In this phase 2 study, investigators evaluated the potential of two vaccines (H4:IC31 and BCG) to prevent the acquisition of tuberculosis infection and the subsequent development of sustained disease.
Background
The aim of this study was to quantify the impact of initial tumor volume (TV) on radiotherapy (RT) outcome in patients with T2 glottic cancer.
Materials and methods
Initial TV was ...calculated for 115 consecutive patients with T2 glottic cancer who had been treated with definitive RT alone at a single institution.
Results
The results showed strong correlations of TV with 3-year local tumor control (LTC) and disease-free survival (DFS). For TV ≤ 0.7 cm
3
, 3-year LTC was 83 %; for TV 0.7–3.6 cm
3
this was 70 % and for TV 3.6–17 cm
3
44 %. Analysis of total dose vs. initial TV showed that larger T2 glottic tumors with a TV of around 5 cm
3
(2–2.5 cm in diameter with 10
10
cancer cells) need an extra 6.5 Gy to achieve similar 3-year LTC rates as for small tumors with a TV of 0.5 cm
3
(~ 1 cm in diameter with 10
9
cancer cells).
Conclusion
Although classification of tumors according to TV cannot replace TNM staging in daily practice, it could represent a valuable numerical supplement for planning the optimal dose fractionation scheme for individual patients.
•Design and conduct of a complex measurement campaign in sea conditions.•Measured data conditioning and transferring into multi-dipole model space.•Multi-dipole model synthesis: model structure and ...parameters identification.•Lasso and Ridge regularisation for model overfitting protection.•The leave-one-out concept application for the purpose of model verification.
The paper presents the partial work done within the framework of the EDA Siramis II project focused on magnetic signature reproduction of ships. Reproduction is understood here as the ability to determine the magnetic anomaly of the local Earth magnetic field in any direction and at any measurement depth due to the presence of the analysed object. The B-91 type hydrographic ship Zodiak was selected as the real case study. The work was divided into two main stages: the development of a measurement campaign taking into account physical measurements, and the development of a mathematical model on the basis of the measured values. The measurement campaign included: preparation of the measuring range, selection of equipment for the measurement of magnetic quantities and geographical location, and data recording while the ship passes the measuring point according to the designated course. As a result of the measurement campaign, magnetic flux density components were collected in different positions in relation to the measuring instruments and the ship's heading. A multi-dipole model was used to build the mathematical model in accordance with the idea of inverse modelling. The effectiveness of this model was previously checked on synthetic data of virtual ships generated using the finite element method. Experiments performed with simulation models were helpful in determining the structure of the model, the nature of the data, and the number of samples needed to properly determine the multi-dipole model parameters. The parameters were determined using the nonlinear least squares method according to the idea of data fitting. The classical Ridge and Lasso regularization methods were applied to prevent the developed multi-dipole model from overfitting. Other regularization methods based on GPS accuracy marks and modification of fitness functions were also considered. The verification was done using real data: the data generated by the model was compared with patterns recorded during the Zodiak measurement campaign. High degree of conformity of the shape of characteristics was obtained. Moreover, the correctness of model execution was confirmed by low values of quantitative indices such as RMSE and MAE representing modelling errors. The methodology presented in the paper is quite universal and can be used to determine the signatures of other ferromagnetic objects.
In addition to helping better understand how the human brain works, the brain-computer interface neuroscience paradigm allows researchers to develop a new class of bioengineering control devices and ...robots, offering promise for rehabilitation and other medical applications as well as exploring possibilities for advanced human-computer interfaces.
Targeting altered cancer cell metabolism with the glycolysis inhibitor, 2-deoxyglucose (2DG), is a viable therapeutic strategy, but the effects of 2DG on lymphoma cells and the mechanism of action ...are unknown. Five T-cell lymphoma lines and two B-cell lymphoma lines were shown to be highly sensitive to 2DG. Examination of the cell death pathway demonstrated pro-apoptotic protein Bax 'activation' and caspase cleavage in 2DG-treated cells. However, Q-VD-OPh, a potent inhibitor of caspase activity provided minimal protection from death. In contrast, overexpressing the anti-apoptotic protein Bcl-2 dramatically enhanced the survival of 2DG-treated cells that was negated by a Bcl-2 antagonist. BH3-only members, Bim and Bmf, were upregulated by 2DG, and shRNAs targeting Bim protected from 2DG toxicity demonstrating that Bim is a critical mediator of 2DG toxicity. 2DG also induced GADD153/CHOP expression, a marker of endoplasmic reticulum (ER) stress and a known activator of Bim. Mannose, a reagent known to alleviate ER stress, transiently protected from 2DG-induced cell death. Examination of the effects of 2DG on energy metabolism showed a drop in ATP levels by 30 min that was not affected by either Bcl-2 or mannose. These results demonstrate that ER stress appears to be rate limiting in 2DG-induced cell death in lymphoma cells, and this cell killing is regulated by the Bcl-2 family of proteins. Bcl-2 inhibition combined with 2DG may be an effective therapeutic strategy for lymphoma.
Tuberculosis (TB) remains the leading cause of infectious disease-related death. Recently, a trial of BCG revaccination and vaccination with H4:IC31, a recombinant protein vaccine, in South African ...adolescents (Aeras C-040-404) showed efficacy in preventing sustained QuantiFERON (QFT) conversion, a proxy for Mycobacterium tuberculosis (M.tb) infection. A phase 1b trial of 84 South African adolescents was conducted, concurrent with Aeras C-040-404, to assess the safety and immunogenicity of H4:IC31, H56:IC31 and BCG revaccination, and to identify and optimize immune assays for identification of candidate correlates of protection in efficacy trials.
Two doses of H4:IC31 and H56:IC31 vaccines were administered intramuscularly (IM) 56 days apart, and a single dose of BCG (2–8 × 105 CFU) was administered intradermally (ID). T-cell and antibody responses were measured using intracellular cytokine staining and binding antibody assays, respectively. Binding antibodies and CD4+/CD8+ T-cell responses to H4- and H56-matched antigens were measured in samples from all participants. The study was designed to characterize safety and immunogenicity and was not powered for group comparisons. (Clinicaltrials.gov NCT02378207).
In total, 481 adolescents (mean age 13·9 years) were screened; 84 were enrolled (54% female). The vaccines were generally safe and well-tolerated, with no reported severe adverse events related to the study vaccines. H4:IC31 and H56:IC31 elicited CD4+ T cells recognizing vaccine-matched antigens and H4- and H56-specific IgG binding antibodies. The highest vaccine-induced CD4+ T-cell response rates were for those recognizing Ag85B in the H4:IC31 and H56:IC31 vaccinated groups. BCG revaccination elicited robust, polyfunctional BCG-specific CD4+ T cells, with no increase in H4- or H56-specific IgG binding antibodies. There were few antigen-specific CD8+ T-cell responses detected in any group.
BCG revaccination administered as a single dose ID and both H4:IC31 and H56:IC31 administered as 2 doses IM had acceptable safety profiles in healthy, QFT-negative, previously BCG-vaccinated adolescents. Characterization of the assays and the immunogenicity of these vaccines may help to identify valuable markers of protection for upcoming immune correlates analyses of C-040-404 and future TB vaccine efficacy trials.
NIAID and Aeras.
Congenital Radioulnar Synostosis Rutkowski, Paul T; Samora, Julie Balch
Journal of the American Academy of Orthopaedic Surgeons,
07/2021, Letnik:
29, Številka:
13
Journal Article
Recenzirano
Congenital radioulnar synostosis is a rare condition resulting in fusion of the proximal portions of the radius and ulna. Patients commonly present in early childhood with functional deficits because ...of limited forearm rotation and fixed positioning of the forearm. Compensatory motion and hypermobility are frequently observed at the wrist and shoulder, which may predispose these joints to overuse injury. Plain radiographs are used for diagnosis and classification. The most commonly used classification does not aid in treatment decisions. Limited high-level evidence exists to guide management because the literature primarily consists of case reports and case series. Nonsurgical management is often used, yet surgical management is most commonly reported in the literature. Resection of the synostosis has been shown to have high-complication rates and lead to subpar outcomes. Currently, surgical management most commonly involves one or more derotational osteotomies.
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