Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial

BACKGROUND: To compare the incidence and timing of bone fractures in postmenopausal women treated with 5 years of adjuvant tamoxifen or letrozole for endocrine-responsive early breast cancer in the Breast International Group (BIG) 1-98 trial. METHODS: We evaluated 4895 patients allocated to 5 years of letrozole or tamoxifen in the BIG 1-98 trial who received at least some study medication (median follow-up 60.3 months). Bone fracture information (grade, cause, site) was collected every 6 months during trial treatment. RESULTS: The incidence of bone fractures was higher among patients treated with letrozole [228 of 2448 women (9.3%)] versus tamoxifen [160 of 2447 women (6.5%)]. The wrist was the most common site of fracture in both treatment groups. Statistically significant risk factors for bone fractures during treatment included age, smoking history, osteoporosis at baseline, previous bone fracture, and previous hormone replacement therapy. CONCLUSIONS: Consistent with other trials comparing aromatase inhibitors to tamoxifen, letrozole was associated with an increase in bone fractures. Benefits of superior disease control associated with letrozole and lower incidence of fracture with tamoxifen should be considered with the risk profile for individual patients.

Age modeling of young non-varved lake sediments: methods and limits. Examples from two lakes in Central Chile

High-resolution and highly precise age models for recent lake sediments (last 100–150 years) are essential for quantitative paleoclimate research. These are particularly important for sedimentological and geochemical proxies, where transfer functions cannot be established and calibration must be based upon the relation of sedimentary records to instrumental data. High-precision dating for the calibration period is most critical as it determines directly the quality of the calibration statistics. Here, as an example, we compare radionuclide age models obtained on two high-elevation glacial lakes in the Central Chilean Andes (Laguna Negra: 33°38′S/70°08′W, 2,680 m a.s.l. and Laguna El Ocho: 34°02′S/70°19′W, 3,250 m a.s.l.). We show the different numerical models that produce accurate age-depth chronologies based on 210Pb profiles, and we explain how to obtain reduced age-error bars at the bottom part of the profiles, i.e., typically around the end of the 19th century. In order to constrain the age models, we propose a method with five steps: (i) sampling at irregularly-spaced intervals for 226Ra, 210Pb and 137Cs depending on the stratigraphy and microfacies, (ii) a systematic comparison of numerical models for the calculation of 210Pb-based age models: constant flux constant sedimentation (CFCS), constant initial concentration (CIC), constant rate of supply (CRS) and sediment isotope tomography (SIT), (iii) numerical constraining of the CRS and SIT models with the 137Cs chronomarker of AD 1964 and, (iv) step-wise cross-validation with independent diagnostic environmental stratigraphic markers of known age (e.g., volcanic ash layer, historical flood and earthquakes). In both examples, we also use airborne pollutants such as spheroidal carbonaceous particles (reflecting the history of fossil fuel emissions), excess atmospheric Cu deposition (reflecting the production history of a large local Cu mine), and turbidites related to historical earthquakes. Our results show that the SIT model constrained with the 137Cs AD 1964 peak performs best over the entire chronological profile (last 100–150 years) and yields the smallest standard deviations for the sediment ages. Such precision is critical for the calibration statistics, and ultimately, for the quality of the quantitative paleoclimate reconstruction. The systematic comparison of CRS and SIT models also helps to validate the robustness of the chronologies in different sections of the profile. Although surprisingly poorly known and under-explored in paleolimnological research, the SIT model has a great potential in paleoclimatological reconstructions based on lake sediments

Differences in Internet Usage - Social Inequality and Informal Education

In the public debate the internet is regarded as a central resource for knowledge and information. Associated with this is the idea that everyone is able and even expected to serve himself or herself according to his or her own needs via this medium. Since more and more services are also delivered online the internet seems to allow its users to enjoy specific advantages in dealing with their everyday life. However, using the internet is based on a range of preconditions. New results of empirical and theoretical research indicate the rise of a social divide in this context. Within the internet, different ways of use can be identified alongside social inequalities. Boundaries of the "real life" are mirrored in the virtual space e.g. in terms of forms of communification and spaces for appropriation. These are not only shaped by invidual preferences but particularly by social structures and processes. In the context of the broader debate on education it is stated that formal educational structures are to be completed by arrangements which are structured in informal respectively nonformal ways. Particularly the internet is suggested to play an important role in this respect. However, the phenomenon of digital inequality points to limitations consolidated by effects of economic, social, and cultural ressources: Economical resources affect opportunities of access, priorities of everyday life shape respective intentions of internet use, social relationships have an impact on the support structures available and ways of appropriation reproduce a specific understanding of informal education ("informelle Bildung"). This produces an early stratification of opportunities especially for the subsequent generation and may lead to extensive inequalities regarding the distribution of advantages in terms of education. Thus the capacity of the virtual space in terms of participatory opportunities and democratic potentials raises concerns of major relevance with respect to social and educational policy. From the perspective of different disciplines involved in these issues it is essential to clarify this question in an empirical as well as in a theoretical way and to make it utilizable for a future-orientied practice. This article discusses central questions regarding young people's internet use and its implications for informal education and social service delivery on the basis of empirical findings. It introduces a methodological approach for this particular perspective and illustrates that the phenomena of digital divide and digital inequality are as much created by social processes as by technical issues.

Different effects of cyclosporin A on bone remodeling in young and adult rats

Reported effects of cyclosporin A (Sandimmun, CsA) on bone have been both contradictory and controversial. Thus, stimulation of new bone formation as well as increased mineral and matrix resorption have been observed. To investigate the response of basal mineral and matrix turnover to CsA treatment at different stages of skeletal development, comparative experiments were conducted in young growing female rats and in adults. Fifty-six young animals (study A) and 40 adults (study B) received orally either the carrier substance or 5, 15, and 30 mg/kg CsA for 30 days. The following parameters were measured: (a) total skeletal mineral content by dual energy X-ray absorptiometry (DEXA) on days 1 and 30; (b) tibial trabecular volume at day 30; (c) serum osteocalcin at 5-day intervals; (d) urinary deoxypyridinoline (Dpd) excretion (days 1, 15, and 30); and (e) plasma levels of CsA. Results can be summarized as follows: in young rats (study A), total skeletal mineral was not modified by the 5- and 15-mg/kg doses of CsA, whereas 30 mg/kg induced a significant decrease (-15%, p < 0.01). This parameter was not significantly modified in adult animals (study B) subjected to the same doses. The administration of 5 mg/kg CsA did not alter tibial trabecular volume in young rats, but 15 and 30 mg/kg significantly lowered this parameter (-16.3%, p < 0.02, and -42%, p < 0.001, respectively). In adult rats, tibial trabecular volume remained unchanged with the exception of the group receiving 30 mg/kg which exhibited significantly lower values (-28%, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Edna Chamberlain (1921 -2005): A Leader through Times of Transition and Change

Professor Edna Chamberlain was an outstanding leader in Australian social work. She contributed extensively to social work education at the University of Queensland, the social work profession through her leadership of the Australian Association of Social Workers and to the community through advocacy for progressive social policies. Her life experiences were influential is shaping her career and her particular teaching and research interests. Early in her life, Chamberlain was exposed to individual deprivation as a result of the Great Depression. This provided the incentive for a career in social work. She worked as a social work practitioner for some years and entered the academic world until after the death of her husband. In the university and profession, she was confronted by conflict between traditionalists and those wanting immediate reform. In managing these tensions, she tried to find the common ground but these tensions also moderated and changed her views about the purpose and practice of social work. Her rich practice and later research and teaching background provided a strong basis for her professional leadership, research activities and curriculum initiatives. Whilst social casework methods were influential early in her career she sought in later years to integrate the private pain of individuals with social policy and community planning by focusing on the purpose of social work – demonstrating her commitment to the disadvantaged in the context of social justice.

The Integration of Formal and Non-formal Education: The Dutch “brede school”

The Dutch “brede school” (BS) development originates in the 1990s and has spread unevenly since: quicker in the primary than secondary educational sector. In 2007, there were about 1000 primary and 350 secondary BS schools and it is the intention of the government as well as the individual municipalities to extend that number and make the BS the dominant school form of the near future. In the primary sector, a BS cooperates with crèche and preschool facilities, besides possible other neighborhood partners. The main targets are, first, to enhance educational opportunities, particularly for children with little (western-) cultural capital, and secondly to increase women’s labor market participation by providing extra familial care for babies and small children. All primary schools are now obliged to provide such care. In the secondary sector, a BS is less neighborhood-orientated than a primary BS because those schools are bigger and more often located in different buildings. As in the primary sector, there are broad and more narrow BS, the first profile cooperating with many non-formal and other partners and facilities and the second with few. On the whole, there is a wide variety of BS schools, with different profiles and objectives, dependent on the needs and wishes of the initiators and the neighborhood. A BS is always the result of initiatives of the respective school and its partners: parents, other neighborhood associations, municipality etc. BS schools are not enforced by the government although the general trend will be that existing school organizations transform into BS. The integration of formal and non-formal education and learning is more advanced in primary than secondary schools. In secondary education, vocational as well as general, there is a clear dominance of formal education; the non-formal curriculum serves mainly two lines and objectives: first, provide attractive leisure activities and second provide compensatory courses and support for under-achievers who are often students with migrant background. In both sectors, primary and secondary, it is the formal school organization with its professionals which determines the character of a BS; there is no full integration of formal and non-formal education resulting in one non-disruptive learning trajectory, nor is there the intention to go in that direction. Non-formal pedagogues are partly professionals, like youth- and social workers, partly volunteers, like parents, partly non-educational partners, like school-police, psycho-medical help or commercial leisure providers. Besides that, the BS is regarded by government educational and social policy as a potential partner and anchor for community development. It is too early to make reliable statements about the effects of the BS movement in the Netherlands concerning the educational opportunities for disadvantaged children and their families, especially those with migrant background, and combat further segregation. Evaluation studies made so far are moderately positive but also point to problems of overly bureaucratized structures and layers, lack of sufficient financial resources and, again, are uncertain about long-term effects.

Kaposi sarcoma-associated herpes virus and response to antiretroviral therapy: a prospective study of HIV-infected adults

BACKGROUND The possible impact of coinfection with the Kaposi sarcoma-associated herpes virus (KSHV) on the response to antiretroviral therapy (ART) is unknown. Prospective studies are rare, particularly in Africa. METHODS We enrolled a prospective cohort of HIV-infected adults initiating ART in Johannesburg, South Africa. The subjects were defined as seropositive to KSHV if they were reactive to either KSHV lytic K8.1 or latent Orf73 antigen or to both. The subjects were followed from ART initiation until 18 months of treatment. HIV viral load and CD4 counts were tested 6 monthly. Linear generalized estimating and log-binomial regression models were used to estimate the effect of KSHV infection on immunologic recovery and response and HIV viral load suppression within 18 months after ART initiation. RESULTS Three hundred eighty-five subjects initiating ART from November 2008 to March 2009 were considered to be eligible including 184 (48%) KSHV+. The KSHV+ group was similar to the KSHV- in terms of age, gender, initiating CD4 count, body mass index, tuberculosis, and hemoglobin levels. The KSHV+ group gained a similar number of cells at 6 [difference of 10 cells per cubic millimeter, 95% confidence interval (CI): -11 to 31], 12 (3 cells per cubic millimeter, 95% CI: -19 to 25), and 18 months (24 cells per cubic millimeter, 95% CI: -13 to 61) compared with that gained by the KSHV- group. Adjusted relative risk of failure to suppress viral load to <400 copies per milliliter (1.03; 95% CI: 0.90 to 1.17) were similar for KSHV+ and KSHV- by 6 months on treatment. CONCLUSIONS In a population with a high KSHV prevalence, HIV-positive adults coinfected with KSHV achieved similar immunologic and virologic responses to ART early after treatment initiation compared with those with KSHV-.

Facial esthetics in children with unilateral cleft lip and palate 3 years after alveolar bonegrafting combined with rhinoplasty between 2 and 4 years of age

OBJECTIVES To evaluate facial esthetics in patients with unilateral cleft lip and palate (UCLP) after alveolar bone grafting combined with rhinoplasty between 2 and 4 years of age. DESIGN Retrospective case-control study. SETTING The Department of Pediatric Surgery, Institute of Mother and Child, Warsaw, Poland. MATERIAL AND METHODS Photographs of full faces and cropped images of five nasolabial components: nasal deviation, nasal form, nasal profile, vermillion border, and inferior view were assessed by 5 professional and 14 layraters in 29 children (23 boys and 6 girls; mean age = 5.3 years, SD 0.5; Early-grafted group) and 30 children (20 boys and 10 girls; mean age = 5.5 years, SD 1.0; Non-grafted group) with complete unilateral cleft lip and palate repaired with a one-stage closure. The groups differed regarding the timing of alveolar bone grafting: in the Early-grafted group, alveolar bone grafting in combination with rhinoplasty (ABG-R) was performed between 2 and 4 years of age (mean age = 2.3 years; SD 0.6); in the Non-grafted group, the alveolar defect was grafted after 9 years of age. No primary nose correction was carried out in any group. To rate esthetics, a modified five-grade esthetic index of Asher-McDade was used, where grade 1 means the most esthetic and grade 5 - the least esthetic outcome. RESULTS Esthetics of full faces and of all nasolabial elements in the Early-grafted group was significantly better than in Non-grafted group. The scores in the Early-grafted group ranged from 2.30 to 2.66 points, whereas in the Non-grafted group ranged from 2.66 to 3.17 points. All intergroup differences were statistically significant (p < 0.05). CONCLUSIONS Three years post-operatively, early alveolar bone grafting combined with rhinoplasty is favorable for facial esthetics in children with UCLP, but a longer follow-up is needed to assess whether the improvement was permanent.

Incident malignancies among older long-term breast cancer survivors and an age-matched and site-matched nonbreast cancer comparison group over 10 years of follow-up

BACKGROUND Of the approximately 2.4 million American women with a history of breast cancer, 43% are aged ≥ 65 years and are at risk for developing subsequent malignancies. METHODS Women from 6 geographically diverse sites included 5-year breast cancer survivors (N = 1361) who were diagnosed between 1990 and 1994 at age ≥ 65 years with stage I or II disease and a comparison group of women without breast cancer (N = 1361). Women in the comparison group were age-matched and site-matched to breast cancer survivors on the date of breast cancer diagnosis. Follow-up began 5 years after the index date (survivor diagnosis date or comparison enrollment date) until death, disenrollment, or through 15 years after the index date. Data were collected from medical records and electronic sources (cancer registry, administrative, clinical, National Death Index). Analyses included descriptive statistics, crude incidence rates, and Cox proportional hazards regression models for estimating the risk of incident malignancy and were adjusted for death as a competing risk. RESULTS Survivors and women in the comparison group were similar: >82% were white, 55% had a Charlson Comorbidity Index of 0, and ≥ 73% had a body mass index ≤ 30 kg/m(2) . Of all 306 women (N = 160 in the survivor group, N = 146 in the comparison group) who developed a first incident malignancy during follow-up, the mean time to malignancy was similar (4.37 ± 2.81 years vs 4.03 ± 2.76 years, respectively; P = .28), whereas unadjusted incidence rates were slightly higher in survivors (1882 vs 1620 per 100,000 person years). The adjusted hazard of developing a first incident malignancy was slightly elevated in survivors in relation to women in the comparison group, but it was not statistically significant (hazard ratio, 1.17; 95% confidence interval, 0.94-1.47). CONCLUSIONS Older women who survived 5 years after an early stage breast cancer diagnosis were not at an elevated risk for developing subsequent incident malignancies up to 15 years after their breast cancer diagnosis.

Correlation between subjective evaluation of symptoms and objective findings in early recurrent head and neck squamous cell carcinoma

IMPORTANCE This study addresses the value of patients' reported symptoms as markers of tumor recurrence after definitive therapy for head and neck squamous cell carcinoma. OBJECTIVE To evaluate the correlation between patients' symptoms and objective findings in the diagnosis of local and/or regional recurrences of head and neck squamous cell carcinomas in the first 2 years of follow-up. DESIGN Retrospective single-institution study of a prospectively collected database. SETTING Regional hospital. PARTICIPANTS We reviewed the clinical records of patients treated for oral cavity, oropharyngeal, laryngeal, and hypopharyngeal carcinomas between January 1, 2008, and December 31, 2009, with a minimum follow-up of 2 years. MAIN OUTCOMES AND MEASURES Correlation between symptoms and oncologic status (recurrence vs remission) in the posttreatment period. RESULTS Of the 101 patients included, 30 had recurrences. Pain, odynophagia, and dysphonia were independently correlated with recurrence (odds ratios, 16.07, 11.20, and 5.90, respectively; P < .001). New-onset symptoms had the best correlation with recurrences. Correlation was better between 6 to 12 and 18 to 21 months after therapy and in patients initially treated unimodally (P < .05). Primary stage and tumor site had no effect. CONCLUSIONS AND RELEVANCE The correlation between symptoms and oncologic status is low during substantial periods within the first 2 years of follow-up. New-onset symptoms, especially pain, odynophagia, or dysphonia, better correlate with tumor recurrence, especially in patients treated unimodally.

Cochlear implantation in children and adults in Switzerland

The cochlear implant (CI) is one of the most successful neural prostheses developed to date. It offers artificial hearing to individuals with profound sensorineural hearing loss and with insufficient benefit from conventional hearing aids. The first implants available some 30 years ago provided a limited sensation of sound. The benefit for users of these early systems was mostly a facilitation of lip-reading based communication rather than an understanding of speech. Considerable progress has been made since then. Modern, multichannel implant systems feature complex speech processing strategies, high stimulation rates and multiple sites of stimulation in the cochlea. Equipped with such a state-of-the-art system, the majority of recipients today can communicate orally without visual cues and can even use the telephone. The impact of CIs on deaf individuals and on the deaf community has thus been exceptional. To date, more than 300,000 patients worldwide have received CIs. In Switzerland, the first implantation was performed in 1977 and, as of 2012, over 2,000 systems have been implanted with a current rate of around 150 CIs per year. The primary purpose of this article is to provide a contemporary overview of cochlear implantation, emphasising the situation in Switzerland.

Influence of Gestational Age and Parental Education on Executive Functions of Children Born Very Preterm

Background: Children born very preterm (<32 weeks’ gestational age; VPT) and/or very low birth weight (<1500 g; VLBW) are at high risk of deficits in executive functions, namely inhibition, working memory, and shifting. Both, gestational age and socioeconomic factors, such as parental education, are known to influence executive functions, with children born at lower gestational age and with lower educated parents displaying worse executive skills. This study aimed to investigate if maternal and paternal education moderated the relationship between gestational age and executive functions in VPT/VLBW children aged 8-12 years. It was hypothesised that the disadvantageous effect of low gestational age could be buffered more easily in families with higher educational background. Methods: Sixty VPT/VLBW children born in the cohort of 1998-2003 were recruited. All children completed executive function tasks (inhibition, working memory, and shifting). Results: There was a significant dose-response-relationship between gestational age and inhibition, with children being born at earlier gestational age showing worse inhibition. However, neither maternal nor paternal education moderated the relationship between gestational age and executive functions significantly. Conclusion: children than parental education. The disadvantageous effect of low gestational age was equal in children with higher and lower educated parents. However, the impact of gestational age and parental education on executive functions may differ depending on the socioeconomic spectrum of the study sample.

Recognition memory across the lifespan: the impact of word frequency and study-test interval on estimates of familiarity and recollection

The goal of this study was to investigate recognition memory performance across the lifespan and to determine how estimates of recollection and familiarity contribute to performance. In each of three experiments, participants from five groups from 14 up to 85 years of age (children, young adults, middle-aged adults, young-old adults, and old-old adults) were presented with high- and low-frequency words in a study phase and were tested immediately afterwards and/or after a one day retention interval. The results showed that word frequency and retention interval affected recognition memory performance as well as estimates of recollection and familiarity. Across the lifespan, the trajectory of recognition memory followed an inverse u-shape function that was neither affected by word frequency nor by retention interval. The trajectory of estimates of recollection also followed an inverse u-shape function, and was especially pronounced for low-frequency words. In contrast, estimates of familiarity did not differ across the lifespan. The results indicate that age differences in recognition memory are mainly due to differences in processes related to recollection while the contribution of familiarity-based processes seems to be age-invariant.

Work Experiences and Well-Being in the First Years of Professional Work in Switzerland: A Ten-Year Follow-Up Study

The ÆQUAS (a German acronym for “Work Experiences and Quality of Life in Switzerland”) study followed young workers in five occupations over their first ten years in the labor market. Participants of the study reported on working conditions and well-being at five occasions. Overall, resources at work as well as well-being, health and personal resources remained stable or increased. Concurrently, task-related stressors increased as well. This result may reflect career progress (e.g., gaining more responsibilities may be accompanied by increasing time pressure) but development in task-related stressors as well as resources may also be related to specific occupations. Several trajectories had their turning point after the first or second year of being in the labor market, which may reflect a successful professional socialization. Even though a substantial number of participants did change their occupation over these ten years (with benefits for their well-being), development over the first ten years after vocational training implies a successful transition into labor market.