bluuebunny/crossref_metadata_2025 huggingface dataset:
Histogram‐based mixed‐signal time‐to‐digital‐converter array for direct time‐of‐flight depth sensors
Authors: Seo H. , Choi J.
Published: January 2019

This Letter introduces a histogram‐based time‐to‐digital‐converter (TDC) array for direct time‐of‐flight depth sensors. The 12‐bit TDC array measures the time of flight (TOF) of a light pulse that is detected using an external single‐photon avalanche diode (SPAD) array. As SPADs are noisy owing to dark electrons and scattered photons, statistical measurements based on histograms are essential, but require a large memory. In this work, the authors propose a mixed‐signal TDC with an integrated histogram generation unit (HGU) that reduces memory requirement significantly as well as filters out invalid TOF readings. In addition, for application of the high‐resolution SPAD array, an area‐efficient TDC array with high uniformity was implemented by the proposed phase‐dependent latching and temporal double sampling schemes. The prototype chip was fabricated using a 180 nm CMOS process, including 8‐channel TDCs. The measurements show an integral non‐linearity (INL)/a differential nonlinearity (DNL) of 0.76/0.49 least significant bit (LSB) and high uniformity under 0.19 LSB. The HGU was designed off‐chip for prior verification, and was post‐simulated with the measured TOF from the fabricated chip. Using the histogram‐based TDC, the authors could detect an object located at a distance of 3 m accurately while reducing memory requirement by more than 128 times.
Distributed temperature sensing based on slope‐assisted Brillouin optical correlation‐domain reflectometry with over 10 km measurement range
Authors: Lee H. , Noda K. , Mizuno Y. , Nakamura K.
Published: January 2019

The authors demonstrate distributed temperature sensing based on slope‐assisted Brillouin optical correlation‐domain reflectometry (BOCDR) with a long measurement range of >10 km. They find that to achieve such a long‐range measurement, a delay line in a reference path needs to be at least four times longer than the sensing fibre. In addition, they show that the use of such a long delay line induces forward‐propagating Brillouin‐scattered light in the reference path, which deteriorates the signal‐to‐noise ratio (SNR) of the system and should be suppressed. Finally, by exploiting a beyond‐nominal‐resolution effect of the slope‐assisted BOCDR, they detect a 3‐m‐long heated section in a 13‐km‐long silica fibre in a distributed manner; the reason for its low SNR is also discussed.
Application of Cole–Cole model to transformer oil‐paper insulation considering distributed dielectric relaxation
Authors: Ojha Sandip Kumar , Purkait Prithwiraj , Chatterjee Biswendu , Chakravorti Sivaji
Published: January 2019

Researchers have been exploring dielectric testing techniques both in time and frequency domain for insulation condition assessment of oil‐paper insulated transformers. In a practical dielectric system, dipoles are found to behave according to a distribution of elementary Debye relaxation properties. Suitable distribution density functions have been proposed to characterise such many‐body interaction processes. Cole–Cole diagrams can be one of the methods for studying the nature of frequency dependency of dielectric materials of complex structure. Cole–Cole plots are commonly used for characterising different materials such as dielectric mixtures, ionic liquids, cable insulating oil, polar liquids etc. The scope of its application for assessing transformer oil‐paper insulation considering distributed relaxation process has not been explored yet. The present contribution discusses mathematical formulations used for transforming the experimentally obtained time domain dielectric response test data to distribution domain and further to frequency domain for obtaining the Cole–Cole plots. Findings about the influence of various operating conditions and insulation status on the Cole–Cole diagram have been reported in this contribution. Results of tests on field transformers are also presented. This paper attempts to employ the features of Cole–Cole diagrams as potential indicators for analysing condition of the oil‐paper insulation considering distributed relaxation process.
Effect of inverted T arrangement on AC pollution flashover characteristics of insulator strings
Authors: Jiang Xingliang , Ren Xiaodong , Wang Han , Han Xingbo , Bi Conglai , Li Zhiyu , Hou Ledong
Published: January 2019

The arrangement of insulator strings has an effect on its pollution flashover characteristics. A new arrangement of insulator strings, inverted T‐type arrangement, is proposed in this study. The electric field distribution is simulated and the pollution flashover characteristics are tested in an artificial climate chamber. The test results indicate that the inverted T‐type arrangement can greatly improve the flashover voltage of polluted insulator strings, the ‘7 + 2’ inverted T‐type arrangement can increase the flashover voltage of each insulator by 8.5% on average, and the ‘3 + 3’ inverted T‐type arrangement can increase the flashover voltage of each insulator by 13.4%. The discharge process is different from that of the normal suspension string when the insulator string is inverted T‐shaped, i.e. a local arc is produced at the low voltage end of the insulator string and develops downward along the suspension part. While as for the horizontal tension string parts, it is difficult to generate arc during discharge development.
Enabling cyber‐physical demand response in smart grids via conjoint communication and controller design
Authors: Mishra Swaroop Ranjan , Korukonda Meher Preetam , Behera Laxmidhar , Shukla Anupam
Published: January 2019

This study proposes a novel user‐centric cyber‐physical framework to achieve distributed demand response (DDR) in a distribution system where local schedulers (LS) present at individual buses program both local and non‐local loads to reduce the maximum load within a sparse communication setting. A COnjoint Methodology for communication and controller DESign (COMDES) has been proposed to design the topology of the communication network while considering various cyber and physical properties of the smart grid like bandwidth, load profile and voltage controller stability margin. The designed communication network provides a unified pathway for exchanging multiple types of data among different points in the grid to consummate the advanced ideas of DDR and multi‐input multi‐output voltage control concurrently. Concepts of Lyapunov stability and linear matrix inequalities are employed to design optimisation frameworks for tuning the values of voltage controllers which, in turn, play a vital role in pooling the loads to be scheduled by the individual LS for execution. Established algorithms like earliest deadline first, least laxity first and dynamic rate priority are used to generate switching schedules for redistributed loads and achieve peak shaving. IEEE 4 bus and 14 bus models have been used to demonstrate the efficacy of the proposed framework.
Modelling and analysis on short‐circuit failure for press‐pack IGBT devices used in VSC‐HVDC converter
Authors: Yao Ran , Li Hui , Lai Wei , Kang Shenyang , Deng Jili , Long Haiyan , Zheng Meimei , Li Jinyuan , Li Yaosheng
Published: January 2019

Press‐pack insulated gate bipolar transistor (IGBT) device is the key component in the voltage source converter high voltage direct current (VSC‐HVDC) due the advantage of the short‐circuit failure. However, it is difficult to analyse the IGBT short‐circuit failure mode due to the complex packaging and the short failure time. This study presents a method on simulation for the short‐circuit failure mode of the press‐pack IGBT device. First, based on the structure of a single‐chip 3.3 kV/50 A press‐pack IGBT, a multi‐physical field model was presented by considering the electro–mechanical–thermal coupling effects, so that the internal weak layer was found by comparing with the different sustained pressures. Then, an equivalent method is proposed by using the different aluminium–silicon reaction osmotic hole in the chip, and the models were presented to simulate the short‐circuit failure. Furthermore, after short‐circuit failure of the device, the thermal resistance variation of each later in press‐pack IGBT device was obtained. Finally, the experiment on the steady state and the short‐circuit tests were performed, by analysing the weak layer and the short‐circuit failure position of the IGBT device, the proposed models and analysis were testified. The achievement is helpful to optimal design of the press‐pack IGBT device to improve the VSC‐HVDC converter reliability.
Combined helioseismic inversions for 3D vector flows and sound-speed perturbations
Authors: Korda David , Švanda Michal
Published: January 2019

Context. Time–distance helioseismology is the method of the study of the propagation of waves through the solar interior via the travel times of those waves. The travel times of wave packets contain information about the conditions in the interior integrated along the propagation path of the wave. The travel times are sensitive to perturbations of a variety of quantities. The usual task is to invert for the vector of plasma flows or the sound–speed perturbations separately. The separate inversions may be polluted by systematic bias, for instance, originating in the leakage of vector flows into the sound–speed perturbations and vice versa (called a cross-talk). Information about the cross-talk is necessary for a proper interpretation of results.

Aims. We introduce an improved methodology of the time-distance helioseismology which allows us to invert for a full 3D vector of plasma flows and the sound–speed perturbations at once. Using this methodology one can also derive the mean value of the vertical component of plasma flows and the cross-talk between the plasma flows and the sound–speed perturbations.

Methods. We used the Subtractive Optimally Localised Averaging method with a minimisation of the cross-talk as a tool for inverse modelling. In the forward model, we use Born approximation travel-time sensitivity kernels with the Model S as a background. The methodology was validated using forward-modelled travel times with both mean and difference point-to-annulus averaging geometries applied to a snapshot of fully self-consistent simulation of the convection.

Results. We tested the methodology on synthetic data. We demonstrate that we are able to recover flows and sound–speed perturbations in the near-surface layers. We have taken the advantage of the sensitivity of our methodology to entire vertical velocity, and not only to its variations as in other available methodologies. The cross-talk from both the vertical flow component and the sound–speed perturbation has only a negligible effect for inversions for the horizontal flow components. Furthermore, this cross-talk can be minimised if needed. The inversions for the vertical component of the vector flows or for the sound–speed perturbations are affected by the cross-talk from the horizontal components, which needs to be minimised in order to provide valid results. It seems that there is a nearly constant cross-talk between the vertical component of the vector flows and the sound–speed perturbations.
Anthrax toxin requires ZDHHC5-mediated palmitoylation of its surface-processing host enzymes
Authors: Sergeeva Oksana A. , van der Goot F. Gisou
Published: January 2019

Significance

Toxins exploit numerous pathways of their host cells to gain cellular entry and promote intoxication. Therefore, studying the action of toxins allows us to better understand basic mechanisms in cell biology. In this study, we found that ZDHHC5, an enzyme that adds a lipid posttranslational modification to cysteines of proteins, is responsible for allowing anthrax toxin to enter cells. This enzyme acts on proprotein convertases that are needed to cleave these toxins to their active forms. ZDHHC5 does not affect the enzymatic activity of these proteases, but allows them to encounter the toxin by favoring their partitioning in microdomains on the cell surface, domains where the toxin has previously been shown to preferentially reside.
Bilingual education and CLIL in the Netherlands
Authors: Mearns Tessa , Graaff Rick de
Published: January 2019

The Netherlands is often held up an example of a ‘success story’ in terms of practices and research regarding the teaching and learning of subject content in a second language (de Graaff & van Wilgenburg, 2015;Pérez-Cañado, 2012). Nearly 30 years after its initial beginnings, bilingual secondary education in the Netherlands continues to thrive and to evolve in fitting with educational demands, as does the research associated with it. This Special Issue includes contributions addressing Content and Language Integrated Learning (CLIL) as a pedagogical approach in the context of bilingual education as a curricular paradigm, both specifically within the Dutch context. The issue contains six research articles from different perspectives, supported by discussions both from an international research standpoint and from the educational field. It is hoped that the publication of this issue will not only indicate a next stage for bilingual education policy and practice, but also give impetus to new areas for research.
How do we measure up?
Authors: Kampen Evelyn van , Mearns Tessa , Meirink Jacobiene , Admiraal Wilfried , Berry Amanda
Published: January 2019

Research into the pedagogies employed by CLIL teachers has been limited to date and, as such, has been identified as a key area in need of further investigation (Pérez-Cañado, 2012;Dalton-Puffer & Smit, 2013). This review uses an elaborated 4Cs Analysis Framework (adapted fromCoyle, Hood, & Marsh, 2010;Coyle, 2015a,2015b) as a basis for analysis of studies of pedagogies implemented by CLIL subject teachers internationally and in Dutch classrooms. This allows us to place the Dutch situation in an international context and to identify avenues for future research and development. The following questions guided the review: (1) What appear to be the most prominent international trends with regard to the implementation of the 4Cs in CLIL subject pedagogies?; and, (2) To what extent do Dutch CLIL subject pedagogies appear to reflect these international trends? Findings about pedagogies reported in the reviewed studies suggest that, in general, studies from the Netherlands stand out compared to international studies in several respects. Specifically, there is evidence of a relatively strong pedagogic focus in the Netherlands on developing students’ intercultural competence. The Dutch studies also stand out, however, for not addressing the role that the L1 can play in CLIL pedagogy. Furthermore, a main finding is that both the Dutch and the international studies reviewed provide little insight into aspects of CLIL pedagogy related to subject-specific culture and into ways in which content and language areintegrated.
Risk-benefit Assessment of Systematic Thoracoabdominal-pelvic Computed Tomography in Infective Endocarditis
Authors: Lecomte Raphaël , Issa Nahéma , Gaborit Benjamin , Le Turnier Paul , Deschanvres Colin , Asseray Nathalie , Le Tourneau Thierry , Michel Magali , Al Habash Ousama , Bizouarn Philippe , Camou Fabrice , Boutoille David
Published: January 2019

Background

In the management of infective endocarditis (IE), the presence of extracardiac complications has an influence on both diagnosis and treatment. Current guidelines suggest that systematic thoracoabdominal-pelvic computed tomography (TAP-CT) may be helpful. Our objective was to describe how systematic TAP-CT affects the diagnosis and the management of IE.

Methods

In this multicenter cohort study, between January 2013 and July 2016 we included consecutive patients who had definite or possible IE according to the Duke modified criteria, validated by endocarditis teams. We analyzed whether the Duke classification and therapeutic management were modified regarding the presence or the absence of IE-related lesion on CT and investigated the tolerance of this examination.

Results

Of the 522 patients included in this study, 217 (41.6%) had 1 or more IE-related lesions. On the basis of CT results in asymptomatic patients, diagnostic classification was upgraded from possible endocarditis to definite endocarditis for only 4 cases (0.8%). The presence of IE-related lesions on CT did not modify the duration of antibiotic treatment (P = .55), nor the decision of surgical treatment (P = .39). Specific treatment of the lesion was necessary in 42 patients (8.0%), but only 9 of these lesions (1.9%) were asymptomatic and diagnosed only on the TAP-CT. Acute kidney injury (AKI) within 5 days of CT was observed in 78 patients (14.9%).

Conclusions

The TAP-CT findings slightly affected diagnosis and treatment of IE in a very small proportion of asymptomatic patients. Furthermore, contrast media should be used with caution because of the high risk of AKI.
Impact of β-Lactam and Daptomycin Combination Therapy on Clinical Outcomes in Methicillin-susceptible Staphylococcus aureus Bacteremia: A Propensity Score–matched Analysis
Authors: Grillo Sara , Cuervo Guillermo , Carratalà Jordi , Grau Immaculada , Pallarès Natàlia , Tebé Cristian , Guillem Tió Lluisa , Murillo Oscar , Ardanuy Carmen , Domínguez M Angeles , Shaw Evelyn , Gudiol Carlota , Pujol Miquel
Published: January 2019

Background

Mortality rates from Staphylococcus aureus bacteremia are high and have only modestly improved in recent decades. We compared the efficacies of a β-lactam in combination with daptomycin (BL/D-C) and β-lactam monotherapy (BL-M) in improving clinical outcomes in methicillin-susceptible S. aureus (MSSA) bacteremia.

Methods

A retrospective cohort study of MSSA bacteremia was performed in a tertiary hospital from January 2011 to December 2017. Patients receiving BL/D-C and BL-M were compared to assess 7-, 30-, and 90-day mortality rates. A 1:2 propensity score matching analysis was performed. Differences were assessed using Cox regression models.

Results

Of the 514 patients with MSSA bacteremia, 164 were excluded as they had received combination therapies other than BL/D-C, had pneumonia, or died within 48 hours of admission. Of the remaining 350 patients, 136 and 214 received BL/D-C and BL-M, respectively. BL/D-C patients had higher Pitt scores and persistent bacteremia more often than BL-M patients. In the raw analysis, there were no differences in mortality rates between groups. After propensity score matching, there were no significant differences between the BL/D-C (110 patients) and BL-M (168 patients) groups for all-cause mortality rates at 7 days (8.18% vs 7.74%; P = 1.000), 30 days (17.3% vs 16.1%; P = .922), and 90 days (22.7% vs 23.2%; P = 1.000), even in a subanalysis of patients with high-risk source of infection and in a subgroup excluding catheter-related bacteremia.

Conclusions

BL/D-C failed to reduce mortality rates in patients with MSSA bacteremia. Treatment strategies to improve survival in MSSA bacteremia are urgently needed.
Prevalence of Congenital Cytomegalovirus Infection and Associated Risk of In Utero Human Immunodeficiency Virus (HIV) Acquisition in a High-HIV Prevalence Setting, South Africa
Authors: Pathirana Jayani , Groome Michelle , Dorfman Jeffrey , Kwatra Gaurav , Boppana Suresh , Cutland Clare , Jones Stephanie , Madhi Shabir A
Published: January 2019

Background

There is a paucity of data on the burden of congenital cytomegalovirus (cCMV) infections in low- and middle-income countries, including their association with maternal human immunodeficiency virus (HIV) infections. We investigated the prevalence of cCMV in a patient population with a high rate of HIV and antiretroviral therapy (ART) use during pregnancy in Soweto, Johannesburg.

Methods

Saliva from neonates were screened for cytomegalovirus (CMV) infection by polymerase chain reaction (PCR) at birth. Additional saliva and urine samples were tested within 3 weeks of birth to confirm positive saliva results. HIV PCR testing was done on the whole blood of HIV-exposed neonates. Maternal and neonatal data were extracted from clinical records.

Results

Of 2685 neonates screened for cCMV, 828 (31%) were born to HIV-infected women, 95% of whom (790/828) were on ART at delivery. The overall prevalence of cCMV was 2.5% (95% confidence interval [CI] 1.9–3.2), with significantly higher cCMV prevalence in HIV-exposed neonates (5.2%, 95% CI 3.8–6.9) than HIV-unexposed neonates (1.4%, 95% CI 0.9–2.0). The risk of in utero HIV infection was 20-fold greater (odds ratio 20.1, 95% CI 6.09–66.46) in HIV-exposed, cCMV-infected neonates, and this increased risk was not associated with the maternal CD4+ T-cell count or the maternal duration of ART.

Conclusions

The prevalence of cCMV in our setting is substantially higher than the global estimate of 0.64%, partly due to the increased susceptibility for cCMV in HIV-exposed neonates. The significantly increased risk of in utero HIV infection in neonates with cCMV indicates that CMV coinfection plays a major role in the residual burden of in utero HIV transmission, even in the era of ART.
Minimal consistent finite element space for the biharmonic equation on quadrilateral grids
Authors: Zhang Shuo
Published: January 2019

This study presents a finite element space comprising piecewise quadratic polynomials on quadrilateral grids. This space provides a minimal-degree consistent discretisation for the biharmonic equation.
Integration or Separation? Malcolm X’s College Debates, Free Speech, and the Challenge to Racial Liberalism on Campus
Authors: Felber Garrett
Published: January 2019

Malcolm X participated in over thirty speaking engagements at prominent colleges and universities between 1960 and 1963. His popularity on campuses coincided with a new epoch of civil rights struggle as students became involved in Freedom Rides and sit-in campaigns to desegregate lunch counters and interstate travel. Most invitations were debates on the topic “Integration or Separation?” which pitted Malcolm against an integrationist opponent. The insertion of racial separatism into a discourse that took integration as an unquestioned aim of the movement pushed students to question and defend their own understandings of racial liberalism. Nearly a dozen invitations were extended by NAACP student chapters that had been revitalized amid the new flurry of student involvement. Years before the founding of the first Black Student Union (BSU) at San Francisco State, these chapters were far more ideologically diverse and active than their forbearers, and often invited Malcolm X to speak out of a commitment to students’ rights to free speech and academic freedom. When administrations blocked and cancelled his visits, students became politicized around issues of academic liberties, thereby situating the Nation of Islam and Malcolm X at the nexus of early debates within the student free speech movement. These became part of the early challenge to university paternalism. While these debates and lectures have often been discussed individually, this essay looks at their cumulative effect by situating them during the emergence of student radicalism on campus and the growth of youth participation in the civil rights movement.
What goes around…
Authors: Weiss Matthew J
Published: January 2019

Health care workers often talk about ‘karma’ regarding how busy a clinical service will be when a certain physician is on service. While often lighthearted, this construction of karma might have some undesirable implications by shifting our focus from our patients to ourselves.
Choosing medications wisely: Is it time to address paediatric polypharmacy?
Authors: Bogler Orly , Roth Daniel , Feinstein James , Strzelecki Marina , Seto Winnie , Cohen Eyal
Published: January 2019

There is a growing focus in the medical community on de-escalating medical treatments where appropriate; however, specific efforts to reduce medication burden in patients with polypharmacy has largely been targeted toward adult populations. Polypharmacy increases the risk of adverse drug reactions in children, and that risk may be further increased by the use of off-label drugs. The paediatric prescribing community should explore pharmacovigilance strategies and deprescription initiatives that prioritize patients with polypharmacy. Currently, best practices may be extrapolated from the adult literature, including medication review algorithms and patient education tools. Enhancing access to nonpharmacological modalities to address child and youth mental health may mitigate psychotropic polypharmacy. The aim of these initiatives should be to improve patient outcomes and experiences by avoiding adverse drug events and drug–drug interactions.
Differences in Opioid Prescribing Among Generalist Physicians, Nurse Practitioners, and Physician Assistants
Authors: Ellenbogen Michael I , Segal Jodi B
Published: January 2019

Objective

To determine if there are differences in opioid prescribing among generalist physicians, nurse practitioners (NPs), and physician assistants (PAs) to Medicare Part D beneficiaries.

Design

Serial cross-sectional analysis of prescription claims from 2013 to 2016 using publicly available data from the Centers for Medicare and Medicaid Services.

Subjects

All generalist physicians, NPs, and PAs who provided more than 10 total prescription claims between 2013 and 2016 were included. These prescribers were subsetted as practicing in a primary care, urgent care, or hospital-based setting.

Methods

The main outcomes were total opioid claims and opioid claims as a proportion of all claims in patients treated by these prescribers in each of the three settings of interest. Binomial regression was used to generate marginal estimates to allow comparison of the volume of claims by these prescribers with adjustment for practice setting, gender, years of practice, median income of the ZIP code, state fixed effects, and relevant interaction terms.

Results

There were 36,999 generalist clinicians (physicians, NPs, and PAs) with at least one year of Part D prescription drug claims data between 2013 and 2016. The number of adjusted total opioid claims across these four years for physicians was 660 (95% confidence interval [CI] = 660–661), for NPs was 755 (95% CI = 753–757), and for PAs was 812 (95% CI = 811–814).

Conclusions

We find relatively high rates of opioid prescribing among NPs and PAs, especially at the upper margins. This suggests that well-designed interventions to improve the safety of NP and PA opioid prescribing, along with that of their physician colleagues, could be especially beneficial.
iTALK: an R Package to Characterize and Illustrate Intercellular Communication
Authors: Wang Yuanxin , Wang Ruiping , Zhang Shaojun , Song Shumei , Jiang Changying , Han Guangchun , Wang Michael , Ajani Jaffer , Futreal Andy , Wang Linghua
Published: January 2019

Crosstalk between tumor cells and other cells within the tumor microenvironment (TME) plays a crucial role in tumor progression, metastases, and therapy resistance. We present iTALK, a computational approach to characterize and illustrate intercellular communication signals in the multicellular tumor ecosystem using single-cell RNA sequencing data. iTALK can in principle be used to dissect the complexity, diversity, and dynamics of cell-cell communication from a wide range of cellular processes.
Effects of Curative-Intent Lung Cancer Therapy on Functional Exercise Capacity and Patient-Reported Outcomes
Authors: Ha Duc , Ries Andrew L. , Lippman Scott M. , Fuster Mark M.
Published: January 2019

Background

Lung cancer treatment can lead to negative health consequences. We analyzed the effects of curative-intent lung cancer treatment on functional exercise capacity (EC) and patient-reported outcomes (PROs).

Methods

We performed a prospective-observational cohort study of consecutive patients with stage I-IIIA lung cancer undergoing curative-intent therapy and assessed functional EC [primary outcome, six-minute walk distance (6MWD)], cancer-specific quality of life (QoL) [secondary outcome, European Organization for Research and Treatment of Cancer QoL Questionnaire Core 30 (EORTC-QLQ-C30) summary score], and exploratory outcomes including dyspnea [University of California San Diego Shortness of Breath Questionnaire (UCSD-SOBQ)] and fatigue [Brief Fatigue Inventory (BFI)] symptoms before and at 1 to 3 months post-treatment. We analyzed the time effect of treatment on outcomes using multivariable generalized estimating equations.

Results

In 35 enrolled participants, treatment was borderline-significantly associated with a clinically-meaningful decline in functional EC [(mean change, 95% CI) 6MWD = −25.4m (−55.3, +4.47), p=0.10], non-significant change in cancer-specific QoL [EORTC-QLQ-C30 summary score = − 3.4 (−9.8, +3.0), p=0.30], and statistically-significant and clinically-meaningful higher dyspnea [UCSD-SOBQ = +13.1 (+5.7, +20.6), p=0.001] and increased fatigue [BFI = +10.0 (+2.9, +17.0), p=0.006].

Conclusions

Among the first prospective analysis of the effect of curative-intent lung cancer treatment on functional EC and PROs, we observed worsening dyspnea and fatigue, and possibly a decline in functional EC but not cancer-specific QoL at 1 to 3 months post-treatment. Interventions to reduce treatment-related morbidities and improve lung cancer survivorship may need to focus on reducing dyspnea, fatigue, and/or improving functional EC.

Consent and Approval

Written informed consent was obtained from each participant included in this study. All human investigations were performed after approval by the VA San Diego Healthcare System institutional review board and in accord with an assurance filed with and approved by the U.S. Department of Health and Human Services.
Rise in mortality involving poisoning by medicaments other than narcotics, including poisoning by psychotropic drugs in different age/racial groups in the US
Authors: Goldstein Edward
Published: January 2019

Background

Increase in mortality involving poisoning, particularly by narcotics, is known to have been one of the factors that affected life expectancy in the US during the last two decades, especially for white Americans and Native Americans. However, the contribution of medicaments other than narcotics to mortality in different racial/age groups is less studied.

Methods

We regressed annual rates of mortality involving poisoning by medicaments but not narcotics/psychodysleptics (ICD-10 codes T36-39.xx or T41-50.8 but not T40.xx present as either underlying or contributing causes of death), as well as annual rates of mortality for certain subcategories of the above, including mortality involving poisoning by psychotropic drugs but not narcotics/psychodysleptics (ICD-10 codes T43.xx but not T40.xx present as either underlying or contributing causes of death) in different age/racial groups for both the 2000-2011 period and the 2011-2017 period against calendar year.

Results

Annual numbers of deaths involving poisoning by medicaments but not narcotics/psychodysleptics grew from 4,332 between 2000-2001 to 11,401 between 2016-2017, with the growth in the rates of those deaths being higher for the 2011-2017 period compared to the 2000-2011 period. The largest increases in the rates of mortality involving poisoning by medicaments but not narcotics/psychodysleptics were in non-elderly Non-Hispanic Native Americans, followed by Non-Hispanic whites. Most of those increases came from increases in the rates of mortality involving poisoning by psychotropic medications; the latter rates grew for the period of 2015-2017 vs. 2000-2002 by factors ranging from 2.75 for ages 35-44y to 5.37 for ages 55-64y.

Conclusions

There were major increases in mortality involving poisoning by non-narcotic, particularly psychotropic medicaments, especially in non-elderly non-Hispanic whites and Native Americans. Our results, and the epidemiological data on mortality involving poisoning by different drugs and medications in the US, which are quite different from the ones in many other countries support the need for a comprehensive evaluation of the effect of various drugs, including psychotropic medications on health-related outcomes, the associated mortality the does not involve poisoning being listed on a death certificate, and the impact of medication misuse.
Factors associated with adherence to the Integrated Management of Childhood Illness (IMCI) guidelines for under-five years’ old care in Burkina Faso primary health care facilities
Authors: Traoré Sabere Anselme , Somda Serge M.A. , Kiendrébéogo Joël Arthur , Kouldiati Jean-Louis , Robyn Paul Jacob , Hien Hervé , Méda Nicolas
Published: January 2019

Objective

To assess the adherence to Integrated Management of Childhood Illness (IMCI) guidelines in primary health care facilities in Burkina Faso and to determine the factors associated.

Materials and Methods

We used data from a large survey on health facilities, held from October 2013 to April 2014. Primary health facilities were evaluated, health workers interviewed and consultations observed. The standard guideline for an under five year’s old child consultation was the Integrated Management of Childhood Illness (IMCI).

Results

1,571 consultations were observed, carried out by 522 different practitioners. The danger signs were usually not checked (13.9% only checking for at least three general danger signs). The adherence for cough (74.8%), diarrhoea (64.9%), fever (83.8%) and anaemia (70.3%) was higher. The principal factors found to be associated with poorer adherence to guidelines of consultation were female sex (Rate Ratio (RR) = 0.91; 95% CI 0.86 – 0.95), non-nurse practitioner (RR=0.93; 95% CI 0.88 – 0.97), IMCI training (RR=1.06; 95% CI 1.01 – 1.11), non-satisfaction of the salary (RR=0.95 95% CI 0.91 – 0.99).

Conclusion

This study highlights a poor adherence to the IMCI guidelines and by then, revealing a poor quality of under-five care. Indeed, many characteristics of health workers including gender, type of profession, training satisfaction with salary were found to be associated with this adherence. Therefore, more initiatives aiming at improving the quality of care should be developed and implemented for improving the child health care.
Blanding’s turtles (Emydoidea blandingii) as a reservoir for Leptospira spp
Authors: Rockwell Kelly E. , Thompson Dan , Maddox Carol , Mitchell Mark A.
Published: January 2019

Leptospira spp. are re-emerging zoonotic pathogens. Previous research has found that Blanding’s turtles (Emydoidea blandingii) experimentally infected with Leptospira interrogans shed leptospires in their urine, suggesting that they could play a role in transmitting pathogen within an aquatic ecosystem. This study investigated whether a population of wild Blanding’s turtles known to be exposed to Leptospira spp. actively shed the pathogen under natural conditions. Blood samples were collected for serologic testing and to assess the health of the turtles. Free catch urine was collected for polymerase chain reaction (PCR) testing. All turtles were seropositive for Leptospira spp. and 73.5% (25/34) of the urine samples were PCR positive. All animals appeared clinically healthy and showed no apparent signs of disease. This study confirms that wild Blanding’s turtles can actively shed Leptospira spp. in their urine and suggests that they may play a role in the epidemiology of this disease in habitats in which they reside.
Patterns of Treatment in Patients with Heart Failure with Preserved Ejection Fraction: the REasons for Geographic And Racial Differences in Stroke study
Authors: Poudel Bharat , Loop Matthew S. , Brown Todd M. , Durant Raegan W. , Safford Monika M. , Goyal Parag , Chen Ligong , Levitan Emily B.
Published: January 2019

Purpose

We described medication use patterns among REasons for Geographic And Racial Differences in Stroke (REGARDS) participants hospitalized for heart failure with preserved ejection fraction (HFpEF) (152 hospitalizations, 101 unique individuals).

Methods

Medication data were obtained from medical record review and Medicare Part D pharmacy claims. We compared discharge medication prescriptions between patients with and without chronic kidney disease (CKD), coronary heart disease (CHD), chronic obstructive pulmonary disease (COPD), and diabetes.

Results

The mean age was 74.8 years, 53.3% were black and 73.7% were female. Hypertension (97.2%), diabetes (65.1%), COPD (51.3%), CKD (41.1%) and history of CHD (60.9%) were common. On admission and discharge, respectively, beta-blockers (66.4%, 72.7%), angiotensin converting enzyme inhibitors or angiotensin receptor blockers (42.8%, 51.7%), diuretics (61.2%, 80.9%), loop diuretics (55.9%, 78.3%), calcium channel blockers (41.0%, 41.2%) and statins (44.7%, 50.3%) were commonly used. Spironolactone, digoxin, hydralazine plus isosorbide dinitrate (HISDN), isosorbide dinitrate alone and aldosterone receptor antagonists were used by <20%. For each medication, prescriptions were more common at discharge than admission. Many participants did not have Medicare claims for filled prescriptions in the year following discharge. A higher percentage of patients with versus without CKD, CHD, and diabetes had discharge prescriptions statins. Participants with CKD were also more likely to receive prescriptions for HISDN.

Conclusion

Beta-blockers and diuretics were commonly prescribed at admission and discharge among HFpEF, but pharmacy claims for these medications within one-year were substantially less common. The comorbidities CHD, CKD, and diabetes were associated with prescriptions of statins at discharge.
IFT88 controls NuMA enrichment at k-fibers minus-ends to facilitate their reincorporation into mitotic spindles
Authors: Taulet Nicolas , Douanier Audrey , Vitre Benjamin , Anguille Christelle , Maurin Justine , Dromard Yann , Georget Virginie , Delaval Benedicte
Published: January 2019

To build and maintain mitotic spindle architecture, molecular motors exert spatially regulated forces on microtubules (MT) minus-ends. This spatial regulation is required to allow proper chromosomes alignment through the organization of kinetochore fibers (k-fibers). NuMA was recently shown to target dynactin to MT minus-ends and thus to spatially regulate dynein activity. However, given that k-fibers are embedded in the spindle, our understanding of the machinery involved in the targeting of proteins to their minus-ends remains limited. Intraflagellar transport (IFT) proteins were primarily studied for their ciliary roles but they also emerged as key regulators of cell division. Taking advantage of MT laser ablation, we show here that IFT88 concentrates at k-fibers minus-ends and is required for their re-anchoring into spindles by controlling NuMA accumulation. Indeed, IFT88 interacts with NuMA and is required for its enrichment at newly generated k-fibers minus-ends. Combining nocodazole washout experiments and IFT88 depletion, we further show that IFT88 is required for the reorganization of k-fibers into spindles and thus for efficient chromosomes alignment in mitosis. Overall, we propose that IFT88 could serve as a mitotic MT minus-end adaptor to concentrate NuMA at minus-ends thus facilitating k-fibers incorporation into the main spindle.
Genetic dissection of femoral and tibial microarchitecture
Authors: Lu Lu , Huang Jinsong , Xu Fuyi , Xiao Zhousheng , Wang Jing , Zhang Bing , David Nicolae Valentin , Arends Danny , Gu Weikuan , Ackert-Bicknell Cheryl , Sabik Olivia L. , Farber Charles R. , Quarles Leigh Darryl , Williams Robert W.
Published: January 2019

Our understanding of the genetic control of bone has relied almost exclusively on estimates of bone mineral density. In contrast, here we have used high-resolution x-ray tomography (8 μm isotropic voxels) to measure femoral and tibial components across a set of ~600 mice belonging to 60 diverse BXD strains of mice. We computed heritabilities of 25 cortical and trabecular compartments. Males and females have well matched trait heritabilities, ranging from 0.25 to 0.75. We mapped 16 QTLs that collectively cover ~8% of all protein-coding genes in mouse. A majority of loci are detected only in females, and there is also a bias in favor of QTLs for cortical traits. To efficiently evaluate candidate genes we developed a method that couples gene ontologies with expression data to compute bone-enrichment scores for almost all protein-coding genes. We carefully collated and aligned murine candidates with recent human BMD genome-wide association results. We highlight a subset of 50 strong candidates that fall into three categories: 1. those linked to bone function that have already been experimentally validated (Adamts4, Ddr2, Darc, Adam12, Fkbp10, E2f6, Adam17, Grem2, Ifi204); 2. candidates with putative bone function but not yet tested (e.g.,Greb1, Ifi202b) but several of which have been linked to phenotypes in humans; and 3. candidates that have high bone-enrichment scores but for which there is not yet any specific link to bone biology or skeletal disease, includingIfi202b, Ly9, Ifi205, Mgmt, F2rl1, Iqgap2. Our results highlight contrasting genetic architecture between the sexes and among major bone compartments. The joint use and alignment of murine and human data should greatly facilitate function analysis and preclinical testing.

Disclosure

The authors declare that no competing interests exist.
The Trouble Interpreting fMRI Studies in Populations with Cerebrovascular Risk: The Use of a Subject-Specific Hemodynamic Response Function in a Study of Age, Vascular Risk, and Memory
Authors: McDonough Ian M. , Bender Andrew , Patihis Lawrence , Stinson Elizabeth A. , Letang Sarah K. , Miller William S.
Published: January 2019

Functional magnetic resonance imaging (fMRI) is commonly used to investigate the neural bases of behavior ranging from basic cognitive mechanisms to aging to psychological disorders. However, the BOLD signal captured by fMRI is an indirect measure of neural function and is affected by many factors that are non-neural in origin. These non-neural factors, however, do affect brain vasculature such as the shape and timing of the hemodynamic response function (HRF) during task-evoked fMRI that, in turn, can cause inappropriate and/or misleading interpretations of fMRI differences between groups. In this study, we tested the proposition that vascular health risks, which often go unmeasured in neuroimaging studies, and aging interact to modify the shape and/or timing of the HRF (height, time-to-peak, width), which then affect the differences in patterns of brain activity in a task-evoked memory encoding paradigm. Adult participants (aged 20–74) answered questions about their health history and underwent two fMRI tasks: viewing of a flashing checkerboard using a slow event-related design and a paired associates memory encoding task during a fast event-related design. We found that aging and vascular risk had the largest impacts on the maximum peak value of the HRF. Using a subject-specific HRF resulted in an overall dampening of the estimated brain activity in both task-positive and task-negative regions due to a reduction in the inter-individual variance of that activity. Across three vascular risk factors, using a subject-specific HRF resulted in more consistent brain regions that reached significance and larger effect sizes compared with the canonical HRF. A slight advantage in the reliability of brain-behavior correlations also was found. The findings from this study have far reaching consequences for the interpretation of task-evoked fMRI activity, especially in populations known to experience alterations to brain vasculature including adults of all ages that have higher vascular risk, the majority of older adults, and people with neurocognitive disorders in which vasculature differences may play a role including dementia.

Highlights

Older age was associated with smaller maximum peak of the hemodynamic response.

Younger and middle-aged adults with more vascular risk had higher HRF peaks.

Using a subject-specific HRF resulted in a “dampening” of brain activity.

A subject-specific HRF resulted in more consistent aging and vascular risk effects.
Adolescent forced swim stress increases social anxiety-like behaviors and alters the dynorphin/kappa opioid receptor system in the basolateral amygdala of males
Authors: Varlinskaya E.I. , Johnson J.M. , Deak T. , Diaz M.R.
Published: January 2019

Adolescence is a developmental period marked by robust neural alterations and heightened vulnerability to stress, a factor that is highly associated with increased risk for emotional processing deficits, such as anxiety. Stress-induced upregulation of the dynorphin/kappa opioid receptor (DYN/KOR) system is thought to, in part, underlie the negative affect associated with stress. The basolateral amygdala (BLA) is a key structure involved in anxiety, and neuromodulatory systems, such as the DYN/KOR system, can 1) regulate BLA neural activity in an age-dependent manner in stress-naïve animals and 2) underlie stress-induced anxiety in adults. However, the role of the DYN/KOR system in modulating stress-induced anxiety in adolescents is unknown. To test this, we examined the impact of an acute, 2-day forced swim stress (FSS – 10 min each day) on adolescent (~postnatal day (P) 35) and adult Sprague-Dawley rats (~P70), followed by behavioral, molecular and electrophysiological assessment 24 hours following FSS. Adolescent males, but not adult males or females of either age, demonstrated social anxiety-like behavioral alterations indexed via significantly reduced social investigation and preference when tested 24 hours following FSS. Conversely, adult males exhibited increased social preference. While there were no FSS-induced changes in expression of genes related to the DYN/KOR system in the BLA, these behavioral alterations were associated with a robust switch in BLA KOR function. Specifically, while the KOR agonist, U69593, significantly increased GABA transmission in the BLA of non-stressed adolescent males, U69593 significantly inhibited BLA GABA transmission in stressed adolescent males, consistent with the observed anxiogenic phenotype in stressed adolescent males. This is the first study to demonstrate a KOR-dependent mechanism that may contribute to stress-induced social anxiety in adolescent males. Importantly, these findings provide evidence for potential KOR-dependent mechanisms that may contribute to pathophysiological interactions with subsequent stress challenges.