Classification of a supersolid: Trial wavefunctions, Symmetry breakings and Excitation spectra

A state of matter is characterized by its symmetry breaking and elementary excitations. A supersolid is a state which breaks both translational symmetry and internal $U(1)$ symmetry. Here, we review some past and recent works in phenomenological Ginsburg-Landau theories, ground state trial wavefunctions and microscopic numerical calculations. We also write down a new effective supersolid Hamiltonian on a lattice. The eigenstates of the Hamiltonian contains both the ground state wavefunction and all the excited states (supersolidon) wavefunctions. We contrast various kinds of supersolids in both continuous systems and on lattices, both condensed matter and cold atom systems. We provide additional new insights in studying their order parameters, symmetry breaking patterns, the excitation spectra and detection methods.Comment: REVTEX4, 19 pages, 3 figure

Trispecific antibody targeting HIV-1 and T cells activates and eliminates latently-infected cells in HIV/SHIV infections.

Agents that can simultaneously activate latent HIV, increase immune activation and enhance the killing of latently-infected cells represent promising approaches for HIV cure. Here, we develop and evaluate a trispecific antibody (Ab), N6/αCD3-αCD28, that targets three independent proteins: (1) the HIV envelope via the broadly reactive CD4-binding site Ab, N6; (2) the T cell antigen CD3; and (3) the co-stimulatory molecule CD28. We find that the trispecific significantly increases antigen-specific T-cell activation and cytokine release in both CD4 <sup>+</sup> and CD8 <sup>+</sup> T cells. Co-culturing CD4 <sup>+</sup> with autologous CD8 <sup>+</sup> T cells from ART-suppressed HIV <sup>+</sup> donors with N6/αCD3-αCD28, results in activation of latently-infected cells and their elimination by activated CD8 <sup>+</sup> T cells. This trispecific antibody mediates CD4 <sup>+</sup> and CD8 <sup>+</sup> T-cell activation in non-human primates and is well tolerated in vivo. This HIV-directed antibody therefore merits further development as a potential intervention for the eradication of latent HIV infection

Effects of pregnancy on the pharmacokinetics of metformin

This study's primary objective was to fully characterize the pharmacokinetics of metformin in pregnant women with gestational diabetes mellitus (GDM) versus nonpregnant controls. Steady-state oral metformin pharmacokinetics in pregnant women with GDM receiving either metformin monotherapy (n 5 24) or a combination with glyburide (n 5 30) as well as in nonpregnant women with type 2 diabetes mellitus (T2DM) (n 5 24) were determined utilizing non-compartmental techniques. Maternal and umbilical cord blood samples were collected at delivery from 38 women. With both 500- and 1000-mg doses, metformin bioavailability, volume of distribution beta (Vb), clearance, and renal clearance were significantly increased during pregnancy. In addition, in the women receiving metformin 500 mg, significantly higher metformin apparent oral clearance (CL/F) (27%), weight-adjusted renal secretion clearance (64%), and apparent oral volume of distribution beta (Vb/F) (33%) were seen during pregnancy. Creatinine clearance was significantly higher during pregnancy. Increasing metformin dose from 500 to 1000 mg orally twice daily significantly increased Vb/F by 28%, weight-adjusted Vb/F by 32% and CL/F by 25%, and weight-adjusted CL/F by 28% during pregnancy. Mean metformin umbilical cord arterial-to-venous plasma concentration ratio was 1.0 6 0.1, venous umbilical cord-to-maternal concentration ratio was 1.4 6 0.5, and arterial umbilical cord-to-maternal concentration ratio was 1.5 6 0.5. Systemic exposure after a 500-mg dose of metformin was lower during pregnancy compared with the nonpregnant women with T2DM. However, in patients receiving metformin 1000 mg, changes in estimated bioavailability during pregnancy offset the changes in clearance leading to no significant change in CL/F with the higher dose. SIGNIFICANCE STATEMENT Gestational diabetes mellitus complicates 5%-13% of pregnancies and is often treated with metformin. Pregnant women undergo physiological changes that alter drug disposition. Preliminary data suggest that pregnancy lowers metformin concentrations, potentially affecting efficacy and safety. This study definitively describes pregnancy's effects on metformin pharmacokinetics and expands the mechanistic understanding of pharmacokinetic changes across the dosage range. Here we report the nonlinearity of metformin pharmacokinetics and the increase in bioavailability, clearance, renal clearance, and volume of distribution during pregnancy

Pharmacodynamics of Glyburide, Metformin, and Glyburide/Metformin Combination Therapy in the Treatment of Gestational Diabetes Mellitus

In gestational diabetes mellitus (GDM), women are unable to compensate for the increased insulin resistance during pregnancy. Data are limited regarding the pharmacodynamic effects of metformin and glyburide during pregnancy. This study characterized insulin sensitivity (SI), β-cell responsivity, and disposition index (DI) in women with GDM utilizing a mixed-meal tolerance test (MMTT) before and during treatment with glyburide monotherapy (GLY, n = 38), metformin monotherapy (MET, n = 34), or GLY and MET combination therapy (COMBO; n = 36). GLY significantly decreased dynamic β-cell responsivity (31%). MET and COMBO significantly increased SI (121% and 83%, respectively). Whereas GLY, MET, and COMBO improved DI, metformin (MET and COMBO) demonstrated a larger increase in DI (P = 0.05) and a larger decrease in MMTT peak glucose concentrations (P = 0.03) than subjects taking only GLY. Maximizing SI with MET followed by increasing β-cell responsivity with GLY or supplementing with insulin might be a more optimal strategy for GDM management than monotherapy

Pharmacodynamics of Metformin in Pregnant Women With Gestational Diabetes Mellitus and Nonpregnant Women With Type 2 Diabetes Mellitus

Gestational diabetes mellitus is a condition similar to type 2 diabetes mellitus (T2DM) in that patients are unable to compensate for the degree of insulin resistance, and both conditions are often treated with metformin. The comparative pharmacodynamic response to metformin in these 2 populations has not been studied. This study characterized insulin sensitivity, β-cell responsivity, and disposition index following a mixed-meal tolerance test utilizing a minimal model of glucose, insulin, and C-peptide kinetics before and during treatment with metformin. The study included women with gestational diabetes mellitus (n = 34), T2DM (n = 14), and healthy pregnant women (n = 30). Before treatment, the gestational diabetes mellitus group had significantly higher baseline (45%), dynamic (68%), static (71%), and total β-cell responsivity (71%) than the T2DM group. Metformin significantly increased insulin sensitivity (51%) as well as disposition index (97%) and decreased mixed-meal tolerance test peak glucose concentrations (8%) in women with gestational diabetes mellitus after adjustment for gestational age–dependent effects; however, in women with T2DM metformin only significantly affected peak glucose concentrations (22%) and had no significant effect on any other parameters. Metformin had a greater effect on the change in disposition index (Δ disposition index) in women with gestational diabetes mellitus than in those with T2DM (P =.01). In conclusion, response to metformin in women with gestational diabetes mellitus is significantly different from that in women with T2DM, which is likely related to the differences in disease severity

Influence of increasing populations of Double-crested Cormorants on soil nutrient characteristics of nesting islands in western Lake Erie

Animals can influence the structure of an ecosystem by changing the levels of nutrient input. This is of particular importance for the islands of western Lake Erie, which are relatively nutrient poor, but have experienced increases in nutrient input from growing double-crested cormorant (Phalacrocorax auritus) populations. The objectives of this study were to evaluate changes in soil characteristics (nutrients [nitrate (NO 3), total P], pH, and δ 13C [as a tracer of cormorant-associated nutrients]) across a gradient of cormorant nest density on two islands (Middle and East Sister) in western Lake Erie. For both islands, soil pH decreased and P concentrations increased with nest density. On Middle Island, soil nitrate concentrations increased with cormorant nest density, and varied with breeding phen

Examining provider perceptions and practices for comprehensive geriatric assessment among cancer survivors: a qualitative study with an implementation science focus

Introduction: Cancer rates increase with age, and older cancer survivors have unique medical care needs, making assessment of health status and identification of appropriate supportive resources key to delivery of optimal cancer care. Comprehensive geriatric assessments (CGAs) help determine an older person’s functional capabilities as cancer care providers plan treatment and follow-up care. Despite its proven utility, research on implementation of CGA is lacking. Methods: Guided by a qualitative description approach and through interviews with primary care providers and oncologists, our goal was to better understand barriers and facilitators of CGA use and identify training and support needs for implementation. Participants were identified through Cancer Prevention and Control Research Network partner listservs and a national cancer and aging organization. Potential interviewees, contacted via email, were provided with a description of the study purpose. Eight semi-structured interviews were conducted via Zoom, recorded, and transcribed verbatim by a professional transcription service. The interview guide explored providers’ knowledge and use of CGAs. For codebook development, three representative transcripts were independently reviewed and coded by four team members. The interpretive process involved reflecting, transcribing, coding, and searching for and identifying themes. Results: Providers shared that, while it would be ideal to administer CGAs with all new patients, they were not always able to do this. Instead, they used brief screening tools or portions of CGAs, or both. There was variability in how CGA domains were assessed; however, all considered CGAs useful and they communicated with patients about their benefits. Identified facilitators of implementation included having clinic champions, an interdisciplinary care team to assist with implementation and referrals for intervention, and institutional resources and buy-in. Barriers noted included limited staff capacity and competing demands on time, provider inexperience, and misaligned institutional priorities. Discussion: Findings can guide solutions for improving the broader and more systematic use of CGAs in the care of older cancer patients. Uptake of processes like CGA to better identify those at risk of poor outcomes and intervening early to modify treatments are critical to maximize the health of the growing population of older cancer survivors living through and beyond their disease. Copyright © 2023 Seaman, Rowland, Werts, Tam, Torres, Hucek, Wickersham, Fairman, Patel, Thomson, Hebert and Friedman.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Polymethylene-interrupted fatty acids: Biomarkers for native and exotic mussels in the Laurentian Great Lakes

Freshwater organisms synthesize a wide variety of fatty acids (FAs); however, the ability to synthesize and/or subsequently modify a particular FA is not universal, making it possible to use certain FAs as biomarkers. Herein we document the occurrence of unusual FAs (polymethylene-interrupted fatty acids; PMI-FAs) in select freshwater organisms in the Laurentian Great Lakes. We did not detect PMI-FAs in: (a) natural seston from Lake Erie and Hamilton Harbor (Lake Ontario), (b) various species of laboratory-cultured algae including a green alga (Scenedesmus obliquus), two cyanobacteria (Aphanizomenon flos-aquae and Synechococystis sp.), two diatoms (Asterionella formosa, Diatoma elongatum) and a chrysophyte (Dinobryon cylindricum) or, (c) zooplankton (Daphnia spp., calanoid or cyclopoid copepods) from Lake Ontario, suggesting that PMI-FAs are not substantively incorporated into consumers at the phytoplankton-zooplankton interface. However, these unusual FAs comprised 4-6% of total fatty acids (on a dry tissue weight basis) of native fat mucket (Lampsilis siliquoidea) and plain pocketbook (L. cardium) mussels and in invasive zebra (Dreissena polymorpha) and quagga (D. bugensis) mussels. We were able to clearly partition Great Lakes' mussels into three separate groups (zebra, quagga, and native mussels) based solely on their PMI-FA profiles. We also provide evidence for the trophic transfer of PMI-FAs from mussels to various fishes in Lakes Ontario and Michigan, further underlining the potential usefulness of PMI-FAs for tracking the dietary contribution of mollusks in food web and contaminant-fate studies