to account for the observed dark matter (DM) abundance. We find that $n_s$ in particular controls the constraints on our model. Whereas previous studies of PBH formation from an ultra-slow-roll phase of inflation have highlighted the need for at least one model parameter to be highly fine-tuned, we identify a degeneracy direction in parameter space such that shifts by $\sim 10\%$ of one parameter can be compensated by comparable shifts in other parameters while preserving a close fit between model predictions and observations. Furthermore, we find this allowed parameter region produces observable gravitational wave (GW) signals in the frequency ranges to which upcoming experiments are projected to be sensitive, including Advanced LIGO and Virgo, the Einstein Telescope (ET), Cosmic Explorer (CE), DECIGO, and LISA.Comment: 27 pages, 10 figures, 2 tables. Minor edits and references added to match published version (forthcoming in Physical Review D), including an additional appendix to discuss effects on the power spectrum from a phase of ultra-slow-roll evolutio

A randomised controlled trial of a complex intervention to reduce children’s exposure to secondhand smoke in the home

Objectives: Exposing children to secondhand tobacco smoke (SHS) causes significant harm and occurs predominantly through smoking by caregivers in the family home. We report a trial of a complex intervention designed to reduce secondhand smoke exposure of children whose primary caregiver feels unable or unwilling to quit smoking. Design: An open-label, parallel, randomised controlled trial. Setting: Deprived communities in Nottingham City and County, England Participants: Caregivers resident in Nottingham City and County in England who were at least 18 years old, the main caregiver of a child aged under 5 years living in their household, and reported that they were smoking tobacco inside their home. Interventions: We compared a complex intervention combining personalised feedback on home air quality, behavioural support and nicotine replacement therapy for temporary abstinence with usual care. Main outcomes: The primary outcome was change in air quality in the home, measured as average 16–24 hours levels of particulate matter of <2.5 µm diameter (PM2.5), between baseline and 12 weeks. Secondary outcomes included changes in maximum PM2.5, proportion of time PM2.5 exceeded WHO recommended levels of maximum exposure of 25 µg/mg3, child salivary cotinine, caregivers’ cigarette consumption, nicotine dependence, determination to stop smoking, quit attempts and quitting altogether during the intervention. Results: Geometric mean PM2.5 decreased significantly more (by 35.2%; 95% CI 12.7% to 51.9%) in intervention than in usual care households, as did the proportion of time PM2.5 exceeded 25 µg/mg3, child salivary cotinine concentrations, caregivers’ cigarette consumption in the home, nicotine dependence, determination to quit and likelihood of having made a quit attempt. Conclusions: By reducing exposure to SHS in the homes of children who live with smokers unable or unwilling to quit, this intervention offers huge potential to reduce children’s’ tobacco-related harm. Trial registration number ISRCTN81701383. This trial was funded by the UK National Institute for Health Research (NIHR): RP-PG-0608-10020 http://dx.doi.org/10.1136/tobaccocontrol-2016-05327

Cost-Effectiveness of Laparoscopic Hysterectomy With Morcellation Compared With Abdominal Hysterectomy for Presumed Myomas

Hysterectomy for presumed leiomyomata is one of the most common surgical procedures performed in non-pregnant women in the United States. Laparoscopic hysterectomy (LH) with morcellation is an appealing alternative to abdominal hysterectomy (AH), but may result in dissemination of malignant cells and worse outcomes in the setting of an occult leiomyosarcoma. We sought to evaluate the cost-effectiveness of LH versus AH

Melanocortin-4 receptor gene: case-control study and transmission disequilibrium test confirm that functionally relevant mutations are compatible with a major gene effect for extreme obesity

We initially performed a mutation screen of the coding region of the MC4R in 808 extremely obese children and adolescents and 327 underweight or normal-weight controls allowing for a case-control study. A total of 16 different missense, nonsense, and frameshift mutations were found in the obese study group; five of these have not been observed previously. In vitro assays revealed that nine [the haplotype (Y35X; D37V) was counted as one mutation] of the 16 mutations led to impaired cAMP responses, compared with wild-type receptor constructs. In contrast, only one novel missense mutation was detected in the controls, which did not alter receptor function. The association test based on functionally relevant mutations was positive (P = 0.006, Fisher's exact test, one-sided). We proceeded by screening a total of 1040 parents of 520 of the aforementioned obese young index patients to perform transmission disequilibrium tests. The 11 parental carriers of functionally relevant mutations transmitted the mutation in 81.8% (P = 0.033; exact one-sided McNemar test). These results support the hypothesis that these MC4R mutations represent major gene effects for obesity

E2F transcription factor-1 modulates expression of glutamine metabolic genes in mouse embryonic fibroblasts and uterine sarcoma cells

Metabolic reprogramming is considered as a hallmark of cancer and is clinically exploited as a novel target for therapy. The E2F transcription factor-1 (E2F1) regulates various cellular processes, including proliferative and metabolic pathways, and acts, depending on the cellular and molecular context, as an oncogene or tumor suppressor. The latter is evident by the observation that E2f1-knockout mice develop spontaneous tumors, including uterine sarcomas. This dual role warrants a detailed investigation of how E2F1 loss impacts metabolic pathways related to cancer progression. Our data indicate that E2F1 binds to the promoter of several glutamine metabolism-related genes. Interestingly, the expression of genes in the glutamine metabolic pathway were increased in mouse embryonic fibroblasts (MEFs) lacking E2F1. In addition, we confirm that E2f1 &lt;sup&gt;-/-&lt;/sup&gt; MEFs are more efficient in metabolizing glutamine and producing glutamine-derived precursors for proliferation. Mechanistically, we observe a co-occupancy of E2F1 and MYC on glutamine metabolic promoters, increased MYC binding after E2F1 depletion and that silencing of MYC decreased the expression of glutamine-related genes in E2f1 &lt;sup&gt;-/-&lt;/sup&gt; MEFs. Analyses of transcriptomic profiles in 29 different human cancers identified uterine sarcoma that showed a negative correlation between E2F1 and glutamine metabolic genes. CRISPR/Cas9 knockout of E2F1 in the uterine sarcoma cell line SK-UT-1 confirmed elevated glutamine metabolic gene expression, increased proliferation and increased MYC binding to glutamine-related promoters upon E2F1 loss. Together, our data suggest a crucial role of E2F1 in energy metabolism and metabolic adaptation in uterine sarcoma cells

Laparoscopic hysterectomy with morcellation vs abdominal hysterectomy for presumed fibroid tumors in premenopausal women: a decision analysis

To model outcomes in laparoscopic hysterectomy with morcellation compared to abdominal hysterectomy for the presumed fibroid uterus, examining short-and long-term complications, as well as mortality

The WiggleZ Dark Energy Survey: the transition to large-scale cosmic homogeneity

We have made the largest-volume measurement to date of the transition to large-scale homogeneity in the distribution of galaxies. We use the WiggleZ survey, a spectroscopic survey of over 200,000 blue galaxies in a cosmic volume of ~1 (Gpc/h)^3. A new method of defining the 'homogeneity scale' is presented, which is more robust than methods previously used in the literature, and which can be easily compared between different surveys. Due to the large cosmic depth of WiggleZ (up to z=1) we are able to make the first measurement of the transition to homogeneity over a range of cosmic epochs. The mean number of galaxies N(<r) in spheres of comoving radius r is proportional to r^3 within 1%, or equivalently the fractal dimension of the sample is within 1% of D_2=3, at radii larger than 71 \pm 8 Mpc/h at z~0.2, 70 \pm 5 Mpc/h at z~0.4, 81 \pm 5 Mpc/h at z~0.6, and 75 \pm 4 Mpc/h at z~0.8. We demonstrate the robustness of our results against selection function effects, using a LCDM N-body simulation and a suite of inhomogeneous fractal distributions. The results are in excellent agreement with both the LCDM N-body simulation and an analytical LCDM prediction. We can exclude a fractal distribution with fractal dimension below D_2=2.97 on scales from ~80 Mpc/h up to the largest scales probed by our measurement, ~300 Mpc/h, at 99.99% confidence.Comment: 21 pages, 16 figures, accepted for publication in MNRA

The Intriguing Effects of Substituents in the N-Phenethyl Moiety of Norhydromorphone: A Bifunctional Opioid from a Set of “Tail Wags Dog” Experiments

This work is licensed under a Creative Commons Attribution 4.0 International License.(−)-N-Phenethyl analogs of optically pure N-norhydromorphone were synthesized and pharmacologically evaluated in several in vitro assays (opioid receptor binding, stimulation of [35S]GTPγS binding, forskolin-induced cAMP accumulation assay, and MOR-mediated β-arrestin recruitment assays). “Body” and “tail” interactions with opioid receptors (a subset of Portoghese’s message-address theory) were used for molecular modeling and simulations, where the “address” can be considered the “body” of the hydromorphone molecule and the “message” delivered by the substituent (tail) on the aromatic ring of the N-phenethyl moiety. One compound, N-p-chloro-phenethynorhydromorphone ((7aR,12bS)-3-(4-chlorophenethyl)-9-hydroxy-2,3,4,4a,5,6-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one, 2i), was found to have nanomolar binding affinity at MOR and DOR. It was a potent partial agonist at MOR and a full potent agonist at DOR with a δ/μ potency ratio of 1.2 in the ([35S]GTPγS) assay. Bifunctional opioids that interact with MOR and DOR, the latter as agonists or antagonists, have been reported to have fewer side-effects than MOR agonists. The p-chlorophenethyl compound 2i was evaluated for its effect on respiration in both mice and squirrel monkeys. Compound 2i did not depress respiration (using normal air) in mice or squirrel monkeys. However, under conditions of hypercapnia (using air mixed with 5% CO2), respiration was depressed in squirrel monkeys.NIDA grant P30 DA13429NIDA grant DA039997NIDA grant DA018151NIDA grant DA035857NIDA grant DA047574NIH Intramural Research Programs of the National Institute on Drug AbuseNational Institute of Alcohol Abuse and AlcoholismNIH Intramural Research Programs of the National Institute on Drug AbuseNIH Intramural Research Program through the Center for Information TechnologyNIH Intramural Research Programs of the National Institute on Drug Abus