bluuebunny/crossref_metadata_2025 huggingface dataset:
Triangulating Intrusion in Privacy Law
Authors: Bennett Thomas D C
Published: June 2019

This article concerns two interrelated, persistent problems for privacy law. The first is the failure of academic scholarship to get adequately to grips with the meaning of privacy. The second is the apparent inability of the English judiciary to resolve the common law lacuna in respect of intrusion-type privacy violations. The two problems are related in that the former is a significant contributor to the latter. Mainstream scholarship has long insisted on pursuing the One True Meaning of privacy, thereby overlooking valid alternative conceptualisations and creating a melange of theories that provides little assistance to judges. However, by adopting a novel, triangulation-based approach to understanding privacy of the sort proposed herein, it is possible to locate points of consensus between these rival theories in respect of particular privacy-violating activities. This consensus can provide the certainty common law judges require for the elaboration of further doctrine in this field.
Unique Far-Lateral Closure Technique: Technical Note
Authors: Scoville Jonathan Perry , Mazur Marcus D , Couldwell William T
Published: June 2019

BACKGROUND

The far-lateral approach is a mainstay in gaining access to the ventrolateral craniocervical junction for tumor removal and the treatment of vascular lesions. It has a reportedly high rate of cerebrospinal fluid leak (up to 20%), which can bring devastating consequences, including meningitis, and may require wound revision associated with a longer hospital stay.

OBJECTIVE

To describe a closure technique employed to close the access corridor provided by the far-lateral approach and present an illustrative case.

METHODS

The far-lateral closure technique employs dural closure, followed by fat buttress, to alleviate dead space and reduce the likelihood of fluid collection and leakage.

RESULTS

This technique has been successfully used by the senior author for more than 14 yr, with a rate of cerebrospinal fluid leak of 2.9%.

CONCLUSION

This unique approach and closure of the far-lateral craniotomy is a reasonable option for the approach to the ventrolateral craniocervical junction. Skull base surgeons can consider the use of this closure technique to ensure watertight closure.
“Reverse Picket Fence” Technique for Clipping of a Large, Anterior Communicating Artery Aneurysm: 2-Dimensional Operative Video
Authors: Mascitelli Justin , Gandhi Sirin , Cavallo Claudio , Hardesty Douglas A , Lawton Michael T
Published: June 2019

The “picket fence” technique is a clipping technique used for large, wide-neck complex aneurysms not suitable for conventional clipping.
1
With this technique, simple or fenestrated straight clips are stacked side-by-side perpendicular to the neck rather than the conventional parallel placement. In complex aneurysms projecting away from the surgeon, the picket fence technique is impossible. Instead, fenestrated clips are applied in a reverse direction from neck-to-dome, using the blade heels to close the neck. This fenestration tube transmits the bifurcation. This video demonstrates a “reverse picket fence” clipping technique of an incidental, large anterior communicating artery (ACoA) aneurysm in a 52-yr-old woman. Bilaterally adherent A2-anterior cerebral artery (ACA) segments led to abortion of a prior clipping attempt at an outside hospital. After obtaining patient consent, a modified orbitozygomatic craniotomy was performed with gyrus rectus removal. Temporary clips were applied to A1-ACA for freeing the adherent A2-ACA segments from the dome. The aneurysm was clipped using a “reverse picket fence” technique transmitting the A1-A2-A2 bifurcation through the fenestration tube. Bilateral recurrent artery of Heubner was preserved. Indocyanine angiography demonstrated parent vessel patency with complete aneurysm exclusion. Postoperatively, the patient experienced short-term memory loss, which resolved over 6 mo with cognitive rehabilitation. The “reverse picket fence” technique can be considered for large aneurysms directed away from the surgeon, obviating the need for difficult dissection of adherent efferent arteries from aneurysmal sac. Adjusting the heel position of each fenestrated clip in this construct allows the patency of hidden perforators behind the aneurysm to be maintained. Video © Barrow Neurological Institute. Used with permission.
Genetics of psoriasis: a basis for precision medicine
Authors: Ran Delin , Cai Minglong , Zhang Xuejun
Published: June 2019

Psoriasis is an inflammatory skin disease with a background of polygenic inheritance. Both environmental and genetic factors are involved in the etiology of the disease. In the last two decades, numerous studies have been conducted through linkage analysis, genome-wide association study (GWAS), and direct sequencing to explore the role of genetic variation in disease pathogenesis and progression. To date, >80 psoriasis susceptibility genes have been identified, including HLA-Cw6, IL12B, IL23R, and LCE3B/3C. Some genetic markers have been applied in disease prediction, clinical diagnosis, treatment, and new drug development, which could further explain the pathogenesis of psoriasis and promote the development of precision medicine. This review summarizes related research on genetic variation in psoriasis and explores implications of the findings in clinical application and the promotion of a personalized medicine project.
Interplay between Plant Cell Walls and Jasmonate Production
Authors: Mielke Stefan , Gasperini Debora
Published: June 2019

Plant cell walls are sophisticated carbohydrate-rich structures representing the immediate contact surface with the extracellular environment, often serving as the first barrier against biotic and abiotic stresses. Notably, a variety of perturbations in plant cell walls result in upregulated jasmonate (JA) production, a phytohormone with essential roles in defense and growth responses. Hence, cell wall-derived signals can initiate intracellular JA-mediated responses and the elucidation of the underlying signaling pathways could provide novel insights into cell wall maintenance and remodeling, as well as advance our understanding on how is JA biosynthesis initiated. This Mini Review will describe current knowledge about cell wall-derived damage signals and their effects on JA biosynthesis, as well as provide future perspectives.
Regulation of Flowering Time by the RNA-Binding Proteins AtGRP7 and AtGRP8
Authors: Steffen Alexander , Elgner Mareike , Staiger Dorothee
Published: June 2019

The timing of floral initiation is a tightly controlled process in plants. The circadian clock regulated glycine-rich RNA-binding protein (RBP) AtGRP7, a known regulator of splicing, was previously shown to regulate flowering time mainly by affecting the MADS-box repressor FLOWERING LOCUS C (FLC). Loss of AtGRP7 leads to elevated FLC expression and late flowering in the atgrp7-1 mutant. Here, we analyze genetic interactions of AtGRP7 with key regulators of the autonomous and the thermosensory pathway of floral induction. RNA interference- mediated reduction of the level of the paralogous AtGRP8 in atgrp7-1 further delays floral transition compared of with atgrp7-1. AtGRP7 acts in parallel to FCA, FPA and FLK in the branch of the autonomous pathway (AP) comprised of RBPs. It acts in the same branch as FLOWERING LOCUS D, and AtGRP7 loss-of-function mutants show elevated levels of dimethylated lysine 4 of histone H3, a mark for active transcription. In addition to its role in the AP, AtGRP7 acts in the thermosensory pathway of flowering time control by regulating alternative splicing of the floral repressor FLOWERING LOCUS M (FLM). Overexpression of AtGRP7 selectively favors the formation of the repressive isoform FLM-β. Our results suggest that the RBPs AtGRP7 and AtGRP8 influence MADS-Box transcription factors in at least two different pathways of flowering time control. This highlights the importance of RBPs to fine-tune the integration of varying cues into flowering time control and further strengthens the view that the different pathways, although genetically separable, constitute a tightly interwoven network to ensure plant reproductive success under changing environmental conditions.
Uniform Pricing in U.S. Retail Chains*
Authors: DellaVigna Stefano , Gentzkow Matthew
Published: June 2019

We show that most U.S. food, drugstore, and mass-merchandise chains charge nearly uniform prices across stores, despite wide variation in consumer demographics and competition. Demand estimates reveal substantial within-chain variation in price elasticities and suggest that the median chain sacrifices ${\$}$16 million of annual profit relative to a benchmark of optimal prices. In contrast, differences in average prices between chains are broadly consistent with the optimal benchmark. We discuss a range of explanations for nearly uniform pricing, highlighting managerial inertia and brand image concerns as mechanisms frequently mentioned by industry participants. Relative to our optimal benchmark, uniform pricing may significantly increase the prices paid by poorer households relative to the rich, dampen the response of prices to local economic shocks, alter the analysis of mergers in antitrust, and shift the incidence of intranational trade costs.
Immunosuppressive B cells expressing PD-1/PD-L1 in solid tumors: a mini review
Authors: Sun X. , Zhang T. , Li M. , Yin L. , Xue J.
Published: June 2019

Expression of programmed cell death-1 (PD-1/CD279) on T cells and the ligand of PD-1, programmed death ligand-1 (PD-L1) (CD274/B7-H1) on tumor cells or other immune cells, such as myeloid-derived suppressor cells, are important mechanisms to induce malignant immunosuppression. PD-1/PD-L1 expression on B-cell subsets, as well as their signaling and inhibitory functions in solid tumors will be discussed in this review with the focus on how B cells expressing PD-1/PD-L1 play immunosuppressive roles in tumor progression, aiming to figure out the potential for development of diagnostic tools and new therapies involving this unique group of cells.
IN-SITU GAMMA-RAY SPECTROMETRY FOR RADIOACTIVITY ANALYSIS OF SOIL USING NaI(Tl) AND LaBr3(Ce) DETECTORS
Authors: Lee Jun-Ho , Byun Jong-In
Published: June 2019

In this study, the full energy peak count rates to radioactivity conversion factors of 3″Ø × 3″ NaI(Tl) and 2″Ø × 2″ LaBr3(Ce) detectors for radioactivity analysis in the soil were determined on site using a semi-empirical method with point-like gamma-ray sources. To validate the conversion factors derived for the detectors, in-situ gamma-ray measurements were performed in wide open fields with almost flat surface and compared with the sampling analysis for the radioactivity of U-series, Th-series, and 40K in the soil. As a result, radioactivity concentrations of 40K, 208Tl and 214Bi by in-situ and laboratory measurements agreed well with each other within 5%, and the MDAs for artificial radionuclides were estimated under the condition of fresh deposition considering a radiation emergency situation.
Factors predicting the severity of dengue in patients with warning signs in Rio de Janeiro, Brazil (1986–2012)
Authors: Gonçalves Bianca De Santis , Nogueira Rita Maria Ribeiro , Bispo de Filippis Ana Maria , Horta Marco Aurélio Pereira
Published: June 2019

Background

Since 1981, >12 million cases of dengue have been reported in Brazil. Early prediction of severe dengue with no warning signs is crucial to avoid progression to severe dengue. Here we aimed to identify early markers of dengue severity and characterize dengue infection in patients in Rio de Janeiro.

Methods

We evaluated early severity markers, serotypes, infection status, number of days of illness and viral loads associated with dengue fever in patients from Rio de Janeiro, Brazil through an observational retrospective study (1986–2012). We compared dengue without warning signs and dengue with warning signs/severe dengue (DWWS/SD). Infection status was classified by enzyme-linked immunosorbent assay and viraemia was quantified by quantitative real-time reverse transcription polymerase chain reaction.

Results

The presence of DWWS/ SD was significantly associated with younger age; patients 13–19 y of age had a significantly greater chance of presenting warning signs. Dengue virus type 3 (DENV3) was more likely to induce DWWS/SD, which was more frequent on days 4–5 of illness.

Conclusions

DENV3, 4–5 d of illness and 13–19 y of age were early biomarkers of dengue severity. To our knowledge, this was the first study to analyse the characteristics of dengue severity in the state of Rio de Janeiro over 27 y of epidemics since the introduction of DENV.
Evidence-based practice and patient-centered care: Doing both well
Authors: Engle Ryann L. , Mohr David C. , Holmes Sally K. , Seibert Marjorie Nealon , Afable Melissa , Leyson Jenniffer , Meterko Mark
Published: June 2019

Background

Health care organizations increasingly strive to deliver care that is both evidence based and patient centered. Although often complementary, fundamental contradictions may exist between these goals, and the organizational culture and infrastructure necessary to be successful in one domain may inherently diminish performance in the other.

Purpose

We assessed the relationship between evidence-based practice (EBP) and patient-centered care (PCC) by seeking to identify specific behavioral and process mechanisms, along with organizational characteristics that distinguish medical centers that are able to provide inpatient care that is both evidence based and patient centered from those where performance is either mixed or low in both domains.

Methodology/Approach

We analyzed interview data from 142 employees at 12 Veterans Affairs Medical Centers selected based on EBP and PCC performance (high, low, or mixed) using a priori constructs consistent with organizational literature, as well as emergent themes.

Results

We confirmed that tensions may arise when attempting to deliver both EBP and PCC and found unique characteristics of organizations that do both well. High-performing sites exhibited organizational cultures of empowerment where both EBP and PCC expectations were emphasized; provided formal and informal institutional supports and structures with regard to PCC and EBP; and fostered multidisciplinary, multidirectional approaches to care and communication that facilitated delivery of both EBP and PCC.

Conclusions and Practice Implications

Organizations that excel in providing both EBP and PCC exhibit unique characteristics and processes. Recognizing that some characteristics such as culture are difficult to change, these findings nonetheless highlight areas that could be enhanced by medical centers striving to deliver care that is both evidence based and patient centered.
Long-term Results of Trabeculectomy With Mitomycin-C in Patients With Bilateral Acute Iris Transillumination
Authors: Bayraktar Serife , Oray Merih , Altan Cigdem , Basarir Berna , Izgi Belgin , Tugal-Tutkun Ilknur
Published: June 2019

Précis:

The present study suggests that immediate trabeculectomy with mitomycin C (MMC) may be performed as a safe and effective intervention in the management of refractory ocular hypertension (OHT)/glaucoma in patients with bilateral acute iris transillumination (BAIT).

Purpose:

To report the long-term results of trabeculectomy with MMC in the management of OHT/glaucoma in patients with BAIT.

Materials and Methods:

In total, 9 eyes of 6 patients with BAIT who underwent trabeculectomy with MMC between 2007 and 2015 were reviewed. Main outcome measures were control of intraocular pressure (IOP), the number of antiglaucomatous medications required to achieve the desired IOP, and complications.

Results:

The postoperative follow-up time ranged between 2 and 9.5 years. IOP at presentation was >21 mm Hg in all patients. Maximum IOP with maximum antiglaucomatous medications during follow-up before surgery ranged between 36 and 55 mm Hg. At last visit, IOP ranged between 8 and 17 mm Hg, and 6 of 9 of the eyes required no antiglaucomatous medications. There was no failure in any patients according to the guidelines of the World Glaucoma Association. The most common complication was cataract formation in 7 eyes.

Conclusions:

The favorable outcomes observed during 2 to almost 10 years following surgical intervention are encouraging. Therefore, trabeculectomy with MMC provides long-term safe and effective results in OHT/glaucoma in patients with BAIT.
Protocolized Versus Nonprotocolized Weaning to Reduce the Duration of Invasive Mechanical Weaning in Neonates
Authors: Bol Bas , van Zanten Henriette , Wielenga Joke , vd Hoogen Agnes , Mansvelt Petri , Blackwood Bronagh , Helder Onno
Published: June 2019

Mechanical ventilation is one of the most commonly used treatments in neonatology. Prolonged mechanical ventilation is associated with deleterious outcomes. To reduce the ventilation duration, weaning protocols have been developed to achieve extubation in adult and pediatric care in a safe and uniform manner. We performed a systematic review to obtain all available evidence on the effect of protocolized versus nonprotocolized weaning on the duration of invasive mechanical ventilation in critically ill neonates. The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, Web of Science, and the International Clinical Trial Registry Platform were searched until January 2018. Quantitative and qualitative studies involving neonates that investigated or described protocolized versus nonprotocolized weaning were included. Primary outcome was the difference in weaning duration. A total of 2099 potentially relevant articles were retrieved. Three studies met the inclusion criteria. Of 2 of these, the separate neonatal data could not be obtained. Only one retrospective study was included for this review. This reported a decrease in the mean weaning time from 18 to 5 and 6 days, respectively. There is no robust evidence in the literature to support or disprove the use of a weaning protocol in critically ill neonates.
Outcome of Children Treated for Infantile Hepatic Hemangioendothelioma
Authors: Emad Ahmed , Fadel Sayed , El wakeel Madeeha , Nagy Nouran , Zamzam Manal , Kieran Mark W. , El Haddad Alaa
Published: June 2019

Purpose:

Infantile hepatic hemangioendothelioma (IHHE) is the most common hepatic vascular tumor in children. We report on the treatment outcome of our large single-center experience of patients with IHHE over a 9-year period.

Materials and Methods:

A retrospective analysis of all IHHE patients treated at the Children Cancer Hospital Egypt from April 2008 through April 2017.

Results:

In total, 28 patients (18 females, 10 males) were diagnosed with IHHE with a median age at diagnosis of 3 months. The lesions were multifocal (n=12), focal (n=10), and diffuse (n=6). Six (21.4%) patients initially had low T3 and T4. Eleven patients did not receive any treatment, whereas 1 patient underwent resectional surgery. Sixteen patients received drug treatment, 9 of whom responded well to first-line propranolol/prednisolone, whereas 7 patients needed salvage treatment. Twenty-five patients are alive, whereas 3 patients have died.

Conclusions:

Overall, patients with IHHE do well, a significant percentage of whom do not require drug therapy, particularly for those with small focal lesions. In patients with multifocal/diffuse disease, there is a high incidence of low T3 and T4 and while some of these patients did well without additional therapy, those with rapidly progressive lesions during treatment may do poorly.
How Should Pancreas Transplant Rejection Be Treated?
Authors: Aziz Fahad , Parajuli Sandesh , Uddin Salah , Harrold Kylie , Djamali Arjang , Astor Brad , Odorico Jon , Mandelbrot Didier
Published: June 2019

Background.

Limited published data exist to guide the treatment of pancreas transplant rejection.

Methods.

We reviewed the treatment and outcomes of 158 first episodes of biopsy-proven pancreas rejection between 1 January 1997 and 31 December 2016. Within each Banff grade of rejection, we compared response rates and long-term outcomes with steroids alone versus steroids plus antithymocyte globulin (ATG).

Results.

Of 158 pancreas recipients with rejection, 65 were treated with steroids alone. Eighty-three percent of patients with grade I, 60% with grade II, and 33.33% with grade III rejection responded to treatment with steroids alone. Ninety-three patients were treated with steroids plus ATG. The response rates were 69% in grade I, 76% in grade II, and 73% in grade III. Response rates and graft survival were not different with grade I rejection treated with steroids alone versus steroids plus ATG. However, response rates and graft survival were significantly better with grade III rejection treated with the addition of ATG, and graft survival rates were significantly better with grade II rejection treated with the addition of ATG.

Conclusions.

Grade I pancreas rejection can usually be successfully treated with steroids alone, whereas grade II and III rejection should usually be treated with steroids plus ATG, as the addition of ATG improves both response rates and graft survival.
Maximizing viral detection with SIV droplet digital PCR (ddPCR) assays
Authors: Long Samuel , Berkemeire Brian
Published: June 2019

Highly sensitive detection of HIV-1 nucleic acids is of critical importance for evaluating treatment interventions superimposed on combination antiretroviral therapy (cART) in HIV-1 infected individuals. SIV infection of rhesus macaques models many key aspects of human HIV-1 infection and plays a key role in evaluation of approaches for prevention, treatment and attempted eradication of HIV infection. Here we describe ultrasensitive droplet digital PCR (ddPCR) DNA and RT-ddPCR RNA assays for detecting simian immunodeficiency virus (SIV) on the Raindance ddPCR platform. We demonstrate that RainDance ddPCR can tolerate significantly higher cell DNA input without inhibition on a per reaction basis, exceeding the Bio-Rad ddPCR per-reaction input limit by about 18-fold, effectively increasing viral detection sensitivity by allowing a large quantity of sample to be analyzed in each reaction. In addition, the combination of a high processivity RT enzyme and RainDance ddPCR could overcome inhibition in severely inhibited viral RNA samples. These assays offer valuable tools for assessing low level viral production/replication and strategies for targeting residual virus in the setting of cART suppression of viral replication. The methodologies presented here can be adapted for a broad range of applications where highly sensitive nucleic acid detection is required.
Changes in the intracranial volume from early adulthood to the sixth decade of life: A longitudinal study
Authors: Caspi Yaron , Brouwer Rachel M. , Schnack Hugo G. , van de Nieuwenhuijzen Marieke E. , Cahn Wiepke , Kahn René S. , Niessen Wiro J. , van der Lugt Aad , Pol Hilleke Hulshoff
Published: June 2019

Normal brain-aging occurs at all structural levels. Excessive pathophysiological changes in the brain, beyond the normal one, are implicated in the etiology of brain disorders such as severe forms of the schizophrenia spectrum and dementia. To account for brain-aging in health and disease, it is critical to study the age-dependent trajectories of brain biomarkers at various levels and among different age groups.

The intracranial volume (ICV) is a key biological marker, and changes in the ICV during the lifespan can teach us about the biology of development, aging, and gene X environment interactions. However, whether ICV changes with age in adulthood is not resolved.

Applying a semi-automatic in-house-built algorithm for ICV extraction on T1w MR brain scans in the Dutch longitudinal cohort (GROUP), we measured ICV changes. Individuals between the ages of 16 and 55 years were scanned up to three consecutive times with 3.32±0.32 years between consecutive scans (N=482, 359, 302). Using the extracted ICVs, we calculated ICV longitudinal aging-trajectories based on three analysis methods; direct calculation of ICV differences between the first and the last scan, fitting all ICV measurements of individuals to a straight line and applying a global linear mixed model fitting. We report statistically significant increases in the ICV in adulthood until the fourth decade of life (average change +0.03%/y, or about 0.5 ml/y, at age 20), and decreases in the ICV afterward (−0.09%/y, or about −1.2 ml/y, at age 55). To account for previous cross-sectional reports of ICV changes, we analyzed the same data using a cross-sectional approach. Our cross-sectional analysis detected ICV changes consistent with the previously reported cross-sectional effect. However, the reported amount of cross-sectional changes within this age range was significantly larger than the longitudinal changes. We attribute the cross-sectional results to a generational effect.

In conclusion, the human intracranial volume does not stay constant during adulthood but instead shows a small increase during young adulthood and a decrease thereafter from the fourth decade of life. The age-related changes in the longitudinal setup are smaller than those reported using cross-sectional approaches and unlikely to affect structural brain imaging studies correcting for intracranial volume considerably. As to the possible mechanisms involved, this awaits further study, although thickening of the meninges and skull bones have been proposed, as well as a smaller amount of brain fluids addition above the overall loss of brain tissue.
Classification of human white blood cells using machine learning for stain-free imaging flow cytometry
Authors: Lippeveld Maxim , Knill Carly , Ladlow Emma , Fuller Andrew , Michaelis Louise J , Saeys Yvan , Filby Andrew , Peralta Daniel
Published: June 2019

Imaging flow cytometry (IFC) produces up to 12 different information-rich images of single cells at a throughput of 5000 cells per second. Yet often, cell populations are still studied using manual gating, a technique that has several drawbacks. Firstly, it is hard to reproduce. Secondly, it is subjective and biased. And thirdly, it is time-consuming for large experiments. Therefore, it would be advantageous to replace manual gating with an automated process, which could be based on stain-free measurements originating from the brightfield and darkfield image channels. To realise this potential, advanced data analysis methods are required, in particular, machine learning. Previous works have successfully tested this approach on cell cycle phase classification with both a classical machine learning approach based on manually engineered features, and a deep learning approach. In this work, we compare both approaches extensively on the complex problem of white blood cell classification. Four human whole blood samples were assayed on an ImageStream-X MK II imaging flow cytometer. Two samples were stained for the identification of 8 white blood cell types, while two other sample sets were stained for the identification of resting and active eosinophils. For both datasets, four machine learning classifiers were evaluated on stain-free imagery using stratified 5-fold cross-validation. On the white blood cell dataset the best obtained results were 0.776 and 0.697 balanced accuracy for classical machine learning and deep learning, respectively. On the eosinophil dataset this was 0.866 and 0.867 balanced accuracy. From the experiments we conclude that classifying distinct cell types based on only stain-free images is possible with these techniques. However, both approaches did not always succeed in making reliable cell subtype classifications. Also, depending on the cell type, we find that even though the deep learning approach requires less expert input, it performs on par with a classical approach.
Multidimensional phenotyping predicts lifespan and quantifies health inC. elegans
Authors: Martineau Céline N. , Brown André E. X. , Laurent Patrick
Published: June 2019

Ageing affects a wide range of phenotypes at all scales, but an objective measure of ageing remains challenging, even in simple model organisms. We assumed that a wide range of phenotypes at the organismal scale rather than a limited number of biomarkers of ageing would best describe the ageing process. Hundreds of morphological, postural and behavioural features are extracted at once from high resolutions videos. A quantitative model using this multi-parametric dataset can predict the biological age and lifespan of individualC. elegans. We show that the quality of predictions on a held-out data set increases with the number of features added to the model, supporting our initial hypothesis. Despite the large diversity of ageing mechanisms, including stochastic insults, our results highlight a robust ageing trajectory, but variable ageing rates along that trajectory. We show that healthspan, which we defined as the range of abilities of the animals, is correlated to lifespan in wild-type worms.
The genome design suite: enabling massive in-silico experiments to design genomes
Authors: Chalkley Oliver , Purcell Oliver , Grierson Claire , Marucci Lucia
Published: June 2019

Motivation

Computational biology is a rapidly developing field, and in-silico methods are being developed to aid the design of genomes to create cells with optimised phenotypes. Two barriers to progress are that in-silico methods are often only developed on a particular implementation of a specific model (e.g. COBRA metabolic models) and models with longer simulation time inhibit the large-scale in-silico experiments required to search the vast solution space of genome combinations.

Results

Here we present the genome design suite (PyGDS) which is a suite of Python tools to aid the development of in-silico genome design methods. PyGDS provides a framework with which to implement phenotype optimisation algorithms on computational models across computer clusters. The framework is abstract allowing it to be adapted to utilise different computer clusters, optimisation algorithms, or design goals. It implements an abstract multi-generation algorithm structure allowing algorithms to avoid maximum simulation times on clusters and enabling iterative learning in the algorithm. The initial case study will be genome reduction algorithms on a whole-cell model of Mycoplasma genitalium for a PBS/Torque cluster and a Slurm cluster.

Availability

The genome design suite is written in Python for Linux operating systems and is available from GitHub on a GPL open-source licence.

Contact

o.chalkley@bristol.ac.uk, lacsg@bristol.ac.uk, and lucia.marucci@bristol.ac.uk.
Real time health monitoring through urine metabolomics
Authors: Miller Ian , Peters Sean R. , Overmyer Katherine A. , Paulson Brett R. , Westphall Michael S. , Coon Joshua J.
Published: June 2019

Current healthcare practices are reactive and based on limited physiological information collected months or years apart. By enabling patients and healthy consumers access to continuous measurements of health, wearable devices and digital medicine stand to realize highly personalized and preventative care. However, most current digital technologies provide information on a limited set of physiological traits, such as heart rate and step count, which alone offer little insight into the etiology of most diseases. Here we propose to integrate data from biohealth smartphone applications with continuous metabolic phenotypes derived from urine metabolites. This combination of molecular phenotypes with quantitative measurements of lifestyle reflect the biological consequences of human behavior in real time. We present data from an observational study involving two healthy subjects and discuss the challenges, opportunities, and implications of integrating this new layer of physiological information into digital medicine. Though our dataset is limited to two subjects, our analysis (also available through an interactiveweb-based visualization tool) provides an initial framework to monitor lifestyle factors, such as nutrition, drug metabolism, exercise, and sleep using urine metabolites.
Decoding and perturbing decision states in real time
Authors: Peixoto Diogo , Verhein Jessica R. , Kiani Roozbeh , Kao Jonathan C. , Nuyujukian Paul , Chandrasekaran Chandramouli , Brown Julian , Fong Sania , Ryu Stephen I. , Shenoy Krishna V. , Newsome William T.
Published: June 2019

In dynamic environments, subjects often integrate multiple samples of a signal and combine them to reach a categorical judgment. The process of deliberation on the evidence can be described by a time-varying decision variable (DV), decoded from neural activity, that predicts a subject’s decision at the end of a trial. However, within trials, large moment-to-moment fluctuations of the DV are observed. The behavioral significance of these fluctuations and their role in the decision process remain unclear. Here we show that within-trial DV fluctuations decoded in real time from motor cortex are tightly linked to choice behavior, and that robust changes in DV sign have the statistical regularities expected from behavioral studies of changes-of-mind. Furthermore, we find single-trial evidence for absorbing decision bounds. As the DV builds up, heavily favoring one or the other choice, moment-to-moment variability in the DV is reduced, and both neural DV and behavioral decisions become resistant to additional pulses of sensory evidence as predicted by diffusion-to-bound and attractor models of the decision process.
Conformational dynamics of FERM-mediated autoinhibition in Pyk2 tyrosine kinase
Authors: Loving Hanna S. , Underbakke Eric S.
Published: June 2019

Pyk2 is a non-receptor tyrosine kinase that evolved from gene duplication of focal adhesion kinase (FAK) and subsequent functional specialization in the brain and hemopoietic cells. Pyk2 shares a domain organization with FAK, with an N-terminal regulatory FERM domain adjoining the kinase domain. FAK regulation involves integrin-mediated membrane clustering to relieve autoinhibitory interactions between FERM and kinase domains. Pyk2 regulation remains cryptic, involving Ca2+ influx and protein scaffolding. While the mechanism of the FAK FERM domain in autoinhibition is well-established, the regulatory role of the Pyk2 FERM is ambiguous. We probed the mechanisms of FERM-mediated autoinhibition of Pyk2 using hydrogen/deuterium exchange mass spectrometry (HDX-MS) and kinase activity profiling. The results reveal FERM-kinase interfaces responsible for autoinhibition. Pyk2 autoinhibition impacts activation loop conformation. In addition, the autoinhibitory FERM-kinase interface exhibits allosteric linkage with the FERM basic patch conserved in both FAK and Pyk2.

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Genetic variant pathogenicity prediction trained using disease-specific clinical sequencing data sets
Authors: Evans Perry , Wu Chao , Lindy Amanda , McKnight Dianalee A. , Lebo Matthew , Sarmady Mahdi , Abou Tayoun Ahmad N.
Published: June 2019

Recent advances in DNA sequencing have expanded our understanding of the molecular basis of genetic disorders and increased the utilization of clinical genomic tests. Given the paucity of evidence to accurately classify each variant and the difficulty of experimentally evaluating its clinical significance, a large number of variants generated by clinical tests are reported as variants of unknown clinical significance. Population-scale variant databases can improve clinical interpretation. Specifically, pathogenicity prediction for novel missense variants can use features describing regional variant constraint. Constrained genomic regions are those that have an unusually low variant count in the general population. Computational methods have been introduced to capture these regions and incorporate them into pathogenicity classifiers, but these methods have yet to be compared on an independent clinical variant data set. Here, we introduce one variant data set derived from clinical sequencing panels and use it to compare the ability of different genomic constraint metrics to determine missense variant pathogenicity. This data set is compiled from 17,071 patients surveyed with clinical genomic sequencing for cardiomyopathy, epilepsy, or RASopathies. We further use this data set to demonstrate the necessity of disease-specific classifiers and to train PathoPredictor, a disease-specific ensemble classifier of pathogenicity based on regional constraint and variant-level features. PathoPredictor achieves an average precision >90% for variants from all 99 tested disease genes while approaching 100% accuracy for some genes. The accumulation of larger clinical variant training data sets can significantly enhance their performance in a disease- and gene-specific manner.
Psychiatric assessment in congenital blindness, ASD and ID: experience from two clinical cases
Authors: Kildahl Arvid Nikolai , Engebretsen Maria Hagen , Horndalsveen Kristin , Hellerud Jane Margrete Askeland , Wiik Jorunn Ytrehorn , Aasen Gro , Helverschou Sissel Berge
Published: June 2019

Purpose

Psychiatric assessment in adults with autism spectrum disorder (ASD) and intellectual disability (ID) is complex and challenging. With co-occurring congenital blindness, this complexity is increased. Systematic knowledge about psychiatric assessment in this combination of challenges is virtually non-existing, and there is little guidance available for clinicians faced with this task. The paper aims to discuss these issues.

Design/methodology/approach

Experiences from comprehensive psychiatric assessments in two adults with congenital blindness, ASD, and ID are explored and discussed.

Findings

Adaptation of assessment procedures usually employed for individuals with ASD and ID involved no major alteration, but co-operation between mental health and visual impairment professionals was important, as was the involvement of the families of the individuals in question. In both cases, the patient met criteria for an anxiety disorder, underlining the vulnerability and the challenges involved in living with this combination of challenges.

Research limitations/implications

There is an urgent need for research into mental health issues for this group, including case studies describing successful treatment or intervention for these issues.

Practical implications

Psychiatric assessment in individuals with this combination of challenges may be feasible, but requires involvement of professionals specializing in mental health in developmental disabilities, and professionals in visual impairment. Assessments need to be individually adapted.

Originality/value

This is the first study systematically describing psychiatric assessment in this group involving the use of checklists and assessment tools. Strategies and tools that were useful are described and discussed to aid other clinicians faced with similar challenges.
Understanding built environment realities
Authors: Salama Ashraf M.
Published: June 2019

Purpose

Following the successful transition of Archnet-IJAR to Emerald, the introduction of new process and editorial teams, and the production of the first issue last March (Volume 13, Issue 1), the purpose of this paper is to outline key aspects of the contributions published in this edition ofArchnet-IJAR: International Journal of Architectural Research, Volume 13, Issue 1, July 2019.

Design/methodology/approach

Premised on two generic understandings of built environment research: conceptual frameworks and experimental fieldworks, a classification of topical contents and an identification of approaches within the studies published in this edition, a narrative on evolving interests and themes is developed to outline these undertakings.

Findings

Five themes are identified from 13 papers contributed by 27 researchers from academic institutions in 13 countries and territories. Themes include: complexity and prosperity of informal settlements and slums; east–west dialectics of environmental design research and sustainable urbanism; educating future built environment professionals; grassroots research and design strategies; and performance, perception and behavior.

Originality/value

Understanding and appreciating various research approaches for unveiling key aspects of built environment realities including the spatial and social dimensions would facilitate effective contributions in architectural and urban research. This is coupled with the advancing thematic aspects that enthuse a re-thinking of the key purpose of architectural and urban research while stimulating future research endeavors.
Criminal history and the workplace: a pathway forward
Authors: Young Nicole C. Jones , Ryan Ann Marie
Published: June 2019

Purpose

The purpose of this paper is to summarize some of the key gaps in knowledge regarding the use of criminal records in employee selection and post-hire challenges that those with a criminal record may continue to face.

Design/methodology/approach

This paper is a general review and introduction to the special issue on criminal history and employment.

Findings

The authors suggest that understanding the “what,” “how,” “why” and “who” may provide researchers with increased clarity regarding the relevance and use of criminal records within the employee selection process.

Research limitations/implications

The authors encourage researchers to explore the management constructs and theories to understand how they may operate and affect this population upon entry into the workplace. Additionally, the authors discuss some of the methodological challenges and considerations related to conducting research on this population.

Originality/value

While researchers continue to seek and better understand the experiences of job seekers with criminal records and specific barriers to fulfilling work, there are many aspects of the pre- and post-employment experience that are not yet well examined. This paper provides a pathway forward for management researchers within the area of criminal history and employment, an understudied yet relevant topic.
Predictive model assessment in PLS-SEM: guidelines for using PLSpredict
Authors: Shmueli Galit , Sarstedt Marko , Hair Joseph F. , Cheah Jun-Hwa , Ting Hiram , Vaithilingam Santha , Ringle Christian M.
Published: June 2019

Purpose

Partial least squares (PLS) has been introduced as a “causal-predictive” approach to structural equation modeling (SEM), designed to overcome the apparent dichotomy between explanation and prediction. However, while researchers using PLS-SEM routinely stress the predictive nature of their analyses, model evaluation assessment relies exclusively on metrics designed to assess the path model’s explanatory power. Recent research has proposed PLSpredict, a holdout sample-based procedure that generates case-level predictions on an item or a construct level. This paper offers guidelines for applying PLSpredict and explains the key choices researchers need to make using the procedure.

Design/methodology/approach

The authors discuss the need for prediction-oriented model evaluations in PLS-SEM and conceptually explain and further advance the PLSpredict method. In addition, they illustrate the PLSpredict procedure’s use with a tourism marketing model and provide recommendations on how the results should be interpreted. While the focus of the paper is on the PLSpredict procedure, the overarching aim is to encourage the routine prediction-oriented assessment in PLS-SEM analyses.

Findings

The paper advances PLSpredict and offers guidance on how to use this prediction-oriented model evaluation approach. Researchers should routinely consider the assessment of the predictive power of their PLS path models. PLSpredict is a useful and straightforward approach to evaluate the out-of-sample predictive capabilities of PLS path models that researchers can apply in their studies.

Research limitations/implications

Future research should seek to extend PLSpredict’s capabilities, for example, by developing more benchmarks for comparing PLS-SEM results and empirically contrasting the earliest antecedent and the direct antecedent approaches to predictive power assessment.

Practical implications

This paper offers clear guidelines for using PLSpredict, which researchers and practitioners should routinely apply as part of their PLS-SEM analyses.

Originality/value

This research substantiates the use of PLSpredict. It provides marketing researchers and practitioners with the knowledge they need to properly assess, report and interpret PLS-SEM results. Thereby, this research contributes to safeguarding the rigor of marketing studies using PLS-SEM.
Two-phase modeling of nanofluid forced convection in different arrangements of elliptical tube banks
Authors: Mousavi Seyed Mohammad , Akbari Omid Ali , Sheikhzadeh Ghanbarali , Marzban Ali , Toghraie Davood , Chamkha Ali J.
Published: June 2019

Purpose

The purpose of this study is two phase modeling of Water/Cu nanofluid forced convection in different arrangements of elliptical tube banks in a two-dimensional space.

Design/methodology/approach

The arrangements of tube banks have been regarded as equal spacing triangle (ES), equilateral triangle (ET) and the rotated square (RS). The obtained results indicate that, among the investigated arrangements, the RS arrangement has the maximum value of heat transfer with cooling fluid. Also, the changes of Nusselt number and the local friction factor are under the influence of three main factors including volume fraction of slid nanoparticles, the changes of fluid velocity parameters on the curved surface of tube and flow separation after crossing from a specified angle of fluid rotation.

Findings

In Reynolds number of 250 and in all arrangements of the tube banks, the behavior of Nusselt number is almost the same and the separation of flow happens in almost 155-165 degrees from fluid rotation on surface. In RS arrangement, due to the strength of vortexes after fluid separation, better mixture is created and because of this reason, after the separation zone, the level of local Nusselt number graph enhances significantly.

Originality/value

In this research, the laminar and two-phase flow of Water/Cu nanofluid in tube banks with elliptical cross section has been numerically investigated in a two-dimensional space with different longitudinal arrangements. In this study, the effects of using nanofluid, different arrangements of tube banks and the elliptical cross section on heat transfer and cooling fluid flow among the tube banks of heat exchanger have been numerically simulated by using finite volume method.
Investigation of viscous fluid flow and dynamic stability of CNTs subjected to axial harmonic load coupled using Bolotin’s method
Authors: Hashemian Mohammad , Vaez Amir Homayoun , Toghraie Davood
Published: June 2019

Purpose

The dynamic stability of nano-tubes is an important issue in engineering applications. Dynamic stability of anti-symmetric coupled-carbon nanotubes (C-CNTs)-systems in thermal environment is presented in this paper. In this system, the top and bottom CNTs are subjected to axial harmonic load and action of the viscous fluid, respectively.

Design/methodology/approach

The coupling and surrounding mediums of the CNTs are simulated by visco-Pasternak foundation containing the spring, shear and damper coefficients. Based on the Timoshenko beam theory and Hamilton’s principle, the coupled motion equations are derived considering size effects using Eringen’s nonlocal theory. Using the exact solution in conjunction with Bolotin’s method, the dynamic instability region (DIR) of the coupled structure is obtained. The effects of various parameters such as small scale parameter, Knudsen number, fluid velocity, static load factor, temperature change, surrounding medium and nanotubes aspect ratio are shown on the DIR of the coupled system.

Findings

Results indicate that considering parameters such as small scale effects, static load factor, Knudsen number and fluid velocity shifts the DIR of C-CNTs to a lower frequency zone.

Originality/value

To the best of our knowledge, analyses of anti-symmetric coupled CNTs have not received enough attentions so far. In order to optimize the nanostructures designing, the main purpose of the present paper is to investigate nonlocal dynamic stability of CNTs subjected to axial harmonic load coupled with CNTs conveying fluid.