Papillary lesions of the breast: To excise or observe?

Papillary lesions of the breast range from benign to atypical to malignant. Although papillomas without frank cancer are benign, their management remains controversial. When a core needle biopsy of a lesion yields a diagnosis of intraductal papilloma with atypia, excision is generally recommended to rule out a concurrent malignant neoplasm. For intraductal papillomas without atypia, however, recommendations for excision versus observation are variable. The aims of this study are to evaluate the rate of concurrent malignancies for intraductal papilloma diagnosed on core needle biopsy and to assess the long‐term risk of developing cancer after the diagnosis of a papillary lesion. This single institution retrospective study analyzed 259 patients that were diagnosed with intraductal papilloma (IDP) by core needle biopsy from 1995 to 2010. Patients were grouped by initial diagnosis into three groups (papilloma without atypia, papilloma with atypia, and papilloma with atypical duct hyperplasia or atypical lobular hyperplasia (ADH/ALH) and followed up for long‐term outcomes. After a core needle biopsy showing IDP with atypia or IDP + ADH/ALH, surgical excision yielded a diagnosis of concomitant invasive or ductal in situ cancer in greater that 30% of cases. For intraductal papilloma without atypia, the likelihood of cancer was much lower. Moreover, even with excision, the finding of intraductal papilloma with atypia carries a significant risk of developing cancer long‐term, and such patients should be followed carefully and perhaps should be considered for chemoprevention.     

Nonlinear functional network connectivity in resting functional magnetic resonance imaging data

In this work, we focus on explicitly nonlinear relationships in functional networks. We introduce a technique using normalized mutual information (NMI) that calculates the nonlinear relationship between different brain regions. We demonstrate our proposed approach using simulated data and then apply it to a dataset previously studied by Damaraju et al. This resting‐state fMRI data included 151 schizophrenia patients and 163 age‐ and gender‐matched healthy controls. We first decomposed these data using group independent component analysis (ICA) and yielded 47 functionally relevant intrinsic connectivity networks. Our analysis showed a modularized nonlinear relationship among brain functional networks that was particularly noticeable in the sensory and visual cortex. Interestingly, the modularity appears both meaningful and distinct from that revealed by the linear approach. Group analysis identified significant differences in explicitly nonlinear functional network connectivity (FNC) between schizophrenia patients and healthy controls, particularly in the visual cortex, with controls showing more nonlinearity (i.e., higher normalized mutual information between time courses with linear relationships removed) in most cases. Certain domains, including subcortical and auditory, showed relatively less nonlinear FNC (i.e., lower normalized mutual information), whereas links between the visual and other domains showed evidence of substantial nonlinear and modular properties. Overall, these results suggest that quantifying nonlinear dependencies of functional connectivity may provide a complementary and potentially important tool for studying brain function by exposing relevant variation that is typically ignored. Beyond this, we propose a method that captures both linear and nonlinear effects in a “boosted” approach. This method increases the sensitivity to group differences compared to the standard linear approach, at the cost of being unable to separate linear and nonlinear effects.     

Quantitative analysis of mannitol polymorphs. FT-Raman spectroscopy

Mannitol is a polymorphic excipient which is usually used in pharmaceutical products as the beta form, although other polymorphs (alpha and delta) are common contaminants. Binary mixtures containing beta and delta mannitol were prepared to quantify the concentration of the beta form using FT-Raman spectroscopy. Spectral regions characteristic of each form were selected and peak intensity ratios of beta peaks to delta peaks were calculated. Using these ratios, a correlation curve was established which was then validated by analysing further samples of known composition. The results indicate that levels down to 2% beta could be quantified using this novel, non-destructive approach. Potential errors associated with quantitative studies using FT-Raman spectroscopy were also researched. The principal source of variability arose from inhomogeneities on mixing of the samples; a significant reduction of these errors was observed by reducing and controlling the particle size range. The results show that FT-Raman spectroscopy can be used to rapidly and accurately quantitate polymorphic mixtures.     

Vλ-light chain genes reconstitute immune responses to defined carbohydrate antigens or haptens by utilizing different VH genes

The contribution of the λ-light chain to the development of peripheral B cell repertoire and generation of specific antibodies to haptens and polysaccharide antigens was studied in genetically manipulated kappa-deficient and λ₂-transgenic mice. The results clearly demonstrate a non-stoichiometric V_H gene family expression in the absence of k-light chain and suggest a non-stochastic pairing between V_H and V_λ genes, expressed in the peripheral B cell repertoire. A shift in V_H gene utilization in the case of Vl_λ⁺ antibodies was evident in response to β2–6 fructosan and TNP hapten. These observations demonstrate the availability of compensatory mechanisms in the absence of V_K genes and are consistent with the hypothesis that V_H gene family expression is controlled by genetic factors from inside the V_H locus. Furthermore, genetic factors from outside the V_H locus, namely restricted available light chain diversity, may lead to a shift in V_H gene utilization in the peripheral B cell repertoire.     

Effectiveness of composite cure associated with different curing modes of LED lights

This study compared the effectiveness of cure of two LED (light-emitting diodes) lights (Elipar FreeLight [FL], 3M-ESPE; GC e-Light [EL], GC) to conventional (Max [MX], Dentsply-Caulk [control]), high intensity (Elipar TriLight [TL], 3M-ESPE) and very high intensity (Astralis 10 [AS], Ivoclar Vivadent) halogen lights. The 10 light-curing regimens investigated were: FL1 400 mW/cm2 [40 seconds], FL2 0-400 mW/cm2 [12 seconds] --> 400 mW/cm2 [28 seconds], EL1 750 mW/cm2 [10 pulses x 2 seconds], EL2 350 mW/cm2 [40 seconds], EL3 600 mW/cm2 [20 seconds], EL4 0-600 mW/cm2 [20 seconds] --> 600 mW/cm2 [20 seconds], TL1 800 mW/cm2 [40 seconds], TL2 100-800 mW/cm2 [15 seconds] --> 800 mW/cm2 [25 seconds], AS1 1200 mW/cm2 [10 seconds], MX 400 mW/cm2 [40 seconds]. Effectiveness of cure with the different modes was determined by measuring the top and bottom surface hardness (KHN) of 2-mm thick composite (Z100, [3M-ESPE]) specimens using a digital microhardness tester (n=5, load=500 g; dwell time=15 seconds). Results were analyzed using one-way ANOVA/Scheffe's post-hoc test and Independent Samples t-test (p<0.05). At the top surface, the mean KHN observed with LED lights ranged from 55.42 +/- 1.47 to 68.54 +/- 1.46, while that of halogen lights was 62.64 +/- 1.87 to 73.14 +/- 0.97. At the bottom surface, the mean KHN observed with LED and halogen lights ranged from 46.90 +/- 1.73 to 66.46 +/- 1.18 and 62.26 +/- 1.93 to 70.50 +/- 0.87, respectively. Significant differences in top and bottom KHN values were observed between different curing regimens for the same light, and between LED and halogen lights. Although curing with most modes of EL resulted in significantly lower top and bottom KHN values than the control, no significant difference was observed for the different modes of FL. Hence, the effectiveness of composite cure with LED LCUs is product dependent.     

Diameter changes of occluded venous coronary artery bypass grafts in electron beam tomography: preliminary findings.

OBJECTIVE: To differentiate acute from chronic graft occlusions through diameter measurements by means of electron beam tomography (EBT). METHODS: Contrast enhanced EBT volume studies were carried out in 37 patients with one or more occluded venous coronary bypass grafts. Seventeen of 37 patients did not meet the inclusion criteria and were excluded from the assessment. The remaining 20 patients had a total of 39 bypasses (16 patent, 23 occluded) and were assigned to one of three groups: group A consisted of patent grafts only (patent grafts, 13 patients). Group B comprised 11 of 23 occluded grafts diagnosed within 10 days after bypass surgery (acutely occluded grafts, ten patients). Group C contained 12 of 23 bypass occlusions that were at least 6 months old as documented by coronary angiography (chronically occluded grafts, ten patients). The mean graft diameter was determined by repetitive measurements on a workstation through blinded readers. The Mann-Whitney-U-test for unpaired samples was used for statistical evaluation. RESULTS: Mean graft diameter for groups A-C (patent, acutely, and chronically occluded bypasses, respectively) was 3.9 mm (+/-0.6; n=16), 5.4 mm (+/-1.9; n=11), and 0.3 mm (+/-.9; n=12), respectively (P<0.01 each). Sensitivity and specificity for the detection of acute and chronic occlusions were 87 and 92% (cut-off 4.5 mm), respectively, and 92 and 96% (cut-off 1 mm), respectively. CONCLUSIONS: EBT may allow for non-invasive differentiation between acute and chronic venous coronary bypass occlusions. This could help prevent unnecessary invasive recanalization procedures. Body veins may conserve their ability to increase in diameter in acute thrombosis when transplanted as coronary bypasses.     

Investigating Agenesis of the Corpus Callosum Using Functional MRI: A Study Examining Interhemispheric Coordination of Motor Control

We report fMRI findings in 3 asymptomatic cases of agenesis of the corpus callosum, the largest white matter bundle in the brain, which is responsible for interhemispheric transfer of information. Sensory information was presented to 1 hemisphere, and the patients had to generate a motor response governed by the contralateral hemisphere. Enhanced ipsilateral motor pathways have been suggested as a compensation method for people with agenesis of the corpus callosums; our functional magnetic resonance imaging data did not support this theory.