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Daniel Rubin

Publications and source records attributed to Daniel Rubin.

6 recordsLinked to original sources
PubMed2006

A method to increase the power of multiple testing procedures through sample splitting.

Consider the standard multiple testing problem where many hypotheses are to be tested, each hypothesis is associated with a test statistic, and large test statistics provide evidence against the null hypotheses. One proposal to provide probabilistic control of Type-I errors is the use of procedures ensuring that the expected number of false positives does not exceed a user-supplied threshold. Among such multiple testing procedures, we derive the most powerful method, meaning the test statistic cutoffs that maximize the expected number of true positives. Unfortunately, these optimal cutoffs depend on the true unknown data generating distribution, so could never be used in a practical setting. We instead consider splitting the sample so that the optimal cutoffs are estimated from a portion of the data, and then testing on the remaining data using these estimated cutoffs. When the null distributions for all test statistics are the same, the obvious way to control the expected number of false positives would be to use a common cutoff for all tests. In this work, we consider the common cutoff method as a benchmark multiple testing procedure. We show that in certain circumstances the use of estimated optimal cutoffs via sample splitting can dramatically outperform this benchmark method, resulting in increased true discoveries, while retaining Type-I error control. This paper is an updated version of the work presented in Rubin et al. (2005), later expanded upon by Wasserman and Roeder (2006).

Algorithms↗
PubMed2004

Using Petri Net tools to study properties and dynamics of biological systems.

Petri Nets (PNs) and their extensions are promising methods for modeling and simulating biological systems. We surveyed PN formalisms and tools and compared them based on their mathematical capabilities as well as by their appropriateness to represent typical biological processes. We measured the ability of these tools to model specific features of biological systems and answer a set of biological questions that we defined. We found that different tools are required to provide all capabilities that we assessed. We created software to translate a generic PN model into most of the formalisms and tools discussed. We have also made available three models and suggest that a library of such models would catalyze progress in qualitative modeling via PNs. Development and wide adoption of common formats would enable researchers to share models and use different tools to analyze them without the need to convert to proprietary formats.

Algorithms↗
PubMed2004

Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects.

Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). The most common mutation, DeltaF508, results in the production of a misfolded CFTR protein that is retained in the endoplasmic reticulum and targeted for degradation. Curcumin is a nontoxic Ca-adenosine triphosphatase pump inhibitor that can be administered to humans safely. Oral administration of curcumin to homozygous DeltaF508 CFTR mice in doses comparable, on a weight-per-weight basis, to those well tolerated by humans corrected these animals' characteristic nasal potential difference defect. These effects were not observed in mice homozygous for a complete knockout of the CFTR gene. Curcumin also induced the functional appearance of DeltaF508 CFTR protein in the plasma membranes of transfected baby hamster kidney cells. Thus, curcumin treatment may be able to correct defects associated with the homozygous expression of DeltaF508 CFTR.

Animals↗
PubMed2004

Metastatic breast cancer in a 54-year-old woman: integrative treatment with yttrium-90 radioembolization.

In 1993, a 54-year-old woman was diagnosed with early-stage breast adenocarcinoma and treated with doxorubicin and cyclophosphamide followed by tamoxifen. Nine years later, the patient presented for integrative treatment, with liver metastases. Carcinoembryonic antigen was significantly elevated. The patient was started on a heavily fractionated, multiple-agent chemotherapy regimen; however, she underwent significant adverse effects and the treatment was suspended. She then started on intravenous nutrition along with specific nutritional supplements. Two months later, a similar chemotherapeutic regimen was started in association with her existing nutritional protocol. One month later, the carcinoembryonic antigen began to rise, and a positron emission tomography scan was ordered that revealed the persistence of multiple and extensive liver metastases as well as possible skeletal metastases. The patient was started on an oral bisphosphonate and referred to interventional radiology for consultation on radioembolization with yttrium-90. After being accepted for treatment, the patient under-went a right hepatic lobe angiogram and radioembolization. Within 2 weeks, she realized significant improvements in her clinical and laboratory status; chemotherapy was discontinued. She later underwent radioembolization to her left lobe. Thirteen months after the yttrium-90 treatment, the patient remains on an integrative program with radiographically and clinically stable disease.

Adenocarcinoma↗
PubMed2003

Hepatic MR imaging with ferumoxides: multicenter study of safety and effectiveness of direct injection protocol.

PURPOSE: To compare the safety and effectiveness of an undiluted direct injection of ferumoxides with those of a diluted slow infusion of ferumoxides during 30 minutes in patients with known liver lesions or in those suspected of having them. MATERIALS AND METHODS: Two hundred thirty-three patients at 16 institutions were randomized to receive either an undiluted direct injection of 0.56 mg of iron per kilogram of body weight of ferumoxides administered during 2 minutes (2 mL/min) or a diluted slow infusion administered during 30 minutes. Safety was assessed with monitoring for adverse events and laboratory tests. For sensitivity, specificity, and accuracy analysis, two independent blinded observers identified and classified lesions as benign or malignant with precontrast images and with pre- and postcontrast images combined. RESULTS: There was no statistically significant difference in adverse events in the group with direct injection compared with those in the group with infusion (21 [18%] of 114 patients vs 19 [17%] of 112 patients, respectively). No serious adverse events were observed. The most common adverse events in the group with direct injection versus the group with infusion were headache (five [4%] of 114 vs three [3%] of 112, respectively) and back pain (five [4%] of 114 vs three [3%] of 112, respectively). Overall, in 68 (62%) of 109 patients with direct injection and 71 (66%) of 108 patients with infusion, additional magnetic resonance (MR) imaging information was obtained after ferumoxides administration (P =.67). Sensitivity, specificity, and accuracy for the diagnosis of malignancy were significantly improved by adding images obtained after ferumoxides administration to the images obtained before contrast agent administration (P <.05 for all comparisons). CONCLUSION: Direct injection of ferumoxides has safety and effectiveness profiles similar to those of slow infusion of the agent. Further findings indicate that the addition of ferumoxides increases the sensitivity and specificity of hepatic MR evaluation when compared with unenhanced MR imaging.

Adult↗