Towards quantitative in situ hybridization

In situ hybridization analysis of tissue mRNA concentrations remains to be accepted as a quantitative technique, even though exposure of tissue sections to photographic emulsion is equivalent to Northern blot analysis. Because of the biological importance of in situ quantification of RNA sequences within a morphological context, we evaluated the quantitative aspects of this technique. In calibrated microscopic samples, autoradiographic signal (density of silver grains) was proportionate to the radioactivity present, to the exposure time, and to time of development of the photographic emulsion. Similar results were obtained with tissue sections, showing that all steps of the in situ hybridization protocol, before and including the detection of the signal, can be reproducibly performed. Furthermore, the integrated density of silver grains produced in liver and intestinal sections by the in situ hybridization procedure using 35S-labeled riboprobes is directly proportionate to the signal obtained by quantitative Northern blot analysis. The significance of this finding is that in situ quantification of RNA can be realized with high sensitivity and with the additional advantage of the possibility of localizing mRNA within the cells of interest. Application of this procedure on fetal and adult intestinal tissue showed that the carbamoylphosphate synthetase (CPS)-expressing epithelial cells of both tissues accumulated CPS mRNA to the same level but that whole-organ CPS mRNA levels decreased four-to fivefold in the same period, owing to a comparable decrease in the number of CPS-expressing cells in total intestinal tissu

Hypertension in older patients, a retrospective cohort study

Background: It is unknown to what extent General Practitioners (GPs) manage hypertension (HT) differently in older patients, as compared to younger age groups. The purpose of our study was to compare HT management in older patients to younger age groups. Methods: We performed a retrospective cohort study of patients of 159 GP's practices in the Integrated Primary Care Information (IPCI) database. The study period lasted from September 2010 through December 2012. The study population consisted of all patients aged 60 years or older with at least one blood pressure (BP) measurement during the inclusion period, without pre-existent HT, diabetes mellitus (DM) or atherosclerotic cardiovascular disease at time of study start. Study outcomes were a diagnosis of HT within one month after cohort entry and the use of antihypertensive medication within 4 months after cohort entry in HT diagnosed patients. We compared the incidence of outcomes between the age groups, stratified by systolic blood pressure (SBP). Logistic regression analysis was used to assess the influence of age-adjusted SBP Z-scores, age and gender on the outcomes. Results: We included 19,500 patients from 159 GP's practices of whom 1,181 (6.1 %) were newly diagnosed with HT. Corrected for age-adjusted SBP, older patients were less likely to be diagnosed with HT (odds ratio per year age increase 0.98, p < 0.001). Corrected for age-adjusted SBP, no significant effect of age on the probability of treatment in newly diagnosed HT patients was observed (p = 0.82). Conclusions: This study showed that GPs are less inclined to diagnose HT with increasing patient age, but do not withhold treatment when they diagnose HT in older patients

Компаративний аналіз привабливості стратегічних зон господарювання підприємства

Запропоновано методику компаративного аналізу привабливості стратегічних зон господарювання підприємства з використанням методів багатокритеріального оцінювання.Предложена методика компаративного анализа привлекательности стратегических зон хозяйствования предприятия с использованием методов многокритериального оценивания.The article proposed a method for comparative analysis of attractiveness of enterprise strategic bussines unit using methods of multi-criteria evaluation

Anomalous Power Law Distribution of Total Lifetimes of Branching Processes Relevant to Earthquakes

We consider a branching model of triggered seismicity, the ETAS (epidemic-type aftershock sequence) model which assumes that each earthquake can trigger other earthquakes (``aftershocks''). An aftershock sequence results in this model from the cascade of aftershocks of each past earthquake. Due to the large fluctuations of the number of aftershocks triggered directly by any earthquake (``productivity'' or ``fertility''), there is a large variability of the total number of aftershocks from one sequence to another, for the same mainshock magnitude. We study the regime where the distribution of fertilities $\mu$ is characterized by a power law $\sim 1/\mu^{1+\gamma}$ and the bare Omori law for the memory of previous triggering mothers decays slowly as $\sim 1/t^{1+\theta}$, with $0 < \theta <1$ relevant for earthquakes. Using the tool of generating probability functions and a quasistatic approximation which is shown to be exact asymptotically for large durations, we show that the density distribution of total aftershock lifetimes scales as $\sim 1/t^{1+\theta/\gamma}$ when the average branching ratio is critical ($n=1$). The coefficient $1<\gamma = b/\alpha<2$ quantifies the interplay between the exponent $b \approx 1$ of the Gutenberg-Richter magnitude distribution $\sim 10^{-bm}$ and the increase $\sim 10^{\alpha m}$ of the number of aftershocks with the mainshock magnitude $m$ (productivity) with $\alpha \approx 0.8$. More generally, our results apply to any stochastic branching process with a power-law distribution of offsprings per mother and a long memory.Comment: 16 pages + 4 figure

Concepts of Cardiac Development in Retrospect

Recent research, enabled by powerful molecular techniques, has revolutionized our concepts of cardiac development. It was firmly established that the early heart tube gives rise to the left ventricle only, and that the remainder of the myocardium is recruited from surrounding mesoderm during subsequent development. Also, the cardiac chambers were shown not to be derived from the entire looping heart tube, but only from the myocardium at its outer curvatures. Intriguingly, many years ago, classic experimental embryological studies reached very similar conclusions. However, with the current scientific emphasis on molecular mechanisms, old morphological insights became underexposed. Since cardiac development occurs in an architecturally complex and dynamic fashion, molecular insights can only fully be exploited when placed in a proper morphological context. In this communication we present excerpts of important embryological studies of the pioneers of experimental cardiac embryology of the previous century, to relate insights from the past to current observations

Involving the patient: A prospective study on use, appreciation and effectiveness of an information system in head and neck cancer care

Objective: To determine use, appreciation and effectiveness of an electronic health information support system in head and neck (H&N) cancer care. Design: A prospective evaluation study. The evaluated system has four different functions: (1) communication amongst health care providers and between health care providers and patients, (2) information for health care providers and patients, (3) contact with fellow sufferers and (4) monitoring of discharged patients by means of electronic questionnaires. Evaluation of the system was done both objectively using automatically created log files and stored messages, and subjectively by using paper questionnaires from patients and general practitioners (GPs). Setting: Department of Otorhinolaryngology and Head and Neck Surgery of a tertiary health care centre in the Netherlands. The system was put at patients' disposal for a period of 6 weeks following discharge from the hospital after surgery for H&N cancer, and was additional to standard care. Participants: Head and neck cancer patients, hospital physicians, members of a hospital-based support team, GPs, district nurses and speech therapists. Main outcome measures: Actual use of the system by patients and health care providers. Patients' appreciation for each of the system's four different functions. GPs' appreciation for the system. Capability to detect potential patient problems with the system. Results: The system was used by 36 H&N cancer patients, 10 hospital physicians, 2 members of the support team, 8 GPs, 2 district nurses and 2 speech therapists. The total number of patient-sessions was 982: an average of 27.3 sessions per patient during the 6 weeks study period. In total, 456 monitoring questionnaires were completed. The support team in hospital responded with 231 actions. In 16 cases, an extra appointment was made for a patient with the hospital physician. Out of these cases, immediate action was considered necessary eight times. Patients appreciated the system highly, rating it with an average score of 8.0 on a 10-point scale. All patients used the monitoring function, and rated 'monitoring' with a mean score of 8.0 on a 10-point scale. Least used and appreciated was the 'contact with fellow sufferers' function. Only 8 out of possible 36 GPs used the system, rating it with an average of 5.6 on a 10-point scale. Conclusions: The electronic health information support system was used intensively and highly appreciated by H&N cancer patients. The system enabled the early detection of occurring health problems that required direct intervention. ICT can play an additional role in the management of patients, also in a relatively elderly and computer illiterate patient population

Manganese superoxide dismutase Ala-9Val polymorphism and risk of breast cancer in a population-based case–control study of African Americans and whites

INTRODUCTION: A polymorphism in the manganese superoxide dismutase (MnSOD) gene, Ala-9Val, has been examined in association with breast cancer risk in several epidemiologic studies. Results suggest that the Ala allele increases the risk of breast cancer and modifies the effects of environmental exposures that produce oxidative damage to DNA. METHODS: We examined the role of the MnSOD Ala-9Val polymorphism in a population-based case–control study of invasive and in situ breast cancer in North Carolina. Genotypes were evaluated for 2025 cases (760 African Americans and 1265 whites) and for 1812 controls (677 African Americans and 1135 whites). RESULTS: The odds ratio for MnSOD Ala/Ala versus any MnSOD Val genotypes was not elevated in African Americans (odds ratio = 0.9, 95% confidence interval = 0.7–1.2) or in whites (odds ratio = 1.0, 95% confidence interval = 0.8–1.2). Greater than additive joint effects were observed for the Ala/Ala genotype and smoking, radiation to the chest, and occupational exposure to ionizing radiation. Antagonism was observed between the Ala/Ala genotype and the use of nonsteroidal anti-inflammatory drugs. CONCLUSIONS: The MnSOD genotype may contribute to an increased risk of breast cancer in the presence of specific environmental exposures. These results provide further evidence for the importance of reactive oxygen species and of oxidative DNA damage in the etiology of breast cancer

Can a leader be seen as too ethical? The curvilinear effects of ethical leadership

Ethical leadership predicts important organizational outcomes such as decreased deviant and increased organizational citizenship behavior (OCB). We argued that due to the distinct nature of these two types of employee behaviors, ethical leadership decreases deviance in a linear manner (i.e., more ethical leadership leading to less deviance), but we expected ethical leadership to reveal a curvilinear relationship with respect to OCB. Specifically, we expected that, at lower levels, ethical leadership promotes OCB. However, at high levels, ethical leadership should lead to a decrease in these behaviors. We also examined a mechanism that explains this curvilinear pattern, that is, followers’ perceptions of moral reproach. Our predictions were supported in three organizational field studies and an experiment. These findings offer a better understanding of the processes that underlie the workings of ethical leadership. They also imply a dilemma for organizations in which they face the choice between limiting deviant employee behavior and promoting OCB