bluuebunny/crossref_metadata_2025 huggingface dataset:
Cerebrovascular Physiology During Pediatric Extracorporeal Membrane Oxygenation: A Multicenter Study Using Transcranial Doppler Ultrasonography*
Authors: O’Brien Nicole F. , Buttram Sandra D.W. , Maa Tensing , Lovett Marlina E. , Reuter-Rice Karin , LaRovere Kerri L.
Published: November 2018

Objectives:

To explore changes to expected, age-related transcranial Doppler ultrasound variables during pediatric extracorporeal membrane oxygenation.

Design:

Prospective, observational, multicenter study.

Setting:

Tertiary care PICUs.

Patients:

Children 1 day to 18 years old requiring veno arterial extracorporeal membrane oxygenation.

Methods:

Participants underwent daily transcranial Doppler ultrasound measurement of bilateral middle cerebral artery flow velocities. Acute neurologic injury was diagnosed if seizures, cerebral hemorrhage, or diffuse cerebral ischemia was detected.

Measurements and Main Results:

Fifty-two children were enrolled and analyzed. In the 44 children without acute neurologic injury, there was a significant reduction in systolic flow velocity and mean flow velocity compared with predicted values over time (F [8, 434] = 60.44; p ≤ 0.0001, and F [8, 434] = 17.61; p ≤ 0.0001). Middle cerebral artery systolic flow velocity was lower than predicted on extracorporeal membrane oxygenation days 1–5, and mean flow velocity was lower than predicted on extracorporeal membrane oxygenation days 1–3. In the six infants less than 90 days old suffering diffuse cerebral ischemia, middle cerebral artery systolic flow velocity, mean flow velocity, and diastolic flow velocity from extracorporeal membrane oxygenation days 1–9 were not significantly different when compared with children of similar age in the cohort that did not suffer acute neurologic injury (systolic flow velocity F [8, 52] = 0.6659; p = 0.07 and diastolic flow velocity F [8, 52] = 1.4; p = 0.21 and mean flow velocity F [8, 52] = 1.93; p = 0.07). Pulsatility index was higher in these infants over time than children of similar age in the cohort on extracorporeal membrane oxygenation that did not suffer acute neurologic injury (F [8, 52] = 3.1; p = 0.006). No patient in the study experienced cerebral hemorrhage.

Conclusions:

Flow velocities in the middle cerebral arteries of children requiring extracorporeal membrane oxygenation are significantly lower than published normative values for critically ill, mechanically ventilated, sedated children. Significant differences in measured systolic flow velocity, diastolic flow velocity, and mean flow velocity were not identified in children suffering ischemic injury compared with those who did not. However, increased pulsatility index may be a marker for ischemic injury in young infants on extracorporeal membrane oxygenation.
EEG functional connectivity metrics wPLI and wSMI account for d distinct types of brain functional interactions
Authors: Imperatori Laura Sophie , Betta Monica , Cecchetti Luca , Johnson André Canales , Ricciardi Emiliano , Siclari Francesca , Pietrini Pietro , Chennu Srivas , Bernardi Giulio
Published: November 2018

Functional connectivity (FC) estimation methods are extensively used in neuroimaging to measure brain inter-regional interactions. The weighted Phase Lag Index (wPLI) and the weighted Symbolic Mutual Information (wSMI) represent relatively robust exemplars of spectral (wPLI) and information-theoretic (wSMI) connectivity measures that recently gained increased popularity due to their relative immunity to volume conduction. wPLI and wSMI are posited to have different sensitivity to linear and nonlinear relationships between neural sources, but their performance has never been directly compared. Here, using simulated high-density (hd-)EEG data, we evaluated the accuracy of these two metrics for detecting distinct types of regional interdependencies characterised by different combinations of linear and nonlinear components. Our results demonstrate that while wPLI performs generally better at detecting functional couplings presenting a mixture of linear and nonlinear interdependencies, only wSMI is able to detect exclusively nonlinear interaction dynamics. To evaluate the potential impact of these differences on real experimental data, we computed wPLI and wSMI connectivity in hd-EEG recordings of 12 healthy adults obtained in wakefulness and deep (N3-)sleep. While both wPLI and wSMI revealed a relative decrease in alpha-connectivity during sleep relative to wakefulness, only wSMI identified a relative increase in theta-connectivity, while wPLI detected an increase in delta-connectivity, likely reflecting the occurrence of traveling slow waves. Overall, our findings indicate that wPLI and wSMI provide distinct but complementary information about functional brain connectivity, and that their combined use could advance our knowledge of neural interactions underlying different behavioural states.
Characterization of intact proviruses in blood and lymph node from HIV-infected individuals undergoing analytical treatment interruption
Authors: Vibholm Line K. , Lorenzi Julio C.C. , Pai Joy A. , Cohen Yehuda Z. , Oliveira Thiago Y. , Barton John P. , Noceda Marco Garcia , Lu Ching-Lan , Ablanedo-Terrazas Yuria , Del Rio Estrada Perla M. , Teran Gustavo Reyes , Tolstrup Martin , Denton Paul W. , Damsgaard Tine , Søgaard Ole S. , Nussenzweig Michel C.
Published: November 2018

The role of lymphoid tissue as a potential source of HIV-1 rebound following interruption of antiretroviral therapy is uncertain. To address this issue, we compared the latent viruses obtained from CD4+ T cells in peripheral blood and lymph nodes to viruses emerging during treatment interruption. Latent viruses were characterized by sequencing near full-length (NFL) proviral DNA, and env from viral outgrowth cultures (VOAs). 5 HIV-1 infected individuals on antiretroviral therapy (ART) were studied, 4 of whom participated in a clinical trial that included an analytical treatment interruption. Intact or replication competent clonal sequences from blood and lymph node overlapped. In contrast, there was no overlap between 205 latent reservoir and 125 rebound sequences in the 4 individuals who underwent treatment interruption. However, rebound viruses could be accounted for by recombination. The data suggests that CD4+ T cells carrying latent viruses circulate between blood and lymphoid tissues in individuals on ART and support the idea that recombination may play a role in the emergence of rebound viremia.
Predicting time to dementia using a quantitative template of disease progression
Authors: Murat Bilgel , Jedynak Bruno M.
Published: November 2018

Introduction

Characterization of longitudinal trajectories of biomarkers implicated in sporadic Alzheimer’s disease (AD) in decades prior to clinical diagnosis is important for disease prevention and monitoring.

Methods

We used a multivariate Bayesian model to temporally align 1369 AD Neuroimaging Initiative participants based on the similarity of their longitudinal biomarker measures and estimated a quantitative template of the temporal evolution cerebrospinal fluid (CSF) Aβ1-42, p-tau181p, and t-tau, hippocampal volume, brain glucose metabolism, and cognitive measurements. We computed biomarker trajectories as a function of time to AD dementia, and predicted AD dementia onset age in a disjoint sample.

Results

Quantitative template showed early changes in verbal memory, CSF Aβ1-42 and p-tau181p, and hippocampal volume. Mean error in predicted AD dementia onset age was < 1.5 years.

Discussion

Our method provides a quantitative approach for characterizing the natural history of AD starting at preclinical stages despite the lack of individual-level longitudinal data spanning the entire disease timeline.
Biomarker-based patient selection improves stroke rehabilitation trial efficiency
Authors: Stinear Cathy M. , Byblow Winston D. , Barber P. Alan , Ackerley Suzanne J. , Smith Marie-Claire , Cramer Steven C.
Published: November 2018

Background and Purpose

Inter-subject variability complicates trials of novel stroke rehabilitation therapies, particularly in the sub-acute phase after stroke. We tested whether selecting patients using motor evoked potential (MEP) status, a physiological biomarker of motor system function, could improve trial efficiency.

Methods

A retrospective analysis of data from 207 patients (103 women, mean (SD) 70.6 (15.1) years) was used to estimate sample sizes and recruitment rates required to detect a 7-point difference between hypothetical control and treatment groups in upper-limb Fugl-Meyer and Action Research Arm Test scores at 90 days post-stroke. Analyses were carried out for the full sample and for subsets defined by motor evoked potential (MEP) status.

Results

Selecting patients according to MEP status reduced the required sample size by 75% compared to an unselected sample. The estimated time needed to recruit the required sample was also reduced by 72% for patients with MEPs, and was increased by 2-3-fold for patients without MEPs.

Conclusions

Using biomarkers to select patients can improve stroke rehabilitation trial efficiency by reducing the sample size and recruitment time needed to detect a clinically meaningful effect of the tested intervention.
Targeting and Vaccine Durability Are Key for Population-level Impact and Cost-Effectiveness of a Pox-Protein HIV Vaccine Regimen in South Africa
Authors: Selinger Christian , Bershteyn Anna , Dimitrov Dobromir T. , Adamson Blythe J.S. , Revill Paul , Hallett Timothy B. , Phillips Andrew N. , Bekker Linda-Gail , Rees Helen , Gray Glenda
Published: November 2018

Background

RV144 is to date the only HIV vaccine trial to demonstrate efficacy, albeit rapidly waning over time. The HVTN 702 trial is currently evaluating in South Africa a similar vaccine formulation to that of RV144 for subtype C HIV with additional boosters (pox-protein regimen). Using a detailed stochastic individualbased network model of disease transmission calibrated to the HIV epidemic, we investigate population-level impact and maximum cost of an HIV vaccine to remain cost-effective.

Methods

Consistent with the original pox-protein regimen, we model a primary series of five vaccinations meeting the goal of 50% cumulative efficacy 24 months after the first dose and include two-yearly boosters that maintain durable efficacy over 10 years. We simulate vaccination programs in South Africa starting in 2027 under various vaccine targeting and HIV treatment and prevention assumptions.

Results

Our analysis shows that this partially effective vaccine could prevent, at catchup vaccination with 60% coverage, up to 941,000 (15.6%) new infections between 2027 and 2047 assuming current trends of antiretroviral treatment. An impact of up to 697,000 (11.5%) infections prevented could be achieved by targeting age cohorts of highest incidence. Economic evaluation indicates that, if treatment scale-up was achieved, vaccination could be cost-effective at a total cost of less than $385 and $62 per 10-year series (cost-effectiveness thresholds of $5,691 and $750).

Conclusions

While a partially effective, rapidly waning vaccine could help to prevent HIV infections, it will not eliminate HIV as a public health priority in sub-Saharan Africa. Vaccination is expected to be most effective under targeted delivery to age groups of highest HIV incidence. Awaiting results of trial, the introduction of vaccination should go in parallel with continued innovation in HIV prevention, including studies to determine the costs of delivery and feasibility and further research into products with greater efficacy and durability.
Real-Time Selective Sequencing with RUBRIC: Read Until with Basecall and Reference-Informed Criteria
Authors: Edwards Harrison S. , Krishnakumar Raga , Sinha Anupama , Bird Sara W. , Patel Kamlesh D. , Bartsch Michael S.
Published: November 2018

The Oxford MinION, the first commercial nanopore sequencer, is also the first to implement molecule-by-molecule real-time selective sequencing or “Read Until”. As DNA transits a MinION nanopore, real-time pore current data can be accessed and analyzed to provide active feedback to that pore. Fragments of interest are sequenced by default, while DNA deemed non-informative is rejected by reversing the pore bias to eject the strand, providing a novel means of background depletion and/or target enrichment. In contrast to the previously published pattern-matching Read Until approach, our RUBRIC method is the first example of real-time selective sequencing where on-line basecalling enables alignment against conventional nucleic acid references to provide the basis for sequence/reject decisions. We evaluate RUBRIC performance across a range of optimizable parameters, apply it to mixed human/bacteria and CRISPR/Cas9-cut samples, and present a generalized model for estimating real-time selection performance as a function of sample composition and computing configuration.
Paradoxical changes in brain reward status during oxycodone self-administration in a novel test of the negative reinforcement hypothesis
Authors: Nguyen Jacques D. , Grant Yanabel , Taffe Michael A.
Published: November 2018

Background and Purpose

The extra-medical use of, and addiction to, prescription opioid analgesics is a growing health problem. To characterize how prescription opioid abuse develops, this study investigated the affective consequences of escalating prescription opioid use using intracranial self-stimulation (ICSS) reward and oxycodone intravenous self-administration (IVSA) models.

Experimental Approach

Male Wistar rats were given access to oxycodone IVSA (0.15 mg/kg/infusion, i.v.) in Short Access (ShA; 1 h) or Long Access (LgA; 12 h) sessions for 5 sessions/week followed by intermittent 60 h discontinuations from drug access, a novel explicit test of the negative reinforcement hypothesis. Separate groups were first trained in the ICSS procedure and then in oxycodone IVSA in 11 h LgA sessions.

Key Results

Rats given LgA to oxycodone escalated their responding more than ShA rats, with further significant increases observed following each 60 h discontinuation. Pre-session brain reward thresholds increased with sequential daily LgA IVSA sessions, consistent with a growing negative affective state consequent to successive daily intoxication/abstinence cycles. A 1 h oxycodone IVSA interval was sufficient to normalize these elevated reward thresholds, as was, paradoxically, a 60 h weekend abstinence. The increase in ICSS thresholds was attenuated in a group treated with the long-acting kappa opioid antagonist norBNI prior to IVSA training.

Conclusions and Implications

Changes in brain reward function during escalation of oxycodone self-administration are driven by an interplay between kappa opioid receptor-mediated negative affective state associated with escalated oxycodone intake and dynamic restoration of brain reward status during longer periods of abstinence.
Low-cost, sub-micron resolution, wide-field computational microscopy using opensource hardware
Authors: Aidukas Tomas , Eckert Regina , Harvey Andrew R. , Waller Laura , Konda Pavan C.
Published: November 2018

The revolution in low-cost consumer photography and computation provides fertile opportunity for a disruptive reduction in the cost of biomedical imaging. Conventional approaches to low-cost microscopy are fundamentally restricted, however, to modest field of view (FOV) and/or resolution. We report a low-cost microscopy technique, implemented with a Raspberry Pi single-board computer and color camera combined with Fourier ptychography (FP), to computationally construct 25-megapixel images with sub-micron resolution. New image-construction techniques were developed to enable the use of the low-cost Bayer color sensor, to compensate for the highly aberrated re-used camera lens and to compensate for misalignments associated with the 3D-printed microscope structure. This high ratio of performance to cost is of particular interest to high-throughput microscopy applications, ranging from drug discovery and digital pathology to health screening in low-income countries. 3D models and assembly instructions of our microscope are made available for open source use.
Tfap2a is a novel gatekeeper of differentiation in renal progenitors during kidney development
Authors: Chambers Brooke E. , Gerlach Gary F. , Chen Karen H. , Clark Eleanor G. , Leshchiner Ignaty , Goessling Wolfram , Wingert Rebecca A.
Published: November 2018

Renal functional units known as nephrons undergo patterning events during development that create a segmental array of cellular populations with discrete physiological tasks. Knowledge about the terminal differentiation programs of each nephron segment has central importance for understanding kidney disease and to advance regenerative medicine, as mammalian nephrons grown in organoid cultures from pluripotent cells fail to terminally differentiate. Here, from a novel forward genetic screen using zebrafish we report the discovery thattranscription factor AP-2 alpha(tfap2a)coordinates a gene regulatory network that controls the progression of nephron distal segment progenitors into the differentiated state. Overexpression oftfap2arescued differentiation in mutants and caused ectopic expression of distal segment markers in wild-type nephrons, indicatingtfap2ais sufficient to instigate the distal segment differentiation program.tfap2a/2bdeficiency exacerbated distal nephron segment differentiation defects, revealing functional redundancy wheretfap2ahas a dominant role upstream of its family member. With further genetic studies, we assembled a blueprint of thetfap2agene regulatory network during nephrogenesis. We demonstrate thattfap2aacts downstream ofIroquois homeobox 3b, a conserved distal lineage transcription factor.tfap2acontrols a circuit consisting ofirx1a, tfap2b,and genes encoding solute transporters that dictate the specialized metabolic functions of the distal nephron segments, and we show for the first time that this regulatory node is distinct from the pathway circuits controlling aspects such as apical-basal polarity and ciliogenesis during the differentiation process. Thus, our studies reveal new insights into the genetic control of differentiation, wheretfap2aregulates the suite of segment transporter traits. These findings have relevance for understanding renal birth defects, as well as efforts to recapitulate nephrogenesisin vivoto make functional units that can facilitate organoid applications such as drug discovery and regenerative therapies.

Summary Statement

Here, we report for the first time thattranscription factor AP-2 alpha(tfap2a) controls the progression from nephron progenitor into the fully differentiated state. This fundamentally deepens our knowledge about the genetic control of kidney development.
Mechanical Interactions between a Cell and an Extracellular Environment Facilitate Durotactic Cell Migration
Authors: Hassan Abdel-Rahman , Biel Thomas , Kim Taeyoon
Published: November 2018

Cell migration is a fundamental process in biological systems, playing an important role for diverse physiological processes. Cells often exhibit directed migration in a specific direction in response to various types of cues. In particular, cells are able to sense the rigidity of surrounding environments and then migrate towards stiffer regions. To understand this mechanosensitive behavior called durotaxis, several computational models have been developed. However, most of the models made phenomenological assumptions to recapitulate durotactic behaviors, significantly limiting insights provided from these studies. In this study, we developed a computational biomechanical model without any phenomenological assumption to illuminate intrinsic mechanisms of durotactic behaviors of cells migrating on a two-dimensional substrate. The model consists of a simplified cell generating contractile forces and a deformable substrate coarse-grained into an irregular triangulated mesh. Using the model, we demonstrated that durotactic behaviors emerge from purely mechanical interactions between the cell and the underlying substrate. We investigated how durotactic migration is regulated by biophysical properties of the substrate, including elasticity, viscosity, and stiffness profile.
Characterization of Pacific oyster (Crassostrea gigas) proteomic response to natural environmental differences
Authors: Venkataraman Yaamini R. , Timmins-Schiffman Emma , Horwith Micah J. , Lowe Alexander T. , Nunn Brook , Vadopalas Brent , Spencer Laura H. , Roberts Steven B.
Published: November 2018

Global climate change is rapidly altering coastal marine ecosystems important for food production. A comprehensive understanding of how organisms will respond to these complex environmental changes can come only from observing and studying species within their natural environment. To this end, the effects of environmental drivers — pH, dissolved oxygen content, salinity, and temperature — on Pacific oyster (Crassostrea gigas) physiology were evaluated in an outplant experiment. Sibling juvenile oysters were outplanted to eelgrass and unvegetated habitat at five different estuarine sites within the Acidification Nearshore Monitoring Network in Washington State, USA to evaluate how regional environmental drivers influence molecular physiology. Within each site, we also determined if eelgrass presence that buffered pH conditions changed the oysters’ expressed proteome. A novel, two-step, gel-free proteomic approach was used to identify differences in protein abundance in C. gigas ctenidia tissue after a 29 day outplant by 1) identifying proteins in a data independent acquisition survey step and 2) comparing relative quantities of targeted environmental response proteins using selected reaction monitoring. While there was no difference in protein abundance detected between habitats or among sites within Puget Sound, C. gigas outplanted at Willapa Bay had significantly higher abundances of antioxidant enzymes and molecular chaperones. Environmental factors at Willapa Bay, such as higher average temperature, may have driven this protein abundance pattern. These findings generate a suite of new hypotheses for lab and field experiments to compare the effects of regional conditions on physiological responses of marine invertebrates.
Calcium imaging in freely-moving mice during electrical stimulation of deep brain structures
Authors: Trevathan J. K. , Asp A. J. , Nicolai E. N. , Trevathan J. M. , Kremer N.A. , Kozai T.D. , Cheng D. , Schachter M. , Nassi J. J. , Otte S. L. , Parker J. G. , Lujan J. L. , Ludwig K. A.
Published: November 2018

After decades of study in humans and animal models, there remains a lack of consensus regarding how the action of electrical stimulation on neuronal and non-neuronal elements – e.g. neuropil, cell bodies, glial cells, etc. – leads to the therapeutic effects of neuromodulation therapies. To further our understanding of neuromodulation therapies, there is a critical need for novel methodological approaches using state-of-the-art neuroscience tools to study neuromodulation therapy in preclinical models of disease. In this manuscript we outline one such approach combining chronic behaving single-photon microendoscope recordings in a pathological mouse model with electrical stimulation of a common deep brain stimulation (DBS) target. We describe in detail the steps necessary to realize this approach, as well as discuss key considerations for extending this experimental paradigm to other DBS targets for different therapeutic indications. Additionally, we make recommendations from our experience on implementing and validating the required combination of procedures that includes: the induction of a pathological model (6-OHDA model of Parkinson’s disease) through an injection procedure, the injection of the viral vector to induce GCaMP expression, the implantation of the GRIN lens and stimulation electrode, and the installation of a baseplate for mounting the microendoscope. We proactively identify unique data analysis confounds occurring due to the combination of electrical stimulation and optical recordings and outline an approach to address these confounds. In order to validate the technical feasibility of this unique combination of experimental methods, we present data to demonstrate that 1) despite the complex multifaceted surgical procedures, chronic optical recordings of hundreds of cells combined with stimulation is achievable over week long periods 2) this approach enables measurement of differences in DBS evoked neural activity between anesthetized and awake conditions and 3) this combination of techniques can be used to measure electrical stimulation induced changes in neural activity during behavior in a pathological mouse model. These findings are presented to underscore the feasibility and potential utility of minimally constrained optical recordings to elucidate the mechanisms of DBS therapies in animal models of disease.
Cantharidin alters GPI-anchored protein sorting by targeting Cdc1 mediated remodeling in Endoplasmic Reticulum
Authors: Kumar Sahu Pushpendra , Singh Tomar Raghuvir
Published: November 2018

Cantharidin (CTD) is a potent anticancer small molecule produced by several species of blister beetle. It has been a traditional medicine for the treatment of warts and tumors for many decades. CTD suppresses the tumor growth by inducing apoptosis, cell cycle arrest, and DNA damage. It is a known inhibitor of PP2A and PP1. In this study, we identified new molecular targets of CTD usingSaccharomyces cerevisiaeas a model organism which expresses a Cantharidin Resistance Gene (CRG1).CRG1encodes a SAM-dependent methyltransferase that inactivates CTD by methylation. CTD alters lipid homeostasis, cell wall integrity, endocytosis, adhesion, and invasion in yeast cells. We found that CTD specifically affects the phosphatidylethanolamine (PE) associated functions which can be rescued by supplementation of ethanolamine (ETA) in the growth media. CTD also perturbed ER homeostasis and cell wall integrity by altering the GPI-anchored protein sorting. The CTD dependent genetic interaction profile ofCRG1revealed that Cdc1 activity in GPI-anchor remodeling is the key target of CTD, which we found to be independent of PP2A and PP1. Furthermore, our experiments with human cells suggest that CTD functions through a conserved mechanism in higher eukaryotes as well. Altogether, we conclude that CTD induces cytotoxicity by targeting Cdc1 activity in GPI-anchor remodeling in the endoplasmic reticulum (ER).
Combined neural tuning in human ventral temporal cortex resolves the perceptual ambiguity of morphed 2-D images
Authors: Rosenke Mona , Davidenko Nicolas , Grill-Spector Kalanit , Weiner Kevin S.
Published: November 2018

We have an amazing ability to categorize objects in the world around us. Nevertheless, how cortical regions in human ventral temporal cortex (VTC), which is critical for categorization, support this behavioral ability, is largely unknown. Here, we examined the relationship between neural responses and behavioral performance during the categorization of morphed silhouettes of faces and hands, which are animate categories processed in cortically adjacent regions in VTC. Our results reveal that the combination of neural responses from VTC face- and body-selective regions more accurately explains behavioral categorization than neural responses from either region alone. Furthermore, we built a model that predicts a person’s behavioral performance using estimated parameters of brain-behavioral relationships from a different group of people. We further show that this brain-behavioral model generalizes to adjacent face- and body-selective regions in lateral occipito-temporal cortex. Thus, while face- and body-selective regions are located within functionally-distinct domain-specific networks, cortically adjacent regions from both networks likely integrate neural responses to resolve competing and perceptually ambiguous information from both categories.
Palliative care for people living with HIV/AIDS: Factors influencing healthcare workers’ knowledge, attitude and practice in public health facilities, Abuja, Nigeria
Authors: Ajisegiri Whenayon Simeon , Abubakar Aisha A. , Gobir Abdulrazaq A. , Balogun Muhammad S. , Sabitu Kabiru
Published: November 2018

Physicians, nurses and allied health staff play very vital roles in addressing palliative care (PC) needs of people living with HIV/AIDS (PLWHA). The healthcare professionals’ experiences determine the success of palliative care delivery. There is paucity of data on palliative care for PLWHA. For this reason, we assessed the knowledge, attitude and practice of palliative care for PLWHA and associated factors among health care professionals.

We conducted a cross-sectional descriptive study among healthcare workers (HCWs) in public health facilities in the Federal Capital Territory, Nigeria between February and May, 2017. Multistage sampling technique with proportionate-to-size allocation was used to determine facility sample size and HCWs per professional discipline. Data were collected with questionnaires adapted from Palliative Care Quiz for Nursing, Frommelt Attitude toward Care of the Dying and practical questions adapted from PC standard guidelines. Univariate analysis was done to compute frequencies and proportions. Odd’s ratios were calculated to assess the statistical association between variables and P-value ≤ 0.05 was considered significant. Multivariate analysis was conducted on variables that were significant with bivariate analysis. Epi-Info software was used for statistical analyses.

The mean age of the 348 participants was 37.5 years (SD: ±8.9) and 201 (57.8%) were female. Thirty-six (10.3%) participants had good knowledge, 344 (98.9%) had favourable attitude and 90 (25.9%) had good practice of PC for PLWHA. Major determinants of good knowledge of PC include being a doctor (aOR = 2.70; 95%CI: 1.28 - 5.56). Determinants of good practice of palliative care include possessing a minimum of a bachelor degree (aOR=2.30; 95%CI : 1.05-5.08) and practicing in a tertiary hospital (aOR=6.67; 95%CI : 3.57-12.5).

HCWs had favourable attitude towards PC for PLWHA despite an overall poor knowledge and practice. We recommended quality in-service training and continuous education on palliative care for HCWs.
Applying non-parametric testing to discrete transfer entropy
Authors: Olin-Ammentorp Wilkie , Cady Nathaniel
Published: November 2018

Transfer entropy (TE) is a powerful algorithm which attempts to detect the transfer of information from one system to another. In neuroscience, it has the potential to track the movement of information through complex neuronal systems, and provide powerful insights into their organization and operation. One such application is the ability to infer the existence of causal connectivity (such as synaptic pathways) between neurons in a culture being recorded by micro-electrode array (MEA).

There are several challenges, however, in applying TE to neurological data; one of these is the ability to robustly classify what experimental TE value qualifies as significant. We find that common methods in spike train analysis such as a Z-test cannot be applied, as their assumptions are not met. Instead, we utilize surrogate data to compute a sample under the null hypothesis (no causal connection), and resample experimental data through Markov chain Monte Carlo (MCMC) methods to create a sample of TE values under experimental conditions. A standard non-parametric test (Mann-Whitney U-test) is then applied to compare these samples, and determine if they represent a significant connection.

We have applied this methodology to MEA recordings of neuronal cultures developing over a period of roughly a month, and find that it provides a wealth of information regarding the cultures' maturity. This includes features such as the directed graph of causal connections across the MEA and identification of information exchange centers. These results are consistent and carry a well-defined significance level.
Grouping effects in numerosity perception under prolonged viewing conditions
Authors: Poom Leo , Lindskog Marcus , Winman Anders , van den Berg Ronald
Published: November 2018

Humans can estimate numerosities – such as the number sheep in a flock – without deliberate counting. A number of biases have been identified in these estimates, which seem primarily rooted in the spatial organization of objects (grouping, symmetry, etc). Most previous studies on the number sense used static stimuli with extremely brief exposure times. However, outside the laboratory, visual scenes are often dynamic and freely viewed for prolonged durations (e.g., a flock of moving sheep). The purpose of the present study is to examine grouping-induced numerosity biases in stimuli that more closely mimic these conditions. To this end, we designed two experiments with limited-dot-lifetime displays (LDDs), in which each dot is visible for a brief period of time and replaced by a new dot elsewhere after its disappearance. The dynamic nature of LDDs prevents subjects from counting even when they are free-viewing a stimulus under prolonged presentation. Subjects estimated the number of dots in arrays that were presented either as a single group or were segregated into two groups by spatial clustering, dot size, dot color, or dot motion. Grouping by color and motion reduced perceived numerosity compared to viewing them as a single group. Moreover, the grouping effect sizes between these two features were correlated, which suggests that the effects may share a common, feature-invariant mechanism. Finally, we find that dot size and total stimulus area directly affect perceived numerosity, which makes it difficult to draw reliable conclusions about grouping effects induced by spatial clustering and dot size. Our results provide new insights into biases in numerosity estimation and they demonstrate that the use of LDDs is an effective method to study the human number sense under prolonged viewing.
Distinct vascular genomic response of proton and gamma radiation
Authors: Emanuela Ricciotti , Sarantopoulou Dimitra , Grant Gregory R. , Sanzari Jenine K. , Krigsfeld Gabriel S. , Kiliti Amber J. , Kennedy Ann R. , Grosser Tilo
Published: November 2018

Purpose. The cardiovascular biology of proton radiotherapy is not well understood. We aimed to compare the genomic dose-response to proton and gamma radiation of the mouse aorta to assess whether their vascular effects may diverge.

Materials and methods.We performed comparative RNA sequencing of the aorta following (4 hrs) total-body proton and gamma irradiation (0.5 - 200 cGy whole body dose, 10 dose levels) of conscious mice. A trend analysis identified genes that showed a dose response.

Results.While fewer genes were dose-responsive to proton than gamma radiation (29 vs. 194 genes;q-value ≤ 0.1), the magnitude of the effect was greater. Highly responsive genes were enriched for radiation response pathways (DNA damage, apoptosis, cellular stress and inflammation;p-value ≤ 0.01). Gamma, but not proton radiation induced additionally genes in vasculature specific pathways. Genes responsive to both radiation types showed almost perfectly superimposable dose-response relationships.

Conclusions.Despite the activation of canonical radiation response pathways by both radiation types, we detected marked differences in the genomic response of the murine aorta. Models of cardiovascular risk based on photon radiation may not accurately predict the risk associated with proton radiation.
Using a continuum model to decipher the mechanics of embryonic tissue spreading from time-lapse image sequences: An approximate Bayesian computation approach
Authors: Stepien Tracy L. , Lynch Holley E. , Yancey Shirley X. , Dempsey Laura , Davidson Lance A.
Published: November 2018

Advanced imaging techniques generate large datasets capable of describing the structure and kinematics of tissue spreading in embryonic development, wound healing, and the progression of many diseases. These datasets can be integrated with mathematical models to infer biomechanical properties of the system, typically identifying an optimal set of parameters for an individual experiment. However, these methods offer little information on the robustness of the fit and are generally ill-suited for statistical tests of multiple experiments. To overcome this limitation and enable efficient use of large datasets in a rigorous experimental design, we use the approximate Bayesian computation rejection algorithm to construct probability density distributions that estimate model parameters for a defined theoretical model and set of experimental data. Here, we demonstrate this method with a 2D Eulerian continuum mechanical model of spreading embryonic tissue. The model is tightly integrated with quantitative image analysis of different sized embryonic tissue explants spreading on extracellular matrix (ECM) and is regulated by a small set of parameters including forces on the free edge, tissue stiffness, strength of cell-ECM adhesions, and active cell shape changes. We find statistically significant trends in key parameters that vary with initial size of the explant, e.g., for larger explants cell-ECM adhesion forces are weaker and free edge forces are stronger. Furthermore, we demonstrate that estimated parameters for one explant can be used to predict the behavior of other similarly sized explants. These predictive methods can be used to guide further experiments to better understand how collective cell migration is regulated during development.

Author Summary

New imaging tools and automated microscopes are able to produce terabytes of detailed images of protein activity and cell movements as tissues change shape and grow. Yet, efforts to infer useful quantitative information from these large datasets have been limited by the inability to integrate image analysis and computational models with rigorous statistical methods. In this paper, we describe a robust methodology for inferring mechanical processes that drive tissue spreading in embryonic development. Tissue spreading is critical during wound healing and the progression of many diseases including cancer. Direct measurement of biomechanical properties during spreading is not possible in many cases, but can be inferred through mathematical and statistical means. This approach identifies model parameters that are able to robustly predict results of new experiments. These methods can be integrated with more general studies of morphogenesis and to guide further experiments to better understand how tissue spreading is regulated during development and potentially control spreading during wound healing and cancer.
Achieving supply chain excellence through supplier management
Authors: Salam Mohammad Asif , Khan Sami A.
Published: November 2018

Purpose

The purpose of this paper is to develop a supplier selection and management program to improve overall supplier performance.

Design/methodology/approach

Supplier performance is measured in terms of quality and delivery within a fast moving consumer goods (FMCG) business of a multinational company based in Thailand using a case study methodology. The quality and delivery related data were collected from daily deliveries at the manufacturing plant both before and after implementing the supplier management program.

Findings

Findings of the study suggest that the selection of suppliers based on their performance is important for manufacturing firms. Moreover, the supplier selection and management program can contribute effectively to improving suppliers’ performance.

Research limitations/implications

This case study has been conducted based on a single company within the FMCG industry. Hence, it limits the generalizability of the findings across industries.

Practical implications

The study provides a real-life tool for practitioners to learn about the importance of strategic decision-making process pertaining to the supplier selection and management program.

Social implications

This study demonstrates that through a transparent supplier evaluation process, the firms can develop trust and long-term relationship with their suppliers for pursuing the goals of product development and innovation.

Originality/value

Implementing a supplier management system is a critical step in enhancing an organization’s overall competitiveness. To develop an effective supplier management system firms must have objective measures and share those with their suppliers. Developing metrics for suppliers’ evaluation is the key to achieving continuous improvement as evidenced in this case.
Purchasing and supply management skills revisited: an extensive literature review
Authors: Karttunen Elina
Published: November 2018

Purpose

Research on purchasing managers and their skills requirements supports the training and education of purchasing professionals. This paper offers an in-depth analytical review of the purchasing skills reported in the supply chain management (SCM) literature. The purpose of this paper is to highlight the most important skills and factors that influence these skills.

Design/methodology/approach

This paper employs a systematic literature review methodology. Two databases, Scopus and Web of Science, are searched for relevant articles. The selected journal articles are used as sources to obtain a view not only on the relevant purchasing and supply management (P/SM) skills, but also on factors that emphasize certain P/SM skills. This paper also summarizes the ten skills ranked as most important (often described as the “top ten”) among the sample articles.

Findings

The paper highlights the essential skills for purchasing professionals, verified both by their frequent appearances in rankings and by citation frequency in the literature. Generic managerial skills, such as communication, cost analysis, teamwork, problem-solving, negotiation, influencing, and persuasion, as well as information technology skills, received the most attention in the literature and rankings of the “top ten” P/SM skills. This paper provides a refined categorization of purchasing skills, which have merged recently with other discussed skills, such as political and entrepreneurial ones, into this categorization. This paper identifies factors that affect purchasing managers’ skills requirements.

Originality/value

This paper presents a structured overview of 57 peer-reviewed articles from high-quality journals about purchasing skills. The review contributes to the purchasing skills literature by showing the most relevant skills and the factors that influence skills requirements. These factors also provide arenas for further research related to purchasing skills.
Strategic human resource practices for innovation performance
Authors: Singh Noopur
Published: November 2018

Purpose

The purpose of this paper is to understand the conception of strategic human resource practices (SHRPs) for establishing innovation performance (IP) in the tourist hotel industry. In this research, the author has also studied the influence of knowledge management capacity (KMC) as a mediator between the two and the role of environmental uncertainty (EU) in moderating the relation between SHRP and KMC.

Design/methodology/approach

Data were collected through survey method from the employees and managers of the tourist hotels in Jharkhand, India. Furthermore, 368 customer contact employees and 46 managers’ responses were analyzed using confirmatory factor analysis and SPSS macro named PROCESS.

Findings

The interpretation of the empirical results signifies SHRP influence on IP and KMC as a mediator between SHRP and IP. Additionally, the role of EU in positively mitigating the interaction between SHRP and KMC was seen.

Originality/value

The present research work adds to the subsisting literature by empirically fortifying the proposed hypotheses. Additionally, current studies focused on hospitality and tourism industry operating in a developed economy, the present study is an attempt to explore a comprehensive and theoretically grounded relationship between SHRP, KMC and IP with the help of resource-based view in an emerging economy.
Efficient courts? A frontier performance assessment
Authors: Ferro Gustavo , Romero Carlos A. , Romero-Gómez Exequiel
Published: November 2018

Purpose

The purpose of this paper is to build performance indicators to assess efficiency for First Instance Federal Courts in Argentina and study the determinants of efficiency in Criminal Instruction Courts.

Design/methodology/approach

The efficiency scores were determined using data envelopment analysis with a database for the period 2006–2010. Then, a search of the efficiency determinants in the Criminal Instruction Courts was performed. Four output-oriented models were developed based on various explanatory and environmental variables.

Findings

Workload is an environmental variable that significantly increased the average levels of efficiency. When analyzing explanatory factors of the efficiency levels of the Criminal Instruction Courts, surrogate judges and temporary staff are more efficient on average than tenured judges and staff.

Research limitations/implications

The method chosen permits flexibility in the analysis. Future research would be interesting to develop the underlying economic model using econometric methods.

Practical implications

This paper’s contribution is twofold: first, to estimate the relative efficiency for all First Instance Federal Courts in every jurisdiction; and second, to explain the differences in efficiency in the Criminal Instruction Courts.

Social implications

This study has the potential to greatly impact the discussion of how to structure judicial procedures (from the benchmarking between different branches of Federal justice) and in the design of incentives in a judicial career (e.g. tenured vs temporary judges and clerical employees, the role of seniority of judges and clerical employees and the impact of gender in performance).

Originality/value

To the authors’ knowledge, this paper is the first scholarly article to measure efficiency in Argentine justice system using mathematical programming and econometric methods. It has academic interest since it advances on the comprehension of the underlying production function of justice service provision. The paper also has social and practical implications since it permits contributing to the institutional design and opens the discussion for further sequels with other methods and complementary purposes.