Favorable Trajectories Research Articles

Telomere length as a marker of cellular aging is associated with prevalence and progression of metabolic syndrome.

Metabolic syndrome (MetS) clusters risk factors for age-related conditions including cardiovascular disease and diabetes. Shorter telomere length (TL), a cellular marker for biological age, may predict an individual's deteriorating metabolic condition. We examined whether shorter baseline TL is associated with a worse metabolic profile and with less favorable trajectories of MetS components over a 6-year follow-up. PARTICIPANTS were part of The Netherlands Study of Depression and Anxiety, an ongoing prospective cohort study with 6-year follow-up. This study included 2848 participants age 18-65 years. Baseline TL from leukocytes was determined using qPCR and MetS components (waist circumference, triglycerides, high-density lipoprotein [HDL] cholesterol, systolic blood pressure, and fasting glucose) were determined at baseline, and after 2 and 6 years. Cross-sectional and longitudinal analyses were adjusted for relevant sociodemographic, lifestyle, and health factors. Shorter baseline TL was cross-sectionally associated with HDL (β = -0.016, SE = 0.008, P = .05), waist circumference (β = 0.647, SE = 0.238, P = .007), triglycerides (β = 0.038, SE = 0.009, P < .001), and fasting glucose (β = 0.011, SE = 0.003, P < .001), as well as with the total number of MetS components (β = 0.075, SE = 0.023, P = .001) and the presence of MetS (OR = 1.19; 95% CI, 1.07-1.33; P = .002). Although baseline differences progressively reduced over time, shorter baseline TL was still significantly associated with unfavorable scores of most MetS components at the 2- or 6-year follow-up. Cellular aging, as assessed by TL, is associated with a higher metabolic risk profile, which remains unfavorable even after a period of 6 years. These findings suggest that cellular aging might play a role in the onset of various aging-related somatic diseases via its effect on metabolic alterations.

Predicting the Naturalistic Course of Major Depressive Disorder Using Clinical and Multimodal Neuroimaging Information: A Multivariate Pattern Recognition Study

BackgroundA chronic course of major depressive disorder (MDD) is associated with profound alterations in brain volumes and emotional and cognitive processing. However, no neurobiological markers have been identified that prospectively predict MDD course trajectories. This study evaluated the prognostic value of different neuroimaging modalities, clinical characteristics, and their combination to classify MDD course trajectories. MethodsOne hundred eighteen MDD patients underwent structural and functional magnetic resonance imaging (MRI) (emotional facial expressions and executive functioning) and were clinically followed-up at 2 years. Three MDD trajectories (chronic n = 23, gradual improving n = 36, and fast remission n = 59) were identified based on Life Chart Interview measuring the presence of symptoms each month. Gaussian process classifiers were employed to evaluate prognostic value of neuroimaging data and clinical characteristics (including baseline severity, duration, and comorbidity). ResultsChronic patients could be discriminated from patients with more favorable trajectories from neural responses to various emotional faces (up to 73% accuracy) but not from structural MRI and functional MRI related to executive functioning. Chronic patients could also be discriminated from remitted patients based on clinical characteristics (accuracy 69%) but not when age differences between the groups were taken into account. Combining different task contrasts or data sources increased prediction accuracies in some but not all cases. ConclusionsOur findings provide evidence that the prediction of naturalistic course of depression over 2 years is improved by considering neuroimaging data especially derived from neural responses to emotional facial expressions. Neural responses to emotional salient faces more accurately predicted outcome than clinical data.

Reanalysis of the Benešov bolide and recovery of polymict breccia meteorites – old mystery solved after 20 years

The main motivation for this work was to explain and solve the old mystery connected with the detailed instrumental observation of the Benesov superbolide on 7 May 1991 over the central part of the Czech Republic. Detailed analyses of this undoubted meteorite fall were published in several papers, and this is one of the best documented bolides (at least of the superbolide category) ever observed. However, despite high-quality data, favorable trajectory, relatively large terminal mass, and especially great efforts and many attempts, no meteorite was found in the weeks and years after the fall. Here we solve and explain this old mystery. In spring 2011, just before the twentieth anniversary of this extraordinary case, we remeasured all available all-sky records and reanalyzed the data. We used slightly different methods and new approaches, which we gradually developed to analyze several recent instrumentally observed meteorite falls (Moravka, Neuschwanstein, Jesenice, Bunburra Rockhole, Mason Gully, and Kosice). We assembled a new consistent picture of the Benesov event, which resulted in a slightly revised impact location and suggested a new strategy that might lead to a recovery of Benesov meteorites after 20 years. The reality completely confirmed all our assumptions and surpassed our expectations. We found four small highly weathered fragments irregular in form and completely without fusion crust with a total mass of 11.63 g (1.54 g (H5), 7.72 g (with achondritic clast), 1.99 g, 0.38 g (all LL3.5)). They were recovered exactly in the predicted impact area for corresponding masses, namely within 40 m from the highest probability line. Although all fragments are very small and their weathering grade is high (W3 for all pieces), their interior was preserved enough for reliable analysis (except for the smallest one). The meteorite is classified as a polymict breccia containing three recognized lithologies with different texture, chemical, and mineralogical composition. This result is pioneering in many aspects. We proved that in some special cases it is still possible to predict and find meteorites a long time after the fall. The most important result, however, is the heterogeneity of the recovered meteorites. This case clearly shows that larger meteoroids can be compositionally very complicated bodies. We discovered that the Benesov meteoroid consisted of at least three different types of material – LL3.5, H5, and primitive achondrite. This case also implies that it is very useful to study as many fragments as possible from one fall because there can be significant differences among them.

Adaptive Dynamic Sliding-Mode Fuzzy CMAC for Voice Coil Motor Using Asymmetric Gaussian Membership Function

When the precise model of a controlled system is difficult to obtain, a model-free control method is suitable for control system design. The design goal of this paper is to propose a more efficient control method to deal with control systems with unknown system dynamic models and to achieve favorable chattering-free trajectory tracking performance. The cerebellar model articulation controller (CMAC) is an efficient neural network that can be applied for model-free control systems. This study proposes an adaptive dynamic sliding-mode fuzzy CMAC (ADSFC) system, which is comprised of a fuzzy CMAC and a fuzzy compensator. A fuzzy CMAC using an asymmetric Gaussian membership function is the main controller and the fuzzy compensator can compensate the approximation error introduced by a fuzzy CMAC. Moreover, a proportional-integral-type adaptation learning algorithm is developed to speed up the parameter learning. Finally, the proposed ADSFC system is applied to control a voice coil motor (VCM). Finally, the experimental results demonstrate the effectiveness of the proposed ADSFC scheme.

Mathematics growth trajectories in first grade: Cumulative vs. compensatory patterns and the role of number sense

We examined mathematics growth trajectories in first grade for overall achievement and three separate competences (Basic Precursors, Advanced Precursors, Computation). 153 German students computed seven web-based progress monitoring tests during the school year. Latent class growth analysis (LCGA) provided evidence for mainly cumulative patterns of performance development: In all competences, we found groups of initially high-performing students with the highest end scores and groups of initially low-performing students with little or no growth. In contrast to this general pattern, compensatory trajectories with groups of initially lower-performing students and steep growth were found. For precursor competences, these catch-up groups did not have increased odds of belonging to low-end outcome groups in higher competences. The findings demonstrate the added value of repeatedly assessing both precursor and grade-level skills for identifying students who follow favorable or unfavorable learning trajectories.

Minimally Invasive (Metrx) Resection of Intradural Spinal Lesions. A Series of 33 Consecutive Cases with Results and Complications

Spinal intradural lesions have been classically treated using open surgical techniques from a direct posterior translaminar approach. This despite the localization of the lesion with respect to the spinal cord. This “one size fits all” strategy works for many lesions, but is very limiting for others, particularly ventrally located lesions. Minimally invasive techniques allow for more flexibility in approach trajectories of almost 180° from one side to the other, while allowing for standard microsurgical techniques intradurally. The approaches are much reduced in size, are faster, and have minimal blood loss, with less muscle destruction. Retrospective patient record review from 2004-2013. Inclusion criteria include intradural spinal pathologies treated using the minimal access techniques with clinical and radiological follow up. 33 cases included in this study in 32 patients (17 male and 15 female) Ave age 50.4 years (20-80). 7 cases were in the cervical spine, 11 in the thoracic spine, and 15 cases were in the lumbosacral spine. Extramedullary pathologies All patients has postoperative MRI: 2 patients with intramedullary lesions: minimum residual teratoma stable at 5 years, AA with progressive disease but alive at 14 months after surgery. Extramedullary: 2 patients with drop mets from ependymoma stable at 8 and 43 months after surgery. 1 patient with recurrent meningioma in the T1 foramen, successfully treated the radiotherapy. 1 patient with tumor left stuck to the anterior spinal artery at C6 with stable disease. Remaining 24 patients with no residual disease. 2 patients with arachnoid cysts had normal CSF flow. Clinical complications (4 cases) Conclusions: 1. Use of minimal access surgical techniques appears to be a safe alternative to standard open approaches. Advantages are rapidity of access and closure, less blood loss, faster recovery postoperatively. 2. These techniques allow standard microsurgical techniques for lesion resection, and may enhance resection with more favorable surgical trajectories. These techniques can be used for highly selective intramedullary lesions.

Concise Review: A Population Shift View of Cellular Reprogramming

Cellular reprogramming can offer valuable insight into disease mechanism and has the potential to provide novel tools for regenerative medicine. Yet it remains an inefficient and often incomplete process. However, experiments show that almost all somatic cells eventually give rise to the pluripotent state, albeit at different latencies, as long as expression of reprogramming transcription factors is maintained. Furthermore, it appears that specific subpopulations of cells can be identified that show enhanced propensities to be reprogrammed to the pluripotent state. It has been proposed that an initial stochastic process is responsible for this initial priming that is followed by a deterministic process that directs the primed cells into the pluripotent state. Here, we propose a population shift view of cellular reprogramming, which explains these observations and reconciles the stochastic and deterministic nature of this process. According to this view, a small population of cells, whose states are closer to the pluripotent state and reside in pre-existing energetically favorable trajectories, will be initially selected for reprogramming. Moreover, by maintaining ectopic expression of reprogramming factors, other cells enter these pathways as a result of transcriptional and epigenetic stochastic variations. Consequently, increasing numbers of cells reach the pluripotent state, and the cell population distribution shifts toward this state. Importantly, additional perturbations can change the epigenetic landscape, allowing cells more access to the reprogramming trajectories, thereby increasing reprogramming efficiency. Knowledge of the initial cellular subpopulations and pathways of states that lead to the final cellular state should allow us to design alternative perturbation strategies to improve reprogramming efficiency and fidelity.

G-protein β3 subunit genetic variation moderates five-year depressive symptom trajectories of primary care attendees

BackgroundGenetic variation in the G-protein β3 subunit (GNB3) has previously been associated with gene splicing that has been further linked to increased signal transduction and major depressive disorder. However, the effect of GNB3 genetic variation on depressive symptom trajectories is currently unknown. The aim of the present study is to examine whether genetic variation in GNB3 moderates depressive symptom trajectories among 301 primary care attendees enrolled in the Diagnosis, Management and Outcomes of Depression in Primary Care (diamond) prospective cohort study. MethodsDepressive symptoms were assessed using three measures: (1) DSM-IV criteria, (2) Primary Care Evaluation of Mental Disorders Patient Health Questionnaire-9 (PHQ-9), and (3) Center for Epidemiologic Studies Depression Scale (CESD). DSM-IV criteria were measured at baseline, 24, 36, 48, and 60 months post-baseline, whereas, PHQ-9 and CESD measurements were taken at baseline, 12, 24, 36, 48, and 60 months post-baseline. Two haplotype-tagging single nucleotide polymorphisms [rs5443 (C825T) and rs5440] spanning the GNB3 gene including ~1Kb upstream and downstream of the gene boundaries were genotyped. ResultsFive-year PHQ-9 and CESD depressive symptom trajectories were moderated by rs5440. Carriers of the rs5440 GG genotype had more favourable depressive symptom trajectories compared to AG or AA genotype carriers. The rs5443 polymorphism did not moderate depressive symptom trajectories, regardless of the measure used. LimitationsGeneralizability to depressed populations outside of the primary care setting may be limited. ConclusionsThese results provide novel evidence suggesting genetic variation in the 5-prime region of GNB3 moderates depressive symptom trajectories among primary care attendees.

Cognitive lifestyle jointly predicts longitudinal cognitive decline and mortality risk

Cognitive lifestyle measures such as education, occupation, and social engagement are commonly associated with late-life cognitive ability although their associations with cognitive decline tend to be mixed. However, longitudinal analyses of cognition rarely account for death and dropout, measurement error of the cognitive phenotype, and differing trajectories for different population sub-groups. This paper applies a joint latent class mixed model (and a multi-state model in a sensitivity analysis) that accounts for these issues to a large (n = 3,653), population-based cohort, Paquid, to model the relationship between cognitive lifestyle and cognitive decline. Cognition was assessed over a 20-year period using the Mini-Mental State Examination. Three cognitive lifestyle variables were assessed: education, mid-life occupation, and late-life social engagement. The analysis identified four latent sub-populations with class-specific longitudinal cognitive decline and mortality risk. Irrespective of the cognitive trajectory, increased social engagement was associated with a decreased mortality risk. High education was associated with the most favourable cognitive trajectory, and after adjusting for cognitive decline, with an increased mortality risk. Mid-life occupational complexity was also associated with more favourable trajectories but not with mortality risk. To realistically examine the link between cognitive lifestyle and cognitive decline, complex statistical models are required. This paper applies and compares in a sensitivity analysis two such models, and shows education to be linked to a compression of cognitive morbidity irrespective of cognitive trajectory. Furthermore, a potentially modifiable variable, late-life social engagement is associated with a decreased mortality risk in all of the population sub-groups.Electronic supplementary materialThe online version of this article (doi:10.1007/s10654-014-9881-8) contains supplementary material, which is available to authorized users.

Stability Assessment of a Dual-Opposing Well Junction

The enhancement of well drilling and construction techniques during the 1990s helped the multilateral technology to become increasingly viable and conventional. Dual-opposed is one of the configurations of this technology, in which one lateral goes down dip and the second one up dip in the formation. The stability of the dual-opposed junction is a crucial issue and several factors are involved in this matter, including in-situ stress magnitude and distribution as well as laterals trajectories. In this research, this issue is evaluated assuming different circumstances for the previously mentioned factors using FLAC3D numerical code. The Normalized Yielded Zone Area (ratio of surrounding yielded cross-sectional area to initial area of well) is determined to be the criterion for assessing the stability of the junction. For each stress regime, the lowest mud pressure is calculated in different laterals orientations in stable condition. Then, the optimum mud pressure along with the favorable trajectory of laterals is selected. The results show that, generally, by the increase of inclination (i.e., reduction of angle between the two opposed laterals), the junction gets more stable. Also, the direction of σH is, in general, the optimum direction in all considered stress regimes.

Molecular Dynamics Simulations of Laser-Induced and pH-Induced Unfolding in β-Lactoglobulin at Different Hydration Levels

Computational molecular dynamics simulations were used to estimate the unfolding effects of a single electron positioned appropriately in a globular protein of interest, β-lactoglobulin (BLG). Two sets of unfolding simulations were conducted: movement of the EF-loop in BLG, which is involved in the Tanford transition and a photo-induced electron transfer event between a non-covalently bound, dye molecule, meso-tetrakis p-sulfanatophenyl porphyrin, (TSPP) and BLG.The first simulations solvated BLG at several hydration levels for two different crystal structures: 3BLG at pH 7 (closed loop) and 2BLG at pH 9 (open loop), which became the reference initial and final structures to determine the accuracy of our simulations. Movement of the EF-loop was induced by placing an excess charge on the carboxyl group of glutamic acid residue GLU 89. After 10 ns, favorable structures were submitted to a residue based, coarse-graining algorithm to enable simulating 0.1 ms of the loop motion. The goal was three-fold: to allow the crystallized form to relax in an aqueous environment, to determine the minimal number of explicit water molecules that are sufficient to retain the thermodynamics of the system, and to verify the charge placement algorithm.For the second phase, the location of the electron transfer event was determined by the most probable binding site of the ligand that correlated with resonance Raman spectra and docking calculations of the TSPP-BLG complex. Residues within 3 A were examined for alignment with the ligand and electron affinity. Candidate sites became the origin of an excess electron on the protein, and a separate computation was conducted with coarse-graining methods applied to favorable trajectories as described above. The unfolding determined by these simulations was compared to previously collected circular dichroism data of TSPP-BLG complexes.

Parametric frequency analysis of oscillatory behavior of mouse Zona Pellucida spherical net model: cases of successful and of unsuccessful fertilization

AbstractThe current paper proposes a model for describing mechanical phenomena that occur during the process of mammal fertilization when spermatozoa impact the surface of Zona Pellucida. Zona pellucida (ZP) is a dynamical 3D matrix that surrounds the mammalian oocyte. In the process of fertilization, sperm cell has to penetrate this structure. To describe impact of sperm cells with velocities that are effective and those that are ineffective relative to the oscillatory behavior of ZP, the discreet continuum model in the form of spherical net model is used. Resultant trajectories of knot mass particles dynamics of mouse ZP spherical net model in the form of generalized Lussajous curves are presented. Using generalized Lussajous curves, parametric frequency analysis of oscillatory behavior of knot material particles in the mouse ZP spherical net model is conducted. The influence of impact angles of sperm cells on corresponding knot mass particle trajectory is discussed. Favorable and unfavorable trajectories of knot mass particle motions are discussed in the context of successful fertilization. (© 2013 Wiley‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)

The rich get richer: international doctoral candidates and scholarly identity

Identity lies at the heart of doctoral study – a mysterious learning process which culminates in Ph.D. students’ metamorphosis into doctors. This paper explores the identity-related experiences of six international Ph.D. students enrolled at an Australian university by examining how different individuals, events and interactions contributed to (or disrupted) their sense of themselves as researchers and scholars. Analysis of the participants’ learning narratives revealed significant disparities in the agency they exercised and the opportunities and support they received, ultimately suggesting that those individuals endowed with the most cultural capital experienced the most favourable identity trajectories. Accordingly, the paper argues that greater efforts are needed to support non-traditional doctoral candidates in their journey to become confident scholars and researchers.

An Approach to Restoration of Acidic Waste Rock at a High-Elevation Gold Mine in Colorado, USA

Heap leach processing for extraction of gold began in 1985 at Summitville Mine in southwestern Colorado, and by 1994 the site was declared a Superfund Site by the USEPA. In 1995, we began a science-based approach aimed at restoring 200 ha of highly disturbed land. The short-term goal of the restoration was aimed at stabilizing soils and preventing off-site movement of metal-containing sediments. The longer-term goal was to encourage development of a plant community that resembled a reference condition. Here, we describe our systematic approach for restoration that included identification of constraints to plant establishment and growth, a greenhouse experiment to screen 36 growth medium treatments, and a field experiment to test a subset of best performing treatments. A greenhouse study identified several promising treatments that were implemented in the field experiment, which ultimately identified a single best approach (30 cm of waste rock amended with lime and mushroom compost and covered with 15 cm of limed, fertilized stockpiled topsoil). From 1999 to 2001, the site was re-contoured, amended, and seeded. From 2002 to 2009, we documented an increase in uniformity of vegetation cover on restored areas, an increase in species richness, and a significant shift from a plant community dominated by seeded species, to one more similar to a reference plant community as evidenced by a non-metric multi-dimensional scaling analysis. Overall, these results demonstrate how initial well-planned treatments can encourage a favorable trajectory for restoration of a seeded site, while also demonstrating the utility of this science-based approach for dealing with restoration of a highly disturbed landscape.

Mediterranean Diet and Cognitive Function in Older Age

Adherence to a Mediterranean diet may help prevent cognitive decline in older age, but studies are limited. We examined the association of adherence to the Mediterranean diet with cognitive function and decline. We included 6174 participants, aged 65+ years, from the cognitive substudy of the Women's Health Study. Women provided dietary information in 1998 and completed a cognitive battery 5 years later, followed by two assessments at 2-year intervals. The primary outcomes were composite scores of global cognition and verbal memory. The alternate Mediterranean diet adherence nine-point score was constructed based on intakes of vegetables, fruits, legumes, whole grains, nuts, fish, red and processed meats, moderate alcohol, and the ratio of monounsaturated-to-saturated fats. After multivariable adjustment, the alternate Mediterranean diet score was not associated with trajectories of repeated cognitive scores (P for score quintiles medians-x-time interaction = 0.26 for global cognition and 0.40 for verbal memory), nor with overall global cognition and verbal memory at older ages, assessed by averaging the three cognitive measures (P trend = 0.63 and 0.44, respectively). Among alternate Mediterranean diet components, a higher monounsaturated-to-saturated fats ratio was associated with more favorable cognitive trajectories (P for ratio quintiles medians-x-time = 0.03 for global cognition and 0.05 for verbal memory). Greater whole grain intake was not associated with cognitive trajectories but was related to better averaged global cognition (P trend = 0.02). In this large study of older women, we observed no association of the Mediterranean diet with cognitive decline. Relations between individual Mediterranean diet components, particularly whole grains, and cognitive function merit further study.

Optimum trajectories for spacecraft mission to asteroid Apophis with a return to the Earth

A topical task for astronautics is to prepare a mission to the asteroid Apophis that is approaching the Earth. Determination of energetically favorable trajectories for a spacecraft involved in this mission with a return to the Earth has been considered. Two possible variants of engines for this mission are analyzed. The first variant employs electric engines with low jet thrust, while the second variant employs a spacecraft accelerated and controlled by only high-thrust engines. It is shown that both variants can be used in the mission to Apophis, but the use of electric engines with low thrust allows the project characteristics to be significantly improved.

Sodium Storage and Transport Properties in Layered Na2Ti3O7 for Room‐Temperature Sodium‐Ion Batteries

AbstractLayered sodium titanium oxide, Na2Ti3O7, is synthesized by a solid‐state reaction method as a potential anode for sodium‐ion batteries. Through optimization of the electrolyte and binder, the microsized Na2Ti3O7 electrode delivers a reversible capacity of 188 mA h g−1 in 1 M NaFSI/PC electrolyte at a current rate of 0.1C in a voltage range of 0.0–3.0 V, with sodium alginate as binder. The average Na storage voltage plateau is found at ca. 0.3 V vs. Na+/Na, in good agreement with a first‐principles prediction of 0.35 V. The Na storage properties in Na2Ti3O7 are investigated from thermodynamic and kinetic aspects. By reducing particle size, the nanosized Na2Ti3O7 exhibits much higher capacity, but still with unsatisfied cyclic properties. The solid‐state interphase layer on Na2Ti3O7 electrode is analyzed. A zero‐current overpotential related to thermodynamic factors is observed for both nano‐ and microsized Na2Ti3O7. The electronic structure, Na+ ion transport and conductivity are investigated by the combination of first‐principles calculation and electrochemical characterizations. On the basis of the vacancy‐hopping mechanism, a quasi‐3D energy favorable trajectory is proposed for Na2Ti3O7. The Na+ ions diffuse between the TiO6 octahedron layers with pretty low activation energy of 0.186 eV.

Cohorts based on decade of death: No evidence for secular trends favoring later cohorts in cognitive aging and terminal decline in the AHEAD study.

Studies of birth-year cohorts examined over the same age range often report secular trends favoring later-born cohorts, who are cognitively fitter and show less steep cognitive declines than earlier-born cohorts. However, there is initial evidence that those advantages of later-born cohorts do not carry into the last years of life, suggesting that pervasive mortality-related processes minimize differences that were apparent earlier in life. Elaborating this work from an alternative perspective on cohort differences, we compared rates of cognitive aging and terminal decline in episodic memory between cohorts based on the year participants had died, earlier (between 1993 and 1999) or later in historical time (between 2000 and 2010). Specifically, we compared trajectories of cognitive decline in 2 death-year cohorts of participants in the Asset and Health Dynamics Among the Oldest Old study that were matched on age at death and education and controlled for a variety of additional covariates. Results revealed little evidence of secular trends favoring later cohorts. To the contrary, the cohort that died in the 2000s showed a less favorable trajectory of age-related memory decline than the cohort that died in the 1990s. In examinations of change in relation to time to death, the cohort dying in the 2000s experienced even steeper terminal declines than the cohort dying in the 1990s. We suggest that secular increases in "manufacturing" survival may exacerbate age- and mortality-related cognitive declines among the oldest old.

Temporal patterns of adherence to medications and behavioral treatment and their relationship to patient characteristics and treatment response

BackgroundThe primary analyses of the COMBINE Study revealed significant naltrexone and Combined Behavioral Intervention (CBI) main effects on drinking outcomes but failed to find additional benefits of the combination of treatments. Investigating differences in patterns of adherence over time may shed light on the treatment effects in COMBINE. The goals of the study were to identify trajectories of medication adherence and participation in CBI, to estimate predictive and moderating effects of adherence trajectories on drinking outcomes and to characterize subjects in adherence trajectories. The results of these analyses may suggest approaches to improving adherence in order to ultimately improve treatment outcome. MethodsWe used a trajectory-based approach to identify patterns of treatment adherence separately for naltrexone, acamprosate and CBI adherence. Logistic regression and general linear models assessed associations among adherence trajectories, drinking outcomes and patient characteristics. ResultsThree trajectories of adherence were identified for each treatment: “excellent adherers”, “late non-adherers” and “early non-adherers” and there was good agreement among adherence trajectories with different treatments. “Excellent adherers” had significantly higher percent days abstinent (PDA) and lower percent heavy drinking days (PHDD). CBI significantly decreased PHDD for subjects on acamprosate in the “early non-adherers with medication” trajectory (p=0.01). Either naltrexone or acamprosate was associated with lower PHDD than placebo for “early non-adherers with CBI” (p<0.01). Receiving active medication decreased the likelihood to be in the excellent medication adherence trajectory. Younger age, greater drinking severity, dissatisfaction with the medicine and session frequency, adverse events and lack of benefit were related to less favorable medication adherence trajectories. “Excellent adherers with CBI” were significantly more satisfied with the CBI counselor. ConclusionsPatterns of treatment adherence appear to be a participant characteristic. Individuals who fail to adhere early in treatment have worse outcomes regardless of treatment. However, treatment outcomes of participants who exhibit early problems with adherence to one treatment modality could potentially be improved by offering an alternative behavioral or pharmacologic treatment.

Dynamic Commercialization Strategies for Disruptive Technologies: Evidence from the Speech Recognition Industry

When startup innovation involves a potentially disruptive technology – initially lagging in the predominant performance metric, but with a potentially favorable trajectory of improvement – incumbents may be wary of engaging in cooperative commercialization with the startup. While the prevailing theory of disruptive innovation suggests that this will lead to (exclusively) competitive commercialization and the eventual replacement of incumbents, we consider a dynamic strategy involving product market entry before switching to a cooperative commercialization strategy. Empirical evidence from the automated speech recognition industry from 1952-2010 confirms our main hypothesis.