Fine‐needle aspiration of gray zone lesions of the breast: Fibroadenoma versus ductal carcinoma

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99655/1/dc22914.pd

SAG/ROC2 E3 ligase regulates skin carcinogenesis by stage-dependent targeting of c-Jun/AP1 and IκB-α/NF-κB

Sensitive to apoptosis gene (SAG)/regulator of cullins-2–Skp1-cullin–F-box protein (SCF) E3 ubiquitin ligase regulates cellular functions through ubiquitination and degradation of protein substrates. We report that, when expressed in mouse epidermis driven by the K14 promoter, SAG inhibited TPA-induced c-Jun levels and activator protein-1 (AP-1) activity in both in vitro primary culture, in vivo transgenic mice, and an AP-1– luciferase reporter mouse model. After AP-1 inactivation, epidermal proliferation induced by 7,12-dimethylbenz(a)-anthracene/12-O-tetradecanoylphorbol-13-acetate at the early stage of carcinogenesis was substantially inhibited. Later stage tumor formation was also substantially inhibited with prolonged latency and reduced frequency of tumor formation. Interestingly, SAG expression increased tumor size, not because of accelerated proliferation, but caused by reduced apoptosis resulting, at least in part, from nuclear factor κB (NF-κB) activation. Thus, SAG, in a manner depending on the availability of F-box proteins, demonstrated early-stage suppression of tumor formation by promoting c-Jun degradation, thereby inhibiting AP-1, and later-stage enhancement of tumor growth, by promoting inhibitor of κBα degradation to activate NF-κB and inhibit apoptosis

Statistics and clinical trials: The case of prednisolone in alcoholic hepatitis

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38385/1/1840160441_ftp.pd

Methods Used to Manage Urinary Incontinence by Older Adults in the Community

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111237/1/j.1532-5415.1989.tb05502.x.pd

P450 3A activity and cyclosporine dosing in kidney and heart transplant recipients

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109917/1/cptclpt1994135.pd

The prediction of radiationâ induced liver dysfunction using a local dose and regional venous perfusion model

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134805/1/mp1081.pd

Dietary fibre to reduce colon cancer risk in Alaska Native people: the Alaska FIRST randomised clinical trial protocol

Introduction Diet, shown to impact colorectal cancer (CRC) risk, is a modifiable environmental factor. Fibre foods fermented by gut microbiota produce metabolites that not only provide food for the colonic epithelium but also exert regulatory effects on colonic mucosal inflammation and proliferation. We describe methods used in a double-blinded, randomised, controlled trial with Alaska Native (AN) people to determine if dietary fibre supplementation can substantially reduce CRC risk among people with the highest reported CRC incidence worldwide. Methods and analyses Eligible patients undergoing routine screening colonoscopy consent to baseline assessments and specimen/data collection (blood, urine, stool, saliva, breath and colon mucosal biopsies) at the time of colonoscopy. Following an 8-week stabilisation period to re-establish normal gut microbiota post colonoscopy, study personnel randomise participants to either a high fibre supplement (resistant starch, n=30) or placebo (digestible starch, n=30) condition, repeating stool sample collection. During the 28-day supplement trial, each participant consumes their usual diet plus their supplement under direct observation. On day 29, participants undergo a flexible sigmoidoscopy to obtain mucosal biopsy samples to measure the effect of the supplement on inflammatory and proliferative biomarkers of cancer risk, with follow-up assessments and data/specimen collection similar to baseline. Secondary outcome measures include the impact of a high fibre supplement on the oral and colonic microbiome and biofluid metabolome. Ethics and dissemination Approvals were obtained from the Alaska Area and University of Pittsburgh Institutional Review Boards and Alaska Native Tribal Health Consortium and Southcentral Foundation research review bodies. A data safety monitoring board, material transfer agreements and weekly study team meetings provide regular oversight throughout the study. Study findings will first be shared with AN tribal leaders, health administrators, providers and community members. Peer-reviewed journal articles and conference presentations will be forthcoming once approved by tribal review bodies

Concurrent whole brain radiotherapy and bortezomib for brain metastasis

Abstract Background Survival of patients with brain metastasis particularly from historically more radio-resistant malignancies remains dismal. A phase I study of concurrent bortezomib and whole brain radiotherapy was conducted to determine the tolerance and safety of this approach in patients with previously untreated brain metastasis. Methods A phase I dose escalation study evaluated the safety of bortezomib (0.9, 1.1, 1.3, 1.5, and 1.7 mg/m2) given on days 1, 4, 8 and 11 of whole brain radiotherapy. Patients with confirmed brain metastasis were recruited for participation. The primary endpoint was the dose-limiting toxicity, defined as any ≥ grade 3 non-hematologic toxicity or grade ≥ 4 hematologic toxicity from the start of treatment to one month post irradiation. Time-to-Event Continual Reassessment Method (TITE-CRM) was used to determine dose escalation. A companion study of brain diffusion tensor imaging MRI was conducted on a subset of patients to assess changes in the brain that might predict delayed cognitive effects. Results Twenty-four patients were recruited and completed the planned therapy. Patients with melanoma accounted for 83% of all participants. The bortezomib dose was escalated as planned to the highest dose of 1.7 mg/m2/dose. No grade 4/5 toxicities related to treatment were observed. Two patients had grade 3 dose-limiting toxicities (hyponatremia and encephalopathy). A partial or minor response was observed in 38% of patients. Bortezomib showed greater demyelination in hippocampus-associated white matter structures on MRI one month after radiotherapy compared to patients not treated with bortezomib (increase in radial diffusivity +16.8% versus 4.8%; p = 0.0023). Conclusions Concurrent bortezomib and whole brain irradiation for brain metastasis is well tolerated at one month follow-up, but MRI changes that have been shown to predict delayed cognitive function can be detected within one month of treatment.http://deepblue.lib.umich.edu/bitstream/2027.42/112849/1/13014_2013_Article_928.pd

Autoregression as a means of assessing the strength of seasonality in a time series

BACKGROUND: The study of the seasonal variation of disease is receiving increasing attention from health researchers. Available statistical tests for seasonality typically indicate the presence or absence of statistically significant seasonality but do not provide a meaningful measure of its strength. METHODS: We propose the coefficient of determination of the autoregressive regression model fitted to the data ([Image: see text]) as a measure for quantifying the strength of the seasonality. The performance of the proposed statistic is assessed through a simulation study and using two data sets known to demonstrate statistically significant seasonality: atrial fibrillation and asthma hospitalizations in Ontario, Canada. RESULTS: The simulation results showed the power of the [Image: see text] in adequately quantifying the strength of the seasonality of the simulated observations for all models. In the atrial fibrillation and asthma datasets, while the statistical tests such as Bartlett's Kolmogorov-Smirnov (BKS) and Fisher's Kappa support statistical evidence of seasonality for both, the [Image: see text] quantifies the strength of that seasonality. Corroborating the visual evidence that asthma is more conspicuously seasonal than atrial fibrillation, the calculated [Image: see text] for atrial fibrillation indicates a weak to moderate seasonality ([Image: see text] = 0.44, 0.28 and 0.45 for both genders, males and females respectively), whereas for asthma, it indicates a strong seasonality ([Image: see text] = 0.82, 0.78 and 0.82 for both genders, male and female respectively). CONCLUSIONS: For the purposes of health services research, evidence of the statistical presence of seasonality is insufficient to determine the etiologic, clinical and policy relevance of findings. Measurement of the strength of the seasonal effect, as can be determined using the [Image: see text] technique, is also important in order to provide a robust sense of seasonality