Superiority of deformable image co-registration in the integration of diagnostic positron emission tomography-computed tomography to the radiotherapy treatment planning pathway for oesophageal carcinoma

Aims To investigate the use of image co-registration in incorporating diagnostic positron emission tomography-computed tomography (PET-CT) directly into the radiotherapy treatment planning pathway, and to describe the pattern of local recurrence relative to the PET-avid volume. Materials and methods Fourteen patients were retrospectively identified, six of whom had local recurrence. The accuracy of deformable image registration (DIR) and rigid registration of the diagnostic PET-CT and recurrence CT, to the planning CT, were quantitatively assessed by comparing co-registration of oesophagus, trachea and aorta contours. DIR was used to examine the correlation between PET-avid volumes, dosimetry and site of recurrence. Results Positional metrics including the dice similarity coefficient (DSC) and conformity index (CI), showed DIR to be superior to rigid registration in the co-registration of diagnostic and recurrence imaging to the planning CT. For diagnostic PET-CT, DIR was superior to rigid registration in the transfer of oesophagus (DSC = 0.75 versus 0.65, P < 0.009 and CI = 0.59 versus 0.48, P < 0.003), trachea (DSC = 0.88 versus 0.65, P < 0.004 and CI = 0.78 versus 0.51, P < 0.0001) and aorta structures (DSC = 0.93 versus 0.86, P < 0.006 and CI = 0.86 versus 0.76, P < 0.006). For recurrence imaging, DIR was superior to rigid registration in the transfer of trachea (DSC = 0.91 versus 0.66, P < 0.03 and CI = 0.83 versus 0.51, P < 0.02) and oesophagus structures (DSC = 0.74 versus 0.51, P < 0.004 and CI = 0.61 versus 0.37, P < 0.006) with a non-significant trend for the aorta (DSC = 0.91 versus 0.75, P < 0.08 and CI = 0.83 versus 0.63, P < 0.06) structure. A mean inclusivity index of 0.93 (range 0.79–1) showed that the relapse volume was within the planning target volume (PTVPET-CT); all relapses occurred within the high dose region. Conclusion DIR is superior to rigid registration in the co-registration of PET-CT and recurrence CT to the planning CT, and can be considered in the direct integration of PET-CT to the treatment planning process. Local recurrences occur within the PTVPET-CT, suggesting that this is a suitable target for dose-escalation strategies

Fast-transient Searches in Real Time with ZTFReST: Identification of Three Optically-discovered Gamma-ray Burst Afterglows and New Constraints on the Kilonova Rate

While optical surveys regularly discover slow transients like supernovae on their own, the most common way to discover extragalactic fast transients, fading away in a few nights, is via follow-up observations of gamma-ray burst and gravitational-wave triggers. However, wide-field surveys have the potential to also identify rapidly fading transients independently of such external triggers. The volumetric survey speed of the Zwicky Transient Facility (ZTF) makes it sensitive to faint and fast-fading objects as kilonovae, the optical counterparts to binary neutron stars and neutron star-black hole mergers, out to almost 200Mpc. We introduce an open-source software infrastructure, the ZTF REaltime Search and Triggering, ZTFReST, designed to identify kilonovae and fast optical transients in ZTF data. Using the ZTF alert stream combined with forced photometry, we have implemented automated candidate ranking based on their photometric evolution and fitting to kilonova models. Automated triggering of follow-up systems, such as Las Cumbres Observatory, has also been implemented. In 13 months of science validation, we found several extragalactic fast transients independent of any external trigger (though some counterparts were identified later), including at least one supernova with post-shock cooling emission, two known afterglows with an associated gamma-ray burst, two known afterglows without any known gamma-ray counterpart, and three new fast-declining sources (ZTF20abtxwfx, ZTF20acozryr, and ZTF21aagwbjr) that are likely associated with GRB200817A, GRB201103B, and GRB210204A. However, we have not found any objects which appear to be kilonovae; therefore, we constrain the rate of GW170817-like kilonovae to $R < 900$Gpc$^{-3}$yr$^{-1}$. A framework such as ZTFReST could become a prime tool for kilonova and fast transient discovery with the Vera C. Rubin Observatory

IRX-2, a novel biologic, favors the expansion of T effector over T regulatory cells in a human tumor microenvironment model

IRX-2, a natural cytokine biological with multiple components, has been used in preclinical and clinical studies to promote antitumor activity of T lymphocytes. To define cellular mechanisms responsible for antitumor effects of IRX-2, its ability to induce effector T cells (Teff) was examined in a model simulating the tumor microenvironment. An in vitro model containing conventional CD4+CD25− cells co-cultured with autologous immature dendritic cells, irradiated tumor cells, and cytokines was used to study differentiation and expansion of regulatory T cells (Treg) and Teff in the presence and absence of IRX-2. Phenotype, suppressor function, signaling, and cytokine production were serially measured using flow cytometry, Western blots, CFSE-based suppressor assays, and Luminex-based analyses. The presence of IRX-2 in the co-cultures promoted the induction and expansion of IFN-γ+Tbet+ Teff and significantly (p < 0.01) decreased the induction of inducible IL-10+TGF-β+ Treg. The responsible mechanism involved IFN-γ-driven T cell polarization towards Teff and suppression of Treg differentiation. In an in vitro model simulating the human tumor microenvironment, IRX-2 promoted Teff expansion and antitumor activity without inducing Treg. Thus, IRX-2 could be considered as a promising component of future antitumor therapies

Functional Studies on the IBD Susceptibility Gene IL23R Implicate Reduced Receptor Function in the Protective Genetic Variant R381Q

Genome-wide association studies (GWAS) in several populations have demonstrated significant association of the IL23R gene with IBD (Crohn's disease (CD) and ulcerative colitis (UC)) and psoriasis, suggesting that perturbation of the IL-23 signaling pathway is relevant to the pathophysiology of these diseases. One particular variant, R381Q (rs11209026), confers strong protection against development of CD. We investigated the effects of this variant in primary T cells from healthy donors carrying IL23RR381 and IL23RQ381 haplotypes. Using a proprietary anti-IL23R antibody, ELISA, flow cytometry, phosphoflow and real-time RT-PCR methods, we examined IL23R expression and STAT3 phosphorylation and activation in response to IL-23. IL23RQ381 was associated with reduced STAT3 phosphorylation upon stimulation with IL-23 and decreased number of IL-23 responsive T-cells. We also observed slightly reduced levels of proinflammatory cytokine secretion in IL23RQ381 positive donors. Our study shows conclusively that IL23RQ381 is a loss-of-function allele, further strengthening the implication from GWAS results that the IL-23 pathway is pathogenic in human disease. This data provides an explanation for the protective role of R381Q in CD and may lead to the development of improved therapeutics for autoimmune disorders like CD

Viewing scenes of the history of chemistry through the opera glass

Artistic creation has always reflected the spirit of the moment and opera has not been an exception. There are several examples of operas which appeared at key moments of the development of science, portraying them. Additionally there are also operas that emerged after scientific events or the lifetime of the scientists they were inspired on. In what concerns chemistry, the first category could be exemplified by the apothecary operas (already discussed by the author in a previous paper of this journal) while the others could be illustrated by recent operas such as Dr. Atomic or Madame Curie. Continuing our endeavor of establishing relations between opera and chemistry, and considering that history of science plays an important role in the process of teaching and learning sciences, some milestones of the history of chemistry are here revisited through the opera glass. The operas analyzed have been grouped in the following categories: Operas of Fire and Metallurgy, Operas of the Philosophers of Antiquity, Operas of Alchemy, Operas of the Age of Enlightenment, Operas of the Revolutions and Operas of Entropy.Thanks are due to the Foundation for Science and Technology (FCT–Portugal) and FEDER (European Fund for Regional Development)-COMPETE/QREN/EU for financial support through the research unity PEst-C/QUI/UI686/2013.

Association of Marek's Disease induced immunosuppression with activation of a novel regulatory T cells in chickens.

Marek’s Disease Virus (MDV) is an alphaherpesvirus that infects chickens, transforms CD4+ T cells and causes deadly lymphomas. In addition, MDV induces immunosuppression early during infection by inducing cell death of the infected lymphocytes, and potentially due to activation of regulatory T (Treg)-cells. Furthermore, immunosuppression also occurs during the transformation phase of the disease; however, it is still unknown how the disease can suppress immune response prior or after lymphoma formation. Here, we demonstrated that chicken TGF-beta+ Treg cells are found in different lymphoid tissues, with the highest levels found in the gut-associated lymphoid tissue (cecal tonsil: CT), fostering an immune-privileged microenvironment exerted by TGF-beta. Surprisingly, significantly higher frequencies of TGF-beta+ Treg cells are found in the spleens of MDV-susceptible chicken lines compared to the resistant line, suggesting an association between TGF-beta+ Treg cells and host susceptibility to lymphoma formation. Experimental infection with a virulent MDV elevated the levels of TGF-beta+ Treg cells in the lungs as early as 4 days post infection, and during the transformation phase of the disease in the spleens. In contrast to TGF-beta+ Treg cells, the levels of CD4+CD25+ T cells remained unchanged during the infection and transformation phase of the disease. Furthermore, our results demonstrate that the induction of TGF-beta+ Treg cells is associated with pathogenesis of the disease, as the vaccine strain of MDV did not induce TGF-beta+ Treg cells. Similar to human haematopoietic malignant cells, MDV-induced lymphoma cells expressed high levels of TGF-beta but very low levels of TGF-beta receptor I and II genes. The results confirm that COX-2/ PGE2 pathway is involved in immunosuppression induced by MDV-lymphoma cells. Taken together, our results revealed a novel TGF-beta+ Treg subset in chickens that is activated during MDV infection and tumour formation.Biotechnology and Biological Sciences Research Counci

Cambio demográfico, migración y salud reproductiva : el papel de las mujeres senegalesas en la constitución de las familias

En aquest paper presentem en primer lloc els trets més característics de la transició de la nupcialitat i de la fecunditat a Senegal fent referència a alguns indicadors de la salut sexual i reproductiva de les dones. A continuació presentem els indicadors que resumeixen la biografia migratòria, nupcial i reproductiva d'un col·lectiu de dones senegaleses que han immigrat a Catalunya i que estan construint les seves famílies a cavall de dues cultures i de dos continents, fent referència entre altres coses a la poligamia, al lloc de naixement i residència dels seus fills i a la utilització de mètodes de planificació familiar. Acabem la comunicació amb algunes reflexions sobre el paper de les dones com agents actius en les decisions en materia de sexualitat i reproducció, en una societat que no és la seva, de la qual agraeixen els serveis de salut públics però sense deixar de banda la seva pròpia concepció de la família i de la salut.En este artículo presentamos en primer lugar los elementos más rellevantes de la transición de la nupcialidad y de la fecundidad en Senegal haciendo referencia a algunos indicadores de salud sexual y reproductiva de las mujeres. A continuación presentamos los indicadores que resumen la biografía migratoria, nupcial y reproductiva de un colectivo de mujeres de Senegal que han inmigrado a Cataluña y que están formando sus familias en el contexto de dos culturas y de dos continentes, haciendo referencia entre otras cosas a la poligamia, al lugar de nacimiento y residencia de sus hijos y a la utilización de métodos de planificación familiar. Finalizamos la comunicación con algunas reflexiones sobre el papel de las mujeres como agentes activos en las decisiones en materia de sexualidad y reproducción, en una sociedad que no es la suya propia, de la que agradecen los servicios de salud públicos pero sin olvidar su propia concepción de la familia y de la salud.In this paper we present the main characteristics from Senegal's nuptuality and fertility transition according to a group of measures related to women's sexual and reproductive health. We then show those indicators that summarise Senegal's women biography in terms of their migration, nuptuality and reproduction for those who have immigrated to Catalunya and have to raise a family between two cultures and two continents. In this way the article makes reference, among other things, to polygamy, the birthplace and residence of their offspring, as well as the existence of family planning. Lastly, we finish this paper with some ideas about the role of Senegal's women making sexual and reproduction decisions in a different society where they can obtain public health services while keeping their own approach to family and health issues

Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial

Background Third-generation aromatase inhibitors are more effective than tamoxifen for preventing recurrence in postmenopausal women with hormone-receptor-positive invasive breast cancer. However, it is not known whether anastrozole is more effective than tamoxifen for women with hormone-receptor-positive ductal carcinoma in situ (DCIS). Here, we compare the efficacy of anastrozole with that of tamoxifen in postmenopausal women with hormone-receptor-positive DCIS. Methods In a double-blind, multicentre, randomised placebo-controlled trial, we recruited women who had been diagnosed with locally excised, hormone-receptor-positive DCIS. Eligible women were randomly assigned in a 1:1 ratio by central computer allocation to receive 1 mg oral anastrozole or 20 mg oral tamoxifen every day for 5 years. Randomisation was stratified by major centre or hub and was done in blocks (six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation and only the trial statistician had access to treatment allocation. The primary endpoint was all recurrence, including recurrent DCIS and new contralateral tumours. All analyses were done on a modified intention-to-treat basis (in all women who were randomised and did not revoke consent for their data to be included) and proportional hazard models were used to compute hazard ratios and corresponding confidence intervals. This trial is registered at the ISRCTN registry, number ISRCTN37546358. Results Between March 3, 2003, and Feb 8, 2012, we enrolled 2980 postmenopausal women from 236 centres in 14 countries and randomly assigned them to receive anastrozole (1449 analysed) or tamoxifen (1489 analysed). Median follow-up was 7·2 years (IQR 5·6–8·9), and 144 breast cancer recurrences were recorded. We noted no statistically significant difference in overall recurrence (67 recurrences for anastrozole vs 77 for tamoxifen; HR 0·89 [95% CI 0·64–1·23]). The non-inferiority of anastrozole was established (upper 95% CI <1·25), but its superiority to tamoxifen was not (p=0·49). A total of 69 deaths were recorded (33 for anastrozole vs 36 for tamoxifen; HR 0·93 [95% CI 0·58–1·50], p=0·78), and no specific cause was more common in one group than the other. The number of women reporting any adverse event was similar between anastrozole (1323 women, 91%) and tamoxifen (1379 women, 93%); the side-effect profiles of the two drugs differed, with more fractures, musculoskeletal events, hypercholesterolaemia, and strokes with anastrozole and more muscle spasm, gynaecological cancers and symptoms, vasomotor symptoms, and deep vein thromboses with tamoxifen. Conclusions No clear efficacy differences were seen between the two treatments. Anastrozole offers another treatment option for postmenopausal women with hormone-receptor-positive DCIS, which may be be more appropriate for some women with contraindications for tamoxifen. Longer follow-up will be necessary to fully evaluate treatment differences