The linear process of somatic evolution

Cancer is the consequence of an unwanted evolutionary process. Cells receive mutations that alter their phenotype. Especially dangerous are those mutations that increase the net reproductive rate of cells, thereby leading to neoplasia and later to cancer. The standard models of evolutionary dynamics consider well mixed populations of individuals in symmetric positions. Here we introduce a spatially explicit, asymmetric stochastic process that captures the essential architecture of evolutionary dynamics operating within tissues of multicellular organisms. The "linear process" has the property of cancelling out selective differences among cells yet retaining the protective function of apoptosis. This design can slow down the rate of somatic evolution dramatically and therefore delay the onset of cancer.     

Connections between attachment prototypes and relationship patterns

Connections between attachment styles and relationship patterns are studied on 32 female psychotherapy patients. Our study gives first hints to a connection between attachment variables, assessed by the German version of the Adult Attachment Prototype Rating (AAPR) and predominant relationship patterns, assessed by the Core Conflictual Relationship Theme Method (CCRT) developed by Luborsky, if both methods are used independently. Subsamples according to the attachment styles show differences in CCRT variables.     

Differential effects of risperidone,olanzapine, clozapine,and conventional antipsychotics on type 2 diabetes: findings from a large health plan database

BACKGROUND: Case series suggest that some antipsychotics may induce or exacerbate type 2 diabetes. This study measured the association of antipsychotic treatments with diabetes at a population level. METHOD: Claims data for psychosis patients (ICD-CM-9 290.xx-299.xx) within health plans encompassing 2.5 million individuals were analyzed. Patients reporting preexisting type 2 diabetes up to 8 months prior to observation were excluded. The frequency of newly reported type 2 diabetes in untreated patients and among patients treated with antipsychotics from 5 categories (risperidone, olanzapine, clozapine, and high-potency and low-potency conventionals) was compared. Logistic regression models compared the odds of diabetes based on exposure to each of the antipsychotic categories. RESULTS: Based on 12 months of exposure, the odds of type 2 diabetes for risperidone-treated patients (odds ratio = 0.88, 95% CI = 0.372 to 2.070) was not significantly different from that for untreated patients, whereas patients receiving other antipsychotics had a significantly greater risk of diabetes than untreated patients (p < .05): olanzapine, 3.10 (95% CI = 1.620 to 5.934); clozapine, 7.44 (95% CI = 0.603 to 34.751); high-potency conventionals, 2.13 (95% CI = 1.097 to 4.134); and low-potency conventionals, 3.46 (95% CI = 1.522 to 7.785). Older age and greater use of non-antipsychotic psychotropic medications also contributed to risk of type 2 diabetes. Olanzapine also showed significantly higher (p < .01) odds of diabetes associated with increasing dose. CONCLUSION: Consistent with previously published literature, these data suggest that olanzapine, clozapine, and some conventional antipsychotics appear to increase the risk of acquiring or exacerbating type 2 diabetes and that the effect may vary by drug. In contrast to these agents, risperidone was not associated with an increased risk of type 2 diabetes.     

Peak inspiratory flow rate after methacholine challenge in asthmatic patients and its impact on the effect of formoterol via different inhalers.

The goal of the present study was to investigate the bronchodilating effects of 6 and 12 microg formoterol delivered by the Turbuhaler, in comparison to salbutamol 200 microg (metered dose inhaler) and to controls without treatment. After inducing acute and severe bronchial obstruction by means of methacholine challenge, peak inspiratory mouth flow (PIMF) was measured through a stenosis, simulating the internal resistance of the Turbuhaler, with the in-check device. In addition the relationship was studied between PIMF and clinical response in the 3 treatment groups. In the 176 patients methacholine caused a mean fall in FEV(1) of 37.1 +/- 6.9% compared to baseline. Ten minutes after bronchodilator inhalation, FEV(1) improved significantly in all three treatment groups. At 30 minutes after bronchodilator administration, only the salbutamol 200 microg and the formoterol 12 microg groups had a significantly greater increase in FEV1 than controls (0.69 +/- 0.43 l and 0.66 +/- 0.37 l vs 0.38 +/- 0.32 l, p < 0.0005), whereas the formoterol 6 microg group showed no significant improvement (0.41 +/- 0.38 l, p = 0.74). Thirteen patients (7.4%) did not reach a minimal PIMF of 30 l/min through the in-check device after challenge. In the four patients in the formoterol 6 microg group with a PIMF below 30 l/min inhalation did not cause bronchodilation. In conclusion, the results demonstrate that 6 microg formoterol via Turbuhaler leads to less and slower onset of bronchodilation compared to the other groups in our setting. If patients fail to generate a PIMF of 30 l/min, 6 microg formoterol via Turbuhaler may provide inadequate relief in a severe asthma attack.     

Trauma 1 as a political tool

Interviews with refugees from Kosovo serve to elucidate the political significance of the concepts dealing with traumatic experiences. Both the Western world and its interventions executed during the Balkan War refer to the concept of trauma as a central topic. Any peace-restoring actions, therapeutic interventions and even military campaigns are legitimized by the core concept of trauma. Therefore granting asylum hinges essentially on this concept. Refugees must successfully convince the authorities of being painfully affected by their traumatic experiences, which serve as an asset towards a safer and just future. Clinging to the trauma and the unconscious attachment to the victim role hence create and affirm the national identity. Consequently, by resorting to trauma, the West is in danger of aggravating the tenuous issues of national identity and idiosyncrasy.     

Hospital use of young children in Switzerland: A nation-wide study based on a complete survey over 4 years

Background  

Young children are known to be the most frequent hospital users compared to older children and young adults. Therefore, they are an important population from economic and policy perspectives of health care delivery. In Switzerland complete hospitalization discharge records for children [<5 years] of four consecutive years [2002–2005] were evaluated in order to analyze variation in patterns of hospital use.     

Can chromosomal instability initiate tumorigenesis?

Cancers result from the accumulation of inherited and somatic mutations in oncogenes and tumor suppressor genes. These genes encode proteins that function in growth regulatory and differentiation pathways. Mutations in those genes increase the net reproductive rate of cells. Chromosomal instability (CIN) is a feature of most human cancers. Mutations in CIN genes increase the rate at which whole chromosomes or large parts of chromosomes are lost or gained during cell division. CIN causes an imbalance in chromosome number (aneuploidy) and an enhanced rate of loss of heterozygosity, which is an important mechanism of inactivating tumor suppressor genes. A crucial question of cancer biology is whether CIN is an early event and thus a driving force of tumorigenesis. Here we discuss mathematical models of situations where inactivation of one or two tumor suppressor genes is required for tumorigenesis. If two tumor suppressor genes have to be inactivated in rate-limiting steps, then CIN is likely to emerge before the inactivation of the first tumor suppressor gene.     

Coprocessing of powdered cellulose and magnesium carbonate: direct tableting versus tableting after roll compaction/dry granulation

Mixtures of magnesium carbonate (MC) with three types of powdered cellulose (M80, P290, A300) were tableted directly or after roll compaction/dry granulation. The fraction of powdered cellulose in the mixture was varied from 0% to 25% (w/w). The properties of the granules, blends, and their corresponding tablets were analyzed. Granules with a low amount of A300 showed the best flow properties, whereas the fibrous shape of the binding agents M80 and P290 impaired the free flow. Heckel plots showed clearly the different behavior of powdered cellulose in blends and granules during the tableting process. The Heckel-Plots for pure MC powder and granulated MC (MCgr) were similar. Increasing the fraction of powdered cellulose resulted in a fan-shaped set of curves, which is a reflection of an increased densification. Physical mixtures of all three powdered celluloses and granulated mixtures of M80 resulted in a higher densification compared with pure MC. In contrast, the granulated mixtures of P290 and A300 resulted in a diminished densification during tableting, which means that the coprocessed mixtures behaved differently during tableting compared with the physical mixtures. The curves were lower than those of pure MC and MCgr most pronounced at a fraction of 5% powdered cellulose. The tablet pore structure was evaluated by mercury porosimetry. The addition of P290 and A300 to the dry granules resulted in tablets with a higher fraction of smaller pores. Comparably high values for tablet tensile strength and low friability resulted from this special tablet structure. Roll compacted/dry granulated MC, coprocessed with 5% of P290 or A300, seems to be a promising excipient for direct compression. This coprocessed product combines good flow and tablet properties, and is superior to pure MC or a physical mixture of MC and PC.     

Selected disorders of connective tissue: pseudoxanthoma elasticum, cutis laxa, and lipoid proteinosis

There has been progress made in the understanding of 3 Mendelian disorders: pseudoxanthoma elasticum, cutis laxa, and lipoid proteinosis cutis and mucosae. While they are primary connective tissue diseases, their names imply a connection to the skin, and in fact, it is often the dermatologist who makes the diagnosis. It seems rational that defects in various extracellular matrix proteins cause lipoid proteinosis or subtypes of cutis laxa, yet the discovery of a liver- and kidney-based transmembrane transporter as the culprit of pseudoxanthoma elasticum was rather surprising and may shed new light on elastic tissue homeostasis.     

Evaluation of a 16-MDCT scanner in an emergency department: initial clinical experience and workflow analysis

OBJECTIVE: MDCT is especially suited for emergency purposes because it allows rapid high-resolution scans of large areas, fast high-quality reformatting in every orientation, and 3D illustration of the data set. In a prospective study, we evaluated the reliability and workflow of a dedicated emergency department 16-MDCT scanner in the management of patients presenting to the emergency department. SUBJECTS AND METHODS: The use of a 16-MDCT scanner for 503 patients in the emergency department of a university clinic was evaluated. For reasons of workflow analysis, seven precise time intervals were recorded during the emergency examinations. A new setting for repositioning multiple-trauma patients after imaging of the head and neck from the head-first position to the feet-first position was introduced. RESULTS: Six (1.2%) of the 503 patients were excluded because of technical malfunction or patient noncompliance. Image quality in the remaining 497 cases, including CT angiography and CT of multiple-trauma patients, was outstanding. Positioning of the patients took from 3 to 13 min depending on the body region examined, representing 33-67% of the mean room time, which ranged from 8 to 21 min. In multiple-trauma patients, the initial positioning took a mean of 6 min and repositioning took 8 min, representing 19% and 26% of total room time, respectively. CONCLUSION: The use of a dedicated 16-MDCT scanner in the emergency department resulted in short examination times even for examinations of multiple body regions under emergency conditions. The introduced setting-repositioning of multiple-trauma patients-allowed high image quality to be maintained. The trade-off in multiple-trauma patients was prolonged room time because of patient repositioning.