Measurement of Electron-Neutrino Charged-Current Cross Sections on

Using an 185-kg NaI[Tl] array, COHERENT has measured the inclusive electron-neutrino charged-current cross section on ^{127}I with pion decay-at-rest neutrinos produced by the Spallation Neutron Source at Oak Ridge National Laboratory. Iodine is one the heaviest targets for which low-energy (≤50 MeV) inelastic neutrino-nucleus processes have been measured, and this is the first measurement of its inclusive cross section. After a five-year detector exposure, COHERENT reports a flux-averaged cross section for electron neutrinos of 9.2_{-1.8}^{+2.1}×10^{-40} cm^{2}. This corresponds to a value that is ∼41% lower than predicted using the MARLEY event generator with a measured Gamow-Teller strength distribution. In addition, the observed visible spectrum from charged-current scattering on ^{127}I has been measured between 10 and 55 MeV, and the exclusive zero-neutron and one-or-more-neutron emission cross sections are measured to be 5.2_{-3.1}^{+3.4}×10^{-40} and 2.2_{-0.5}^{+0.4}×10^{-40} cm^{2}, respectively.

Multimodality imaging review of breast vascular lesions.

Breast vasculature is visualised on all screening and diagnostic imaging of the breast. Various vascular breast lesions exist, spanning from chronic systemic processes, congenital malformations, post-traumatic sequela, benign masses, to malignant tumours. Accurate diagnosis of vascular lesions on breast imaging can be difficult due to overlapping characteristics. Radiologists should be aware of key multi-technique imaging features to make an accurate diagnosis and to avoid unnecessary biopsies. This article reviews the normal vascular anatomy of the breast, commonly used imaging techniques to diagnose vascular lesions, and an in-depth review of various vascular breast lesions. Finally, management recommendations and clinical guidance are discussed so that the radiologist can appropriately triage these patients.

The nipple-areolar complex: comprehensive imaging review.

The nipple-areolar complex can be affected by a variety of benign and malignant entities that can present with non-specific symptoms. Benign pathologies commonly affecting the nipple-areolar complex include nipple calcifications, nipple adenoma, abscess of Montgomery tubercles, ductal ectasia, periductal mastitis, and papilloma. Malignant pathologies that affect the nipple-areolar complex include Paget's disease of the breast, ductal carcinoma in-situ, and invasive ductal carcinoma. Clinical history and examination, imaging, and tissue sampling when appropriate are co-dependent factors that guide the assessment of nipple-areolar pathologies. This article provides a review of the normal anatomy, common anatomical variants, benign and malignant pathologies, and imaging techniques to guide the diagnostic assessment of the nipple-areolar complex.

Canadian Guidelines for Controlled Pediatric Donation After Circulatory Determination of Death-Summary Report

OBJECTIVES: Create trustworthy, rigorous, national clinical practice guidelines for the practice of pediatric donation after circulatory determination of death in Canada. METHODS: We followed a process of clinical practice guideline development based on World Health Organization and Canadian Medical Association methods. This included application of Grading of Recommendations Assessment, Development, and Evaluation methodology. Questions requiring recommendations were generated based on 1) 2006 Canadian donation after circulatory determination of death guidelines (not pediatric specific), 2) a multidisciplinary symposium of national and international pediatric donation after circulatory determination of death leaders, and 3) a scoping review of the pediatric donation after circulatory determination of death literature. Input from these sources drove drafting of actionable questions and Good Practice Statements, as defined by the Grading of Recommendations Assessment, Development, and Evaluation group. We performed additional literature reviews for all actionable questions. Evidence was assessed for quality using Grading of Recommendations Assessment, Development, and Evaluation and then formulated into evidence profiles that informed recommendations through the evidence-to-decision framework. Recommendations were revised through consensus among members of seven topic-specific working groups and finalized during meetings of working group leads and the planning committee. External review was provided by pediatric, critical care, and critical care nursing professional societies and patient partners. RESULTS: We generated 63 Good Practice Statements and seven Grading of Recommendations Assessment, Development, and Evaluation recommendations covering 1) ethics, consent, and withdrawal of life-sustaining therapy, 2) eligibility, 3) withdrawal of life-sustaining therapy practices, 4) ante and postmortem interventions, 5) death determination, 6) neonatal pediatric donation after circulatory determination of death, 7) cardiac and innovative pediatric donation after circulatory determination of death, and 8) implementation. For brevity, 48 Good Practice Statement and truncated justification are included in this summary report. The remaining recommendations, detailed methodology, full Grading of Recommendations Assessment, Development, and Evaluation tables, and expanded justifications are available in the full text report. CONCLUSIONS: This process showed that rigorous, transparent clinical practice guideline development is possible in the domain of pediatric deceased donation. Application of these recommendations will increase access to pediatric donation after circulatory determination of death across Canada and may serve as a model for future clinical practice guideline development in deceased donation

Phase II study of MLN8237 (Alisertib) in advanced/metastatic sarcoma.

BACKGROUND: Aurora kinase A (AURKA) is commonly overexpressed in sarcoma. The inhibition of AURKA by shRNA or by a specific AURKA inhibitor blocks in vitro proliferation of multiple sarcoma subtypes. MLN8237 (alisertib) is a novel oral adenosine triphosphate-competitive AURKA inhibitor. PATIENTS AND METHODS: This Cancer Therapy Evaluation Program-sponsored phase II study of alisertib was conducted through the Alliance for Clinical Trials in Oncology (A091102). Patients were enrolled into histology-defined cohorts: (i) liposarcoma, (ii) leiomyosarcoma, (iii) undifferentiated sarcoma, (iv) malignant peripheral nerve sheath tumor, or (v) other. Treatment was alisertib 50 mg PO b.i.d. d1-d7 every 21 days. The primary end point was response rate; progression-free survival (PFS) was secondary. One response in the first 9 patients expanded enrollment in a cohort to 24 using a Simon two-stage design. RESULTS: Seventy-two patients were enrolled at 24 sites [12 LPS, 10 LMS, 11 US, 10 malignant peripheral nerve sheath tumor (MPNST), 29 Other]. The median age was 55 years; 54% were male; 58%/38%/4% were ECOG PS 0/1/2. One PR expanded enrollment to the second stage in the other sarcoma cohort. The histology-specific cohorts ceased at the first stage. There were two confirmed PRs in the other cohort (both angiosarcoma) and one unconfirmed PR in dedifferentiated chondrosarcoma. Twelve-week PFS was 73% (LPS), 44% (LMS), 36% (US), 60% (MPNST), and 38% (Other). Grade 3-4 adverse events: oral mucositis (12%), anemia (14%), platelet count decreased (14%), leukopenia (22%), and neutropenia (42%). CONCLUSIONS: Alisertib was well tolerated. Occasional responses, yet prolonged stable disease, were observed. Although failing to meet the primary RR end point, PFS was promising. TRIAL REGISTRATION ID: NCT01653028.

Assessing 30-day quantity-frequency of U.S. adolescent cigarette smoking as a predictor of adult smoking 14 years later.

BACKGROUND: To improve measures of monthly tobacco cigarette smoking among non-daily smokers, predictive of future non-daily monthly and daily smoking. METHODS: Data from United States National Longitudinal Study of Adolescent to Adult Health, tracking adolescents, ages 12-21, over 14 years were analyzed. At baseline, 6501 adolescents were assessed; 5114 individuals provided data at waves 1 and 4. Baseline past 30-day non-daily smokers were classified using quantity-frequency measures: cigarettes smoked/day by number of days smoked in the past 30 days. RESULTS: Three categories of past 30-day non-daily smokers emerged using cigarettes/month (low:1-5, moderate: 6-60, high: 61+) and predicted past 30-day smoking at follow-up (low: 44.5%, moderate: 60.0%, high: 77.0%, versus 74.2% daily smokers; rτ=-0.2319, p<0.001). Two categories of non-smokers plus low, moderate and high categories of non-daily smokers made up a five-category non-daily smoking index (NDSI). High NDSI (61+ cigs/mo.) and daily smokers were equally likely to be smoking 14 years later (High NDSI OR=0.97, 95% CI=0.53-1.80 [daily as reference]). Low (1-5 cigs/mo.) and moderate (6-60 cigs/mo.) NDSI were distinctly different from high NDSI, but similar to one another (OR=0.21, 95% CI=0.15-0.29 and OR=0.22, 95% CI=0.14-0.34, respectively) when estimating future monthly smoking. Among those smoking at both waves, wave 1 non-daily smokers, overall, were less likely than wave 1 daily smokers to be smoking daily 14 years later. CONCLUSIONS: Non-daily smokers smoking over three packs/month were as likely as daily smokers to be smoking 14-years later. Lower levels of non-daily smoking (at ages 12-21) predicted lower likelihood of future monthly smoking. In terms of surveillance and cessation interventions, high NDSI smokers might be treated similar to daily smokers.

Oestradiol Exposure Early in Life Programs Daily and Circadian Activity Rhythms in Adult Mice.

Hormone signalling during critical periods organises the adult circadian timekeeping system by altering adult hormone sensitivity and shaping fundamental properties of circadian rhythmicity. However, the timing of when developmental oestrogens modify the timekeeping system is poorly understood. To test the hypothesis that alterations in postnatal oestrogenic signalling organise adult daily activity rhythms, we utilised aromatase knockout mice (ArKO), which lack the enzyme required for oestradiol synthesis. ArKO and wild-type (WT) males and females were administered either oestradiol (E) or oil (OIL) daily for the first 5 postnatal days (p1-5E and p1-5OIL , respectively) because this time encompasses the emergence of clock gene rhythmicity and light responsiveness in the suprachiasmatic nucleus, a bilateral hypothalamic structure regarded as the 'master oscillator'. After sexual maturation, gonadectomy and exogenous oestradiol supplementation, locomotor parameters were assessed. We determined that altered oestrogenic signalling in early life exerts organisational control over the expression of daily and circadian activity rhythms in adult mice. Specifically, p1-5E reduced total wheel running activity in male and female ArKO and female WT mice but had no effect on WT male activity levels. In females, wheel running was consolidated by p1-5E to the early versus late evening, a phenomenon characteristic of male mice. The time of peak activity was advanced by p1-5E in WT and ArKO females but not males. P1-5E shortened the length of the active phase (alpha) in WT males but had no effect on ArKO males or females of either genotypes. Finally, p1-5E altered the magnitude of photic-induced shifts, suggesting that developmental oestrogenic signalling impacts adult circadian functions. In the present study, we further define both a critical period of development of the adult timekeeping system and the role that oestrogenic signalling plays in the expression of daily and circadian activity rhythms throughout life.

Enjoyment and other reasons for electronic cigarette use: Results from college students in New York.

BACKGROUND: Young people are more likely to have experimented with e-cigarettes (e-cigs) compared with older adults. Few studies identify reasons for experimentation/use of e-cigs among young people; we sought to discover what drives college students to use e-cigs. METHODS: Undergraduate students (ages 18-23) at four universities in New York State were surveyed. Among e-cig ever users (n=429), reasons for use were examined. A multinomial logistic regression model analyzed the relative risk of reasons for using e-cigs among discontinued, current non-daily and current daily e-cig users. RESULTS: Using e-cigs for enjoyment was associated with current non-daily (RR=2.11, 95% CI=1.18-3.75) and current daily use (RR=19.1, 95% CI=3.71-98.54). Non-daily use was related to use because e-cigs are less toxic than cigarettes (RR=2.80, 95% CI=1.75-4.50). More daily users reported use to quit smoking compared with either non-daily or discontinued users (53.3% vs. 12.2% and 13.3%, respectively; p<0.05). Among current users, 72.3% used for enjoyment, compared with 42.9% of discontinued users (p<0.05). DISCUSSION: In contrast to adults, who often report e-cig use to quit smoking, young people are less likely to use for this reason. The exception was daily e-cig users, who often reported use for quitting/reduction of smoking. Rather, college students report usage reasons related to affect (e.g. enjoyment). Overall, enjoyment was reported more often than was use for quitting smoking; affective reasons likely play a role in the popularity of e-cigs and should be considered in future assessments of e-cig users.

Risky behaviors, e-cigarette use and susceptibility of use among college students.

BACKGROUND: Since 2007, there has been a rise in the use of electronic cigarettes (e-cigarettes). The present study uses cross-sectional data (2013) to examine prevalence, correlates and susceptibility to e-cigarettes among young adults. METHODS: Data were collected using an Internet survey from a convenience sample of 1437, 18-23 year olds attending four colleges/universities in Upstate New York. Results were summarized using descriptive statistics; logistic regression models were analyzed to identify correlates of e-cigarette use and susceptibility to using e-cigarettes. RESULTS: Nearly all respondents (95.5%) reported awareness of e-cigarettes; 29.9% were ever users and 14.9% were current users. Younger students, males, non-Hispanic Whites, respondents reporting average/below average school ability, ever smokers and experimenters of tobacco cigarettes, and those with lower perceptions of harm regarding e-cigarettes demonstrated higher odds of ever use or current use. Risky behaviors (i.e., tobacco, marijuana or alcohol use) were associated with using e-cigarettes. Among never e-cigarette users, individuals involved in risky behaviors or, with lower harm perceptions for e-cigarettes, were more susceptible to future e-cigarette use. CONCLUSIONS: More e-cigarette users report use of another nicotine product besides e-cigarettes as the first nicotine product used; this should be considered when examining whether e-cigarette use is related to cigarette susceptibility. Involvement in risky behaviors is related to e-cigarette use and susceptibility to e-cigarette use. Among college students, e-cigarette use is more likely to occur in those who have also used other tobacco products, marijuana, and/or alcohol.

A dual-reporter, diagnostic vector for prostate cancer detection and tumor imaging.

Detection of prostate-specific antigen (PSA) as a screening strategy for prostate cancer is limited by the inability of the PSA test to differentiate between malignant cancer and benign hyperplasia. Here, we report the use of a cancer-specific promoter, inhibition of differentiation-1 (Id1), to drive a dual-reporter system (Ad5/3-Id1-SEAP-Id1-mCherry) designed for detection of prostate cancer using a blood-based reporter-secreted embryonic alkaline phosphatase (SEAP) and tumor visualization using a fluorescent reporter protein, mCherry. In human prostate tumors, Id1 levels are correlated with increased Gleason grade and disease progression. To evaluate the performance of the dual-reporter system, a prostate cell panel with varying aggressive phenotypes was tested. Following infection with the Ad5/3-Id1-SEAP-Id1-mCherry vector, expression of the SEAP and mCherry reporters was shown to increase with increasing levels of cellular Id1. No correlation was observed between Id1 and PSA. To evaluate in vivo performance, flank tumors were grown in athymic male mice using three prostate cancer cell lines. Following intra-tumoral injection of the vector, tumors formed by cells with high Id1 had the greatest reporter expression. Interestingly, tumors with the lowest levels of Id1 and reporter expression produced the greatest amounts of PSA. These data support the use of Ad5/3-Id1-SEAP-Id1-mCherry as a predictor of prostate cancer malignancy and as a strategy for tumor localization.

ESR1 and ESR2 differentially regulate daily and circadian activity rhythms in female mice.

Estrogenic signaling shapes and modifies daily and circadian rhythms, the disruption of which has been implicated in psychiatric, neurologic, cardiovascular, and metabolic disease, among others. However, the activational mechanisms contributing to these effects remain poorly characterized. To determine the activational impact of estrogen on daily behavior patterns and differentiate between the contributions of the estrogen receptors ESR1 and ESR2, ovariectomized adult female mice were administered estradiol, the ESR1 agonist propylpyrazole triol, the ESR2 agonist diarylpropionitrile, or cholesterol (control). Animals were singly housed with running wheels in a 12-hour light, 12-hour dark cycle or total darkness. Estradiol increased total activity and amplitude, consolidated activity to the dark phase, delayed the time of peak activity (acrophase of wheel running), advanced the time of activity onset, and shortened the free running period (τ), but did not alter the duration of activity (α). Importantly, activation of ESR1 or ESR2 differentially impacted daily and circadian rhythms. ESR1 stimulation increased total wheel running and amplitude and reduced the proportion of activity in the light vs the dark. Conversely, ESR2 activation modified the distribution of activity across the day, delayed acrophase of wheel running, and advanced the time of activity onset. Interestingly, τ was shortened by estradiol or either estrogen receptor agonist. Finally, estradiol-treated animals administered a light pulse in the early subjective night, but no other time, had an attenuated response compared with controls. This decreased phase response was mirrored by animals treated with diarylpropionitrile, but not propylpyrazole triol. To conclude, estradiol has strong activational effects on the temporal patterning and expression of daily and circadian behavior, and these effects are due to distinct mechanisms elicited by ESR1 and ESR2 activation.

Promoting cancer control training in resource limited environments: Lagos, Nigeria.

In resource limited nations, cancer control is often a lower priority issue creating challenges for the prevention, early diagnosis, and treatment of cancer. Training and education are vital components of efforts to tackle this problem. A 3-day cancer control workshop was conducted at the Lagos State University Teaching Hospital (LASUTH), Nigeria, in 2013. The curriculum included didactic lectures, panel discussions, and interactive sessions on local cancer statistics, preventive strategies, cancer registries, screening and diagnostic options, and treatment approaches with limited resources (chemotherapy, radiotherapy, surgery, and palliative care) and several site-specific (breast, lung, cervical, prostate, and colon) topics. Pre-workshop and post-workshop questionnaires were completed by participants. Eighty-six percent of the 50 workshop participants completed at least one questionnaire. Participants were mainly nurses and physicians (89% of responders), and 40% reported >25 years of practice experience. The more common local needs identified were professional education (65%) and increasing public cancer awareness (63%). The greatest interest for future programs was on research collaborations (70%). An immediate impact of the workshop was the commencement of monthly tumor board conferences and a review of the current cancer registry data. Capacity building is critical for the execution of effective cancer control strategies. Conducting collaborative workshops represents a cost-effective means of launching programs and energizing the medical community to pursue ongoing education and research addressing the anticipated cancer epidemic on the African continent.

Intraductal therapy of ductal carcinoma in situ: a presurgery study.

INTRODUCTION: Ductal carcinoma in situ (DCIS) is a noninvasive breast cancer wherein malignant cells are confined within a ductal lobular unit. Although less than half the cases of DCIS will progress to invasive disease, most women are treated aggressively with surgery, radiation, and/or hormone therapy due to the inability to clinically evaluate the extent and location of the disease. Intraductal therapy, in which a drug is administered directly into the mammary duct through the nipple, is a promising approach for treating DCIS, but the feasibility of instilling drug into a diseased duct has not been established. PATIENTS AND METHODS: Four to 6 weeks before their scheduled surgery, 13 women diagnosed with DCIS were subjected to cannulation of the affected duct. After both the absence of perforation and presence of dye in the duct were confirmed by ductogram, pegylated liposomal doxorubicin was instilled. Histopathologic assessment was performed after surgery to assess the treatment effects. RESULTS: Of the 13 women enrolled in the study, 6 had their DCIS duct successfully cannulated without perforation and instilled with the drug. The treatment was well tolerated, and no serious adverse events have been reported. Biomarker studies indicated a general decrease in Ki-67 levels but an increase in annexin-1 and 8-hydroxydeoxyguanosine in the lumen of DCIS-containing ducts, which suggests a local response to pegylated liposomal doxorubicin treatment. CONCLUSIONS: Intraductal therapy offers a nonsurgical strategy to treat DCIS at the site of disease, potentially minimizing the adverse effects of systemic treatment while preventing development of invasive cancer.

Circadian parameters are altered in two strains of mice with transgenic modifications of estrogen receptor subtype 1.

There are sex differences in free-running rhythms, activity level and activity distribution that are attributed, in part, to the action of gonadal hormones. We tested the hypothesis that non-classical estrogenic signaling pathways at estrogen receptor subtype 1 (ESR1) modify the amplitude and phase of activity. We used ESR1 knock-out mice (ERKO) and non-classical estrogen receptor knock-in mice (NERKI). ERKO animals are unable to respond to estrogen at the ESR1 and NERKI animals lack the ability to respond to estrogens via the estrogen response element-mediated pathway, but can still respond via non-classical mechanisms. We compared intact male and female ERKO, NERKI and wildtype (WT) mice with respect to total wheel-running activity, activity distribution across the 24-h day, phase angle of activity onset and free-running period (τ) and the duration of activity in constant conditions. WT females had significantly greater activity than WT males, and this activity was more consolidated to the dark phase of the light:dark cycle. These sex differences were absent in the NERKI and ERKO animals. Among females, NERKI and ERKO animals had greater activity during the light phase than WT counterparts. Additionally, we have identified a novel contribution of non-classical estrogen signaling pathways on the distribution of activity. Our data suggest that total activity is ESR1-dependent and daily activity patterns depend on both classical and non-classical actions of estrogens. These data will aid in identifying the mechanisms underlying sex differences in sleep-wake cycles and the influence of steroid hormones on circadian patterns.

The impact of computer display performance on the quality of digital radiographs: a review.

Radiography makes an essential contribution to the processes of examination, diagnosis and treatment planning in dentistry. While the use of film-based imaging still predominates in dentistry, digital imaging is gaining wider acceptance and the use of this modality is anticipated to expand in the future. Two concerns associated with this transition have been raised in the literature. The first of these is the dissatisfaction experienced by many dental professionals with quality of digital radiographs when compared to plain film. In addition, there are indications that practitioners feel limited in their understanding of those factors impacting on digital image quality. One key area highlighted in the literature as having a significant influence on digital radiographic quality and interpretation concerns the performance of the display device. Within the last decade, research derived from the fields of medical radiology and physics have demonstrated that suboptimally performing displays degrade image quality, thereby increasing the potential for compromised diagnostic outcomes. In the field of medicine, this has resulted in the establishment of standards applicable to computer displays used in diagnostic radiology. Conversely, limited guidelines exist in the field of dentistry. The aim of this review is to provide an outline of these standards and highlight the important relationship between computer display performance and digital image quality.

Relationship between breast cancer risk factors and mammographic breast density in the Fernald Community Cohort.

BACKGROUND: We investigated associations of known breast cancer risk factors with breast density, a well-established and very strong predictor of breast cancer risk. METHODS: This nested case-control study included breast cancer-free women, 265 with high and 860 with low breast density. Women were required to be 40-80 years old and should have a body mass index (BMI) <35 at the time of the index mammogram. Information on covariates was obtained from annual questionnaires. RESULTS: In the overall analysis, breast density was inversely associated with BMI at mammogram (P for trend<0.001), and parity (P for trend=0.02) and positively associated with alcohol consumption (ever vs never: odds ratio 2.0, 95% confidence interval 1.4-2.8). Alcohol consumption was positively associated with density, and the association was stronger in women with a family history of breast cancer (P<0.001) and in women with hormone replacement therapy (HRT) history (P<0.001). Parity was inversely associated with density in all subsets, except premenopausal women and women without a family history. The association of parity with density was stronger in women with HRT history (P<0.001). CONCLUSION: The associations of alcohol and parity with breast density appear to be in reverse direction, but stronger in women with a family history of breast cancer and women who ever used HRT.

The effects of extended pre-quit varenicline treatment on smoking behavior and short-term abstinence: a randomized clinical trial.

Preclinical research and learning theory suggest that a longer duration of varenicline treatment prior to the target quit date (TQD) would reduce smoking rates before cessation and improve abstinence outcomes. A double-blind randomized controlled trial tested this hypothesis in 60 smokers randomized to either an Extended run-in group (4 weeks of pre-TQD varenicline) or a Standard run-in group (3 weeks of placebo, 1 week of pre-TQD varenicline); all the participants received 11 weeks of post-TQD varenicline and brief counseling. During the pre-quit run-in, the reduction in smoking rates was greater in the Extended run-in group than in the Standard run-in group (42% vs. 24%, P < 0.01), and this effect was greater in women than in men (57% vs. 26%, P = 0.001). The rate of continuous abstinence during the final 4 weeks of treatment was higher among women in the Extended group compared to women in the Standard run-in group (67% vs. 35%). Although these data suggest that extension of varenicline treatment reduces smoking during the pre-quit period and may further enhance cessation rates, confirmatory evidence is needed from phase III clinical trials.

A role for caveolin-1 in desmoglein binding and desmosome dynamics.

Desmoglein-2 (Dsg2) is a desmosomal cadherin that is aberrantly expressed in human skin carcinomas. In addition to its well-known role in mediating intercellular desmosomal adhesion, Dsg2 regulates mitogenic signaling that may promote cancer development and progression. However, the mechanisms by which Dsg2 activates these signaling pathways and the relative contribution of its signaling and adhesion functions in tumor progression are poorly understood. In this study we show that Dsg2 associates with caveolin-1 (Cav-1), the major protein of specialized membrane microdomains called caveolae, which functions in both membrane protein turnover and intracellular signaling. Sequence analysis revealed that Dsg2 contains a putative Cav-1-binding motif. A permeable competing peptide resembling the Cav-1 scaffolding domain bound to Dsg2, disrupted normal Dsg2 staining and interfered with the integrity of epithelial sheets in vitro. Additionally, we observed that Dsg2 is proteolytically processed; resulting in a 95-kDa ectodomain shed product and a 65-kDa membrane-spanning fragment, the latter of which localizes to lipid rafts along with full-length Dsg2. Disruption of lipid rafts shifted Dsg2 to the non-raft fractions, leading to the accumulation of these proteins. Interestingly, Dsg2 proteolytic products are elevated in vivo in skin tumors from transgenic mice overexpressing Dsg2. Collectively, these data are consistent with the possibility that accumulation of truncated Dsg2 protein interferes with desmosome assembly and/or maintenance to disrupt cell-cell adhesion. Furthermore, the association of Dsg2 with Cav-1 may provide a mechanism for regulating mitogenic signaling and modulating the cell-surface presentation of an important adhesion molecule, both of which could contribute to malignant transformation and tumor progression.

Dental CT metal artefact reduction based on sequential substitution.

OBJECTIVE: Metal artefacts can seriously degrade the visual quality and interpretability of dental CT images. Existing image processing algorithms for metal artefact reduction (MAR) are either too computationally expensive to be used in clinical scanners or effective only in correcting mild artefacts. The aim of the present study was to investigate whether it is possible to improve the efficacy of the computationally efficient projection-correction approach to MAR by exploiting the spatial dependency or autocorrelation between adjacent CT slices. METHODS: A new projection-correction algorithm [MAR by sequential substitution (MARSS)] was developed based on the idea that the corrupted portions of the projection data can be substituted with the corresponding portions from an unaffected adjacent slice. The performance of MARSS was evaluated relative to the projection-correction method of Watzke and Kalendar using a two-alternative forced choice (2AFC) visual trial involving 20 observers and 20 clinical CT data sets.16 RESULTS: The Cochran Q test revealed no significant difference in the responses across all observers. The data were then pooled and analysed using a one-tailed exact binomial test. This revealed that the proportion of responses in favour of MARSS was significant (P < 2.2 × 10(-16)). A second Cochran Q test revealed no significant difference in the responses across all images. CONCLUSIONS: It is possible to improve the efficacy of projection correction by exploiting spatial autocorrelation. The 2AFC results suggest that the proposed MARSS algorithm outperforms competing computationally efficient algorithms in terms of reducing metal artefacts whilst at the same time preserving/revealing anatomic detail.