Inferring a consensus problem list using penalized multistage models for ordered data

A patient\u27s medical problem list describes his or her current health status and aids in the coordination and transfer of care between providers, among other things. Because a problem list is generated once and then subsequently modified or updated, what is not usually observable is the provider-effect. That is, to what extent does a patient\u27s problem in the electronic medical record actually reflect a consensus communication of that patient\u27s current health status? To that end, we report on and analyze a unique interview-based design in which multiple medical providers independently generate problem lists for each of three patient case abstracts of varying clinical difficulty. Due to the uniqueness of both our data and the scientific objectives of our analysis, we apply and extend so-called multistage models for ordered lists and equip the models with variable selection penalties to induce sparsity. Each problem has a corresponding non-negative parameter estimate, interpreted as a relative log-odds ratio, with larger values suggesting greater importance and zero values suggesting unimportant problems. We use these fitted penalized models to quantify and report the extent of consensus. For the three case abstracts, the proportions of problems with model-estimated non-zero log-odds ratios were 10/28, 16/47, and 13/30. Physicians exhibited consensus on the highest ranked problems in the first and last case abstracts but agreement quickly deteriorates; in contrast, physicians broadly disagreed on the relevant problems for the middle and most difficult case abstract

Hematopoietic stem cell gene replacement therapy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29678/1/0000005.pd

Effects of depressive symptomatology on cancer‐related symptoms during oral oncolytic treatment

ObjectiveThis manuscript assesses association between depressive symptoms and symptoms from cancer and its treatment during the first 12 weeks of a new oral oncolytic treatment.MethodsThis secondary analysis used data from a recently completed trial of an intervention to improve adherence to oral oncolytic treatment and manage symptoms. Following the initiation of the new oral oncolytic medication, 272 patients were interviewed at intake and weeks 4, 8, and 12 to assess depressive symptoms, and symptoms from cancer and its treatment. Depressive symptoms were measured using the Center for Epidemiologic Studies‐Depression (CES‐D20). The summed index of 18 cancer‐related and treatment‐related symptoms as well as the number of symptoms above threshold at intake, weeks 4, 8, and 12 were related to intake and time‐varying CES‐D20 using linear mixed effects models.ResultsDepressive symptomatology was a significant predictor of cancer‐related and treatment‐related symptoms at all‐time points, but the strength of this relationship was greatest at the time of oral oncolytic agent initiation and at week 4. The strength of this relationship was the same for both summed symptom severity index and the number of symptoms above threshold, and using either intake or time‐varying CES‐D20.ConclusionIntroducing strategies to treat and manage symptoms of depression along with other symptoms might have added benefits among patients who start a new oral oncolytic treatment and report modest to higher levels of depressive symptoms. Assessments for the impact of strategies to lower depressive symptoms can be taken within the first 4 weeks.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147865/1/pon4916.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147865/2/pon4916_am.pd

Accelerated Growth Plate Mineralization and Foreshortened Proximal Limb Bones in Fetuin-A Knockout Mice

PMCID: PMC3473050This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

HOMO–HOMO Electron Transfer : An Elegant Strategy for p-Type Doping of Polymer Semiconductors toward Thermoelectric Applications

Unlike the conventional p‐doping of organic semiconductors (OSCs) using acceptors, here, an efficient doping concept for diketopyrrolopyrrole‐based polymer PDPP[T]$_{2}$‐EDOT (OSC‐1) is presented using an oxidized p‐type semiconductor, Spiro‐OMeTAD(TFSI)$_{2}$ (OSC‐2), exploiting electron transfer from HOMO$_{OSC-1}$ to HOMO$_{OSC-2}$. A shift of work function toward the HOMO$_{OSC-1}$ upon doping is confirmed by ultraviolet photoelectron spectroscopy (UPS). Detailed X‐ray photoelectron spectroscopy (XPS) and UV–vis–NIR absorption studies confirm HOMO$_{OSC-1}$ to HOMO$_{OSC-2}$ electron transfer. The reduction products of Spiro‐OMeTAD(TFSI)$_{2}$ to Spiro‐OMeTAD(TFSI) and Spiro‐OMeTAD is also confirmed and their relative amounts in doped samples is determined. Mott–Schottky analysis shows two orders of magnitude increase in free charge carrier density and one order of magnitude increase in the charge carrier mobility. The conductivity increases considerably by four orders of magnitude to a maximum of 10 S m$^{-1}$ for a very low doping ratio of 8 mol%. The doped polymer films exhibit high thermal and ambient stability resulting in a maximum power factor of 0.07 µW m$^{-1}$ K$^{-2}$ at a Seebeck coefficient of 140 µV K$^{-1}$ for a very low doping ratio of 4 mol%. Also, the concept of HOMO$_{OSC-1}$ to HOMO$_{OSC-2}$ electron transfer is a highly efficient, stable and generic way to p‐dope other conjugated polymers

Do treatment patterns alter beliefs cancer patients hold regarding oral oncolytic agents?

ObjectiveCancer patients, particularly those prescribed with oral oncolytic medications, face treatment side effects and temporary and permanent stoppages of treatment. This research examines how events during treatment affect patients’ beliefs regarding oral oncolytic medications.MethodsA total of 272 cancer patients initiating 1 of 28 oral oncolytic agents were followed for 12 weeks. Assessments of Beliefs About Medications Questionnaire, symptoms, physical function, and depression measures were performed during telephone interviews at intake (medication start) and 4, 8, and 12 weeks. Electronic medical record audits identified dates of temporary and permanent medication stoppages. Linear mixed‐effects models were used for longitudinal analyses of the Beliefs About Medications Questionnaire scores in relation to patient characteristics, symptom severity, and medication stoppages.ResultsOver the initial 12 weeks, beliefs about the necessity of oral medications have increased, concerns have decreased, and interference of medications with daily lives has increased. Permanent stoppage of a medication predicted significant declines in beliefs about its necessity over time. Male patients, those less educated, those reporting higher symptom severity, and those experiencing temporary stoppages had greater concerns. Interference of medications with daily life was higher for males, increased with higher symptom severity, and differed by drug category.ConclusionsPatients’ beliefs in the necessity of their oral medication were affected only by a permanent drug stoppage. Symptom severity, education, and patient sex affected patients’ beliefs about their concerns with their medications and the interference medications posed for their daily lives. Interventions may need to target the distinct dimensions of beliefs during treatment with oral oncolytic agents.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142470/1/pon4606.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142470/2/pon4606_am.pd

A CHANDRA SURVEY OF NEARBY SPIRAL GALAXIES. I. POINT SOURCE CATALOGS

Emission from discrete point sources dominates the X-ray luminosity in spiral galaxies. We present results from a survey of 11 nearby, nearly face-on spiral galaxies with the Chandra X-ray Observatory. These galaxies span the Hubble sequence for spirals, allowing insights into the X-ray source population of many diverse systems. In this paper, we present source lists for the 11 galaxies along with fluxes, luminosities, X-ray colors, and variability properties. We briefly discuss X-ray luminosity functions and how they relate to star formation of the host galaxies. We also discuss source colors and variability and what these can tell us about the composition of the X-ray source population

Stochastic evolution of cosmological parameters in the early universe

We develop a stochastic formulation of cosmology in the early universe, after considering the scatter in the redshift-apparent magnitude diagram in the early epochs as an observational evidence for the non-deterministic evolution of early universe. We consider the stochastic evolution of density parameter in the early universe after the inflationary phase qualitatively, under the assumption of fluctuating $w$ factor in the equation of state, in the Fokker-Planck formalism. Since the scale factor for the universe depends on the energy density, from the coupled Friedmann equations we calculated the two variable probability distribution function assuming a flat space geometry.Comment: 10 page

Rapid, ultra low coverage copy number profiling of cell-free DNA as a precision oncology screening strategy.

Current cell-free DNA (cfDNA) next generation sequencing (NGS) precision oncology workflows are typically limited to targeted and/or disease-specific applications. In advanced cancer, disease burden and cfDNA tumor content are often elevated, yielding unique precision oncology opportunities. We sought to demonstrate the utility of a pan-cancer, rapid, inexpensive, whole genome NGS of cfDNA approach (PRINCe) as a precision oncology screening strategy via ultra-low coverage (~0.01x) tumor content determination through genome-wide copy number alteration (CNA) profiling. We applied PRINCe to a retrospective cohort of 124 cfDNA samples from 100 patients with advanced cancers, including 76 men with metastatic castration-resistant prostate cancer (mCRPC), enabling cfDNA tumor content approximation and actionable focal CNA detection, while facilitating concordance analyses between cfDNA and tissue-based NGS profiles and assessment of cfDNA alteration associations with mCRPC treatment outcomes. Therapeutically relevant focal CNAs were present in 42 (34%) cfDNA samples, including 36 of 93 (39%) mCRPC patient samples harboring AR amplification. PRINCe identified pre-treatment cfDNA CNA profiles facilitating disease monitoring. Combining PRINCe with routine targeted NGS of cfDNA enabled mutation and CNA assessment with coverages tuned to cfDNA tumor content. In mCRPC, genome-wide PRINCe cfDNA and matched tissue CNA profiles showed high concordance (median Pearson correlation = 0.87), and PRINCe detectable AR amplifications predicted reduced time on therapy, independent of therapy type (Kaplan-Meier log-rank test, chi-square = 24.9, p < 0.0001). Our screening approach enables robust, broadly applicable cfDNA-based precision oncology for patients with advanced cancer through scalable identification of therapeutically relevant CNAs and pre-/post-treatment genomic profiles, enabling cfDNA- or tissue-based precision oncology workflow optimization

Acoustic Attenuation by Two-dimensional Arrays of Rigid Cylinders

In this Letter, we present a theoretical analysis of the acoustic transmission through two-dimensional arrays of straight rigid cylinders placed parallelly in the air. Both periodic and completely random arrangements of the cylinders are considered. The results for the sound attenuation through the periodic arrays are shown to be in a remarkable agreement with the reported experimental data. As the arrangement of the cylinders is randomized, the transmission is significantly reduced for a wider range of frequencies. For the periodic arrays, the acoustic band structures are computed by the plane-wave expansion method and are also shown to agree with previous results.Comment: 4 pages, 3 figure