Individual and group decision-making on an optimal stopping problem

Michael J Paradowski, Gary J Ewing and Michael R Web

Knee complaints vary with age and gender in the adult population. Population-based reference data for the Knee injury and Osteoarthritis Outcome Score (KOOS)

BACKGROUND: Self-reported knee complaints may vary with age and gender. Reference data from the adult population would help to better interpret the outcome of interventions due to knee complaints. The objectives of the present study were to describe the variation of self-reported knee pain, function and quality of life with age and gender in the adult population and to establish population-based reference data for the Knee injury and Osteoarthritis Outcome Score (KOOS). METHODS: Population-based cohort retrieved from the national population register. The knee-specific Knee injury and Osteoarthritis Outcome Score (KOOS) was mailed to 840 subjects aged 18–84 yrs. RESULTS: 68% response rate. Women in the age group 55–74 reported more knee-related complaints in all the KOOS subscales than age-matched men. The differences were significant for the subscales Pain (p = 0.027), Symptoms (p = 0.003) and ADL function (p = 0.046). In men, worse ADL and Sport and Recreation function was seen in the oldest age group 75–84 years compared to the younger age groups (p < 0.030). In women, worse Pain (p < 0.007), ADL (p < 0.030), Sport and Recreation (p < 0.001) and QOL (p < 0.002) were seen already in the age group 55–74 compared to the younger age groups. CONCLUSION: We found pain and other symptoms, physical function, and knee-related quality of life to vary with age and gender implying the use of age- and gender matched reference values for improved understanding of the outcome after interventions due to knee injury and knee OA

IL-6-174 G/C and -572 C/G Polymorphisms and Risk of Alzheimer’s Disease

Associations between interleukin 6 (IL-6) polymorphisms and Alzheimer’s disease (AD) remain controversial and ambiguous. The aim of this meta-analysis is to explore more precise estimations for the relationship between IL-6-174 G/C and -572 C/G polymorphisms and risk for AD. Electronic searches for all publications in databases PubMed and EMBASE were conducted on the associations between IL-6 polymorphisms and risk for AD until January 2012. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated using fixed and random effects models. Twenty-seven studies were included with a total of 19,135 individuals, involving 6,632 AD patients and 12,503 controls. For IL-6-174 G/C polymorphism, the combined results showed significant differences in recessive model (CC vs. CG+GG: OR = 0.65, 95%CI = 0.52–0.82). As regards IL-6-572 C/G polymorphism, significant associations were shown in dominant model (CG+GG vs. CC: OR  = 0.73, 95% CI = 0.62–0.86) and in additive model (GG vs. CC, OR  = 0.66, 95% CI = 0.46–0.96). In conclusion, genotype CC of IL-6-174 G/C and genotype GG plus GC of IL-6-572 C/G could decrease the risk of AD

Mode of action of DNA-competitive small molecule inhibitors of tyrosyl DNA phosphodiesterase 2

TDP2 is a 5’-tyrosyl DNA phosphodiesterase important for the repair of DNA adducts generated by non-productive (abortive) activity of topoisomerase II. TDP2 facilitates therapeutic resistance to topoisomerase poisons, which are widely used in the treatment of a range of cancer types. Consequently, TDP2 is an interesting target for the development of small molecule inhibitors that could restore sensitivity to topoisomerase-directed therapies. Previous studies identified a class of deazaflavin-based molecules that showed inhibitory activity against TDP2 at therapeutically useful concentrations, but their mode of action was uncertain. We have confirmed that the deazaflavin series inhibits TDP2 enzyme activity in a fluorescence-based assay, suitable for HTS-screening. We have gone on to determine crystal structures of these compounds bound to a ‘humanised’ form of murine TDP2. The structures reveal their novel mode of action as competitive ligands for the binding site of an incoming DNA substrate, and point the way to generating novel and potent inhibitors of TDP2

Improved results of lung transplantation for patients with cystic fibrosis

AbstractPatients with cystic fibrosis pose particular challenges for lung transplantation surgeons. Earlier reports from North America centers suggested that patients with cystic fibrosis were greater risk for heart-lung or isolated lung transplantation than other patients with end-stage pulmonary disease. During a 3 ½ year period, 44 patients with end-stage lung disease resulting from cystic fibrosis underwent double lung transplantation at this institution. During the same interval, 18 patients with cystic fibrosis, died while waiting for a double lung transplantation. The ages of the recipients ranged from 8 to 45 years, and mean forced expiratory volume in 1 second was 21% predicted. Seven patients had Pseudomonas cepacia bacteria before transplantation. Bilateral sequential implantation with omentopexy was used in all patients. There were no operative deaths, although two patients required urgent retransplantation because of graft failure. Cardiopulmonary bypass was necessary in six procedures in five patients and was associated with an increased blood transfusion requirement, longer postoperative ventilation, and longer hospital stay. Actuarial survival rate was 85% at 1 year and 67% at 2 years. Infection was the most common cause of death within 6 months of transplantation ( Pseudomonas cepacia pneumonia was the cause of death in two patients), and bronchitis obliterans was the most common cause of death after 6 months. Actuarial freedom form development of clinically significant bronchiolitis obliterans was 59% at 2 years. Results of pulmonary function tests improved substantially in survivors, with forced expiratory volume in 1 second averaging 78% predicted 2 years after transplantation. Double lung transplantation can be accomplished with acceptable morbidity and mortality in patients with cystic fibrosis. (J THORAC CARDIOVAS SURG 1995;109-:204-35

Towards a plurilingual habitus: engendering interlinguality in urban spaces

This article focuses on the potential of the multilingual city to create spaces in which monolingual hegemonies may be challenged, inclusive, intercultural values may be nurtured, and plurilingualism may be valorised. Following a contextualisation of linguistic diversity in theories of globalisation and superdiversity, discourses of deficit and power are addressed, arguing that the problematisation of multilingualism and pathologisation of plurilingualism reflect a monolingual habitus. Bringing about a shift towards a plurilingual habitus requires a Deep Approach, as it involves a critical revaluing of deep-seated dispositions. It suggests that the city offers spaces, which can engender interlinguality, a construct that includes interculturality, criticality and a commitment to creative and flexible use of other languages in shared, pluralistic spaces. It then proposes critical, participatory and ethnographic research in three multidimensional spaces: the urban school and a potential interlingual curriculum; networks, lobbying for inclusive policy and organising celebratory events in public spaces; and grass roots-level local spaces, some created by linguistic communities to exercise agency and maintain their languages and cultures, and some emerging as linguistically hybrid spaces for convivial encounter