Experimental quantum key distribution certified by Bell's theorem.

Cryptographic key exchange protocols traditionally rely on computational conjectures such as the hardness of prime factorization1 to provide security against eavesdropping attacks. Remarkably, quantum key distribution protocols such as the Bennett-Brassard scheme2 provide information-theoretic security against such attacks, a much stronger form of security unreachable by classical means. However, quantum protocols realized so far are subject to a new class of attacks exploiting a mismatch between the quantum states or measurements implemented and their theoretical modelling, as demonstrated in numerous experiments3-6. Here we present the experimental realization of a complete quantum key distribution protocol immune to these vulnerabilities, following Ekert's pioneering proposal7 to use entanglement to bound an adversary's information from Bell's theorem8. By combining theoretical developments with an improved optical fibre link generating entanglement between two trapped-ion qubits, we obtain 95,628 key bits with device-independent security9-12 from 1.5 million Bell pairs created during eight hours of run time. We take steps to ensure that information on the measurement results is inaccessible to an eavesdropper. These measurements are performed without space-like separation. Our result shows that provably secure cryptography under general assumptions is possible with real-world devices, and paves the way for further quantum information applications based on the device-independence principle.

Noisy Preprocessing Facilitates a Photonic Realization of Device-Independent Quantum Key Distribution.

Device-independent quantum key distribution provides security even when the equipment used to communicate over the quantum channel is largely uncharacterized. An experimental demonstration of device-independent quantum key distribution is however challenging. A central obstacle in photonic implementations is that the global detection efficiency, i.e., the probability that the signals sent over the quantum channel are successfully received, must be above a certain threshold. We here propose a method to significantly relax this threshold, while maintaining provable device-independent security. This is achieved with a protocol that adds artificial noise, which cannot be known or controlled by an adversary, to the initial measurement data (the raw key). Focusing on a realistic photonic setup using a source based on spontaneous parametric down conversion, we give explicit bounds on the minimal required global detection efficiency.

T cells, natural killer cells, and γδT cells in a large patient cohort with rheumatoid arthritis: influence of age and anti-rheumatic therapy.

Objective: The aim of this cohort study was to evaluate the distribution of natural killer (NK) cells and T-cell subsets, including γδT cells, in the peripheral blood of patients with rheumatoid arthritis (RA) in a large real-life patient cohort, taking into account the patients' demographics, disease characteristics, and anti-rheumatic therapy.Method: The study recruited 508 RA patients between November 2013 and August 2015. Lymphocyte differentiation using eight-colour flow cytometry (fluorescence-activated cell sorting) of the peripheral blood was performed for all patients. Clinical data, including age, gender, disease duration, serostatus, disease activity, antibody status, immunosuppressive therapy including use of different biological disease-modifying anti-rheumatic drugs (bDMARDs) and conventional synthetic DMARDs, were retrospectively assessed using electronic patient files. Multivariate regression analysis was performed to assess the effect of these variables on T-cell, NK-cell, and γδT-cell counts.Results: The median patient age was 61.0 years and 74.1% were female. The median disease duration of RA was 12.0 years. Median Disease Activity Score based on 28-joint count was 2.8 and 56.3% were treated with bDMARDs. There were no differences in immunosuppressive therapy between different age groups. While rituximab, abatacept, and tocilizumab had no influence on lymphocyte subdifferentiation, tumour necrosis factor (TNF) inhibitors and age significantly influenced the numbers of T cells, T-helper cells, T-NK cells, NK cells, and γδT cells.Conclusion: Age and TNF-inhibition therapy influence lymphocyte subdifferentiation in patients with RA. It may be prudent to use age- and therapy-adjusted standard values for lymphocyte subsets during clinical trials and treatment of RA.

The genetic basis for most patients with pustular skin disease remains elusive.

BACKGROUND: Rare variants in the genes IL36RN, CARD14 and AP1S3 have been identified to cause or contribute to pustular skin diseases, primarily generalized pustular psoriasis (GPP). OBJECTIVES: To better understand the disease relevance of these genes, we screened our cohorts of patients with pustular skin diseases [primarily GPP and palmoplantar pustular psoriasis (PPP)] for coding changes in these three genes. Carriers of single heterozygous IL36RN mutations were screened for a second mutation in IL36RN. METHODS: Coding exons of IL36RN, CARD14 and AP1S3 were sequenced in 67 patients - 61 with GPP, two with acute generalized exanthematous pustulosis and four with acrodermatitis continua of Hallopeau. We screened IL36RN and AP1S3 for intragenic copy-number variants and 258 patients with PPP for coding changes in AP1S3. Eleven heterozygous IL36RN mutations carriers were analysed for a second noncoding IL36RN mutation. Genotype-phenotype correlations in carriers/noncarriers of IL36RN mutations were assessed within the GPP cohort. RESULTS: The majority of patients (GPP, 64%) did not carry rare variants in any of the three genes. Biallelic and monoallelic IL36RN mutations were identified in 15 and five patients with GPP, respectively. Noncoding rare IL36RN variants were not identified in heterozygous carriers. The only significant genotype-phenotype correlation observed for IL36RN mutation carriers was early age at disease onset. Additional rare CARD14 or AP1S3 variants were identified in 15% of IL36RN mutation carriers. CONCLUSIONS: The identification of IL36RN mutation carriers harbouring additional rare variants in CARD14 or AP1S3 indicates a more complex mode of inheritance of pustular psoriasis. Our results suggest that, in heterozygous IL36RN mutation carriers, there are additional disease-causing genetic factors outside IL36RN.

Analysis of the German DRG data for livedoid vasculopathy and calciphylaxis.

BACKGROUND: Livedoid vasculopathy and calciphylaxis are rare skin disorders. Large cohorts of patients have been missing so far for detailed analysis. PATIENTS AND METHODS: Data from diagnosis-related groups (DRGs) of hospitalized cases of livedoid vasculopathy (ntotal = 1357) and calciphylaxis (ntotal = 699) were analysed for the years 2008-2013 concerning sex, age and frequency of diagnosis. To avoid deviations to non-relevant secondary diagnosis and due to changes in ICD-10 indices, we selected the two most recent available years 2013 and 2014 for evaluation of the accompanying diagnoses for both, livedoid vasculopathy (n = 519) and calciphylaxis (n = 324). Those were additionally evaluated as possible comorbidity. RESULTS: The male-female ratio for livedoid vasculopathy was 2.1:1. Patients older than 45 years comprehended 74.7% of all patients with peaks between the ages of 45-50 and 70-75. Livedoid vasculopathy patients suffered from cardiovascular and renal diseases. Coding of coagulation disorders was found rarely in our analysis. For calciphylaxis, we calculated a male-female ratio of 1.7:1. Most of the patients were at an age between 65 and 80 years. Diagnosis at an age under 35 years was rare. In general, most calciphylaxis patients showed end-stage renal disease with need of dialysis and presented with the resulting complications. CONCLUSIONS: Our data analysis shows relevant comorbidity and cofactors of these rare diseases like livedoid vasculopathy and calciphylaxis in Germany by a large number of cases.

[Current detection rates of multiresistant gram negative bacteria (3MRGN, 4MRGN) in patients with chronic leg ulcers]. / Aktuelle Nachweisraten multiresistenter Gram-negativer Bakterien (3MRGN, 4MRGN) bei Patienten mit chronischem Ulcus cruris.

BACKGROUND: Due to the increasing problem of antibiotic resistance in gram-negative pathogens, the Commission for Hospital Hygiene and Infection Prevention (KRINKO) decided to establish a new clinically oriented definition of multi-resistance. Gram-negative pathogens with a multidrug-resistance (MRGN) are divided into those with resistance to three (3MRGN) or four (4MRGN) antibiotic groups. PATIENTS AND METHODS: In this multicenter study which was done in ten dermatological wound clinics, the bacteriological swabs from up to 100 patients with chronic leg ulcers per center were analyzed according to the current classification KRINKO and evaluated. RESULTS: Overall, the results of 970 patients (553 women, 417 men) could be evaluated. We found 681 gram-positive and 1155 gram-negative bacteria. Pseudomonas aeruginosa was with a detection-rate of 31.1% the most frequent gram-negative pathogen, followed by Proteus mirabilis with 13.7% and various enterobacteria with 28.6%. According to the current KRINKO classification,eight patients with 4MRGN and 34 patients with 3MRGN could be identified. CONCLUSIONS: Our results demonstrate the current spectrum of bacteria in patients with chronic leg ulcers with a variety of gram-negative pathogens, some of which are classified as multi-drug resistant. As a clinical consequence some of the patients require individualized preventive measures and therapy.

W.A.R. scores in patients with chronic leg ulcers: results of a multicentre study.

OBJECTIVE: To assess the individual patient's risk of wound infection using the wounds-at-risk (W.A.R.) score developed by a group of interdisciplinary experts. METHOD: The W.A.R. score is a clinical test in which, based on anamnestic and clinical criteria, wound patients are assigned point values, where a score of less than or equal to 3 indicates a need for antimicrobial treatment. RESULTS: The data of 970 patients (553 women, 417 men) with chronic leg ulcers were evaluated at 10 dermatological wound clinics in different regions within Germany. The age of the patients was between 10 and 100 years (mean of 69.8 years); the duration of the wounds was between 2 months and 68 years (mean of 41.1 months). Wound sizes were between 1 and 736 cm² (mean of 42.8 cm²). Overall, W.A.R. scores of <3 points were found in 73.1% of patients and scores of greater than or equal to 3 were found in 26.9% [corrected] of patients. There were significant differences in W.A.R. scores by regions with respect to the bacterial species detected and the aetiologies of the wounds. CONCLUSION: Our multicentre study is the first evaluation of clinical data using the newly established W.A.R. scores. We were able to show that the W.A.R. scores are able to identify a segment of the patient population for whom it can be assumed that they are prone to an increased risk of wound infections unless appropriate antimicrobial action is taken. The W.A.R. score is a simple clinical score that identifies patients with an increased risk of wound infection.

Who can provide effective and safe termination of pregnancy care? A systematic review*.

BACKGROUND: Unsafe termination of pregnancy is a major contributor to maternal morbidity and mortality. Task sharing termination of pregnancy services between physicians and mid-level providers, a heterogeneous group of trained healthcare providers, such as nurses, midwives and physician assistants, has become a key strategy to increase access to safe pregnancy termination care. OBJECTIVES: To systematically review the evidence to assess whether termination of pregnancy services by nonphysician providers can be performed safely and effectively. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, MEDLINE in process and other nonindexed citations and POPLINE. SELECTION CRITERIA: We included randomised controlled trials (RCTs), as well as clinical studies, using study designs that compared efficacy, safety and acceptability of termination of pregnancy services by physicians versus other provider groups. Data collection and analysis Two reviewers independently extracted the data, and we performed a meta-analysis where appropriate using RevMan. Quality assessment of the data used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: We identified five controlled studies comprising 8908 women undergoing first-trimester surgical termination of pregnancy (one RCT and three prospective cohort studies) and medical termination of pregnancy (one RCT). The mid-level provider group included midwives, nurses, auxiliary nurse midwives and physician assistants trained in termination of pregnancy services. Safety and efficacy outcomes, including incomplete termination of pregnancy, haemorrhage, injury to the uterus or cervix, did not differ significantly between providers. AUTHOR'S CONCLUSIONS: Limited evidence indicates that trained mid-level providers may effectively and safely provide first-trimester surgical and medical termination of pregnancy services. Data are limited by the scarcity of RCTs and biases of the cohort studies.

Training alters the skeletal muscle antioxidative capacity in non-insulin-dependent type 2 diabetic men.

The present study analyzes the oxidative stress situation in the skeletal muscle of overweight/obese men suffering from non-insulin-dependent type 2 diabetes mellitus [T2DM, n=16, years=61±7, body mass index (BMI)=31±4 kg/m(2) ] and BMI-matched non-diabetic male control subjects (CON, n=7, years=53±6, BMI=30±4 kg/m(2) ). Furthermore, it investigates whether physical training can alter the skeletal muscle antioxidative capacity of T2DM patients at rest. Molecule content analyses (immunohistochemical stainings) of 8-iso-prostaglandin-F2α (8-Iso-PGF), superoxide dismutase-2 (SOD2), glutathione peroxidase-1 (GPX1), peroxiredoxin isoforms (PRDX 1-6) and heat-shock-protein-70 (HSP70) were performed in biopsies taken from the vastus lateralis muscle. Under basal conditions, 8-Iso-PGF was significantly decreased in T2DM patients (-35.7%), whereas PRDX2 and PRDX6 were significantly increased relative to CON (+82.6%; +82.3%). Differences were neither observed in SOD2 nor in GPX1 or PRDX1, 3, 4, 5 density. Regular physical activity (moderate endurance or resistance training twice a week for 3 months) did not alter PRDX1, 2, 3, 4, 6 in the skeletal muscle of T2DM patients, but significantly increased SOD2 (+65.9%), GPX1 (+62.4%), PRDX5 (+37.5%), and HSP70 (+48.5%). Overweight/obese men with non-insulin-dependent T2DM exhibit up-regulated cytosolic peroxiredoxin contents relative to BMI-matched controls. Regular training further up-regulates cytosolic and mitochondrial antioxidative enzymes in T2DM patients and improves their cellular protection systems. This may contribute to a retardation of the disease's progression.

Exercise-induced adaptations of cardiac redox homeostasis and remodeling in heterozygous SOD2-knockout mice.

A reduced expression of the manganese-dependent superoxide dismutase (SOD2) is characterized by increased cardiac oxidative stress. Oxidative stress has also been described in situations of physical exercise. We investigated the influence of physical exercise (EX; treadmill 1 h/day at 15 m/min, 5 days/wk, at an angle of 5° for a duration of 8 wk) on cardiac function [heart frequency (HF), echocardiography, morphometry], oxidative stress [reactive oxygen species (ROS)], and antioxidative defence capacity (peroxiredoxin 1-6) in male SOD2-knockout (SOD2_EX) and wild-type mice (WT_EX) compared with untrained age-matched animals (WT_CON; SOD2_CON). In SOD2_CON, heart weight, cardiomyocyte diameter, and cardiac ROS were significantly larger and peroxiredoxin isoforms 4-6 lower than in WT_CON. The vessel-to-cardiomyocyte ratio, cardiac VEGF-concentration, and cardiac function were similar in SOD2_CON and WT_CON. Both groups tolerated the exercise protocol well. In WT, exercise significantly increased vessel-to-cardiomyocyte ratio and ROS-generation and downregulated peroxiredoxin isoforms 4-6 and VEGF generation. The vessel-to-cardiomyocyte ratio, cardiac VEGF concentration, and cardiac ROS were not altered in SOD2_EX compared with SOD2_CON, but a significant upregulation of cardiac peroxiredoxin 1 and 4 was observed. Similar to the result observed in WT_EX, peroxiredoxin 3 was upregulated in SOD2_EX. Chronic exercise shifted the (mal)adaptive hypertrophic into a compensated dilated cardiac phenotype in SOD2_EX. In conclusion, downregulation of SOD2 induces a maladaptive cardiac hypertrophy. In this situation, physical exercise results in a further deterioration of cardiac remodeling despite an upregulation of the antioxidative defense system.

[Necrotizing fasciitis caused by Acinetobacter baumannii : A case report]. / Nekrotisierende Fasziitis durch Acinetobacter baumannii : Ein Fallbericht.

A 42-year-old man developed necrotizing fasciitis on the right leg. A multidrug-resistant Acinetobacter baumannii was cultivated from the deep wound. Following therapy with imipenem and tobramycin as well as extensive debridement, the lesions improved slowly. A. baumannii is today an important cause of nosocomial infections, especially in intensive care units.

[Chronic inflammatory and autoimmune mediated dermatoses during pregnancy. Course and prognosis for mother and child]. / Chronisch entzündliche und autoimmun vermittelte Dermatosen in der Schwangerschaft. Verlauf und Prognose für Mutter und Kind.

Chronic inflammatory dermatoses during pregnancy can take varying courses in mother and child. The dominant Th2-response characteristic for pregnancy may explain why atopic eczema or lupus erythematosus may deteriorate while psoriasis vulgaris may improve. In contrast, impetigo herpetiformis frequently shows a severe course. Lupus erythematosus and other autoantibody-triggered dermatoses like pemphigus vulgaris pose an increased risk for the child because of placental transfer of autoantibodies with specific skin changes or systemic manifestations of the disease as well as placental insufficiency, growth retardation and premature birth. Such risks are not associated with linear IgA dermatosis. A severe pityriasis rosea during the first 20 weeks of pregnancy may lead to an increased risk of abortion or premature delivery. Early diagnosis and individually adjusted therapy of skin diseases is mandatory to avoid any risk for mother or child.

[Mid-dermal elastolysis]. / Elastolyse der mittleren Dermis.

Mid-dermal elastolysis is a rare dermatosis of still unknown etiology with a characteristic mid-dermal loss of elastic tissue on histopatholoy. Papular and plaque-like wrinkling of the skin as well as inflammatory and non-inflammatory variants have been described. We present a 39-year-old patient with extended skin wrinkling of the trunk and upper extremities after extensive UV light exposure and describe the clinical and histopathological findings. Based on our case, differential diagnoses are discussed and the literature is reviewed.

Respiration triggered magnetic drug targeting in the lungs.

Lung cancer kills per year 1.3 million people worldwide. It is the most fatal cancer type as far as men are concerned and the second deadliest for women. One of the recent technologies to treat carcinomas in the lungs consists in delivering drugs through the pulmonary pathways directly to the tumor cells over actively loaded superparamagnetic nanoparticles that are encapsulated in aerosols and guided by external magnetic fields. However, first implementations of this technique assumed a continuous application of the magnetic field all through the inspiration and expiration phases of the artificial respiratory act that supplies the patient. We observed that applying the field this way forced the magnetic aerosols to sediment at regions far from the target, mainly in the trachea and main bronchioles, because of the force inducing magnetic field gradients that are present over the whole field application area. We developed an approach to avoid this effect by punctually generating the aerosol cloud exactly at the beginning of the inspiration phase, which would propel the particles to the deepest parts of the lung and therefore to the targeted cells as well, and by synchronizing the magnetic field activation with the breathing process. Our developed system analyzes the relevant respiration parameters such as pressure and flow and detects the end of the inspiration phase to trigger the magnet exactly at that point in time, when particles have reached the deepest alveoli, including the targeted zones, and do not experience forces due to the streaming any more. The magnetic field is then held on during the expiration phase to assure the retention of the aerosols at the targeted sites, which increases the efficiency and focality of the treatment. This way, only target cells are subjected to the deposition of the drug carrying aerosols, while the other healthy regions of the lungs remain unaltered by side effects.

[Chronic venous insufficiency (CVI)]. / Die chronisch venöse Insuffizienz (CVI).

Chronic venous insufficiency (CVI) is an important and frequent disease for dermatologists, phlebologists and general practitioners. There are various hypotheses for the ethiopathology in CVI, e. g. hormone receptors and impairments concerning the venous contraction or relaxation of the vessel wall and the venous valves might play an important role. At the moment, colour doppler-duplex sonography seems to be the diagnostic method of choice. Modern therapeutic options include compression systems alone or in combination with topical or systemic treatment including minimal invasive methods like endovenous laser or radiofrequency obliteration or foam sclerotherapy.

[Changes in treatment of squamous cell carcinoma over time. A process analysis]. / Adaptierte Behandlungsmodalitäten bei Patienten mit Plattenepithelkarzinomen im Wandel der Zeit. Eine Prozessanalyse.

BACKGROUND: The incidence of squamous cell carcinoma is rapidly increasing and requires process-optimized treatment dependent on the course of the patient's individual disease. Patient-based data on squamous cell carcinoma were used to analyze the treatment modalities before DRGs were introduced, after their introduction and after discussion about process-optimization in context of clinical pathways. PATIENTS AND METHODS: From the recorded data in the department of dermatology, all squamous cell carcinoma cases were identified and evaluated. In addition to patient characteristics, parameters describing the process, for example, length of stay in hospital, pre- and post-interventional days, were collected. RESULTS: Between 1998-2002, 2004-2006 and January to June 2007, 658 patients were treated for squamous cell carcinoma. In contrast to the times before DRGs, the treatment process has been significantly optimized, reducing the pre- and post-operative days and thus the duration of stay. Analysis of clinical pathways as part of the continuous improvement process was hardly able to detect further improvement. However, the weekly distribution of the admitted patients has been improved. CONCLUSIONS: Patients with squamous cell carcinoma requiring surgical excision benefit from an optimized process, just as do impatient facilities. However, optimized treatment modalities carry hardly any potential of improvement by the invention of clinical pathways.

De Finetti representation theorem for infinite-dimensional quantum systems and applications to quantum cryptography.

We show that the quantum de Finetti theorem holds for states on infinite-dimensional systems, provided they satisfy certain experimentally verifiable conditions. This result can be applied to prove the security of quantum key distribution based on weak coherent states or other continuous variable states against general attacks.

The different faces of cutaneous lupus erythematosus.

Lupus erythematosus is a chronic and inflammatory multiorgan disease with variable clinical appearance and variable course. Most patients with systemic lupus erythematosus show cutaneous manifestations and conversely, all forms of cutaneous LE may change into a systemic involvement. Specific lesions of cutaneous LE are classified in different subtypes of acute cutaneous lupus erythematosus (ACLE), subacute cutaneous lupus erythematosus (SCLE), chronic cutaneous lupus erythematosus (CDLE) and intermittent cutaneous lupus erythematosus (ICLE) according to clinical, histological and immunoserological parameters. Regular laboratory tests are important to monitor the activity and course of the disease or side effects of the therapy. In case of clinical or laboratory dysfunctions of internal organs, additional technical investigations are necessary. Histology is needed to support clinical diagnosis. A large number of drugs are able to induce SCLE, e.g. hydrochlorothiazide, terbinafine, or angiotensin-converting enzyme inhibitors. Drug-induced SCLE can be differentiated by possible complementary immunoserological parameters. Neonatal lupus can be induced by transplacental transmission of maternal anti-Ro(SS-A) and anti-La(SS-B)-antibodies. Children with neonatal lupus might suffer from congenital atrioventricular block. Their mothers may suffer from active LE, but can be clinically healthy as well. As a consequence, pregnancies at risk should be monitored in short intervals by serial echocardiographic interventions. Protection against UV light is recommended for all types of CLE. There are some topical and many systemic treatment options e.g. topical and systemic glucocorticosteroids, antimalarial drugs, dapsone, azathioprine, or mycophenolate mofetil with different response to skin or organ involvement.