The impact of intraclonal heterogeneity on the outcomes of Multiple Myeloma patients treated with new drugs

Understanding the biology of Multiple Myeloma (MM) is of primary importance in the struggle to achieve a cure for this yet incurable neoplasm. A better knowledge of the mechanism underlying the development of MM can guide us in the development of new treatment strategies. Studies both on solid and haematological tumours have shown that cancer comprises a collection of related but subtly different clones, a feature that has been termed “intra-clonal heterogeneity”. This intra-clonal heterogeneity is likely, from a “Darwinian” natural selection perspective, to be the essential substrate for cancer evolution, disease progression and relapse. In this context the critical mechanism for tumour progression is competition between individual clones (and cancer stem cells) for the same microenvironmental “niche”, combined with the process of adaptation and natural selection. The Darwinian behavioural characteristics of cancer stem cells are applicable to MM. The knowledge that intra-clonal heterogeneity is an important feature of tumours’ biology has changed our way to addressing cancer, now considered as a composite mixture of clones and not as a linear evolving disease. In this variable therapeutic landscape it is important for clinicians and researchers to consider the impact that evolutionary biology and intra-clonal heterogeneity have on the treatment of myeloma and the emergence of treatment resistance. It is clear that if we want to effectively cure myeloma it is of primarily importance to understand disease biology and evolution. Only by doing so will we be able to effectively use all of the new tools we have at our disposal to cure myeloma and to use treatment in the most effective way possible. The aim of the present research project was to investigate at different levels the presence of intra-clonal heterogeneity in MM patients, and to evaluate the impact of treatment on clonal evolution and on patients’ outcomes.

Landscape and well-being: a scoping study on the health-promoting impact of outdoor environments

OBJECTIVES: The present literature review conceptualises landscape as a health resource that promotes physical, mental, and social well-being. Different health-promoting landscape characteristics are discussed. METHODS: This article is based on a scoping study which represents a special kind of qualitative literature review. Over 120 studies have been reviewed in a five-step-procedure, resulting in a heuristic device. RESULTS: A set of meaningful pathways that link landscape and health have been identified. Landscapes have the potential to promote mental well-being through attention restoration, stress reduction, and the evocation of positive emotions; physical well-being through the promotion of physical activity in daily life as well as leisure time and through walkable environments; and social well-being through social integration, social engagement and participation, and through social support and security. CONCLUSION: This scoping study allows us to systematically describe the potential of landscape as a resource for physical, mental and social well-being. A heuristic framework is presented that can be applied in future studies, facilitating systematic and focused research approaches and informing practical public health interventions.

Impact of long-term corticosteroid therapy on the distribution pattern of lower limb atherosclerosis

OBJECTIVE: Ectopic calcification and mediacalcinosis can be promoted by corticosteroid use. Aim of the present investigation is to describe macrovascular disease features in patients with long-term corticosteroid therapy and symptomatic lower limb peripheral arterial occlusive disease (PAD). METHODS: A consecutive series of 2783 patients undergoing clinical and angiographic work-up of PAD were screened for long-term (>5 years) corticosteroid use (group A). Comparison was performed to a randomly selected age-, sex- and risk factor-matched PAD control cohort from the same series without corticosteroid use (group B). Patients with diabetes mellitus or severe renal failure were excluded. Arterial calcification was evaluated by qualitative assessment on radiographic images. Severity of atherosclerotic lesions was analysed from angiographic images using a semi-quantitative score (Bollinger score). RESULTS: In general, 12 patients (5 males, mean age 78.5 +/- 9.0 years) with 15 ischaemic limbs qualified to be enrolled in group A and were compared to 23 matching control patients (6 2 males, mean age 79.5 +/- 6 years) with 32 ischaemic limbs. Incompressibility of ankle arteries determined by measurement of the ankle-brachial index was seen in 12 limbs (80%) in group A compared to 3 limbs (9%) in group B (p = 0.0009). No significant difference was found comparing group A and B for segmental calcification, whereas comparison of the atherosclerotic burden using the angiographic severity score showed a significantly higher score at the infragenicular arterial level in group A (p = 0.001). CONCLUSION: Findings suggest that the long-term corticosteroid therapy is associated with a distally accentuated, calcifying peripheral atherosclerosis inducing arterial incompressibility. This occlusion pattern is comparable to patients with renal failure or diabetes. Further research is required to support our observations.

Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials

Pathological complete response (pCR) to neoadjuvant treatment correlates with outcome in breast cancer. We determined whether characteristics of neoadjuvant therapy are associated with pCR. We used multi-level models, which accounted for heterogeneity in pCR across trials and trial arms, to analyze individual patient data from 3332 women included in 7 German neoadjuvant trials with uniform protocols. PCR was associated with an increase in number of chemotherapy cycles (odds ratio [OR] 1.2 for every two additional cycles; P = 0.009), with higher cumulative anthracycline doses (OR 1.6; P = 0.002), higher cumulative taxane doses (OR 1.6; P = 0.009), and with capecitabine containing regimens (OR 1.62; P = 0.022). Association of pCR with increase in number of cycles appeared more pronounced in hormone receptor (HR)-positive tumors (OR 1.35) than in HR-negative tumors (OR 1.04; P for interaction = 0.046). Effect of anthracycline dose was particularly pronounced in HER2-negative tumors (OR 1.61), compared to HER2-positive tumors (OR 0.83; P for interaction = 0.14). Simultaneous trastuzumab treatment in HER2-positive tumors increased odds of pCR 3.2-fold (P < 0.001). No association of pCR and number of trastuzumab cycles was found (OR 1.20, P = 0.39). Dosing characteristics appear important for successful treatment of breast cancer. Longer treatment, higher cumulative doses of anthracyclines and taxanes, and the addition of capecitabine and trastuzumab are associated with better response. Tailoring according to breast cancer phenotype might be possible: longer treatment in HR-positive tumors, higher cumulative anthracycline doses for HER2-negative tumors, shorter treatment at higher cumulative doses for triple-negative tumors, and limited number of preoperative trastuzumab cycles in HER2-positive tumors.

Impact of acquired enamel pellicle modification on initial dental erosion

The acquired enamel pellicle that forms on the tooth surface serves as a natural protective barrier against dental erosion. Numerous proteins composing the pellicle serve different functions within this thin layer. Our study examined the effect of incorporated mucin and casein on the erosion-inhibiting potential of the acquired enamel pellicle. Cyclic acidic conditions were applied to mimic the erosive environment present at the human enamel interface during the consumption of soft drinks. One hundred enamel specimens were prepared for microhardness tests and distributed randomly into 5 groups (n = 20) that received the following treatment: deionized water, humidity chamber, mucin, casein, or a combination of mucin and casein. Each group was exposed to 3 cycles of a 2-hour incubation in human saliva, followed by a 2-hour treatment in the testing solution and a 1-min exposure to citric acid. The microhardness analysis demonstrated that the mixture of casein and mucin significantly improved the erosion-inhibiting properties of the human pellicle layer. The addition of individual proteins did not statistically impact the function of the pellicle. These data suggest that protein-protein interactions may play an important role in the effectiveness of the pellicle to prevent erosion.

Reporting of research quality characteristics of studies published in 6 major clinical dental specialty journals

The objective of this article was to record reporting characteristics related to study quality of research published in major specialty dental journals with the highest impact factor (Journal of Endodontics, Journal of Oral and Maxillofacial Surgery, American Journal of Orthodontics and Dentofacial Orthopedics; Pediatric Dentistry, Journal of Clinical Periodontology, and International Journal of Prosthetic Dentistry). The included articles were classified into the following 3 broad subject categories: (1) cross-sectional (snap-shot), (2) observational, and (3) interventional. Multinomial logistic regression was conducted for effect estimation using the journal as the response and randomization, sample calculation, confounding discussed, multivariate analysis, effect measurement, and confidence intervals as the explanatory variables. The results showed that cross-sectional studies were the dominant design (55%), whereas observational investigations accounted for 13%, and interventions/clinical trials for 32%. Reporting on quality characteristics was low for all variables: random allocation (15%), sample size calculation (7%), confounding issues/possible confounders (38%), effect measurements (16%), and multivariate analysis (21%). Eighty-four percent of the published articles reported a statistically significant main finding and only 13% presented confidence intervals. The Journal of Clinical Periodontology showed the highest probability of including quality characteristics in reporting results among all dental journals.

Lost in translation: the impact of publication language on citation frequency in the scientific dental literature

Citation metrics are commonly used as a proxy for scientific merit and relevance. Papers published in English, however, may exhibit a higher citation frequency than research articles published in other languages, though this issue has not yet been investigated from a Swiss perspective where English is not the native language.

Impact of Bone Harvesting Techniques on Cell Viability and the Release of Growth Factors of Autografts

Background: Autogenous bone grafts obtained by different harvesting techniques behave differently during the process of graft consolidation; the underlying reasons are however not fully understood. One theory is that harvesting techniques have an impact on the number and activity of the transplanted cells which contribute to the process of graft consolidation. Materials and Methods: To test this assumption, porcine bone grafts were harvested with four different surgical procedures: bone mill, piezosurgery, bone drilling (bone slurry), and bone scraper. After determining cell viability, the release of molecules affecting bone formation and resorption was assessed by reverse transcription polymerase chain reaction and immunoassay. The mitogenic and osteogenic activity of the conditioned media was evaluated in a bioassay with isolated bone cells. Results: Cell viability and the release of molecules affecting bone formation were higher in samples harvested by bone mill and bone scraper when compared with samples prepared by bone drilling and piezosurgery. The harvesting procedure also affected gene expression, for example, bone mill and bone scraper samples revealed significantly higher expression of growth factors such as bone morphogenetic protein-2 and vascular endothelial growth factor compared with the two other modalities. Receptor activator of nuclear factor kappa B ligand expression was lowest in bone scraper samples. Conclusion: These data can provide a scientific basis to better understand the impact of harvesting techniques on the number and activity of transplanted cells, which might contribute to the therapeutic outcome of the augmentation procedure.

The Blue Dog Coalition: Impact of a Single-Issue Caucus from the 104th to the 110th Congress

The Blue Dog Coalition is an informal organization of legislators within the House of Representatives that strives to influence policy on fiscal responsibility, attract the attention of the electorate, They are a group that elicits wide range of reactions covering the length of the political spectrum, but despite this, their claims of special defense of fiscal conservatism within the Democratic Party have gone relatively undocumented by the academic community.This project has integrated a party literature with a caucus literature, in the attempt of building a novel framework for research. Work on polarization, the significance of parties, the purpose and history of caucuses all have been fused in such away that the Blue Dogs have created an opportunity to test broad congressional questions on a caucus-microcosm scale. Three important questions have emerged from the many possible avenues of exploration on the topic: How does admission into the Blue Dog Coalition effect voting behavior - measured by interest, ideology, and party unityscores? How does party leadership delegate prestigious committee assignments, a traditional indicator of partisan favor and influence, towards Blue Dogs? Can we use the Blue Dog Coalition as an indicator of fiscal conservatism? To each of these questions, a number of interesting results emerged. Blue Dogs, in the 104th scored higher in conservative interest group scores, more towards the center in ideological methods, and lower in party unity Dogs began to behave closer to their Democratic counterparts. In addition, membership on these select committees rose from a very small number to greater proportional parity within the Democratic Party. Perhaps most interesting, the Blue Dog Coalition does behave as a significant, independent predictor effect on NTU scores, a variable used to demonstrate fiscal conservatism. This research has shown, first and foremost, that it is useful and practical to applyold arguments within the party literature to a smaller, caucus level of analysis that is relatively untouched by the political science field. For the Blue Dogs, specifically, we have tested the validity of their claims in an attempt to reach broader questions ofdemocratic responsibility and electoral clarity. This work, and other work I have drawn upon, has barely scratched the surface on Blue Dog Democrats and other caucuses of comparable influence and popularity, and there remains a wealth of research material onthis caucus alone to be explored by scholars in the field of congressional politics.

Relationships Past and Present: Examining the Impact of One's Relationship with His/her Opposite-sex Parent on His/her Attitudes Toward and Engagement in Hookup Culture

Hooking up has become a common and public practice on university campuses across the country. While much research has determined who is doing it, with whom they are doing it, and what they are hoping to get out of it, little work has been done to determine what personal factors motivate students to participate in the culture. A total of 407 current students were surveyed to assess the impact of one’s relationship with his/her opposite-sex parent on his/her attitudestoward and engagement in hookup culture on campus. Scores were assigned to the participants to divide them into categories of high and low attachment with their parent. It was hypothesizedthat heterosexual students who do not perceive themselves as having a strong, close, positive relationship with their opposite-sex parent would be more likely to engage in or attempt to engage in casual sexual behavior. This pattern was expected to be strongest for women on campus. Men and women differed in their reasons for hooking up, with whom they hook up, to what they attribute the behaviors of their peers, and what they hope to gain from their sexual interactions. Effects of parent-child relationships were significant only for women who reported hooking up because “others are doing it,” men’s agreement with the behavior of their peers, and women’s overall satisfaction with their hookups. Developmental, social, and evolutionary perspectives are employed to explain the results. University status was determined to be most telling of the extent to which a student is engaged in hookup culture.

Effectively Engaging with a Dragon: Examining the Nature and Impact of the Most Recent Decade of Sino-African Multilateral Relations

The goal of my research is to examine in detail the impact of the increase in Sino-African trade on African political and economic development. The primary focus will be on two central aspects of Sino-African trade: the effects of China’s natural resource binge coupled with the flood of textiles and other manufactured goods from China to Africa. This thesis will determine the precise nature and extent ofSino-African trade in these sectors and will attempt to determine whether or not Chinese trade is having a net positive impact on long-term African economic development. I will investigate this issue from numerous perspectives using English, Chinese, and African sources.

The impact of social presence on team performance in social networking platforms

Next to the extensive use of social networking platforms (SNPs) for communication and relationship building with friends and relatives, SNPs are also increasingly used for enhancing collaboration at work. SNP usage at the workplace is fundamentally different and it is unclear how SNPs can improve collaboration as well as in what way their designs should be modified and adapted to collaboration settings. This research identifies specific SNP functions that enhance social presence as particularly beneficial for collaboration. Consequently, two designs of SNPs, one with high social presence and one with low social presence, are outlined and its impacts on collaboration are discussed. A framework is constructed that illustrates how social presence in SNPs can improve team performance through enhancing transactive memory within teams (intra-group collaboration) and relational capital across teams (inter-group collaboration). In addition, it is outlined how this framework could be evaluated in an experimental setting of teams working on a complex group task.