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## ‣ Dementia Coding, Workup, and Treatment in the VA New England Healthcare System

Cho, Kelly; Gagnon, David R.; Driver, Jane A.; Altincatal, Arman; Kosik, Nicole; Lanes, Stephan; Lawler, Elizabeth V.
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
Português
Growing evidence suggests that Alzheimer's disease and other types of dementia are underdiagnosed and poorly documented. In our study, we describe patterns of dementia coding and treatment in the Veteran's Administration New England Healthcare System. We conducted a retrospective cohort study with new outpatient ICD-9 codes for several types of dementia between 2002 and 2009. We examined healthcare utilization, medication use, initial dementia diagnoses, and changes in diagnoses over time by provider type. 8,999 veterans received new dementia diagnoses during the study period. Only 18.3% received a code for cognitive impairment other than dementia, most often “memory loss” (65.2%) prior to dementia diagnosis. Two-thirds of patients received their initial code from a PCP. The etiology of dementia was often never specified by ICD-9 code, even by specialists. Patients followed up exclusively by PCPs had lower rates of neuroimaging and were less likely to receive dementia medication. Emergency room visits and hospitalizations were frequent in all patients but highest in those seen by dementia specialists. Dementia medications are commonly used off-label. Our results suggest that, for the majority the patients, no prodrome of the dementia syndrome is documented with diagnostic code...

## ‣ Natural History of Untreated Prostate Specific Antigen Radiorecurrent Prostate Cancer in Men with Favorable Prognostic Indicators

Martin, Neil E.; Chen, Ming-Hui; Beard, Clair J.; Nguyen, Paul L.; Loffredo, Marian J.; Renshaw, Andrew A.; Kantoff, Philip W.; D'Amico, Anthony V.
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
Português

## ‣ Utilizing Fast Spin Echo MRI to Reduce Image Artifacts and Improve Implant/Tissue Interface Detection in Refractory Parkinson's Patients with Deep Brain Stimulators

Sarkar, Subhendra N.; Sarkar, Pooja R.; Papavassiliou, Efstathios; Rojas, Rafael R.
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
Português
Introduction:. In medically refractory Parkinson's disease (PD) deep-brain stimulation (DBS) is an effective therapeutic tool. Postimplantation MRI is important in assessing tissue damage and DBS lead placement accuracy. We wanted to identify which MRI sequence can detect DBS leads with smallest artifactual signal void, allowing better tissue/electrode edge conspicuity. Methods:. Using an IRB approved protocol 8 advanced PD patients were imaged within MR conditional safety guidelines at low RF power (SAR ≤ 0.1 W/kg) in coronal plane at 1.5T by various sequences. The image slices were subjectively evaluated for diagnostic quality and the lead contact diameters were compared to identify a sequence least affected by metallic leads. Results and Discussion. Spin echo and fast spin echo based low SAR sequences provided acceptable image quality with comparable image blooming (enlargement) of stimulator leads. The mean lead diameters were 2.2 ± 0.1 mm for 2D, 2.1 ± 0.1 mm for 3D, and 4.0 ± 0.2 mm for 3D MPRAGE sequence. Conclusion:. Low RF power spin echo and fast spin echo based 2D and 3D FSE sequences provide acceptable image quality adjacent to DBS leads. The smallest artifactual blooming of stimulator leads is present on 3D FSE while the largest signal void appears in the 3D MPRAGE sequence.

## ‣ An Application of Evolutionary Game Theory to Social Dilemmas: The Traveler's Dilemma and the Minimum Effort Coordination Game

Iyer, Swami; Reyes, Joshua; Killingback, Timothy
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Português
The Traveler's Dilemma game and the Minimum Effort Coordination game are two social dilemmas that have attracted considerable attention due to the fact that the predictions of classical game theory are at odds with the results found when the games are studied experimentally. Moreover, a direct application of deterministic evolutionary game theory, as embodied in the replicator dynamics, to these games does not explain the observed behavior. In this work, we formulate natural variants of these two games as smoothed continuous-strategy games. We study the evolutionary dynamics of these continuous-strategy games, both analytically and through agent-based simulations, and show that the behavior predicted theoretically is in accord with that observed experimentally. Thus, these variants of the Traveler's Dilemma and the Minimum Effort Coordination games provide a simple resolution of the paradoxical behavior associated with the original games.

## ‣ The potential role of 'non-rheumatic’ therapies in rheumatic disease

Massarotti, Elena M; Solomon, Daniel H
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Outros
Português
The relationship between inflammation and insulin resistance is complex and not fully understood. Patients with rheumatoid arthritis are at increased risk of mortality from cardiovascular disease, which is known to be associated with insulin resistance. In the previous issue of Arthritis Research & Therapy, Ormseth and colleagues report the results of an 8-week trial of pioglitazone, an agent commonly used to treat type 2 diabetes mellitus, upon the DAS-28 (disease activity score using 28 joint counts). Modest improvements in the DAS-28 CRP (DAS-28 C-reactive protein) were shown, with no effect on DAS-28 ESR (DAS-28 erythrocyte sedimentation rate). Other variables that improved with pioglitazone were the CRP, IL-6, and patient-reported assessment of global health. The authors discuss the contribution of insulin resistance to the inflammation noted in rheumatoid arthritis.

## ‣ A controlled trial of Partners in Dementia Care: veteran outcomes after six and twelve months

Bass, David M; Judge, Katherine S; Snow, A Lynn; Wilson, Nancy L; Morgan, Robert O; Maslow, Katie; Randazzo, Ronda; Moye, Jennifer A; Odenheimer, Germaine L; Archambault, Elizabeth; Elbein, Richard; Pirraglia, Paul; Teasdale, Thomas A; McCarthy, Catherine
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Português
Introduction: “Partners in Dementia Care” (PDC) tested the effectiveness of a care-coordination program integrating healthcare and community services and supporting veterans with dementia and their caregivers. Delivered via partnerships between Veterans Affairs medical centers and Alzheimer’s Association chapters, PDC targeted both patients and caregivers, distinguishing it from many non-pharmacological interventions. Hypotheses posited PDC would improve five veteran self-reported outcomes: 1) unmet need, 2) embarrassment about memory problems, 3) isolation, 4) relationship strain and 5) depression. Greater impact was expected for more impaired veterans. A unique feature was self-reported research data collected from veterans with dementia. Methods and Findings: Five matched communities were study sites. Two randomly selected sites received PDC for 12 months; comparison sites received usual care. Three structured telephone interviews were completed every 6 months with veterans who could participate. Results: Of 508 consenting veterans, 333 (65.6%) completed baseline interviews. Among those who completed baseline interviews, 263 (79.0%) completed 6-month follow-ups and 194 (58.3%) completed 12-month follow-ups. Regression analyses showed PDC veterans had significantly less adverse outcomes than those receiving usual care...

## ‣ What we don't know about open access: research questions in need of researchers

Suber, Peter
Tipo: Artigo de Revista Científica
Português

## ‣ The Practitioner's Toolbox

Corbin, Alexandra kraeler
Fonte: Harvard University Publicador: Harvard University
Tipo: Outros
Português
Psychology

## ‣ Mass and Radius Determinations for Five Transiting M-Dwarf Stars

Fernandez, Jose M.; Latham, David W.; Everett, Mark E.; Mandushev, Georgi; Charbonneau, David; O'Donovan, Francis T.; Alonso, Roi; Hergenrother, Carl W.; Stefanik, Robert P.; Torres, Guilermo; Esquerdo, Gilbert A.
Fonte: Institute of Physics Publicador: Institute of Physics
Tipo: Artigo de Revista Científica
Português
We have derived masses and radii for both components in five short-period single-lined eclipsing binary stars discovered by the TrES wide-angle photometric survey for transiting planets. All these systems consist of a visible F-star primary and an unseen M-star secondary (M A ≥ 0.8 M sun, M B ≤ 0.45 M sun). The spectroscopic orbital solution combined with a high-precision transit light curve for each system gives sufficient information to calculate the density of the primary star and the surface gravity of the secondary. The masses of the primary stars were obtained using stellar evolution models, which requires accurate determinations of metallicities and effective temperatures. In our case, the uncertainty in the metallicity of the primary stars is the most important limiting factor in order to obtain accurate results for the masses and radii of the unseen M-dwarf secondaries. The solutions were compared with results obtained by calculating the radius of the primary stars under the assumption of rotational synchronization with the orbital period and alignment between their spin axis and the axis of the orbit, using the observed broadening of the spectral lines as an indicator of stellar rotation. Four systems show an acceptable match between the two sets of results when their metallicity is allowed to vary around solar values (–0.5 ≤ [Fe/H] ≤ +0.5)...

## ‣ Leveraging public health nurses for disaster risk communication in Fukushima City: a qualitative analysis of nurses' written records of parenting counseling and peer discussions

Goto, Aya; Rudd, Rima E; Lai, Alden Y; Yoshida, Kazuki; Suzuki, Yuu; Halstead, Donald D; Yoshida-Komiya, Hiromi; Reich, Michael R
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Português
Background: Local public health nurses (PHNs) have been recognized as the main health service providers in communities in Japan. The Fukushima nuclear disaster in 2011 has, however, created a major challenge for them in responding to mothers’ concerns. This was in part due to difficulties in assessing, understanding and communicating health risks on low-dose radiation exposure. In order to guide the development of risk communication plans, this study sought to investigate mothers’ primary concerns and possible solutions perceived by a core healthcare profession like the PHNs. Methods: A total of 150 records from parenting counseling sessions conducted between PHNs and mothers who have attended mandatory 18-month health checkups for their children at the Fukushima City Health and Welfare Center in 2010, 2011 (year of disaster) and 2012 were examined. Discussion notes of three peer discussions among PHNs organized in response to the nuclear disaster in 2012 and 2013 were also analyzed. All transcribed data were first subjected to text mining to list the words according to their frequencies and inter-relationships. The Steps Coding and Theorization method was then undertaken as a framework for qualitative analysis. Results: PHNs noted mothers to have considerable needs for information on radiation risks as they impact on decisions related to relocations...

## ‣ Genome-wide Association Analysis Identifies 14 New Risk Loci for Schizophrenia

Ripke, Stephan; O'Dushlaine, Colm; Chambert, Kimberly; Moran, Jennifer L; Kähler, Anna K; Akterin, Susanne; Bergen, Sarah; Collins, Ann L; Crowley, James J; Fromer, Menachem; Kim, Yunjung; Lee, Sang Hong; Magnusson, Patrik KE; Sanchez, Nick; Stahl, Eli A
Fonte: Harvard University Publicador: Harvard University
Tipo: Artigo de Revista Científica
Português
Schizophrenia is a heritable disorder with substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases, 6,243 controls) followed by meta-analysis with prior schizophrenia GWAS (8,832 cases, 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls, and 581 trios). In total, 22 regions met genome-wide significance (14 novel and one previously implicated in bipolar disorder). The results strongly implicate calcium signaling in the etiology of schizophrenia, and include genome-wide significant results for CACNA1C and CACNB2 whose protein products interact. We estimate that ∼8,300 independent and predominantly common SNPs contribute to risk for schizophrenia and that these collectively account for most of its heritability. Common genetic variation plays an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this devastating disorder.

## ‣ Whole exome sequencing identifies a recurrent NAB2-STAT6 fusion in solitary fibrous tumors

Chmielecki, Juliann; Crago, Aimee M.; Rosenberg, Mara; O'Connor, Rachael; Walker, Sarah R.; Ambrogio, Lauren; Auclair, Daniel; McKenna, Aaron; Heinrich, Michael C.; Frank, David A.; Meyerson, Matthew
Fonte: Harvard University Publicador: Harvard University
Tipo: Artigo de Revista Científica
Português

## ‣ Modeling sporadic Alzheimer's disease using induced pluripotent stem cells

McLaughlin, Heather Ward
Fonte: Harvard University Publicador: Harvard University
Tipo: Thesis or Dissertation
Português
Despite being the leading cause of neurodegeneration and dementia in the aging brain, the cause of Alzheimer's disease (AD) remains unknown in most patients. The terminal pathological hallmarks of abnormal protein aggregation and neuronal cell death are well-known from the post-mortem brain tissue of Alzheimer's disease patients, but research into the earliest stages of disease development is hindered by limited model systems. In this thesis, an in vitro human neuronal system was derived from induced pluripotent stem (iPS) cell lines reprogrammed from dermal fibroblasts of AD patients and age-matched controls. This allows us to investigate the cellular mechanisms of AD neurodegeneration in the human neurons of sporadic AD (SAD) patients, whose development of the disease cannot be explained by our current understanding of AD. We show that neural progenitors and neurons derived from SAD patients show an unexpected expression profile of enhanced neuronal gene expression resulting in premature differentiation in the SAD neuronal cells. This difference is accompanied by the decreased binding of the repressor element 1-silencing transcription/neuron-restrictive silencer factor (REST/NRSF) transcriptional inhibitor of neuronal differentiation in the SAD neuronal cells. The SAD neuronal cells also have increased production of $$amyloid-\beta$$ and higher levels of tau protein...

Brea-Solís, Humberto; Casadesus-Masanell, Ramon; Grifell-Tatjé, Emili
Fonte: Harvard University Publicador: Harvard University
Tipo: Artigo de Revista Científica
Português
We develop an analytical framework on the basis of the economics of business performance to provide quantitative insight into the link between a firm's business model choices and its profit consequences. The method is applied to Walmart by building a qualitative representation of its business model and mapping that representation on an analytical model that quantifies the company's sources of advantage over time. The analysis suggests that the effectiveness of a particular business model depends not only on its design (its levers and how they relate to one another) but also, most importantly, on its implementation (how the levers are pulled).

## ‣ Political Reservations and Women’s Entrepreneurship in India

Ghani, Ejaz; Kerr, William Robert; O'Connell, Stephen D.
Tipo: Artigo de Revista Científica
Português
We quantify the link between the timing of state-level implementations of political reservations for women in India with the role of women in India's manufacturing sector. While overall employment of women in manufacturing does not increase after the reforms, we find significant evidence that more women-owned establishments were created in the unorganized/informal sector. These new establishments were concentrated in industries where women entrepreneurs have been traditionally active and the entry was mainly found among household-based establishments. We measure and discuss the extent to which this heightened entrepreneurship is due to channels like greater finance access or heightened inspiration for women entrepreneurs.

## ‣ Cancer Cell-Derived Clusterin Modulates the Phosphatidylinositol 3'-Kinase-Akt Pathway through Attenuation of Insulin-Like Growth Factor 1 during Serum Deprivation

Jo, Hakryul; Jia, Yonghui; Subramanian, Kulandayan K.; Hattori, Hidenori; Luo, Hongbo
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Português
Cancer cells in their respective microenvironments must endure various growth-constraining stresses. Under these conditions, the cancer cell-derived factors are thought to modulate the signaling pathways between cell growth and dormancy. Here, we describe a cancer cell-derived regulatory system that modulates the phosphatidylinositol 3'-kinase (PI3K)-Akt pathway under serum deprivation stress. Through the use of biochemical purification, we reveal that cancer cell-secreted insulin-like growth factor 1 (IGF-1) and clusterin, an extracellular stress protein, constitute this regulatory system. We show that secreted clusterin associates with IGF-1 and inhibits its binding to the IGF-1 receptor and hence negatively regulates the PI3K-Akt pathway during serum deprivation. This inhibitory function of clusterin appears to prefer IGF-1, as it fails to exert any effects on epidermal growth factor signaling. We demonstrate furthermore that the constitutive activation of oncogenic signaling downstream of IGF-1 confers insensitivity to the inhibitory effects of clusterin. Thus, the interplay between cancer cell-derived clusterin and IGF-1 may dictate the outcome of cell growth and dormancy during tumorigenic progression.

## ‣ Algorithmic Approaches to Playing Minesweeper

Becerra, David J.
Fonte: Harvard University Publicador: Harvard University
Tipo: Thesis or Dissertation; text Formato: application/pdf
Português
This thesis explores the challenges associated with designing a Minesweeper solving algorithm. In particular, it considers how to best start a game, various heuristics for handling guesses, and different strategies for making deterministic deductions. The paper explores the single point approach and the constraint satisfaction problem model for playing Minesweeper. I present two novel implementations of both of these approaches called double set single point and connected components CSP. The paper concludes that the coupled subsets CSP model performs the best overall because of its sophisticated probabilistic guessing and its ability to find deterministic moves.

## ‣ Measuring Political Preferences of the U.S. Voting Population

Nahm, Alison
Fonte: Harvard University Publicador: Harvard University
Tipo: Thesis or Dissertation; text Formato: application/pdf
Português
Political polarization is a common topic in the news and media, but not much has been done to understand the distribution of the preferences of the U.S. voting population. Political scientists have drawn different conclusions on the current state of political polarization within the U.S. voting population based on survey data and basic spatial voting models. In this work, I present a spatial voting model that analyzes voting data at a more fine-grained level in order to use Bayesian techniques to infer the underlying distribution of political preferences of the population. Further, I verify these results by comparing it to alternative public opinion measurements and measuring the accuracy in completing prediction tasks. This work adds a new perspective to the current discussion within the political science community of the recent trends of political polarization.

## ‣ Assistive Exoskeleton for Injury Prevention During Downhill Walking

Rogers, Emily Ann
Fonte: Harvard University Publicador: Harvard University
Tipo: Thesis or Dissertation; text Formato: application/pdf
Português
This thesis presents a device designed to reduce muscular effort during downhill walking. The designed solution is a soft wearable exoskeleton consisting of an air spring, a wearable soft fabric interface that attaches the air spring to the user's body, and an integrated smart sensing and pneumatic control system. After prototyping of the device, initial evaluation was performed, showing that the device successfully produced a resistive torque of 5 Nm, decreasing torque on the knee by 10% for a 58 kg individual on a -20 degree slope. Following initial evaluation, human subject testing was conducted in order to determine the effect of the device on muscle activity and gait. Initial results show that on a -5 degree slope, the device can reduce muscle activity by up to 17%. Additionally, joint angle data showed that there were no substantial negative effects on the users natural gait pattern. This device is a low-cost solution that will help the active, elderly, and physically impaired alike by decreasing muscle fatigue, decreasing risk of overuse injuries, increasing independence, and improving overall quality of life.

## ‣ SEATURTLE: Sustained Engagement Autonomous Tracking of Underwater RepTiLEs

Budd, Johnathan
Fonte: Harvard University Publicador: Harvard University
Tipo: Thesis or Dissertation; text Formato: application/pdf
Português
While oceans cover the majority of our planet, these vast expanses remain relatively unexplored. Among the most interesting parts of the ocean are the shallow reef systems, which contain a huge amount of the planet’s biodiversity. The Sustained Engagement Autonomous Tracking of Underwater RepTiLEs or SEATURTLE is a low cost Autonomous Underwater Vehicle designed to carry out missions in these shallow environments. Its small displacement and precise movement make it ideal for navigating tight spaces, and its package of sensors make it easily adaptable to a variety of missions. For this project the vehicle was configured to autonomously track tagged objects underwater, using image recognition and the April Tags system.