Experimental quantum speed-up in reinforcement learning agents.

As the field of artificial intelligence advances, the demand for algorithms that can learn quickly and efficiently increases. An important paradigm within artificial intelligence is reinforcement learning1, where decision-making entities called agents interact with environments and learn by updating their behaviour on the basis of the obtained feedback. The crucial question for practical applications is how fast agents learn2. Although various studies have made use of quantum mechanics to speed up the agent's decision-making process3,4, a reduction in learning time has not yet been demonstrated. Here we present a reinforcement learning experiment in which the learning process of an agent is sped up by using a quantum communication channel with the environment. We further show that combining this scenario with classical communication enables the evaluation of this improvement and allows optimal control of the learning progress. We implement this learning protocol on a compact and fully tunable integrated nanophotonic processor. The device interfaces with telecommunication-wavelength photons and features a fast active-feedback mechanism, demonstrating the agent's systematic quantum advantage in a setup that could readily be integrated within future large-scale quantum communication networks.

Projecting boreal bird responses to climate change: the signal exceeds the noise.

For climate change projections to be useful, the magnitude of change must be understood relative to the magnitude of uncertainty in model predictions. We quantified the signal-to-noise ratio in projected distributional responses of boreal birds to climate change, and compared sources of uncertainty. Boosted regression tree models of abundance were generated for 80 boreal-breeding bird species using a comprehensive data set of standardized avian point counts (349,629 surveys at 122,202 unique locations) and 4-km climate, land use, and topographic data. For projected changes in abundance, we calculated signal-to-noise ratios and examined variance components related to choice of global climate model (GCM) and two sources of species distribution model (SDM) uncertainty: sampling error and variable selection. We also evaluated spatial, temporal, and interspecific variation in these sources of uncertainty. The mean signal-to-noise ratio across species increased over time to 2.87 by the end of the 21st century, with the signal greater than the noise for 88% of species. Across species, climate change represented the largest component (0.44) of variance in projected abundance change. Among sources of uncertainty evaluated, choice of GCM (mean variance component = 0.17) was most important for 66% of species, sampling error (mean= 0.12) for 29% of species, and variable selection (mean =0.05) for 5% of species. Increasing the number of GCMs from four to 19 had minor effects on these results. The range of projected changes and uncertainty characteristics across species differed markedly, reinforcing the individuality of species' responses to climate change and the challenges of one-size-fits-all approaches to climate change adaptation. We discuss the usefulness of different conservation approaches depending on the strength of the climate change signal relative to the noise, as well as the dominant source of prediction uncertainty.

Reducing mitochondrial fission results in increased life span and fitness of two fungal ageing models.

Ageing of biological systems is accompanied by alterations in mitochondrial morphology, including a transformation from networks and filaments to punctuate units. The significance of these alterations with regard to ageing is not known. Here, we demonstrate that the dynamin-related protein 1 (Dnm1p), a mitochondrial fission protein conserved from yeast to humans, affects ageing in the two model systems we studied, Podospora anserina and Saccharomyces cerevisiae. Deletion of the Dnm1 gene delays the transformation of filamentous to punctuate mitochondria and retards ageing without impairing fitness and fertility typically observed in long-lived mutants. Our data further suggest that reduced mitochondrial fission extends life span by increasing cellular resistance to the induction of apoptosis and links mitochondrial dynamics, apoptosis and life-span control.

Evolution of the magnetic structure in CeCu(5.5)Au(0.5) under pressure towards quantum criticality.

In the prototypical heavy-fermion system CeCu(6-x)Au(x), a magnetic quantum critical point can be tuned by Au concentration x, hydrostatic pressure p, or magnetic field B. A striking equivalence of the tuning behavior with x or p had been found with respect to thermodynamic and transport properties. By means of elastic neutron scattering on single crystalline CeCu(5.5)Au(0.5), we demonstrate this x-p equivalence on a microscopic level by showing that the magnetic ordering wave vector q(m) can be tuned accordingly. At ambient pressure,CeCu(5.5)Au(0.5) orders at q(m)≈(0.59 0 0). Upon applying p=4.1 kbar, q(m)≈(0.61 0 0.21) is found corresponding to CeCu(5.6)Au(0.4) at ambient pressure. The transition seems to occur in a first-order fashion and to be governed by slight changes in the nesting properties of the Fermi surface.

Medical graphics to improve patient understanding and anxiety in elderly and cognitively impaired patients scheduled for transcatheter aortic valve implantation (TAVI).

BACKGROUND: Anxiety and limited patient comprehension may pose significant barriers when informing elderly patients about complex procedures such as transcatheter aortic valve implantation (TAVI). OBJECTIVES: We aimed to evaluate the utility of medical graphics to improve the patient informed consent (IC) before TAVI. METHODS: In this prospective, randomized dual center study, 301 patients were assigned to a patient brochure containing medical graphics (Comic group, n = 153) or sham information (Control group, n = 148) on top of usual IC. Primary outcomes were patient understanding of central IC-related aspects and periprocedural anxiety assessed by the validated Spielberger State Trait Anxiety Inventory (STAI), both analyzed by cognitive status according to the Montreal Cognitive Assessment (MoCA). RESULTS: Patient understanding was significantly higher in the Comic group [mean number of correct answers 12.8 (SD 1.2) vs. 11.3 (1.8); mean difference 1.5 (95% CI 1.2-1.8); p < 0.001]. This effect was more pronounced in the presence of cognitive dysfunction (MoCA < 26) [12.6 (1.2) in the Comic vs. 10.9 (1.6) in the Control group; mean difference 1.8 (1.4-2.2), p < 0.001]. Mean STAI score declined by 5.7 (95% CI 5.1-6.3; p < 0.001) in the Comic and 0.8 points (0.2-1.4; p = 0.015) in the Control group. Finally, mean STAI score decreased in the Comic group by 4.7 (3.8-5.6) in cognitively impaired patients and by 6.6 (95% CI 5.8 to 7.5) in patients with normal cognitive function (p < 0.001 each). CONCLUSIONS: Our results prove beneficial effects for using medical graphics to inform elderly patients about TAVI by improving patient understanding and reducing periprocedural anxiety (DRKS00021661; 23/Oct/2020). Medical graphics entailed significant beneficial effects on the primary endpoints, patient understanding and periprocedural anxiety, compared to the usual patient informed consent (IC) procedure. Patient understanding of IC-related aspects was significantly higher in the Comic group, with a more pronounced benefit in patients with cognitive impairment (p for IC method and cognitive status < 0.001, respectively; p for IC method x MoCA category interaction = 0.017). There further was a significant decline of periprocedural anxiety in patients with and without cognitive impairment (p for IC method x measuring time point < 0.001; p for IC method x MoCA category x measuring time point interaction = 0.018).

Informed Consent before coronary angiography and percutaneous coronary intervention from the patient's perspective: A picture is worth a thousand words.

Background: Patients scheduled for coronary angiography may feel insufficiently informed about the planned procedure. We aimed to evaluate the patient-rated quality of the Informed Consent (IC) process and to investigate the efficacy of medical graphics to assist and improve the IC procedure. Methods: A graphic-based information broschure illustrating central steps of the procedure was created in collaboration with scientific illustrators. In a randomized, controlled, prospective trial, 121 patients undergoing coronary angiography/PCI were randomized to a group obtaining the usual IC (Control group) or to a group that additionally obtained a graphic-based IC (Comic group). The perceived quality of the IC was compared between groups using single items of the Client Satisfaction Questionnaire-8 and self-designed single items. Results: Only 67.8% of patients stated to have completely read the standard written IC sheet. The quality of the IC was perceived to be very good in 45.0% of patients in the Comic group compared to 24.6% in the Control group (p =.023). 57.4% of the Control group compared to 76.7% of the Comic group stated that all of their questions were satisfactorily adressed (p =.015). 43.3% of the Comic group, in contrast to only 18.0% of the Control group, declared to feel "very satisfied" with the obtained IC procedure (p =.002). The acceptance of this new IC approach was very high: no patient expressed feelings of not being taken seriously when reading medical graphics. Conclusions: Our data confirm pronounced limitations of the usual IC practice. The use of medical graphics positively impacts on patient-evaluated endpoints and may significantly improve the IC procedure.

Magnetic blue phase in the chiral itinerant magnet MnSi.

Chiral nematic liquid crystals sometimes form blue phases characterized by spirals twisting in different directions. By combining model calculations with neutron-scattering experiments, we show that the magnetic analogue of blue phases does form in the chiral itinerant magnet MnSi in a large part of the phase diagram. The properties of this blue phase explain a number of previously reported puzzling features of MnSi such as partial magnetic order and a two-component specific-heat and thermal-expansion anomaly at the magnetic transition.

Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin action.

The regulation of body weight and composition involves input from genes and the environment, demonstrated, for example, by the variable susceptibility of inbred strains of mice to obesity when offered a high-fat diet. The identification of the gene responsible for obesity in the ob/ob mouse provides a new approach to defining links between diet and genetics in the regulation of body weight. The ob gene protein product, leptin, is an adipocyte-derived circulating protein. Administration of recombinant leptin reduces food intake and increases energy expenditure in ob/ob mice, suggesting that it signals to the brain the magnitude of fat stores. Information on the regulation of this protein is limited. In several rodent models of obesity including db/db, fa/fa, yellow (Ay/a) VMH-lesioned, and those induced by gold thioglucose, monosodium glutamate, and transgenic ablation of brown adipose tissue, leptin mRNA expression and the level of circulating leptin are increased, suggesting resistance to one or more of its actions. We have assessed the impact of increased dietary fat on circulating leptin levels in normal FVB mice and FVB mice with transgene-induced ablation of brown adipose tissue. We find that high-fat diet evokes a sustained increase in circulating leptin in both normal and transgenic mice, with leptin levels accurately reflecting the amount of body lipid across a broad range of body fat. However, despite increased leptin levels, animals fed a high-fat diet became obese without decreasing their caloric intake, suggesting that a high content of dietary fat changes the 'set point' for body weight, at least in part by limiting the action of leptin.

[Interhospital transport of intensive care patients in Lower Saxony : statewide need-based and effective management]. / Intensivverlegung in Niedersachsen : Landesweite bedarfsgerechte und effektive Sicherstellung.

BACKGROUND: Since 2007 interhospital transport of intensive care patients in Lower Saxony appertains to the performance requirements of emergency medical services. Against this background the Working Group for Evaluation of Intensive Care Transport (Arbeitsgemeinschaft Evaluation Intensivverlegung) was established. This group formulated standardized definitions for the requirements of intensive care transport vehicles and a federal statewide monitoring of intensive care transport was implemented to analyze if simultaneously on-call intensive care transport systems (intensive care helicopter and ground based mobile intensive care units) can be deployed need-based and efficiently. METHODS: A prospective follow-up study and evaluation of intensive care transport in Lower Saxony between April 1(st) 2008 and July 31(st) 2010 was carried out. RESULTS: A total of 6,779 data records were evaluated in this study of which 4,941 (72.9%) missions were located in Lower Saxony, 2,928 (43.2%) missions were carried out by helicopters and 3,851 (56.8%) by ground based mobile intensive care units. The mean duration of a mission was 3 h 59min±2 h 25 min, 4 h 39 min±2 h 23 min by ground based mobile intensive care units and 2 h 21 in±30 min by helicopter units. All systems proved to be feasible for intensive care transport. The degree of urgency was estimated correctly in 94.8% of the evaluated missions and 58.0% of the transfers could not be deployed. In 76.8% patients were transferred to hospitals with a higher level of medical care, 51.7% of patients were transferred for intensive care therapy and 40.4% for an operation/intervention. Of the patients 38.2% required mechanical ventilation and in 48.3% invasive monitoring was carried out. CONCLUSION: Interhospital transfer of intensive care patients can be carried out need-based with a limited number of intensive care transport vehicles if the missions are deployed effectively by standardized disposition in accordance with performance requirements.

Quantum-accessible reinforcement learning beyond strictly epochal environments.

In recent years, quantum-enhanced machine learning has emerged as a particularly fruitful application of quantum algorithms, covering aspects of supervised, unsupervised and reinforcement learning. Reinforcement learning offers numerous options of how quantum theory can be applied, and is arguably the least explored, from a quantum perspective. Here, an agent explores an environment and tries to find a behavior optimizing some figure of merit. Some of the first approaches investigated settings where this exploration can be sped-up, by considering quantum analogs of classical environments, which can then be queried in superposition. If the environments have a strict periodic structure in time (i.e. are strictly episodic), such environments can be effectively converted to conventional oracles encountered in quantum information. However, in general environments, we obtain scenarios that generalize standard oracle tasks. In this work, we consider one such generalization, where the environment is not strictly episodic, which is mapped to an oracle identification setting with a changing oracle. We analyze this case and show that standard amplitude-amplification techniques can, with minor modifications, still be applied to achieve quadratic speed-ups. In addition, we prove that an algorithm based on Grover iterations is optimal for oracle identification even if the oracle changes over time in a way that the "rewarded space" is monotonically increasing. This result constitutes one of the first generalizations of quantum-accessible reinforcement learning.

Requirements for hyaluronic acid binding by CD44: a role for the cytoplasmic domain and activation by antibody.

The CD44-negative T lymphoma AKR1 (CD44.2 genotype) was transfected with a CD44.1 cDNA. The intact cDNA conferred on the transfected cells the ability to bind hyaluronic acid (HA) both from solution and immobilized on culture plates. It also conferred a CD44-dependent and hyaluronidase-sensitive increase in adhesion to a lymph node endothelial cell line. A mutant cDNA which codes for a CD44 molecule lacking most of the cytoplasmic domain of CD44 was also transfected into AKR1, and cell sorting was used to select transfectants expressing levels of cell surface CD44 expression comparable with the line transfected with the wild-type CD44 cDNA. The cells transfected with the mutant construct bound fluoresceinated HA from solution very poorly, but did adhere to immobilized HA, though less well than cells transfected with the wild-type construct. This result indicates that the cytoplasmic domain of CD44 is necessary for binding of HA from solution but is not required for binding to immobilized HA, although it may contribute to adhesion following ligand recognition. A monoclonal antibody (mAb), IRAWB 14, which reacts with CD44 on all CD44+ cells dramatically induced HA binding by some CD44+ cell lines that did not constitutively bind HA. The transfectant expressing a CD44 molecule with a truncated cytoplasmic domain could be induced by this antibody to bind fluoresceinated-HA from solution. Splenic T cells did not bind fluoresceinated HA constitutively. In the presence of the IRAWB 14 mAb, virtually all CD44+ splenic T cells bound HA. Induction was immediate and occurred equally well at room temperature and at 4 degrees C, indicating that the new HA-binding activity was due to preexistent CD44 molecules. These results are compatible with an antibody-induced activation of CD44 by either a conformational change in the CD44 molecule or a change in the distribution of CD44 molecules on the cell surface.

P-selectin glycoprotein ligand-1 (PSGL-1) on T helper 1 but not on T helper 2 cells binds to P-selectin and supports migration into inflamed skin.

We have shown recently that mouse Th1 cells but not Th2 cells are selectively recruited into inflamed sites of a delayed-type hypersensitivity (DTH) reaction of the skin. This migration was blocked by monoclonal antibodies (mAb) against P- and E-selectin. Here we show that Th1 cells bind to P-selectin via the P-selectin glycoprotein ligand-1 (PSGL-1). This is the only glycoprotein ligand that was detectable by affinity isolation with a P-selectin-Ig fusion protein. Binding of Th1 cells to P-selectin, as analyzed by flow cytometry and in cell adhesion assays, was completely blocked by antibodies against PSGL-1. The same antibodies blocked partially the migration of Th1 cells into cutaneous DTH reactions. This blocking activity, in combination with that of a mAb against E-selectin, was additive. PSGL-1 on Th2 cells, although expressed at similar levels as on Th1 cells, did not support binding to P-selectin. Thus, the P-selectin-binding form of PSGL-1 distinguishes Th1 cells from Th2 cells. Furthermore, PSGL-1 is relevant for the entry of Th1 cells into inflamed areas of the skin. This is the first demonstration for the importance of PSGL-1 for mouse leukocyte recruitment in vivo.

Lymphocyte migration in lymphocyte function-associated antigen (LFA)-1-deficient mice.

Using lymphocyte function-associated antigen (LFA)-1(-/-) mice, we have examined the role of LFA-1 and other integrins in the recirculation of lymphocytes. LFA-1 has a key role in migration to peripheral lymph nodes (pLNs), and influences migration into other LNs. Second, the alpha4 integrins, alpha4beta7 and alpha4beta1, have a hitherto unrecognized ability to compensate for the lack of LFA-1 in migration to pLNs. These findings are confirmed using normal mice and blocking LFA-1 and alpha4 monoclonal antibodies. Unexpectedly, vascular cell adhesion molecule (VCAM)-1, which is essential in inflammatory responses, serves as the ligand for the alpha4 integrins on pLN high endothelial venules. VCAM-1 also participates in trafficking into mesenteric LNs and Peyer's patch nodes where mucosal addressin cell adhesion molecule 1 (MAdCAM-1), the alpha4beta7-specific ligand, dominates. Both alpha4beta1, interacting with ligand VCAM-1, and also LFA-1 participate in substantial lymphocyte recirculation through bone marrow. These observations suggest that organ-specific adhesion receptor usage in mature lymphocyte recirculation is not as rigidly adhered to as previously considered, and that the same basic sets of adhesion receptors are used in both lymphocyte homing and inflammatory responses.

The -174G>C IL-6 gene promoter polymorphism and diabetic microvascular complications.

This study examined a possible association of the G>C polymorphism at nucleotide -174 in the promoter region of the interleukin-6 (IL-6) gene (rs1800795) with the prevalence of diabetic complications in 235 patients with type 1 and 498 patients with type 2 diabetes. Genotyping was performed using polymerase chain reaction (PCR) and subsequent cleavage by Nla III restriction endonuclease. Analyzing all diabetic patients together demonstrated that 301 patients (41.1%) carried the GG genotype, 114 (15.6%) the CC genotype, and 318 (43.3%) were heterozygous for the GC genotype. However, there was no correlation of any of the genotypes with the prevalence of diabetic nephropathy or diabetic neuropathy, but subjects with the CC genotype had a significantly higher prevalence of diabetic retinopathy compared to patients with the GC and GG genotype (p=0.016). This association was mainly lost when a logistic regression model was adjusted for diabetes duration (p=0.07). Consistently, a weak but not significant association of the polymorphism with diabetic retinopathy was observed when type 1 and type 2 diabetic patients were analyzed separately (patients with type 1 diabetes: p=0.12; patients with type 2 diabetes: p=0.09). Analogically, no association of the polymorphism was found for diabetic nephropathy or diabetic neuropathy in these groups. In conclusion these data suggest no major influence of the -174G>C variant in the promoter region of the IL-6 gene on the development of microvascular complications in patients with diabetes.

[Tissue retention of T cells as a therapeutic target in rheumatoid arthritis]. / T-Zell-Retention im Gewebe: Ein potenzielles therapeutisches Ziel bei rheumatoider Arthritis.

Autoreactive T cells are instrumental for the induction and chronification of autoimmune diseases. While immigration of T cells into inflamed tissue is strongly enhanced during acute inflammatory phases, retention of antigen specific T cells rather than subsequent recruitment of recirculating effector cells appears to contribute to the inflammatory infiltrate seen during chronic inflammation. Patients suffering from rheumatoid arthritis also show accumulation of oligoclonal T cells within the inflamed synovia, where environmental signals seem to promote the prolonged survival of these chronically activated T cells. The survival signals and mechanisms controlling retention of T cells within the inflamed synovia are poorly characterized. However, the specific interference with these mechanisms could be a therapeutic approach in chronic inflammatory diseases like rheumatoid arthritis that are accompanied by a strong local accumulation of immune cells.

Potential benefits of early addition of rosiglitazone in combination with glimepiride in the treatment of type 2 diabetes.

AIM: To assess the efficacy and tolerability of early combination therapy with rosiglitazone (RSG) and glimepiride (GLIM) vs. GLIM monotherapy in patients with type 2 diabetes mellitus (T2DM). METHODS: Strategies for the addition of RSG in combination with GLIM were evaluated with data from two randomized, double-blind, placebo (PBO)-controlled studies. Study A - addition of RSG (4 or 8 mg) or PBO to continued GLIM 3 mg once daily; study B - addition of low-dose RSG (4 mg) prior to uptitration of GLIM (from 2 to 4 mg) vs. continued uptitration of GLIM (from 2 to 8 mg). RESULTS: Study A reported significant reductions in fasting plasma glucose (FPG) from baseline to week 26 with the addition of both 4 and 8 mg RSG to GLIM 3 mg [-21 mg/dl (-1.2 mmol/l), p = 0.0019 and -43 mg/dl (-2.4 mmol/l), p < 0.0001, respectively] and in haemoglobin A(1c) (HbA(1c)) (-0.63%, p = 0.00015 and -1.17%, p < 0.0001, respectively) from a baseline of 8.2 and 8.1%, respectively. At the end of the study, target HbA(1c) <7.0% was achieved in 43 and 68% of patients in the RSG 4 mg + GLIM and RSG 8 mg + GLIM groups, respectively, compared with 32% in the PBO + GLIM (GLIM alone) group. In study B, addition of RSG to GLIM reduced mean FPG and HbA(1c) levels at week 24 from baseline [-28 mg/dl (-1.5 mmol/l), p < 0.0001, and -0.68%, p < 0.0001, respectively]. There were no significant changes with GLIM monotherapy in either study. Favourable effects of RSG + GLIM on insulin sensitivity, beta-cell function and cardiovascular disease biomarkers were also observed. All treatments were similarly well tolerated. CONCLUSIONS: Early addition of RSG to GLIM is an effective and well-tolerated treatment option to improve glycaemic control in sulphonylurea-treated patients with T2DM.

Comparison of fixed-dose rosiglitazone/metformin combination therapy with sulphonylurea plus metformin in overweight individuals with Type 2 diabetes inadequately controlled on metformin alone.

AIM: This 52-week, randomized, double-blind, parallel-group study was designed to compare rosiglitazone/metformin fixed-dose combination therapy with combination sulphonylurea plus metformin therapy in overweight individuals with inadequately controlled type 2 diabetes mellitus. METHOD: Individuals with inadequate glycaemic control (HbA (1c)> or =7%) while on metformin monotherapy (> or =0.85 g/day) entered a 4-week run-in period during which they received metformin 2 g/day. At the end of the run-in, individuals with fasting plasma glucose > or =7.0 mmol/l were randomized to treatment with metformin (2 g/day) and either rosiglitazone (4 mg/day; RSG+MET [N=294]) or a sulphonylurea (glibenclamide 5 mg/day or gliclazide 80 mg/day; SU+MET [N=302]). Medications were up-titrated to maximum tolerated doses (rosiglitazone 8 mg, glibenclamide 15 mg or gliclazide 320 mg plus metformin 2 g/day) during the first 12 weeks of double-blind treatment. The primary efficacy end point was the change in HbA (1c) from baseline after 52 weeks of treatment. RESULTS: RSG+MET was non-inferior to SU+MET with respect to changes in HbA (1c) after one year of treatment (DeltaHbA (1c)= -0.78% and -0.86%, respectively; treatment difference =0.09%, 95% CI=-0.08, 0.25). The HbA (1c) reductions with RSG+MET, but not SU+MET, were accompanied by significant improvements in measures of beta-cell function including proinsulin:insulin ratio. The degree of beta-cell failure was significantly greater with SU+MET compared to RSG+MET as measured by the coefficient of failure (0.543 vs. 0.055 HbA (1c)%/year, respectively, p=0.0002). The proportion of individuals who experienced hypoglycaemic events was significantly (p<0.0001) lower with RSG+MET (6%) than with SU+MET (30%). Diastolic ambulatory blood pressure and cardiovascular biomarkers (high-sensitivity C-reactive protein and plasminogen activator inhibitor-1) were also reduced following one year of treatment with RSG+MET but not SU+MET. Both treatments were generally well tolerated. CONCLUSION: Fixed-dose combination therapy with rosiglitazone/metformin is non-inferior to sulphonylurea plus metformin combination therapy in reducing HbA (1c) over one year of treatment. Improvements in measures of beta-cell function suggest that the improvements in glycaemic control may be better maintained in long-term therapy with the rosiglitazone/metformin combination.

A M55V polymorphism in the SUMO4 gene is associated with a reduced prevalence of diabetic retinopathy in patients with Type 1 diabetes.

AIMS: We studied the association between a functionally relevant M55V polymorphism in the SUMO4 gene with microvascular diabetic complications in patients with type 1 diabetes. METHODS: 223 patients with type 1 diabetes were studied using polymerase chain reaction and subsequent cleavage by restriction endonucleases for the M55V SUMO4 gene variant. RESULTS: No effect of the polymorphism on diabetic neuropathy or diabetic nephropathy was found, but heterozygous or homozygous patients for the M55V polymorphism in the SUMO4 gene had a markedly reduced prevalence of diabetic retinopathy (odds ratio 0.37, 95%-confidence interval (CI) [0.32;0.43]; p=0.004). Furthermore, a multiple logistic regression model showed an age and diabetes duration independent effect of the M55V polymorphisms on the prevalence of diabetic retinopathy (p=0.03), but not of diabetic neuropathy or nephropathy. CONCLUSIONS: Our data indicate that the M55V polymorphism in the SUMO4 gene is associated with a reduced risk of diabetic retinopathy in type 1 diabetes. Thus, the results of our study suggest that posttranslational modification of proteins via SUMO4 could contribute to the development of certain diabetic complications.

[Pharmacotherapy of obesity]. / Pharmakotherapie der Adipositas.

Diet, exercise and behavioral therapy are the basics for every treatment of obesity. If lifestyle intervention does not result in a weight loss of 5% within 3 to 6 months, an additional pharmacotherapy can be considered. Treated patients should have a BMI >/=30 kg/m(2) or at least a BMI >/=27 kg/m(2) plus accompanying comorbidities, such as type 2 diabetes, dyslipidemia or hypertension. Current guidelines list orlistat, sibutramine and rimonabant as possible options for the pharmacotherapy of obesity. These compounds result in moderate weight reduction and improvement of cardiovascular risk profile. Especially the improvement of glucose metabolism can be considered as clinically relevant. Different side effects of the various compounds need to be considered before their use. Additional options for the pharmacotherapy of obesity are currently developed, their approval, however, is unlikely to happen within the next couple of years.