Wigner Glass, Spin-liquids, and the Metal-Insulator Transition

Recent experiments on the two dimensional electron gas in various semiconductor devices have revealed an unexpected metal-insulator transition and have challenged the previously held assumption that there is no such transition in two dimensions. While the experiments are still at the stage of rapid development, it is becoming evident that they cannot be understood from the conventional perspective of weak interactions. In the present paper, we propose the following. (1) The low-density insulating state is the Wigner Glass, a phase with quasi-long-range translational order and competing ferromagnetic and antiferromagnetic spin-exchange interactions. (2) The transition is the melting of this Wigner Glass, disorder being the agent allowing the transition to be second order. (3) Within the Wigner Glass phase, there are at least two, distinct magnetic ground-states, a ferromagnetic state at very low electron density and a spin-liquid state with a spin pseudo-gap at higher densities. (4) The metallic side of the transition is a non-Fermi liquid. These conclusions are encapsulated in Figure 1 which presents the proposed phase diagram as a function of disorder strength and density; we also suggest experimental signatures of the various phases and transitions.Comment: Revised manuscript 6 pages, 1 figure redrawn for clarity; discussion of experiments expande

The insulin polymorphism -23Hph increases the risk for type 1 diabetes mellitus in the Romanian population

The insulin -23Hph and IGF2 Apa polymorphisms were genotyped in Romanian patients with T1DM (n = 204), T2DM (n = 215) or obesity (n = 200) and normoponderal healthy subjects (n = 750). The genotypes of both polymorphisms were distributed in concordance with Hardy-Weinberg equilibrium in all groups. The -23Hph AA genotype increased the risk for T1DM (OR: 3.22, 95%CI: 2.09-4.98, p < 0,0001), especially in patients without macroalbuminuria (OR: 4.32, 95%CI: 2.54-7.45, p < 0,0001). No other significant association between the alleles or genotypes of insulin -23Hph and IGF2 Apa and diabetes or obesity was identified

Efficacy and Safety of Lacosamide in Painful Diabetic Neuropathy

OBJECTIVE: To evaluate efficacy and safety of lacosamide compared with placebo in painful diabetic polyneuropathy. RESEARCH DESIGN AND METHODS: Diabetic patients with at least moderate neuropathic pain were randomized to placebo or lacosamide 400 (in a slow or standard titration) or 600 mg/day over 6-week titration and 12-week maintenance periods. Primary efficacy criterion was intra-individual change in average daily Numeric Pain Rating Scale score from baseline to the last 4 weeks. RESULTS: For the primary end point, pain reduction was numerically but not statistically greater with lacosamide compared with placebo (400 mg/day, P = 0.12; 600 mg/day, P = 0.18). Both doses were significantly more effective compared with placebo over the titration (P = 0.03, P = 0.006), maintenance (P = 0.01, P = 0.005), and entire treatment periods (P = 0.03, P = 0.02). Safety profiles between titration schemes were similar. CONCLUSIONS: Lacosamide reduced neuropathic pain and was well tolerated in diabetic patients, but the primary efficacy criterion was not met, possibly due to an increased placebo response over the last 4 weeks.status: publishe

Prepackaged therapy for urethritis: the "MSTOP" experience in Cameroon

RATIONALE: The social marketing of STD treatment may be a strategy to increase the availability of effective therapy for urethritis in male patients. OBJECTIVE: To evaluate a pilot project of social marketing of urethritis treatment packages. The project, initially designed for over the counter sale in private pharmacies, was finally restricted by national health authorities to primary healthcare settings in Yaounde and Douala, Cameroon. METHODS: Monthly sales of packages containing antibiotics, condoms, partner referral cards, and written information on STDs were monitored by the social marketing agency. Structured interviews were conducted with a sample of traceable patients who had consulted for urethritis. Structured interviews completed by focus group discussions were conducted among healthcare providers. Interview findings were further validated by a "mystery patient" survey, using surrogate patients. Lastly, 15 key informants among the decision markers involved in the project were interviewed in depth. Local independent consultants carried out the whole evaluation. RESULTS: A total of 1392 treatment packages were sold in 10 months. Patients who had purchased the package reported high compliance with the treatment, with 99% taking the single dose of cefuroxime-axetil and 83% completing the course of doxycycline. 76% notified all or some partners, and 84% of those who had sex during treatment used condoms. In contrast, only 27% of trained healthcare providers prescribed "MSTOP". They questioned the omission of laboratory diagnosis, the selection of antibiotics, and the duration of therapy. Public health authorities were also sceptical about the choice of antibiotics and viewed the initial project as an overt encouragement of self medication. CONCLUSIONS: Although the MSTOP project was not implemented in the way it had initially been designed, it highlighted the patients' interest in the product. Public health authorities in Cameroon should have been made aware of the limitations of the formal sector's response to STD care among men before over the counter sale of prepackaged therapy could have been considered as an alternative approach to inadequate self medication. 



Endoplasmic Reticulum Chaperone Glucose-Regulated Protein 94 Is Essential for Proinsulin Handling

Although endoplasmic reticulum (ER) chaperone binding to mutant proinsulin has been reported, the role of protein chaperones in the handling of wild-type proinsulin is underinvestigated. Here, we have explored the importance of glucose-regulated protein 94 (GRP94), a prominent ER chaperone known to fold insulin-like growth factors, in proinsulin handling within b-cells. We found that GRP94 coimmunoprecipitated with proinsulin and that inhibition of GRP94 function and/or expression reduced glucose-dependent insulin secretion, shortened proinsulin half-life, and lowered intracellular proinsulin and insulin levels. This phenotype was accompanied by post-ER proinsulin misprocessing and higher numbers of enlarged insulin granules that contained amorphic material with reduced immunogold staining for mature insulin. Insulin granule exocytosis was accelerated twofold, but the secreted insulin had diminished bioactivity. Moreover, GRP94 knockdown or knockout in b-cells selectively activated protein kinase R–like endoplasmic reticulum kinase (PERK), without increasing apoptosis levels. Finally, GRP94 mRNA was overexpressed in islets from patients with type 2 diabetes. We conclude that GRP94 is a chaperone crucial for proinsulin handling and insulin secretion.Fil: Ghiasi, Seyed Mojtaba. Universidad de Copenhagen; DinamarcaFil: Dahlby, Tina. Universidad de Copenhagen; DinamarcaFil: Andersen, Caroline Hede. Universidad de Copenhagen; DinamarcaFil: Haataja, Leena. University of Michigan; Estados UnidosFil: Petersen, Sólrun. Universidad de Copenhagen; DinamarcaFil: Omar-Hmeadi, Muhmmad. Uppsala Universitet; SueciaFil: Yang, Mingyu. Uppsala Universitet; SueciaFil: Pihl, Celina. Universidad de Copenhagen; DinamarcaFil: Bresson, Sophie Emilie. Universidad de Copenhagen; DinamarcaFil: Khilji, Muhammad Saad. Universidad de Copenhagen; DinamarcaFil: Klindt, Kristian. Universidad de Copenhagen; DinamarcaFil: Cheta, Oana. Universidad de Copenhagen; DinamarcaFil: Perone, Marcelo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina. Universidad de Copenhagen; DinamarcaFil: Tyrberg, Björn. Astrazeneca. IMED Biotech Unit; SueciaFil: Prats, Clara. Universidad de Copenhagen; DinamarcaFil: Barg, Sebastian. Uppsala Universitet; SueciaFil: Tengholm, Anders. Uppsala Universitet; SueciaFil: Arvan, Peter. University of Michigan; Estados UnidosFil: Mandrup-Poulsen, Thomas. Universidad de Copenhagen; DinamarcaFil: Marzec, Michal Tomasz. Universidad de Copenhagen; Dinamarc