The Emerging Aversion to Inequality: Evidence from Poland 1992-2005

This paper provides an illustration of the changing tolerance for inequality in a context of radical political and economic transformation and rapid economic growth. We focus on the Polish experience of transition and explore self-declared attitudes of the citizens. Using monthly representative surveys of the population, realized by the Polish poll institute (CBOS) from 1992 to 2005, we identify a structural break in the relation between income inequality and subjective evaluation of well-being. The downturn in the tolerance for inequality (1997) coincides with the increasing distrust of political elites.http://deepblue.lib.umich.edu/bitstream/2027.42/64387/1/wp919.pd

Signs and symptoms of temporomandibular disorders and oral parafunctions in urban Saudi arabian adolescents: a research report

BACKGROUND: The aim of this study was to evaluate the prevalence of signs and symptoms of temporomandibular disorders (TMD) and oral parafunction habits among Saudi adolescents in the permanent dentition stage. METHODS: A total of 385 (230 females and 155 males) school children age 12–16, completed a questionnaire and were examined clinically. A stratified selection technique was used for schools allocation. RESULTS: The results showed that 21.3% of the subjects exhibited at least one sign of TMD and females were generally more affected than males. Joint sounds were the most prevalent sign (13.5%) followed by restricted opening (4.7%) and opening deviation (3.9%). The amplitude of mouth opening, overbite taken into consideration, was 46.5 mm and 50.2 mm in females and males respectively. TMJ pain and muscle tenderness were rare (0.5%). Reported symptoms were 33%, headache being the most frequent symptom 22%, followed by pain during chewing 14% and hearing TMJ noises 8.7%. Difficulty during jaw opening and jaw locking were rare. Lip/cheek biting was the most common parafunction habit (41%) with females significantly more than males, followed by nail biting (29%). Bruxism and thumb sucking were only 7.4% and 7.8% respectively. CONCLUSION: The prevalence of TMD signs were 21.3% with joint sounds being the most prevalent sign. While TMD symptoms were found to be 33% as, with headache being the most prevalent. Among the oral parafunctions, lip/cheek biting was the most prevalent 41% followed by nail biting 29%

A micro costing of NHS cancer genetic services

This paper presents the first full micro costing of a commonly used cancer genetic counselling and testing protocol used in the UK. Costs were estimated for the Cardiff clinic of the Cancer Genetics Service in Wales by issuing a questionnaire to all staff, conducting an audit of clinic rooms and equipment and obtaining gross unit costs from the finance department. A total of 22 distinct event pathways were identified for patients at risk of developing breast, ovarian, breast and ovarian or colorectal cancer. The mean cost per patient were £97–£151 for patients at moderate risk, £975–£3072 for patients at high risk of developing colorectal cancer and £675–£2909 for patients at high risk of developing breast or ovarian cancer. The most expensive element of cancer genetic services was labour. Labour costs were dependent upon the amount of labour, staff grade, number of counsellors used and the proportion of staff time devoted to indirect patient contact. With the growing demand for cancer genetic services and the growing number of national and regional cancer genetic centers, there is a need for the different protocols being used to be thoroughly evaluated in terms of costs and outcomes

Uptake of genetic testing and long-term tumor surveillance in von Hippel-Lindau disease

<p>Abstract</p> <p>Background</p> <p>von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome caused by germline mutations in the <it>VHL </it>gene. Patients have significant morbidity and mortality secondary to vascular tumors. Disease management is centered on tumor surveillance that allows early detection and treatment. Presymptomatic genetic testing is therefore recommended, including in at-risk children.</p> <p>Methods</p> <p>We tested 17 families (n = 109 individuals) for <it>VHL </it>mutations including 43 children under the age of 18. Personalized genetic counseling was provided pre and post-test and the individuals undergoing presymptomatic testing filled out questionnaires gathering socio-demographic, psychological and psychiatric data. Mutation analysis was performed by direct sequencing of the <it>VHL </it>gene. Mutation-carriers were screened for VHL disease-related tumors and were offered follow-up annual examinations.</p> <p>Results</p> <p>Mutations were identified in 36 patients, 17 of whom were asymptomatic. In the initial screening, we identified at least one tumor in five of 17 previously asymptomatic individuals. At the end of five years, only 38.9% of the mutation-carriers continued participating in our tumor surveillance program. During this time, 14 mutation carriers developed a total of 32 new tumors, three of whom died of complications. Gender, education, income, marital status and religiosity were not found to be associated with adherence to the surveillance protocol. Follow-up adherence was also independent of pre-test depression, severity of disease, or number of affected family members. The only statistically significant predictor of adherence was being symptomatic at the time of testing (OR = 5; 95% CI 1.2 - 20.3; p = 0.02). Pre-test anxiety was more commonly observed in patients that discontinued follow-up (64.7% vs. 35.3%; p = 0.01).</p> <p>Conclusions</p> <p>The high initial uptake rate of genetic testing for VHL disease, including in minors, allowed the discontinuation of unnecessary screening procedures in non mutation-carriers. However, mutation-carriers showed poor adherence to long-term tumor surveillance. Therefore, many of them did not obtain the full benefit of early detection and treatment, which is central to the reduction of morbidity and mortality in VHL disease. Studies designed to improve adherence to vigilance protocols will be necessary to improve treatment and quality of life in patients with hereditary cancer syndromes.</p

Homo-PROTACs:bivalent small-molecule dimerizers of the VHL E3 ubiquitin ligase to induce self-degradation

E3 ubiquitin ligases are key enzymes within the ubiquitin proteasome system which catalyze the ubiquitination of proteins, targeting them for proteasomal degradation. E3 ligases are gaining importance as targets to small molecules, both for direct inhibition and to be hijacked to induce the degradation of non-native neo-substrates using bivalent compounds known as PROTACs (for 'proteolysis-targeting chimeras'). We describe Homo-PROTACs as an approach to dimerize an E3 ligase to trigger its suicide-type chemical knockdown inside cells. We provide proof-of-concept of Homo-PROTACs using diverse molecules composed of two instances of a ligand for the von Hippel-Lindau (VHL) E3 ligase. The most active compound, CM11, dimerizes VHL with high avidity in vitro and induces potent, rapid and proteasome-dependent self-degradation of VHL in different cell lines, in a highly isoform-selective fashion and without triggering a hypoxic response. This approach offers a novel chemical probe for selective VHL knockdown, and demonstrates the potential for a new modality of chemical intervention on E3 ligases.Targeting the ubiquitin proteasome system to modulate protein homeostasis using small molecules has promising therapeutic potential. Here the authors describe Homo-PROTACS: small molecules that can induce the homo-dimerization of E3 ubiquitin ligases and cause their proteasome-dependent degradation