Contamination Estimation via Convex Relaxations

Identifying anomalies and contamination in datasets is important in a wide variety of settings. In this paper, we describe a new technique for estimating contamination in large, discrete valued datasets. Our approach considers the normal condition of the data to be specified by a model consisting of a set of distributions. Our key contribution is in our approach to contamination estimation. Specifically, we develop a technique that identifies the minimum number of data points that must be discarded (i.e., the level of contamination) from an empirical data set in order to match the model to within a specified goodness-of-fit, controlled by a p-value. Appealing to results from large deviations theory, we show a lower bound on the level of contamination is obtained by solving a series of convex programs. Theoretical results guarantee the bound converges at a rate of $O(\sqrt{\log(p)/p})$, where p is the size of the empirical data set.Comment: To appear, ISIT 201

The Sample Complexity of Search over Multiple Populations

This paper studies the sample complexity of searching over multiple populations. We consider a large number of populations, each corresponding to either distribution P0 or P1. The goal of the search problem studied here is to find one population corresponding to distribution P1 with as few samples as possible. The main contribution is to quantify the number of samples needed to correctly find one such population. We consider two general approaches: non-adaptive sampling methods, which sample each population a predetermined number of times until a population following P1 is found, and adaptive sampling methods, which employ sequential sampling schemes for each population. We first derive a lower bound on the number of samples required by any sampling scheme. We then consider an adaptive procedure consisting of a series of sequential probability ratio tests, and show it comes within a constant factor of the lower bound. We give explicit expressions for this constant when samples of the populations follow Gaussian and Bernoulli distributions. An alternative adaptive scheme is discussed which does not require full knowledge of P1, and comes within a constant factor of the optimal scheme. For comparison, a lower bound on the sampling requirements of any non-adaptive scheme is presented.Comment: To appear, IEEE Transactions on Information Theor

Stretch Activated Channels in Proprioceptive Organs of Crab and Crayfish Are Sensitive to Gadolinium but not Amiloride, Ruthenium Red or Low pH

The type of stretch activated receptors (SARs) in the chordotonal organs in the crab walking leg and of the muscle receptor organ (MRO) in the crayfish abdomen have not yet been classified as to their molecular or pharmacological profile. The purpose of this study is to examine the pharmacological profile of SARs in the proprioceptive neurons in the crab and crayfish models. Since many SARs share the pharmacological profile of displaying low pH or being proton sensitive (i.e. being more active) or blocked by the diuretic amiloride or ruthenium red as well as being blocked by the broad stretch activated channel blocker gadolinium (Gd3+), we used these agents to screen the receptors. Various displacement rates as well as static positions that activate the stretch activated receptors were used in examining their pharmacological profiles. Hour-long exposure to low pH decreased neural activity of the chordotonal organ of the crab more so than to amiloride or ruthenium red. The crayfish MRO did not show pH sensitivity or sensitivity to amiloride or ruthenium red. Gd3+ rapidly blocked neural activity in both the crab and crayfish. It appears these stretch activated receptors may not have a classification that is suited to the standard pharmacological profiles. The molecular makeup of the channels also awaits characterization. This could reveal a novel SAR subtype. Our neurophysiology course1 took this project on as a course-based undergraduate research experience (CURE) to address an authentic research question

The Effect of CO\u3csub\u3e2\u3c/sub\u3e, Intracellular pH and Extracellular pH on Mechanosensory Proprioceptor Responses in Crayfish and Crab

Proprioceptive neurons monitor the movements of limbs and joints to transduce the movements into electrical signals. These neurons function similarly in species from arthropods to humans. These neurons can be compromised in disease states and in adverse environmental conditions such as with changes in external and internal pH. We used two model preparations (the crayfish muscle receptor organ and a chordotonal organ in the limb of a crab) to characterize the responses of these proprioceptors to external and internal pH changes as well as raised CO2. The results demonstrate the proprioceptive organs are not highly sensitive to changes in extracellular pH, when reduced to 5.0 from 7.4. However, if intracellular pH is decreased by exposure to propionic acid or saline containing CO2, there is a rapid decrease in firing rate in response to joint movements. The responses recover quickly upon reintroduction of normal pH (7.4) or saline not tainted with CO2. These basic understandings may help to address the mechanistic properties of mechanosensitive receptors in other organisms, such as muscle spindles in skeletal muscles of mammals and tactile as well as pressure (i.e., blood pressure) sensory receptors

Impact of American Joint Committee on Cancer Eighth Edition clinical stage and smoking history on oncologic outcomes in human papillomavirus‐associated oropharyngeal squamous cell carcinoma

BackgroundThe purpose of this study was to evaluate the AJCC eighth edition clinical staging system for human papillomavirus (HPV)‐associated oropharyngeal squamous cell carcinoma and to further understand how clinical stage and smoking history affect oncologic outcomes. The purpose of this study was to present the understanding of how clinical stage and smoking history affect oncologic outcomes in human papillomavirus (HPV)‐associated oropharyngeal squamous cell carcinoma (SCC) is critical for selecting patients for treatment deintensification.MethodsKaplan‐Meier and Cox regression were used to evaluate overall survival (OS), locoregional recurrence‐free survival (LRFS), and distant recurrence‐free survival (DRFS). Concordance statistics (C‐indices) were used to compare discriminating ability.ResultsThe OS and DRFS but not LRFS were significantly distributed using the American Joint Committee on Cancer (AJCC) seventh and eighth editions criteria. The C‐indices for OS, LRFS, and DRFS were 0.57, 0.54, and 0.60, respectively, using the AJCC seventh edition, and 0.63, 0.53, and 0.65, respectively, using the AJCC eighth edition. On multivariate analysis, 1 + pack‐year smoking history correlated with OS (hazard ratio [HR] 1.96; 95% confidence interval [CI] 1.2‐3.1; P < .01) but not LRFS or DRFS.ConclusionThese results support implementation of the AJCC eighth edition for HPV‐associated oropharyngeal SCC. Clinical stage may be more important than smoking history in selection for deintensification.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148352/1/hed25336_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148352/2/hed25336.pd

Paired phase II trials evaluating cetuximab and radiotherapy for low risk HPV associated oropharyngeal cancer and locoregionally advanced squamous cell carcinoma of the head and neck in patients not eligible for cisplatin

BackgroundAlternative therapeutic strategies are needed for localized oropharyngeal carcinoma. Cetuximab represents a potential option for those ineligible for cisplatin or, until recently, an agent for de‐escalation in low risk HPV+ oropharyngeal carcinoma (OPSCC). Our objective was to define the toxicity and efficacy of cetuximab‐radiotherapy.MethodsWe conducted paired phase II trials evaluating cetuximab‐radiotherapy in two cohorts (a) low risk HPV+ OPSCC and (b) cisplatin ineligible. The mean follow‐up was 48 months.ResultsForty‐two patients were enrolled in cohort A with a 2‐year disease free survival (DFS) of 81%. Twenty‐one patients were enrolled in cohort B prior to closure due to adverse outcomes with a 2‐year DFS of 37%. Severe toxicities were seen in 60% of patients, 30% required enteral nutrition.ConclusionAmong cisplatin ineligible patients, cetuximab treatment engendered poor outcomes. Rates of severe toxicities were on par with platinum‐based regimens suggesting that cetuximab is not a benign treatment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156234/2/hed26085.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156234/1/hed26085_am.pd