Mammographic density and risk of breast cancer according to tumor characteristics and mode of detection: a Spanish population-based case-control study

It is not clear whether high mammographic density (MD) is equally associated with all subtypes of breast cancer (BC). We investigated the association between MD and subsequent BC, considering invasiveness, means of detection, pathologic subtype, and the time elapsed since mammographic exploration and BC diagnosis. METHODS: BC cases occurring in the population of women who attended screening from 1997 through 2004 in Navarre, a Spanish region with a fully consolidated screening program, were identified via record linkage with the Navarre Cancer Registry (n = 1,172). Information was extracted from the records of their first attendance at screening in that period. For each case, we randomly selected four controls, matched by screening round, year of birth, and place of residence. Cases were classified according to invasiveness (ductal carcinoma in situ (DCIS) versus invasive tumors), pathologic subtype (considering hormonal receptors and HER2), and type of diagnosis (screen-detected versus interval cases). MD was evaluated by a single, experienced radiologist by using a semiquantitative scale. Data on BC risk factors were obtained by the screening program in the corresponding round. The association between MD and tumor subtype was assessed by using conditional logistic regression. RESULTS: MD was clearly associated with subsequent BC. The odds ratio (OR) for the highest MD category (MD >75%) compared with the reference category (MD <10%) was similar for DCIS (OR = 3.47; 95% CI = 1.46 to 8.27) and invasive tumors (OR = 2.95; 95% CI = 2.01 to 4.35). The excess risk was particularly high for interval cases (OR = 7.72; 95% CI = 4.02 to 14.81) in comparison with screened detected tumors (OR = 2.17; 95% CI = 1.40 to 3.36). Sensitivity analyses excluding interval cases diagnosed in the first year after MD assessment or immediately after an early recall to screening yielded similar results. No differences were seen regarding pathologic subtypes. The excess risk associated with MD persisted for at least 7 to 8 years after mammographic exploration. CONCLUSIONS: Our results confirm that MD is an important risk factor for all types of breast cancer. High breast density strongly increases the risk of developing an interval tumor, and this excess risk is not completely explained by a possible masking effect.This work was supported by research grants from Eli Lilly and Company (EV1 1082/08); and the Spanish Federation of Breast Cancer Patients (Federación Española de Cáncer de Mama) (FECMA 485 EPY 1170-10).S

Uncertainties in steric sea level change estimation during the satellite altimeter era: concepts and practices

This article presents a review of current practice in estimating steric sea level change, focussed on the treatment of uncertainty. Steric sea level change is the contribution to the change in sea level arising from the dependence of density on temperature and salinity. It is a significant component of sea level rise and a reflection of changing ocean heat content. However tracking these steric changes remains still a significant challenge for the scientific community. We review the importance of understanding the uncertainty in estimates of steric sea level change. Relevant concepts of uncertainty are discussed and illustrated with the example of observational uncertainty propagation from a single profile of temperature and salinity measurements to steric height. We summarise and discuss the recent literature on methodologies and techniques used to estimate steric sea level in the context of the treatment of uncertainty. Our conclusions are that progress in quantifying steric sea level uncertainty will benefit from: greater clarity and transparency in published discussions of uncertainty, including exploitation of international standards for quantifying and expressing uncertainty in measurement; and the development of community ‘recipes’ for quantifying the error covariances in observations and from sparse sampling, and for estimating and propagating uncertainty across spatio-temporal scales

Advances, challenges and future directions for stem cell therapy in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative condition where loss of motor neurons within the brain and spinal cord leads to muscle atrophy, weakness, paralysis and ultimately death within 3–5 years from onset of symptoms. The specific molecular mechanisms underlying the disease pathology are not fully understood and neuroprotective treatment options are minimally effective. In recent years, stem cell transplantation as a new therapy for ALS patients has been extensively investigated, becoming an intense and debated field of study. In several preclinical studies using the SOD1G93A mouse model of ALS, stem cells were demonstrated to be neuroprotective, effectively delayed disease onset and extended survival. Despite substantial improvements in stem cell technology and promising results in preclinical studies, several questions still remain unanswered, such as the identification of the most suitable and beneficial cell source, cell dose, route of delivery and therapeutic mechanisms. This review will cover publications in this field and comprehensively discuss advances, challenges and future direction regarding the therapeutic potential of stem cells in ALS, with a focus on mesenchymal stem cells. In summary, given their high proliferation activity, immunomodulation, multi-differentiation potential, and the capacity to secrete neuroprotective factors, adult mesenchymal stem cells represent a promising candidate for clinical translation. However, technical hurdles such as optimal dose, differentiation state, route of administration, and the underlying potential therapeutic mechanisms still need to be assessed

Subtotal Carbon Dioxide Laser Arytenoidectomy for the Treatment of Bilateral Vocal Fold Immobility: Long-Term Results

Sixty-nine patients underwent subtotal carbon dioxide laser arytenoidectomy for treatment of bilateral vocal fold immobility between 1985 and 2000. The population included 69 patients whose mean age was 56 years (SD, 16 years; range, I I to 82 years). The mean follow-up was 50 months (SD, 44 months; range, I to 181 months). The overall postoperative peak expiratory/peak inspiratory flow ratio (normal value, 1) significantly improved (closer to 1; p = .0036). Voice analyses were also undertaken for 27 patients, almost exclusively after operation, given the context of initial emergency. The maximum phonation time averaged 6.57 seconds (median, 6 seconds). The phonation quotient remained high, with a mean of 503 (median, 440), and the mean conversational voice intensity remained around 59 dB. The median frequency analysis type was 3. The advantage of subtotal arytenoidectomy ties in the fact that it maintains a certain degree of rigidity along the posterior limit of the arytenoid frame, preventing inward collapse of the mucosa and thus lowering the risk of aspiration