Application of microarray analysis on computer cluster and cloud platforms.

BACKGROUND: Analysis of recent high-dimensional biological data tends to be computationally intensive as many common approaches such as resampling or permutation tests require the basic statistical analysis to be repeated many times. A crucial advantage of these methods is that they can be easily parallelized due to the computational independence of the resampling or permutation iterations, which has induced many statistics departments to establish their own computer clusters. An alternative is to rent computing resources in the cloud, e.g. at Amazon Web Services. OBJECTIVES: In this article we analyze whether a selection of statistical projects, recently implemented at our department, can be efficiently realized on these cloud resources. Moreover, we illustrate an opportunity to combine computer cluster and cloud resources. METHODS: In order to compare the efficiency of computer cluster and cloud implementations and their respective parallelizations we use microarray analysis procedures and compare their runtimes on the different platforms. RESULTS: Amazon Web Services provide various instance types which meet the particular needs of the different statistical projects we analyzed in this paper. Moreover, the network capacity is sufficient and the parallelization is comparable in efficiency to standard computer cluster implementations. CONCLUSION: Our results suggest that many statistical projects can be efficiently realized on cloud resources. It is important to mention, however, that workflows can change substantially as a result of a shift from computer cluster to cloud computing.

Costs of cloud computing for a biometry department. A case study.

BACKGROUND: "Cloud" computing providers, such as the Amazon Web Services (AWS), offer stable and scalable computational resources based on hardware virtualization, with short, usually hourly, billing periods. The idea of pay-as-you-use seems appealing for biometry research units which have only limited access to university or corporate data center resources or grids. OBJECTIVES: This case study compares the costs of an existing heterogeneous on-site hardware pool in a Medical Biometry and Statistics department to a comparable AWS offer. METHODS: The "total cost of ownership", including all direct costs, is determined for the on-site hardware, and hourly prices are derived, based on actual system utilization during the year 2011. Indirect costs, which are difficult to quantify are not included in this comparison, but nevertheless some rough guidance from our experience is given. To indicate the scale of costs for a methodological research project, a simulation study of a permutation-based statistical approach is performed using AWS and on-site hardware. RESULTS: In the presented case, with a system utilization of 25-30 percent and 3-5-year amortization, on-site hardware can result in smaller costs, compared to hourly rental in the cloud dependent on the instance chosen. Renting cloud instances with sufficient main memory is a deciding factor in this comparison. CONCLUSIONS: Costs for on-site hardware may vary, depending on the specific infrastructure at a research unit, but have only moderate impact on the overall comparison and subsequent decision for obtaining affordable scientific computing resources. Overall utilization has a much stronger impact as it determines the actual computing hours needed per year. Taking this into ac count, cloud computing might still be a viable option for projects with limited maturity, or as a supplement for short peaks in demand.

[Medial mobilisation of the left hemicolon]. / Die Mobilisation des linken Hemikolons von medial.

INTRODUCTION: Laparoscopic surgery of the colon is becoming more and more popular. However, regarding sigmoid resection, controversy remains concerning the extent of mobilisation, particularly regarding the splenic flexure. We developed a technique for anterior resection that meets all surgical standards: the anterior approach. MATERIALS AND METHODS: From October 1999 to March 2001, 50 patients with benign diseases of the colon underwent laparoscopically assisted sigmoid resection. A completely anterior approach for mobilisation of the left hemicolon was used in all cases. Positioning the patients in Trendelenburg position on the extreme right side enabled primary ligation of the inferior mesenteric vein and artery as well as complete mobilisation of the splenic flexure from the middle. A transanal circular stapling device was used to reanastomose the colon 10-12 cm from the anus. RESULTS: There were conversion and complication rates of 10% each, and three patients needed to be reoperated. The median operating time was 180 min. Patients could be dismissed on the 14th postoperative day. CONCLUSION: To establish an operative standard, this technique has so far been used only for benign colon diseases. According to our experience, we think that it meets all oncological standards. Use of this technique in the treatment of malignant diseases seems therefore justified.

The urinary bladder angiotensin system: response to infusions of angiotensin I and angiotensin-converting enzyme inhibitors.

The circulating and urinary bladder tissue concentrations of angiotensin I (ANG I) and angiotensin II [ANG-(1-8)] were examined in anesthetized Sprague-Dawley male rats given an intravenous bolus infusion of either ANG I, the angiotensin-converting enzyme (ACE) inhibitors enalaprilat or ramiprilat, or saline. The mean concentrations of ANG I and ANG-(1-8) were markedly higher in the urinary bladder tissue than in whole blood. There was a significant increase in the concentration of ANG I and ANG-(1-8), both in the urinary bladder tissue and the circulation, after the ANG I infusion. Both ACE inhibitors were associated with an increase in the concentration of whole blood ANG I; however, tissue ANG I levels were significantly increased only following ACE inhibition with ramiprilat but not with enalaprilat. Both plasma and urinary bladder tissue ANG-(1-8) levels decreased significantly following ACE inhibition, but only with ramiprilat. The elevated urinary bladder tissue levels of ANG I and ANG-(1-8) at baseline, compared with circulating levels, and the maintenance of ANG-(1-8) in bladder tissue in the face of inhibition of the circulatory renin-angiotensin system with enalaprilat support the presence of an autocrine/paracrine renin-angiotensin system in the urinary bladder. Under the current experimental conditions, ramiprilat appears to have enhanced bladder activity compared with enalaprilat.

[Bisphosphonate therapy of Paget's disease of bone with pamidronate]. / Bisphosphonattherapie des Morbus Paget des Knochens mit Pamidronat.

BACKGROUND: Paget's disease of bone is a disease with massive focal increase of bone turnover. Bisphosphonates like etidronate inhibit of osteoclastic bone resorption and are therefore established in the treatment of Paget's disease. The aminobisphosphonate pamidronate is 100 times more potent than etidronate. To assess the therapeutic potential for Paget's disease, we have investigated the long-term efficacy of two different dosages of pamidronate. PATIENTS AND METHODS: 40 consecutive patients with Paget's disease received a total dose of either 180 mg (n = 21) or 100 mg (n = 19) of pamidronate i.v. over 9 or 5 days respectively in two independent phases of a prospective trial. Efficacy and side effects were monitored for a follow up period of up to two years. RESULTS: For both dosages a significant reduction of urinary 24-h-hydroxyprolin excretion and serum alkaline phosphatase (AP) levels as parameters of disease activity was recorded. AP levels fell to a minimum of 31 +/- 3% (180 mg) and 41 +/- 5% (100 mg) of pretreatment values, respectively. Two years after treatment, a significant reduction of disease activity could still be detected. Side effects, including transient fever, head ache or bone pain occurred in one third of the patients. CONCLUSION: Pamidronate treatment for Paget's disease of bone leads to a sustained inhibition of elevated bone turnover.

Glomerular function and structure in the sodium-replete and sodium-deplete uninephrectomized spontaneously hypertensive rat: effect of blood pressure reduction, glomerular structure, and blood pressure reduction.

To assess the effects of chronic dietary sodium restriction and blood pressure reduction on glomerular function and structure during the pathogenesis of hypertensive renal disease, experiments were conducted in uninephrectomized (UNX) spontaneously hypertensive rats (SHR) using the dihydropyridine calcium antagonist manidipine. Male SHRs underwent UNX at age 10-11 weeks and subsequently were assigned to one of four groups: sodium-replete (0.4%); sodium-replete and a predetermined antihypertensive dose of manidipine (20 mg/kg body weight); sodium-deplete (0.09%); and sodium-deplete and manidipine (20 mg/kg body weight). Twelve weeks later, renal morphologic and functional studies were performed. Sodium restriction had no significant effect on systolic blood pressure, but creatinine clearance and urinary protein excretion were decreased. Importantly, mean glomerular volume and the prevalence of mesangial expansion were lower with sodium restriction. This occurred in the presence of high concentrations of plasma and renal tissue angiotensin II. Manidipine significantly reduced systolic blood pressure in the sodium-replete and sodium-deplete UNX-SHRs. This therapy was not associated with significant changes in creatinine clearance and urinary protein excretion in the sodium-deplete or sodium-replete UNX-SHRs. The prevalence of mesangial expansion in the sodium-replete UNX-SHR was approximately 50% lower with manidipine. Plasma and renal tissue angiotensin II concentrations were not affected by the drug. In the sodium-deplete UNX-SHR, the prevalence of mesangial expansion was not reduced further by manidipine. However, plasma and renal tissue angiotensin II concentrations were increased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Intraoperative catheter thrombolysis as an adjunct to surgical revascularisation for infrainguinal limb-threatening ischaemia.

The objective of this study was to assess the benefits of intraoperative thrombolysis (IOL) on patients with acute leg ischaemia. This study was conducted in the Department of Cardiovascular Surgery, Inselspital, Berne, Switzerland. IOL was prospectively assessed in 25 patients with infrainguinal limb-threatening ischaemia due to acute thrombosis of atherosclerotic lesions and aneurysms (44%), occluded grafts (32%), arterial injuries (12%), delayed embolism (8%) and trash foot (8%). Three hundred and seventy-five thousand units of urokinase were delivered over 30 min with inflow occlusion to the profunda femoral artery in 8%, to the calf arteries via exposed trifurcation in 88% and to the pedal arch via exposed posterior tibial artery at the ankle in 8% of the patients. This was followed by graft thrombectomy in 24%, femoropopliteal bypass in 60%, intraoperative percutaneous transluminal angioplasty in 12% and vein patch angioplasty in 16%. Chief outcome measures were: postoperative morbidity; mortality; patency and limb salvage up to a maximum of 2 years. Postoperative bleeding complications occurred in two patients (8%) and consisted of two wound haematomas. Four patients died within 30 days after IOL, but no death could be attributed to IOL. All remaining patients were followed with a mean follow-up time of 10.9 months. The patency and limb salvage rate remained stable at 71 and 86% after 6 and 2 months, respectively. Conclusions were that IOL followed by surgical inflow restoration is a straightforward procedure for limb-threatening ischaemia with rewarding results regarding side effects, patency and limb salvage.

Detection of localized breast cancer by prospective mammographic screening criteria.

From 1983 to 1986, 1110 gynecology office patients met our prospective mammographic screening criteria. Ninety-eight mammographically guided, needle-localized breast biopsies were performed on 89 patients (8.0%). Twenty-one nonpalpable breast cancers (22.0%) were diagnosed in 18 patients with these methods. Treatment alternatives chosen in patients with positive biopsy specimens are presented. The importance of establishing consistent criteria for mammography and breast biopsy in the early diagnosis of localized breast cancer is discussed. The unique opportunity of the gynecologist to change the morality rate of breast cancer is emphasized.

The detection of nongenital pelvic tumors mimicking gynecologic disease.

Nongenital pelvic tumors frequently remain undiagnosed until operation. Of 470 patients operated upon for suspected tubal or ovarian pathologic conditions, 25 were found to have inflammatory or neoplastic gastrointestinal lesions; one patient had a paraganglioma of the urinary bladder and one, a malignant retroperitoneal tumor. A variety of other extragenital pelvic tumors have been reported in the literature. Select utilization of the newer diagnostic modalities, combined with traditional methods, promise more accurate preoperative assessment of the suspicious pelvic mass.

[The problem of overpopulation in Asia]. / Zum Problem der Ubervölkerung in Asien.

PIP: The relation between medicine and overpopulation is seen in the following: 1) achievements in medicine have decreased mortality leading to population explosion, 2) lack of food supply leads to deficiency diseases, and 3) starvation and overpopulation leads to the social diseases of unemployment and poverty. Population control can be achieved by medical methods of contraception. Japan's overpopulation is contrasted with that of India. In Japan the standard of living is high and food supply adequate because Japan's technological products are exported and food imported. The mostly rural areas of India promote families with many children. The available farmland is not sufficient for all family members. Growing children seek occupations in the cities leading to slum conditions and great poverty and misery as exemplified by Calcutta. In Europe there is a mostly balanced population because industrialization counteracts population growth. Too many children are a financial burden to the parents and the getting of children is prevented by contraception and/or abortion. In developing countries this balance is not yet achieved; industrialization lags behind the application of medical technology which promotes population explosion. To counteract this, medical methods of contraception must be used. In India with an annual population growth of 2.1% (this would lead to a population of 1.17 billion by the year 2008) this control would be best achieved through tubal ligation and/or vasectomy. There is little motivation for other methods in family planning because of the attitude toward poverty and hardship. To achieve a shrinking of their population, vasectomy (easier and less hazardous than tubal ligation) should be performed after the 2nd child. This, obviously, would need a national well-organized, program and a change in attitude of India's inhabitants. If not, the future might lead to rebellion by the poor and starving masses; civil war might break out and thus decimate the population.^ieng