A palaeopathological analysis of skeletal remains from Bronze Age Mongolia.

Little is known about the lifeways of the people who inhabited the Mongolian steppe during the Bronze Age (c. 4450-2650 BP). Palaeopathological analysis allows us to draw inferences about the lifeways of past people from the indicators of health and lifestyle recorded in human remains. This paper presents results of analysis of the remains of 25 individuals excavated in northern Mongolia. Overall, the remains demonstrated very little pathology. In particular the lack of evidence for both infectious and non-communicable diseases, along with the patterns of dental pathology indicate a group of people who experienced few health insults and little stress. The types of trauma, Schmorl's nodes and patterns of degenerative joint disease present in the sample are suggestive of interpersonal violence and horse riding. The findings are consistent with a traditional pastoral lifeway where people live in small groups, rely on a protein-rich diet and use animals for transportation.

Quantum key distribution with hacking countermeasures and long term field trial.

Quantum key distribution's (QKD's) central and unique claim is information theoretic security. However there is an increasing understanding that the security of a QKD system relies not only on theoretical security proofs, but also on how closely the physical system matches the theoretical models and prevents attacks due to discrepancies. These side channel or hacking attacks exploit physical devices which do not necessarily behave precisely as the theory expects. As such there is a need for QKD systems to be demonstrated to provide security both in the theoretical and physical implementation. We report here a QKD system designed with this goal in mind, providing a more resilient target against possible hacking attacks including Trojan horse, detector blinding, phase randomisation and photon number splitting attacks. The QKD system was installed into a 45 km link of a metropolitan telecom network for a 2.5 month period, during which time the system operated continuously and distributed 1.33 Tbits of secure key data with a stable secure key rate over 200 kbit/s. In addition security is demonstrated against coherent attacks that are more general than the collective class of attacks usually considered.

Near perfect mode overlap between independently seeded, gain-switched lasers.

We drastically improve the mode overlap between independently seeded, gain-switched laser diodes operating at gigahertz repetition rates by implementing a pulsed light seeding technique. Injecting pulsed light reduces the emission time jitter and enables frequency chirp synchronization while maintaining random optical phases of the emitted laser pulses. We measure interference of these pulsed sources both in the macroscopic regime, where we demonstrate near perfect mode overlap, and in the single photon regime, where we achieve a Hong-Ou-Mandel dip visibility of 0.499 ± 0.004, thus saturating the theoretical limit of 0.5. The measurement results are reproduced by Monte-Carlo simulations with no free parameters. Our light source is an ideal solution for generation of high rate, indistinguishable coherent pulses for quantum information applications.

Quantum key distribution over multicore fiber.

We present the first quantum key distribution (QKD) experiment over multicore fiber. With space division multiplexing, we demonstrate that weak QKD signals can coexist with classical data signals launched at full power in a 53 km 7-core fiber, while showing negligible degradation in performance. Based on a characterization of intercore crosstalk, we perform additional simulations highlighting that classical data bandwidths beyond 1Tb/s can be supported with high speed QKD on the same fiber.

Development of curative therapies for Ewing sarcomas by interdisciplinary cooperative groups in Europe.

Curative therapies for Ewing sarcoma have been developed within cooperative groups. Consecutive clinical trials have systematically assessed the impact and timing of local therapy and the activity of cytotoxic drugs and their combinations. They have led to an increase of long-term disease-free survival to around 70% in patients with localized disease. Translational research in ES remains an area in which interdisciplinary and international cooperation is essential for future progress. This article reviews current state-of-the art therapy, with a focus on trials performed in Europe, and summarizes novel strategies to further advance both the cure rates and quality of survival.

High speed prototype quantum key distribution system and long term field trial.

Securing information in communication networks is an important challenge in today's world. Quantum Key Distribution (QKD) can provide unique capabilities towards achieving this security, allowing intrusions to be detected and information leakage avoided. We report here a record high bit rate prototype QKD system providing a total of 878 Gbit of secure key data over a 34 day period corresponding to a sustained key rate of around 300 kbit/s. The system was deployed over a standard 45 km link of an installed metropolitan telecommunication fibre network in central Tokyo. The prototype QKD system is compact, robust and automatically stabilised, enabling key distribution during diverse weather conditions. The security analysis includes an efficient protocol, finite key size effects and decoy states, with a quantified key failure probability of ε = 10⁻¹°.

[Adherence to Long-term Follow-up in Paediatric Oncology--Results of a Monocentric Analysis]. / Nachsorgeadhärenz in der Pädiatrischen Onkologie - Ergebnisse einer monozentrischen Analyse.

BACKGROUND: Cured paediatric-oncology patients frequently present with health problems even years after treatment. Hence long-term follow-up (LTFU) is essential. This analysis tries to identify factors that influence regular LTFU attendance. STUDY POPULATION: Between 1991 and 2010, 2 153 children and adolescents were treated at Muenster University Department of Paediatric Hematology and Oncology (UKM). 1 708 patients with permanent residence in Germany and completed therapy have been included into this analysis. METHODS: Patients were reviewed for the duration and regularity of LTFU at UKM. Prospective analyses with postponed starting-points have been conducted as well as descriptive analyses to validate correlations. Prospective data were evaluated by Kaplan-Meier-Analyses, the analysis of multivariate correlations by Cox Proportional Hazard Model. RESULTS: 2 years after the end of therapy 83% of the patients were still in LTFU. After 5 and 10 years this percentage decreased to 67 and 42%. Patients diagnosed after the year 2000 and younger patients attended LTFU for a longer period (p<0,005). There were no significant gender differences. Statutory insured patients stayed longer in LTFU than private health insured (p<0,005). The multivariate examination showed only small differences between systemic diseases and solid tumours. The residential distance had no significant influence. CONCLUSIONS: Younger, more recently treated and statutory insured patients showed a significantly longer LTFU.

Efficient decoy-state quantum key distribution with quantified security.

We analyse the finite-size security of the efficient Bennett-Brassard 1984 protocol implemented with decoy states and apply the results to a gigahertz-clocked quantum key distribution system. Despite the enhanced security level, the obtained secure key rates are the highest reported so far at all fibre distances.

Two-dimensional Fermi liquid with attractive interactions.

We realize and study an attractively interacting two-dimensional Fermi liquid. Using momentum-resolved photoemission spectroscopy, we measure the self-energy, determine the contact parameter of the short-range interaction potential, and find their dependence on the interaction strength. We successfully compare the measurements to a theoretical analysis, properly taking into account the finite temperature, harmonic trap, and the averaging over several two-dimensional gases with different peak densities.

The glucose-dependent insulinotropic polypeptide receptor is overexpressed amongst GNAS1 mutation-negative somatotropinomas and drives growth hormone (GH)-promoter activity in GH3 cells.

Somatic mutations in the GNAS1 gene, encoding the α-subunit of the heterotrimeric stimulatory G protein (Gαs), occur in approximately 40% of growth hormone (GH)-secreting pituitary tumours. By altering the adenylate cyclase-cAMP-protein kinase A pathway, they unequivocally give somatotroph cells a growth advantage. Hence, the pathogenesis of somatotropinomas could be linked to anomalies in receptors coupled to the cAMP second-messenger cascade. Among them, the glucose-dependent insulinotropic polypeptide receptor (GIPR) is already known to play a primary role in the impaired cAMP-dependent cortisol secretion in patients affected by food-dependent Cushing's syndrome. In the present study, 43 somatotropinomas and 12 normal pituitary glands were investigated for GIPR expression by quantitative reverse transcriptase-polymerase chain reaction, western blotting and immunohistochemistry. Tumoural specimens were also evaluated for GNAS1 mutational status. The effect of GIPR overexpression on cAMP levels and GH transcription was evaluated in an in vitro model of somatotropinomas, the GH-secreting pituitary cell line GH3. GIPR was expressed at higher levels compared to normal pituitaries in 13 GNAS1 mutation-negative somatotropinomas. GIP stimulated adenylyl cyclase and GH-promoter activity in GIPR-transfected GH3 cells, confirming a correct coupling of GIPR to Gαs. In a proportion of acromegalic patients, GIPR overexpression appeared to be associated with a paradoxical increase in GH after an oral glucose tolerance test. Whether GIPR overexpression in acromegalic patients may be associated with this paradoxical response or more generally involved in the pathogenesis of acromegaly, as suggested by the mutually exclusive high GIPR levels and GNAS1 mutations, remains an open question.

d-wave collapse and explosion of a dipolar bose-einstein condensate.

We investigate the collapse dynamics of a dipolar condensate of 52Cr atoms when the s-wave scattering length characterizing the contact interaction is reduced below a critical value. A complex dynamics, involving an anisotropic, d-wave symmetric explosion of the condensate, is observed. The atom number decreases abruptly during the collapse. We find good agreement between our experimental results and those of a numerical simulation of the three-dimensional Gross-Pitaevskii equation, including contact and dipolar interactions as well as three-body losses. The simulation indicates that the collapse induces the formation of two vortex rings with opposite circulations.

Novel mutations in the folliculin gene associated with spontaneous pneumothorax.

Spontaneous pneumothorax is mostly sporadic but may also occur in families with genetic disorders, such as Birt-Hogg-Dubé syndrome, which is caused by mutations in the folliculin (FLCN) gene. The aim of the present study was to investigate the presence and type of mutation in a Swiss pedigree and in a sporadic case. Clinical examination, lung function tests and high-resolution computed tomography were performed. All coding exons and flanking intronic regions of FLCN were amplified by PCR and directly sequenced. The amount of FLCN transcripts was determined by quantitative real-time RT-PCR. Two novel mutations in FLCN were identified. Three investigated family members with a history of at least one spontaneous pneumothorax were heterozygous for a single nucleotide substitution (c.779G>A) that leads to a premature stop codon (p.W260X). Quantitative real-time RT-PCR revealed a reduction of FLCN transcripts from the patient compared with an unaffected family member. DNA from the sporadic case carried a heterozygous missense mutation (c.394G>A). Lung function of this patient was normal and computed tomography showed similar bilateral cysts, as observed in the two members of the unrelated Swiss family. Mutations in the folliculin gene are associated with cystic lung lesions in an otherwise morphological normal lung and predispose to spontaneous pneumothorax.

Two-frequency acousto-optic modulator driver to improve the beam pointing stability during intensity ramps.

We report on a scheme to improve the pointing stability of the first order beam diffracted by an acousto-optic modulator (AOM). Due to thermal effects inside the crystal, the angular position of the beam can change by as much as 1 mrad when the radio-frequency power in the AOM is reduced to decrease the first order beam intensity. This is done, for example, to perform forced evaporative cooling in ultracold atom experiments using far-off-resonant optical traps. We solve this problem by driving the AOM with two radio frequencies f(1) and f(2). The power of f(2) is adjusted relative to the power of f(1) to keep the total power constant. Using this, the beam displacement is decreased by a factor of 20. The method is simple to implement in existing experimental setups, without any modification of the optics.

Arylpropanolamines: selective beta3 agonists arising from strategies to mitigate phase I metabolic transformations.

Utilization of N-substituted-4-hydroxy-3-methylsulfonanilidoethanolamines 1 as selective beta(3) agonists is complicated by their propensity to undergo metabolic oxidative N-dealkylation, generating 0.01-2% of a very potent alpha(1) adrenergic agonist 2. A summary of the SAR for this hepatic microsomal conversion precedes presentation of strategies to maintain the advantages of chemotype 1 while mitigating the consequences of N-dealkylation. This effort led to the identification of 4-hydroxy-3-methylsulfonanilidopropanolamines 15 for which the SAR for the unique stereochemical requirements for binding to the beta adrenergic receptors culminated in the identification of the potent, selective beta(3) agonist 15f.

Protocol design and current status of CLIVIT: a randomized controlled multicenter relevance trial comparing clips versus ligatures in thyroid surgery.

BACKGROUND: Annually, more than 90000 surgical procedures of the thyroid gland are performed in Germany. Strategies aimed at reducing the duration of the surgical procedure are relevant to patients and the health care system especially in the context of reducing costs. However, new techniques for quick and safe hemostasis have to be tested in clinically relevance randomized controlled trials before a general recommendation can be given. The current standard for occlusion of blood vessels in thyroid surgery is ligatures. Vascular clips may be a safe alternative but have not been investigated in a large RCT. METHODS/DESIGN: CLIVIT (Clips versus Ligatures in Thyroid Surgery) is an investigator initiated, multicenter, patient-blinded, two-group parallel relevance randomized controlled trial designed by the Study Center of the German Surgical Society. Patients scheduled for elective resection of at least two third of the gland for benign thyroid disease are eligible for participation. After surgical exploration patients are randomized intraoperatively into either the conventional ligature group, or into the clip group. The primary objective is to test for a relevant reduction in operating time (at least 15 min) when using the clip technique. Since April 2004, 121 of the totally required 420 patients were randomized in five centers. DISCUSSION: As in all trials the different forms of bias have to be considered, and as in this case, a surgical trial, the role of surgical expertise plays a key role, and will be documented and analyzed separately. This is the first randomized controlled multicenter relevance trial to compare different vessel occlusion techniques in thyroid surgery with adequate power and other detailed information about the design as well as framework. If significant, the results might be generalized and may change the current surgical practice.

Comparison of Venae Sectio vs. modified Seldinger Technique for totally implantable access ports; Portas-trial [ISRCTN:52368201].

BACKGROUND: The insertion of a Totally Implantable Access Port (TIAP) is a routinely employed technique in patients who need a safe and permanent venous access. The number of TIAP implantations is increasing constantly mainly due to advanced treatment options for malignant diseases. Therefore it is important to identify the implantation technique which has the optimal benefit/risk ratio for the patient. STUDY DESIGN: A single-centre, randomized, controlled superiority trial to compare two different TIAP implantation techniques. SAMPLE SIZE: 160 patients will be included and randomized intra-operatively. ELIGIBILITY CRITERIA: Age equal or older than 18 years, patients scheduled for primary elective implantation of a TIAP in local anaesthesia and a signed informed consent. Primary endpoint: Primary success rate of the randomized technique. INTERVENTION: Venae Sectio in combination with the Seldinger Technique (guide wire and a peel away sheath) will be used to place a TIAP. Reference treatment: Conventional Venae Sectio will be used with a direct insertion of the TIAP without guide wire or peel away sheath. Duration of study: Approximately 20 months. ORGANISATION/RESPONSIBILITY: The trial will be conducted in compliance with the protocol and in accordance with the moral, ethical, and scientific principles governing clinical research as set out in the Declaration of Helsinki (1989) and Good Clinical Practice (GCP). The trial will also be carried out in keeping with local and regulatory requirements. The Klinisches Studienzentrum Chirurgie (KSC)--Centre of Clinical Trials in Surgery at the Department of Surgery, University Hospital Heidelberg is responsible for planning and conduction of the trial. Documentation of patient's data will be accomplished via electronical Case Report Files (eCRF) with MACRO-Software by the KSC. Randomization, data management, monitoring and biometry are provided by the independent Koordinierungszentrum für Klinische Studien (KKS)--Coordination Centre for Clinical Trails at the University of Heidelberg.

Clinical impact of cachexia on survival and outcome of cancer patients.

Approximately one half of all cancer patients experience a complex metabolic status involving progressive exhaustion of adipose and skeletal muscle tissue. This condition, known as cachexia, is responsible for more than 20% of the overall deaths in cancer patients. Although its main mechanisms remain unknown, several hypotheses have been proposed. One of the pathogenic mechanisms involves leptin and hypothalamic neuropeptide-containing pathways. Orexigenic and anorexigenic neuropeptides are down-regulated respectively upregulated as a result of cancer. Other pathogenic theories consider tumour derived factors, such as LMF (Lipid Mobilising Factor) and PIF (Proteolysis-inducing Factor), to be responsible for the weight losing pattern of cancer patients via activation of various catabolic pathways (e.g. ubiquitin-proteasome proteolytic-pathway, etc.). Despite the controversial discussion of cachexia-inducing mechanisms it is clear that proinflammatory cytokines, such as TNFalpha, IFNgamma, IL-1, IL-6 and IL-8, are linked to all pathways that induce cachexia. Although only limited treatment exists for patients with cancer cachexia, recent studies with eicosapaentanoic acid showed promising effects in reversing weight losing pattern of cachectic patients. Cytokine targeted monoclonal antibodies, cytokine traps and genetic therapies are also evaluated for future therapeutic strategies.

BMS-201620: a selective beta 3 agonist.

A series of N-(4-hydroxy-3-methylsulfonanilidoethanol)arylglycinamides were prepared and evaluated for their human beta3 adrenergic receptor agonist activity. SAR studies led to the identification of BMS-201620 (39), a potent beta3 full agonist (Ki = 93 nM, 93% activation). Based on its favorable safety profile, BMS-201620 was chosen for clinical evaluation.

Raman spectroscopic study of spatial distribution of propolis in comb of Apis mellifera carnica (Pollm.).

Micro-Raman spectroscopy and Raman mapping are applied to investigate the spatial distribution and chemical composition of wax and propolis in the comb of Apis mellifera carnica (Pollm). A thick layer of propolis at the rim of some cells is identified by Raman spectroscopy. Raman mapping is applied to resolve the distribution of propolis and wax on a micron scale. Both components are connected at the rim of the cell with a mixture of wax and propolis. A layer of almost pure propolis is found on top of the mixture. It appears that even in the mixture, where both components come into close contact, the propolis and the wax remain separated and keep their chemical identity.