White Matter Biomarkers Associated with Motor Change in Individuals with Stroke: A Continuous Theta Burst Stimulation Study.

Continuous theta burst stimulation (cTBS) is a form of noninvasive repetitive brain stimulation that, when delivered over the contralesional hemisphere, can influence the excitability of the ipsilesional hemisphere in individuals with stroke. cTBS applied prior to skilled motor practice interventions may augment motor learning; however, there is a high degree of variability in individual response to this intervention. The main objective of the present study was to assess white matter biomarkers of response to cTBS paired with skilled motor practice in individuals with chronic stroke. We tested the effects of stimulation of the contralesional hemisphere at the site of the primary motor cortex (M1c) or primary somatosensory cortex (S1c) and a third group who received sham stimulation. Within each stimulation group, individuals were categorized into responders or nonresponders based on their capacity for motor skill change. Baseline diffusion tensor imaging (DTI) indexed the underlying white matter microstructure of a previously known motor learning network, named the constrained motor connectome (CMC), as well as the corticospinal tract (CST) of lesioned and nonlesioned hemispheres. Across practice, there were no differential group effects. However, when categorized as responders vs. nonresponders using change in motor behaviour, we demonstrated a significant difference in CMC microstructural properties (as measured by fractional anisotropy (FA)) for individuals in M1c and S1c groups. There were no significant differences between responders and nonresponders in clinical baseline measures or microstructural properties (FA) in the CST. The present study identifies a white matter biomarker, which extends beyond the CST, advancing our understanding of the importance of white matter networks for motor after stroke.

Outcome of long benign esophageal strictures undergoing endoscopictherapy: a tertiary center experience.

COMPLEX BENIGN ESOPHAGEAL STRICTURES ARE DEFINED BY LENGTH (≥2 CM), SMALL DIAMETER, AND STRICTURE ANGULATION OR TORTUOSITY. THE LONG-TERM COURSE OF COMPLEX ESOPHAGEAL STRICTURES BASED ON LENGTH IS CURRENTLY UNCLEAR. WE SUSPECT THAT THE ESOPHAGEAL STRICTURE LENGTH MIGHT IMPACT THE EFFECTIVENESS OF ENDOSCOPIC DILATION THERAPY. WE PERFORMED A RETROSPECTIVE STUDY OF ALL BENIGN ESOPHAGEAL STRICTURES OF 2 CM OR LONGER TREATED AT A SINGLE CENTER BETWEEN JULY 1, 2010, AND MAY 31, 2014. PRIMARY OUTCOMES WERE CHANGED IN DYSPHAGIA SCORE AT THE END OF FOLLOW-UP COMPARED TO FIRST DILATION AT OUR FACILITY AND THE NEED FOR GASTROSTOMY PLACEMENT OR ESOPHAGECTOMY DURING FOLLOW-UP. DATA WERE STRATIFIED INTO FOUR SUBGROUPS ACCORDING TO STRICTURE LENGTH 20­29, 30­49, 50­99, AND 100 MM OR LONGER. EIGHTY-SEVEN PATIENTS (MEAN AGE 66 YEARS, 54% WOMEN) WERE FOLLOWED OVER A MEDIAN OF 40 MONTHS. PATIENTS UNDERWENT A MEDIAN OF 6 DILATIONS, AVERAGING 0.3 DILATIONS PER MONTH. MEDIAN DYSPHAGIA SCORE REMAINED UNCHANGED AT 2; 37 (43%) PATIENTS REPORTED RESOLUTION OR IMPROVED DYSPHAGIA AND 50 (57%) PATIENTS REPORTED NO IMPROVEMENT OR WORSENED DYSPHAGIA. GASTROSTOMY PLACEMENT OR ESOPHAGECTOMY WAS NEEDED FOR 23 (26%) AND 3 (3%) PATIENTS, RESPECTIVELY. MEDIAN DEGREE OF DYSPHAGIA AT THE END OF FOLLOW-UP DID NOT DIFFER BETWEEN THE FOUR STRICTURE LENGTH SUBGROUPS, YET NO PATIENT HAD IMPROVEMENT IN THE 100 MM OR LONGER SUBGROUP. MORE THAN HALF OF PATIENTS WITH LONG BENIGN ESOPHAGEAL STRICTURES HAD UNCHANGED DYSPHAGIA OR DEVELOPED WORSE DYSPHAGIA DURING FOLLOW-UP. LONG-TERM OUTCOMES DID NOT DIFFER BETWEEN DIFFERENT STRICTURE LENGTHS: .

Acceptance of evidence-supported hypotheses generates a stronger signal from an underlying functionally-connected network.

Choosing one's preferred hypothesis requires multiple brain regions to work in concert as a functionally connected network. We predicted that a stronger network signal would underlie cognitive coherence between a hypothesis and the available evidence. In order to identify such functionally connected networks in magnetoencephalography (MEG) data, we first localized the generators of changes in oscillatory power within three frequency bands, namely alpha (7-13 Hz), beta (18-24 Hz), and theta (3-7 Hz), with a spatial resolution of 5mm and temporal resolution of 50 ms. We then used principal component analysis (PCA) to identify functionally connected networks reflecting co-varying post-stimulus changes in power. As predicted, PCA revealed a functionally connected network with a stronger signal when the evidence supported accepting the hypothesis being judged. This difference was driven by beta-band power decreases in the left dorsolateral prefrontal cortex (DLPFC), ventromedial prefrontal cortex (VMPFC), posterior cingulate cortex (PCC), and midline occipital cortex.

Photonic-lantern-based coherent LIDAR system.

In this work, a photonic-lantern-based coherent LIDAR system is experimentally demonstrated and the voltage signal-to-noise ratio improvement is analyzed. A voltage signal-to-noise ratio (SNR(V)) improvement of 2.8 is demonstrated experimentally for photonic-lantern-based coherent receivers relative to single-mode coherent receivers. The voltage signal-to-noise ratio improvement is obtained when other parameters are kept constant. We have also analyzed the effect of random optical power distribution among the single-mode fibers. We found that the distribution does not significantly impact the SNR(V) improvement. The mean value of voltage signal-to-noise ratio improvement is found to be ~ 2.4.

Impaired integration of disambiguating evidence in delusional schizophrenia patients.

BACKGROUND: It has been previously demonstrated that a cognitive bias against disconfirmatory evidence (BADE) is associated with delusions. However, small samples of delusional patients, reliance on difference scores and choice of comparison groups may have hampered the reliability of these results. In the present study we aimed to improve on this methodology with a recent version of the BADE task, and compare larger groups of schizophrenia patients with/without delusions to obsessive-compulsive disorder (OCD) patients, a population with persistent and possibly bizarre beliefs without psychosis. METHOD: A component analysis was used to identify cognitive operations underlying the BADE task, and how they differ across four groups of participants: (1) high-delusional schizophrenia, (2) low-delusional schizophrenia, (3) OCD patients and (4) non-psychiatric controls. RESULTS: As in past studies, two components emerged and were labelled 'evidence integration' (the degree to which disambiguating information has been integrated) and 'conservatism' (reduced willingness to provide high plausibility ratings when justified), and only evidence integration differed between severely delusional patients and the other groups, reflecting delusional subjects giving higher ratings for disconfirmed interpretations and lower ratings for confirmed interpretations. CONCLUSIONS: These data support the finding that a reduced willingness to adjust beliefs when confronted with disconfirming evidence may be a cognitive underpinning of delusions specifically, rather than obsessive beliefs or other aspects of psychosis such as hallucinations, and illustrates a cognitive process that may underlie maintenance of delusions in the face of counter-evidence. This supports the possibility of the BADE operation being a useful target in cognitive-based therapies for delusions.

ZIP4 is a novel diagnostic and prognostic marker in human pancreatic cancer: a systemic comparison between EUS-FNA and surgical specimens.

Aberrant expression of a zinc transporter ZIP4 in pancreatic ductal adenocarcinoma (PDAC) has been shown to contribute to tumor progression and is a potential target for individualized therapy. The overall objective of this study was to determine whether ZIP4 could serve as a novel diagnostic and prognostic marker in human PDAC, and if it can be assessed by minimally invasive sampling using endoscopic ultrasound guided fine needle aspiration (EUS-FNA). Immunohistochemistry was performed to compare ZIP4 expression in the PDAC samples obtained from EUS-FNA and matched surgical tumors (parallel control). Samples were reported by sensitivity, specificity, and predictive values, all with 95% confidence intervals (CI). A total of 23 cases with both FNA and surgical specimens were evaluated. We found that ZIP4 was significantly overexpressed in tumor cells from both sets of samples. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ZIP4 for the diagnosis of PDAC were 72.9%, 72.5%, 76.1%, and 69.0% in EUS-FNA samples, and were 97.9%, 65.4%, 83.9%, and 94.4% in surgical specimens, respectively. The association between the positive rate of ZIP4 expression in FNA and surgical samples is statistically significant (P=0.0216). Both the intensity and percentage of ZIP4 positive cells from the surgical samples correlated significantly with tumor stage (P=0.0025 and P=0.0002). ZIP4 intensity level in FNA samples was significantly associated with tumor differentiation and patient survival. These results indicate that EUS-FNA is capable of non-operative detection of ZIP4, thus offering the potential to direct pre-operative detection and targeted therapy of PDAC.

Free-space to single-mode collection efficiency enhancement using photonic lanterns.

We demonstrate single-mode collection efficiency enhancement for free space optical systems using a photonic lantern to collect scattered infrared light from diffuse objects at far- and near-field distances. A single-mode collection efficiency improvement of ∼8 dB is demonstrated in the near-field region relative to standard single-mode fiber. The insertion loss properties of the photonic lantern are also analyzed, and an additional insertion loss penalty is observed for near-field distances when the transmitted beam is collimated. The photonic lantern can be used for coherent detection systems such as light detection and ranging and free-space optical communication with improved collection efficiency and nearly perfect mode matching.

Risk of gastric or peritoneal recurrence, and long-term outcomes, following pancreatic cancer resection with preoperative endosonographically guided fine needle aspiration.

BACKGROUND AND STUDY AIMS: There have been concerns regarding tumor cell seeding along the needle track or within the peritoneum caused by preoperative endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). The aim of this study was to evaluate whether preoperative EUS-FNA is associated with increased risk of stomach/peritoneal recurrence and whether the procedure affects long term survival. METHODS: The records of patients diagnosed with malignant solid and cystic pancreatic neoplasms who underwent surgery with curative intent between 1996 and 2012 were reviewed. RESULTS: A total of 256 patients with similar baseline characteristics were included: 48 patients in the non-EUS-FNA group and 208 in the EUS-FNA group. Recurrence data were available for 207 patients. Median length of follow-up was 23 months (range 0 - 111 months). A total of 19 patients had gastric or peritoneal recurrence; 6 (15.4 %) in the non-EUS-FNA group vs. 13 (7.7 %) in the EUS-FNA group (P = 0.21). Three patients had recurrence in the stomach wall: one (2.6 %) patient in the non-EUS-FNA group vs. two patients (1.2 %) in EUS-FNA group (P = 0.46). A total of 16 patients had peritoneal recurrence: 5 patients (12.8 %) in the non-EUS-FNA group and 11 patients (6.5 %) in the EUS-FNA group (P = 0.19). In a multivariate analysis, undergoing EUS-FNA was not associated with increased cancer recurrence or decreased overall survival. CONCLUSION: Pre-operative EUS-FNA was not associated with an increased rate of gastric or peritoneal cancer recurrence in patients with resected pancreatic cancer. Two patients had gastric wall recurrence following the procedure, but this may be explained by direct tumor extension. This suggests that EUS-FNA is not associated with an increased risk of needle track seeding.

Accuracy of real-time vs. blinded offline diagnosis of neoplastic colorectal polyps using probe-based confocal laser endomicroscopy: a pilot study.

BACKGROUND AND STUDY AIMS: Probe-based confocal laser endomicroscopy (pCLE) is a new imaging modality that enables histological examination of gastrointestinal mucosa during endoscopic procedures. Most studies have evaluated offline interpretation of pCLE images. In clinical practice, real-time interpretation is necessary to assist decision-making during the procedure. The aim of this pilot study was to compare the accuracy of real-time pCLE diagnosis made during the procedure with that of blinded offline interpretation to provide accuracy estimates that will aid the planning of future studies. PATIENTS AND METHODS: pCLE was performed in patients undergoing screening and surveillance colonoscopy. Once a polyp had been identified, one endoscopist analyzed pCLE images during the procedure and made a provisional "real-time" diagnosis. Saved video recordings were de-identified, randomized, and reviewed "offline" 1 month later by the same endoscopist, who was blinded to the original diagnoses. RESULTS: Images from a total of 154 polyps were recorded (80 neoplastic, 74 non-neoplastic). The overall accuracy of real-time pCLE diagnosis (accuracy 79%, sensitivity 81%, specificity 76%) and offline pCLE diagnosis (83%, 88%, and 77%, respectively) for all 154 polyps were similar. Among polyps < 10 mm in size, the accuracy of real-time interpretation was significantly lower (accuracy 78%, sensitivity 71%, specificity 83%) than that of offline pCLE interpretation (81%, 86%, 78%, respectively). For polyps ≥ 10 mm, the accuracy of pCLE diagnosis in real-time was better (accuracy 85%, sensitivity 90%, specificity 75%) than offline pCLE diagnosis (81%, 97%, and 50%, respectively). CONCLUSIONS: These results suggest that real-time and offline interpretations of pCLE images are moderately accurate. Real-time interpretation is slightly less accurate than offline diagnosis, but overall both are comparable. Additionally, there was contrasting accuracy between the two methods for small and large polyps.

A comparison of high definition-image enhanced colonoscopy and standard white-light colonoscopy for colorectal polyp detection.

BACKGROUND AND STUDY AIMS: Colonoscopy is widely used to detect and remove precancerous polyps, but fails to detect some polyps. Recent studies evaluating different image-enhanced methods have revealed conflicting results. The efficacy of colonoscopy imaging with simultaneous use of commercially available improvements, including high definition narrow band imaging (HD-NBI), and monochromatic charge-coupled device (CCD) video, was compared with a widely used standard definition white light (SDWL) colonoscopy system for detecting colorectal polyps. The primary aim was to determine whether the combination of image-enhanced colonoscopy systems resulted in fewer missed polyps compared with conventional colonoscopy. PATIENTS AND METHODS: In a randomized controlled trial (Clinicaltrials.gov. study number NCT00825292) patients having routine screening and surveillance underwent tandem colonoscopies with SDWL and image-enhanced (HD-NBI) colonoscopy. The main outcome measurement was the per-polyp false-negative ("miss") rate. Secondary outcomes were adenoma miss rate, and per-patient polyp and adenoma miss rates. RESULTS: 100 patients were randomized and 96 were included in the analysis. In total, 177 polyps were detected; of these, 72 (41 %) were adenomatous. Polyp and adenoma miss rates for SDWL colonoscopy were 57 % (60/105) and 49 % (19/39); those for image-enhanced colonoscopy were 31 % (22/72) and 27 % (9/33) (P = 0.005 and P = 0.036 for polyps and adenomas, respectively). Image-enhanced and SDWL approaches had similar per-patient miss rates for polyps (6/35 vs. 9/32, P = 0.27) and adenomas (4/22 vs. 8/20, P = 0.11). CONCLUSIONS: Utilization of multiple recent improvements in image-enhanced colonoscopy was associated with a reduced miss rate for all polyps and for adenomatous polyps. It is not known which individual feature or combination of image-enhancement features led to the improvement.

Further evidence for the efficacy of a metacognitive group training in schizophrenia.

Metacognitive training (MCT) for patients with schizophrenia is a novel psychological group treatment targeting cognitive biases putatively involved in the pathogenesis of schizophrenia (e.g. jumping to conclusions, overconfidence in errors). Its eight modules are available cost-free online in many languages. In the present study, 36 subacute or remitted patients were randomly allocated to either the MCT or a wait-list group who received treatment-as-usual (TAU). Baseline and post assessments were 8 weeks apart and were performed blind to group status. MCT showed significantly greater improvement on the following parameters relative to the TAU group: delusion distress (PSYRATS), memory and social quality of life. In the MCT group, the rate of jumping to conclusions bias was reduced after training. No differences occurred on the PANSS. The present study confirms prior reports that MCT exerts beneficial effects on some cognitive and symptomatic parameters.

Antipsychotic treatment beyond antipsychotics: metacognitive intervention for schizophrenia patients improves delusional symptoms.

BACKGROUND: Although antipsychotic medication still represents the treatment of choice for schizophrenia, its objective impact on symptoms is only in the medium-effect size range and at least 50% of patients discontinue medication in the course of treatment. Hence, clinical researchers are intensively looking for complementary therapeutic options. Metacognitive training for schizophrenia patients (MCT) is a group intervention that seeks to sharpen the awareness of schizophrenia patients on cognitive biases (e.g. jumping to conclusions) that seem to underlie delusion formation and maintenance. The present trial combined group MCT with an individualized cognitive-behavioural therapy-oriented approach entitled individualized metacognitive therapy for psychosis (MCT+) and compared it against an active control. METHOD: A total of 48 patients fulfilling criteria of schizophrenia were randomly allocated to either MCT+ or cognitive remediation (clinical trial NCT01029067). Blind to intervention, both groups were assessed at baseline and 4 weeks later. Psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Psychotic Symptom Rating Scales (PSYRATS). Jumping to conclusions was measured using a variant of the beads task. RESULTS: PANSS delusion severity declined significantly in the combined MCT treatment compared with the control condition. PSYRATS delusion conviction as well as jumping to conclusions showed significantly greater improvement in the MCT group. In line with prior studies, treatment adherence and subjective efficacy was excellent for the MCT. CONCLUSIONS: The results suggest that the combination of a cognition-oriented and a symptom-oriented approach ameliorate psychotic symptoms and cognitive biases and represents a promising complementary treatment for schizophrenia.

GHz-bandwidth optical filters based on high-order silicon ring resonators.

Previously demonstrated high-order silicon ring filters typically have bandwidths larger than 100 GHz. Here we demonstrate 1-2 GHz-bandwidth filters with very high extinction ratios (~50 dB). The silicon waveguides employed to construct these filters have propagation losses of ~0.5 dB/cm. Each ring of a filter is thermally controlled by metal heaters situated on the top of the ring. With a power dissipation of ~72 mW, the ring resonance can be tuned by one free spectral range, resulting in wavelength-tunable optical filters. Both second-order and fifth-order ring resonators are presented, which can find ready application in microwave/radio frequency signal processing.

Safety and efficacy of cytology brushings versus standard fine-needle aspiration in evaluating cystic pancreatic lesions: a controlled study.

BACKGROUND AND STUDY AIMS: Cystic pancreatic lesions (CPLs) are increasingly detected by various imaging studies. Mucinous CPLs carry a risk of malignant transformation but this is often difficult to diagnose preoperatively. In a previous report of 10 suspected mucinous CPLs, the cellular yield of endoscopic ultrasonography (EUS)-guided cytology brushings was found to be superior to the yield from standard fine-needle aspiration (FNA). The aim of this prospective and blinded study was to compare the cytology yield of mucinous epithelium from brushing with FNA in suspected mucinous CPLs. PATIENTS AND METHODS: In total, 37 patients with 39 CPLs measuring at least 20 mm were enrolled between June 2006 and July 2008 for EUS-cytobrushing and EUS-FNA of CPLs. Demographic, clinical, EUS, cytopathologic, and surgical data were recorded whenever available. Yield of cytology brushings was compared with that of FNA. Procedure morbidity was evaluated after 30 days. The main outcome assessed was yield of intracellular mucin (ICM) on cytobrushing specimens compared with EUS-FNA for the diagnosis of suspected mucinous CPL. RESULTS: Cytobrushings were more likely to detect ICM than the EUS-FNA method ( P = 0.001). In three patients with hypocellular FNA, dysplasia was found on cytology brushing and later confirmed by surgical pathology. Significant complications occurred in three patients (8 %): one postbrushing bleeding and two acute pancreatitis. CONCLUSIONS: Cytology brushings are more likely to provide an adequate mucinous epithelium specimen than standard FNA and could aid the diagnosis of CPLs in a selective group of patients.

Analytical expression for large signal transfer function of an optically filtered analog link.

We present an analytical expression for the transfer function of an optically-filtered radio frequency photonic link using phase modulation and coherent detection. This solution is applicable to quadrature passband signals and is significant for evaluating the distortion and consequently improving the linearity of such electrical-optical-electrical links. We show that the nonlinearity appears as an envelope distortion and discuss linearization techniques along with experimental validation.

Decision making under uncertainty and mood induction: further evidence for liberal acceptance in schizophrenia.

BACKGROUND: Cognitive biases, especially jumping to conclusions (JTC), are ascribed a vital role in the pathogenesis of schizophrenia. This study set out to explore motivational factors for JTC using a newly developed paradigm. METHOD: Twenty-seven schizophrenia patients and 32 healthy controls were shown 15 classical paintings, divided into three blocks. Four alternative titles (one correct and three lure titles) had to be appraised according to plausibility (0-10). Optionally, participants could decide for one option and reject one or more alternatives. In random order across blocks, anxiety-evoking music, happy music or no music was played in the background. RESULTS: Patients with schizophrenia, particularly those with delusions, made more decisions than healthy subjects. In line with the liberal acceptance (LA) account of schizophrenia, the decision threshold was significantly lowered in patients relative to controls. Patients were also more prone than healthy controls to making a decision when the distance between the first and second best alternative was close. Furthermore, implausible alternatives were judged as significantly more plausible by patients. Anxiety-evoking music resulted in more decisions in currently deluded patients relative to non-deluded patients and healthy controls. CONCLUSIONS: The results confirm predictions derived from the LA account and assert that schizophrenia patients decide hastily under conditions of continued uncertainty. The fact that mood induction did not exert an overall effect could be due to the explicit nature of the manipulation, which might have evoked strategies to counteract their influence.

Cardiac cholinergic NO-cGMP signaling following acute myocardial infarction and nNOS gene transfer.

Myocardial infarction (MI) is associated with oxidative stress, which may cause cardiac autonomic impairment. We tested the hypothesis that acute MI disrupts cardiac cholinergic signaling by impairing nitric oxide (NO)-cGMP modulation of acetylcholine (ACh) release and whether the restoration of this pathway following cardiac neuronal NO synthase (nNOS) gene transfer had any bearing on the neural phenotype. Guinea pigs underwent four ligature coronary artery surgery (n = 50) under general anesthesia to induce MI or sham surgery (n = 32). In a separate group, at the time of MI surgery, adenovirus encoding nNOS (n = 29) or enhanced green fluorescent protein (eGFP; n = 30) was injected directly into the right atria, where the postganglionic cholinergic neurons reside. In vitro-evoked right atrial [3H]ACh release, right atrial NOS activity, and cGMP levels were measured at 3 days. Post-MI 24% of guinea pigs died compared with 9% in the sham-operated group. Evoked right atrial [3H]ACh release was significantly (P < 0.05) decreased in the MI group as was NOS activity and cGMP levels. Tetrahydrobiopterin levels were not significantly different between the sham and MI groups. Infarct sizes between gene-transferred groups were not significantly different. The nNOS transduced group had significantly increased right atrial [3H]ACh release, right atrial NOS activity, cGMP levels, and decreased cAMP levels. Fourteen percent of the nNOS transduced animals died compared with 31% mortality in the MI + eGFP group at 3 days. In conclusion, cardiac nNOS gene transfer partially restores the defective NO-cGMP cholinergic pathway post-MI, which was associated with a trend of improved survival at 3 days.