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1.  Non-signalling energy use in the developing rat brain 
Energy use in the brain constrains its information processing power, but only about half the brain's energy consumption is directly related to information processing. Evidence for which non-signalling processes consume the rest of the brain's energy has been scarce. For the first time, we investigated the energy use of the brain's main non-signalling tasks with a single method. After blocking each non-signalling process, we measured oxygen level changes in juvenile rat brain slices with an oxygen-sensing microelectrode and calculated changes in oxygen consumption throughout the slice using a modified diffusion equation. We found that the turnover of the actin and microtubule cytoskeleton, followed by lipid synthesis, are significant energy drains, contributing 25%, 22% and 18%, respectively, to the rate of oxygen consumption. In contrast, protein synthesis is energetically inexpensive. We assess how these estimates of energy expenditure relate to brain energy use in vivo, and how they might differ in the mature brain.
doi:10.1177/0271678X16648710
PMCID: PMC5322833  PMID: 27170699
ATP; brain development; brain slice; energy metabolism; lipids
2.  A case study for a psychographic-behavioral segmentation approach for targeted demand generation in voluntary medical male circumcision 
eLife  null;6:e25923.
Public health programs are starting to recognize the need to move beyond a one-size-fits-all approach in demand generation, and instead tailor interventions to the heterogeneity underlying human decision making. Currently, however, there is a lack of methods to enable such targeting. We describe a novel hybrid behavioral-psychographic segmentation approach to segment stakeholders on potential barriers to a target behavior. We then apply the method in a case study of demand generation for voluntary medical male circumcision (VMMC) among 15–29 year-old males in Zambia and Zimbabwe. Canonical correlations and hierarchical clustering techniques were applied on representative samples of men in each country who were differentiated by their underlying reasons for their propensity to get circumcised. We characterized six distinct segments of men in Zimbabwe, and seven segments in Zambia, according to their needs, perceptions, attitudes and behaviors towards VMMC, thus highlighting distinct reasons for a failure to engage in the desired behavior.
eLife digest
Companies invest a significant amount of time and money into market research that helps them to understand the behaviors, beliefs and motivations of their potential customers. By then “segmenting” people into groups according to these characteristics, marketing messages can be produced that target specific groups more effectively.
Most public health efforts are either mass communication campaigns or target particular age groups. However, some public health organizations are starting to study whether the segmenting tactics used by companies could also help to promote healthy behaviors. For example, male circumcision has been shown to reduce the transmission of HIV in Africa. Identifying the beliefs, emotions, motivations or other barriers that stop men from getting circumcised and then targeting specific messages to different groups could help to increase the number of men who opt for circumcision.
Sgaier et al. now present evidence that suggests that segmentation could help to promote circumcision in Zimbabwe and Zambia. 4,000 men from these countries answered a survey that had been designed based on previous research that investigated how men make the decision whether to be circumcised. Analyzing the results using k-means clustering, a machine learning algorithm, enabled Sgaier et al. to identify six distinct segments in the men from Zimbabwe and seven in the men from Zambia. Further analyses found that the risk of contracting HIV also varied by segment.
Sgaier et al. then demonstrated that field workers could use a series of questions to allocate men to each of the groups with an accuracy of over 60%. The segmentation method therefore looks like a promising tool that could be applied to a wide range of public health campaigns. As well as targeting specific groups of people with messaging that resonates specifically with them, segmentation could also highlight those people who are likely to be most easily convinced by a particular health intervention. More research is now needed to improve the usability of the tools that field workers can use to segment their audience.
doi:10.7554/eLife.25923
PMCID: PMC5628013  PMID: 28901285
voluntary medical male circumcision; segmentation; demand generation; None
3.  The semiclassical propagator in Fock space: dynamical echo and many-body interference 
We present a semiclassical approach to many-body quantum propagation in terms of coherent sums over quantum amplitudes associated with the solutions of corresponding classical nonlinear wave equations. This approach adequately describes interference effects in the many-body space of interacting bosonic systems. The main quantity of interest, the transition amplitude between Fock states when the dynamics is driven by both single-particle contributions and many-body interactions of similar magnitude, is non-perturbatively constructed in the spirit of Gutzwiller’s derivation of the van Vleck propagator from the path integral representation of the time evolution operator, but lifted to the space of symmetrized many-body states. Effects beyond mean-field, here representing the classical limit of the theory, are semiclassically described by means of interfering amplitudes where the action and stability of the classical solutions enter. In this way, a genuinely many-body echo phenomenon, coherent backscattering in Fock space, is presented arising due to coherent quantum interference between classical solutions related by time reversal.
doi:10.1098/rsta.2015.0159
PMCID: PMC4855400  PMID: 27140976
semiclassics; many-body dynamics; ultracold atoms; coherent backscattering; interference
4.  The digestive and defensive basis of carcass utilization by the burying beetle and its microbiota 
Nature Communications  2017;8:15186.
Insects that use ephemeral resources must rapidly digest nutrients and simultaneously protect them from competitors. Here we use burying beetles (Nicrophorus vespilloides), which feed their offspring on vertebrate carrion, to investigate the digestive and defensive basis of carrion utilization. We characterize gene expression and microbiota composition in the gut, anal secretions, and on carcasses used by the beetles. We find a strict functional compartmentalization of the gut involving differential expression of immune effectors (antimicrobial peptides and lysozymes), as well as digestive and detoxifying enzymes. A distinct microbial community composed of Firmicutes, Proteobacteria and a clade of ascomycetous yeasts (genus Yarrowia) is present in larval and adult guts, and is transmitted to the carcass via anal secretions, where the yeasts express extracellular digestive enzymes and produce antimicrobial compounds. Our results provide evidence of potential metabolic cooperation between the host and its microbiota for digestion, detoxification and defence that extends from the beetle's gut to its nutritional resource.
Burying beetles feed their offspring on the carrion of vertebrate animals. Here, the authors study gene expression in the insect's gut, as well as the composition of the microbiota in the gut and in carcasses, providing evidence for metabolic cooperation between host and specific microbes.
doi:10.1038/ncomms15186
PMCID: PMC5436106  PMID: 28485370
5.  Non-signalling energy use in the developing rat brain 
Energy use in the brain constrains its information processing power, but only about half the brain's energy consumption is directly related to information processing. Evidence for which non-signalling processes consume the rest of the brain's energy has been scarce. For the first time, we investigated the energy use of the brain's main non-signalling tasks with a single method. After blocking each non-signalling process, we measured oxygen level changes in juvenile rat brain slices with an oxygen-sensing microelectrode and calculated changes in oxygen consumption throughout the slice using a modified diffusion equation. We found that the turnover of the actin and microtubule cytoskeleton, followed by lipid synthesis, are significant energy drains, contributing 25%, 22% and 18%, respectively, to the rate of oxygen consumption. In contrast, protein synthesis is energetically inexpensive. We assess how these estimates of energy expenditure relate to brain energy use in vivo, and how they might differ in the mature brain.
doi:10.1177/0271678X16648710
PMCID: PMC5322833  PMID: 27170699
ATP; brain development; brain slice; energy metabolism; lipids
6.  Serotonin improves glucose metabolism by Serotonylation of the small GTPase Rab4 in L6 skeletal muscle cells 
Background
Serotonin (5-HT) improves insulin sensitivity and glucose metabolism, however, the underlying molecular mechanism has remained elusive. Previous studies suggest that 5-HT can activate intracellular small GTPases directly by covalent binding, a process termed serotonylation. Activated small GTPases have been associated with increased GLUT4 translocation to the cell membrane. Therefore, we investigated whether serotonylation of small GTPases may be involved in improving Insulin sensitivity and glucose metabolism.
Methods
Using fully differentiated L6 rat skeletal muscle cells, we studied the effect of 5-HT in the absence or presence of insulin on glycogen synthesis, glucose uptake and GLUT4 translocation. To prove our L6 model we additionally performed preliminary experiments in C2C12 murine skeletal muscle cells.
Results
Incubation with 5-HT led to an increase in deoxyglucose uptake in a concentration-dependent fashion. Accordingly, GLUT4 translocation to the cell membrane and glycogen content were increased. These effects of 5-HT on Glucose metabolism could be augmented by co-incubation with insulin and blunted by co incubation of 5-HT with monodansylcadaverine, an inhibitor of protein serotonylation. In accordance with this observation, incubation with 5-HT resulted in serotonylation of a protein with a molecular weight of approximately 25 kDa. We identified this protein as the small GTPase Rab4, the activity of which has been shown to be stimulated by both insulin signalling and serotonylation.
Conclusion
Our data suggest that 5-HT elicits its beneficial effects on Glucose metabolism through serotonylation of Rab4, which likely represents the converging point between the insulin and the 5-HT signalling cascades.
doi:10.1186/s13098-016-0201-1
PMCID: PMC5209910  PMID: 28053672
Serotonin; GLUT4; Rab4; L6 skeletal muscle cells; Glucose uptake; Serotonylation
7.  Detection of early DJ-stent encrustation by sonographic twinkling-artifacts – a pilot study 
Introduction
Ureter obstruction caused by a retro-peritoneal tumor is treated by inserting an indwelling ureter splint (DJ-stent). Indwelling duration is limited by cumulative crystalline deposits into the splint, eventually causing the repeated impairment of urine flow. Deciding when a DJ-stent must be replaced is important since belated removal can be accompanied by severe complications. X-ray or conventional sonography do not allow satisfactory evaluation of early incrustation, therefore, the use of sonographic twinkling artifacts (TA) to provide accurate stent surveillance was investigated.
Material and methods
26 patients with indwelling ureter splints carrying a high risk of developing tumor lysis syndrome (TLS), which is often accompanied by early splint incrustation, were investigated utilizing TA the day after DJ-stent implantation and weekly thereafter. Serum creatinine, uric acid, and urine pH were measured at all TA exams.
Results
Early incrustation of the ureter splint was detected by TA in all patients 1–4 weeks after implantation. Incrustation occurred sooner with increased uric acid levels, and high creatinine or acidic urine accelerated early implant incrustation.
Conclusions
TA can be used to monitor early crystalline deposits in implanted ureter splints, before they can be detected by conventional sonography or X-ray imaging and before complications occur.
doi:10.5173/ceju.2017.912
PMCID: PMC5407330
twinkling-artifact; DJ-stent; stent incrustation; encrusted urologic implant; color Doppler; tumor lysis syndrome; hydronephrosis
8.  Fatigue, depression, and quality of life in patients with prostatic diseases 
Introduction
Fatigue and depression are commonly attributed to malignant and chronic benign diseases. However, these phenomena have been little investigated to date in prostatic diseases. Our aim was to compare fatigue and depression in prostate cancer patients treated with Androgen Deprivation Therapy (ADT) and in patients with Lower Urinary Tract Symptoms (LUTS) / Benign Prostatic Syndrome.
Material and methods
100 patients each with PCa (prostate cancer) and BPS (Benign Prostatic Syndrome) were surveyed using the Brief Fatigue Inventory (BFI), EORTC-QLQ C30 [1], and Beck Depression Inventory (BDI). EORTC-QLQ-C30 was analyzed by the Mann-Whitney-U-Test. Results were analyzed using the MWUT, CST and ST.
Results
No differences were found between both groups in terms of fatigue (BFI). The prostate cancer group showed a significantly higher impairment in the EORTC-QLQ-C30 role function and fatigue score. We found differences on the BDI in regards to self-criticism with higher mean scores for LUTS patients, whereas loss of energy and loss of sexual interest were more relevant in prostate cancer patients. However, the overall mean score of both groups showed no difference.
Conclusions
This study compared fatigue, depression, and the quality of life in prostate cancer patients treated with ADT and patients with BPS/LUTS. The two groups do not differ in fatigue and depression levels.
doi:10.5173/ceju.2017.940
PMCID: PMC5407337
prostate cancer; BPS; fatigue; depression
9.  Impact of vasectomy on the sexual satisfaction of couples: experience from a specialized clinic 
Introduction
Vasectomy is the simplest, safest, and most effective form of definitive fertility control in men [1]. Vasectomy is used for 10% of contraception worldwide but only for 2% in Germany [2]. The aim of this study was to investigate the impact of vasectomy on the sexual satisfaction of sterilized men and their partners.
Material and methods
Vasectomized men and their partners were surveyed by means of the IIEF (International Index for Erectile Function) and the FSFI (Female Sexual Function Index) questionnaires. A total of 294 couples were surveyed; 90 men answered the IIEF, and 74 women answered the FSFI. The results of the questionnaires were compared to a historical comparison group. The men were also surveyed with a not validated questionnaire, which was returned by 95 men. The two-sample t-test for independent samples, the chi-squared test, and the Wilcoxon-Mann-Whitney test were carried out.
Results
The vasectomized men had significantly better results than the healthy historical comparison group in the IIEF domains of erectile function, orgasm, sexual desire, and intercourse satisfaction. For the female partners of the sterilized men, there were almost no significant differences in any questions of the FSFI in comparison to the control group. A significant difference was observed only in the domain ‘arousal’.
Conclusions
Vasectomy does not have a negative impact on the sexual satisfaction of the affected couples. In fact, sexual satisfaction improved for the sterilized men, while the satisfaction of the women was not reduced by the vasectomy.
doi:10.5173/ceju.2017.1294
PMCID: PMC5656365
vasectomy; sexual satisfaction; IIEF; FSF
10.  Efficacy, safety, tolerability and pharmacokinetics of a novel human immune globulin subcutaneous, 20%: a Phase 2/3 study in Europe in patients with primary immunodeficiencies 
Summary
A highly concentrated (20%) immunoglobulin (Ig)G preparation for subcutaneous administration (IGSC 20%), would offer a new option for antibody replacement therapy in patients with primary immunodeficiency diseases (PIDD). The efficacy, safety, tolerability and pharmacokinetics of IGSC 20% were evaluated in a prospective trial in Europe in 49 patients with PIDD aged 2–67 years. Over a median of 358 days, patients received 2349 IGSC 20% infusions at monthly doses equivalent to those administered for previous intravenous or subcutaneous IgG treatment. The rate of validated acute bacterial infections (VASBIs) was significantly lower than 1 per year (0·022/patient‐year, P < 0·0001); the rate of all infections was 4·38/patient‐year. Median trough IgG concentrations were ≥ 8 g/l. There was no serious adverse event (AE) deemed related to IGSC 20% treatment; related non‐serious AEs occurred at a rate of 0·101 event/infusion. The incidence of local related AEs was 0·069 event/infusion (0·036 event/infusion, when excluding a 13‐year‐old patient who reported 79 of 162 total related local AEs). The incidence of related systemic AEs was 0·032 event/infusion. Most related AEs were mild, none were severe. For 64·6% of patients and in 94·8% of IGSC 20% infusions, no local related AE occurred. The median infusion duration was 0·95 (range = 0·3‐4·1) h using mainly one to two administration sites [median = 2 sites (range = 1–5)]. Almost all infusions (99·8%) were administered without interruption/stopping or rate reduction. These results demonstrate that IGSC 20% provides an effective and well‐tolerated therapy for patients previously on intravenous or subcutaneous treatment, without the need for dose adjustment.
doi:10.1111/cei.12866
PMCID: PMC5167020  PMID: 27613250
20% immunoglobulin; immunoglobulin replacement therapy; pharmacokinetics; primary immunodeficiency diseases; subcutaneous administration
11.  Improving quality of care in general practices by self-audit, benchmarking and quality circles 
Wiener Klinische Wochenschrift  2016;128(19):706-718.
Summary
Guideline adherence of general practitioners (GP) regarding treatment of chronic conditions shows room for improvement. Thus, concepts have to be designed to promote quality of care. The aim of the interventional study “Improvement of Quality by Benchmarking” was to assess whether quality can be improved by self-auditing, benchmarking and quality circles in Salzburg (Austria) and South Tyrol (Italy). In this publication we present the Austrian results. Quality indicators were developed in a consensus process for eight chronic diseases based on pre-existing quality management systems. A quality score consisting of 35 indicators was calculated (0–5 points per indicator depending on fulfilment, maximum 175 points). Data were extracted from the electronic health records of participating practices in 2012, 2013 and 2014. A statistical pre-post analysis was performed using Wilcoxon signed-rank tests. A total of 20 GPs participated in the project. The mean quality score increased from 62.0 at baseline to 84.0 at the second follow-up (p = 0.003). Regarding the individual quality indicators, strong improvements were achieved between baseline and first follow-up, especially in process indicators concerning documentation. Between the first and second follow-up, quality remained in most cases at the same level. The validity of results is limited because of structural and technical problems. Due to the uncontrolled pre-post design we cannot exclude external influences on the results. Nevertheless, the intervention was able to improve measured quality of care. Barriers were detected that should be considered in a possible implementation of quality control programs.
doi:10.1007/s00508-016-1064-z
PMCID: PMC5052301  PMID: 27599700
General practice; Healthcare quality; Quality indicators; Chronic diseases; Quality circles
12.  Non-signalling energy use in the brain 
The Journal of Physiology  2015;593(Pt 16):3417-3429.
Energy use limits the information processing power of the brain. However, apart from the ATP used to power electrical signalling, a significant fraction of the brain's energy consumption is not directly related to information processing. The brain spends just under half of its energy on non-signalling processes, but it remains poorly understood which tasks are so energetically costly for the brain. We review existing experimental data on subcellular processes that may contribute to this non-signalling energy use, and provide modelling estimates, to try to assess the magnitude of their ATP consumption and consider how their changes in pathology may compromise neuronal function. As a main result, surprisingly little consensus exists on the energetic cost of actin treadmilling, with estimates ranging from < 1% of the brain's global energy budget up to one-half of neuronal energy use. Microtubule treadmilling and protein synthesis have been estimated to account for very small fractions of the brain's energy budget, whereas there is stronger evidence that lipid synthesis and mitochondrial proton leak are energetically expensive. Substantial further research is necessary to close these gaps in knowledge about the brain's energy-expensive non-signalling tasks.
doi:10.1113/jphysiol.2014.282517
PMCID: PMC4560575  PMID: 25639777
13.  Cellular and molecular phenotypes depending upon the RNA repair system RtcAB of Escherichia coli 
Nucleic Acids Research  2016;44(20):9933-9941.
RNA ligases function pervasively across the three kingdoms of life for RNA repair, splicing and can be stress induced. The RtcB protein (also HSPC117, C22orf28, FAAP and D10Wsu52e) is one such conserved ligase, involved in tRNA and mRNA splicing. However, its physiological role is poorly described, especially in bacteria. We now show in Escherichia coli bacteria that the RtcR activated rtcAB genes function for ribosome homeostasis involving rRNA stability. Expression of rtcAB is activated by agents and genetic lesions which impair the translation apparatus or may cause oxidative damage in the cell. Rtc helps the cell to survive challenges to the translation apparatus, including ribosome targeting antibiotics. Further, loss of Rtc causes profound changes in chemotaxis and motility. Together, our data suggest that the Rtc system is part of a previously unrecognized adaptive response linking ribosome homeostasis with basic cell physiology and behaviour.
doi:10.1093/nar/gkw628
PMCID: PMC5175333  PMID: 27402162
14.  Long-Term Tolerability, Safety, and Efficacy of Recombinant Human Hyaluronidase-Facilitated Subcutaneous Infusion of Human Immunoglobulin for Primary Immunodeficiency 
Purpose
Treatment of primary immunodeficiency diseases (PIDD) with subcutaneous (SC) infusions of IgG preceded by injection of recombinant human hyaluronidase (rHuPH20) (IGHy) to increase SC tissue permeability was evaluated in two consecutive, prospective, non-controlled, multi-center studies.
Methods
Subjects >4 years of age received SC IgG replacement at a weekly dose equivalent of 108 % of their previous intravenous (IV) dose, facilitated by prior injection of 75 U/g IgG of rHuPH20. Starting with weekly SC infusions, the interval was increased (ramped-up) to a 3- or 4-week schedule.
Results
Eighty-three subjects (24 < 18 years; 59 ≥ 18 years) received 2729 infusions (excluding ramp-up) at a mean dose of 0.155 g/kg/week in the pivotal and 0.156 g/kg/week in the extension study. IGHy exposure exceeded 30 months in 48 subjects.
During 187.7 subject-years of IGHy exposure, 2005 adverse events (AEs) (10.68 per subject-year) occurred. The rate of related systemic AEs during consecutive 1-year periods remained low; the rate of related local AEs decreased from 3.68/subject-year in months 1–12 to approximately 1.50/subject-year after 30 months of treatment. Fifteen subjects transiently developed anti-rHuPH20 binding antibody. There was no difference in AE rates in these subjects before and after the first titer increase to ≥1:160.
The rate of infections during IGHy exposure was 2.99 per subject-year and did not increase during the studies. Annual infection rates were 3.02 in subjects <18 years and 2.98 in subjects ≥18 years.
Conclusions
Long-term replacement therapy with IGHy was safe and effective in 83 pediatric and adult subjects with PIDD.
Electronic supplementary material
The online version of this article (doi:10.1007/s10875-016-0298-x) contains supplementary material, which is available to authorized users.
doi:10.1007/s10875-016-0298-x
PMCID: PMC4940441  PMID: 27220317
Subcutaneous IgG replacement; recombinant human hyaluronidase; primary immunodeficiency; efficacy; tolerability
15.  Non‐signalling energy use in the brain 
The Journal of Physiology  2015;593(16):3417-3429.
Abstract
Energy use limits the information processing power of the brain. However, apart from the ATP used to power electrical signalling, a significant fraction of the brain's energy consumption is not directly related to information processing. The brain spends just under half of its energy on non‐signalling processes, but it remains poorly understood which tasks are so energetically costly for the brain. We review existing experimental data on subcellular processes that may contribute to this non‐signalling energy use, and provide modelling estimates, to try to assess the magnitude of their ATP consumption and consider how their changes in pathology may compromise neuronal function. As a main result, surprisingly little consensus exists on the energetic cost of actin treadmilling, with estimates ranging from < 1% of the brain's global energy budget up to one‐half of neuronal energy use. Microtubule treadmilling and protein synthesis have been estimated to account for very small fractions of the brain's energy budget, whereas there is stronger evidence that lipid synthesis and mitochondrial proton leak are energetically expensive. Substantial further research is necessary to close these gaps in knowledge about the brain's energy‐expensive non‐signalling tasks.
doi:10.1113/jphysiol.2014.282517
PMCID: PMC4560575  PMID: 25639777
16.  A Prophylactic Role for Creatine in Hypoxia? 
The Journal of Neuroscience  2015;35(25):9249-9251.
doi:10.1523/JNEUROSCI.1195-15.2015
PMCID: PMC4478245  PMID: 26109649
17.  Energy-Efficient Information Transfer by Visual Pathway Synapses 
Current Biology  2015;25(24):3151-3160.
Summary
The architecture of computational devices is shaped by their energy consumption. Energetic constraints are used to design silicon-based computers but are poorly understood for neural computation. In the brain, most energy is used to reverse ion influxes generating excitatory postsynaptic currents (EPSCs) and action potentials. Thus, EPSCs should be small to minimize energy use, but not so small as to impair information transmission. We quantified information flow through the retinothalamic synapse in the visual pathway in brain slices, with cortical and inhibitory input to the postsynaptic cell blocked. Altering EPSC size with dynamic clamp, we found that a larger-than-normal EPSC increased information flow through the synapse. Thus, the evolutionarily selected EPSC size does not maximize retinal information flow to the cortex. By assessing the energy used on postsynaptic ion pumping and action potentials, we show that, instead, the EPSC size optimizes the ratio of retinal information transmitted to energy consumed. These data suggest maximization of information transmission per energy used as a synaptic design principle.
Highlights
•How do synapses optimize energy consumption on information transmission?•We find that increasing synaptic current size increases information transmission•But larger or smaller EPSCs decrease the information transmitted per energy used•Thus, the biologically observed EPSC size maximizes synapse energy efficiency
Synapses transmit information between neurons, but the energetic cost of postsynaptic currents is high. How are synaptic properties set to balance this trade-off? Harris et al. show that thalamic relay synapse properties are tuned to maximize not bits of information transmitted per second but bits of information transmitted per ATP molecule used.
doi:10.1016/j.cub.2015.10.063
PMCID: PMC4691239  PMID: 26671670
18.  Use of complementary and alternative medicine before and after organ removal due to urologic cancer 
Objective
Many patients use complementary and alternative medicine (CAM) as primary treatment or symptom relief for a variety of illnesses. This study was designed to investigate the influence of surgical removal of a tumor-bearing urogenital organ on CAM use.
Methods
From 2007 to 2011, 350 patients underwent major urological surgery for kidney, prostate, or bladder cancer at the Goethe-University Hospital, Frankfurt, Germany. Data from 172 patients (49%), who returned a questionnaire, were retrospectively evaluated using the hospital information system along with the questionnaire to objectify CAM use 2 years before and after surgery.
Results
From the 172 patients returning questionnaires, 56 (33%) used CAM before and/or after surgery and 116 (67%) never used CAM. Of the 56 CAM users, 30 (54%) used CAM presurgery and 53 (95%) used CAM postsurgery, indicating a significant change of mind about CAM use. Patients of German nationality used CAM significantly more than patients of other nationalities. Higher educational status (high-school diploma or higher) was a significant factor in favor of CAM use. The most common type of CAM used before/after surgery was an alternative medical system (63/49%), a manipulative and body-based method (50/19%), and a biological-based therapy (37/32%). Information about CAM, either provided by medical professionals or by other sources, was the main reason determining whether patients used CAM or not.
Conclusion
The number of patients using CAM almost doubled after surgical removal of a cancer-bearing organ. Better awareness and understanding of CAM use by medical professionals could improve patient counseling.
doi:10.2147/PPA.S90061
PMCID: PMC4599187  PMID: 26491269
complementary and alternative medicine; surgery; urologic cancer
19.  Genome wide interactions of wild-type and activator bypass forms of σ54 
Nucleic Acids Research  2015;43(15):7280-7291.
Enhancer-dependent transcription involving the promoter specificity factor σ54 is widely distributed amongst bacteria and commonly associated with cell envelope function. For transcription initiation, σ54-RNA polymerase yields open promoter complexes through its remodelling by cognate AAA+ ATPase activators. Since activators can be bypassed in vitro, bypass transcription in vivo could be a source of emergent gene expression along evolutionary pathways yielding new control networks and transcription patterns. At a single test promoter in vivo bypass transcription was not observed. We now use genome-wide transcription profiling, genome-wide mutagenesis and gene over-expression strategies in Escherichia coli, to (i) scope the range of bypass transcription in vivo and (ii) identify genes which might alter bypass transcription in vivo. We find little evidence for pervasive bypass transcription in vivo with only a small subset of σ54 promoters functioning without activators. Results also suggest no one gene limits bypass transcription in vivo, arguing bypass transcription is strongly kept in check. Promoter sequences subject to repression by σ54 were evident, indicating loss of rpoN (encoding σ54) rather than creating rpoN bypass alleles would be one evolutionary route for new gene expression patterns. Finally, cold-shock promoters showed unusual σ54-dependence in vivo not readily correlated with conventional σ54 binding-sites.
doi:10.1093/nar/gkv597
PMCID: PMC4551910  PMID: 26082500
20.  Muon reconstruction efficiency and momentum resolution of the ATLAS experiment in proton–proton collisions at \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sqrt{s}=7$$\end{document}s=7 TeV in 2010 
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This paper presents a study of the performance of the muon reconstruction in the analysis of proton–proton collisions at \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sqrt{s}=7$$\end{document}s=7 TeV at the LHC, recorded by the ATLAS detector in 2010. This performance is described in terms of reconstruction and isolation efficiencies and momentum resolutions for different classes of reconstructed muons. The results are obtained from an analysis of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$J/\psi $$\end{document}J/ψ meson and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$Z$$\end{document}Z boson decays to dimuons, reconstructed from a data sample corresponding to an integrated luminosity of 40 pb\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^{-1}$$\end{document}-1. The measured performance is compared to Monte Carlo predictions and deviations from the predicted performance are discussed.
doi:10.1140/epjc/s10052-014-3034-9
PMCID: PMC4371051  PMID: 25814911
21.  The differential production cross section of the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\phi $$\end{document}ϕ(1020) meson in \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sqrt{s}$$\end{document}s = 7 TeV \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$pp$$\end{document}pp collisions measured with the ATLAS detector 
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A measurement is presented of the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\phi \times \mathcal {BR}(\phi \rightarrow K^{+}K^{-})$$\end{document}ϕ×BR(ϕ→K+K-) production cross section at \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sqrt{s}$$\end{document}s = 7 TeV using \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$pp$$\end{document}pp collision data corresponding to an integrated luminosity of 383 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mathrm {\upmu b^{-1}}$$\end{document}μb-1, collected with the ATLAS experiment at the LHC. Selection of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\phi $$\end{document}ϕ(1020) mesons is based on the identification of charged kaons by their energy loss in the pixel detector. The differential cross section is measured as a function of the transverse momentum, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p_{\mathrm {T,\phi }}$$\end{document}pT,ϕ, and rapidity, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$y_{\phi }$$\end{document}yϕ, of the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\phi $$\end{document}ϕ(1020) meson in the fiducial region 500 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$$$\end{document}pT,K> 230 MeV and kaon momentum \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$p_{K}<$$\end{document}pK< 800 MeV. The integrated \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\phi (1020)$$\end{document}ϕ(1020)-meson production cross section in this fiducial range is measured to be \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\sigma _{\phi } \times \mathcal {BR}(\phi \rightarrow K^{+}K^{-}) $$\end{document}σϕ×BR(ϕ→K+K-) = 570 \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\pm $$\end{document}± 8 (stat) \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\pm $$\end{document}± 66 (syst) \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\pm $$\end{document}± 20 (lumi) \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mathrm {\upmu b}$$\end{document}μb.
doi:10.1140/epjc/s10052-014-2895-2
PMCID: PMC4371126  PMID: 25814898
22.  Chp8, a Diguanylate Cyclase from Pseudomonas syringae pv. Tomato DC3000, Suppresses the Pathogen-Associated Molecular Pattern Flagellin, Increases Extracellular Polysaccharides, and Promotes Plant Immune Evasion 
mBio  2014;5(3):e01168-14.
ABSTRACT
The bacterial plant pathogen Pseudomonas syringae causes disease in a wide range of plants. The associated decrease in crop yields results in economic losses and threatens global food security. Competition exists between the plant immune system and the pathogen, the basic principles of which can be applied to animal infection pathways. P. syringae uses a type III secretion system (T3SS) to deliver virulence factors into the plant that promote survival of the bacterium. The P. syringae T3SS is a product of the hypersensitive response and pathogenicity (hrp) and hypersensitive response and conserved (hrc) gene cluster, which is strictly controlled by the codependent enhancer-binding proteins HrpR and HrpS. Through a combination of bacterial gene regulation and phenotypic studies, plant infection assays, and plant hormone quantifications, we now report that Chp8 (i) is embedded in the Hrp regulon and expressed in response to plant signals and HrpRS, (ii) is a functional diguanylate cyclase, (iii) decreases the expression of the major pathogen-associated molecular pattern (PAMP) flagellin and increases extracellular polysaccharides (EPS), and (iv) impacts the salicylic acid/jasmonic acid hormonal immune response and disease progression. We propose that Chp8 expression dampens PAMP-triggered immunity during early plant infection.
IMPORTANCE
The global demand for food is projected to rise by 50% by 2030 and, as such, represents one of the major challenges of the 21st century, requiring improved crop management. Diseases caused by plant pathogens decrease crop yields, result in significant economic losses, and threaten global food security. Gaining mechanistic insights into the events at the plant-pathogen interface and employing this knowledge to make crops more resilient is one important strategy for improving crop management. Plant-pathogen interactions are characterized by the sophisticated interplay between plant immunity elicited upon pathogen recognition and immune evasion by the pathogen. Here, we identify Chp8 as a contributor to the major effort of the plant pathogen Pseudomonas syringae pv. tomato DC3000 to evade immune responses of the plant.
doi:10.1128/mBio.01168-14
PMCID: PMC4030453  PMID: 24846383
23.  Measurement of jet shapes in top-quark pair events at \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\sqrt{s} = 7 \ \mbox{TeV}$\end{document} using the ATLAS detector 
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A measurement of jet shapes in top-quark pair events using 1.8 fb−1 of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\sqrt{s} = 7 \ \mbox{TeV}$\end{document}pp collision data recorded by the ATLAS detector at the LHC is presented. Samples of top-quark pair events are selected in both the single-lepton and dilepton final states. The differential and integrated shapes of the jets initiated by bottom-quarks from the top-quark decays are compared with those of the jets originated by light-quarks from the hadronic W-boson decays \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$W\rightarrow q\bar{q}'$\end{document} in the single-lepton channel. The light-quark jets are found to have a narrower distribution of the momentum flow inside the jet area than b-quark jets.
doi:10.1140/epjc/s10052-013-2676-3
PMCID: PMC4370876  PMID: 25814852
24.  Management of low back pain in general practice – is it of acceptable quality: an observational study among 25 general practices in South Tyrol (Italy) 
BMC Family Practice  2013;14:148.
Background
There are several guidelines dealing with the management of low back pain (LBP), but only few studies on the quality of care provided within General Practices as judged against those guidelines.
The objective of this study is to analyse the management of LBP in Italian General Practice and compare it with guideline recommendations.
Methods
In this observational study, all patients visiting their General Practitioners (GPs) for treatment of LBP within a 8-week period were monitored for at least four weeks with regard to symptoms and diagnostic and therapeutic interventions. Management of LBP was judged by pre-defined quality indicators based on guideline recommendations.
Results
Twenty-five of 114 eligible GPs participated in the study, representing a total of 43,012 registered patients. Of the 475 patients complaining of LBP and monitored for four weeks, 55.8% were diagnosed as having acute lumbar pain, 13.5% chronic lumbar pain, 17.1% acute sciatica, and 12.6% chronic sciatica; 76.0% underwent no technical investigations, 21.7% underwent x-rays, 5.5% MRI and 4% CT scans; 20.4% were referred to secondary care; 93.3% of all patients received some medication. In those receiving a medication, in 88.3% it was an NSAID, in 6.3% Paracetamol, in 10.4% Paracetamol combined with Codeine, and in 9% a muscle relaxants. When physiotherapy was prescribed (17,1%), it was mostly massage. Hardly more than 50% of GPs (partially) followed locally established guidelines, while the remainder seemed not to follow guidelines at all.
Conclusions
Our study reveals gross deviations of GP management of LBP from current guidelines and points to two different types of deviators: those who partially follow guidelines, and those who do not follow them at all. Further research should evaluate whether these two types of deviation are best addressed by different foci of education, i.e. on knowledge versus attitudes, respectively.
doi:10.1186/1471-2296-14-148
PMCID: PMC3850994  PMID: 24090155
Low back pain; General practice; Guideline adherence; Diagnostic imaging
25.  Improved luminosity determination in pp collisions at \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\sqrt {s} = 7\ \mathrm{TeV}$\end{document} using the ATLAS detector at the LHC 
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The luminosity calibration for the ATLAS detector at the LHC during pp collisions at \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\sqrt{s} = 7~\mathrm{TeV}$\end{document} in 2010 and 2011 is presented. Evaluation of the luminosity scale is performed using several luminosity-sensitive detectors, and comparisons are made of the long-term stability and accuracy of this calibration applied to the pp collisions at \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\sqrt{s} = 7~\mathrm{TeV}$\end{document}. A luminosity uncertainty of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\delta\mathcal{L}/ \mathcal{L} = \pm 3.5~\%$\end{document} is obtained for the 47 pb−1 of data delivered to ATLAS in 2010, and an uncertainty of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\delta\mathcal{L}/ \mathcal{L} = \pm1.8~\%$\end{document} is obtained for the 5.5 fb−1 delivered in 2011.
doi:10.1140/epjc/s10052-013-2518-3
PMCID: PMC4370906  PMID: 25814867

Results 1-25 (62)