Finding associations in a heterogeneous setting: statistical test for aberration enrichment

Most two-group statistical tests find broad patterns such as overall shifts in mean, median, or variance. These tests may not have enough power to detect effects in a small subset of samples, e.g., a drug that works well only on a few patients. We developed a novel statistical test targeting such effects relevant for clinical trials, biomarker discovery, feature selection, etc. We focused on finding meaningful associations in complex genetic diseases in gene expression, miRNA expression, and DNA methylation. Our test outperforms traditional statistical tests in simulated and experimental data and detects potentially disease-relevant genes with heterogeneous effects.

Mechanical cell competition in heterogeneous epithelial tissues

Mechanical cell competition is important during tissue development, cancer invasion, and tissue ageing. Heterogeneity plays a key role in practical applications since cancer cells can have different cell stiffness and different proliferation rates than normal cells. To study this phenomenon, we propose a one-dimensional mechanical model of heterogeneous epithelial tissue dynamics that includes cell-length-dependent proliferation and death mechanisms. Proliferation and death are incorporated into the discrete model stochastically and arise as source/sink terms in the corresponding continuum model that we derive. Using the new discrete model and continuum description, we explore several applications including the evolution of homogeneous tissues experiencing proliferation and death, and competition in a heterogeneous setting with a cancerous tissue competing for space with an adjacent normal tissue. This framework allows us to postulate new mechanisms that explain the ability of cancer cells to outcompete healthy cells through mechanical differences rather than by having some intrinsic proliferative advantage. We advise when the continuum model is beneficial and demonstrate why naively adding source/sink terms to a continuum model without considering the underlying discrete model may lead to incorrect results.

In-hospital symptomatic venous thromboembolism and antithrombotic prophylaxis in Internal Medicine

SummaryHospitalised medical patients are at increased risk of venous thromboembolism (VTE), but the incidence of hospitalisation-related VTE in unselected medical inpatients has not been extensively studied, and uncertainties remain about the optimal use of thromboprophylaxis in this setting. Aims of our prospective, observational study were to assess the prevalence of VTE and the incidence of symptomatic, hospitalisation-related events in a cohort of consecutive patients admitted to 27 Internal Medicine Departments, and to evaluate clinical factors associated with the use of thromboprophylaxis. Between March and September 2006, a total of 4,846 patients were included in the study. Symptomatic VTE with onset of symptoms later than 48 hours after admission (”hospital-acquired” events, primary study end-point) occurred in 26 patients (0.55٪), while the overall prevalence of VTE (including diagnosis prior to or at admission) was 3.65٪. During hospital stay antithrombotic prophylaxis was administered in 41.6٪ of patients, and in 58.7% of those for whom prophylaxis was recommended according to the 2004 Guidelines of the American College of Chest Physicians. The choice of administering thromboprophylaxis or not appeared qualitatively adherent to indications from randomised clinical trials and international guidelines, and bed rest was the strongest determinant of the use of prophylaxis. Data from our real-world study confirm that VTE is a relevant complication in patients admitted to Internal Medicine Departments, and recommended tromboprophylaxis is still under-used, in particular in some patients groups. Further efforts are needed to better define risk profile and to optimise prophylaxis in the heterogeneous setting of medical inpatients.

“Because We Are Refugees” – Utilizing a Legal Label

The contribution challenges and differentiates the debate on neo-institutionalism with an empirical analysis from the core of the international refugee regime. The central point of reference for this comprehensive institutional regime is the legal label ‘refugee.’ To understand processes of proliferation, cultural adoptions, and bypasses of such institutional concepts and rules, it is crucial to study their varying interpretations and uses on the micro-level. This is done here in the case of refugee camps, which represent an organizationally and culturally heterogeneous setting, while its elements are all part of the international refugee regime. Emic modes of interpreting and utilizing this label on camp level are analyzed. Empirically, the contribution is mainly based on research material from a six months field study in two Zambian refugee camps, conducted in 2003.The use of the refugee label as a legal concept equipped with specific rights is only one possibility of employing the concept. It is interpreted in the frame of ‘legalism,’ reasoning that being a refugee, and thus vulnerable, implies certain rights, the fulfillment of which is then claimed. Secondly, camp inhabitants also utilize the refugee label in the interpretative frame of ‘compassionism.’ Applying to the cultural connection between refugees and suffering, they expect to evoke compassion and to receive a pittance. Beside these two utilizations of the ‘refugee’ label, there are also perspectives that do not relate to this institutional concept. In a third interpretation, the situation of encampment in a country of refuge is seen as being a guest, which allows for a temporary acceptance of limitations. Fourthly, some camp inhabitants see the camp not as temporary and extraordinary refuge, but as permanent home, whereby the ‘refugee’ concept becomes largely irrelevant in daily life.Interpreting the results in the realm of the sociological neo-institutionalism, the international refugee regime can be seen as a ‘world polity’ domain. The respective theoretical approach helps to explain where institutionalized figures like the ‘refugee’ come from. However, there are great variations in the ways in which these institutional concepts and rules are employed on the micro-level. Here, ‘world polity’ research leaves an explanatory desideratum. The plurality of interpretations and utilizations of the ‘refugee’ label indicates an active and refractory functioning of the micro-level, rather than an isomorphic enactment of the legal elements of ‘world culture.’