Aggressive Squamous Cell Carcinoma in Organ Transplant Recipients.

Importance: Squamous cell carcinoma (SCC) is the most frequent malignant neoplasm found in solid organ transplant recipients and is associated with a more aggressive disease course and higher risk of metastasis and death than in the general population. Objectives: To report the clinicopathologic features of and identify factors associated with aggressive SCC in solid organ transplant recipients. Methods: This retrospective multicentric case series included 51 patients who underwent solid organ transplantation and were found to have aggressive SCC, defined by nodal or distant metastasis or death by local progression of primary SCC. Standard questionnaires were completed by the researchers between July 18, 2005, and January 1, 2015. Data were analyzed between February 22, 2016, and July 12, 2016. Results: Of the 51 participants, 43 were men and 8 were women, with a median age of 51 years (range, 19-71 years) at time of transplantation and 62 years (range, 36-77 years) at time of diagnosis of aggressive SCC. The distribution of aggressive SCC was preferentially on the face (34 [67%]) and scalp (6 [12%]), followed by the upper extremities (6 [12%]). A total of 21 tumors (41%) were poorly differentiated, with a median tumor diameter of 18.0 mm (range, 4.0-64.0 mm) and median tumor depth of 6.2 mm (range, 1.0-20.0 mm). Perineural invasion was present in 20 patients (39%), while 23 (45%) showed a local recurrence. The 5-year overall survival rate was 23%, while 5-year disease-specific survival was 30.5%. Conclusions and Relevance: Results of this case series suggest that anatomical site, differentiation, tumor diameter, tumor depth, and perineural invasion are important risk factors in aggressive SCC in solid organ transplant recipients.

Maternal and neonatal outcomes in pregnant women with PCOS: comparison of different diagnostic definitions.

STUDY QUESTION: Does the prevalence of adverse maternal and neonatal outcomes vary in women diagnosed with polycystic ovary syndrome (PCOS) according to different definitions? SUMMARY ANSWER: A comparison of different criteria revealed that there is a substantial risk for perinatal complications in PCOS women, regardless of the used definition. WHAT IS KNOWN ALREADY: Pregnant women with PCOS are susceptible to perinatal complications. At present, there are three main definitions for PCOS. So far, we are aware of only one study, which found that the elevated risk for complications varied widely depending on the different phenotypes and features but only considered a relatively small sample size for some of the phenotypes. STUDY DESIGN, SIZE, DURATION: Retrospective matched cohort study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data of primiparous women with PCOS according to ESHRE/ASRM 2003 criteria and healthy controls giving birth to neonates ≥500 g were included. A total of 885 women were analysed: out of 177 women with PCOS, 85 (48.0%) met the National Institutes of Health (NIH) 1990 criteria, another 14 (7.9%) featured the additional phenotypes defined by The Androgen Excess and PCOS Society (AE-PCOS) 2006 criteria, 78 (44.1%) were classified as PCOS exclusively by the ESHRE/ASRM 2003 definition, and 708 represented the control group. MAIN RESULTS AND THE ROLE OF CHANCE: The prevalence of adverse maternal (49.4 versus 64.3 versus 60.3%, P = 0.313) and neonatal (27.1 versus 35.7 versus 23.1%, P = 0.615) outcomes did not differ within the three PCOS groups (ESHRE/ASRM, NIH, AE-PCOS, respectively). Compared with healthy controls, the risk for maternal complications was increased in PCOS patients [odds ratio (OR) 2.57; 95% confidence interval (CI) 1.82-3.64; P < 0.001] while there was no difference in neonatal complications (OR 0.83; 95% CI 0.56-1.21; P = 0.343). LIMITATIONS, REASONS FOR CAUTION: A limitation of our study is its retrospective design and the relatively small sample size, particularly in the AE-PCOS subgroup. WIDER IMPLICATIONS OF THE FINDINGS: Since women with PCOS have, regardless of the used definition, a high risk of maternal and neonatal complications they should be informed and advised to follow regular checks in units where problems can be detected early to allow specialized care. STUDY FUNDING/COMPETING INTERESTS: Marietta Blau Grant (Austrian Agency for International Cooperation in Education and Research; OeAD-GmbH) and mobility scholarship (Medical University of Graz).

Auditory-motor interactions in pediatric motor speech disorders: neurocomputational modeling of disordered development.

BACKGROUND/PURPOSE: Differentiating the symptom complex due to phonological-level disorders, speech delay and pediatric motor speech disorders is a controversial issue in the field of pediatric speech and language pathology. The present study investigated the developmental interaction between neurological deficits in auditory and motor processes using computational modeling with the DIVA model. METHOD: In a series of computer simulations, we investigated the effect of a motor processing deficit alone (MPD), and the effect of a motor processing deficit in combination with an auditory processing deficit (MPD+APD) on the trajectory and endpoint of speech motor development in the DIVA model. RESULTS: Simulation results showed that a motor programming deficit predominantly leads to deterioration on the phonological level (phonemic mappings) when auditory self-monitoring is intact, and on the systemic level (systemic mapping) if auditory self-monitoring is impaired. CONCLUSIONS: These findings suggest a close relation between quality of auditory self-monitoring and the involvement of phonological vs. motor processes in children with pediatric motor speech disorders. It is suggested that MPD+APD might be involved in typically apraxic speech output disorders and MPD in pediatric motor speech disorders that also have a phonological component. Possibilities to verify these hypotheses using empirical data collected from human subjects are discussed. LEARNING OUTCOMES: The reader will be able to: (1) identify the difficulties in studying disordered speech motor development; (2) describe the differences in speech motor characteristics between SSD and subtype CAS; (3) describe the different types of learning that occur in the sensory-motor system during babbling and early speech acquisition; (4) identify the neural control subsystems involved in speech production; (5) describe the potential role of auditory self-monitoring in developmental speech disorders.

Long-term effects of an outpatient rehabilitation program in patients with chronic recurrent low back pain.

PURPOSE: This longitudinal study investigated long-term effects of a multidisciplinary rehabilitation program consisting of resistance and sensorimotor training, patient education, and stress management over 6 months in patients with chronic low back pain. METHODS: Ninety-six patients with chronic recurrent low back pain performed a multidisciplinary rehabilitation program. We assessed pain-free lumbar spine range of motion (ROM), strength of the lumbar extensor muscles, and pain by visual analog scale (VAS). Furthermore, the Roland-Morris (RM) questionnaire and SF-36 were used. The examinations were performed before and after rehabilitation, and a long-term follow-up was performed after 18 months. RESULTS: All outcome measurements (ROM, VAS, RM, muscle strength, and SF-36 scores) improved significantly from baseline to the post-rehabilitation evaluation. These improvements were found to persist until a follow-up evaluation 18 months after cessation of the intervention. CONCLUSIONS: Our findings confirm the results of former studies evaluating the short-term effects of multidisciplinary rehabilitation programs. In addition, our data demonstrate that well-balanced outpatient rehabilitation programs may induce persistent improvements in muscle strength, pain, function and quality of life in patients with chronic low back pain.

White matter impairment in the speech network of individuals with autism spectrum disorder.

Impairments in language and communication are core features of Autism Spectrum Disorder (ASD), and a substantial percentage of children with ASD do not develop speech. ASD is often characterized as a disorder of brain connectivity, and a number of studies have identified white matter impairments in affected individuals. The current study investigated white matter integrity in the speech network of high-functioning adults with ASD. Diffusion tensor imaging (DTI) scans were collected from 18 participants with ASD and 18 neurotypical participants. Probabilistic tractography was used to estimate the connection strength between ventral premotor cortex (vPMC), a cortical region responsible for speech motor planning, and five other cortical regions in the network of areas involved in speech production. We found a weaker connection between the left vPMC and the supplementary motor area in the ASD group. This pathway has been hypothesized to underlie the initiation of speech motor programs. Our results indicate that a key pathway in the speech production network is impaired in ASD, and that this impairment can occur even in the presence of normal language abilities. Therapies that result in normalization of this pathway may hold particular promise for improving speech output in ASD.

Contrast ultrasound for the quantification of deep vein thrombosis in living mice: effects of enoxaparin and P2Y12 receptor inhibition.

BACKGROUND/OBJECTIVES: We examined the applicability of contrast-enhanced ultrasound (CEUS) for imaging of murine deep vein thrombosis (DVT) and measured the effects of enoxaparin, ticagrelor and P2Y(12) receptor deficiency in vivo. METHODS: Deep vein thrombosis was induced by exposure to ferric chloride or ligation of the infrarenal vena cava of C57BL/6 mice after pretreatment with enoxaparin, ticagrelor or vehicle and in P2Y(12-/-) mice. Initial thrombus growth was visualized by intravital microscopy. Thrombi were weighed and examined by immunohistochemistry. CEUS was performed with a standard ultrasound system (Vivid 7, GE Healthcare) in the open abdominal cavity after injection of stabilized sulphur hexafluoride microbubbles. RESULTS: Incubation with ferric chloride resulted in non-occluding platelet-containing thrombus growth within 15-25 min. Sham-operated mice, enoxaparin- and ticagrelor-pretreated wild-type and P2Y(12-/-) mice developed only small thrombi. After injection of the contrast agent, growing thrombi were delineated clearly as negative contrast on CEUS. Thrombus size on CEUS after 25 min was significantly smaller in enoxaparin- (0.3 ± 0.1 mm(2)) and ticagrelor-treated (0.5 ± 0.1 mm(2)) wild-type and in P2Y(12-/-) mice (0.4 ± 0.1 mm(2)) as compared with vehicle-treated wild-type mice (2.0 ± 0.3 mm(2)) in the maximal sagittal plane (P < 0.001, n = 5-10). CEUS-derived thrombus size correlated linearly with thrombus weight and also reflected the extent of ligation-induced DVT. CONCLUSIONS: Contrast-enhanced ultrasound allowed the real-time quantification of DVT in living mice. Genetic and pharmacologic antithrombotic interventions were well reflected by CEUS and suggested an important role of the platelet P2Y(12) receptor in early DVT formation.

The integration of large-scale neural network modeling and functional brain imaging in speech motor control.

Speech production demands a number of integrated processing stages. The system must encode the speech motor programs that command movement trajectories of the articulators and monitor transient spatiotemporal variations in auditory and somatosensory feedback. Early models of this system proposed that independent neural regions perform specialized speech processes. As technology advanced, neuroimaging data revealed that the dynamic sensorimotor processes of speech require a distributed set of interacting neural regions. The DIVA (Directions into Velocities of Articulators) neurocomputational model elaborates on early theories, integrating existing data and contemporary ideologies, to provide a mechanistic account of acoustic, kinematic, and functional magnetic resonance imaging (fMRI) data on speech acquisition and production. This large-scale neural network model is composed of several interconnected components whose cell activities and synaptic weight strengths are governed by differential equations. Cells in the model are associated with neuroanatomical substrates and have been mapped to locations in Montreal Neurological Institute stereotactic space, providing a means to compare simulated and empirical fMRI data. The DIVA model also provides a computational and neurophysiological framework within which to interpret and organize research on speech acquisition and production in fluent and dysfluent child and adult speakers. The purpose of this review article is to demonstrate how the DIVA model is used to motivate and guide functional imaging studies. We describe how model predictions are evaluated using voxel-based, region-of-interest-based parametric analyses and inter-regional effective connectivity modeling of fMRI data.

[Reversible complete heart block by re-infection with Borrelia burgdorferi with negative IgM-antibodies]. / Reversibler totaler AV-Block durch Reinfektion mit Borrelien bei negativen IgM-Titern.

UNLABELLED: PAST HISTORY AND PHYSICAL EXAMINATION: A 38-year-old farmer presented at his general practitioner with dizziness. Physical examination was notable for a heart rate of 35 beats/min. The electrocardiogram (ECG) showed a complete (third degree) heart block with a bradycardic ventricular escape rhythm. The patient reported having had an rash on his right lower leg six weeks previously. After spreading centrifugally it had turned pale in its centre, then regressed and finally disappeared. After having been supplied with a temporary pacemaker in a county hospital the patient was transferred to our hospital. ADMISSION FINDINGS: The ECG showed pacemaker stimulation of the ventricle at about 60 beats/min. Without this stimulation the complete atrioventricular block persisted. Coronary heart disease was excluded by angiography and levocardiography revealed normal systolic left ventricular function. Serological findings were a positive titre of IgG-antibodies against Borrelia while the IgM titre was negative. THERAPY AND COURSE: The heart block disappeared under antibiotic therapy with ceftriaxon within eight days, after first changing to transitory second and first-degree atrioventricular block, and the pacemaker was removed. The patient did not develop any neurological symptoms. CONCLUSION: Cardiac involvement in Lyme disease can be the only manifestation of borreliosis. Possible reversibility under antibiotic therapy is an important aspect of diagnosis. In spite of atypical serology the combination of history, symptoms and serological findings will lead to the diagnosis Lyme disease.

Beneficial effects of chronic low-frequency stimulation of thigh muscles in patients with advanced chronic heart failure.

AIMS: Patients with chronic heart failure (CHF) exhibit detrimental changes in skeletal muscle that contribute to their impaired physical performance. This study investigates the possibility of counteracting these changes by chronic low-frequency electrical stimulation (CLFS) of left and right thigh muscles. METHODS AND RESULTS: (mean+/-SD) 32 CHF patients (53+/-10 years) with an LVEF of 22+/-5%, NYHA II-IV, undergoing optimized drug therapy, were randomized in a CLFS group (CLFSG) or a control group (controls). The groups differed in terms of the intensity of stimulation, which elicited strong muscle contractions only in the CLFSG, whereas the controls received current input up to the sensory threshold without muscle contractions. Functional capacity was assessed by peak VO(2), work capacity, and a 6-min-walk (6-MW). Muscle biopsies were analyzed for myosin heavy chain (MHC) isoforms, citrate synthase (CS) and glyceraldehydephosphate dehydrogenase (GAPDH) activities. Peak VO(2)(mlmin(-1)kg -1) increased from 9.6+/-3.5 to 11.6+/-2.8 (P<0.001) in the CLFSG, and decreased from 10.6+/-2.8 to 9.4+/-3.2 (P<0.05) in the controls. The increase in the CLFSG was paralleled by increases in maximal workload (P<0.05) and oxygen uptake at the anaerobic threshold (P<0.01). The corresponding values of the controls were unchanged, as also the 6-MW values, the MHC isoform distribution, and both CS and GAPDH activities. In the CLFSG, the 6-MW values increased (P<0.001), CS activity was elevated (P<0.05), GAPDH activity decreased (P<0.01), and the MHC isoforms were shifted in the slow direction with increases in MHCI at the expense of MHCIId/x (P<0.01). CONCLUSIONS: Our results suggest that CLFS is a suitable treatment to counteract detrimental changes in skeletal muscle and to increase exercise capacity in patients with severe CHF.

A modeling study of potential sources of curvature in human reaching movements.

The authors of this article suggest that the slight but consistent posture-dependent curvature of the spatial paths in the kinematic transformation between intrinsic and extrinsic coordinates may result in a systematic curvature of movements initially planned as straight-line trajectories toward the target. A kinematic planning model is presented that takes into account the anisotropy of the intrinsic and extrinsic transformation and tends to avoid movements that require excessive joint rotations by introducing slight deviations from a straight-line trajectory. Preliminary simulations showed reasonably good agreement with experimental data, especially considering that the current model is strictly based on kinematics. A quantitative analysis showed that the strategy used in the model achieves a favorable compromise between straight-line movements and angular joint changes: By slightly increasing the spatial length of the movement (i.e., by introducing curvature), an individual can greatly reduce the total amount of joint rotation required to produce the movement.

An auditory-feedback-based neural network model of speech production that is robust to developmental changes in the size and shape of the articulatory system.

The purpose of this article is to demonstrate that self-produced auditory feedback is sufficient to train a mapping between auditory target space and articulator space under conditions in which the structures of speech production are undergoing considerable developmental restructuring. One challenge for competing theories that propose invariant constriction targets is that it is unclear what teaching signal could specify constriction location and degree so that a mapping between constriction target space and articulator space can be learned. It is predicted that a model trained by auditory feedback will accomplish speech goals, in auditory target space, by continuously learning to use different articulator configurations to adapt to the changing acoustic properties of the vocal tract during development. The Maeda articulatory synthesis part of the DIVA neural network model (Guenther et al., 1998) was modified to reflect the development of the vocal tract by using measurements taken from MR images of children. After training, the model was able to maintain the 11 English vowel targets in auditory planning space, utilizing varying articulator configurations, despite morphological changes that occur during development. The vocal-tract constriction pattern (derived from the vocal-tract area function) as well as the formant values varied during the course of development in correspondence with morphological changes in the structures involved with speech production. Despite changes in the acoustical properties of the vocal tract that occur during the course of development, the model was able to demonstrate motor-equivalent speech production under lip-restriction conditions. The model accomplished this in a self-organizing manner even though there was no prior experience with lip restriction during training.

Effects of categorization and discrimination training on auditory perceptual space.

Psychophysical phenomena such as categorical perception and the perceptual magnet effect indicate that our auditory perceptual spaces are warped for some stimuli. This paper investigates the effects of two different kinds of training on auditory perceptual space. It is first shown that categorization training using nonspeech stimuli, in which subjects learn to identify stimuli within a particular frequency range as members of the same category, can lead to a decrease in sensitivity to stimuli in that category. This phenomenon is an example of acquired similarity and apparently has not been previously demonstrated for a category-relevant dimension. Discrimination training with the same set of stimuli was shown to have the opposite effect: subjects became more sensitive to differences in the stimuli presented during training. Further experiments investigated some of the conditions that are necessary to generate the acquired similarity found in the first experiment. The results of these experiments are used to evaluate two neural network models of the perceptual magnet effect. These models, in combination with our experimental results, are used to generate an experimentally testable prediction concerning changes in the brain's auditory maps under different training conditions.

Articulatory tradeoffs reduce acoustic variability during American English /r/ production.

The American English phoneme /r/ has long been associated with large amounts of articulatory variability during production. This paper investigates the hypothesis that the articulatory variations used by a speaker to produce /r/ in different contexts exhibit systematic tradeoffs, or articulatory trading relations, that act to maintain a relatively stable acoustic signal despite the large variations in vocal tract shape. Acoustic and articulatory recordings were collected from seven speakers producing /r/ in five phonetic contexts. For every speaker, the different articulator configurations used to produce /r/ in the different phonetic contexts showed systematic tradeoffs, as evidenced by significant correlations between the positions of transducers mounted on the tongue. Analysis of acoustic and articulatory variabilities revealed that these tradeoffs act to reduce acoustic variability, thus allowing relatively large contextual variations in vocal tract shape for /r/ without seriously degrading the primary acoustic cue. Furthermore, some subjects appeared to use completely different articulatory gestures to produce /r/ in different phonetic contexts. When viewed in light of current models of speech movement control, these results appear to favor models that utilize an acoustic or auditory target for each phoneme over models that utilize a vocal tract shape target for each phoneme.

A theoretical investigation of reference frames for the planning of speech movements.

Does the speech motor control system use invariant vocal tract shape targets when producing vowels and semivowels? A 4-part theoretical treatment favoring models whose only invariant targets are regions in auditory perceptual space over models that posit invariant constriction targets is presented. Auditory target regions are hypothesized to arise during development as an emergent property of neural map formation in the auditory system. Furthermore, speech movements are planned as trajectories in auditory perceptual space. These trajectories are then mapped into articulator movements through a neural mapping that allows motor equivalent variability in constriction locations and degrees when needed. These hypotheses are illustrated using computer simulations of the DIVA model of speech acquisition and production. Finally, several difficult challenges to proponents of constriction theories based on this theoretical treatment are posed.

A self-organizing neural network architecture for navigation using optic flow.

This article describes a self-organizing neural network architecture that transforms optic flow and eye position information into representations of heading, scene depth, and moving object locations. These representations are used to navigate reactively in simulations involving obstacle avoidance and pursuit of a moving target. The network's weights are trained during an action-perception cycle in which self-generated eye and body movements produce optic flow information, thus allowing the network to tune itself without requiring explicit knowledge of sensor geometry. The confounding effect of eye movement during translation is suppressed by learning the relationship between eye movement outflow commands and the optic flow signals that they induce. The remaining optic flow field is due to only observer translation and independent motion of objects in the scene. A self-organizing feature map categorizes normalized translational flow patterns, thereby creating a map of cells that code heading directions. Heading information is then recombined with translational flow patterns in two different ways to form maps of scene depth and moving object locations. Most of the learning processes take place concurrently and evolve through unsupervised learning. Mapping the learned heading representations onto heading labels or motor commands requires additional structure. Simulations of the network verify its performance using both noise-free and noisy optic flow information.

On-Demand Generation of a Formaldehyde-in-Air Standard.

The feasibility of using catalytic conversion of methanol to formaldehyde to produce standard amount of substance fractions of formaldehyde was examined. The conversion efficiencies of several catalysts were measured as a function of temperature, balance gas, catalyst bed length, and methanol amount of substance fraction in an effort to identify conditions which yield high and consistent conversion of methanol to formaldehyde. The highest observed conversion rate was (97 ± 4) % using a molybdenum catalyst, where the error is the 2σ uncertainty. The conversion efficiency was found to be consistent over repeated cycles and over a long lifetime test, suggesting that a molybdenum catalyst is a viable candidate for a standard formaldehyde generator, particularly for low formaldehyde amount of substance fractions (< 15 µmol/mol).

The perceptual magnet effect as an emergent property of neural map formation.

The perceptual magnet effect is one of the earliest known language-specific phenomena arising in infant speech development. The effect is characterized by a warping of perceptual space near phonemic category centers. Previous explanations have been formulated within the theoretical framework of cognitive psychology. The model proposed in this paper builds on research from both psychology and neuroscience in working toward a more complete account of the effect. The model embodies two principal hypotheses supported by considerable experimental and theoretical research from the neuroscience literature: (1) sensory experience guides language-specific development of an auditory neural map, and (2) a population vector can predict psychological phenomena based on map cell activities. These hypotheses are realized in a self-organizing neural network model. The magnet effect arises in the model from language-specific nonuniformities in the distribution of map cell firing preferences. Numerical simulations verify that the model captures the known general characteristics of the magnet effect and provides accurate fits to specific psychophysical data.

Speech sound acquisition, coarticulation, and rate effects in a neural network model of speech production.

This article describes a neural network model of speech motor skill acquisition and speech production that explains a wide range of data on variability, motor equivalence, coarticulation, and rate effects. Model parameters are learned during a babbling phase. To explain how infants learn language-specific variability limits, speech sound targets take the form of convex regions, rather than points, in orosensory coordinates. Reducing target size for better accuracy during slower speech leads to differential effects for vowels and consonants, as seen in experiments previously used as evidence for separate control processes for the 2 sound types. Anticipatory coarticulation arises when targets are reduced in size on the basis of context; this generalizes the well-known look-ahead model of coarticulation. Computer simulations verify the model's properties.

A neural network model of speech acquisition and motor equivalent speech production.

This article describes a neural network model that addresses the acquisition of speaking skills by infants and subsequent motor equivalent production of speech sounds. The model learns two mappings during a babbling phase. A phonetic-to-orosensory mapping specifies a vocal tract target for each speech sound; these targets take the form of convex regions in orosensory coordinates defining the shape of the vocal tract. The babbling process wherein these convex region targets are formed explains how an infant can learn phoneme-specific and language-specific limits on acceptable variability of articulator movements. The model also learns an orosensory-to-articulatory mapping wherein cells coding desired movement directions in orosensory space learn articulator movements that achieve these orosensory movement directions. The resulting mapping provides a natural explanation for the formation of coordinative structures. This mapping also makes efficient use of redundancy in the articulator system, thereby providing the model with motor equivalent capabilities. Simulations verify the model's ability to compensate for constraints or perturbations applied to the articulators automatically and without new learning and to explain contextual variability seen in human speech production.