Responds to Brock's comments on the current author's original article which talks about the original 1964 Kitty Genovese murder 38-witness account. Manning, Levine, and Collins wish to leave it to readers of this journal to judge whether it is wise to continue to use in textbooks inaccurate accounts presented as facts, and whether it is sensible to conclude that despite being read by many thousands of students and researchers, the story of the 38 witnesses has had "negligible scholarly impact."(PsycINFO Database Record (c) 2008 APA, all rights reserved).

PURPOSE: Pharmacologic concentrations of ascorbate may be effective in cancer therapeutics. We hypothesized that ascorbate concentrations achievable with i.v. dosing would be cytotoxic in pancreatic cancer for which the 5-year survival is <3%. EXPERIMENTAL DESIGN: Pancreatic cancer cell lines were treated with ascorbate (0, 5, or 10 mmol/L) for 1 hour, then viability and clonogenic survival were determined. Pancreatic tumor cells were delivered s.c. into the flank region of nude mice and allowed to grow at which time they were randomized to receive either ascorbate (4 g/kg) or osmotically equivalent saline (1 mol/L) i.p. for 2 weeks. RESULTS: There was a time- and dose-dependent increase in measured H(2)O(2) production with increased concentrations of ascorbate. Ascorbate decreased viability in all pancreatic cancer cell lines but had no effect on an immortalized pancreatic ductal epithelial cell line. Ascorbate decreased clonogenic survival of the pancreatic cancer cell lines, which was reversed by treatment of cells with scavengers of H(2)O(2). Treatment with ascorbate induced a caspase-independent cell death that was associated with autophagy. In vivo, treatment with ascorbate inhibited tumor growth and prolonged survival. CONCLUSIONS: These results show that pharmacologic doses of ascorbate, easily achievable in humans, may have potential for therapy in pancreatic cancer.

This study was performed to quantify the fraction of excreted creatinine not attributable to creatinine filtration for accurately determining the glomerular filtration rate in mice. To measure this we compared creatinine filtration with the simultaneous measurement of inulin clearance using both single-bolus fluorescein isothiocyanate (FITC)-inulin elimination kinetics and standard FITC-inulin infusion. During anesthesia, creatinine filtration was found to be systematically higher than inulin clearance in both male and female C57BL/6J mice. The secretion fraction was significantly less in female mice. Administration of either cimetidine or para-aminohippuric acid, competitors of organic cation and anion transport respectively, significantly reduced the secretion fraction in male and female mice and both significantly increased the plasma creatinine level. Creatinine secretion in both genders was not mediated by the organic cation transporters OCT1 or OCT 2 since secretion fraction levels were identical in FVB wild-type and OCT1/2 knockout mice. Thus, secretion accounts for about 50 and 35% of excreted creatinine in male and female mice, respectively. Increasing plasma creatinine threefold by infusion further increased the secretion fraction. Renal organic anion transporter 1 mRNA expression was higher in male than in female mice, reflecting the gender difference in creatinine secretion. Hence we show that there is a major secretory contribution to creatinine excretion mediated through the organic anion transport system. This feature adds to problems associated with measuring endogenous creatinine filtration in mice.Kidney International advance online publication, 23 December 2009; doi:10.1038/ki.2009.501.

PURPOSE: The uptake of new health care technologies is usually driven by industry promotion, physician interest, patient demand, and institutional ability to acquire the technology. The introduction of positron emission tomography (PET) scanning in the province of Ontario, Canada, followed a different path. METHODS: The Ontario provincial government, through its Ministry of Health and Long-Term Care, commissioned a systematic review of the literature. When this found only weak evidence that PET has a positive impact on clinical outcomes, the Ministry introduced a provincial PET evaluation program to close the evidence gap. RESULTS: This article describes the challenges encountered establishing the PET evaluation program. These included the design and conduct of the initial clinical trials, the establishment of a PET cancer registry, standardizing how PET scans were performed and reported, and gaining acceptance by health professionals for the evaluative program. CONCLUSION: The proliferation of health technologies is a key driver of increasing health care costs. The Ontario approach to the introduction of PET is a model worth consideration by health systems seeking to ensure that they receive value for money based on a strong evidentiary base when introducing new health technologies.

To the Editor: On the basis of cell and animal experiments with dehydroascorbic acid, Heaney and colleagues state,"These results suggest that supplementary vitamin C may have adverse consequences in patients receiving cancer therapy"(1). Selectively referring to dehydroascorbic acid as vitamin C throughout the majority of this work may send a clouded message to patients and their caregivers. All known actions of vitamin C are mediated by the reduced molecule ascorbate, not the oxidized molecule dehydroascorbic acid. Mice lacking the tissue transport protein specific for ascorbate (Slc23a2) do not survive because of severe vitamin C deficiency, despite having no impairments in dehydroascorbic acid transport (2). The suggestion that "...study conditions were relevant to clinical conditions"(1) should be viewed cautiously. Compared with cells devoid of any ascorbate, researchers attenuated cytotoxicity to antineoplastic agents in vitro (11-27%) by prior treatment with 500 mumol/L dehydroascorbic acid, which rapidly elevated intracellular ascorbate concentrations up to 18 mmol/L within 1 hour (1). In vivo, numerous reductive systems ensure plasma concentrations of dehydroascorbic acid do not exceed 1 mumol/L (3, 4). Although alluded to, the actual level of dehydroascorbic acid formed endogenously within the oxidative environments of tumors was not measured in either this (1) or the previous studies cited by this group (5, 6). Most cells in vivo, including cancer cells, maintain a constant intracellular ascorbate concentration of 1 to 5 mmol/L, which never decreases to zero. Data collected in vitro by comparing two extremes, 0 and 18 mmol/L ascorbate for instance, are implausible with regard to tumors and other tissues in general. The investigators conclude that "This finding could have important clinical relevance given the wide use of vitamin C as a nutritional supplement"(1). However, to produce an effect in xenografted mice, a course of 8 x 250 mg/kg dehydroascorbic acid was administered intravenously (1). This regimen does not simulate oral ingestion of vitamin C supplements. In fact, irreversible diabetes can be induced in rats after intravenous injection of 700 mg/kg dehydroascorbic acid (7). Because meaningful differences exist in regard to chemistry, bioavailability, and metabolism, it may be imprudent to connect data gathered with dehydroascorbic acid to vitamin C (ascorbate) and oral supplements. Numerous randomized human clinical trials have not shown decreased chemotherapeutic efficacy with dietary supplement usage, including vitamin C (8). Scientific dialogue on the subject may benefit from further preclinical testing of oral vitamin C (ascorbate) supplementation and cancer treatment in addition to experiments deigned solely with dehydroascorbic acid. Disclosure of Potential Conflicts of Interest No potential conflicts of interest were disclosed.

Most sociological theories consider murder an outcome of the differential distribution of individual, neighborhood, or social characteristics. And while such studies explain variation in aggregate homicide rates, they do not explain the social order of murder, that is, who kills whom, when, where, and for what reason. This article argues that gang murder is best understood not by searching for its individual determinants but by examining the social networks of action and reaction that create it. In short, the social structure of gang murder is defined by the manner in which social networks are constructed and by people's placement in them. The author uses a network approach and incident-level homicide records to recreate and analyze the structure of gang murders in Chicago. Findings demonstrate that individual murders between gangs create an institutionalized network of group conflict, net of any individual's participation or motive. Within this network, murders spread through an epidemic-like process of social contagion as gangs evaluate the highly visible actions of others in their local networks and negotiate dominance considerations that arise during violent incidents.

The Authors reconstruct the vicissitudes that led to the murder of Georg Wirsüng on the evening of 22nd August 1643 in Padua. Among the motives for the murder, it was later assumed, was jealousy over the discovery of the main pancreatic duct. The Authors recall that this discovery, which removed the pancreas from the sphere of amorphous organs in order to correctly place it among the glands, was not originally made by the celebrated scientist himself but is attributable to his young co-worker Moritz Hoffmann. However, Georg Wirsüng had the merit of confirming and disclosing the discovery. This circumstance, which even today is not widely recognised among the scientific community, is worth remembering in the name of respect for the historical truth.