The efficacy of tissue factor −603A/G and +5466A>G polimorphisms at the development of venous thromboembolism in cancer patients

Background and Aim: Venous thromboembolism (VTE) is one of the most common complications in cancer patients. Although factor V Leiden (FVL) is the most common genetic defect causing thrombosis, the impact of gene abnormalities on thrombotic tendency in cancer patients remains poorly explored. Tissue factor (TF) is a major physiologic initiator of blood coagulation. This is the first study regarding the association of TF gene −603A/G and +5466A>G polymorphisms with VTE in malignancy. Materials and Me thods: The study consists of two groups: cancer patients with VTE were included as Group 1 (n = 46); Group 2 comprises 196 cancer patients without VTE. Restriction fragment length polymorphism method was used for the detection of polymorphisms of TF −603A/G in the 5՛upstream region and TF 5466A/G in intron 2. FVL, PT G20210A and MTHFR C677T polymorphisms were determined by using commercially available Light Cycler kits. The genotype and allele frequencies between the groups were compared using χ² or Fisher exact test, if appropriate. Results: No differences were observed in the distribution of TF gene −603A/G genotype frequencies between the groups. Although a slightly increased incidence of +5466GA genotype was in Group 1 (17.4% vs 11.2%), it did not achieve statistical significance. The prevalence of FVL was significantly greater in Group 1 compared with Group 2 (41.3% vs 4.1%, p 0.05). Conclusions: The present study did not show significant association of TF gene −603A/G and +5466A>G polymorphisms with VTE in malignancy, however, further larger studies including different ethnic population are needed to confirm our findings.Background and Aim: Venous thromboembolism (VTE) is one of the most common complications in cancer patients. Although factor V Leiden (FVL) is the most common genetic defect causing thrombosis, the impact of gene abnormalities on thrombotic tendency in cancer patients remains poorly explored. Tissue factor (TF) is a major physiologic initiator of blood coagulation. This is the first study regarding the association of TF gene −603A/G and +5466A>G polymorphisms with VTE in malignancy. Materials and Me thods: The study consists of two groups: cancer patients with VTE were included as Group 1 (n = 46); Group 2 comprises 196 cancer patients without VTE. Restriction fragment length polymorphism method was used for the detection of polymorphisms of TF −603A/G in the 5՛upstream region and TF 5466A/G in intron 2. FVL, PT G20210A and MTHFR C677T polymorphisms were determined by using commercially available Light Cycler kits. The genotype and allele frequencies between the groups were compared using χ² or Fisher exact test, if appropriate. Results: No differences were observed in the distribution of TF gene −603A/G genotype frequencies between the groups. Although a slightly increased incidence of +5466GA genotype was in Group 1 (17.4% vs 11.2%), it did not achieve statistical significance. The prevalence of FVL was significantly greater in Group 1 compared with Group 2 (41.3% vs 4.1%, p 0.05). Conclusions: The present study did not show significant association of TF gene −603A/G and +5466A>G polymorphisms with VTE in malignancy, however, further larger studies including different ethnic population are needed to confirm our findings

Incorporating Learning Analytics into Basic Course Administration: How to Embrace the Opportunity to Identify Inconsistencies and Inform Responses

Consistency is imperative to the success of a multi-section basic course. However, establishing consistent practices is a difficult task, especially when coupled with maintaining instructor autonomy. Learning analytics tools, designed to improve learning and teaching by collecting and analyzing pertinent information through interactive databases, can be used by basic course administrators to improve consistency. Using a reflective case study methodology we share our experience incorporating a learning analytics platform into our basic course. In doing so, we highlight the role this technology can play in terms of identifying areas of inconsistency as well as informing ways to improve overall course delivery. Three major areas of inconsistency were uncovered: (1) the use of online grade books; (2) utilization of course-wide rubrics; (3) and instances of grade inflation. Stemming from these findings is a set of very practical implications regarding the coupling of learning analytics and basic course administration. These include clarifying the two-step process of identifying inconsistencies and informing solutions as well as introducing the concept of collaborative consistency, the term we use to describe the co-construction of course materials (e.g., rubrics, schedules) and activities (e.g., norming). The case ultimately provides the opportunity for basic course directors to embrace the role of learning analytics technology

European climate response to tropical volcanic eruptions over the last half millennium

We analyse the winter and summer climatic signal following 15 major tropical volcanic eruptions over the last half millennium based on multi-proxy reconstructions for Europe. During the first and second post-eruption years we find significant continental scale summer cooling and somewhat drier conditions over Central Europe. In the Northern Hemispheric winter the volcanic forcing induces an atmospheric circulation response that significantly follows a positive NAO state connected with a significant overall warm anomaly and wetter conditions over Northern Europe. Our findings compare well with GCM studies as well as observational studies, which mainly cover the substantially shorter instrumental period and thus include a limited set of major eruptions

Benzothiazole derivatives as human DNA topoisomerase IIα inhibitors

Benzothiazole derivatives resembling the structure of DNA purine bases were tested to determine their topoisomerase inhibition activities. Based on DNA topoisomerase I and II relaxation assay results, all 12 derivatives acted as human topoisomerase IIα inhibitors, whereas only two compounds inhibited Calf thymus topoisomerase I. 3-amino-2-(2-bromobenzyl)-1,3-benzothiazol-3-ium 4-methylbenzensulfonate (BM3) was observed to be the most effective human topoisomerase IIα inhibitor with the lowest IC50 value of 39 nM. The mechanistic studies suggested that BM3 was neither a DNA intercalator nor a topoisomerase poison, it was only a DNA minor groove-binding agent. BM3 initially bound to the DNA topoisomerase IIα enzyme, then to DNA. As a result, the tested benzothiazole derivatives were obtained as strong topoisomerase IIα inhibitors. The benzothiazole tosylated salt form BM3 was found as the most effective topoisomerase IIα inhibitor. BM3's mechanisms of action might be its direct interaction with the enzyme. BM3's minor groove-binding property might also contribute to this action. Hence, BM3 could be a good candidate as a new anticancer agent. © 2013 Springer Science+Business Media New York

Oncology-led early identification of nutritional risk: a pragmatic, evidence-based protocol (PRONTO)

Simple Summary Early identification of patients on antineoplastic therapy who are at risk for or already malnourished is critical for optimizing treatment success. Malnourished patients are at increased risk for being unable to tolerate the most effective 'level' and 'duration' of treatment, with grave implications for both the short- (during treatment) and long-term outcomes. Herein, we provide a practical PROtocol for NuTritional risk in Oncology (PRONTO) to enable oncologists to identify patients with or at risk of malnutrition for further evaluation and follow-up with members of the multidisciplinary care team (MDT). Additional guidance is included on the oncologist-led provision of nutritional support if referral to a dietary service is not available. Nutritional issues, including malnutrition, low muscle mass, sarcopenia (i.e., low muscle mass and strength), and cachexia (i.e., weight loss characterized by a continuous decline in skeletal muscle mass, with or without fat loss), are commonly experienced by patients with cancer at all stages of disease. Cancer cachexia may be associated with poor nutritional status and can compromise a patient's ability to tolerate antineoplastic therapy, increase the likelihood of post-surgical complications, and impact long-term outcomes including survival, quality of life, and function. One of the primary nutritional problems these patients experience is malnutrition, of which muscle depletion represents a clinically relevant feature. There have been recent calls for nutritional screening, assessment, treatment, and monitoring as a consistent component of care for all patients diagnosed with cancer. To achieve this, there is a need for a standardized approach to enable oncologists to identify patients commencing and undergoing antineoplastic therapy who are or who may be at risk of malnutrition and/or muscle depletion. This approach should not replace existing tools used in the dietitian's role, but rather give the oncologist a simple nutritional protocol for optimization of the patient care pathway where this is needed. Given the considerable time constraints in day-to-day oncology practice, any such approach must be simple and quick to implement so that oncologists can flag individual patients for further evaluation and follow-up with appropriate members of the multidisciplinary care team. To enable the rapid and routine identification of patients with or at risk of malnutrition and/or muscle depletion, an expert panel of nutrition specialists and practicing oncologists developed the PROtocol for NuTritional risk in Oncology (PRONTO). The protocol enables the rapid identification of patients with or at risk of malnutrition and/or muscle depletion and provides guidance on next steps. The protocol is adaptable to multiple settings and countries, which makes implementation feasible by oncologists and may optimize patient outcomes. We advise the use of this protocol in countries/clinical scenarios where a specialized approach to nutrition assessment and care is not available

Early-stage breast cancer is not associated with the risk of marital dissolution in a large prospective study of women

Background: As breast cancer and its treatment are likely to interfere with traditional expectations of womanhood, it may affect marital stability. Methods: The risk of marital dissolution was analysed with respect to diagnosis of early-stage (T1-4N0-3M0) breast cancer in a cohort of 134 435 married Finnish women followed for a median of 17.0 married years. Age, socioeconomic status, education, number of children, duration of marriage and earlier marriages were taken into account and the effects of surgery, chemotherapy, radiotherapy and endocrine therapy were analysed separately. Results: Women with a diagnosis of early-stage breast cancer did not show increase in marital dissolution (hazard ratio -0.96, 95% confidence interval = 0.79-1.17). Neither the type of surgical procedure nor any of the oncologic treatments was associated with an increase in the risk of divorce. Conclusions: Any evidence of excess risk of marital breakdown after the diagnosis of early-stage breast cancer and its treatment was not demonstrated.Peer reviewe

Stable Isotope Records from Mount Logan, Eclipse Ice Cores and Nearby Jellybean Lake. Water Cycle of the North Pacific Over 2000 Years and Over Five Vertical Kilometres: Sudden Shifts and Tropical Connections

Three ice cores recovered on or near Mount Logan, together with a nearby lake record (Jellybean Lake), cover variously 500 to 30 000 years. This suite of records offers a unique view of the lapse rate in stable isotopes from the lower to upper troposphere. The region is climatologically important, being beside the Cordilleran pinning-point of the Rossby Wave system and the Aleutian Low. Comparison of stable isotope series over the last 2000 years and model simulations suggest sudden and persistent shifts between modern (mixed) and zonal flow regimes of water vapour transport to the Pacific Northwest. The last such shift was in A.D. 1840. Model simulations for modern and “pure” zonal flow suggest that these shifts are consistent regime changes between these flow types, with predominantly zonal flow prior to ca. A.D. 1840 and modern thereafter. The 5.4 and 0.8 km asl records show a shift at A.D. 1840 and another at A.D. 800. It is speculated that the A.D. 1840 regime shift coincided with the end of the Little Ice Age and the A.D. 800 shift with the beginning of the European Medieval Warm Period. The shifts are very abrupt, taking only a few years at most.Trois carottes de glace prélevées à proximité du mont Logan, combinées à une coupe stratigraphique du lac Jellybean, couvrent une période comprise entre 500 et 30 000 ans. Elles renseignent sur les taux de changement de la composition isotopique de la troposphère. La région étudiée est importante au niveau climatologique puisqu’elle est au point de convergence des ondes de Rossby et de la dépression des Aléoutiennes. La comparaison entre la composition isotopique depuis 2000 ans et les résultats des simulations suggère des changements brusques et persistants entre les régimes de transport de vapeur d’eau modernes et zonaux dans le nord-est du Pacifique, où le dernier changement s’est produit en 1840 de notre ère. Les simulations indiquent que les changements de flux correspondent aux changements de régime, avec un flux zonal avant ca 1840 pour passer au type moderne ensuite. Les forages à 5,4 et 0,8 km d’altitude montrent un changement en A.D. 1840 et un autre en l’an 800. On présume que ces changements de régime coïncident respectivement avec la fin du Petit Âge Glaciaire et le début de la période médiévale chaude, ces changements s’étant produits en quelques années seulement