The effect of mirabegron on patient-related outcomes in patients with overactive bladder: the results of post hoc correlation and responder analyses using pooled data from three randomized Phase III trials

Purpose To understand how improvements in the symptoms of overactive bladder (OAB) seen with the b3-adrenoceptor agonist mirabegron 50 mg, correlate with patient experience as measured by validated and standard patient-reported outcomes (PROs), and to identify whether there is overall directional consistency in the responsiveness of PROs to treatment effect. Methods In a post hoc analysis of pooled data from three randomized, double-blind, placebo-controlled, 12-week Phase III trials of mirabegron 50 mg once daily, responder rates for incontinence frequency (C50 % reduction in incontinence episodes/24 h from baseline to final visit), micturition frequency (B8 micturitions/24 h at final visit), and PROs [minimally important differences in patient perception of bladder condition (PPBC) and subsets of the overactive bladder questionnaire (OAB-q) measuring total health-related quality of life (HRQoL), and symptom bother] were evaluated individually and in combination. Results Mirabegron 50 mg demonstrated greater improvement from baseline to final visit than placebo for each of the responder analyses, whether for individual objective and subjective outcomes or combinations thereof. These improvements versus placebo were statistically significant for all double and triple responder analyses and for all single responder analyses except PPBC. PRO measurements showed directional consistency and significant correlations, and there were also significant correlations between objective and subjective measures of efficacy. Conclusions The improvements in objective measures seen with mirabegron 50 mg translate into a meaningful clinical benefit as evident by the directional consistency seen in HRQoL measures of benefit

Mejora de un suelo degradado por exceso de sal para su uso en cultivos gracias al tratamiento con plantas.

Motivación: la producción de alimentos es limitada por diversos factores siendo la salinización del suelo uno de los principales debido a que disminuye la capacidad de producción de los campos agrícolas. Diversos estudios han demostrado que casi la mitad de las zonas agrícolas bajo riego, principalmente de zonas áridas y semiáridas, son afectadas por la salinización del suelo. Muchas de estas áreas son zonas rurales de escaso desarrollo económico y dependientes en gran medida de trabajo en el campo. Un nuevo camino para la recuperación de éstas zonas contaminadas es la fitodesalinización, que es la eliminación del exceso de sales de un suelo por medio de plantas, que son capaces de captarla del suelo y retenerla en su interior, permitiendo que la concentración de sal de dicho suelo disminuya recuperándolos. La fitodesalinización es un proceso rentable, sostenible, no invasivo, alternativo o complementario a otros métodos para solucionar el problema de estos suelos degradados. Arthrocnemum macrostachyum es una especie vegetal de marisma que se utiliza en el proceso de fitodesalinización de este trabajo por ser una planta halófita, es decir, que depende de la sal para tener un buen desarrollo.Métodos: Las plántulas de Arthrocnemum crecieron en solución Hoagland hasta alcanzar el tamaño adecaudo (5 cm). Se plantaron en suelos con un problema de salinidad durante un mes. Tras el tratamiento se usó el suelo problema para comprobar que germinaban trigo y centeno. Tanto el material vegetal como suelo fueron analizados cabo mediante la técnica de espectrometría de masas.Resultados: tras el tratamiento durante un mes con A. macrostachyum se obtuvieron resultados muy interesantes en el campo de la restauración de suelos para el uso agrícola. Así el suelo que sufría problemas con el exceso de sal, tras ser tratado con A. macrostachyum se consiguió que se rebajase casi un 50% la cantidad de sales disueltas en el suelo. Hecho que se ratificó al conseguir que dos cultivos de interés agrícola como el trigo y  la cebada, que no germinaban en el suelo salinizado volviesen a hacerlo, aproximadamente una media del 40% respecto a un suelo control. Además se comprobó que no sólo germinaban sino que las plantas consiguieron desarrollarse durante un mes sin problemas.Conclusiones: la especie Arthrocnemum macrostachyum puede ser muy útil en la restauración de suelos degradados por la presencia de sales, y por tanto en la recuperación de zonas para su uso agrícola

The Use of Case Study Competitions to Prepare Students for the World of Work

As we continue into the new millennium, it is imperative that educational institutions equip graduates with the knowledge and skills that are increasingly needed and valued by business and industry. In this article, the authors argue that the case study approach and, specifically, case study competitions constitute an ideal pedagogical strategy for achieving this objective in an effective and efficient manner, with resulting benefits for both students and employers

European and Asian contribution to the genetic diversity of mainland South American chickens

Chickens (Gallus gallus domesticus) from the Americas have long been recognized as descendants of European chickens, transported by early Europeans since the fifteenth century. However, in recent years, a possible pre-Columbian introduction of chickens to South America by Polynesian seafarers has also been suggested. Here, we characterize the mitochondrial control region genetic diversity of modern chicken populations from South America and compare this to a worldwide dataset in order to investigate the potential maternal genetic origin of modern-day chicken populations in South America. The genetic analysis of newly generated chicken mitochondrial control region sequences from South America showed that the majority of chickens from the continent belong to mitochondrial haplogroup E. The rest belongs to haplogroups A, B and C, albeit at very low levels. Haplogroup D, a ubiquitous mitochondrial lineage in Island Southeast Asia and on Pacific Islands is not observed in continental South America. Modern-day mainland South American chickens are, therefore, closely allied with European and Asian chickens. Furthermore, we find high levels of genetic contributions from South Asian chickens to those in Europe and South America. Our findings demonstrate that modern-day genetic diversity of mainland South American chickens appear to have clear European and Asian contributions, and less so from Island Southeast Asia and the Pacific Islands. Furthermore, there is also some indication that South Asia has more genetic contribution to European chickens than any other Asian chicken populations.Michael B. Herrera, Spiridoula Kraitsek, Jose A. Alcalde, Daniel Quiroz .... Vicki Thomson ... Jeremy J. Austin ... et al

The 3-3-1 model with S_4 flavor symmetry

We construct a 3-3-1 model based on family symmetry S_4 responsible for the neutrino and quark masses. The tribimaximal neutrino mixing and the diagonal quark mixing have been obtained. The new lepton charge \mathcal{L} related to the ordinary lepton charge L and a SU(3) charge by L=2/\sqrt{3} T_8+\mathcal{L} and the lepton parity P_l=(-)^L known as a residual symmetry of L have been introduced which provide insights in this kind of model. The expected vacuum alignments resulting in potential minimization can origin from appropriate violation terms of S_4 and \mathcal{L}. The smallness of seesaw contributions can be explained from the existence of such terms too. If P_l is not broken by the vacuum values of the scalar fields, there is no mixing between the exotic and the ordinary quarks at the tree level.Comment: 20 pages, revised versio

Experimental Tests of Factorization in Charmless Non-Leptonic Two-Body B Decays

Using a theoretical framework based on the next-to-leading order QCD-improved effective Hamiltonian and a factorization Ansatz for the hadronic matrix elements of the four-quark operators, we reassess branching fractions in two-body non-leptonic decays $B \to PP, PV, VV$, involving the lowest lying light pseudoscalar $(P)$ and vector $(V)$ mesons in the standard model. Using the sensitivity of the decay rates on the effective number of colors, $N_c$, as a criterion of theoretical predictivity, we classify all the current-current (tree) and penguin transitions in five different classes. The recently measured charmless two-body $B \to PP$ decays $(B^+ \to K^+ \eta^\prime, B^0 \to K^0 \eta^\prime, B^0 \to K^+\pi^-, B^+ \to \pi^+ K^0$ and charge conjugates) are dominated by the $N_c$-stable QCD penguins (class-IV transitions) and their estimates are consistent with data. The measured charmless $B \to PV$ $(B^+ \to \omega K^+, ~B^+ \to \omega h^+)$ and $B\to VV$ transition $(B \to \phi K^*)$, on the other hand, belong to the penguin (class-V) and tree (class-III) transitions. The class-V penguin transitions are in general more difficult to predict. We propose a number of tests of the factorization framework in terms of the ratios of branching ratios for some selected $B \to h_1 h_2$ decays involving light hadrons $h_1$ and $h_2$, which depend only moderately on the form factors. We also propose a set of measurements to determine the effective coefficients of the current-current and QCD penguin operators. The potential impact of $B \to h_1 h_2$ decays on the CKM phenomenology is emphasized by analyzing a number of decay rates in the factorization framework.Comment: 64 pages (LaTex) including 13 figures, requires epsfig.sty; submitted to Phys. Rev.

Effect of copulation on potentially precancerous prostate lesions, serum testosterone and prolactin levels in rats

The prostate is an exocrine reproductive gland that participates in ejaculation and it is prone to diseases, including cancer. Aim: In the present study, we assessed the long­term effects of copulation on the development of precancerous lesions in rats, and compared them with testosterone­induced prostatic lesions. Materials and Methods: One group of Wistar males was given 10 copulatory sessions to one ejaculation with ovariectomized, hormone­primed females. Sessions occurred twice per week for a total of ten trials. A second group was exposed to females during the same trials, but physical contact was prevented. In addition, each group received a subcutaneous implant in the back either filled with testosterone propionate (T, 100 mg/kg) or empty. This resulted in four subgroups: 1) Control + No sex, 2) Control + Sex, 3) T + No sex and 4) T + Sex. Two days after the 10th trial all the males were sacrificed for prostate histo logy (H&E) and hormone analysis (testosterone and prolactin). Results: Males from the group Control + No sex expressed normal histo logy. However, those in the groups Control + Sex and T + No sex expressed metaplasia and dysplasia in both the dorsolateral and ventral portions of the prostate, respectively. Interestingly, males from the group T + Sex expressed dysplasia in the dorsolateral prostate only, but not in the ventral prostate. Conclusions: These results indicate that constant copulation may facilitate the development of prostatic lesions in males with normal levels of testosterone. However, copulation induces less lesions in the ventral prostate of males treated with testosterone

Revista de Vertebrados de la Estación Biológica de Doñaña

Alimentación de la boga del Guadiana (Chondrostoma polylepis wi/lkommi, Stein. 1866) en la interfase río-embalse de Sierra Boyera (Córdoba. España)Predación del búho real (Bubo bubo) sobre la perdiz roja (Alectoris rufa): selección de edad y sexoAlimentación de la nutria (Lutra lufra L, 1758)en el Nordeste de la Península IbéricaDatos sobre la distribución espacialde micromamíferos en el Parque Nacionalde DoñanaGuía para el reconocimiento microscópico de los pelos de los mamíferos de la Patagonia.Sobre la distribución geográfica de Anaecypris hispanica (STEINDACHNER, 1866) (OSTEICHTHYES, CYPRINIDAE)Cronología del periodo reproductor de Rana temporaria L. en La Coruña (NW de España).Un nuevo caso de melanismo en Natrix natrix (LINNAEUS 1758) procedente de Fuente Dé (Santander)Nuevas citas de anfibios y reptiles para el SE de la Península Ibérica.Datos sobre la dieta invernal del Búho chico (Asia atus) en la provinvia de LeónLa Distribucióndel Mara (Dolichotis patagonum) según criterios ecológicos e históricosSolapamiento entre la dieta de la cabra montés (Capra pyrenaica) y la del muflón (Ovis musimon)Nota sobre dietas de carnívoros e índices de abundancia en una Reserva de caza del norte de España.Discriminación osteométrica en el géneroTalpa (LINNEO, 1758), en el norte IbéricoObservaciones sobre el comportamiento depredativo de algunos colúbridos Ibéricos en estado salvajePeer reviewe

A precision medicine test predicts clinical response after idarubicin and cytarabine induction therapy in AML patients

Complete remission (CR) after induction therapy is the first treatment goal in acute myeloid leukemia (AML) patients and has prognostic impact. Our purpose is to determine the correlation between the observed CR/CRi rate after idarubicin (IDA) and cytarabine (CYT) 3 + 7 induction and the leukemic chemosensitivity measured by an ex vivo test of drug activity. Bone marrow samples from adult patients with newly diagnosed AML were included in this study. Whole bone marrow samples were incubated for 48 h in well plates containing IDA, CYT, or their combination. Pharmacological response parameters were estimated using population pharmacodynamic models. Patients attaining a CR/CRi with up to two induction cycles of 3 + 7 were classified as responders and the remaining as resistant. A total of 123 patients fulfilled the inclusion criteria and were evaluable for correlation analyses. The strongest clinical predictors were the area under the curve of the concentration response curves of CYT and IDA. The overall accuracy achieved using MaxSpSe criteria to define positivity was 81%, predicting better responder (93%) than non-responder patients (60%). The ex vivo test provides better yet similar information than cytogenetics, but can be provided before treatment representing a valuable in-time addition. After validation in an external cohort, this novel ex vivo test could be useful to select AML patients for 3 + 7 regimen vs. alternative schedules

Genetic insights into the introduction history of black rats into the eastern Indian Ocean

Islands can be powerful demonstrations of how destructive invasive species can be on endemic faunas and insular ecologies. Oceanic islands in the eastern Indian Ocean have suffered dramatically from the impact of one of the world’s most destructive invasive species, the black rat, causing the loss of endemic terrestrial mammals and ongoing threats to ground-nesting birds. We use molecular genetic methods on both ancient and modern samples to establish the origins and minimum invasion frequencies of black rats on Christmas Island and the Cocos-Keeling Islands. We find that each island group had multiple incursions of black rats from diverse geographic and phylogenetic sources. Furthermore, contemporary black rat populations on these islands are highly admixed to the point of potentially obscuring their geographic sources. These hybridisation events between black rat taxa also pose potential dangers to human populations on the islands from novel disease risks. Threats of ongoing introductions from yet additional geographic sources is highlighted by genetic identifications of black rats found on ships, which provides insight into how recent ship-borne human smuggling activity to Christmas Island can negatively impact its endemic species.Vicki A. Thomson, Andrew S. Wiewel, Russell Palmer, Neil Hamilton, Dave Algar, Caitlyn Pink, Harriet Mills, Ken P. Aplin, Geoffrey Clark, Atholl Anderson, Michael B. Herrera, Steven Myers, Terry Bertozzi, Philip J. Piper, Hitoshi Suzuki, and Steve Donnella