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1.  Impaired movement timing in neurological disorders: rehabilitation and treatment strategies 
Timing abnormalities have been reported in many neurological disorders, including Parkinson’s disease (PD). In PD, motor-timing impairments are especially debilitating in gait. Despite impaired audiomotor synchronization, PD patients’ gait improves when they walk with an auditory metronome or with music. Building on that research, we make recommendations for optimizing sensory cues to improve the efficacy of rhythmic cuing in gait rehabilitation. Adaptive rhythmic metronomes (that synchronize with the patient’s walking) might be especially effective. In a recent study we showed that adaptive metronomes synchronized consistently with Parkinson patients’ footsteps without requiring attention; this improved stability and reinstated healthy gait dynamics. Other strategies could help optimize sensory cues for gait rehabilitation. Groove music strongly engages the motor system and induces movement; bass-frequency tones are associated with movement and provide strong timing cues. Thus, groove and bass-frequency pulses could deliver potent rhythmic cues. These strategies capitalize on the close neural connections between auditory and motor networks; and auditory cues are typically preferred. However, moving visual cues greatly improve visuomotor synchronization and could warrant examination in gait rehabilitation. Together, a treatment approach that employs groove, auditory, bass-frequency, and adaptive (GABA) cues could help optimize rhythmic sensory cues for treating motor and timing deficits.
doi:10.1111/nyas.12615
PMCID: PMC4363094  PMID: 25773624
gait rehabilitation; Parkinson’s disease; rhythmic auditory stimulation; adaptive timing; groove
2.  Individual Differences in Rhythmic Cortical Entrainment Correlate with Predictive Behavior in Sensorimotor Synchronization 
Scientific Reports  2016;6:20612.
The current study aims at characterizing the mechanisms that allow humans to entrain the mind and body to incoming rhythmic sensory inputs in real time. We addressed this unresolved issue by examining the relationship between covert neural processes and overt behavior in the context of musical rhythm. We measured temporal prediction abilities, sensorimotor synchronization accuracy and neural entrainment to auditory rhythms as captured using an EEG frequency-tagging approach. Importantly, movement synchronization accuracy with a rhythmic beat could be explained by the amplitude of neural activity selectively locked with the beat period when listening to the rhythmic inputs. Furthermore, stronger endogenous neural entrainment at the beat frequency was associated with superior temporal prediction abilities. Together, these results reveal a direct link between cortical and behavioral measures of rhythmic entrainment, thus providing evidence that frequency-tagged brain activity has functional relevance for beat perception and synchronization.
doi:10.1038/srep20612
PMCID: PMC4742877  PMID: 26847160
3.  Rhythm in joint action: psychological and neurophysiological mechanisms for real-time interpersonal coordination 
Human interaction often requires simultaneous precision and flexibility in the coordination of rhythmic behaviour between individuals engaged in joint activity, for example, playing a musical duet or dancing with a partner. This review article addresses the psychological processes and brain mechanisms that enable such rhythmic interpersonal coordination. First, an overview is given of research on the cognitive-motor processes that enable individuals to represent joint action goals and to anticipate, attend and adapt to other's actions in real time. Second, the neurophysiological mechanisms that underpin rhythmic interpersonal coordination are sought in studies of sensorimotor and cognitive processes that play a role in the representation and integration of self- and other-related actions within and between individuals' brains. Finally, relationships between social–psychological factors and rhythmic interpersonal coordination are considered from two perspectives, one concerning how social-cognitive tendencies (e.g. empathy) affect coordination, and the other concerning how coordination affects interpersonal affiliation, trust and prosocial behaviour. Our review highlights musical ensemble performance as an ecologically valid yet readily controlled domain for investigating rhythm in joint action.
doi:10.1098/rstb.2013.0394
PMCID: PMC4240961  PMID: 25385772
rhythm; joint action; interpersonal coordination; musical ensembles; sensorimotor synchronization; social neuroscience
4.  The time course of phase correction: A kinematic investigation of motor adjustment to timing perturbations during sensorimotor synchronization 
Synchronizing movements with a beat requires rapid compensation for timing errors. The phase-correction response (PCR) has been studied extensively in finger tapping by shifting a metronome onset and measuring the adjustment of the following tap time. How the response unfolds during the subsequent tap cycle remains unknown. Using motion capture, we examined finger kinematics during the PCR. Participants tapped with a metronome containing phase perturbations. They tapped in ‘legato’ and ‘staccato’ style at various tempi, which altered the timing of the constituent movement stages (dwell at the surface, extension, flexion). After a phase perturbation, tapping kinematics changed compared to baseline, and the PCR was distributed differently across movement stages. In staccato tapping, the PCR trajectory changed primarily during finger extension across tempi. In legato tapping, at fast tempi the PCR occurred primarily during extension, whereas at slow tempi most phase correction was already completed during dwell. Across conditions, timing adjustments occurred primarily 100-250 ms into the following tap cycle. The change in movement around 100 ms represents the time to integrate information into an already planned movement and the rapidity suggests a subcortical route.
doi:10.1037/a0037826
PMCID: PMC4244310  PMID: 25151103
sensorimotor synchronization; phase correction; motion capture; timing; movement kinematics
5.  The E-music box: an empirical method for exploring the universal capacity for musical production and for social interaction through music 
Royal Society Open Science  2015;2(11):150286.
Humans are assumed to have a natural—universal—predisposition for making music and for musical interaction. Research in this domain is, however, typically conducted with musically trained individuals, and therefore confounded with expertise. Here, we present a rediscovered and updated invention—the E-music box—that we establish as an empirical method to investigate musical production and interaction in everyone. The E-music box transforms rotatory cyclical movements into pre-programmable digital musical output, with tempo varying according to rotation speed. The user’s movements are coded as continuous oscillatory data, which can be analysed using linear or nonlinear analytical tools. We conducted a proof-of-principle experiment to demonstrate that, using this method, pairs of non-musically trained individuals can interact according to conventional musical practices (leader/follower roles and lower-pitch dominance). The results suggest that the E-music box brings ‘active’ and ‘interactive’ musical capacities within everyone’s reach. We discuss the potential of this method for exploring the universal predisposition for music making and interaction in developmental and cross-cultural contexts, and for neurologic musical therapy and rehabilitation.
doi:10.1098/rsos.150286
PMCID: PMC4680608  PMID: 26715993
music box; music production; joint action; universals; neurologic music therapy; non-musicians
6.  Rational Therapy of Clostridium difficile Infections 
Viszeralmedizin  2014;30(5):304-309.
Summary
Background
Clostridium difficile infections (CDI) are increasingly important in patients with antibiotic treatments, ranging from mild, self-limiting to severe, life-threatening disease. Currently, diagnostic algorithms and treatment guidelines are being adapted to novel tests and therapeutic options for recurrent CDI.
Methods
A systematic literature search using the terms ‘Clostridium difficile’ and ‘treatment’ was carried out. Current guidelines are being discussed from a clinical point of view.
Results
State-of-the-art diagnostics for C. difficile diagnosis rely on the patient's history, clinical symptoms, and laboratory examination of stool. Recommendations are in favour of glutamate dehydrogenase (GDH) screening tests and confirmatory detection of C. difficile toxin genes (polymerase chain reaction (PCR)). Therapeutic strategies depend on disease severity (mild vs. severe) and endorse metronidazole and vancomycin as well as fidaxomycin for recurrent disease. In very severe cases, surgical therapy is recommended. For relapsing diseases, faecal transfer is considered as a therapeutic option if available.
Conclusion
Current guidelines have been adapted to new pathways in diagnosing CDI and have included statements on novel therapeutic options such as fidaxomycin and faecal transplant for recurrent disease. Depending on the severity of the disease, standard therapy with either metronidazole or vancomycin is recommended.
doi:10.1159/000366302
PMCID: PMC4513822  PMID: 26288096
Clostridium difficile; Diagnostics; Guidelines; Therapy
7.  Motor simulation and the coordination of self and other in real-time joint action 
Joint actions require the integration of simultaneous self- and other-related behaviour. Here, we investigated whether this function is underpinned by motor simulation, that is the capacity to represent a perceived action in terms of the neural resources required to execute it. This was tested in a music performance experiment wherein on-line brain stimulation (double-pulse transcranial magnetic stimulation, dTMS) was employed to interfere with motor simulation. Pianists played the right-hand part of piano pieces in synchrony with a recording of the left-hand part, which had (Trained) or had not (Untrained) been practiced beforehand. Training was assumed to enhance motor simulation. The task required adaptation to tempo changes in the left-hand part that, in critical conditions, were preceded by dTMS delivered over the right primary motor cortex. Accuracy of tempo adaptation following dTMS or sham stimulations was compared across Trained and Untrained conditions. Results indicate that dTMS impaired tempo adaptation accuracy only during the perception of trained actions. The magnitude of this interference was greater in empathic individuals possessing a strong tendency to adopt others’ perspectives. These findings suggest that motor simulation provides a functional resource for the temporal coordination of one’s own behaviour with others in dynamic social contexts.
doi:10.1093/scan/nst086
PMCID: PMC4127011  PMID: 23709353
motor simulation; TMS; music; joint action; temporal coordination; empathy
8.  Perception of ‘Back-Channeling’ Nonverbal Feedback in Musical Duo Improvisation 
PLoS ONE  2015;10(6):e0130070.
In witnessing face-to-face conversation, observers perceive authentic communication according to the social contingency of nonverbal feedback cues (‘back-channeling’) by non-speaking interactors. The current study investigated the generality of this function by focusing on nonverbal communication in musical improvisation. A perceptual experiment was conducted to test whether observers can reliably identify genuine versus fake (mismatched) duos from musicians’ nonverbal cues, and how this judgement is affected by observers’ musical background and rhythm perception skill. Twenty-four musicians were recruited to perform duo improvisations, which included solo episodes, in two styles: standard jazz (where rhythm is based on a regular pulse) or free improvisation (where rhythm is non-pulsed). The improvisations were recorded using a motion capture system to generate 16 ten-second point-light displays (with audio) of the soloist and the silent non-soloing musician (‘back-channeler’). Sixteen further displays were created by splicing soloists with back-channelers from different duos. Participants (N = 60) with various musical backgrounds were asked to rate the point-light displays as either real or fake. Results indicated that participants were sensitive to the real/fake distinction in the free improvisation condition independently of musical experience. Individual differences in rhythm perception skill did not account for performance in the free condition, but were positively correlated with accuracy in the standard jazz condition. These findings suggest that the perception of back-channeling in free improvisation is not dependent on music-specific skills but is a general ability. The findings invite further study of the links between interpersonal dynamics in conversation and musical interaction.
doi:10.1371/journal.pone.0130070
PMCID: PMC4473276  PMID: 26086593
9.  The Self-Reported Clinical Practice Behaviors of Australian Optometrists as Related to Smoking, Diet and Nutritional Supplementation 
PLoS ONE  2015;10(4):e0124533.
Objective
The primary aim of this study was to examine the self-reported, routine clinical practice behaviors of Australian optometrists with respect to advice regarding smoking, diet and nutritional supplementation. The study also sought to assess the potential influence of practitioner age, gender, practice location (major city versus regional), therapeutic-endorsement status and personal nutritional supplementation habits upon management practices in these areas.
Methods
A survey was electronically distributed to Australian optometrists (n = 4,242). Respondents anonymously provided information about their personal demographics and lifestyle behaviors (i.e., age, gender, practice location, therapeutic-endorsement status, smoking status, nutritional supplement intake) and routine patient management practices with respect to advice across three domains: smoking, diet and nutritional supplementation. Multivariate logistic regression analyses were performed to assess for potential effects of the listed factors on practitioner behavior.
Results
A total of 283 completed surveys were received (completed survey response rate: 6.7%). Fewer than half of respondents indicated routinely asking their patients about smoking status. Younger practitioners were significantly (p < 0.05) less likely to enquire about patients’ smoking behaviors, but this did not extend to counseling for smoking cessation. Almost two-thirds of respondents indicated routinely counseling patients about diet. About half of practitioners specified routinely asking their patients about nutritional supplement intake; this form of questioning was significantly more likely if the respondent was female (p < 0.05). Practitioners who recommended nutritional supplements most commonly did so for age-related macular degeneration (91.2%) and dry eye disease (63.9%). The primary source of evidence used to guide practitioners’ nutrition-related patient management was reported to be peer-reviewed publications.
Conclusions
These findings demonstrate that there are no clear predictors of practitioner behavior across the three domains. Overall, this study suggests that there is scope for Australian optometrists to improve their routine engagement by questioning patients, as well as providing evidence-based clinical advice, about smoking status, diet and nutritional supplement behaviors, being key modifiable lifestyle risk factors with long-term implications for eye health.
doi:10.1371/journal.pone.0124533
PMCID: PMC4401759  PMID: 25886641
10.  Detection of Pneumonia Associated Pathogens Using a Prototype Multiplexed Pneumonia Test in Hospitalized Patients with Severe Pneumonia 
PLoS ONE  2014;9(11):e110566.
Severe pneumonia remains an important cause of morbidity and mortality. Polymerase chain reaction (PCR) has been shown to be more sensitive than current standard microbiological methods – particularly in patients with prior antibiotic treatment – and therefore, may improve the accuracy of microbiological diagnosis for hospitalized patients with pneumonia. Conventional detection techniques and multiplex PCR for 14 typical bacterial pneumonia-associated pathogens were performed on respiratory samples collected from adult hospitalized patients enrolled in a prospective multi-center study. Patients were enrolled from March until September 2012. A total of 739 fresh, native samples were eligible for analysis, of which 75 were sputa, 421 aspirates, and 234 bronchial lavages. 276 pathogens were detected by microbiology for which a valid PCR result was generated (positive or negative detection result by Curetis prototype system). Among these, 120 were identified by the prototype assay, 50 pathogens were not detected. Overall performance of the prototype for pathogen identification was 70.6% sensitivity (95% confidence interval (CI) lower bound: 63.3%, upper bound: 76.9%) and 95.2% specificity (95% CI lower bound: 94.6%, upper bound: 95.7%). Based on the study results, device cut-off settings were adjusted for future series production. The overall performance with the settings of the CE series production devices was 78.7% sensitivity (95% CI lower bound: 72.1%) and 96.6% specificity (95% CI lower bound: 96.1%). Time to result was 5.2 hours (median) for the prototype test and 43.5 h for standard-of-care. The Pneumonia Application provides a rapid and moderately sensitive assay for the detection of pneumonia-causing pathogens with minimal hands-on time.
Trial Registration
Deutsches Register Klinischer Studien (DRKS) DRKS00005684
doi:10.1371/journal.pone.0110566
PMCID: PMC4232251  PMID: 25397673
11.  Dynamics of soluble and cellular inflammatory markers in nasal lavage obtained from Cystic Fibrosis patients during intravenous antibiotic treatment 
Background
In cystic fibrosis (CF) patients, the upper airways display the same ion channel defect as evident in the lungs, resulting in chronic inflammation and infection. Recognition of the sinonasal area as a site of first and persistent infection with pathogens, such as Pseudomonas aeruginosa, reinforces the “one-airway” hypothesis. Therefore, we assessed the effect of systemic antibiotics against pulmonary pathogens on sinonasal inflammation.
Methods
Nasal lavage fluid (NLF) from 17 CF patients was longitudinally collected prior to and during elective intravenous (i.v.) antibiotic treatment to reduce pathogen burden and resulting inflammation (median treatment time at time of analysis: 6 days). Samples were assessed microbiologically and cytologically. Cytokine and chemokine expression was measured by Cytometric Bead Array and ELISA (interleukin (IL)-1β, IL-6, IL-8, MPO, MMP9, RANTES and NE). Findings were compared with inflammatory markers from NLF obtained from 52 healthy controls.
Results
Initially, the total cell count of the NLF was significantly higher in CF patients than in controls. However after i.v. antibiotic treatment it decreased to a normal level. Compared with controls, detection frequencies and absolute concentrations of MPO, IL-8, IL-6 and IL-1β were also significantly higher in CF patients. The detection frequency of TNF was also higher. Furthermore, during i.v. therapy sinonasal concentrations of IL-6 decreased significantly (P = 0.0059), while RANTES and MMP9 levels decreased 10-fold and two-fold, respectively. PMN-Elastase, assessed for the first time in NFL, did not change during therapy.
Conclusions
Analysis of NLF inflammatory markers revealed considerable differences between controls and CF patients, with significant changes during systemic i.v. AB treatment within just 6 days. Thus, our data support further investigation into the collection of samples from the epithelial surface of the upper airways by nasal lavage as a potential diagnostic and research tool.
doi:10.1186/1471-2466-14-82
PMCID: PMC4024110  PMID: 24885494
Cystic Fibrosis; Paediatric pulmonology; Upper airways (UAW); Nasal lavage; Inflammation; Cytokines; Antibiotic treatment; Permanent UAW colonization; Cytology
12.  A case of EDTA-dependent pseudothrombocytopenia: simple recognition of an underdiagnosed and misleading phenomenon 
Background
EDTA-dependent pseudothrombocytopenia (EDTA-PTCP) is a common laboratory phenomenon with a prevalence ranging from 0.1-2% in hospitalized patients to 15-17% in outpatients evaluated for isolated thrombocytopenia. Despite its harmlessness, EDTA-PTCP frequently leads to time-consuming, costly and even invasive diagnostic investigations. EDTA-PTCP is often overlooked because blood smears are not evaluated visually in routine practice and histograms as well as warning flags of hematology analyzers are not interpreted correctly. Nonetheless, EDTA-PTCP may be diagnosed easily even by general practitioners without any experiences in blood film examinations. This is the first report illustrating the typical patterns of a platelet (PLT) and white blood cell (WBC) histograms of hematology analyzers.
Case presentation
A 37-year-old female patient of Caucasian origin was referred with suspected acute leukemia and the crew of the emergency unit arranged extensive investigations for work-up. However, examination of EDTA blood sample revealed atypical lymphocytes and an isolated thrombocytopenia together with typical patterns of WBC and PLT histograms: a serrated curve of the platelet histogram and a peculiar peak on the left side of the WBC histogram. EDTA-PTCP was confirmed by a normal platelet count when examining citrated blood.
Conclusion
Awareness of typical PLT and WBC patterns may alert to the presence of EDTA-PTCP in routine laboratory practice helping to avoid unnecessary investigations and over-treatment.
doi:10.1186/1472-6890-14-19
PMCID: PMC4012027  PMID: 24808761
Thrombocytopenia; Laboratory hematology; Hematology analyzers
13.  Basic Timing Abilities Stay Intact in Patients with Musician's Dystonia 
PLoS ONE  2014;9(3):e92906.
Task-specific focal dystonia is a movement disorder that is characterized by the loss of voluntary motor control in extensively trained movements. Musician's dystonia is a type of task-specific dystonia that is elicited in professional musicians during instrumental playing. The disorder has been associated with deficits in timing. In order to test the hypothesis that basic timing abilities are affected by musician's dystonia, we investigated a group of patients (N = 15) and a matched control group (N = 15) on a battery of sensory and sensorimotor synchronization tasks. Results did not show any deficits in auditory-motor processing for patients relative to controls. Both groups benefited from a pacing sequence that adapted to their timing (in a sensorimotor synchronization task at a stable tempo). In a purely perceptual task, both groups were able to detect a misaligned metronome when it was late rather than early relative to a musical beat. Overall, the results suggest that basic timing abilities stay intact in patients with musician's dystonia. This supports the idea that musician's dystonia is a highly task-specific movement disorder in which patients are mostly impaired in tasks closely related to the demands of actually playing their instrument.
doi:10.1371/journal.pone.0092906
PMCID: PMC3965486  PMID: 24667273
14.  Sinonasal inhalation of tobramycin vibrating aerosol in cystic fibrosis patients with upper airway Pseudomonas aeruginosa colonization: results of a randomized, double-blind, placebo-controlled pilot study 
Rationale
In cystic fibrosis (CF), the paranasal sinuses are sites of first and persistent colonization by pathogens such as Pseudomonas aeruginosa. Pathogens subsequently descend to the lower airways, with P. aeruginosa remaining the primary cause of premature death in patients with the inherited disease. Unlike conventional aerosols, vibrating aerosols applied with the PARI Sinus™ nebulizer deposit drugs into the paranasal sinuses. This trial assessed the effects of vibrating sinonasal inhalation of the antibiotic tobramycin in CF patients positive for P. aeruginosa in nasal lavage.
Objectives
To evaluate the effects of sinonasal inhalation of tobramycin on P. aeruginosa quantification in nasal lavage; and on patient quality of life, measured with the Sino-Nasal Outcome Test (SNOT-20), and otologic and renal safety and tolerability.
Methods
Patients were randomized to inhalation of tobramycin (80 mg/2 mL) or placebo (2 mL isotonic saline) once daily (4 minutes/nostril) with the PARI Sinus™ nebulizer over 28 days, with all patients eligible for a subsequent course of open-label inhalation of tobramycin for 28 days. Nasal lavage was obtained before starting and 2 days after the end of each treatment period by rinsing each nostril with 10 mL of isotonic saline.
Results
Nine patients participated, six initially receiving tobramycin and three placebo. Sinonasal inhalation was well tolerated, with serum tobramycin <0.5 mg/L and stable creatinine. P. aeruginosa quantity decreased in four of six (67%) patients given tobramycin, compared with zero of three given placebo (non-significant). SNOT-20 scores were significantly lower in the tobramycin than in the placebo group (P=0.033).
Conclusion
Sinonasal inhalation of vibrating antibiotic aerosols appears promising for reducing pathogen colonization of paranasal sinuses and for control of symptoms in patients with CF.
doi:10.2147/DDDT.S54064
PMCID: PMC3930477  PMID: 24596456
PARI Sinus; nasal lavage; SNOT-20; cystic fibrosis; Pseudomonas aeruginosa; sinonasal; upper airways
15.  HIV post exposure prophylaxis induced bicytopenia: a case report 
Long and short term side effects of antiretroviral drugs are not fully understood yet. Here a case of reversible blood count changes following post exposure prophylaxis with tenofovir/emtricitabin and lopinavir/ritonavir is reported. We propose that antiretroviral drugs used in post exposure prophylaxis may have a significant impact on hematopoiesis.
doi:10.1186/1742-6405-11-11
PMCID: PMC3922541  PMID: 24506969
HIV; Post exposure prophylaxis; Leukopenia; Thrombocytopenia; Tenofovir; Emtricitabin; Lopinavir; Ritonavir
16.  Segregation and Integration of Auditory Streams when Listening to Multi-Part Music 
PLoS ONE  2014;9(1):e84085.
In our daily lives, auditory stream segregation allows us to differentiate concurrent sound sources and to make sense of the scene we are experiencing. However, a combination of segregation and the concurrent integration of auditory streams is necessary in order to analyze the relationship between streams and thus perceive a coherent auditory scene. The present functional magnetic resonance imaging study investigates the relative role and neural underpinnings of these listening strategies in multi-part musical stimuli. We compare a real human performance of a piano duet and a synthetic stimulus of the same duet in a prioritized integrative attention paradigm that required the simultaneous segregation and integration of auditory streams. In so doing, we manipulate the degree to which the attended part of the duet led either structurally (attend melody vs. attend accompaniment) or temporally (asynchronies vs. no asynchronies between parts), and thus the relative contributions of integration and segregation used to make an assessment of the leader-follower relationship. We show that perceptually the relationship between parts is biased towards the conventional structural hierarchy in western music in which the melody generally dominates (leads) the accompaniment. Moreover, the assessment varies as a function of both cognitive load, as shown through difficulty ratings and the interaction of the temporal and the structural relationship factors. Neurally, we see that the temporal relationship between parts, as one important cue for stream segregation, revealed distinct neural activity in the planum temporale. By contrast, integration used when listening to both the temporally separated performance stimulus and the temporally fused synthetic stimulus resulted in activation of the intraparietal sulcus. These results support the hypothesis that the planum temporale and IPS are key structures underlying the mechanisms of segregation and integration of auditory streams, respectively.
doi:10.1371/journal.pone.0084085
PMCID: PMC3901649  PMID: 24475030
17.  A conceptual review on action-perception coupling in the musicians’ brain: what is it good for? 
Experience with a sensorimotor task, such as practicing a piano piece, leads to strong coupling of sensory (visual or auditory) and motor cortices. Here we review behavioral and neurophysiological (M/EEG, TMS and fMRI) research exploring this topic using the brain of musicians as a model system. Our review focuses on a recent body of evidence suggesting that this form of coupling might have (at least) two cognitive functions. First, it leads to the generation of equivalent predictions (concerning both when and what event is more likely to occur) during both perception and production of music. Second, it underpins the common coding of perception and action that supports the integration of the motor output of multiple musicians’ in the context of joint musical tasks. Essentially, training-based coupling of perception and action might scaffold the human ability to represent complex (structured) actions and to entrain multiple agents—via reciprocal prediction and adaptation—in the pursuit of shared goals.
doi:10.3389/fnhum.2014.00603
PMCID: PMC4139714  PMID: 25191246
action-perception coupling; music; training; prediction; joint action
18.  Quality of blood culture testing - a survey in intensive care units and microbiological laboratories across four European countries 
Critical Care  2013;17(5):R248.
Introduction
Blood culture (BC) testing before initiation of antimicrobial therapy is recommended as a standard of care in international sepsis guidelines and has been shown to reduce intensive care unit (ICU) stay, antibiotic use, and costs in hospitalized patients. Whereas microbiological laboratory practice has been highly standardized, shortfalls in the preanalytic procedures in the ICU (that is indication, time-to-incubation, blood volume and numbers of BC sets) have a significant effect on the diagnostic yield. The objective of this study was to gain insights into current practices regarding BC testing in intensive care units.
Methods
Qualitative survey, data collection by 138 semi-structured telephone interviews in four European countries (Italy, UK, France and Germany) between September and November 2009 in 79 clinical microbiology laboratories (LABs) and 59 ICUs.
Results
Whereas BC testing is expected to remain the gold standard for sepsis diagnostics in all countries, there are substantial differences regarding preanalytic procedures. The decision to launch BC testing is carried out by physicians vs. ICU nurses in the UK in 92 vs. 8%, in France in 75 vs. 25%, in Italy in 88 vs. 12% and in Germany in 92 vs. 8%. Physicians vs. nurses collect BCs in the UK in 77 vs. 23%, in France in 0 vs. 100%, in Italy in 6 vs. 94% and in Germany in 54 vs. 46%. The mean time from blood collection to incubation in the UK is 2 h, in France 3 h, in Italy 4 h, but 20 h in German remote LABs (2 h in in-house LABs), due to the large number of remote nonresident microbiological laboratories in Germany. There were major differences between the perception of the quality of BC testing between ICUs and LABs. Among German ICU respondents, 62% reported that they have no problems with BC testing, 15% reported time constraints, 15% cost pressure, and only 8% too long time to incubation. However, the corresponding LABs of these German ICUs reported too many false positive results due to preanalytical contaminations (49%), insufficient numbers of incoming BC sets (47%), long transportation time (41%) or cost pressure (18%).
Conclusions
There are considerable differences in the quality of BC testing across European countries. In Germany, time to incubation is a considerable problem due to the increasing number of remote LABs. This is a major issue of concern to physicians aiming to implement sepsis guidelines in the ICUs.
doi:10.1186/cc13074
PMCID: PMC4056044  PMID: 24144084
19.  A Sequence Identification Measurement Model to Investigate the Implicit Learning of Metrical Temporal Patterns 
PLoS ONE  2013;8(9):e75163.
Implicit learning (IL) occurs unconsciously and without intention. Perceptual fluency is the ease of processing elicited by previous exposure to a stimulus. It has been assumed that perceptual fluency is associated with IL. However, the role of perceptual fluency following IL has not been investigated in temporal pattern learning. Two experiments by Schultz, Stevens, Keller, and Tillmann demonstrated the IL of auditory temporal patterns using a serial reaction-time task and a generation task based on the process dissociation procedure. The generation task demonstrated that learning was implicit in both experiments via motor fluency, that is, the inability to suppress learned information. With the aim to disentangle conscious and unconscious processes, we analyze unreported recognition data associated with the Schultz et al. experiments using the sequence identification measurement model. The model assumes that perceptual fluency reflects unconscious processes and IL. For Experiment 1, the model indicated that conscious and unconscious processes contributed to recognition of temporal patterns, but that unconscious processes had a greater influence on recognition than conscious processes. In the model implementation of Experiment 2, there was equal contribution of conscious and unconscious processes in the recognition of temporal patterns. As Schultz et al. demonstrated IL in both experiments using a generation task, and the conditions reported here in Experiments 1 and 2 were identical, two explanations are offered for the discrepancy in model and behavioral results based on the two tasks: 1) perceptual fluency may not be necessary to infer IL, or 2) conscious control over implicitly learned information may vary as a function of perceptual fluency and motor fluency.
doi:10.1371/journal.pone.0075163
PMCID: PMC3783451  PMID: 24086461
20.  The Role of Oxidative Stress in Nervous System Aging 
PLoS ONE  2013;8(7):e68011.
While oxidative stress is implicated in aging, the impact of oxidative stress on aging in the peripheral nervous system is not well understood. To determine a potential mechanism for age-related deficits in the peripheral nervous system, we examined both functional and morphological changes and utilized microarray technology to compare normal aging in wild-type mice to effects in copper/zinc superoxide dismutase-deficient (Sod1−/−) mice, a mouse model of increased oxidative stress. Sod1−/− mice exhibit a peripheral neuropathy phenotype with normal sensory nerve function and deficits in motor nerve function. Our data indicate that a decrease in the synthesis of cholesterol, which is vital to myelin formation, correlates with the structural deficits in axons, myelin, and the cell body of motor neurons in the Sod1+/+ mice at 30 months and the Sod1−/− mice at 20 months compared with mice at 2 months. Collectively, we have demonstrated that the functional and morphological changes within the peripheral nervous system in our model of increased oxidative stress are manifested earlier and resemble the deficits observed during normal aging.
doi:10.1371/journal.pone.0068011
PMCID: PMC3699525  PMID: 23844146
21.  Close Geographic Association of Human Neoehrlichiosis and Tick Populations Carrying “Candidatus Neoehrlichia mikurensis” in Eastern Switzerland 
Journal of Clinical Microbiology  2013;51(1):169-176.
Neoehrlichiosis caused by “Candidatus Neoehrlichia mikurensis” is an emerging zoonotic disease. In total, six patients have been described in Europe, with the first case detected in 2007. In addition, seven patients from China were described in a report published in October 2012. In 2009, we diagnosed the first human case of “Ca. Neoehrlichia mikurensis” infection in the Zurich area (Switzerland). Here, we report two additional human cases from the same region, which were identified by broad-range 16S rRNA gene PCR. Both patients were immunocompromised and presented with similar clinical syndromes, including fever, malaise, and weight loss. A diagnostic multiplex real-time PCR was developed for specific detection of “Ca. Neoehrlichia mikurensis” infections. The assay is based on the signature sequence of a 280-bp fragment of the “Ca. Neoehrlichia mikurensis” 16S rRNA gene and incorporates a “Ca. Neoehrlichia mikurensis” species, a “Ca. Neoehrlichia” genus, and an Anaplasmataceae family probe for simultaneous screening. The analytical sensitivity was determined to be below five copies of the “Ca. Neoehrlichia mikurensis” 16S rRNA gene. Our results show that the assay is suitable for the direct detection of “Ca. Neoehrlichia mikurensis” DNA in clinical samples from, for example, blood and bone marrow. In addition, it allows for monitoring treatment response during antibiotic therapy. Using the same assay, DNA extracts from 1,916 ticks collected in four forests in close proximity to the patients' residences (<3 km) were screened. At all sampling sites, the minimal prevalence of “Ca. Neoehrlichia mikurensis” was between 3.5 to 8% in pools of either nymphs, males, or females, showing a strong geographic association between the three patients and the assumed vector.
doi:10.1128/JCM.01955-12
PMCID: PMC3536216  PMID: 23115262
22.  Knowing too little or too much: the effects of familiarity with a co-performer's part on interpersonal coordination in musical ensembles 
Expert ensemble musicians produce exquisitely coordinated sounds, but rehearsal is typically required to do so. Ensemble coordination may thus be influenced by the degree to which individuals are familiar with each other's parts. Such familiarity may affect the ability to predict and synchronize with co-performers' actions. Internal models related to action simulation and anticipatory musical imagery may be affected by knowledge of (1) the musical structure of a co-performer's part (e.g., in terms of its rhythm and phrase structure) and/or (2) the co-performer's idiosyncratic playing style (e.g., expressive micro-timing variations). The current study investigated the effects of familiarity on interpersonal coordination in piano duos. Skilled pianists were required to play several duets with different partners. One condition included duets for which co-performers had previously practiced both parts, while another condition included duets for which each performer had practiced only their own part. Each piece was recorded six times without joint rehearsal or visual contact to examine the effects of increasing familiarity. Interpersonal coordination was quantified by measuring asynchronies between pianists' keystroke timing and the correlation of their body (head and torso) movements, which were recorded with a motion capture system. The results suggest that familiarity with a co-performer's part, in the absence of familiarity with their playing style, engenders predictions about micro-timing variations that are based instead upon one's own playing style, leading to a mismatch between predictions and actual events at short timescales. Predictions at longer timescales—that is, those related to musical measures and phrases, and reflected in head movements and body sway—are, however, facilitated by familiarity with the structure of a co-performer's part. These findings point to a dissociation between interpersonal coordination at the level of keystrokes and body movements.
doi:10.3389/fpsyg.2013.00368
PMCID: PMC3691551  PMID: 23805116
interpersonal coordination; body movement; music; ensembles; sensorimotor synchronization
23.  Streptococcus tigurinus, a Novel Member of the Streptococcus mitis Group, Causes Invasive Infections 
Journal of Clinical Microbiology  2012;50(9):2969-2973.
We recently described the novel species Streptococcus tigurinus sp. nov. belonging to the Streptococcus mitis group. The type strain AZ_3aT of S. tigurinus was originally isolated from a patient with infective endocarditis. According to its phenotypic and molecular characteristics, S. tigurinus is most closely related to Streptococcus mitis, Streptococcus pneumoniae, Streptococcus pseudopneumoniae, Streptococcus oralis, and Streptococcus infantis. Accurate identification of S. tigurinus is facilitated by 16S rRNA gene analysis. We retrospectively analyzed our 16S rRNA gene molecular database, which contains sequences of all clinical samples obtained in our institute since 2003. We detected 17 16S rRNA gene sequences which were assigned to S. tigurinus, including sequences from the 3 S. tigurinus strains described previously. S. tigurinus originated from normally sterile body sites, such as blood, cerebrospinal fluid, or heart valves, of 14 patients and was initially detected by culture or broad-range 16S rRNA gene PCR, followed by sequencing. The 14 patients had serious invasive infections, i.e., infective endocarditis (n = 6), spondylodiscitis (n = 3), bacteremia (n = 2), meningitis (n = 1), prosthetic joint infection (n = 1), and thoracic empyema (n = 1). To evaluate the presence of Streptococcus tigurinus in the endogenous oral microbial flora, we screened saliva specimens of 31 volunteers. After selective growth, alpha-hemolytic growing colonies were analyzed by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) and subsequent molecular methods. S. tigurinus was not identified among 608 strains analyzed. These data indicate that S. tigurinus is not widely distributed in the oral cavity. In conclusion, S. tigurinus is a novel agent of invasive infections, particularly infective endocarditis.
doi:10.1128/JCM.00849-12
PMCID: PMC3421813  PMID: 22760039
24.  The ADaptation and Anticipation Model (ADAM) of sensorimotor synchronization 
A constantly changing environment requires precise yet flexible timing of movements. Sensorimotor synchronization (SMS)—the temporal coordination of an action with events in a predictable external rhythm—is a fundamental human skill that contributes to optimal sensory-motor control in daily life. A large body of research related to SMS has focused on adaptive error correction mechanisms that support the synchronization of periodic movements (e.g., finger taps) with events in regular pacing sequences. The results of recent studies additionally highlight the importance of anticipatory mechanisms that support temporal prediction in the context of SMS with sequences that contain tempo changes. To investigate the role of adaptation and anticipatory mechanisms in SMS we introduce ADAM: an ADaptation and Anticipation Model. ADAM combines reactive error correction processes (adaptation) with predictive temporal extrapolation processes (anticipation) inspired by the computational neuroscience concept of internal models. The combination of simulations and experimental manipulations based on ADAM creates a novel and promising approach for exploring adaptation and anticipation in SMS. The current paper describes the conceptual basis and architecture of ADAM.
doi:10.3389/fnhum.2013.00253
PMCID: PMC3677131  PMID: 23772211
sensorimotor synchronization; computational model; temporal adaptation; error correction; temporal anticipation; predictive internal models
25.  Neural correlates of auditory temporal predictions during sensorimotor synchronization 
Musical ensemble performance requires temporally precise interpersonal action coordination. To play in synchrony, ensemble musicians presumably rely on anticipatory mechanisms that enable them to predict the timing of sounds produced by co-performers. Previous studies have shown that individuals differ in their ability to predict upcoming tempo changes in paced finger-tapping tasks (indexed by cross-correlations between tap timing and pacing events) and that the degree of such prediction influences the accuracy of sensorimotor synchronization (SMS) and interpersonal coordination in dyadic tapping tasks. The current functional magnetic resonance imaging study investigated the neural correlates of auditory temporal predictions during SMS in a within-subject design. Hemodynamic responses were recorded from 18 musicians while they tapped in synchrony with auditory sequences containing gradual tempo changes under conditions of varying cognitive load (achieved by a simultaneous visual n-back working-memory task comprising three levels of difficulty: observation only, 1-back, and 2-back object comparisons). Prediction ability during SMS decreased with increasing cognitive load. Results of a parametric analysis revealed that the generation of auditory temporal predictions during SMS recruits (1) a distributed network of cortico-cerebellar motor-related brain areas (left dorsal premotor and motor cortex, right lateral cerebellum, SMA proper and bilateral inferior parietal cortex) and (2) medial cortical areas (medial prefrontal cortex, posterior cingulate cortex). While the first network is presumably involved in basic sensory prediction, sensorimotor integration, motor timing, and temporal adaptation, activation in the second set of areas may be related to higher-level social-cognitive processes elicited during action coordination with auditory signals that resemble music performed by human agents.
doi:10.3389/fnhum.2013.00380
PMCID: PMC3748321  PMID: 23970857
temporal prediction; sensorimotor synchronization; medial prefrontal cortex; motor timing; dual-task interference

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