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The processing elements of many modern tightly coupled multicomputers are connected via mesh or toroidal networks. Such interconnects are simple and highly scalable, but suffer from high fragmentation, low utilization, and insufficient fault tolerance when the resources allocated to each job are dedicated. High-dimensional interconnects may be more efficient in certain cases, but are based on complex and expensive components and scale poorly. We present a novel hardware/software architectural approach that detaches the processing elements of the system from the interconnect and augments the traditional toroidal topology to provide additional connectivity options and additional link redundancy. We explore the properties of the new "multitoroidal" topology and the improvements it offers in resource utilization and failure tolerance. We present the results of extensive simulation studies to show that for practically important types of workloads, the resource utilization may be increased by 50 percent and, in certain cases, as much as 100 percent compared to toroidal machines and is, in fact, close to the theoretically optimal case of a full crossbar interconnect. The combined hardware/software architectural innovation is a major significant improvement in resource utilization on top of the state of the art in scheduling algorithm research. Also, multitoroidal multicomputers are able to work under link failure rates of 0.002 failures per week that would shut down toroidal machines. A variant of the multitoroidal architecture is implemented in the Blue Gene/L supercomputer. more...

Central nervous system (CNS) metastases from breast cancer are common and can present as the first or solitary site of disease progression. The CNS has been reported to act as a sanctuary site that denies access to many chemotherapeutic agents. We present here, a series of 10 metastatic breast cancer patients who developed CNS metastases after an initial response to trastuzumab treatment. Forty one patients with metastatic HER2-overexpressing breast cancer, without evidence of CNS involvement prior to the initiation of trastuzumab treatment, were followed during trastuzumab treatment. A neurological evaluation was performed in those patients who developed neurological signs or symptoms during the course of treatment. The clinical course and pattern of CNS involvement in these patients are discussed. Thirty two patients (78%) showed an initial response to trastuzumab treatment. Ten (31%) of the responding patients developed either isolated CNS relapse or concurrent CNS and systemic progression at a median of 43 weeks after the initiation of trastuzumab treatment. Trastuzumab as a single agent was continued following control of brain symptoms in three patients, two showed signs of systemic disease progression at 11 and 15 weeks following the diagnosis of CNS metastases, respectively. In two other patients, trastuzumab in combination with weekly chemotherapy was continued for more than 20 weeks after CNS relapse without evidence of disease progression. The incidence of CNS involvement in our group of patients was higher than expected. With more successful and prolonged systemic anti-tumour effects achieved by novel drug combinations, the risk of developing CNS metastases might be even greater. Evaluation of prophylactic cranial irradiation strategies might be studied for high-risk patients. more...

Summary Background Primary papillary serous carcinoma of the peritoneum is a well-known entity in women The tumour is derived from the extraovanan mesothelium and the pelvis and lower abdomen mesothelia The treatment strategies are similar to ovarian serous papillary carcinoma Patients and methods A case of primary serous papillary carcinoma of the peritoneum in a man is presented The patient, 53 years old, died 2 months after diagnosis Results The histologic and immunohistochemical studies of the tumour will be presented These studies, made during lifetime and at autopsy of the patient, confirm a diagnosis of primary serous papillary carcinoma of the peritoneum Conclusions primary serous papillary carcinoma of the peritoneum can occur in men, and should be considered in the differential diagnosis in cases of abdominal carcinomatosis of unknown origin Treatment options remain to be determined more...

Hyperinsulinemic euglycemic clamps were performed on six patients with compensated alcoholic cirrhosis and on six normal comparison subjects. As in previous studies, glucose uptake in the cirrhotic patients was only 21% of the comparison value. The cirrhotic patients had high growth hormone (GH) and low insulin-like growth factor-I (IGF-I) levels, with low insulin-like growth factor-binding protein (IGFBP)-3 levels, but surprisingly high IGFBP-I levels (26.8 +/- 8.4 microgH vs. 3.2 +/- 0.2 microm/L, P < .001). The log IGFBP-1 level was inversely correlated with the log insulin sensitivity (r = -.95). The clamps were repeated with a somatostatin infusion to suppress GH secretion. IGFBP-1 increased in both groups, especially in the cirrhotic subjects. Insulin sensitivity increased in the normal subjects but was unchanged in the cirrhotic patients. Following GH treatment (0.13 U/kg/d for 5 days), the clamps were repeated. GH, IGF-1, and IGFBP-3 levels were now similar in the two groups; IGFBP-1 levels decreased in the cirrhotic patients but remained fivefold higher than the comparison value (10.6 +/- 3.7 vs. 2.1 +/- 0.4, P < .05). Glucose uptake in the cirrhotic patients remained only 29% of the comparison value, but the change in their insulin sensitivity was inversely correlated with the change in their IGFB-1 levels (r = -.84). These results suggests an important role for IGFBP-1 in modulating insulin sensitivity in cirrhosis. more...

Summary The aminosalicylate group of drugs, used in the treatment of inflammatory bowel disease, has a variety of adverse effects, which include: Common adverse reactions Nausea, vomiting, abdominal pain — Up to 40% with sulphasalazine; much less with mesalazine or olsalazine Headache — 1–15% with sulphasalazine; less with mesalazine or olsalazine Blood dyscrasias — 1–3% with sulphasalazine Rare with mesalazine or olsalazine. Male intertility — 80% with sulphasalazine, None with mesalazine or alsalazine. Watery diarrhoea — All 5-ASA preparations; obout 15% with olsalazine. Rash fever — 0.5–5% with sulphasalazine; rare with mesalazine or olsalazine. Rare adverse reactions Nephrotoxicity — All drugs. Possibly more common with mesalazine. Pancreatitis — Possibly more common with mesalazine. Exacerbation of coiltis, hepatotoxicity, pulmonary fibrosis, polyarteritis — Very rare with a ninosalicylates. more...

Forearm glucose uptake during a hyperglycaemic (10 mmol/l) glucose clamp was diminished to 33% of the normal value (p = 0.012) in six cirrhotic patients compared with matched control subjects. Fasting insulin concentrations were significantly elevated in the cirrhotic patients confirming insulin resistance which may have been induced by chronic hyperinsulinaemia. The cirrhotic patients received one week of treatment with 50 micrograms octreotide subcutaneously three times daily which reduced pre-dose fasting insulin levels from 26.2 +/- 7.9 to 18.1 +/- 6.2 mU/l p < 0.005, and post dose levels to 7.0 +/- 3.5 mU/l p < 0.005. However when the glucose clamp was repeated 20 hours after the last dose of octreotide no change was detected in clamp glucose requirements, forearm glucose uptake, or stimulated insulin secretion. It was concluded that one week of lowering insulin levels does not reverse the insulin resistance of cirrhosis. more...

Background Reports of the risk of colorectal neoplasia associated with a variant of the adenomatous polyposis coli (APC E1317Q) gene are conflicting. Using a case–control design, we investigated this relationship within a clinic-based cohort followed through the Integrated Cancer Prevention Center and the Tel-Aviv Sourasky Medical Center. Materials and Methods All study subjects were tested for the APC E1317Q variant at enrollment. Subjects underwent colonoscopic evaluation (±biopsy and/or polypectomy) and had cancer history and colorectal neoplasia risk factors assessed. The crude and adjusted risks of neoplasia associated with the E1317Q variant were calculated. Results The prevalence of the E1317Q variant was 1.4% in the entire study sample and 3.2% in Sephardic Jews. E1317Q was more prevalent among cases: 15 of 458 (3.3%) cases were carriers compared with 11 of 1431 (0.8%) controls [odds ratio (OR) 4.4, 95% CI 2.0–9.6]. When stratified by neoplasia type, adenoma risk was significantly elevated in carriers (OR 4.1, 95% CI 1.8–9.4) but colorectal cancer risk was not (OR 2.1, 95% CI 0.8–5.3). After adjustment, the E1317Q variant remained a significant predictor of colorectal adenoma (OR 4.6, 95% CI 2.0–10.8). Conclusions The APC E1317Q variant is associated with colorectal neoplasia, particularly colorectal adenomas, but further studies are still needed. Variant prevalence is elevated in Sephardic Jews. more...

BACKGROUND: Laser treatment for malignant dysphagia is limited by recurrent intraluminal tumour requiring repeated treatment at four to eight week intervals. AIMS: To reduce the need for follow up treatment and to improve survival, patients successfully palliated by laser were treated with intraluminal radiotherapy. PATIENTS: 32 patients with inoperable oesophageal carcinoma (18 adeno and 14 squamous cell carcinoma). METHODS: The patients were initially palliated by a median of three laser treatments. They were then treated with intraluminal radiotherapy, receiving 10-15 Gy at 1 cm from the source as a single treatment with the Selectron system. Patients with squamous cell carcinoma also received external radiotherapy (30 to 50 Gy). RESULTS: After the radiotherapy nine patients survived a median of 22 (range 4-40) weeks without requiring any further endoscopic treatment. The remaining patients survived a median of 40 (range 4-102) weeks and required a median of three follow up endoscopic treatments over that time. Eleven patients developed fibrous strictures with no intraluminal tumour and were treated by dilatation. Twelve patients required dilatation and repeat laser therapy for a combination of fibrous stricture and recurrent intraluminal tumour. Six patients eventually required Atkinson tubes. CONCLUSIONS: The combination of laser treatment with intraluminal radiotherapy provides good palliation and may reduce the need for repeated endoscopic treatment. Fibrous stricture formation is a common complication. more...

Aim To evaluate the effectiveness of various treatment regimens for bronchiolitis in hospitalised children in three general paediatric wards in which different treatment protocols are customary. Patients and methods Data was retrospectively collected for all hospitalised children under two years of age with clinical bronchiolitis, between October 2012 and March 2013. Results During the study, a total of two hundred eighty six children were hospitalised with bronchiolitis in wards A, B and C. Clinical and laboratory parameters upon admission were similar among the patients in the three wards. The treatment differed between the wards, as in ward C, use of antibiotics and hypertonic saline inhalations was significantly less (p Multivariate analysis showed that low saturation upon admission, higher WBC count and the use of hypertonic saline inhalations were predictive of a longer period of saturation Conclusions No proof was found as to the added effectiveness of different treatments in bronchiolitis. Furthermore, the use of hypertonic saline inhalations might be associated with a longer period of low saturation and a longer hospital stay. more...

Aim To examine daytime liver glycogen accumulation in prepubertal children with Type 1 diabetes mellitus (Type 1 DM) compared with non-diabetic controls. Methods Liver glycogen content was ascertained in the fasting (morning) and fed (afternoon) state using 13C magnetic resonance (MR) spectroscopy. Data were analysed from six children with Type 1 DM (median (range) age 8.7 (6.3–12.2) years), who were all on conventional insulin regimens, and six healthy controls (age 8.9 (7–10.2) years). Results Children with diabetes tended to have lower fasting glycogen values than controls but this did not reach statistical significance (median (range) 154 (70–177) vs. 178 (120–203) mM glycosyl units, Type 1 DM vs. controls respectively; P = 0.06). Glycogen increased in all children with diabetes during the day and concentrations were similar to those in controls by the afternoon (175 (157–299) vs. 172 (136–238) mM glycosyl units; P = 0.7). Conclusions The ability of young children with Type 1 DM to replace liver glycogen depleted after an overnight fast was at least as good as that in control subjects, suggesting that impaired glycogen storage is not a contributory factor in nocturnal hypoglycaemia. Diabet. Med. 18, 659–662 (2001) more...

Of 86 patients with inoperable malignant dysphagia, 68 (79 per cent) underwent successful palliation by endoscopic laser therapy, of whom 24 remained well palliated until the time of death. In 18 patients laser treatment was unsuccessful and nine of these underwent intubation, eight successfully. After successful laser therapy, dysphagia recurred in 44 patients a mean of 7.8 weeks later. Of these, 31 received palliation until death by dilatation with or without laser therapy, and 13 required intubation. The overall laser-related complication rate was 12 per cent with a mortality rate of 4 per cent. The intubation-related mortality rate was 9 per cent. more...

494 Background: FOLFOX4 + q1w cetuximab is a standard 1st-line regimen in KRAS wt mCRC. This trial evaluated FOLFOX4 + q1w cetuximab (Arm A) and FOLFOX4 + q2w cetuximab (Arm B) as 1st-line therapy in KRAS wt mCRC. Methods: Pts with KRAS wt mCRC were randomized to q1w cetuximab (400 mg/m2initial dose then 250 mg/m2/wk) or q2w cetuximab (500 mg/m2 every 2 wks). Both arms received FOLFOX4 (folinic acid 200 mg/m2, then 5-FU 400 mg/m2bolus, then 5-FU 600mg/m2 over 22 h on days 1+2, plus oxaliplatin 85 mg/m2 on day 1 q2w). Primary endpoint is objective response rate (ORR) which was analyzed in a protocol specified interim analysis. Secondary efficacy endpoints are progression- free survival (PFS) and overall survival. Results: From Sep 2007 to Sep 2009, 152 pts with KRAS wt tumors (22 centers in 12 countries) were randomized and received ≥1 dose of study treatment, arm A (n=75) and arm B (n=77). Baseline characteristics were well balanced (A vs B): mean age: 57 vs 60 years, Karnofsky Performance Score (PS) 80: 15% vs 18%, PS 90: 45% vs 40%, PS 100: 40% vs 42%, male gender: 40% vs 45%, prior adjuvant or neoadjuvant therapy: 23% vs 17%, metastases at initial diagnosis: 65% vs 64%, and >2 involved organs: 24% vs 29%. Median follow up was 12 months. ORR (CR + PR) was 51% in arm A and 63% in arm B, respectively, the difference between arm B and A was 12% (95% CI: -4% to 27%). Preliminary results for PFS time did not indicate relevant differences between both arms. Mature PFS results will be presented at the symposium. Based on current data, most common grade 3-4 adverse events (≥ 10% in any arm, A vs B) were neutropenia/neutrophil count decreased in 32 vs 34%, rash in 15 vs 16% and diarrhea in 7 vs 10% of the pts. Conclusions: These data suggest that cetuximab q2w has comparable efficacy and an equivalent safety profile as q1w dosing in combination with FOLFOX4. Data collection and analysis is ongoing. [Table: see text] [Table: see text] more...

13082 Background: The A3 adenosine Gi protein-coupled receptor is highly expressed in malignant compared to normal cells. Activating the A3 adenosine receptor (A3AR) with the highly selective non-cytotoxic agonist, CF101 (IB-MECA), inhibit of colon, prostate, melanoma, pancreatic and hepatocellular cancer growth in experimental animal models, via down-regulation of the Wnt and NF-κB signal transduction pathways. Oral CF101 has been shown to inhibit colon, prostate, melanoma, pancreatic and hepatocellular cancer growth in experimental animal models. Methods: A phase II dose-finding, randomized, blinded study of oral CF101 (0.1, 1& 4 mg PO BID), was conducted to define activity and safety in heavily pre-treated metastatic colorectal cancer pts. From 6/1/2003–7/4/2004, 70 pts, median age 62 with measurable colorectal cancer, PS ≤2 were enrolled, 21 pts progressed after irinotecan and 49 pts after both irinotecan and oxaliplatin-based regimens. Results: The median time on treatment was 10.3 weeks. No objective response was observed; however, SD for 8 wks duration was achieved in 24 pts (34%), for 16 weeks in 8 pts (11%) and 2 pts were treated for more than 24 weeks. The median time to treatment progression was 72 days and for overall survival was 254 days without any significant difference among the 3 trial doses [8 survivors till today]. There were no obvious treatment related serious adverse events. Conclusions: The final results of the study show that CF101 is well tolerated and may stabilize disease for at least 2 months in 35% of the pts. The median survival time (8 months) compared with other targeted therapy investigated lately is encouraging. Combining CF101 with chemotherapy may be beneficial in the treatment of metastatic colorectal cancer. No significant financial relationships to disclose. more...

Owing to the rapid growth of world population and the resulting development of industry and agriculture, there is a constantly increasing demand for fresh water. At the same time, the quality of the available resources is being affected by salinity and pollution (Marshall, 1972). Consequently, the problem of water supply, which is directly related to the supply of food, is gradually becoming one of the crucial issues facing mankind. more...

Citrus is the largest agricultural production and export crop in Israel. In 1965, it represented about 17% of total production and about 80% of total export. The area planted with citrus was then approximately 45,200 ha, and water consumption was 323.1 million m3, representing about one-third of the total water allocation to agriculture. more...