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Abstract Drug-free macromolecular therapeutics (DFMT) is a new paradigm for the treatment of B cell malignancies. Apoptosis is initiated by the biorecognition of complementary oligonucleotide motifs at the cell surface resulting in crosslinking of CD20 receptors. DMFT is composed from two nanoconjugates: 1) bispecific engager, Fab'-MORF1 (anti-CD20 Fab' fragment conjugated with morpholino oligonucleotide), and 2) a crosslinking (effector) component P-(MORF2) X (N -(2-hydroxypropyl)methacrylamide (HPMA) copolymer grafted with multiple copies of complementary morpholino oligonucleotide). We evaluated this concept in 44 samples isolated from patients diagnosed with various subtypes of B cell malignancies. Apoptosis was observed in 65.9% of the samples tested. Pretreatment of cells with gemcitabine (GEM) or polymer-gemcitabine conjugate (2P-GEM) enhanced CD20 expression levels thus increasing apoptosis induced by DFMT. These positive results demonstrated that DFMT has remarkable therapeutic potential in various subtypes of B cell malignancies. Graphical Abstract Drug-free macromolecular therapeutics (DFMT) is a new paradigm for the treatment of B cell malignancies. Apoptosis is initiated by crosslinking of CD20 receptors triggered by the biorecognition of complementary oligonucleotide motifs at the cell surface. The therapeutic efficacy of DFMT on 44 primary patient samples with various B-cell malignancies has been evaluated. Pretreatment of cells with gemcitabine or polymer-gemcitabine conjugate enhanced CD20 expression and increased levels of apoptosis. The results indicate that DFMT has significant translational potential. Unlabelled Image [ABSTRACT FROM AUTHOR]

Objectives: To investigate changes in the patient population and treatment case-mix within an expanded primary care dental training facility in Southern England. Study design: Cross-sectional analysis of patient management system data. Method: Electronic data for patients with a closed/completed treatment plan in the 12- month period prior to, and following, dental service expansion were extracted for analysis (n = 4343). Descriptive analysis involved age, sex, payment status, deprivation status and treatment activity. Logistic regression was used to model the likelihood of treatment involving laboratory constructed devices (crowns, bridges, dentures), in relation to demography and deprivation in each time period. Results: The volume of patients using the service increased by 48.3% (1749 cf 2594). The average age increased from 31.97 (95%CI: 30.8, 32.5) to 36.4 years (95%CI: 35.6, 37.1); greatest increase was in the over 75 years age-group (96%). The patient base became less deprived: patients exempt from payment reduced from 43.2% (n = 755) to 28.6% (n = 741) (P = 0.001) and the mean population deprivation score (IMD) reduced from 24.5 (95%CI: 23.8, 25.2) to 22.3 (95%CI: 21.7, 22.8). The volume and proportion of care involving laboratory constructed devices increased from 8.3% (n = 145) to 15.8% (n = 411) whilst assessments without interventive care decreased (34.5%-26.3%). On a logistic regression, the odds of having treatment involving laboratory constructed devices, increased with increasing age in both time periods 7% (95% CI: 1.06-1.08) and 6% (95% CI: 1.05-1.07) respectively. Furthermore, the odds increased by 38% OR: 1.38 (95% CI: 1.01-1.89) in period 2, for white patients. After adjusting for these effects, the odds of having care that involved laboratory constructed devices were less in period 2 than period 1 (100% cf 43%) for those who were technically exempt from payment (OR = 2.0; 95% CI 1.34 to 2.90 cf, OR = 1.43; 95% CI 1.13-1.81). Conclusion: The patient population altered in relation to age and socio-economic status. The expanded service had greater uptake by older people while users were less likely to be deprived. The expanded service, free at the point of delivery, attracted a higher proportion of patients who would normally have to pay health service charges. The service also showed an increase in treatment case-mix that involved laboratory constructed dental devices. [ABSTRACT FROM AUTHOR]

Two 1− levels at 5.35(10) and 6.85(5) MeV were observed for the first time in 20O. The strong direct excitation and subsequent γ-ray decay of these states in virtual photon scattering at 100 MeV/nucleon, along with B(Eλ) predictions for 20O states in this energy region, established their dipole character. The extracted B(E1)↑ values of ≃0.062(16) e2 fm2 and ≃0.035(9) e2 fm2 for the 5.35 and 6.85 MeV states, respectively, are significantly larger than shell model calculations predict. Such large dipole strengths are not observed for low-lying 1− states in 18O, indicating a shift of dipole strength towards lower energies as one approaches the neutron drip-line. [Copyright &y& Elsevier]