Description and pilot evaluation of the Metabolic Irregularities Narrowing down Device software: a case analysis of physician programming

Background: There is a gap between the abilities and the everyday applications of Computerized Decision Support Systems (CDSSs). This gap is further exacerbated by the different ‘worlds’ between the software designers and the clinician end-users. Software programmers often lack clinical experience whereas practicing physicians lack skills in design and engineering. Objective: Our primary objective was to evaluate the performance of Metabolic Irregularities Narrowing down Device (MIND) intelligent medical calculator and differential diagnosis software through end-user surveys and discuss the roles of CDSS in the inpatient setting. Setting: A tertiary care, teaching community hospital. Study participants: Thirty-one responders answered the survey. Responders consisted of medical students, 24%; attending physicians, 16%, and residents, 60%. Results: About 62.5% of the responders reported that MIND has the ability to potentially improve the quality of care, 20.8% were sure that MIND improves the quality of care, and only 4.2% of the responders felt that it does not improve the quality of care. Ninety-six percent of the responders felt that MIND definitely serves or has the potential to serve as a useful tool for medical students, and only 4% of the responders felt otherwise. Thirty-five percent of the responders rated the differential diagnosis list as excellent, 56% as good, 4% as fair, and 4% as poor. Discussion: MIND is a suggesting, interpreting, alerting, and diagnosing CDSS with good performance and end-user satisfaction. In the era of the electronic medical record, the ongoing development of efficient CDSS platforms should be carefully considered by practicing physicians and institutions

Derandomization of auctions

We study the role of randomization in seller optimal (i.e., profit maximization) auctions. Bayesian optimal auctions (e.g., Myerson, 1981) assume that the valuations of the agents are random draws from a distribution and prior-free optimal auctions either are randomized (e.g., Goldberg et al., 2006) or assume the valuations are randomized (e.g., Segal, 2003). Is randomization fundamental to profit maximization in auctions? Our main result is a general approach to derandomize single-item multi-unit unit-demand auctions while approximately preserving their performance (i.e., revenue). Our general technique is constructive but not computationally tractable. We complement the general result with the explicit and computationally-simple derandomization of a particular auction. Our results are obtained through analogy to hat puzzles that are interesting in their own right

Are Boredom Prone Individuals Creative and Curious About Their Environment?

After controlling for overall personality characteristics, boredom proneness did not predict creativity, but did positively predict people’s motivation to seek out novel experiences and find answers to things they do not understand. Thus, future work should explore how to use these relationships to help individuals respond effectively to the experience of boredom.Knowledge Mobilization at York - York University’s Knowledge Mobilization Unit provides services for faculty, graduate students, community and government seeking to maximize the impact of academic research and expertise on public policy, social programming, and professional practice. This summary has been supported by the Office of the Vice-President Research and Innovation at York and project funding from SSHRC and CIHR. [email protected] www.researchimpact.c

A Soluble Peripherin/Rds C-Terminal Polypeptide Promotes Membrane Fusion and Changes Conformation Upon Membrane Association

Photoreceptor rod cells contain a unique tetraspanin fusion protein known as peripherin/rds. This protein is important in membrane fusion events hypothesized to be essential to disk membrane morphogenesis and disk shedding. In vivo and in vitro fusogenic activity has been mapped to the C-terminal domain of peripherin/rds. Moreover, a fusion peptide domain localized to a 15 amino acid long region (residues 311–325) is essential for mediating lipid bilayer fusion of model membranes. To address the functional and structural properties required for peripherin/rds dependent membrane fusion, constructs of the entire C-terminal domain (residues 284–346) were generated and polypeptides expressed. A wild type-peripherin/rds C-terminal GST fusion construct that included the entire C-terminus (PERCTER) or a C-terminal truncation mutant (PERCTN) were engineered with a thrombin cleavage site. Protein expression was induced in E. coli with IPTG, expressed proteins cleaved from the GST with thrombin and purified to homogeneity on a Superdex 75 column. Purity was confirmed by SDS–PAGE and Western blot analysis. The purified wt C-terminal protein resolved as a monomer under reducing conditions on SDS–PAGE (15%) and was immunoreactive with anti peripherin/rds antibody 2B6 (gift from Dr R. Molday). The purified polypeptide promoted the requisite steps of fusion, membrane destabilization, lipid mixing and aqueous contents mixing. Conversely, the truncation mutant lacking a portion of the fusion domain was unable to promote these steps. A common feature of most membrane fusion proteins is a change in conformation upon membrane association. Structural changes in the C-terminal polypeptide were investigated using far UV CD. The far UV CD spectra of the purified C-terminal polypeptide indicated substantial α-helical content in the wt peptide in isotonic aqueous buffer. An increase in intensity of 208 and 222 nm CD bands upon addition of DPC vesicles indicated an increase in α-helical content of the polypeptide. These results demonstrate that a purified soluble form of the C-terminus of peripherin/rds can interact with biological phospholipids; moreover, this interaction promotes a conformational change that is most consistent with an increase in α-helical content

A Soluble Peripherin/Rds C-Terminal Polypeptide Promotes Membrane Fusion and Changes Conformation Upon Membrane Association

Photoreceptor rod cells contain a unique tetraspanin fusion protein known as peripherin/rds. This protein is important in membrane fusion events hypothesized to be essential to disk membrane morphogenesis and disk shedding. In vivo and in vitro fusogenic activity has been mapped to the C-terminal domain of peripherin/rds. Moreover, a fusion peptide domain localized to a 15 amino acid long region (residues 311–325) is essential for mediating lipid bilayer fusion of model membranes. To address the functional and structural properties required for peripherin/rds dependent membrane fusion, constructs of the entire C-terminal domain (residues 284–346) were generated and polypeptides expressed. A wild type-peripherin/rds C-terminal GST fusion construct that included the entire C-terminus (PERCTER) or a C-terminal truncation mutant (PERCTN) were engineered with a thrombin cleavage site. Protein expression was induced in E. coli with IPTG, expressed proteins cleaved from the GST with thrombin and purified to homogeneity on a Superdex 75 column. Purity was confirmed by SDS–PAGE and Western blot analysis. The purified wt C-terminal protein resolved as a monomer under reducing conditions on SDS–PAGE (15%) and was immunoreactive with anti peripherin/rds antibody 2B6 (gift from Dr R. Molday). The purified polypeptide promoted the requisite steps of fusion, membrane destabilization, lipid mixing and aqueous contents mixing. Conversely, the truncation mutant lacking a portion of the fusion domain was unable to promote these steps. A common feature of most membrane fusion proteins is a change in conformation upon membrane association. Structural changes in the C-terminal polypeptide were investigated using far UV CD. The far UV CD spectra of the purified C-terminal polypeptide indicated substantial α-helical content in the wt peptide in isotonic aqueous buffer. An increase in intensity of 208 and 222 nm CD bands upon addition of DPC vesicles indicated an increase in α-helical content of the polypeptide. These results demonstrate that a purified soluble form of the C-terminus of peripherin/rds can interact with biological phospholipids; moreover, this interaction promotes a conformational change that is most consistent with an increase in α-helical content

Predictions for the Cosmogenic Neutrino Flux in Light of New Data from the Pierre Auger Observatory

The Pierre Auger Observatory (PAO) has measured the spectrum and composition of the ultrahigh energy cosmic rays with unprecedented precision. We use these measurements to constrain their spectrum and composition as injected from their sources and, in turn, use these results to estimate the spectrum of cosmogenic neutrinos generated in their propagation through intergalactic space. We find that the PAO measurements can be well fit if the injected cosmic rays consist entirely of nuclei with masses in the intermediate (C, N, O) to heavy (Fe, Si) range. A mixture of protons and heavier species is also acceptable but (on the basis of existing hadronic interaction models) injection of pure light nuclei (p, He) results in unacceptable fits to the new elongation rate data. The expected spectrum of cosmogenic neutrinos can vary considerably, depending on the precise spectrum and chemical composition injected from the cosmic ray sources. In the models where heavy nuclei dominate the cosmic ray spectrum and few dissociated protons exceed GZK energies, the cosmogenic neutrino flux can be suppressed by up to two orders of magnitude relative to the all-proton prediction, making its detection beyond the reach of current and planned neutrino telescopes. Other models consistent with the data, however, are proton-dominated with only a small (1-10%) admixture of heavy nuclei and predict an associated cosmogenic flux within the reach of upcoming experiments. Thus a detection or non-detection of cosmogenic neutrinos can assist in discriminating between these possibilities.Comment: 10 pages, 7 figure

Intensive Induction Chemotherapy Followed by Early High-Dose Therapy and Hematopoietic Stem Cell Transplantation Results in Improved Outcome for Patients with Hepatosplenic T-Cell Lymphoma: A Single Institution Experience

AbstractIntroductionHepatosplenic T-cell lymphoma is a rare form of extranodal non-Hodgkin lymphoma, first recognized as a distinct entity in the Revised European-American Lymphoma classification. Typical presentation includes lymphomatous infiltration of spleen and liver, and peripheral lymphadenopathy is rarely seen. The prognosis is almost uniformly poor, and there are no prospective studies of treatment of HSTCL.Patients and MethodsFor this report, we conducted a retrospective review of all pts who underwent treatment for HSTCL at our institution. Individual chart review was performed to report clinical presentation, management, and outcome.ResultsWe identified 14 pts with HSTCL managed at our center, 7 of which remain alive with median follow-up of 65.6 months. Six of 7 received alternative induction chemotherapy regimens such as ICE (ifosfamide, carboplatin, etoposide) or IVAC (ifosfamide, etoposide, high-dose cytarabine) as opposed to CHOP and all surviving pts had proceeded to undergo either autologous or allogeneic SCT.ConclusionOur results suggest that use of non-CHOP induction regimen and early use of high dose therapy and SCT consolidation may translate to improved survival for pts with HSTCL

Survival after hospital discharge for ST-segment elevation and non-ST-segment elevation acute myocardial infarction: a population-based study

BACKGROUND: Limited recent data are available describing differences in long-term survival, and factors affecting prognosis, after ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI), especially from the more generalizable perspective of a population-based investigation. The objectives of this study were to examine differences in post-discharge prognosis after hospitalization for STEMI and NSTEMI, with a particular focus on factors associated with reduced long-term survival. METHODS: We reviewed the medical records of residents of the Worcester, MA, USA metropolitan area hospitalized at eleven central Massachusetts medical centers for acute myocardial infarction (AMI) during 2001, 2003, 2005, and 2007. RESULTS: A total of 3762 persons were hospitalized with confirmed AMI; of these, 2539 patients (67.5%) were diagnosed with NSTEMI. The average age of study patients was 70.3 years and 42.9% were women. Patients with NSTEMI experienced higher post-discharge death rates with 3-month, 1-year, and 2-year death rates of 12.6%, 23.5%, and 33.2%, respectively, compared to 6.1%, 11.5%, and 16.4% for patients with STEMI. After multivariable adjustment, patients with NSTEMI were significantly more likely to have died after hospital discharge (adjusted hazards ratio 1.28; 95% confidence interval 1.14-1.44). Several demographic (eg, older age) and clinical (eg, history of stroke) factors were associated with reduced long-term survival in patients with NSTEMI and STEMI. CONCLUSIONS: The results of this study in residents of central Massachusetts suggest that patients with NSTEMI are at higher risk for dying after hospital discharge, and several subgroups are at particularly increased risk

Application of Proximal Alternating Linearized Minimization (PALM) and inertial PALM to dynamic 3D CT

The foot and ankle is a complex structure consisting of 28 bones and 30 joints that changes from being completely mobile when positioning the foot on the floor to a rigid closed pack position during propulsion such as when running or jumping. An understanding of this complex structure has largely been derived from cadaveric studies. In vivo studies have largely relied on skin surface markers and multi-camera systems that are unable to differentiate small motions between the bones of the foot. MRI and CT based studies have struggled to interpret functional weight bearing motion as imaging is largely static and non-load bearing. Arthritic diseases of the foot and ankle are treated either by fusion of the joints to remove motion, or joint replacement to retain motion. Until a better understanding of the biomechanics of these joints can be achieved

Molecular diagnosis of Huntington disease in Portugal : implications for genetic counselling and clinical practice

Huntington disease (HD) is a eurodegenerative, autosomal dominant disorder of late-onset, caused by the expansion of a CAG repeat in the coding region of the gene. Ours is the reference laboratory for genetic testing in HD, in Portugal, since 1998; 90.1% of all 158 families known were identified for the first time, including patients with unusual presentation or without family history. A total of 338 genetic tests were performed: 234 for diagnosis, 96 for presymptomatic and four for prenatal testing (four were done for family studies). Most referring physicians were neurologists (90.6%); 82.8% of all clinical diagnosis were confirmed, while 83.1% of those sent for exclusion were in fact excluded. In presymptomatic testing, an excess of female subjects (59.4%) was again verified; 37.5% of the consultands were found to be carriers. None of the foetuses, in four prenatal tests, were mutation carriers. One juvenile case was inherited from her mother. Our patient population is very similar to others described so far, namely in terms of mean age at onset and (CAG)n distribution, except perhaps for a higher frequency of large normal (class 2) alleles (3.7%). We also identify cases posing particular problems for genetic counselling, such as, ‘homozygosity’ that can pose a serious ethical dilemma, carriers of large normal alleles, and ‘homoallelism’ for a normal gene, which will demand further procedures and may delay results in presymptomatic and prenatal testing