bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient portal utilization: before and after stage 2 electronic health record meaningful use
Authors: Turner Kea , Hong Young-Rock , Yadav Sandhya , Huo Jinhai , Mainous Arch G
Published: February 2019

Objective

Patient portal functionalities, such as patient–physician e-communication, can benefit patients by improving clinical outcomes. Utilization has historically been low but may have increased in recent years due to the implementation of Stage 2 Meaningful Use for electronic health records. This study has 2 objectives: 1) to compare patient portal utilization rates before Stage 2 (2011–2013) and after Stage 2 (2014–2017), and 2) to examine whether disparities in patient portal utilization attenuate after Stage 2.

Materials and Methods

We conducted an observational study using a pooled cross-sectional analysis of 2011–2017 National Health Interview Survey data (n = 254 183).

Results

The mean percent use of patient portals significantly increased from the pre-Stage 2 to the post-Stage 2 period (6.9%, 95% CI, 6.2–7.5; P < .001). Non-Hispanic Black individuals (OR 0.81, 95% CI, 0.76–0.86; P < .0001) and Hispanic individuals (OR 0.79, 95% CI, 0.74–0.84; P < .0001) have lower odds of using patient portals compared to non-Hispanic White individuals. Although we found independent effects of race/ethnicity, we did not find a statistically significant interaction between race/ethnicity and time. We found a similar level of increase in patient portal utilization from the pre- to postperiod across racial and ethnic groups.

Discussion

Health care policies such as Stage 2 Meaningful Use are likely contributing to increased patient portal utilization across all patients and helping to attenuate disparities in utilization between subgroups of patients.

Conclusion

Further research is needed to explore which patient portal functionalities are perceived as most beneficial to patients and whether patients have access to those functionalities.
Provider perspectives on the integration of patient-reported outcomes in an electronic health record
Authors: Zhang Renwen , Burgess Eleanor R , Reddy Madhu C , Rothrock Nan E , Bhatt Surabhi , Rasmussen Luke V , Butt Zeeshan , Starren Justin B
Published: February 2019

Objective

Integrating patient-reported outcomes (PROs) into electronic health records (EHRs) can improve patient-provider communication and delivery of care. However, new system implementation in health-care institutions is often accompanied by a change in clinical workflow and organizational culture. This study examines how well an EHR-integrated PRO system fits clinical workflows and individual needs of different provider groups within 2 clinics.

Materials and Methods

Northwestern Medicine developed and implemented an EHR-integrated PRO system within the orthopedics and oncology departments. We conducted interviews with 11 providers who had interacted with the system. Through thematic analysis, we synthesized themes regarding provider perspectives on clinical workflow, individual needs, and system features.

Results

Our findings show that EHR-integrated PROs facilitate targeted conversation with patients and automated triage for psychosocial care. However, physicians, psychosocial providers, and medical assistants faced different challenges in their use of the PRO system. Barriers mainly stemmed from a lack of actionable data, workflow disruption, technical issues, and a lack of incentives.

Discussion

This study sheds light on the ecosystem around EHR-integrated PRO systems (such as user needs and organizational factors). We present recommendations to address challenges facing PRO implementation, such as optimizing data collection and auto-referral processes, improving data visualizations, designing effective educational materials, and prioritizing the primary user group.

Conclusion

PRO integration into routine care can be beneficial but also require effective technology design and workflow configuration to reach full potential use. This study provides insights into how patient-generated health data can be better integrated into clinical practice and care delivery processes.
Time-Varying Coefficient Estimation in SURE Models. Application to Portfolio Management*
Authors: Casas Isabel , Ferreira Eva , Orbe Susan
Published: February 2019

This paper provides a detailed analysis of the asymptotic properties of a kernel estimator for a seemingly unrelated regression equations model with time-varying coefficients (tv-SURE) under general conditions. Theoretical results together with a simulation study differentiate the cases for which the estimation of a tv-SURE outperforms the estimation of a single regression equations model with time-varying coefficients. The study shows that Zellner’s results cannot be straightforwardly extended to the time-varying case. The tv-SURE is applied to the Fama and French five-factor model using data from four different international markets. Finally, we provide the estimation under cross-restriction and discuss a testing procedure.
‘You can’t have a good integration when you don’t have a good communication’: English-language Learning Among Resettled Refugees in England
Authors: Morrice Linda , Tip Linda K. , Collyer Michael , Brown Rupert
Published: February 2019

The research presented here is based on a large-scale, multi-methods study of refugees who have been resettled to the United Kingdom. We analyse quantitative data on language proficiency four or more years after resettlement to identify the key characteristics of those who are most likely to have low language proficiency and to be at risk of long-term dependency and exclusion. Qualitative interviews on experiences of language learning suggest that English-language policy and provision serve to exacerbate and compound the risk of social exclusion, rather than ameliorate the risk. Our findings draw attention to the lack of recognition and understanding of the diversity of resettled refugees and their differential capacities, needs and opportunities for learning. They also highlight the conflict between the policy goal of rapid entry into the labour market and the goal of language learning. These findings have clear implications for integration strategies and policy.
And Quiet Flows the Don: the Sholokhov-Kryukov authorship debate
Authors: Iosifyan Marina , Vlasov Igor
Published: February 2019

‘And Quiet Flows the Don’ is an epic novel, considered one of the most significant works of Russian and world literature. The debate on the authorship of ‘And Quiet Flows the Don’ had been surrounding the novel since its first release in 1928 by Mikhail Sholokhov, who was repeatedly accused of plagiarism. The supporters of the plagiarism theory often indicate that the real author of the novel is the Cossack writer, Fyodor Kryukov, who died before ‘And Quiet Flows the Don’ was published. In the present study we applied the information-based similarity analysis (Yang et al., 2003a, Linguistic analysis of human heartbeats using frequency and rank order statistics. Physical Review Letters, 90: 108103; Yang et al., 2003b, Information categorization approach to literary authorship disputes. Physica A, 329, 473) and Burrows's Delta (Burrows, 2002, ‘Delta’: a measure of stylistic difference and a guide to likely authorship. Literary and Linguistic Computing, 17(3):267–87) to a corpus of Russian literature of XIX and XX centuries. We next used these two methods to compare ‘And Quiet Flows the Don’ to Sholokhov’s and Kryukov’s writings. It was found that Fyodor Kryukov writings are distinct from ‘And Quiet Flows the Don’, whilst Sholokhov’s writings being close to the Don novel. The results also highlight how both information similarity analysis and Delta analysis can be used Russian language.
Digital studies and transcontextualization of the humanities: The case of organology
Authors: Nikolić Sanela
Published: February 2019

This research starts from the observation that Bernard Stiegler’™s general organology draws from the philosophical rethinking of the original practice of organology in musicology. Stiegler’™s main philosophical concepts that led to the establishment of general organology, as well as the trajectory of development of Stiegler’ general organology from his musical/musicological experience are discussed and explained. The main claim of this article is that the philosophical platform of general organology has an activist potential for the revitalization of the contemporary humanities and the transformation of the humanities into digital studies. This transformation takes place in the manner of two-level transcontextualization. The first level concerns the transcontextualization of the musicological organology into the general organology as a philosophical platform for understanding the phenomenological and ontological questions of a human being in the world mediated by digital technology. The second level concerns the activist potential of the general organology in relation to the humanities. The transformation of the humanities into digital studies is enabled through the transcontextualization of the general organology as the new, revitalized philosophical ground of the humanities that are dealing with the conditions of humanity in our contemporaneity. This means that digital studies involve not only the digital mediation of the knowledge, but researching that should be implemented in improving the humans' skills, knowledge, attention, and perceptive capabilities through digital technologies.
Personality Disorders as Collections of Traits
Authors: Miller Joshua D.
Published: February 2019

This chapter argues that personality disorders can and should be understood as collections of basic personality traits from a general model of personality, namely the five-factor model (FFM). It reviews evidence for the convergence of FFM personality disorder profiles across multiple approaches—expert ratings (i.e., researchers and clinicians) and empirical relations. It discusses how to score the personality disorders from the FFM and provides evidence for the convergent, discriminant, and construct validity of this approach. The chapter also demonstrates how the new alternative model for personality disorders can be embedded within the more established and robust FFM literature.
Using Basic Personality Process Models to Inform the Personality Disorders
Authors: Fleeson William , Furr R. Michael , Mneimne Malek , Mayfield Arnold Elizabeth
Published: February 2019

This chapter argues that models articulating the processes underlying normal personality traits, even more so than the structure of normal traits, may help to inform research on personality disorders (PDs). It first describes whole trait theory as a model of normal traits that focuses on process at the same time that it is based on normal personality structure. The chapter then shows how this model makes an easy translation to process models of borderline personality disorder, thereby forming a connection between normal personality and pathological personality at a process level. The resulting general model of borderline personality disorder suggests viewing PD symptoms as distinct, momentary events rather than as stable, enduring features of people. It argues that etiological theorizing should include the proximal mechanisms that lead to temporally bounded symptoms. For example, relationship instability is seen not as a feature of the person but as an event that flares up and then fades repeatedly, in response to events and interpretations of those events. Accumulating evidence in support of this model is described. A model connecting normal personality trait processes to pathological personality processes may strengthen the connection between normal personality and pathological personality more firmly.
Personality Dysfunction and Trait Extremity
Authors: Clark Lee Anna , Daly Elizabeth J. , Larew Stephanie , Nuzum Hallie , Kingsbury Thomas , Shapiro Jaime L. , Allen Xia , Ro Eunyoe
Published: February 2019

This chapter discusses the alternative model for personality disorders and its two criteria: impairment/dysfunction and personality disordered traits. Specifically, the chapter explores the distinctiveness between the two criteria. It notes that there is descriptive overlap between them, and it reports on a study examining the degree of empirical overlap. This overlap was reported to be extremely high, with correlations of .76 and .80 for self-report and interview ratings, respectively.
Advances in Child Personality Research and Relevance for Personality Pathology
Authors: Tackett Jennifer L. , Reardon Kathleen W. , Herzhoff Kathrin , Kushner Shauna C.
Published: February 2019

This chapter reviews the current state of research on defining and organizing normal-range personality traits in youth, the work defining and organizing maladaptive personality traits in youth, and evidence for the hierarchical organization of both normal-range and maladaptive early personality traits. Direct comparisons of work on younger populations to existing research on adults are made throughout the chapter, in order to facilitate an integrative life-span perspective of personality and personality pathology. These comparisons highlight areas in which there are important differences from work with adults that may be missed if the field neglects such a comprehensive, life-span view. Finally, implications of the work on child personality are drawn and important future directions for the field are highlighted.
The Prevalence, Stability, and Impact of Personality Pathology in Later Life
Authors: Oltmanns Thomas F. , Balsis Steve
Published: February 2019

This chapter notes that much research has examined the onset and stability of personality disorders through early adulthood with very little research examining personality disorders from middle adulthood to later life. The chapter outlines important issues and questions that should be addressed by studies concerned with personality pathology in older adults. It also reviews key findings from the St. Louis Personality and Aging Network (SPAN) Study.
Goals of Psychodynamic Therapy
Authors: Sharpless Brian A.
Published: February 2019

After briefly discussing the process of “translating” a patient’s desire for change into usable psychodynamic targets for change, eight specific therapy goals are described. These include several that have been discussed since the earliest days of psychoanalysis (e.g., the generation of insight, an increased ability to love and work, personality change) as well as the more transtheoretical goals of autonomy from the therapist and symptom reduction. Goals derived from existential versions of dynamic therapy are also considered (e.g., acceptance of that which cannot be changed; an increased sense of meaning and purpose). Specific suggestions for assessing clinical progress (e.g., questionnaires and interviews) and relevant citations are listed in a table and at the end of each section.
Characteristics of “Good” Psychodynamic Interventions
Authors: Sharpless Brian A.
Published: February 2019

This chapter describes eleven characteristics of “good” interventions that have been extracted from a number of psychodynamic texts and manuals. It is argued that interventions be logically-derived from a good case formulation, based upon accurate clinical data, and potentially falsifiable. Interventions should also be formulated using standard psychodynamic principles (e.g., precision, concision, parsimony) and reflect the patient’s location on the supportive-expressive continuum. Good interventions are also worded in a respectful manner and, at least in most cases, “experience-near” for the patient. Interventions can also be used to instantiate the psychodynamic therapy process for patients (i.e., learn by doing) and socialize them into therapy. Examples and practical advice are provided.
How to Assess the Impacts of Interventions
Authors: Sharpless Brian A.
Published: February 2019

Whenever individual psychodynamic techniques are applied, it is important to quickly assess their proximal clinical impacts. Therefore, this chapter focuses on helping clinicians identify the many, and sometimes subtle, signs that an intervention was either corroborated or disconfirmed. Common examples of both sets of patient signs are included. Some characteristic indicators of corroboration include the generation of new and emotionally rich clinical material. Signs of disconfirmation may include the patient verbally rejecting the intervention, stalled free association, or an alliance rupture. However, clinical context is important to consider, as indicators may vary greatly across patients and according to their relative location on the supportive–expressive continuum. Finally, the concept of a corrective emotional experience is discussed as another possible clinical impact. Clinical criteria for an in-session corrective emotional experience are proposed.
The Process of Confrontation
Authors: Sharpless Brian A.
Published: February 2019

Confrontations direct attention to important but overlooked, denied, or incongruous patient communications. These interventions are used to (a) encourage the patient to resolve inconsistencies, (b) note denial or acting out behaviors, (c) help the patient face an uncomfortable reality, or (d) indicate that clinical material has psychodynamic importance. This chapter outlines three specific forms of confrontation (i.e., spotlight, connective, and prohibitive), provides suggestions for when to confront patients, and includes detailed clinical examples. Although they are potentially powerful interventions, confrontations are not without clinical risk. Improperly worded or poorly timed confrontations can lead to alliance ruptures or unnecessary patient distress. They can also be overused or underused by psychodynamic therapists. Suggestions for wording and the appropriate using confrontations are provided.
Inadequate Decompressive Craniectomy Following a Wartime Traumatic Brain Injury – An Illustrative Case of Why Size Matters
Authors: Janatpour Zachary C , Szuflita Nicholas S , Spinelli Joseph , Coughlin Daniel J , Rosenfeld Jeffrey V , Bell Randy S
Published: February 2019

Traumatic brain injury has been called the “signature injury” of the wars in Iraq and Afghanistan, and the management of severe and penetrating brain injury has evolved considerably based on the experiences of military neurosurgeons. Current guidelines recommend that decompressive hemicraniectomy be performed with large, frontotemporoparietal bone flaps, but practice patterns vary markedly. The following case is illustrative of potential clinical courses, complications, and efforts to salvage inadequately-sized decompressive craniectomies performed for combat-related severe and penetrating brain injury. The authors follow this with a review of the current literature pertaining to decompressive craniectomy, and finally provide their recommendations for some of the technical nuances of performing decompressive hemicraniectomy after severe or penetrating brain injury.
Heating of Milky Way disc stars by dark matter fluctuations in cold dark matter and fuzzy dark matter paradigms
Authors: Church Benjamin V , Mocz Philip , Ostriker Jeremiah P
Published: February 2019

Although highly successful on cosmological scales, cold dark matter (CDM) models predict unobserved overdense ‘cusps’ in dwarf galaxies and overestimate their formation rate. We consider an ultralight axion-like scalar boson which promises to reduce these observational discrepancies at galactic scales. The model, known as fuzzy dark matter (FDM), avoids cusps, suppresses small-scale power, and delays galaxy formation via macroscopic quantum pressure. We compare the substructure and density fluctuations of galactic dark matter haloes comprised of ultralight axions to conventional CDM results. Besides self-gravitating subhaloes, FDM includes non-virialized overdense wavelets formed by quantum interference patterns, which are an efficient source of heating to galactic discs. We find that, in the solar neighbourhood, wavelet heating is sufficient to give the oldest disc stars a velocity dispersion of ${\sim } {30}{\, \mathrm{km\, s}^{-1}}$ within a Hubble time if energy is not lost from the disc, the velocity dispersion increasing with stellar age as σD ∝ t0.4 in agreement with observations. Furthermore, we calculate the radius-dependent velocity dispersion and corresponding scaleheight caused by the heating of this dynamical substructure in both CDM and FDM with the determination that these effects will produce a flaring that terminates the Milky Way disc at $15\!-\!20{\, \mathrm{kpc}}$. Although the source of thickened discs is not known, the heating due to perturbations caused by dark substructure cannot exceed the total disc velocity dispersion. Therefore, this work provides a lower bound on the FDM particle mass of ma > 0.6 × 10−22 eV. Furthermore, FDM wavelets with this particle mass should be considered a viable mechanism for producing the observed disc thickening with time.
Three-dimensional supernova explosion simulations of 9-, 10-, 11-, 12-, and 13-M⊙ stars
Authors: Burrows Adam , Radice David , Vartanyan David
Published: February 2019

Using the new state-of-the-art core-collapse supernova (CCSN) code fornax, we have simulated the three-dimensional dynamical evolution of the cores of 9-, 10-, 11-, 12-, and 13-M⊙ stars from the onset of collapse. Stars from 8 to 13 M⊙ constitute roughly 50 per cent of all massive stars, so the explosive potential for this mass range is important to the overall theory of CCSNe. We find that the 9-, 10-, 11-, and 12-M⊙ models explode in 3D easily, but that the 13-M⊙ model does not. From these findings, and the fact that slightly more massive progenitors seem to explode, we suggest that there is a gap in explodability near 12 to 14 M⊙ for non-rotating progenitor stars. Factors conducive to explosion are turbulence behind the stalled shock, energy transfer due to neutrino–matter absorption and neutrino–matter scattering, many-body corrections to the neutrino–nucleon scattering rate, and the presence of a sharp silicon–oxygen interface in the progenitor. Our 3D exploding models frequently have a dipolar structure, with the two asymmetrical exploding lobes separated by a pinched waist where matter temporarily continues to accrete. This process maintains the driving neutrino luminosity, while partially shunting matter out of the way of the expanding lobes, thereby modestly facilitating explosion. The morphology of all 3D explosions is characterized by multiple bubble structures with a range of low-order harmonic modes. Though much remains to be done in CCSN theory, these and other results in the literature suggest that, at least for these lower mass progenitors, supernova theory is converging on a credible solution.
Formation of the Cassini Division – I. Shaping the rings by Mimas inward migration
Authors: Baillié Kévin , Noyelles Benoît , Lainey Valéry , Charnoz Sébastien , Tobie Gabriel
Published: February 2019

In 2017, the Cassini mission Grand Finale provided hints at the total mass of Saturn’s ring system, constraining the age of the rings: they could actually be about 200 million years old or even younger. However, the present radial mass distribution across the rings is not well understood. The most prominent structure, visible from Earth, is the Cassini Division, a 4500 km-wide gap that separates the massive inner B ring and the outer A ring. Though early models of the formation of the Cassini Division suggested that the resonant interaction of ring particles with the external satellite Mimas (Lindblad resonance 2:1) could open a significant gap (slightly narrower than the observed Cassini Division) in 5 billion years, we investigate here an alternative scenario involving much shorter time-scales based on the new constraints on the age of the rings. In this article, we present a numerical model of satellite-ring interactions that can explain the formation of the Cassini Division by the orbital migration of Mimas and the different densities of the current A and B rings. Such a scenario implies that the Cassini Division could have opened in the last 4–11 million years and that it might disappear in the next 40 million years from now.
Large Ly α opacity fluctuations and low CMB τ in models of late reionization with large islands of neutral hydrogen extending to z < 5.5
Authors: Kulkarni Girish , Keating Laura C , Haehnelt Martin G , Bosman Sarah E I , Puchwein Ewald , Chardin Jonathan , Aubert Dominique
Published: February 2019

High-redshift quasi-stellar object (QSO) spectra show large spatial fluctuations in the Ly α opacity of the intergalactic medium on surprisingly large scales at $z$ ≳ 5.5. We present a radiative transfer simulation of cosmic reionization driven by galaxies that reproduces this large scatter and the rapid evolution of the Ly α opacity distribution at 5 < $z$ < 6. The simulation also reproduces the low Thomson scattering optical depth reported by the latest cosmic microwave background (CMB) measurement and is consistent with the observed short near-zones and strong red damping wings in the highest redshift QSOs. It also matches the rapid disappearance of observed Ly α emission by galaxies at $z$ ≳ 6. Reionization is complete at $z$ = 5.3 in our model, and 50 per cent of the volume of the Universe is ionized at $z$ = 7. Agreement with the Ly α forest data in such a late reionization model requires a rapid evolution of the ionizing emissivity of galaxies that peaks at $z$ ∼ 6.8. The late end of reionization results in a large scatter in the photoionization rate and the neutral hydrogen fraction at redshifts as low as $z$ ≲ 5.5 with large residual neutral ‘islands’ that can produce very long Gunn–Peterson troughs resembling those seen in the data.
Predictions of the pseudo-complex theory of gravity for EHT observations – I. Observational tests
Authors: Boller Th , Hess P O , Müller A , Stöcker H
Published: February 2019

A modified theory of gravity, avoiding singularities in the standard theory of gravitation, has been developed by Hess & Greiner, known as the pseudo-complex theory of gravitation. The pseudo-complex General Relativity (pc-GR) theory shows remarkable observational differences with respect to standard GR. The intensity profiles are significantly different between both theories, which is a rare phenomenon in astrophysics. This will allow robust tests of both theories using Event Horizon Telescope observations of the Galactic Centre. We also predict the time evolution of orbiting matter. In this paper we summarize the observational tests we have developed to date. The theory is described in the second paper of this series (referred to as paper II hereafter).
Role of CD8+ T cells in crescentic glomerulonephritis
Authors: Chen Anqun , Lee Kyung , Guan Tianjun , He John Cijiang , Schlondorff Detlef
Published: February 2019

Crescentic glomerulonephritis (cGN) comprises three main types according to the pathogenesis and immunofluorescence patterns: anti-glomerular basement membrane antibody cGN, vasculitis-associated cGN and post-infectious immune complex cGN. In this brief review of the immune-pathogenesis of cGN, the focus is mainly on the role of CD8+ T cells in the progression of cGN. Under control conditions, Bowman’s capsule (BC) provides a protected immunological niche by preventing access of cytotoxic CD8+ T cells to Bowman’s space and thereby podocytes. Even in experimental nephrotoxic nephritis, leukocytes accumulate around the glomeruli, but remain outside of BC, as long as the latter remains intact. However, when and where breaches in BC occur, the inflammatory cells can gain access to and destroy podocytes, thus converting cGN into rapidly progressive glomerulonephritis (RPGN). These conclusions also apply to human cGN, where biopsies show that loss of BC integrity is associated with RPGN and progression to end-stage kidney disease. We propose a two-hit hypothesis for the role of cytotoxic CD8+ T cells in the progression of cGN. The initial insult occurs in response to the immune complex formation or deposition, resulting in local capillary and podocyte injury (first hit). The injured podocytes release neo-epitopes, eventually causing T-cell activation and migration to the glomerulus. Upon generation of breaches in BC, macrophages and CD8+ T cells can now gain access to the glomerular space and destroy neo-epitope expressing podocytes (second hit), resulting in RPGN. While further investigation will be required to test this hypothesis, future therapeutic trials should consider targeting of CD8+ T cells in the therapy of progressive cGN.
Surveillance of Rifampicin Resistance With GeneXpert MTB/RIF in the National Reference Laboratory for Tuberculosis at the Institut Pasteur in Bangui, 2015–2017
Authors: Farra Alain , Manirakiza Alexandre , Yambiyo Brice Martial , Zandanga Germain , Lokoti Boris , Berlioz-Arthaud Alain , Ngaya Gilles , Hermana Georges , Ourandji Louis Médard , Ignaleamoko Albert , Komangoya-Nzonzo Aristide Désiré , Simelo Jean Pierre , Iragena Jean de Dieu
Published: February 2019

Background

The Central African Republic (CAR) has one of the heaviest burdens of tuberculosis (TB) in the world, with an incidence of 423 cases per 100 000 population. Surveillance of resistance to rifampicin with GeneXpert MTB/RIF was instituted in the National TB Reference Laboratory in 2015. The aim of this study was to evaluate, after 3 years, resistance to rifampicin, the most effective firstline drug against TB.

Methods

The surveillance database on cases of rifampicin resistance was retrospectively analyzed. The populations targeted by the National TB Programme were failure, relapse, default, and contacts of multidrug-resistant TB (MDR-TB). Statistical analyses were performed with Stata software, version 14, using chi-square tests and odds ratios.

Results

Six hundred seventeen cases were registered; 63.7% were male, 36.3% were female, and the mean age was 35.5 years (range from 2 to 81). GeneXpert MTB/RIF tests were positive in 79.1% (488/617), and resistance to rifampicin was positive in 42.2% (206/488), with 49.1% (56/114) in 2015, 34.7% (57/164) in 2016, and 44.3% (93/210) in 2017. Failure cases had the highest rate of resistance (70.4%), with a significant difference (P < .0001; odds ratio, 9.5; 95% confidence interval, 4.4–20.5). Resistance was observed in 40% of contacts of MDR-TB, 28.2% of the relapses and 20% of the defaults without significant difference.

Conclusions

Resistance to rifampicin is still high in the CAR and is most strongly associated with treatment failure. The Ministry of Health must to deploy GeneXpert MTB/RIF tests in the provinces to evaluate resistance to TB drugs in the country.
The Effect of Framing and Placement on Linkage Consent
Authors: Sakshaug Joseph W , Schmucker Alexandra , Kreuter Frauke , Couper Mick P , Singer Eleanor
Published: February 2019

Numerous surveys link interview data to administrative records, conditional on respondent consent, in order to explore new and innovative research questions. Optimizing the linkage consent rate is a critical step toward realizing the scientific advantages of record linkage and minimizing the risk of linkage consent bias. Linkage consent rates have been shown to be particularly sensitive to certain design features, such as where the consent question is placed in the questionnaire and how the question is framed. However, the interaction of these design features and their relative contributions to the linkage consent rate have never been jointly studied, raising the practical question of which design feature (or combination of features) should be prioritized from a consent rate perspective. We address this knowledge gap by reporting the results of a placement and framing experiment embedded within separate telephone and Web surveys. We find a significant interaction between placement and framing of the linkage consent question on the consent rate. The effect of placement was larger than the effect of framing in both surveys, and the effect of framing was only evident in the Web survey when the consent question was placed at the end of the questionnaire. Both design features had negligible impact on linkage consent bias for a series of administrative variables available for consenters and non-consenters. We conclude this research note with guidance on the optimal administration of the linkage consent question.
Uncertainty Shocks as Second-Moment News Shocks
Authors: Berger David , Dew-Becker Ian , Giglio Stefano
Published: February 2019

We provide evidence on the relationship between aggregate uncertainty and the macroeconomy. Identifying uncertainty shocks using methods from the news shocks literature, the analysis finds that innovations in realized stock market volatility are robustly followed by contractions, while shocks to forward-looking uncertainty have no significant effect on the economy. Moreover, investors have historically paid large premia to hedge shocks to realized but not implied volatility. A model in which fundamental shocks are skewed left can match those facts. Aggregate volatility matters, but it is the realization of volatility, rather than uncertainty about the future, that has been associated with declines.
An Early Developmental Marker of Deficit versus Nondeficit Schizophrenia
Authors: Kirkpatrick Brian , Gürbüz Oflezer Özlem , Delice Arslan Mehtap , Hack Gary , Fernandez-Egea Emilio
Published: February 2019

People with schizophrenia and primary negative symptoms (deficit schizophrenia) differ from those without such symptoms (nondeficit schizophrenia) on risk factors, course of illness, other signs and symptoms, treatment response, and biological correlates. These differences suggest that the 2 groups may also have developmental differences. A previous study found that people with schizophrenia have a wider palate than comparison subjects. We tested the hypothesis that those with deficit and nondeficit schizophrenia would differ on palate width. A dentist made blinded measurements of palate shape in deficit (N = 21) and nondeficit (N = 25) patients and control subjects (N = 127), matched for age and gender. The deficit group had significantly wider palates than either nondeficit or control subjects (respective means [standard deviation] 37.5 [3.9], 33.7 [3.1], and 34.0 [2.9]; P < .001 for both deficit/nondeficit and deficit/control comparisons, respective effect sizes 1.08 and 1.01). The nondeficit/control difference in width was not significant (P = .83), and there were no significant group differences in length or depth. The power to detect a nondeficit/control difference in width equal in size to that of the deficit/control difference in width (3.5 mm) was 0.99 and 0.92 for a 2.0-mm difference. This difference in palate width may reflect a divergence in development between deficit and nondeficit patients that occurs by the early second trimester and is consistent with the hypothesis that deficit schizophrenia is a separate disease within the syndrome of schizophrenia.
Obstructive sleep apnea and longitudinal Alzheimer’s disease biomarker changes
Authors: Bubu Omonigho M , Pirraglia Elizabeth , Andrade Andreia G , Sharma Ram A , Gimenez-Badia Sandra , Umasabor-Bubu Ogie Q , Hogan Megan M , Shim Amanda M , Mukhtar Fahad , Sharma Nidhi , Mbah Alfred K , Seixas Azizi A , Kam Korey , Zizi Ferdinand , Borenstein Amy R , Mortimer James A , Kip Kevin E , Morgan David , Rosenzweig Ivana , Ayappa Indu , Rapoport David M , Jean-Louis Girardin , Varga Andrew W , Osorio Ricardo S
Published: February 2019

Study Objectives

To determine the effect of self-reported clinical diagnosis of obstructive sleep apnea (OSA) on longitudinal changes in brain amyloid PET and CSF biomarkers (Aβ42, T-tau, and P-tau) in cognitively normal (NL), mild cognitive impairment (MCI), and Alzheimer’s disease (AD) elderly.

Methods

Longitudinal study with mean follow-up time of 2.52 ± 0.51 years. Data were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Participants included 516 NL, 798 MCI, and 325 AD elderly. Main outcomes were annual rate of change in brain amyloid burden (i.e. longitudinal increases in florbetapir PET uptake or decreases in CSF Aβ42 levels); and tau protein aggregation (i.e. longitudinal increases in CSF total tau [T-tau] and phosphorylated tau [P-tau]). Adjusted multilevel mixed effects linear regression models with randomly varying intercepts and slopes was used to test whether the rate of biomarker change differed between participants with and without OSA.

Results

In NL and MCI groups, OSA+ subjects experienced faster annual increase in florbetapir uptake (B = .06, 95% CI = .02, .11 and B = .08, 95% CI = .05, .12, respectively) and decrease in CSF Aβ42 levels (B = −2.71, 95% CI = −3.11, −2.35 and B = −2.62, 95% CI = −3.23, −2.03, respectively); as well as increases in CSF T-tau (B = 3.68, 95% CI = 3.31, 4.07 and B = 2.21, 95% CI = 1.58, 2.86, respectively) and P-tau (B = 1.221, 95% CI = 1.02, 1.42 and B = 1.74, 95% CI = 1.22, 2.27, respectively); compared with OSA− participants. No significant variations in the biomarker changes over time were seen in the AD group.

Conclusions

In both NL and MCI, elderly, clinical interventions aimed to treat OSA are needed to test if OSA treatment may affect the progression of cognitive impairment due to AD.
Haplotype-Phased Genome Assembly of VirulentPhytophthora ramorumIsolate ND886 Facilitated by Long-Read Sequencing Reveals Effector Polymorphisms and Copy Number Variation
Authors: Malar C Mathu , Yuzon Jennifer D. , Das Subhadeep , Das Abhishek , Panda Arijit , Ghosh Samrat , Tyler Brett M. , Kasuga Takao , Tripathy Sucheta
Published: February 2019

Phytophthora ramorum is a destructive pathogen that causes sudden oak death disease. The genome sequence of P. ramorum isolate Pr102 was previously produced, using Sanger reads, and contained 12 Mb of gaps. However, isolate Pr102 had shown reduced aggressiveness and genome abnormalities. In order to produce an improved genome assembly for P. ramorum, we performed long-read sequencing of highly aggressive P. ramorum isolate CDFA1418886 (abbreviated as ND886). We generated a 60.5-Mb assembly of the ND886 genome using the Pacific Biosciences (PacBio) sequencing platform. The assembly includes 302 primary contigs (60.2 Mb) and nine unplaced contigs (265 kb). Additionally, we found a ‘highly repetitive’ component from the PacBio unassembled unmapped reads containing tandem repeats that are not part of the 60.5-Mb genome. The overall repeat content in the primary assembly was much higher than the Pr102 Sanger version (48 versus 29%), indicating that the long reads have captured repetitive regions effectively. The 302 primary contigs were phased into 345 haplotype blocks and 222,892 phased variants, of which the longest phased block was 1,513,201 bp with 7,265 phased variants. The improved phased assembly facilitated identification of 21 and 25 Crinkler effectors and 393 and 394 RXLR effector genes from two haplotypes. Of these, 24 and 25 RXLR effectors were newly predicted from haplotypes A and B, respectively. In addition, seven new paralogs of effector Avh207 were found in contig 54, not reported earlier. Comparison of the ND886 assembly with Pr102 V1 assembly suggests that several repeat-rich smaller scaffolds within the Pr102 V1 assembly were possibly misassembled; these regions are fully encompassed now in ND886 contigs. Our analysis further reveals that Pr102 is a heterokaryon with multiple nuclear types in the sequences corresponding to contig 10 of ND886 assembly.
Botrytispolyphyllae: A NewBotrytisSpecies Causing Gray Mold onParis polyphylla
Authors: Zhong Shan , Zhang Jing , Zhang Guo-Zhen
Published: February 2019

Paris polyphylla is an important perennial medicinal plant in China. A disease similar to gray mold on P. polyphylla occurred at the seedling stage in March 2016 and 2017 in Tengchong city, Yunnan Province of China. The disease resulted in up to 50% mortality in serious cases. Isolates from diseased plants grew 10.6 mm/day at 20°C on PDA. After 21 days, sclerotia were spherical to elliptical (0.4–2.5 × 0.3–1.8 mm). Conidia from diseased tissues were hyaline to pale brown, long, ovoid, unicellular, and measured 15.1–24.5 × 8.8–13.4 μm; conidiophores were 526–1,064 ×12–15 μm. Isolates did not form conidiophores or conidia on PDA or MYA. A phylogenetic analysis based on G3PDH, RPB2, and HSP60 sequence data supported assignment of three representative isolates as a new species of Botrytis. Based on morphological, phylogenetic characteristics and Koch’s Postulates, the causal agent of gray mold on P. polyphylla was identified as a novel species, Botrytis polyphyllae.
Inhibition of Tomato Early Blight Disease by Culture Extracts of a Streptomyces puniceus Isolate from Mangrove Soil
Authors: Hao Lingyun , Zheng Xiaoli , Wang Yu , Li Shuangfei , Shang Chenjing , Xu Ying
Published: February 2019

This study investigates the potential of natural products derived from a mangrove rhizosphere bacterium in tomato early blight management. A Streptomyces puniceus strain L75 was isolated from the rhizosphere of Acanthus ilicifolius Linn in the Mai Po Reserve, Hong Kong. The crude ethyl acetate (EA) extract of L75 fermentation cultures has broad-spectrum antifungal bioactivities. L75 EA extract was significantly more effective in Alternaria solani growth inhibition at 25 μg/ml or lower compared with Mancozeb, with no observable negative impacts on tomato leaves or root development. Furthermore, L75 EA extract had significantly lower aquatic toxicity than Mancozeb at the same concentrations. L75 EA extract targets germ tube elongation of A. solani conidia, with a fungistatic mode of action. Liquid chromatography-quadrupole time-of-flight mass spectrometry analysis identified two possible antifungal compounds, Alteramide A and the Heat-Stable Antifungal Factor, which together contribute partially to the bioactivity of L75 EA extract. On detached tomato leaves, coinoculation of A. solani with L75 EA extract of 50, 25, or 5 μg/ml reduced diseased areas by ∼98, ∼90, and ∼48%, respectively, relative to the control after 5 days. This study demonstrates the potential of natural products from mangrove rhizosphere bacteria in agricultural applications.
Embryonic stem cells become mechanoresponsive upon exit from ground state of pluripotency
Authors: Verstreken C. M. , Labouesse C. , Agley C. C. , Chalut K. J.
Published: February 2019

Stem cell fate decisions are driven by a broad array of signals, both chemical and mechanical. Although much progress has been made in our understanding of the impact of chemical signals on cell fate choice, much less is known about the role and influence of mechanical signalling, particularly in embryonic stem (ES) cells. Many studies use substrates with different stiffness to study mechanical signalling, but changing substrate stiffness can induce secondary effects which are difficult to disentangle from the direct effects of forces/mechanical signals. To probe the direct impact of mechanical stress on cells, we developed an adaptable cell substrate stretcher to exert specific, reproducible forces on cells. Using this device to test the response of ES cells to tensile strain, we found that cells experienced a transient influx of calcium followed by an upregulation of the so-called immediate and early genes. On longer time scales, however, ES cells in ground state conditions were largely insensitive to mechanical stress. Nonetheless, as ES cells exited the ground state, their susceptibility to mechanical signals increased, resulting in broad transcriptional changes. Our findings suggest that exit from ground state of pluripotency is unaffected by mechanical signals, but that these signals could become important during the next stage of lineage specification. A better understanding of this process could improve our understanding of cell fate choice in early development and improve protocols for differentiation guided by mechanical cues.
In silico screen identifies a new Toxoplasma gondii mitochondrial ribosomal protein essential for mitochondrial translation
Authors: Lacombe Alice , Maclean Andrew E. , Ovciarikova Jana , Tottey Julie , Sheiner Lilach
Published: February 2019

Apicomplexan parasites cause diseases such as malaria and toxoplasmosis. The apicomplexan mitochondrion shows striking differences from common model organisms, including in fundamental processes such as mitochondrial translation. Despite evidence that mitochondrial translation is essential for parasites survival, it is largely understudied. Progress has been restricted by the absence of functional assays to detect apicomplexan mitochondrial translation, a lack of knowledge of proteins involved in the process and the inability to identify and detect mitoribosomes.

Using mRNA expression patterns, 279 candidate mitochondrial housekeeping components were identified in Toxoplasma. 11 were validated, including the mitoribosomal small subunit protein 35 (TgmS35). TgmS35 tagging enabled the detection of a macromolecular complex corresponding to the mitoribosomal small subunit for the first time in apicomplexans. A new analytical pipeline detected defects in mitochondrial translation upon TgmS35 depletion, while other mitochondrial functions remain unaffected. Our work lays a foundation for the study of apicomplexan mitochondrial translation.

Abbreviated summary

The apicomplexan mitochondrion is divergent and essential yet poorly studied. Mitochondrial translation is predicted to utilize ribosomes assembled from fragmented rRNA but this was never shown. Knowing the mitochondrial protein content is critical for these studies. We identified 11 new mitochondrial proteins via in-silico searches. Tagging and depletion of a mitoribosomal small subunit protein enabled the first detection of a macromolecular ribosomal complex, and provided proof of principle for our new mitochondrial translation analytic pipeline.
Altered brain morphology in boys with attention-deficit/hyperactivity disorder with and without comorbid conduct disorder/oppositional defiant disorder
Authors: Vetter Nora C. , Backhausen Lea L. , Buse Judith , Roessner Veit , Smolka Michael N.
Published: February 2019

About 50% of ADHD patients suffer from comorbidity with oppositional defiant disorder/conduct disorder (ODD/CD). Most previous studies on structural morphology did not differentiate between pure ADHD (ADHD-only) and ADHD with comorbid ODD/CD (ADHD+ODD/CD) and only focused on specific measures (e.g. volumetric differences), leading to inconsistent results. Therefore, we aimed to investigate the structural profile of ADHD-only versus ADHD+ODD/CD spanning different indices, i.e. subcortical and cortical volume, cortical thickness, and surface area. We aimed to disentangle disorder-specific etiological contributions regarding structural brain alterations and expected similar and differential alterations between the patient groups.

We acquired structural images from an adolescent sample range (11 to 17 years) matched with regard to age, pubertal status, and IQ - including 36 boys with ADHD-only, 26 boys with ADHD+ODD/CD, and 30 typically developing boys (TD). We analyzed subcortical and cortical volume, cortical thickness, and surface area with FreeSurfer.

We found reductions in total gray matter and right cerebellar volume as well as total surface area for both patient groups. For the left cerebellar volume ADHD+ODD/CD, but not ADHD only differed from TD. Boys with ADHD+ODD/CD had a thicker cortex than the other groups in a right rostral middle frontal cluster, which was related to stronger ODD/CD symptoms, even when controlling for ADHD symptoms. No group differences in local cortical volume or surface area emerged.

Overall, we found similarities but also differences in brain morphology between the two related disorders. Patients with a “double burden” seem to be even more affected than patients with pure ADHD.