The androgen receptor and signal-transduction pathways in hormone-refractory prostate cancer. Part 1: modifications to the androgen receptor

Prostate cancer is the second most common male malignancy in the western world an increasing incidence in an ageing population. Treatment of advanced prostate cancer relies on androgen deprivation. Although the majority of patients initially respond favourably to androgen deprivation therapy, the mean time to relapse is 12-18 months. Currently there are few treatments available for men who have developed resistance to hormone therapy, due to the lack of understanding of the molecular mechanisms underlying development of this disease. Recently, however, major advances have been made in understanding both androgen receptor (AR) dependent and independent pathways which promote development of hormone resistant prostate cancer. This review will focus on modifications to the AR and associated pathways. Molecular modifications to the androgen receptor itself, e.g. mutations and/or amplification, although involved in the development of hormone resistance cannot explain all cases. Phosphorylation of AR, via either Ras/MAP kinase or PI3K/Akt signal transduction pathways, have been shown to activate AR in both a ligand (androgen) dependent and independent fashion. During this review we will discuss the clinical evidence to support AR dependent pathways as mediators of hormone resistance

Further properties on the core partial order and other matrix partial orders

This paper carries further the study of core partial order initiated by Baksalary and Trenkler [Core inverse of matrices, Linear Multilinear Algebra. 2010;58:681-697]. We have extensively studied the core partial order, and some new characterizations are obtained in this paper. In addition, simple expressions for the already known characterizations of the minus, the star (and one-sided star), the sharp (and one-sided sharp) and the diamond partial orders are also obtained by using a Hartwig-Spindelbck decomposition.This author was partially supported by Ministry of Education of Spain [grant number DGI MTM2010-18228] and by Universidad Nacional de La Pampa, Argentina, Facultad de Ingenieria [grant number Resol. No 049/11].Malik, SB.; Rueda, LC.; Thome, N. (2014). Further properties on the core partial order and other matrix partial orders. Linear and Multilinear Algebra. 62(12):1629-1648. https://doi.org/10.1080/03081087.2013.839676S162916486212Mitra, S. K., & Bhimasankaram, P. (2010). MATRIX PARTIAL ORDERS, SHORTED OPERATORS AND APPLICATIONS. SERIES IN ALGEBRA. doi:10.1142/9789812838452Baksalary, J. K., & Hauke, J. (1990). A further algebraic version of Cochran’s theorem and matrix partial orderings. Linear Algebra and its Applications, 127, 157-169. doi:10.1016/0024-3795(90)90341-9Baksalary, O. M., & Trenkler, G. (2010). Core inverse of matrices. Linear and Multilinear Algebra, 58(6), 681-697. doi:10.1080/03081080902778222Baksalary, J. K., Baksalary, O. M., & Liu, X. (2003). Further properties of the star, left-star, right-star, and minus partial orderings. Linear Algebra and its Applications, 375, 83-94. doi:10.1016/s0024-3795(03)00609-8Groβ, J., Hauke, J., & Markiewicz, A. (1999). Partial orderings, preorderings, and the polar decomposition of matrices. Linear Algebra and its Applications, 289(1-3), 161-168. doi:10.1016/s0024-3795(98)10108-8Mosić, D., & Djordjević, D. S. (2012). Reverse order law for the group inverse in rings. Applied Mathematics and Computation, 219(5), 2526-2534. doi:10.1016/j.amc.2012.08.088Patrício, P., & Costa, A. (2009). On the Drazin index of regular elements. Open Mathematics, 7(2). doi:10.2478/s11533-009-0015-6Rakić, D. S., & Djordjević, D. S. (2012). Space pre-order and minus partial order for operators on Banach spaces. Aequationes mathematicae, 85(3), 429-448. doi:10.1007/s00010-012-0133-2Tošić, M., & Cvetković-Ilić, D. S. (2012). Invertibility of a linear combination of two matrices and partial orderings. Applied Mathematics and Computation, 218(9), 4651-4657. doi:10.1016/j.amc.2011.10.052Hartwig, R. E., & Spindelböck, K. (1983). Matrices for whichA∗andA†commute. Linear and Multilinear Algebra, 14(3), 241-256. doi:10.1080/03081088308817561Baksalary, O. M., Styan, G. P. H., & Trenkler, G. (2009). On a matrix decomposition of Hartwig and Spindelböck. Linear Algebra and its Applications, 430(10), 2798-2812. doi:10.1016/j.laa.2009.01.015Mielniczuk, J. (2011). Note on the core matrix partial ordering. Discussiones Mathematicae Probability and Statistics, 31(1-2), 71. doi:10.7151/dmps.1134Meyer, C. (2000). Matrix Analysis and Applied Linear Algebra. doi:10.1137/1.978089871951

Evaluation of the Swedish breeding program for cavalier King Charles spaniels

A breeding program with the aim of reducing the prevalence of mitral regurgitation (MR) caused by myxomatous mitral valve disease (MMVD) in Cavalier King Charles Spaniels (CKCS) is currently ongoing in Sweden. In this investigation 353 CKCS were selected as a sample of the population and 150 were examined by auscultation for heart murmurs when they reached the age of six years in 2007 and 2009. The aim with this investigation was to study the prevalence of heart murmurs in six-year-old CKCS and to estimate if prevalence has decreased since the breeding program was introduced 2001. The effect of the breeding program was evaluated by comparing the prevalence of heart murmurs in the two groups. In 2007, the prevalence of heart murmurs was 52% (50% for females and 54% for males) and in 2009, the prevalence was 55% (44% for females and 67% for males). No significant difference was found in the prevalence of heart murmurs between 2007 and 2009 (P = 0.8). For all six-year-old CKCS, the prevalence of heart murmur was 53% (females 46% and males 61%), which is higher than previous Swedish investigations

Measuring the effect of enhanced cleaning in a UK hospital : a prospective cross-over study

Increasing hospital-acquired infections have generated much attention over the last decade. There is evidence that hygienic cleaning has a role in the control of hospital-acquired infections. This study aimed to evaluate the potential impact of one additional cleaner by using microbiological standards based on aerobic colony counts and the presence of Staphylococcus aureus including meticillin-resistant S. aureus. We introduced an additional cleaner into two matched wards from Monday to Friday, with each ward receiving enhanced cleaning for six months in a cross-over design. Ten hand-touch sites on both wards were screened weekly using standardised methods and patients were monitored for meticillin-resistant S. aureus infection throughout the year-long study. Patient and environmental meticillin-resistant S. aureus isolates were characterised using molecular methods in order to investigate temporal and clonal relationships. Enhanced cleaning was associated with a 32.5% reduction in levels of microbial contamination at handtouch sites when wards received enhanced cleaning (P < 0.0001: 95% CI 20.2%, 42.9%). Near-patient sites (lockers, overbed tables and beds) were more frequently contaminated with meticillin-resistant S. aureus/S. aureus than sites further from the patient (P = 0.065). Genotyping identified indistinguishable strains from both handtouch sites and patients. There was a 26.6% reduction in new meticillin-resistant S. aureus infections on the wards receiving extra cleaning, despite higher meticillin-resistant S. aureus patient-days and bed occupancy rates during enhanced cleaning periods (P = 0.032: 95% CI 7.7%, 92.3%). Adjusting for meticillin-resistant S. aureus patient-days and based upon nine new meticillin-resistant S. aureus infections seen during routine cleaning, we expected 13 new infections during enhanced cleaning periods rather than the four that actually occurred. Clusters of new meticillin-resistant S. aureus infections were identified 2 to 4 weeks after the cleaner left both wards. Enhanced cleaning saved the hospital £30,000 to £70,000.Introducing one extra cleaner produced a measurable effect on the clinical environment, with apparent benefit to patients regarding meticillin-resistant S. aureus infection. Molecular epidemiological methods supported the possibility that patients acquired meticillin-resistant S. aureus from environmental sources. These findings suggest that additional research is warranted to further clarify the environmental, clinical and economic impact of enhanced hygienic cleaning as a component in the control of hospital-acquired infection

A weak group inverse for rectangular matrices

[EN] In this paper, we extend the notion of weak group inverse to rectangular matrices (called WweightedWGinverse) by using the weighted core EP inverse recently investigated. This new generalized inverse also generalizes the well-known weighted group inverse given by Cline and Greville. In addition, we give several representations of the W-weighted WG inverse, and derive some characterizations and properties.First author was partially supported by UNRC (Grant PPI 18/C472) and CONICET (Grant PIP 112-201501-00433CO). Third author was partially supported by Ministerio de Economia, Industria y Competitividad of Spain (Grants DGI MTM2013-43678-P and Red de Excelencia MTM2017-90682-REDT).Ferreyra, DE.; Orquera, V.; Thome, N. (2019). A weak group inverse for rectangular matrices. Revista de la Real Academia de Ciencias Exactas Físicas y Naturales Serie A Matemáticas. 113(4):3727-3740. https://doi.org/10.1007/s13398-019-00674-9S372737401134Ben-Israel, A., Greville, T.N.E.: Generalized Inverses: Theory and Applications, 2nd edn. Springer, New York (2003)Baksalary, O.M., Trenkler, G.: Core inverse of matrices. Linear Multilinear Algebra 58, 681–697 (2010)Baksalary, O.M., Trenkler, G.: On a generalized core inverse. Appl. Math. Comput. 236, 450–457 (2014)Bajodah, A.H.: Servo-constraint generalized inverse dynamics for robot manipulator control design. Int. J. Robot. Autom. 25, (2010). https://doi.org/10.2316/Journal.206.2016.1.206-3291Campbell, S.L., Meyer Jr., C.D.: Generalized Inverses of Linear transformations. SIAM, Philadelphia (2009)Cline, R.E., Greville, T.N.E.: A Drazin inverse for rectangular matrices. Linear Algebra Appl. 29, 53–62 (1980)Dajić, A., Koliha, J.J.: The weighted g-Drazin inverse for operators. J. Aust. Math. Soc. 2, 163–181 (2007)Doty, K.L., Melchiorri, C., Bonivento, C.: A theory of generalized inverses applied to robotics. Int. J. Rob. Res. 12, 1–19 (1993)Drazin, M.P.: Pseudo-inverses in associate rings and semirings. Am. Math. Mon. 65, 506–514 (1958)Ferreyra, D.E., Levis, F.E., Thome, N.: Revisiting of the core EP inverse and its extension to rectangular matrices. Quaest. Math. 41, 265–281 (2018)Ferreyra, D.E., Levis, F.E., Thome, N.: Maximal classes of matrices determining generalized inverses. Appl. Math. Comput. 333, 42–52 (2018)Gigola, S., Lebtahi, L., Thome, N.: The inverse eigenvalue problem for a Hermitian reflexive matrix and the optimization problem. J. Comput. Appl. Math. 291, 449–457 (2016)Hartwig, R.E.: The weighted $$*$$ ∗ -core-nilpotent decomposition. Linear Algebra Appl. 211, 101–111 (1994)Kirkland, S.J., Neumann, M.: Group inverses of M-matrices and their applications. Chapman and Hall/CRC, London (2013)Malik, S., Thome, N.: On a new generalized inverse for matrices of an arbitrary index. Appl. Math. Comput. 226, 575–580 (2014)Male $${{\check{\rm s}}}$$ s ˇ ević, B., Obradović, R., Banjac, B., Jovović, I., Makragić, M.: Application of polynomial texture mapping in process of digitalization of cultural heritage. arXiv:1312.6935 (2013). Accessed 14 June 2018Manjunatha Prasad, K., Mohana, K.S.: Core EP inverse. Linear Multilinear Algebra 62, 792–802 (2014)Mehdipour, M., Salemi, A.: On a new generalized inverse of matrices. Linear Multilinear Algebra 66, 1046–1053 (2018)Meng, L.S.: The DMP inverse for rectangular matrices. Filomat 31, 6015–6019 (2017)Mosić, D.: The CMP inverse for rectangular matrices. Aequaetiones Math. 92, 649–659 (2018)Penrose, R.: A generalized inverse for matrices. Proc. Cambrid. Philos. Soc. 51, 406–413 (1955)Soleimani, F., Stanimirović, P.S., Soleymani, F.: Some matrix iterations for computing generalized inverses and balancing chemical equations. Algorithms 8, 982–998 (2015)Xiao, G.Z., Shen, B.Z., Wu, C.K., Wong, C.S.: Some spectral techniques in coding theory. Discrete Math. 87, 181–186 (1991)Wang, H.: Core-EP decomposition and its applications. Linear Algebra Appl. 508, 289–300 (2016)Wang, H., Chen, J.: Weak group inverse. Open Math. 16, 1218–1232 (2018)Wei, Y.: A characterization for the $$W$$ W -weighted Drazin inverse and a Crammer rule for the $$W$$ W -weighted Drazin inverse solution. Appl. Math. Comput. 125, 303–310 (2002

Evidence for Centromere Drive in the Holocentric Chromosomes of Caenorhabditis

In monocentric organisms with asymmetric meiosis, the kinetochore proteins, such as CENH3 and CENP-C, evolve adaptively to counterbalance the deleterious effects of centromere drive, which is caused by the expansion of centromeric satellite repeats. The selection regimes that act on CENH3 and CENP-C genes have not been analyzed in organisms with holocentric chromosomes, although holocentrism is speculated to have evolved to suppress centromere drive. We tested both CENH3 and CENP-C for positive selection in several species of the holocentric genus Caenorhabditis using the maximum likelihood approach and sliding-window analysis. Although CENP-C did not show any signs of positive selection, positive selection has been detected in the case of CENH3. These results support the hypothesis that centromere drive occurs in Nematoda, at least in the telokinetic meiosis of Caenorhabditis

Use of complementary and alternative medicine by cancer patients at the University of Nigeria Teaching Hospital, Enugu, Nigeria

<p>Abstract</p> <p>Background</p> <p>The use of Complementary and Alternative Medicine (CAM) by cancer patients is very common and varies between populations. The referenced English literature has no local study from Africa on this subject. This study was conducted to define the prevalence, pattern of use, and factors influencing the use of CAM by cancer patients at the University of Nigeria Teaching Hospital Enugu (UNTH-E), Nigeria</p> <p>Method</p> <p>Face-to-face interviews using semi-structured questionnaire were used to determine the use of CAM by cancer patients. All consenting cancer patients were interviewed as they presented at the core surgical units of the UNTH- E, from June 2003 to September 2005.</p> <p>Results</p> <p>160 patients were interviewed; 68 (42.5%) were males and 94 (57.5%) were females. Ages ranged from 13–86 years. Breast, urogenital system, gastrointestinal system, and soft tissue cancers predominated. One hundred and four patients (65.0%) have used CAM at some time during their current cancer illness; 56 (35.0%) patients have not used any form of CAM. There were more females than males among the non-CAM users. The use of CAM was not affected by age, marital status, level of education, religious affiliation, or socioeconomic status. The most frequently used CAMs were herbs (51.9%), faith/prayer healing (49.4%), aloe vera (23.1%), Forever Living Products (16.3%), medicinal tea (14.4%), and Blackstone (12.5%). Over 23% of those who used CAM were satisfied, but 68.3% were disappointed. Most users (67.3%) did not see any benefit from the CAM, but 25% could describe some specific benefits. More than 21% of users reported various unwanted effects. While 86.5% of CAM users will use orthodox medicine instead of CAM in the future, 9.6% will use the two together to help each other. Most users (79.8%) will not repeat CAM or recommend its use for cancer. The majority of patients (55.8%) did not mention their use of CAM to their doctors – mostly because the doctor did not ask.</p> <p>Conclusion</p> <p>CAM use is common among cancer patients in Nigeria. Most users do not obtain the expected benefits, and adverse events are not uncommon. Every clinician in the field of oncology should ask his/her patients about the use of CAM; this knowledge will enable them to better counsel the patients.</p

Validity and reliability of the semi-quantitative self-report Home Food Availability Inventory Checklist (HFAI-C) in White and South Asian populations.

Despite interest in the importance of the home food environment and its potential influence on children's diets and social norms, there remain few self-report checklist methods that have been validated against the gold standard of researcher-conducted inventories. This study aimed to assess the criterion validity and reliability of the 'Home Food Availability Inventory Checklist' (HFAI-C), a 39-item checklist including categories of fruit, vegetables, snacks and drinks.The HFAI-C was completed by 97 participants of White and Pakistani origin in the UK. Validity was determined by comparing participant-reported HFAI-C responses to data from researcher observations of home food availability using PABAK and weighted kappa statistics. The validity of measuring the amount of items (in addition to presence/absence) available was also determined. Test-retest reliability compared repeated administrations of the HFAI-C using intra-class correlation coefficients.Validity and reliability was fair to moderate overall. For validity, the average category-level PABAK ranged from 0.31 (95 % CI: 0.25, 0.37) for vegetables to 0.44 (95 % CI: 0.40, 0.49) for fruits. Assessment of the presence/absence of items demonstrated higher validity compared to quantity measurements. Reliability was increased when the HFAI-C was repeated close to the time of the first administration. For example, ICCs for reliability of the measurement of fruits were 0.52 (95 %CI: 0.47, 0.56) if re-administered within 5 months, 0.58 (95 % CI: 0.51, 0.64) within 30 days and 0.97 (95 %CI: 0.94, 1.00) if re-administered on the same day.Overall, the HFAI-C demonstrated fair to moderate validity and reliability in a population of White and South Asian participants. This evaluation is consistent with previous work on other checklists in less diverse, more affluent populations. Our research supports the use of the HFAI-C as a useful, albeit imperfect, representation of researcher-conducted inventories. The feasibility of collecting information using the HFAI-C in large, multi-ethnic samples can facilitate examination of home food availability in relation to exposures such as ethnicity and outcomes including behavioural, social and health outcomes. Future work using the HFAI-C could provide important insights into a modifiable influence with potential to impact health

Intravenous dosing of tocilizumab in patients younger than two years of age with systemic juvenile idiopathic arthritis

The anti-interleukin-6 receptor-alpha antibody tocilizumab was approved for intravenous (IV) injection in the treatment of patients with systemic juvenile idiopathic arthritis (sJIA) aged 2 to 17 years based on results of a randomized controlled phase 3 trial. Tocilizumab treatment in systemic juvenile idiopathic arthritis (sJIA) patients younger than 2 was investigated in this open-label phase 1 trial and compared with data from the previous trial in patients aged 2 to 17 years.Patients younger than 2 received open-label tocilizumab 12 mg/kg IV every 2 weeks (Q2W) during a 12-week main evaluation period and an optional extension period. The primary end point was comparability of pharmacokinetics during the main evaluation period to that of the previous trial (in patients aged 2-17 years), and the secondary end point was safety; pharmacodynamics and efficacy end points were exploratory. Descriptive comparisons for pharmacokinetics, pharmacodynamics, safety, and efficacy were made with sJIA patients aged 2 to 17 years weighing < 30 kg (n = 38) who received tocilizumab 12 mg/kg IV Q2W in the previous trial (control group).Eleven patients (mean age, 1.3 years) received tocilizumab during the main evaluation period. The primary end point was met: tocilizumab exposures for patients younger than 2 were within the range of the control group (mean [±SD] μg/mL concentration at the end-of-dosing interval [Cmin]: 39.8 [±14.3] vs 57.5 [±23.3]; maximum concentration [Cmax] postdose: 288 [±40.4] vs 245 [±57.2]). At week 12, pharmacodynamic measures were similar between patients younger than 2 and the control group; mean change from baseline in Juvenile Arthritis Disease Activity Score-71 was - 17.4 in patients younger than 2 and - 28.8 in the control group; rash was reported by 14.3 and 13.5% of patients, respectively. Safety was comparable except for the incidence of serious hypersensitivity reactions (27.3% in patients younger than 2 vs 2.6% in the control group).Tocilizumab 12 mg/kg IV Q2W provided pharmacokinetics, pharmacodynamics, and efficacy in sJIA patients younger than 2 comparable to those in patients aged 2 to 17 years. Safety was comparable except for a higher incidence of serious hypersensitivity events in patients younger than 2 years.Juvenile idiopathic arthritis.ClinicalTrials.gov, NCT01455701 . Registered, October 20, 2011, Date of enrollment of first participant: October 26, 2012