Unleashing the full power of LHCb to probe stealth new physics.

In this paper, we describe the potential of the LHCb experiment to detect stealth physics. This refers to dynamics beyond the standard model that would elude searches that focus on energetic objects or precision measurements of known processes. Stealth signatures include long-lived particles and light resonances that are produced very rarely or together with overwhelming backgrounds. We will discuss why LHCb is equipped to discover this kind of physics at the Large Hadron Collider and provide examples of well-motivated theoretical models that can be probed with great detail at the experiment.

Extended evaluation of the efficacy of a proactive forced oscillation technique-based auto-CPAP algorithm.

PURPOSE: Previous studies revealed substantially varying therapy efficacy of automatic continuous positive airway pressure (APAP) devices in the treatment of obstructive sleep apnea (OSA). We evaluated the efficacy of a new APAP device using the forced oscillation technique (FOT) to evaluate upper airway obstruction during apneas and flow contour analyses during hypopneas. METHODS: Forty-six initially diagnosed OSA patients were included and the pressure range was set from 5 to 20 hPa. Therapy efficacy was assessed based on the reduction of apnea-hypopnea index (AHI), improvement of objective sleep quality parameters, and the appropriateness of the device's pressure regulation. RESULTS: AHI and arousal index significantly decreased during APAP therapy (median [interquartile range]: AHI 36 [23-55] vs. 2 [1-6]/h, arousal index 30 [22-45] vs. 15 [10-19]/h, both p < 0.001). The amount of slow wave sleep (SWS) and rapid-eye-movement (REM) sleep significantly increased (SWS 20 [14-29] vs. 29 [19-34]%, REM 16 [11-21] vs. 24 [14-30]%, both p < 0.01). Most residual respiratory events during therapy were of central etiology and attributable to five patients, who presented with treatment-emergent central sleep apnea. The device's pressure regulation abolished most obstructive respiratory events (n = 6.7 residual obstructive events per patient). Of central respiratory events, 534/646 (83%) did not lead to pressure increases. CONCLUSION: This pilot study provides a proof of concept that the APAP device combining FOT and evaluation of flow contour allows for the suppression of obstructive events without relevant false reactions.

[TEG-guided treatment of a dabigatran overdose in a patient with acute kidney failure]. / TEG-unterstützte Therapie einer Dabigatranüberdosierung bei einem Patienten mit akutem Nierenversagen.

This article presents the case of a multimorbid male patient with an accidental dabigatran overdose caused by kidney failure in the context of an acute intestinal disorder. After effective initial antagonizing of the dabigatran effect using idarucizumab a dabigatran rebound was detected caused by a single hemodialysis leading to a severe intrapulmonary hemorrhage. As dabigatran plasma level testing was not available and conventional coagulation analysis was out of interpretable range due to the impact of dabigatran, continuous thrombelastography (TEG) was used to detect the effect of dabigatran and monitor the treatment results. The most significant parameter used in the kaolin activated clotting time was the R­time parameter, which was massively prolonged by the interrupted coagulation cascade.

[RAS mutations at the molecular tumor conference]. / RAS-Mutationen in der molekularen Tumorkonferenz.

Members of the rat sarcoma (RAS) gene family belong to the most frequently mutated genes that drive pathogenesis and therapy response. As the discovery of their malignant potential dates back more than three decades, cellular mutated RAS genes and their products belong to the best characterized cancer genes. Despite urgent clinical needs, RAS therapies are still elusive and limited to preclinical studies. However, very recently, novel and promising approaches have become a reality in clinical applications and trials. In the near future, interesting therapeutic options will emerge that are capable of targeting "undruggable" RAS. This will be even more important as the detection of RAS mutations has already been an integral part of routine molecular diagnostics for many years.

Spin-orbit effects in optical spectra of gold-silver trimers.

Cationic gold-silver trimers are ideal model systems for the evaluation of relativistic electronic structure theories. The closed-shell triangles allow one to test density functional and wavefunction-based methods in their prediction of optical properties, as dependent on composition and symmetry. Here we present the gas-phase optical spectra of AgNAu3-N+ (N = 0-3) clusters recorded by longitudinal photodissociation spectroscopy in the photon energy range 1.9-4.4 eV. The experimental data are compared to excited electronic state calculations in the framework of all-electron range-separated time-dependent density functional and equation-of-motion coupled cluster theory using two-component as well as the spin-free scalar relativistic theories. In particular, it is shown that for mixed trimers scalar-relativistic corrections are insufficient and a two-component approach becomes obligatory for a correct description of optical response properties including both spin-orbit coupling and charge-transfer effects.

Pathogen-reduced Ebola virus convalescent plasma: first steps towards standardization of manufacturing and quality control including assessment of Ebola-specific neutralizing antibodies.

BACKGROUND: Ebola virus disease is a public health emergency of international concern, and enormous efforts are being made in the development of vaccines and therapies. Ebola virus convalescent plasma is a promising anti-infective treatment of Ebola virus disease. Therefore, we developed and implemented a pathogen-reduced Ebola virus convalescent plasma concept in accordance with national, European and global regulatory framework. MATERIALS AND METHODS: Ebola virus convalescent plasma manufacture and distribution was managed by a collection centre, two medical centres and an expert group from the European Blood Alliance. Ebola virus convalescent plasma was collected twice with an interval of 61 days from a donor recovering from Ebola virus disease in Germany. After pathogen reduction, the plasma was analysed for Ebola virus-specific immunoglobulin G (IgG) antibodies and its Ebola virus neutralizing activity. RESULTS: Convalescent plasma could be collected without adverse events. Anti-Ebola virus IgG titres and Ebola-specific neutralizing antibodies in convalescent plasma were only slightly reduced after pathogen reduction treatment with S59 amotosalen/UVA. A patient in Italy with Ebola virus disease was treated with convalescent plasma without apparent adverse effects. DISCUSSION: As proof of principle, we describe a concept and practical implementation of pathogen-reduced Ebola virus convalescent plasma manufacture, quality control and its clinical application to an Ebola virus disease patient.

[Mesenchymal stem/stroma cells : Therapeutic potential in the treatment of autoimmune diseases]. / Mesenchymale Stamm-/Stromazellen : Therapeutisches Potenzial in der Behandlung von Autoimmunerkrankungen.

Mesenchymal stem and stromal cells (MSC) are propagated for the treatment of autoimmune and autoinflammatory processes. These cells can be relatively easily obtained from various tissues. The MSC feature anti-inflammatory and immunosuppressive properties in vitro as well as in animal models. Initial reports on the clinical application of MSC for various diseases are available, some with promising results and so far no reported toxicity; however, data from phase III studies are still lacking and crucial questions are still unanswered. The MSC preparations used are heterogeneous and also differ depending on the source and it is unclear whether autologous (own) or allogeneic (foreign) MSC are more suitable for therapeutic use. Long-term consequences, such as possible malignant transformation and possible endogenous tumor growth stimulation cannot be completely excluded. Ultimately, these questions can only be answered through randomized controlled trials for defined clinical indications with defined MSC.

Pool-BCGA: a parallelised generation-free genetic algorithm for the ab initio global optimisation of nanoalloy clusters.

The Birmingham cluster genetic algorithm is a package that performs global optimisations for homo- and bimetallic clusters based on either first principles methods or empirical potentials. Here, we present a new parallel implementation of the code which employs a pool strategy in order to eliminate sequential steps and significantly improve performance. The new approach meets all requirements of an evolutionary algorithm and contains the main features of the previous implementation. The performance of the pool genetic algorithm is tested using the Gupta potential for the global optimisation of the Au10Pd10 cluster, which demonstrates the high efficiency of the method. The new implementation is also used for the global optimisation of the Au10 and Au20 clusters directly at the density functional theory level.

Charge-induced dipole vs. relativistically enhanced covalent interactions in Ar-tagged Au-Ag tetramers and pentamers.

Vibrational spectra of Au(n)Ag(m)(+)⋅Ar(k) (n + m = 4, 5; k = 1-4) clusters are determined by far-infrared resonant multiple photon dissociation spectroscopy in the range ν̃=100-250 cm(-1). The experimental spectra are assigned using density functional theory for geometries obtained by the Birmingham cluster genetic algorithm. Putative global minimum candidates of the Ar complexes are generated by adding Ar atoms to the Au(n)Ag(m)(+) low energy isomers and subsequent local optimization. Differential Ar binding energies indicate exceptionally strong Au-Ar bonds in Au-rich clusters, leading to fundamental changes to the IR spectra. The stronger Ar binding is attributed to a relativistically enhanced covalent character of the Au-Ar bond, while in Au-rich species charge-induced dipole interactions overcompensate the relativistic affinity to Au. Moreover, not only the absolute composition but also the topologies are essential in the description of Ar binding to a certain cluster.

[PALME--Arrival in Reality]. / PALME--Ankunft in der Wirklichkeit.

PALME is an emotion-centred parental training for single mothers and their children based on attachment theory. It was designed for the prevention of maternal depression and its long-term effects on the mother-child relation and the infant's development. Using the example of the PALME programme, inherent and external factors are demonstrated which can contribute to the successful transfer of prevention programmes into psychosocial care and other practice areas.

The current and future role of the medical oncologist in the professional care for cancer patients: a position paper by the European Society for Medical Oncology (ESMO).

The number of cancer patients in Europe is rising and significant advances in basic and applied cancer research are making the provision of optimal care more challenging. The concept of cancer as a systemic, highly heterogeneous and complex disease has increased the awareness that quality cancer care should be provided by a multidisciplinary team (MDT) of highly qualified healthcare professionals. Cancer patients also have the right to benefit from medical progress by receiving optimal treatment from adequately trained and highly skilled medical professionals. Built on the highest standards of professional training and continuing medical education, medical oncology is recognised as an independent medical specialty in many European countries. Medical oncology is a core member of the MDT and offers cancer patients a comprehensive and systemic approach to treatment and care, while ensuring evidence-based, safe and cost-effective use of cancer drugs and preserving the quality of life of cancer patients through the entire 'cancer journey'. Medical oncologists are also engaged in clinical and translational research to promote innovation and new therapies and they contribute to cancer diagnosis, prevention and research, making a difference for patients in a dynamic, stimulating professional environment. Medical oncologists play an important role in shaping the future of healthcare through innovation and are also actively involved at the political level to ensure a maximum contribution of the profession to Society and to tackle future challenges. This position paper summarises the multifarious and vital contributions of medical oncology and medical oncologists to today's and tomorrow's professional cancer care.

Communication: Global minimum search of Ag10⁺ with molecular beam optical spectroscopy.

The present study is focused on the optical properties of the Ag10⁺ cluster in the photon energy range ℏω = 1.9-4.4 eV. Absorption spectra are recorded by longitudinal molecular beam depletion spectroscopy and compared to optical response calculations using time-dependent density functional theory. Several cluster isomers obtained by the new pool-based parallel implementation of the Birmingham Cluster Genetic Algorithm, coupled with density functional theory, are used in excited state calculations. The experimental observations, together with additional simulations of ion mobilities for the several geometries found within this work using different models, clearly identify the ground state isomer of Ag10⁺ to be composed of two orthogonal interpenetrating pentagonal bipyramids, having overall D(2d) symmetry.

Optical and electronic properties of mixed Ag-Au tetramer cations.

We present experimental and theoretical studies of the optical response of mixed Ag(n)Au(+)(4-n) (n=1-3) clusters in the photon energy range ℏω = 1.9-3.5 eV. Absorption spectra are recorded by a newly built longitudinal molecular beam depletion spectroscopy apparatus providing lower limits to absolute photodissociation cross sections. The experimental data are compared to optical response calculations in the framework of long-range corrected time-dependent density functional theory with initial cluster geometries obtained by the unbiased Birmingham Cluster Genetic Algorithm coupled with density functional theory. Experiments and excited state calculations shed light on the structural and electronic properties of the mixed Ag-Au tetramer cations.

Influence of spin-orbit effects on structures and dielectric properties of neutral lead clusters.

Combining molecular beam electric deflection experiments and global optimization techniques has proven to be a powerful tool for resolving equilibrium structures of neutral metal and semiconductor clusters. Herein, we present electric molecular beam deflection experiments on PbN (N = 7-18) clusters. Promising structures are generated using the unbiased Birmingham Cluster Genetic Algorithm approach based on density functional theory. The structures are further relaxed within the framework of two-component density functional theory taking scalar relativistic and spin orbit effects into account. Quantum chemical results are used to model electric molecular beam deflection profiles based on molecular dynamics calculations. Comparison of measured and simulated beam profiles allows the assignment of equilibrium structures for the most cluster sizes in the examined range for the first time. Neutral lead clusters adopt mainly spherical geometries and resemble the structures of lead cluster cations apart from Pb10. Their growth pattern deviates strongly from the one observed for tin and germanium clusters.

Evaluation of photodissociation spectroscopy as a structure elucidation tool for isolated clusters: a case study of Ag4(+) and Au4(+).

Resolving the structure of clusters in the gas phase often requires the comparison of experimental data to quantum chemical calculations. Herein, we present the variation of a straightforward approach, in which photodissociation spectra of isolated clusters are compared to optical response calculations in order to elucidate cluster structures. Our absorption spectra were measured using a newly built longitudinal beam depletion spectroscopy apparatus and recorded in the photon energy range hω = 1.9-3.5 eV. Cluster geometries were obtained using the unbiased Birmingham Cluster Genetic Algorithm coupled with density functional theory, while the optical response was calculated in the framework of time-dependent density functional theory. Experiments and excited state calculations are in excellent agreement using long-range corrected exchange correlation functionals for both ground and excited state calculations. Our methodology indicates a contribution of Y shaped Au4(+) whereas for Ag4(+) only the ground state isomer has to be considered to explain the experimental absorption spectrum. Our extended methodology shows two nearly degenerate isomers of Au4(+) probably being present in the molecular beam and therefore shows promise for the further structure determination of pure and binary transition-metal clusters.

Perioperative and long-term development of anxiety and depression in CABG patients.

BACKGROUND: The high incidence of symptomatic anxiety and depression in coronary artery bypass graft (CABG) patients may lead to impaired quality of life and increased morbidity and mortality. This prospective longitudinal study on CABG patients should provide data for future preoperative and postoperative psychotherapeutic interventions. METHODS: From 2009 to 2010, 135 consecutive patients who were able and prepared were consulted by one interviewer immediately before 1 week (early) and 6 months (late) after surgery to complete the "Hospital Anxiety and Depression Scale" questionnaire. RESULTS: Compared with the standard population, anxiety scores (AS) were preoperatively elevated in 39.3% of the patients. Early and late after surgery, AS had decreased to 34.4% (not significant [n.s.]) and 28.9% (p < 0.01). Before surgery, depression scores (DS) were elevated in 20.7%. Early and late after surgery, DS further increased to 24.0% (n.s.) and 28.0% (n.s.).Preoperative elevated DS appeared to correlate with increased complications. Mortality was not associated with elevated AS or DS. Both scores were not affected by on- or off-pump surgery. CONCLUSION: Remarkably high AS and elevated DS late postoperatively require psychotherapeutic support even after seemingly successful CABG.

A genome-wide survey of RAS transformation targets.

An important aspect of multi-step tumorigenesis is the mutational activation of genes of the RAS family, particularly in sporadic cancers of the pancreas, colon, lung and myeloid system. RAS genes encode small GTP-binding proteins that affect gene expression in a global way by acting as major switches in signal transduction processes, coupling extracellular signals with transcription factors. Oncogenic forms of RAS are locked in their active state and transduce signals essential for transformation, angiogenesis, invasion and metastasis via downstream pathways involving the RAF/MEK/ERK cascade of cytoplasmic kinases, the small GTP-binding proteins RAC and RHO, phosphatidylinositol 3-kinase and others. We have used subtractive suppression hybridization (SSH), a PCR-based cDNA subtraction technique, to contrast differential gene expression profiles in immortalized, non-tumorigenic rat embryo fibroblasts and in HRAS- transformed cells. Sequence and expression analysis of more than 1,200 subtracted cDNA fragments revealed transcriptional stimulation or repression of 104 ESTs, 45 novel sequences and 244 known genes in HRAS- transformed cells compared with normal cells. Furthermore, we identified common and distinct targets in cells transformed by mutant HRAS, KRAS and NRAS, as well as 61 putative target genes controlled by the RAF/MEK/ERK pathway in reverted cells treated with the MEK-specific inhibitor PD 98059.

Ionization potentials of metal clusters studied with a broad range, tunable vacuum ultraviolet light source.

In this work, we present an alternative to complex laser setups or synchrotron light sources to accurately measure the ionization potentials of metal clusters. The setup is based on a commercial Xe flash lamp, combined with a vacuum monochromator, and has been applied to determine the ionization potentials of Snn clusters with n = 8-12 atoms. The uncertainty in the determination of the ionization potentials is mainly caused by the bandwidth of the monochromator. The adiabatic ionization potentials (AIPs) are extracted from experimental photoionization efficiency curves. Franck-Condon simulations are additionally used to interpret the shape and onset of the photo-ion yield. The obtained AIPs are (all energies are in eV) Sn8 (6.53 ± 0.05), Sn9 (6.69 ± 0.04), Sn10 (6.93 ± 0.03), Sn11 (6.34 ± 0.05), and Sn12 (IsoI 6.64 ± 0.04 and IsoIII 6.36 ± 0.05). Furthermore, the impact of multiple isomers present in the experiment on the photo-ion yield is addressed and compared with other experimental data in the literature.