[Current possibilities and challenges in the diagnosis of laryngopharyngeal reflux]. / Aktuelle Möglichkeiten und Herausforderungen bei der Diagnostik des laryngopharyngealen Refluxes.

Laryngopharyngeal reflux (LPR) is defined as backflow of gastral or gastroduodenal content into the upper aerodigestive tract and characterized by a variety of unspecific symptoms such as chronic cough, globus sensation, or mucus hypersecretion. Due to the lack of a gold standard and the heterogeneity of studies, the diagnosis of LPR is still problematic and challenging. However, in patients with characteristic symptoms and endoscopic findings, with an increased reflux symptom index, a pathologic reflux finding score (RFS), pathologic 24 h esophageal or oropharyngeal pH monitoring, and without any other underlying condition, the diagnosis of LPR is probable. In the following review, we critically discuss the abovementioned methods as well as more recent tools such as measurements of pepsin concentrations in the saliva for diagnosis of LPR.

Induction Mapping of the 3D-Modulated Spin Texture of Skyrmions in Thin Helimagnets.

Envisaged applications of Skyrmions in magnetic memory and logic devices crucially depend on the stability and mobility of these topologically nontrivial magnetic textures in thin films. We present for the first time quantitative maps of the magnetic induction that provide evidence for a 3D modulation of the Skyrmionic spin texture. The projected in-plane magnetic induction maps as determined from in-line and off-axis electron holography carry the clear signature of Bloch Skyrmions. However, the magnitude of this induction is much smaller than the values expected for homogeneous Bloch Skyrmions that extend throughout the thickness of the film. This finding can only be understood if the underlying spin textures are modulated along the out-of-plane z direction. The projection of (the in-plane magnetic induction of) helices is further found to exhibit thickness-dependent lateral shifts, which show that this z modulation is accompanied by an (in-plane) modulation along the x and y directions.

TEM investigations on the local microstructure of electrodeposited galfenol nanowires.

The local microstructure of Fe-Ga nanowires is investigated considering dependence on the deposition technique. Using a complexed electrolyte, smooth and homogeneous Fe80Ga20 nanowires are deposited into anodic aluminum oxide templates by either applying pulse potential or potentiostatic deposition technique. At optimized deposition conditions the wires show the desired composition of Fe80±2Ga20±2 without a gradient along the growth direction. Composition distribution, structure and microstructure are examined in detail and reveal only minor differences. Line EELS and crystal lattice measurements reveal a negligible oxygen content for both preparation routines. Neither Fe/Ga oxides nor hydroxides were found. Both potentiostatically deposited as well as pulse deposited nanowires exhibit a preferred 〈110〉orientation, the latter with slightly larger crystals. Different contrast patterns were found by TEM that appear more pronounced in the case of pulse deposited wires. High resolution transmission electron microscopy analysis and comparison of differently prepared focused ion beam lamellas reveal that these contrasts are caused by defects in the alternating potential deposition itself and are not induced during the TEM preparation process. The alternating potential mode causes periodic growth thereby inducing different layers with reduced wire thickness/defects at the layer interfaces.

MRI and clinicopathological correlation of childhood primary central nervous system angiitis.

AIM: To review the long-term clinical and imaging follow-up of eight children with histopathologically proven childhood primary central nervous system angiitis (cPACNS). MATERIALS AND METHODS: Eight children (5-17 years, five female and three male patients) with biopsy-proven cPACNS vasculitis were reviewed retrospectively. All children were followed at the Children's Hospital of Eastern Ontario. Magnetic resonance imaging (MRI) images of the brain parenchyma and vessel pattern of the arteries of the circle of Willis were reviewed at baseline and follow-up(s). All MRI images were correlated with clinical and histopathological findings. RESULTS: Seven (87.5%) children demonstrated parenchymal abnormalities: five of the seven (71.4%) presented with non-haemorrhagic lesions, one (14.3%) presented with a parenchymal bleed, and one (14.3%) showed diffuse oedema. One child remained negative for brain parenchymal abnormality at baseline and follow-up. Of the seven children with a parenchymal abnormality, parenchymal enhancement was seen in two (28.5%) and leptomeningeal enhancement was seen in one child. Only two children had positive diffusion-weighted imaging (DWI) restriction at baseline. Five of the seven children (71.4%) showed no magnetic resonance angiography (MRA) abnormalities at baseline. In one, MRA detected complete absence of flow. Follow-up MRA (24-74 months) demonstrated that five of the seven (71.4%) children had progressive paucity of the peripheral vascularity. Two children (28.5%) with shorter-term follow-up (7 and 13 months) did not demonstrate MRA changes. CONCLUSION: Long-term follow-up MRA demonstrated progressive paucity of peripheral vessels, which could be secondary to the inflammation affecting the peripheral vasculature causing reduction in vessel lumen size beyond the resolution of the maximum intensity projection (MIP) reconstruction.

Determinants and effects of sinus worm Skrjabingylus nasicola (Nematoda: Metastrongyloidae) infestation in invasive American mink Neovison vison in Germany.

Skrjabingylus nasicola (Leuckart, 1842) are geographically widespread nematodes that parasitize the nasal and frontal sinus cavities of smaller mustelids. As most prior work was solely based on the analysis of bone injuries of museum skull, little is known about the determinants and effects of infestation in the host species. Working on fresh skulls, we aimed to analyze infestation patterns in American mink (Neovison vison Schreber, 1777) from nine study areas in northern Germany and to identify factors that explained infestation prevalence and intensity in the host species. The prevalence (46.7-62.9 %) and infestation intensity values (4.5-10.89 nematodes) reported here were relatively large, especially compared to other American mink populations in Europe. Considering mink diet, our study sites probably harbored a larger number of infested paratenic hosts and climate did not have a substantial negative influence on survival of S. nasicola larvae. We did not observe any significant sex-age differences in either prevalence or intensity of S. nasicola infestation. We did not find a negative impact of an infestation on the host animals' body weight, confirming prior results that the parasite is not a significant mortality factor in mustelids. Our study suggests that this holds even outside the native distributional range where the host's defenses might not be optimally adapted to an autochthonous parasite.

On the stability of AuFe alloy nanoparticles.

AuFe nanoparticles with mean diameters d p  = 13.2 nm have been prepared by inert-gas condensation. Conventional and high-resolution transmission electron microscopy and energy-dispersive x-ray spectroscopy investigations show that the particles are mostly icosahedra. Scanning transmission electron microscopy-energy-dispersive x-ray spectroscopy and scanning transmission electron microscopy-electron energy-loss spectroscopy show that the as-grown particles exhibit a core-shell structure. The shell is mainly composed of an amorphous FeO layer. Although Fe and Au are immiscible in the bulk, the particle cores are found to be homogeneously mixed at the atomic level with a local composition of around Au84Fe16 (at.%). AuFe nanoparticles exhibit a complex magnetic structure in which the core behaves as a spin glass with a freezing temperature of 35 K, whereas the amorphous FeO shell behaves as a ferro-ferrimagnetic system. On annealing above 300 °C, the AuFe icosahedra phases separate into their elemental constituents. Hence the as-grown AuFe icosahedra are metastable, thereby implying that the bulk phase diagram also applies for nanoscopic materials.

Wireless 'mini' multichannel intraluminal impedance-pH: what is the optimal design of a miniature wireless device?

Catheter-based methods for multichannel intraluminal impedance-pH monitoring are invasive and uncomfortable. The current alternative is a wireless system that clips to the esophageal mucosa, but which only measures pH. A shorter two-site wireless sensor that detects impedance and pH, and can be clipped to the esophagus, would be desirable. This study compares sensor positions and separations to determine the optimal configuration of a two-site wireless sensor. Records of 20 patients (10 on and 10 off proton pump inhibitor) who had ambulatory reflux testing with a multichannel intraluminal impedance-pH system (Sandhill Scientific Inc., Highlands Ranch, CO, USA) with six impedance and two pH sensors were reviewed. An investigator was blinded to four combinations of impedance channels plus pH. He read a 3-hour postprandial section from each of the combinations (total of 80 studies) and marked reflux episodes. Results were compared with his own interpretation of the full tracing. Two hundred and two total reflux episodes were analyzed, 113 acid (pH < 4) and 89 nonacid (pH > 4). Mean and median numbers of total reflux episodes were calculated. In the full study, the interpreter detected a mean of 10 reflux episodes per study. In the 5 cm and 7 cm, 3 cm and 7 cm, and 3 cm and 5 cm studies, the interpreter found a mean of 8.1, 11.1, and 9.8 reflux episodes per study, respectively. One-way analysis of variance yielded a P-value of 0.43. The trend of these preliminary findings suggests that the 3 cm and 5 cm site is the most sensitive and the 5 cm and 7 cm is the least, with the 3 cm and 7 cm site perhaps as the preferred location. The lack of a significant difference, at the very least, suggests that any of the 'mini' locations could be used. The small number of observations could have resulted in a Type II statistical error.

Persisting myelin oligodendrocyte glycoprotein antibodies in aquaporin-4 antibody negative pediatric neuromyelitis optica.

BACKGROUND: Recently we showed that antibodies to myelin oligodendrocyte glycoprotein (MOG) can be found in aquaporin-4 (AQP4)-immunoglobulin (IgG) seronegative pediatric and adult patients with definite and high-risk neuromyelitis optica (NMO). OBJECTIVE: The purpose of this study was to describe the clinical characteristics and temporal dynamics of MOG-IgG in AQP4-IgG seronegative pediatric patients presenting with definite NMO. METHODS: Children with definite NMO who were referred for further testing of serum antibodies for AQP4 and MOG with a cell-based assay were included in this study. Clinical disease course, cerebrospinal fluid and magnetic resonance imaging (MRI) studies of these patients were reviewed. RESULTS: Between 2008 and 2012 eight children who fulfilled the diagnostic criteria of definite NMO were recruited. Two children with definite NMO tested positive for AQP4-IgG but were negative for MOG-IgG antibodies. Three children had an absence of AQP4-IgG and MOG-IgG antibodies. Three children with definite NMO had high titers of serum MOG-IgG antibodies (≥1: 160), but no AQP4-directed humoral immune response. Longitudinal analysis of serum samples of the latter three children showed persisting high MOG-IgG titers over time. CONCLUSION: Pediatric patients presenting with clinical symptoms and MRI findings highly suggestive of NMO but with high and persisting MOG-IgG antibody titers are most likely to represent a distinct subgroup of acute demyelinating diseases with important clinical and therapeutic implications.

Swallowing activity assessed by ambulatory impedance-pH monitoring predicts awake and asleep periods at night.

INTRODUCTION: Voluntary muscle activity, including swallowing, decreases during the night. The association between nocturnal awakenings and swallowing activity is under-researched with limited information on the frequency of swallows during awake and asleep periods. AIM: The aim of this study was to assess nocturnal swallowing activity and identify a cut-off predicting awake and asleep periods. METHODS: Patients undergoing impedance-pH monitoring as part of GERD work-up were asked to wear a wrist activity detecting device (Actigraph(®)) at night. Swallowing activity was quantified by analysing impedance changes in the proximal esophagus. Awake and asleep periods were determined using a validated scoring system (Sadeh algorithm). Receiver operating characteristics (ROC) analyses were performed to determine sensitivity, specificity and accuracy of swallowing frequency to identify awake and asleep periods. RESULTS: Data from 76 patients (28 male, 48 female; mean age 56 ± 15 years) were included in the analysis. The ROC analysis found that 0.33 sw/min (i.e. one swallow every 3 min) had the optimal sensitivity (78 %) and specificity (76 %) to differentiate awake from asleep periods. A swallowing frequency of 0.25 sw/min (i.e. one swallow every 4 min) was 93 % sensitive and 57 % specific to identify awake periods. A swallowing frequency of 1 sw/min was 20 % sensitive but 96 % specific in identifying awake periods. Impedance-pH monitoring detects differences in swallowing activity during awake and asleep periods. Swallowing frequency noticed during ambulatory impedance-pH monitoring can predict the state of consciousness during nocturnal periods.

Quantitative measurement of the surface self-diffusion on Au nanoparticles by aberration-corrected transmission electron microscopy.

We present a method that allows for a quantitative measurement of the surface self-diffusion on nanostructures, such as nanoparticles, at the atomic scale using aberration-corrected high-resolution transmission electron microscopy (HRTEM). The diffusion coefficient can be estimated by measuring the fluctuation of the atom column occupation at the surface of Au nanoparticles, which is directly observable in temporal sequences of HRTEM images. Both a Au icosahedron and a truncated Au octahedron are investigated, and their diffusion coefficients are found to be in the same order of magnitude, D = 10(-17) to 10(-16) cm(2)/s. It is to be assumed that the measured surface diffusion is affected by the imaging electron beam. This assumption is supported by the observed instability of a (5 × 1) surface reconstruction on a {100} Au facet.

Pharmacologic treatment of gastroparesis: What is (still) on the horizon?

Gastroparesis is a neuromuscular disorder of the upper gastrointestinal tract. Patients typically complain about early satiety, postprandial fullness, nausea and vomiting. Etiology is multifactorial. Treatment strategies include nutritional support, pharmacologic agents or surgery for refractory cases. Metoclopramide is the first and only FDA approved pharmacologic agent for (diabetic) Gastroparesis. A couple of compounds are currently in clinical testing. Some beacons of hope have failed recently, however. Here we present an update on possible future treatment options.

Consensus statement: evaluation of new and existing therapeutics for pediatric multiple sclerosis.

New therapies are being evaluated by clinical trials and, if efficacious, introduced for the treatment of adult MS. The role of these new and existing agents in the management of pediatric MS has yet to be defined. Pediatric investigation plans are now required by the Food and Drug Administration and European Medicines Agency for approval of new biological agents, providing an important opportunity to gather much-needed data for clinicians caring for children and adolescents with MS. However, challenges include the small number of patients, and the need for efficient yet comprehensive study designs incorporating factors necessary to inform the clinical care of children with MS. The elected Steering committee of the International Pediatric MS Study Group (IPMSSG) conducted a structured review of existing data on the disease-modifying therapies in pediatric MS and developed a consensus statement, which was further modified by the IPMSSG general membership, using an online survey tool. Fifty-one IPMSSG members from 21 countries responded to the survey, and 50 approved the final statement. Consensus recommendations regarding use of existing first- and second-line therapies, as well as a proposed definition for inadequate treatment response, are presented. Recommendations for the use and evaluation of emerging therapies (currently in phase III clinical trials or recently approved for adult MS) are discussed. The IPMSSG endorses the inclusion of pediatric MS patients in trials evaluating appropriate new and emerging therapies. Mechanisms for conducting high-impact, multicenter studies, including long-term follow-up in pediatric MS, are required to ensure that all MS patients, irrespective of age, benefit from advances in MS therapeutics.

Extraesophageal gastroesophageal reflux disease (GERD) symptoms are not more frequently associated with proximal esophageal reflux than typical GERD symptoms.

Extraesophageal (EE) symptoms such as cough and throat clearing are common in patients referred for reflux testing, but are less commonly associated with gastroesophageal reflux disease (GERD). Patients with reflux associated EE symptoms often lack typical GERD symptoms of heartburn and regurgitation. Our aim was to compare the frequency of proximal esophageal reflux between esophageal (typical) symptoms and EE (atypical) symptoms. Combined multichannel intraluminal impedance-pH (MII-pH) tracings were blinded by an investigator so that symptom markers were relabeled with a number without disclosure of symptom type. We selected 40 patients with at least five reflux-related symptom events for one of four symptoms (heartburn, regurgitation, cough, or throat clearing). A blinded investigator analyzed all 200 reflux episodes, reporting the proximal esophageal extent of the reflux for all symptoms. The percentage of symptom-related reflux extending proximally to 17 cm above the LES was similar among all four symptom types. At least 50% of all symptoms were associated with proximal esophageal reflux to 17 cm, with regurgitation having the highest frequency at 60%. Our data indicate that EE symptoms are not more frequently associated with proximal esophageal reflux than typical esophageal symptoms.

Real-time detection of neonatal seizures improves with on demand EEG interpretation.

OBJECTIVE: Under- and overtreatment of seizures may result in adverse outcomes; thus, early, reliable seizure identification is crucial. Continuous conventional ElectroEncephaloGram (cEEG) is the gold standard, but amplitude integrated EEG (aEEG) is most widely-used in the Neonatal Intensive Care Unit (NICU). We aimed to determine whether a novel pathway combining cEEG and aEEG for seizure detection would improve real-time seizure identification. METHODS: A single-center, prospective quality improvement project cohort. Patients at-risk of seizures were monitored by cEEG and aEEG concurrently, with the option for the neonatologist to contact a neurologist for real-time cEEG interpretation. The primary outcome was correct identification of seizures by the new combined pathway compared to aEEG alone. RESULTS: Seizure detection using aEEG had a sensitivity of 46.2%; specificity of 93.3%; PPV of 66.7%; and NPV of 85.7%. Utilizing the new on-demand, real-time cEEG interpretation by a neurologist, correct seizure identification increased by 27% (95%CI: 10-56%). Over-diagnosis of seizures was avoided in 33.3% (95% CI: 12.1-64.6%) and misuse of anti-seizure medication was prevented. CONCLUSIONS: Combining aEEG with on-demand cEEG interpretation improved accurate seizure detection in a high-risk NICU population, with the potential to avoid over-treatment. SIGNIFICANCE: We describe a novel combined EEG monitoring pathway to improve seizure detection, and prevent unnecessary treatment.

Understanding the metal-carbon interface in FePt catalyzed carbon nanotubes.

Any tip functionalization of carbon nanotubes, for which the relative orientation between their (metallic) catalyst particle and the nanotube axis is essential, requires a detailed knowledge of the nature of the internal interface between the particle and the outgrown tube. In the present work, this interface is characterized with atomic precision using state-of-the-art low-voltage aberration-corrected transmission electron microscopy in combination with molecular dynamics simulations for the case of hard-magnetically terminated carbon nanotubes. Our results indicate that the physical principle based upon which the interfacial metal facet is chosen is a reduction of the desorption energy for carbon.

Intrathecal IgM synthesis in pediatric MS is not a negative prognostic marker of disease progression: quantitative versus qualitative IgM analysis.

BACKGROUND: Intrathecal IgM synthesis is reported to be associated with a worse prognosis in adults with multiple sclerosis (MS). OBJECTIVE: To study the predictive value of intrathecal IgM synthesis for the clinical course of pediatric MS. METHODS: Seventy children with onset of MS before the age of 16 years and followed for a median period of 10.4 years (range: 0.4-22.8 years) were studied. The two subgroups with (n=44) or without (n=26) intrathecal IgM synthesis were distinguished by a new, very sensitive, evaluation of quantitative analysis in cerebrospinal fluid (CSF)/serum quotient diagrams (Reibergrams). The clinical course and EDSS (Expanded Disability Status Scale) scores at five and ten years were compared with IgM frequencies between both groups with a new statistics program for CSF data. RESULTS: The cohort of children without intrathecal IgM production had higher numbers of attacks in the first two years and shorter time intervals between first and second attack, although this was not statistically significant (p=0.04, p=0.15 respectively). In addition there was also a trend for girls without intrathecal IgM synthesis to have a higher EDSS score after 10 years compared with the group with IgM synthesis. CONCLUSION: Intrathecal IgM synthesis is not associated with a more rapid progression of disability in pediatric MS. Reevaluation of data from previous reports about the negative predictive value of intrathecal IgM synthesis in adult MS with a CSF statistics tool show that the apparent contradiction is due to a methodological bias in the qualitative detection of 'oligoclonal' IgM or linear IgM index.

Excellent agreement between genetic and hydrogen breath tests for lactase deficiency and the role of extended symptom assessment.

Clinical manifestations of lactase (LCT) deficiency include intestinal and extra-intestinal symptoms. Lactose hydrogen breath test (H2-BT) is considered the gold standard to evaluate LCT deficiency (LD). Recently, the single-nucleotide polymorphism C/T(-13910) has been associated with LD. The objectives of the present study were to evaluate the agreement between genetic testing of LCT C/T(-13910) and lactose H2-BT, and the diagnostic value of extended symptom assessment. Of the 201 patients included in the study, 194 (139 females; mean age 38, range 17-79 years, and 55 males, mean age 38, range 18-68 years) patients with clinical suspicion of LD underwent a 3-4 h H2-BT and genetic testing for LCT C/T(-13910). Patients rated five intestinal and four extra-intestinal symptoms during the H2-BT and then at home for the following 48 h. Declaring H2-BT as the gold standard, the CC(-13910) genotype had a sensitivity of 97% and a specificity of 95% with a κ of 0.9 in diagnosing LCT deficiency. Patients with LD had more intense intestinal symptoms 4 h following the lactose challenge included in the H2-BT. We found no difference in the intensity of extra-intestinal symptoms between patients with and without LD. Symptom assessment yielded differences for intestinal symptoms abdominal pain, bloating, borborygmi and diarrhoea between 120 min and 4 h after oral lactose challenge. Extra-intestinal symptoms (dizziness, headache and myalgia) and extension of symptom assessment up to 48 h did not consistently show different results. In conclusion, genetic testing has an excellent agreement with the standard lactose H2-BT, and it may replace breath testing for the diagnosis of LD. Extended symptom scores and assessment of extra-intestinal symptoms have limited diagnostic value in the evaluation of LD.

Transforming insulating rutile single crystal into a fully ordered nanometer-thick transparent semiconductor.

Rutile single crystals treated with ion-beam preferential etching (IBPE) are investigated with electrical transport and transmission electron microscopy. The initially insulating single crystals show the formation of an oxygen vacancy-rich, highly ordered, thin conducting layer, below a crystalline rutile TiO(2) surface layer. Carrier concentrations of 10(19) cm(-3) and very high mobilities of the order of 300 cm(2) V(-1) s(-1) are observed in the nanolayers. The observations indicate that rutile single crystals can be effectively transformed into controlled conducting material using IBPE for creating a new breakthrough in transparent conducting media.