Treatment of newly diagnosed acute promyelocytic leukemia (APL): a comparison of French-Belgian-Swiss and PETHEMA results

All-trans retinoic acid (ATRA) plus anthracycline chemotherapy is the reference treatment of newly diagnosed acute promyelocytic leukemia (APL), whereas the role of cytosine arabinoside (AraC) remains disputed. We performed a joint analysis of patients younger than 65 years included in Programa para el Estudio de la Terapéutica en Hemopatía Maligna (PETHEMA) LPA 99 trial, where patients received no AraC in addition to ATRA, high cumulative dose idarubicin, and mitoxantrone, and APL 2000 trial, where patients received AraC in addition to ATRA and lower cumulative dose daunorubicin. In patients with white blood cell (WBC) count less than 10 x 10(9)/L, complete remission (CR) rates were similar, but 3-year cumulative incidence of relapse (CIR) was significantly lower in LPA 99 trial: 4.2% versus 14.3% (P = .03), although 3-year survival was similar in both trials. This suggested that AraC is not required in APL with WBC count less than 10 x 10(9)/L, at least in trials with high-dose anthracycline and maintenance treatment. In patients with WBC of 10 x 10(9)/L or more, however, the CR rate (95.1% vs 83.6% P = .018) and 3-year survival (91.5% vs 80.8%, P = .026) were significantly higher in APL 2000 trial, and there was a trend for lower 3-year CIR (9.9% vs 18.5%, P = .12), suggesting a beneficial role for AraC in those patients.

The performance of computer-aided detection when analyzing prior mammograms of newly detected breast cancers with special focus on the time interval from initial imaging to detection

PURPOSE: The clinical role of CAD systems to detect breast cancer, which have not been on cancer containing mammograms not detected by the radiologist was proven retrospectively. METHODS: All patients from 1992 to 2005 with a histologically verified malignant breast lesion and a mammogram at our department, were analyzed in retrospect focussing on the time of detection of the malignant lesion. All prior mammograms were analyzed by CAD (CADx, USA). The resulting CAD printout was matched with the cancer containing images yielding to the radiological diagnosis of breast cancer. CAD performance, sensitivity as well as the association of CAD and radiological features were analyzed. RESULTS: 278 mammograms fulfilled the inclusion criteria. 111 cases showed a retrospectively visible lesion (71 masses, 23 single microcalcification clusters, 16 masses with microcalcifications, in one case two microcalcification clusters). 54/87 masses and 34/41 microcalcifications were detected by CAD. Detection rates varied from 9/20 (ACR 1) to 5/7 (ACR 4) (45% vs. 71%). The detection of microcalcifications was not influenced by breast tissue density. CONCLUSION: CAD might be useful in an earlier detection of subtle breast cancer cases, which might remain otherwise undetected.

The Hidden World of Multilateralism? Treaty Commitments of Newly Democratized States in Europe

Why do new EU democracies engage in multilateralism? The dominant explanation proposes that new democracies use international treaties to lock in domestic reforms. This article offers a novel explanation as to why new EU democracies participate in multilateral treaties. We argue that ratifying a treaty serves three external signaling purposes (addressing recognition concerns; increasing strategic autonomy, and pleasing the EU). We test our argument through a mix of quantitative and qualitative methods. First, we apply event history analysis. Drawing on a new ratification data set comprising 76 multilateral treaties, we illustrate the prominent role of new EU democracies in multilateralism as compared to other new democracies. Second, to assess the importance of external signaling in the decision to ratify multilateral treaties, we examine parliamentary ratification debates in selected Central and Eastern European countries. Third, we compare parliamentary discussions across European and non-European new democracies to demonstrate the different motives driving their approaches toward multilateralism.

Cilengitide treatment of newly diagnosed glioblastoma patients does not alter patterns of progression

The integrin antagonist cilengitide has been explored as an adjunct with anti-angiogenic properties to standard of care temozolomide chemoradiotherapy (TMZ/RT → TMZ) in newly diagnosed glioblastoma. Preclinical data as well as anecdotal clinical observations indicate that anti-angiogenic treatment may result in altered patterns of tumor progression. Using a standardized approach, we analyzed patterns of progression on MRI in 21 patients enrolled onto a phase 2 trial of cilengitide added to TMZ/RT → TMZ in newly diagnosed glioblastoma. Thirty patients from the experimental treatment arm of the EORTC/NCIC pivotal TMZ trial served as a reference. MRIcro software was used to map location and extent of initial preoperative and recurrent tumors on MRI of both groups into the same stereotaxic space which were then analyzed using an automated tool of image analysis. Clinical and outcome data of the cilengitide-treated patients were similar to those of the EORTC/NCIC trial except for a higher proportion of patients with a methylated O(6)-methylguanyl-DNA-methyltransferase gene promoter. Analysis of recurrence pattern revealed neither a difference in the size of the recurrent tumor nor in the distance of the recurrences from the preoperative tumor location between groups. Overall frequencies of distant recurrences were 20 % in the reference group and 19 % (4/21 patients) in the cilengitide group. Compared with TMZ/RT → TMZ alone, the addition of cilengitide does not alter patterns of progression. This analysis does not support concerns that integrin antagonism by cilengitide may induce a more aggressive phenotype at progression, but also provides no evidence for an anti-invasive activity of cilengitide in patients with newly diagnosed glioblastoma.

Evaluation of study competence in pupils between 12-14 years old

There are three main study areas of guidance needs for pupils in Compulsory Secondary Education (CSE) which are academic development, personal and social development and the area of professional career. The area of academic development is where the knowledge to be acquired by the pupils, attitudes towards efficient learning in schools and the skills of efficient study are inculcated, the latter being the objective of our study. The research was taken from a sample of 80 school children between twelve and sixteen years old in a Secondary School in Santiago of Compostela ( Spain ). After analysing the results obtained we can see several motivations that justify the need to improve learning and study skills used by pupils. Normative arguments exist, needs that are exhibited by pupils and by teachers, especially tutors, of a scientific nature (connection with academic work) and to develop new strategies taking into account the contributions to the pedagogic research in this field. In this sense the application of an innovative programme of skills and study strategies in communication could be of interest.

Evaluation of study competence in pupils between 12-14 years old

There are three main study areas of guidance needs for pupils in Compulsory Secondary Education (CSE) which are academic development, personal and social development and the area of professional career. The area of academic development is where the knowledge to be acquired by the pupils, attitudes towards efficient learning in schools and the skills of efficient study are inculcated, the latter being the objective of our study. The research was taken from a sample of 80 school children between twelve and sixteen years old in a Secondary School in Santiago of Compostela ( Spain ). After analysing the results obtained we can see several motivations that justify the need to improve learning and study skills used by pupils. Normative arguments exist, needs that are exhibited by pupils and by teachers, especially tutors, of a scientific nature (connection with academic work) and to develop new strategies taking into account the contributions to the pedagogic research in this field. In this sense the application of an innovative programme of skills and study strategies in communication could be of interest.

Evaluation of study competence in pupils between 12-14 years old

There are three main study areas of guidance needs for pupils in Compulsory Secondary Education (CSE) which are academic development, personal and social development and the area of professional career. The area of academic development is where the knowledge to be acquired by the pupils, attitudes towards efficient learning in schools and the skills of efficient study are inculcated, the latter being the objective of our study. The research was taken from a sample of 80 school children between twelve and sixteen years old in a Secondary School in Santiago of Compostela ( Spain ). After analysing the results obtained we can see several motivations that justify the need to improve learning and study skills used by pupils. Normative arguments exist, needs that are exhibited by pupils and by teachers, especially tutors, of a scientific nature (connection with academic work) and to develop new strategies taking into account the contributions to the pedagogic research in this field. In this sense the application of an innovative programme of skills and study strategies in communication could be of interest.

Importance of newly generated neurons in the adult olfactory bulb for odor discrimination

In adult rodents, neurons are continually generated in the subventricular zone of the forebrain, from where they migrate tangentially toward the olfactory bulb, the only known target for these neuronal precursors. Within the main olfactory bulb, they ascend radially into the granule and periglomerular cell layers, where they differentiate mainly into local interneurons. The functional consequences of this permanent generation and integration of new neurons into existing circuits are unknown. To address this question, we used neural cell adhesion molecule-deficient mice that have documented deficits in the migration of olfactory-bulb neuron precursors, leading to about 40% size reduction of this structure. Our anatomical study reveals that this reduction is restricted to the granule cell layer, a structure that contains exclusively γ-aminobutyric acid (GABA)ergic interneurons. Furthermore, mutant mice were subjected to experiments designed to examine the behavioral consequences of such anatomical alteration. We found that the specific reduction in the newly generated interneuron population resulted in an impairment of discrimination between odors. In contrast, both the detection thresholds for odors and short-term olfactory memory were unaltered, demonstrating that a critical number of bulbar granule cells is crucial only for odor discrimination but not for general olfactory functions.

Real-time detection of the surface delivery of newly synthesized membrane proteins.

Newly synthesized membrane proteins travel from the Golgi complex to the cell surface in transport vesicles. We have exploited the ion channel properties of the nicotinic acetylcholine receptor (AChR) to observe in real time the constitutive delivery of newly synthesized AChR proteins to the plasma membrane in cultured muscle cells. Whole-cell voltage clamp was employed to monitor the current fluctuations induced by carbamylcholine upon the insertion into the plasma membrane of newly synthesized AChRs, following release from a 20 degrees C temperature block. We find that the transit of vesicles to the cell surface occurs within a few minutes after release of the block. The time course of electrical signals is consistent with many of the fusion events being instantaneous, although some appear to reveal the flickering of a fusion pore. AChR-containing vesicles can fuse individually or as conglomerates. Intracellular application of guanosine 5'-[gamma-thio]triphosphate inhibits the constitutive traffic of AChRs in most cells. Individual exocytotic vesicles carry between 10 and 300 AChR molecules, suggesting that AChRs may be packed extremely densely.

Europe’s reactive and protective muddling through: the results of a summit in fire fighting mode. EPC Post-Summit Analysis, 19 October 2015

The EU’s October summit was dominated by one issue; the migration and refugee crisis, with EU leaders intent on putting on a public display of unity after weeks of bitter arguments, and concentrating on fire-fighting and immediate measures to tackle the most pressing reasons for, and impacts of, the crisis. Longer-term measures to address some of the root causes of increased migratory flows, support for the integration of newly arrived refugees or the introduction of new channels of legal migration, were not discussed. The Summit also spent little time on two issues that had originally been expected to be a key part of the agenda: the forthcoming British referendum on EU membership, where irritation with the slow pace of talks and British vagueness about its demands were in evidence; and the governance of Economic and Monetary Union (EMU), where EU leaders missed another opportunity for a thorough debate about future perspectives on the basis of the ‘Five Presidents’ Report’.

Hartshorn genealogy : some descendants of Lieut. John, second son of Thomas, the immigrant : complete lines of Ryal, Ira and Asa from 7th to 12th and 13th generations : notes on allied families: Burnham, Perkins, Cooke, Pettingill /

Mode of access: Internet.