Recent Stanford Publications in PubMed
- Self-Passivation of Defects: Effects of High-Energy Particle Irradiation on the Elastic Modulus of Multilayer Graphene.Liu K, Hsin CL, Fu D, Suh J, Tongay S, Chen M, Sun Y, Yan A, Park J, Yu KM, Guo W, Zettl A, Zheng H, Chrzan DC, Wu JAdv Mater
- Emotion-relevant impulsivity predicts sustained anger and aggression after remission in bipolar I disorder.Johnson SL, Carver CSJ Affect Disord
- Chemogenetic profiling identifies RAD17 as synthetically lethal with checkpoint kinase inhibition.Shen JP, Srivas R, Gross A, Li J, Jaehnig EJ, Sun SM, Bojorquez-Gomez A, Licon K, Sivaganesh V, Xu JL, Klepper K, Yeerna H, Pekin D, Qiu CP, van Attikum H, Sobol RW, Ideker TOncotarget
- Synaptotagmin-1 and -7 Are Redundantly Essential for Maintaining the Capacity of the Readily-Releasable Pool of Synaptic Vesicles.Bacaj T, Wu D, Burré J, Malenka RC, Liu X, Südhof TCPLoS Biol
- A Decad(e) of Reasons to Contribute to a PLOS Community-Run Journal.Copenhaver GP, Barsh GSPLoS Genet
- A fibrous papule with abundant CD34-immunoreactive ganglion-like multinucleated giant cells: a case report and review of the literature.Schaberg KB, Chiou AS, Wang KC, Egbert BMDermatol Online J
- Cup tool use by squirrel monkeys.Buckmaster CL, Hyde SA, Parker KJ, Lyons DMAm J Primatol
- The Battle Hymn of the Tiger Child.Nagata JMJAMA Pediatr
- Projections from neocortex mediate top-down control of memory retrieval.Rajasethupathy P, Sankaran S, Marshel JH, Kim CK, Ferenczi E, Lee SY, Berndt A, Ramakrishnan C, Jaffe A, Lo M, Liston C, Deisseroth KNature
- β-Blocker-Associated Risks in Patients With Uncomplicated Hypertension Undergoing Noncardiac Surgery.Jørgensen ME, Hlatky MA, Køber L, Sanders RD, Torp-Pedersen C, Gislason GH, Jensen PF, Andersson CJAMA Intern Med
- Dynamic acousto-optic control of a strongly coupled photonic molecule.Kapfinger S, Reichert T, Lichtmannecker S, Müller K, Finley JJ, Wixforth A, Kaniber M, Krenner HJNat Commun
- The Falsified Medicines Directive: How to secure your supply chain.Smith G, Smith JA, Brindley DAJ Generic Med
- Improving Research Standards to Restore Trust in Intranasal Oxytocin.Carson DS, Yuan H, Labuschagne IBiol Psychiatry
- Formation of a Neurosensory Organ by Epithelial Cell Slithering.Kuo CS, Krasnow MACell
- Whole-Exome Sequencing of 10 Scientists: Evaluation of the Process and Outcomes.Lindor NM, Schahl KA, Johnson KJ, Hunt KS, Mensink KA, Wieben ED, Klee E, Black JL, Highsmith WE, Thibodeau SN, Ferber MJ, Aypar U, Ji Y, Graham RP, Fiksdal AS, Sarangi V, Ormond KE, Riegert-Johnson DL, McAllister TM, Farrugia G, McCormick JBMayo Clin Proc
- Number of Lymph Nodes Removed and Survival after Gastric Cancer Resection: An Analysis from the US Gastric Cancer Collaborative.Gholami S, Janson L, Worhunsky DJ, Tran TB, Squires MH, Jin LX, Spolverato G, Votanopoulos KI, Schmidt C, Weber SM, Bloomston M, Cho CS, Levine EA, Fields RC, Pawlik TM, Maithel SK, Efron B, Norton JA, Poultsides GAJ Am Coll Surg
- Repeat Courses of Stereotactic Radiosurgery (SRS), Deferring Whole-Brain Irradiation, for New Brain Metastases After Initial SRS.Shultz DB, Modlin LA, Jayachandran P, Von Eyben R, Gibbs IC, Choi CY, Chang SD, Harsh GR, Li G, Adler JR, Hancock SL, Soltys SGInt J Radiat Oncol Biol Phys
- Effect of Structured Physical Activity on Sleep-Wake Behaviors in Sedentary Elderly Adults with Mobility Limitations.Vaz Fragoso CA, Miller ME, King AC, Kritchevsky SB, Liu CK, Myers VH, Nadkarni NK, Pahor M, Spring BJ, Gill TM, Lifestyle Interventions and Independence for Elders Study GroupJ Am Geriatr Soc
- Trajectory Modulated Arc Therapy: A Fully Dynamic Delivery With Synchronized Couch and Gantry Motion Significantly Improves Dosimetric Indices Correlated With Poor Cosmesis in Accelerated Partial Breast Irradiation.Liang J, Atwood T, von Eyben R, Fahimian B, Chin E, Horst K, Otto K, Hristov DInt J Radiat Oncol Biol Phys
- Colorectal Histology Is Associated With an Increased Risk of Local Failure in Lung Metastases Treated With Stereotactic Ablative Radiation Therapy.Binkley MS, Trakul N, Jacobs LR, von Eyben R, Le QT, Maxim PG, Loo BW, Shultz DB, Diehn MInt J Radiat Oncol Biol Phys
- Radiological Evaluation of Abdominal Endovascular Aortic Aneurysm Repair.Thakor AS, Tanner J, Ong SJ, Hughes-Roberts Y, Ilyas S, Cousins C, See TC, Klass D, Winterbottom APCan Assoc Radiol J
- Post-radiotherapy prostate biopsies reveal heightened apex positivity relative to other prostate regions sampled.Huang KT, Stoyanova R, Walker G, Sandler K, Studenski MT, Dogan N, Al-Saleem T, Buyyounouski MK, Horwitz EM, Pollack ARadiother Oncol
- Ultrafast energy transfer from rigid, branched side-chains into a conjugated, alternating copolymer.Griffin GB, Lundin PM, Rolczynski BS, Linkin A, McGillicuddy RD, Bao Z, Engel GSJ Chem Phys
- Suppression of unimolecular decay of laser desorbed peptide and protein ions by entrainment in rarefied supersonic gas jets under weak electric fields.Hieke AJ Chem Phys
- Potential implications of research on genetic or heritable contributions to pedophilia for the objectives of criminal law.Berryessa CMRecent Adv DNA Gene Seq
- Sleep characteristics as predictor variables of stress systems markers in insomnia disorder.Floam S, Simpson N, Nemeth E, Scott-Sutherland J, Gautam S, Haack MJ Sleep Res
- The misunderstood consequences of Shelley v. Kraemer.Kucheva Y, Sander RSoc Sci Res
- Regulatory logic and pattern formation in the early sea urchin embryo.Sun M, Cheng X, Socolar JEJ Theor Biol
- Excitatory and inhibitory synaptic connectivity to layer V fast-spiking interneurons in the freeze lesion model of cortical microgyria.Jin X, Jiang K, Prince DAJ Neurophysiol
- Identifying best-fitting inputs in health-economic model calibration: a Pareto frontier approach.Enns EA, Cipriano LE, Simons CT, Kong CYMed Decis Making
- Neighborhood environments and objectively measured physical activity in 11 countries.Cerin E, Cain KL, Conway TL, Van Dyck D, Hinckson E, Schipperijn J, De Bourdeaudhuij I, Owen N, Davey RC, Hino AA, Mitáš J, Orzanco-Garralda R, Salvo D, Sarmiento OL, Christiansen LB, Macfarlane DJ, Schofield G, Sallis JFMed Sci Sports Exerc
- Modeling and calibration for exposure to time-varying, modifiable risk factors: the example of smoking behavior in India.Goldhaber-Fiebert JD, Brandeau MLMed Decis Making
Self-Passivation of Defects: Effects of High-Energy Particle Irradiation on the Elastic Modulus of Multilayer Graphene.
Adv Mater. 2015 Oct 5;
Authors: Liu K, Hsin CL, Fu D, Suh J, Tongay S, Chen M, Sun Y, Yan A, Park J, Yu KM, Guo W, Zettl A, Zheng H, Chrzan DC, Wu J
The elastic modulus of multilayer graphene is found to be more robust to damage created by high-energy α-particle irradiation as compared to monolayer graphene. Theoretical analysis indicates that irradiation of multilayer graphene generates interlayer links that potentially increase the stiffness of the multilayer by passivating local defects.
PMID: 26437308 [PubMed - as supplied by publisher]
Emotion-relevant impulsivity predicts sustained anger and aggression after remission in bipolar I disorder.
J Affect Disord. 2015 Sep 25;189:169-175
Authors: Johnson SL, Carver CS
Recent evidence suggests that anger and aggression are of concern even during remission for persons with bipolar I disorder, although there is substantial variability in the degree of anger and aggression across individuals. Little research is available to examine psychological models of anger and aggression for those with remitted bipolar disorder, and that was the goal of this study. Participants were 58 persons diagnosed with bipolar I disorder using the Structured Clinical Interview for DSM-IV, who were followed with monthly symptom severity interviews until they achieved remission, and then assessed using the Aggression-Short Form. We examined traditional predictors of clinical parameters and trauma exposure, and then considered three trait domains that have been shown to be elevated in bipolar disorder and have also been linked to aggression outside of bipolar disorder: emotion-relevant impulsivity, approach motivation, and dominance-related constructs. Emotion-relevant impulsivity was related to anger, hostility, verbal aggression, and physical aggression, even after controlling for clinical variables. Findings extend the importance of emotion-relevant impulsivity to another important clinical outcome and suggest the promise of using psychological models to understand the factors driving aggression and anger problems that persist into remission among persons with bipolar disorder.
PMID: 26437231 [PubMed - as supplied by publisher]
Chemogenetic profiling identifies RAD17 as synthetically lethal with checkpoint kinase inhibition.
Oncotarget. 2015 Sep 30;
Authors: Shen JP, Srivas R, Gross A, Li J, Jaehnig EJ, Sun SM, Bojorquez-Gomez A, Licon K, Sivaganesh V, Xu JL, Klepper K, Yeerna H, Pekin D, Qiu CP, van Attikum H, Sobol RW, Ideker T
Chemical inhibitors of the checkpoint kinases have shown promise in the treatment of cancer, yet their clinical utility may be limited by a lack of molecular biomarkers to identify specific patients most likely to respond to therapy. To this end, we screened 112 known tumor suppressor genes for synthetic lethal interactions with inhibitors of the CHEK1 and CHEK2 checkpoint kinases. We identified eight interactions, including the Replication Factor C (RFC)-related protein RAD17. Clonogenic assays in RAD17 knockdown cell lines identified a substantial shift in sensitivity to checkpoint kinase inhibition (3.5-fold) as compared to RAD17 wild-type. Additional evidence for this interaction was found in a large-scale functional shRNA screen of over 100 genotyped cancer cell lines, in which CHEK1/2 mutant cell lines were unexpectedly sensitive to RAD17 knockdown. This interaction was widely conserved, as we found that RAD17 interacts strongly with checkpoint kinases in the budding yeast Saccharomyces cerevisiae. In the setting of RAD17 knockdown, CHEK1/2 inhibition was found to be synergistic with inhibition of WEE1, another pharmacologically relevant checkpoint kinase. Accumulation of the DNA damage marker γH2AX following chemical inhibition or transient knockdown of CHEK1, CHEK2 or WEE1 was magnified by knockdown of RAD17. Taken together, our data suggest that CHEK1 or WEE1 inhibitors are likely to have greater clinical efficacy in tumors with RAD17 loss-of-function.
PMID: 26437225 [PubMed - as supplied by publisher]
Synaptotagmin-1 and -7 Are Redundantly Essential for Maintaining the Capacity of the Readily-Releasable Pool of Synaptic Vesicles.
PLoS Biol. 2015 Oct;13(10):e1002267
Authors: Bacaj T, Wu D, Burré J, Malenka RC, Liu X, Südhof TC
In forebrain neurons, Ca2+ triggers exocytosis of readily releasable vesicles by binding to synaptotagmin-1 and -7, thereby inducing fast and slow vesicle exocytosis, respectively. Loss-of-function of synaptotagmin-1 or -7 selectively impairs the fast and slow phase of release, respectively, but does not change the size of the readily-releasable pool (RRP) of vesicles as measured by stimulation of release with hypertonic sucrose, or alter the rate of vesicle priming into the RRP. Here we show, however, that simultaneous loss-of-function of both synaptotagmin-1 and -7 dramatically decreased the capacity of the RRP, again without altering the rate of vesicle priming into the RRP. Either synaptotagmin-1 or -7 was sufficient to rescue the RRP size in neurons lacking both synaptotagmin-1 and -7. Although maintenance of RRP size was Ca2+-independent, mutations in Ca2+-binding sequences of synaptotagmin-1 or synaptotagmin-7-which are contained in flexible top-loop sequences of their C2 domains-blocked the ability of these synaptotagmins to maintain the RRP size. Both synaptotagmins bound to SNARE complexes; SNARE complex binding was reduced by the top-loop mutations that impaired RRP maintenance. Thus, synaptotagmin-1 and -7 perform redundant functions in maintaining the capacity of the RRP in addition to nonredundant functions in the Ca2+ triggering of different phases of release.
PMID: 26437117 [PubMed - as supplied by publisher]
A Decad(e) of Reasons to Contribute to a PLOS Community-Run Journal.
PLoS Genet. 2015 Oct;11(10):e1005557
Authors: Copenhaver GP, Barsh GS
Will be part of a Tenth Anniversary Collection.
PMID: 26436996 [PubMed - as supplied by publisher]
A fibrous papule with abundant CD34-immunoreactive ganglion-like multinucleated giant cells: a case report and review of the literature.
Dermatol Online J. 2015;21(7)
Authors: Schaberg KB, Chiou AS, Wang KC, Egbert BM
Fibrous papules present clinically as benign, asymptomatic, dome-shaped, flesh colored papules on the face. Histologically, fibrous papules are characterized by fibrous stroma with fibroblasts and dilated blood vessels. Multiple variants of fibrous papules have been reported. Although scattered multinucleated cells in fibrous papules have been well described, we report a fibrous papule with abundant multinucleated ganglion-like giant cells that were immunoreactive with CD34. Recognition of such fibrous papule variants is important to avoid misdiagnosis as potentially more worrisome and/or aggressive melanocytic, soft tissue, or neural lesions that may require more aggressive treatment. Indeed, fibrous papules do not commonly appear on the differential diagnosis for lesions with multinucleated giant cells or ganglion-like cells and consideration should be given to their inclusion in the appropriate clinical setting.
PMID: 26436978 [PubMed - as supplied by publisher]
Cup tool use by squirrel monkeys.
Am J Primatol. 2015 Oct 5;
Authors: Buckmaster CL, Hyde SA, Parker KJ, Lyons DM
Captive-born male and female squirrel monkeys spontaneously 'invented' a cup tool use technique to Contain (i.e., hold and control) food they reduced into fragments for consumption and to Contain water collected from a valve to drink. Food cup use was observed more frequently than water cup use. Observations indicate that 68% (n = 39/57) of monkeys in this population used a cup (a plastic slip cap) to Contain food, and a subset of these monkeys, 10% (n = 4/39), also used a cup to Contain water. Cup use was optional and did not replace, but supplemented, the hand/arm-to-mouth eating and direct valve drinking exhibited by all members of the population. Strategies monkeys used to bring food and cups together for food processing activity at preferred upper-level perching areas, in the arboreal-like environment in which they lived, provides evidence that monkeys may plan food processing activity with the cups. Specifically, prior to cup use monkeys obtained a cup first before food, or obtained food and a cup from the floor simultaneously, before transporting both items to upper-level perching areas. After food processing activity with cups monkeys rarely dropped the cups and more often placed the cups onto perching. Monkeys subsequently returned to use cups that they previously placed on perching after food processing activity. The latter behavior is consistent with the possibility that monkeys may keep cups at preferred perching sites for future food processing activity and merits experimental investigation. Reports of spontaneous tool use by squirrel monkeys are rare and this is the first report of population-level tool use. These findings offer insights into the cognitive abilities of squirrel monkeys and provide a new context for behavior studies with this genus and for comparative studies with other primates. Am. J. Primatol. © 2015 Wiley Periodicals, Inc.
PMID: 26436899 [PubMed - as supplied by publisher]
The Battle Hymn of the Tiger Child.
JAMA Pediatr. 2015 Oct 5;:1
Authors: Nagata JM
PMID: 26436537 [PubMed - as supplied by publisher]
Projections from neocortex mediate top-down control of memory retrieval.
Nature. 2015 Oct 5;
Authors: Rajasethupathy P, Sankaran S, Marshel JH, Kim CK, Ferenczi E, Lee SY, Berndt A, Ramakrishnan C, Jaffe A, Lo M, Liston C, Deisseroth K
Top-down prefrontal cortex inputs to the hippocampus have been hypothesized to be important in memory consolidation, retrieval, and the pathophysiology of major psychiatric diseases; however, no such direct projections have been identified and functionally described. Here we report the discovery of a monosynaptic prefrontal cortex (predominantly anterior cingulate) to hippocampus (CA3 to CA1 region) projection in mice, and find that optogenetic manipulation of this projection (here termed AC-CA) is capable of eliciting contextual memory retrieval. To explore the network mechanisms of this process, we developed and applied tools to observe cellular-resolution neural activity in the hippocampus while stimulating AC-CA projections during memory retrieval in mice behaving in virtual-reality environments. Using this approach, we found that learning drives the emergence of a sparse class of neurons in CA2/CA3 that are highly correlated with the local network and that lead synchronous population activity events; these neurons are then preferentially recruited by the AC-CA projection during memory retrieval. These findings reveal a sparsely implemented memory retrieval mechanism in the hippocampus that operates via direct top-down prefrontal input, with implications for the patterning and storage of salient memory representations.
PMID: 26436451 [PubMed - as supplied by publisher]
β-Blocker-Associated Risks in Patients With Uncomplicated Hypertension Undergoing Noncardiac Surgery.
JAMA Intern Med. 2015 Oct 5;:1-9
Authors: Jørgensen ME, Hlatky MA, Køber L, Sanders RD, Torp-Pedersen C, Gislason GH, Jensen PF, Andersson C
Importance: Perioperative β-blocker strategies are important to reduce risks of adverse events. Effectiveness and safety may differ according to patients' baseline risk.
Objective: To determine the risk of major adverse cardiovascular events (MACEs) associated with long-term β-blocker therapy in patients with uncomplicated hypertension undergoing noncardiac surgery.
Design, Setting, and Participants: Association study based on in-hospital records and out-of-hospital pharmacotherapy use using a Danish nationwide cohort of patients with uncomplicated hypertension treated with at least 2 antihypertensive drugs (β-blockers, thiazides, calcium antagonists, or renin-angiotensin system [RAS] inhibitors) undergoing noncardiac surgery between 2005 and 2011.
Interventions: Various antihypertensive treatment regimens, chosen as part of usual care.
Main Outcomes and Measures: Thirty-day risk of MACEs (cardiovascular death, nonfatal ischemic stroke, nonfatal myocardial infarction) and all-cause mortality, assessed using multivariable logistic regression models and adjusted numbers needed to harm (NNH).
Results: The baseline characteristics of the 14 644 patients who received β-blockers (65% female, mean [SD] age, 66.1 [12.0] years) were similar to those of the 40 676 patients who received other antihypertensive drugs (57% female, mean [SD] age, 65.9 [11.8] years). Thirty-day MACEs occurred in 1.3% of patients treated with β-blockers compared with 0.8% of patients not treated with β-blockers (P < .001). β-Blocker use was associated with increased risks of MACEs in 2-drug combinations with RAS inhibitors (odds ratio [OR], 2.16 [95% CI, 1.54-3.04]), calcium antagonists (OR, 2.17 [95% CI, 1.48-3.17]), and thiazides (OR, 1.56 [95% CI, 1.10-2.22]), compared with the reference combination of RAS inhibitors and thiazides. Results were similar for all-cause mortality. Risk of MACEs associated with β-blocker use seemed especially pronounced for patients at least 70 years old (number needed to harm [NNH], 140 [95% CI, 86-364]), for men (NNH, 142 [95% CI, 93-195]), and for patients undergoing acute surgery (NNH, 97 [95% CI, 57-331]), compared with patients younger than 70 years, women, and patients undergoing elective surgery, respectively.
Conclusions and Relevance: Antihypertensive treatment with a β-blocker may be associated with increased risks of perioperative MACEs and all-cause mortality in patients with uncomplicated hypertension.
PMID: 26436291 [PubMed - as supplied by publisher]
Dynamic acousto-optic control of a strongly coupled photonic molecule.
Nat Commun. 2015;6:8540
Authors: Kapfinger S, Reichert T, Lichtmannecker S, Müller K, Finley JJ, Wixforth A, Kaniber M, Krenner HJ
Strongly confined photonic modes can couple to quantum emitters and mechanical excitations. To harness the full potential in quantum photonic circuits, interactions between different constituents have to be precisely and dynamically controlled. Here, a prototypical coupled element, a photonic molecule defined in a photonic crystal membrane, is controlled by a radio frequency surface acoustic wave. The sound wave is tailored to deliberately switch on and off the bond of the photonic molecule on sub-nanosecond timescales. In time-resolved experiments, the acousto-optically controllable coupling is directly observed as clear anticrossings between the two nanophotonic modes. The coupling strength is determined directly from the experimental data. Both the time dependence of the tuning and the inter-cavity coupling strength are found to be in excellent agreement with numerical calculations. The demonstrated mechanical technique can be directly applied for dynamic quantum gate operations in state-of-the-art-coupled nanophotonic, quantum cavity electrodynamic and optomechanical systems.
PMID: 26436203 [PubMed - as supplied by publisher]
The Falsified Medicines Directive: How to secure your supply chain.
J Generic Med. 2014 Sep;11(3-4):169-172
Authors: Smith G, Smith JA, Brindley DA
PMID: 26435721 [PubMed - as supplied by publisher]
Improving Research Standards to Restore Trust in Intranasal Oxytocin.
Biol Psychiatry. 2015 Sep 3;
Authors: Carson DS, Yuan H, Labuschagne I
PMID: 26435223 [PubMed - as supplied by publisher]
Formation of a Neurosensory Organ by Epithelial Cell Slithering.
Cell. 2015 Sep 29;
Authors: Kuo CS, Krasnow MA
Epithelial cells are normally stably anchored, maintaining their relative positions and association with the basement membrane. Developmental rearrangements occur through cell intercalation, and cells can delaminate during epithelial-mesenchymal transitions and metastasis. We mapped the formation of lung neuroepithelial bodies (NEBs), innervated clusters of neuroendocrine/neurosensory cells within the bronchial epithelium, revealing a targeted mode of cell migration that we named "slithering," in which cells transiently lose epithelial character but remain associated with the membrane while traversing neighboring epithelial cells to reach cluster sites. Immunostaining, lineage tracing, clonal analysis, and live imaging showed that NEB progenitors, initially distributed randomly, downregulate adhesion and polarity proteins, crawling over and between neighboring cells to converge at diametrically opposed positions at bronchial branchpoints, where they reestablish epithelial structure and express neuroendocrine genes. There is little accompanying progenitor proliferation or apoptosis. Activation of the slithering program may explain why lung cancers arising from neuroendocrine cells are highly metastatic.
PMID: 26435104 [PubMed - as supplied by publisher]
Whole-Exome Sequencing of 10 Scientists: Evaluation of the Process and Outcomes.
Mayo Clin Proc. 2015 Oct;90(10):1327-37
Authors: Lindor NM, Schahl KA, Johnson KJ, Hunt KS, Mensink KA, Wieben ED, Klee E, Black JL, Highsmith WE, Thibodeau SN, Ferber MJ, Aypar U, Ji Y, Graham RP, Fiksdal AS, Sarangi V, Ormond KE, Riegert-Johnson DL, McAllister TM, Farrugia G, McCormick JB
OBJECTIVE: To understand motivations, educational needs, and concerns of individuals contemplating whole-exome sequencing (WES) and determine what amount of genetic information might be obtained by sequencing a generally healthy cohort so as to more effectively counsel future patients.
PATIENTS AND METHODS: From 2012 to 2014, 40 medically educated, generally healthy scientists at Mayo Clinic were invited to have WES conducted on a research basis; 26 agreed to be in a drawing from which 10 participants were selected. The study involved pre- and posttest genetic counseling and completion of 4 surveys related to the experience and outcomes. Whole-exome sequencing was conducted on DNA from blood from each person.
RESULTS: Most variants (76,305 per person; range, 74,505-77,387) were known benign allelic variants, variants in genes of unknown function, or variants of uncertain significance in genes of known function. The results of suspected pathogenic/pathogenic variants in Mendelian disorders and pharmacogenomic variants were disclosed. The mean number of suspected pathogenic/pathogenic variants was 2.2 per person (range, 1-4). Four pharmacogenomic genes were included for reporting; variants were found in 9 of 10 participants.
CONCLUSION: This study provides data that may be useful in establishing reality-based patient expectations, outlines specific points to cover during counseling, and increases confidence in the feasibility of providing adequate preparation and counseling for WES in generally healthy individuals.
PMID: 26434960 [PubMed - in process]
Number of Lymph Nodes Removed and Survival after Gastric Cancer Resection: An Analysis from the US Gastric Cancer Collaborative.
J Am Coll Surg. 2015 Aug;221(2):291-9
Authors: Gholami S, Janson L, Worhunsky DJ, Tran TB, Squires MH, Jin LX, Spolverato G, Votanopoulos KI, Schmidt C, Weber SM, Bloomston M, Cho CS, Levine EA, Fields RC, Pawlik TM, Maithel SK, Efron B, Norton JA, Poultsides GA
BACKGROUND: Examination of at least 16 lymph nodes (LNs) has been traditionally recommended during gastric adenocarcinoma resection to optimize staging, but the impact of this strategy on survival is uncertain. Because recent randomized trials have demonstrated a therapeutic benefit from extended lymphadenectomy, we sought to investigate the impact of the number of LNs removed on prognosis after gastric adenocarcinoma resection.
STUDY DESIGN: We analyzed patients who underwent gastrectomy for gastric adenocarcinoma from 2000 to 2012, at 7 US academic institutions. Patients with M1 disease or R2 resections were excluded. Disease-specific survival (DSS) was calculated using the Kaplan-Meier method and compared using log-rank and Cox regression analyses.
RESULTS: Of 742 patients, 257 (35%) had 7 to 15 LNs removed and 485 (65%) had ≥16 LNs removed. Disease-specific survival was not significantly longer after removal of ≥16 vs 7 to 15 LNs (10-year survival, 55% vs 47%, respectively; p = 0.53) for the entire cohort, but was significantly improved in the subset of patients with stage IA to IIIA (10-year survival, 74% vs 57%, respectively; p = 0.018) or N0-2 disease (72% vs 55%, respectively; p = 0.023). Similarly, for patients who were classified to more likely be "true N0-2," based on frequentist analysis incorporating both the number of positive and of total LNs removed, the hazard ratio for disease-related death (adjusted for T stage, R status, grade, receipt of neoadjuvant and adjuvant therapy, and institution) significantly decreased as the number of LNs removed increased.
CONCLUSIONS: The number of LNs removed during gastrectomy for adenocarcinoma appears itself to have prognostic implications for long-term survival.
PMID: 26206635 [PubMed - indexed for MEDLINE]
Repeat Courses of Stereotactic Radiosurgery (SRS), Deferring Whole-Brain Irradiation, for New Brain Metastases After Initial SRS.
Int J Radiat Oncol Biol Phys. 2015 Aug 1;92(5):993-9
Authors: Shultz DB, Modlin LA, Jayachandran P, Von Eyben R, Gibbs IC, Choi CY, Chang SD, Harsh GR, Li G, Adler JR, Hancock SL, Soltys SG
PURPOSE: To report the outcomes of repeat stereotactic radiosurgery (SRS), deferring whole-brain radiation therapy (WBRT), for distant intracranial recurrences and identify factors associated with prolonged overall survival (OS).
PATIENTS AND METHODS: We retrospectively identified 652 metastases in 95 patients treated with 2 or more courses of SRS for brain metastases, deferring WBRT. Cox regression analyzed factors predictive for OS.
RESULTS: Patients had a median of 2 metastases (range, 1-14) treated per course, with a median of 2 courses (range, 2-14) of SRS per patient. With a median follow-up after first SRS of 15 months (range, 3-98 months), the median OS from the time of the first and second course of SRS was 18 (95% confidence interval [CI] 15-24) and 11 months (95% CI 6-17), respectively. On multivariate analysis, histology, graded prognostic assessment score, aggregate tumor volume (but not number of metastases), and performance status correlated with OS. The 1-year cumulative incidence, with death as a competing risk, of local failure was 5% (95% CI 4-8%). Eighteen (24%) of 75 deaths were from neurologic causes. Nineteen patients (20%) eventually received WBRT. Adverse radiation events developed in 2% of SRS sites.
CONCLUSION: Multiple courses of SRS, deferring WBRT, for distant brain metastases after initial SRS, seem to be a safe and effective approach. The graded prognostic assessment score, updated at each course, and aggregate tumor volume may help select patients in whom the deferral of WBRT might be most beneficial.
PMID: 26194677 [PubMed - indexed for MEDLINE]
Effect of Structured Physical Activity on Sleep-Wake Behaviors in Sedentary Elderly Adults with Mobility Limitations.
J Am Geriatr Soc. 2015 Jul;63(7):1381-90
Authors: Vaz Fragoso CA, Miller ME, King AC, Kritchevsky SB, Liu CK, Myers VH, Nadkarni NK, Pahor M, Spring BJ, Gill TM, Lifestyle Interventions and Independence for Elders Study Group
OBJECTIVES: To evaluate the effect of structured physical activity on sleep-wake behaviors in sedentary community-dwelling elderly adults with mobility limitations.
DESIGN: Multicenter, randomized trial of moderate-intensity physical activity versus health education, with sleep-wake behaviors prespecified as a tertiary outcome over a planned intervention period ranging from 24 to 30 months.
SETTING: Lifestyle Interventions and Independence for Elders Study.
PARTICIPANTS: Community-dwelling persons aged 70 to 89 who were initially sedentary and had a Short Physical Performance Battery score less than 10 (N = 1,635).
MEASUREMENTS: Sleep-wake behaviors were evaluated using the Insomnia Severity Index (ISI) (≥8 defined insomnia), Epworth Sleepiness Scale (ESS) (≥10 defined daytime drowsiness), and Pittsburgh Sleep Quality Index (PSQI) (>5 defined poor sleep quality) administered at baseline and 6, 18, and 30 months.
RESULTS: The randomized groups were similar in terms of baseline demographic variables, including mean age (79) and sex (67% female). Structured physical activity resulted in a significantly lower likelihood of having poor sleep quality (adjusted odds ratios (aOR) for PSQI >5 = 0.80, 95% confidence interval (CI) = 0.68-0.94), including fewer new cases (aOR for PSQI >5 = 0.70, 95% CI = 0.54-0.89), than health education but not in resolution of prevalent cases (aOR for PSQI ≤5 = 1.13, 95% CI = 0.90-1.43). No significant intervention effects were observed for the ISI or ESS.
CONCLUSION: Structured physical activity resulted in a lower likelihood of developing poor sleep quality (PSQI >5) over the intervention period than health education but had no effect on prevalent cases of poor sleep quality or on sleep-wake behaviors evaluated using the ISI or ESS. These results suggest that the benefit of physical activity in this sample was preventive and limited to sleep-wake behaviors evaluated using the PSQI.
PMID: 26115386 [PubMed - indexed for MEDLINE]
Trajectory Modulated Arc Therapy: A Fully Dynamic Delivery With Synchronized Couch and Gantry Motion Significantly Improves Dosimetric Indices Correlated With Poor Cosmesis in Accelerated Partial Breast Irradiation.
Int J Radiat Oncol Biol Phys. 2015 Aug 1;92(5):1148-56
Authors: Liang J, Atwood T, von Eyben R, Fahimian B, Chin E, Horst K, Otto K, Hristov D
PURPOSE: To develop planning and delivery capabilities for linear accelerator-based nonisocentric trajectory modulated arc therapy (TMAT) and to evaluate the benefit of TMAT for accelerated partial breast irradiation (APBI) with the patient in prone position.
METHODS AND MATERIALS: An optimization algorithm for volumetrically modulated arc therapy (VMAT) was generalized to allow for user-defined nonisocentric TMAT trajectories combining couch rotations and translations. After optimization, XML scripts were automatically generated to program and subsequently deliver the TMAT plans. For 10 breast patients in the prone position, TMAT and 6-field noncoplanar intensity modulated radiation therapy (IMRT) plans were generated under equivalent objectives and constraints. These plans were compared with regard to whole breast tissue volume receiving more than 100%, 80%, 50%, and 20% of the prescription dose.
RESULTS: For TMAT APBI, nonisocentric collision-free horizontal arcs with large angular span (251.5 ± 7.9°) were optimized and delivered with delivery time of ∼4.5 minutes. Percentage changes of whole breast tissue volume receiving more than 100%, 80%, 50%, and 20% of the prescription dose for TMAT relative to IMRT were -10.81% ± 6.91%, -27.81% ± 7.39%, -14.82% ± 9.67%, and 39.40% ± 10.53% (P≤.01).
CONCLUSIONS: This is a first demonstration of end-to-end planning and delivery implementation of a fully dynamic APBI TMAT. Compared with IMRT, TMAT resulted in marked reduction of the breast tissue volume irradiated at high doses.
PMID: 26050608 [PubMed - indexed for MEDLINE]
Colorectal Histology Is Associated With an Increased Risk of Local Failure in Lung Metastases Treated With Stereotactic Ablative Radiation Therapy.
Int J Radiat Oncol Biol Phys. 2015 Aug 1;92(5):1044-52
Authors: Binkley MS, Trakul N, Jacobs LR, von Eyben R, Le QT, Maxim PG, Loo BW, Shultz DB, Diehn M
PURPOSE: Stereotactic ablative radiation therapy (SABR) is increasingly used to treat lung oligometastases. We set out to determine the safety and efficacy of this approach and to identify factors associated with outcomes.
METHODS AND MATERIALS: We conducted a retrospective study of patients treated with SABR for metastatic lung tumors at our institution from 2003 to 2014. We assessed the association between various patient and treatment factors with local failure (LF), progression, subsequent treatment, systemic treatment, and overall survival (OS), using univariate and multivariate analyses.
RESULTS: We identified 122 tumors in 77 patients meeting inclusion criteria for this study. Median follow-up was 22 months. The 12- and 24-month cumulative incidence rates of LF were 8.7% and 16.2%, respectively; the 24-month cumulative incidence rates of progression, subsequent treatment, and subsequent systemic treatment were 75.2%, 64.5%, and 35.1%, respectively. Twenty-four-month OS was 74.6%, and median OS was 36 months. Colorectal metastases had a significantly higher cumulative incidence of LF at 12 and 24 months (25.5% and 42.2%, respectively), than all other histologies (4.4% and 9.9%, respectively; P<.0004). The 24-month cumulative incidences of LF for colorectal metastases treated with a biologically effective dose at α/β = 10 (BED10) of <100 Gy versus BED10 of ≥100 Gy were 62.5% and 16.7%, respectively (P=.08). Toxicity was minimal, with only a single grade 3 or higher event observed.
CONCLUSIONS: SABR for metastatic lung tumors appears to be safe and effective with excellent local control, treatment-free intervals, and OS. An exception is metastases from colorectal cancer, which have a high LF rate consistent with a radioresistant phenotype, suggesting a potential role for dose escalation.
PMID: 26025776 [PubMed - indexed for MEDLINE]
Radiological Evaluation of Abdominal Endovascular Aortic Aneurysm Repair.
Can Assoc Radiol J. 2015 Aug;66(3):277-90
Authors: Thakor AS, Tanner J, Ong SJ, Hughes-Roberts Y, Ilyas S, Cousins C, See TC, Klass D, Winterbottom AP
Endovascular aortic aneurysm repair (EVAR) is an alternative to open surgical repair of aortic aneurysms offering lower perioperative mortality and morbidity. As experience increases, clinicians are undertaking complex repairs with hostile aortic anatomy using branched or fenestrated devices or extra components such as chimneys to ensure perfusion to visceral branch vessels whilst excluding the aneurysm. Defining the success of EVAR depends on both clinical and radiographic criteria, but ultimately depends on complete exclusion of the aneurysm from the circulation. Aortic stent grafts are monitored using a combination of imaging modalities including computed tomography angiography (CTA), ultrasonography, magnetic resonance imaging, plain films, and nuclear medicine studies. This article describes when and how to evaluate aortic stent grafts using each of these modalities along with the characteristic features of several of the main stent grafts currently used in clinical practice. The commonly encountered complications from EVAR are also discussed and how they can be detected using each imaging modality. As the radiation burden from serial follow up CTA imaging is now becoming a concern, different follow-up imaging strategies are proposed depending on the complexity of the repair and based on the relative merits and disadvantages of each imaging modality.
PMID: 25978867 [PubMed - indexed for MEDLINE]
Post-radiotherapy prostate biopsies reveal heightened apex positivity relative to other prostate regions sampled.
Radiother Oncol. 2015 Apr;115(1):101-6
Authors: Huang KT, Stoyanova R, Walker G, Sandler K, Studenski MT, Dogan N, Al-Saleem T, Buyyounouski MK, Horwitz EM, Pollack A
BACKGROUND AND PURPOSE: Prostate biopsy positivity after radiotherapy (RT) is a significant determinant of eventual biochemical failure. We mapped pre- and post-treatment tumor locations to determine if residual disease is location-dependent.
MATERIALS AND METHODS: There were 303 patients treated on a randomized hypofractionation trial. Of these, 125 underwent prostate biopsy 2-years post-RT. Biopsy cores were mapped to a sextant template, and 86 patients with both pre-/post-treatment systematic sextant biopsies were analyzed.
RESULTS: The pretreatment distribution of positive biopsy cores was not significantly related to prostate region (base, mid, apex; p=0.723). Whereas all regions post-RT had reduced positive biopsies, the base was reduced to the greatest degree and the apex the least (p=0.045). In 38 patients who had a positive post-treatment biopsy, there was change in the rate of apical positivity before and after treatment (76 vs. 71%; p=0.774), while significant reductions were seen in the mid and base.
CONCLUSION: In our experience, persistence of prostate tumor cells after RT increases going from the base to apex. MRI was used in planning and image guidance was performed daily during treatment, so geographic miss of the apex is unlikely. Nonetheless, the pattern observed suggests that attention to apex dosimetry is a priority.
PMID: 25963053 [PubMed - indexed for MEDLINE]
Ultrafast energy transfer from rigid, branched side-chains into a conjugated, alternating copolymer.
J Chem Phys. 2014 Jan 21;140(3):034903
Authors: Griffin GB, Lundin PM, Rolczynski BS, Linkin A, McGillicuddy RD, Bao Z, Engel GS
We present the synthesis and characterization of a benzodithiophene/thiophene alternating copolymer decorated with rigid, singly branched pendant side chains. We characterize exciton migration and recombination dynamics in these molecules in tetrahydrofuran solution, using a combination of static and time-resolved spectroscopies. As control experiments, we also measure electronic relaxation dynamics in isolated molecular analogues of both the side chain and polymer moieties. We employ semi-empirical and time-dependent density functional theory calculations to show that photoexcitation of the decorated copolymer using 395 nm laser pulses results in excited states primarily localized on the pendant side chains. We use ultrafast transient absorption spectroscopy to show that excitations are transferred to the polymer backbone faster than the instrumental response function, ∼250 fs.
PMID: 25669410 [PubMed - indexed for MEDLINE]
Suppression of unimolecular decay of laser desorbed peptide and protein ions by entrainment in rarefied supersonic gas jets under weak electric fields.
J Chem Phys. 2014 Jan 21;140(3):034201
Authors: Hieke A
Unimolecular decay of sample ions imposes a limit on the usable laser fluence in matrix-assisted laser desorption/ionization (MALDI) ion sources. Traditionally, some modest degree of collisional sample ion cooling has been achieved by connecting MALDI ion sources directly to gas-filled radio frequency (RF) multipoles. It was also discovered in the early 1990s that gas-filled RF multipoles exhibit increased ion transmission efficiency due to collisional ion focusing effects. This unexpected experimental finding was later supported by elementary Monte Carlo simulations. Both experiments and simulations assumed a resting background gas with typical pressures of the order of 1 Pa. However, considerable additional improvements can be achieved if laser desorbed sample ions are introduced immediately after desorption, still within the ion source, in an axisymmetric rarefied supersonic gas jet with peak pressure of the order of 100 Pa and flow velocities >300 m/s, and under weak electric fields. We describe here the design principle and report performance data of an ion source coined "MALDI-2," which incorporates elements of both rarefied aerodynamics and particle optics. Such a design allows superb suppression of metastable fragmentation due to rapid collisional cooling in <10 μs and nearly perfect injection efficiency into the attached RF ion guide, as numerous experiments have confirmed.
PMID: 25669372 [PubMed - indexed for MEDLINE]
Potential implications of research on genetic or heritable contributions to pedophilia for the objectives of criminal law.
Recent Adv DNA Gene Seq. 2014;8(2):65-77
Authors: Berryessa CM
In recent years, there has been increasing scientific research on possible genetic or heritable influences to the etiology of pedophilia, driven by national and public concerns about better understanding the disorder in order to reduce children's vulnerabilities to pedophilic and child sex offenders. This research has corresponded to growing academic dialogue on how advances in genetic research, especially concerning the causes and development of particular mental disorders or behaviors, may affect traditional practices of criminal law and how the justice system views, manages, and adjudicates different types of criminal behavior and offenders. This paper strives to supplement this dialogue by exploring several of the many possible effects and implications of research surrounding genetic or heritable contributions to pedophilia for the five widely accepted objectives that enforce and regulate the punishment of criminal law. These include retribution, incapacitation, deterrence, rehabilitation, and restoration. Although still currently in early stages, genetic and heritability research on the etiology of pedophilia may have the potential moving forward to influence the current and established punitive methods and strategies of how the justice system perceives, adjudicates, regulates, and punishes pedophilic and sex offenders, as well as how to best prevent sexual offending against children by pedophilic offenders in the future.
PMID: 25557668 [PubMed - indexed for MEDLINE]
Sleep characteristics as predictor variables of stress systems markers in insomnia disorder.
J Sleep Res. 2015 Jun;24(3):296-304
Authors: Floam S, Simpson N, Nemeth E, Scott-Sutherland J, Gautam S, Haack M
This study investigates the extent to which sleep characteristics serve as predictor variables for inflammatory, hypothalamic-pituitary-adrenal and autonomic systems markers. Twenty-nine participants with a diagnosis of insomnia disorder based on the Diagnostic Statistical Manual of Mental Disorders, Fifth Edition (age 25.3 ± 1.6 years, insomnia duration 6.6 ± 0.8 years) and 19 healthy control sleepers (age 25.4 ± 1.4 years) underwent a 2-week at-home evaluation keeping a sleep diary and wearing an actigraph, followed by a visit to the Research Center to measure blood pressure, and collect blood and urine samples. The actigraphy- and diary-based variables of sleep duration, sleep-onset latency, wake after sleep onset and sleep fragmentation/number of night-time awakenings were averaged and entered as dependent variables in regression analyses. Composite scores were calculated for the autonomic (blood pressure, norepinephrine), inflammatory (monocyte counts, interleukin-6, C-reactive protein) and hypothalamic-pituitary-adrenal systems (cortisol), and used as predictor variables in regression models. Compared with controls, individuals with insomnia had a shorter sleep duration (P < 0.05), and a higher hypothalamic-pituitary-adrenal and inflammatory composite score (P < 0.05). The higher inflammatory score was mainly due to higher circulating monocytes (P < 0.05), rather than differences in interleukin-6 or C-reactive protein. In persistent insomnia disorder, cortisol is upregulated and associated with actigraphy- and diary-based wake after sleep onset, suggesting that wake after sleep onset may serve as a marker to identify individuals at increased risks for disorders associated with a hyperactive hypothalamic-pituitary-adrenal system. The absence of autonomic and pro-inflammatory changes (interleukin-6, C-reactive protein), despite a substantial decrease in actigraphic sleep duration, may relate to a higher resilience to the adverse biological consequences of insomnia in this young age group.
PMID: 25524529 [PubMed - indexed for MEDLINE]
The misunderstood consequences of Shelley v. Kraemer.
Soc Sci Res. 2014 Nov;48:212-33
Authors: Kucheva Y, Sander R
Shelley v. Kraemer (1948) was a landmark civil rights ruling, in which the Supreme Court held that private racial covenants could not be enforced by the state to evict black buyers of "restricted" homes. Fair housing scholars have generally dismissed or downplayed the practical effects of Shelley, since other forms of housing discrimination remained very powerful. Using spatial lag models and detailed geographic data on the location of covenants and patterns of intra-urban black migration, we compare the role of Shelley with other forces shaping mid-century neighborhood change. We find that Shelley precipitated white-to-black neighborhood transitions after 1948 and changed the nature of the dual housing market in important ways. We also show that increased black mobility produced a sharp increase in intra-black economic segregation during the 1950s and 1960s.
PMID: 25131286 [PubMed - indexed for MEDLINE]
Regulatory logic and pattern formation in the early sea urchin embryo.
J Theor Biol. 2014 Dec 21;363:80-92
Authors: Sun M, Cheng X, Socolar JE
We model the endomesoderm tissue specification process in the vegetal half of the early sea urchin embryo using Boolean models with continuous-time updating to represent the regulatory network that controls gene expression. Our models assume that the network interaction rules remain constant over time and the dynamics plays out on a predetermined program of cell divisions. An exhaustive search of two-node models, in which each node may represent a module of several genes in the real regulatory network, yields a unique network architecture that can accomplish the pattern formation task at hand--the formation of three latitudinal tissue bands from an initial state with only two distinct cell types. Analysis of an eight-gene model constructed from available experimental data reveals that it has a modular structure equivalent to the successful two-node case. Our results support the hypothesis that the gene regulatory network provides sufficient instructions for producing the correct pattern of tissue specification at this stage of development (between the fourth and tenth cleavages in the urchin embryo).
PMID: 25093827 [PubMed - indexed for MEDLINE]
Excitatory and inhibitory synaptic connectivity to layer V fast-spiking interneurons in the freeze lesion model of cortical microgyria.
J Neurophysiol. 2014 Oct 1;112(7):1703-13
Authors: Jin X, Jiang K, Prince DA
A variety of major developmental cortical malformations are closely associated with clinically intractable epilepsy. Pathophysiological aspects of one such disorder, human polymicrogyria, can be modeled by making neocortical freeze lesions (FL) in neonatal rodents, resulting in the formation of microgyri. Previous studies showed enhanced excitatory and inhibitory synaptic transmission and connectivity in cortical layer V pyramidal neurons in the paramicrogyral cortex. In young adult transgenic mice that express green fluorescent protein (GFP) specifically in parvalbumin positive fast-spiking (FS) interneurons, we used laser scanning photostimulation (LSPS) of caged glutamate to map excitatory and inhibitory synaptic connectivity onto FS interneurons in layer V of paramicrogyral cortex in control and FL groups. The proportion of uncaging sites from which excitatory postsynaptic currents (EPSCs) could be evoked (hotspot ratio) increased slightly but significantly in FS cells of the FL vs. control cortex, while the mean amplitude of LSPS-evoked EPSCs at hotspots did not change. In contrast, the hotspot ratio of inhibitory postsynaptic currents (IPSCs) was significantly decreased in FS neurons of the FL cortex. These alterations in synaptic inputs onto FS interneurons may result in an enhanced inhibitory output. We conclude that alterations in synaptic connectivity to cortical layer V FS interneurons do not contribute to hyperexcitability of the FL model. Instead, the enhanced inhibitory output from these neurons may partially offset an earlier demonstrated increase in synaptic excitation of pyramidal cells and thereby maintain a relative balance between excitation and inhibition in the affected cortical circuitry.
PMID: 24990567 [PubMed - indexed for MEDLINE]
Identifying best-fitting inputs in health-economic model calibration: a Pareto frontier approach.
Med Decis Making. 2015 Feb;35(2):170-82
Authors: Enns EA, Cipriano LE, Simons CT, Kong CY
BACKGROUND: To identify best-fitting input sets using model calibration, individual calibration target fits are often combined into a single goodness-of-fit (GOF) measure using a set of weights. Decisions in the calibration process, such as which weights to use, influence which sets of model inputs are identified as best-fitting, potentially leading to different health economic conclusions. We present an alternative approach to identifying best-fitting input sets based on the concept of Pareto-optimality. A set of model inputs is on the Pareto frontier if no other input set simultaneously fits all calibration targets as well or better.
METHODS: We demonstrate the Pareto frontier approach in the calibration of 2 models: a simple, illustrative Markov model and a previously published cost-effectiveness model of transcatheter aortic valve replacement (TAVR). For each model, we compare the input sets on the Pareto frontier to an equal number of best-fitting input sets according to 2 possible weighted-sum GOF scoring systems, and we compare the health economic conclusions arising from these different definitions of best-fitting.
RESULTS: For the simple model, outcomes evaluated over the best-fitting input sets according to the 2 weighted-sum GOF schemes were virtually nonoverlapping on the cost-effectiveness plane and resulted in very different incremental cost-effectiveness ratios ($79,300 [95% CI 72,500-87,600] v. $139,700 [95% CI 79,900-182,800] per quality-adjusted life-year [QALY] gained). Input sets on the Pareto frontier spanned both regions ($79,000 [95% CI 64,900-156,200] per QALY gained). The TAVR model yielded similar results.
CONCLUSIONS: Choices in generating a summary GOF score may result in different health economic conclusions. The Pareto frontier approach eliminates the need to make these choices by using an intuitive and transparent notion of optimality as the basis for identifying best-fitting input sets.
PMID: 24799456 [PubMed - indexed for MEDLINE]
Neighborhood environments and objectively measured physical activity in 11 countries.
Med Sci Sports Exerc. 2014 Dec;46(12):2253-64
Authors: Cerin E, Cain KL, Conway TL, Van Dyck D, Hinckson E, Schipperijn J, De Bourdeaudhuij I, Owen N, Davey RC, Hino AA, Mitáš J, Orzanco-Garralda R, Salvo D, Sarmiento OL, Christiansen LB, Macfarlane DJ, Schofield G, Sallis JF
PURPOSE: Environmental changes are potentially effective population-level physical activity (PA) promotion strategies. However, robust multisite evidence to guide international action for developing activity-supportive environments is lacking. We estimated pooled associations of perceived environmental attributes with objectively measured PA outcomes, between-site differences in such associations, and the extent to which perceived environmental attributes explain between-site differences in PA.
METHODS: This was a cross-sectional study conducted in 16 cities located in Belgium, Brazil, Colombia, Czech Republic, Denmark, China, Mexico, New Zealand, Spain, United Kingdom, and United States of America. Participants were 6968 adults residing in administrative units stratified by socioeconomic status and transport-related walkability. Predictors were 10 perceived neighborhood environmental attributes. Outcome measures were accelerometry-assessed weekly minutes of moderate-to-vigorous PA (MVPA) and meeting the PA guidelines for cancer/weight gain prevention (420 min·wk of MVPA).
RESULTS: Most perceived neighborhood attributes were positively associated with the PA outcomes in the pooled, site-adjusted, single-predictor models. Associations were generalizable across geographical locations. Aesthetics and land use mix-access were significant predictors of both PA outcomes in the fully adjusted models. Environmental attributes accounted for within-site variability in MVPA, corresponding to an SD of 3 min·d or 21 min·wk. Large between-site differences in PA outcomes were observed; 15.9%-16.8% of these differences were explained by perceived environmental attributes. All neighborhood attributes were associated with between-site differences in the total effects of the perceived environment on PA outcomes.
CONCLUSIONS: Residents' perceptions of neighborhood attributes that facilitate walking were positively associated with objectively measured MVPA and meeting the guidelines for cancer/weight gain prevention at the within- and between-site levels. Associations were similar across study sites, lending support for international recommendations for designing PA-friendly built environments.
PMID: 24781892 [PubMed - indexed for MEDLINE]
Modeling and calibration for exposure to time-varying, modifiable risk factors: the example of smoking behavior in India.
Med Decis Making. 2015 Feb;35(2):196-210
Authors: Goldhaber-Fiebert JD, Brandeau ML
BACKGROUND: Risk factors increase the incidence and severity of chronic disease. To examine future trends and develop policies addressing chronic diseases, it is important to capture the relationship between exposure and disease development, which is challenging given limited data.
OBJECTIVE: To develop parsimonious risk factor models embeddable in chronic disease models, which are useful when longitudinal data are unavailable.
DESIGN: The model structures encode relevant features of risk factors (e.g., time-varying, modifiable) and can be embedded in chronic disease models. Calibration captures time-varying exposures for the risk factor models using available cross-sectional data. We illustrate feasibility with the policy-relevant example of smoking in India.
METHODS: The model is calibrated to the prevalence of male smoking in 12 Indian regions estimated from the 2009-2010 Indian Global Adult Tobacco Survey. Nelder-Mead searches (250,000 starting locations) identify distributions of starting, quitting, and restarting rates that minimize the difference between modeled and observed age-specific prevalence. We compare modeled life expectancies to estimates in the absence of time-varying risk exposures and consider gains from hypothetical smoking cessation programs delivered for 1 to 30 years.
RESULTS: Calibration achieves concordance between modeled and observed outcomes. Probabilities of starting to smoke rise and fall with age, while quitting and restarting probabilities fall with age. Accounting for time-varying smoking exposures is important, as not doing so produces smaller estimates of life expectancy losses. Estimated impacts of smoking cessation programs delivered for different periods depend on the fact that people who have been induced to abstain from smoking longer are less likely to restart.
CONCLUSIONS: The approach described is feasible for important risk factors for numerous chronic diseases. Incorporating exposure-change rates can improve modeled estimates of chronic disease outcomes and of the long-term effects of interventions targeting risk factors.
PMID: 24477078 [PubMed - indexed for MEDLINE]
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