bluuebunny/crossref_metadata_2025 huggingface dataset:
Reversibility of Gland Dropout and Significance of Eyelid Hygiene Treatment in Meibomian Gland Dysfunction
Authors: Yin Yue , Gong Lan
Published: October 2016

Purpose:

To observe reversibility of meibomian gland (MG) dropout and analyze correlated factors and to compare the treatment efficiency with and without eyelid hygiene in patients with meibomian gland dysfunction (MGD).

Methods:

Consecutive 78 eyes of 78 MGD (stage 2–3) patients who finished follow-up examination after 1-month of treatment were recruited in this retrospective study. All patients were treated with artificial lubricant and eyelid hygiene. Related ocular surface evaluation and meibomian gland assessment were examined.

Results:

There were 26 (33%) patients (included in group 1) who ignored doctors' order for eyelid hygiene, and 52 (67%) patients (included in group 2) were compliant. There was no statistical difference between group 1 (age, 44.4 ± 12.2) and group 2 (age, 38.9 ± 16.6) in characteristics and pretreatment clinical indexes. However, after 1-month of treatment, only the ocular surface disease index of group 1 improved (P = 0.048), whereas all clinical indexes of group 2, except the Schirmer test result, improved (including expressibility, all P < 0.05). A 5% decrease in MG dropout of both upper (5.4%) and lower (4.6%) eyelids in group 2 was observed. Improvement in upper-eyelid dropout and expressibility were the predictors of lower-eyelid dropout improvement. The reversibility had no correlation with age, sex, pretreatment MGD stage, disease duration, and use of topical antiinflammation medication.

Conclusions:

With expressibility-improving treatment, MG dropout was reversible to some extent. Eyelid hygiene is an efficient treatment of MGD; however, there is a need for ophthalmologists to instruct patients on conduct and supervise patients' compliance.
How Often the Goldmann Applanation Tonometer Should be Checked for Calibration Error?
Authors: Choudhari Nikhil S. , Rao Harsha L. , Ramavath Suresh , Rekha Gunturu , Rao Aparna , Senthil Sirisha , Garudadri Chandra S.
Published: October 2016

Purpose:

To evaluate the frequency of Goldmann applanation tonometer (GAT) calibration error (CE) check.

Methods:

One observer at each of the 3 tertiary care ophthalmic centers was involved. The tonometers were checked at baseline for CE. A tonometer was defined as faulty when CE exceeded 2 mm Hg at any testing level. Faulty GATs were repaired in-house. Subsequent CE check was done once per month for 6 months. GATs were divided into 3 groups: group 1 (G1)≤1 year, group 2 (G2)>1 to 10 years, and group 3 (G3)>10 years of usage.

Results:

In total, 76 slit-lamp mounted GATs were included. The number of GATs in groups 1 to 3 was 19, 36, and 21, respectively. Seven (9.2%) tonometers were faulty at the baseline. None in G1, 5 in G2, and 16 in G3 demonstrated unacceptable CE over the study course (P<0.01). The survival function of G1 tonometers was 1.0 throughout, whereas that (95% confidence interval) of the G2 and G3 tonometers were 0.97 (0.81-0.99) and 0.76 (0.51-0.89) at 1 month, and 0.86 (0.69-0.93) and 0.23 (0.08-0.43) at 6 months, respectively. The probability of CE development increased with increasing age of the tonometer. The frequency of use of the tonometer was not associated with the development of CE (odds ratio=1.00).

Conclusions:

CE occurs more frequently in older tonometers. Although newer GATs (<1 y old) can be checked twice yearly, GATs older than a year should be checked at least monthly.
Optic Disc Characteristics and Visual Field Progression in Normal Tension Glaucoma Patients With Tilted Optic Discs
Authors: Kwun Youngkyo , Han Gyule , Choy Yoon-Jung , Han Jong Chul , Kee Changwon
Published: October 2016

Purpose of the Study:

The purpose of the study was to evaluate the optic disc characteristics associated with visual field (VF) progression in normal tension glaucoma (NTG) eyes with tilted optic discs.

Methods:

Sixty-six eyes of 66 NTG patients with tilted optic disc were included in this cross-sectional study, who were examined by at least 5 Humphrey 30-2 VFs. Glaucomatous VF progression was evaluated using pointwise linear regression. Optic nerve heads were scanned with enhanced-depth imaging optical coherence tomography (EDI-OCT), and evaluated for the focal lamina cribrosa (LC) defects and LC thicknesses. Optic disc torsion degrees and tilt ratios were measured from disc photographs. Logistic regression analyses were used to identify the risk factors for VF progression and focal LC defects.

Results:

Multivariate analysis showed that VF progression was associated with the presence of focal LC defects and greater number of VFs. The eyes with focal LC defects were associated with greater torsion degree and tilt ratio in multivariate analysis. The VF mean deviation slopes and localized VF progression rates in eyes with focal LC defects were greater than those without defects.

Conclusions:

The greater optic disc tilt and torsion in NTG eyes with tilted optic disc were associated with focal LC defects, but not with VF progression. The focal LC defects were associated with VF progression. This study suggests that the focal LC defects in NTG patients with tilted optic disc may be an independent risk factor for glaucomatous VF progression, and the development of focal LC defects could be influenced by optic disc torsion or tilt.
A Novel Method of Extending Glaucoma Drainage Tube: “Tube-in-Tube” Technique
Authors: Chiang Mark Yu-Ming , Camuglia Jayne E. , Khaw Peng Tee
Published: October 2016

Purpose:

To describe a new and simple technique of glaucoma tube extension that carries several advantages over previously described techniques.

Patients and Methods:

A retrospective noncomparative case series of 3 patients (1 adult and 2 pediatric cases) with glaucoma tube retraction managed by the “tube-in-tube” technique. The follow-up duration ranges from 1 month to 3 years.

Results:

Adequate tube position and length were seen in all cases throughout the follow-up period. No tube migration was seen. The intraocular pressures were significantly reduced and maintained in all cases. There was no visual loss as a result of the procedure.

Conclusions:

This new “tube-in-tube” glaucoma drainage device tube extension technique is safe and simple to perform, and has many advantages over previously reported techniques. It can be used in both the adult and pediatric glaucoma population, and is not limited to the type of drainage implants.
Effect of Head Position and Weight Loss on Intraocular Pressure in Obese Subjects
Authors: Lam Cindy T.Y. , Trope Graham E. , Buys Yvonne M.
Published: October 2016

Purpose:

To measure the influence of body weight on postural intraocular pressure (IOP) changes and to determine if significant weight loss effects IOP.

Patients and Methods:

In this prospective case-control study 25 morbidly obese subjects scheduled for bariatric surgery and 25 age-matched and sex-matched normal weight controls were recruited. Subjects had tonometry performed in 7 positions with the order randomized: sitting with the neck in neutral position, neck flexion at 30 degrees, extension at 30 degrees, supine, right, and left lateral decubitus, and with the head and upper body elevated at 30 degrees. The obese subjects were reassessed 1 to 2 years after bariatric surgery.

Results:

Mean IOP in the obese group was significantly higher than the control group across all positions by a mean of 2.5±0.4 mm Hg (P<0.02). There was no significant difference in the magnitude of postural IOP change between obese and control subjects. In total, 19 obese subjects completed follow-up after bariatric surgery. Mean weight loss was 49.1±17.2 kg, 36% of total body weight. Mean IOP was significantly lower after bariatric surgery by 1.6±0.5 mm Hg (P<0.001). Linear regression demonstrated that every 10% body weight loss was correlated with 1.4 mm Hg decrease in IOP (r=−0.46).

Conclusions:

Obesity is associated with increased IOP compared with normal weight controls, but not with the magnitude of postural IOP change across different seated and supine positions. Significant weight loss after bariatric surgery is weakly associated with IOP lowering. The relationship between IOP, glaucoma, and obesity deserves further study.
Discharge of Non–Acute Coronary Syndrome Chest Pain Patients From Emergency Care to an Advanced Nurse Practitioner–Led Chest Pain Clinic
Authors: Ingram Shirley J. , McKee Gabrielle , Quirke Mary B. , Kelly Niamh , Moloney Ashling
Published: October 2016

Background:

Chest pain is a common presentation to emergency departments (EDs). Pathways for patients with non–acute coronary syndrome (ACS) chest pain are not optimal. An advanced cardiology nurse–led chest pain service was commenced to address this. The aim of the study was to assess the outcomes of non-ACS patients discharged from ED to an advanced cardiology nurse–led chest pain clinic and compare by referral type (nurse or ED physician).

Methods:

The service consisted of advanced cardiology nurse or ED physician consultation in the ED and discharge to advanced nurse–led chest pain clinic review less than 72 hours after discharge. Referrals were by the advanced nurses during consult hours and out-of-hours were by the ED physicians. Data were extracted from case notes. This was a 1-site cross-sectional study of patients attending the chest pain clinic over 2 years.

Results:

Confirmed coronary disease was diagnosed in 24% of patients. Of the 1041 patients, 45% were referred by the advanced nurses, who referred significantly more patients who were older (56.5 years/52.3 years), had positive exercise stress test results (21%/12%), and were diagnosed with stable coronary artery disease (19%/11%) and less patients with musculoskeletal diagnosis (5%/13%) and other noncardiac pain (36%/45%).

Conclusions:

The study fills a gap in the literature on the follow up of non-ACS patients who present to ED and used advanced cardiology nursing expertise in the ED and chest pain clinic. The advanced nurse referred more patients who were diagnosed with coronary disease, reflecting the expertise, experience, and efficiency of the advanced cardiology nurse–led service.
Prescriber Continuity and Disease Control of Older Adults
Authors: Maciejewski Matthew L. , Hammill Bradley G. , Bayliss Elizabeth A. , Ding Laura , Voils Corrine I. , Curtis Lesley H. , Wang Virginia
Published: October 2016

Background:

Medicare beneficiaries with multiple chronic conditions are typically seen by multiple providers, particularly specialists. Clinically appropriate referrals to multiple specialists may compromise the continuity of care for multiple chronic condition beneficiaries and create care plans that patients may find challenging to reconcile, which may impact patient outcomes.

Objective:

The objective was to examine whether glycemic control or lipid control was associated with the number of prescribers of cardiometabolic medications.

Research Design, Subjects, and Measures:

A retrospective cross-sectional cohort analysis of 51,879 elderly Medicare fee-for-service beneficiaries with diabetes and 129,762 beneficiaries with dyslipidemia living in 10 east coast states. Glycemic control was defined as having an HbA1c<7.5. Lipid control was defined as an low-density lipoprotein<100 for beneficiaries with heart disease or diabetes or an low-density lipoprotein<130 for all other beneficiaries. We examined the association between the number of prescribers of cardiometabolic medications and disease or lipid control in 2011 through logistic regression, controlling for age, sex, race, Medicaid enrollment, 17 chronic conditions and state-fixed effects.

Results:

Among beneficiaries with diabetes, 76% with one prescriber had well-controlled diabetes in 2011, which decreased to 65% for beneficiaries with 5+ prescribers. In adjusted analyses, Medicare beneficiaries with 3 or more prescribers were less likely to have glycemic control than beneficiaries with a single prescriber. Among those with dyslipidemia, nearly all (91%–92%) beneficiaries had lipid control. After adjustment for demographics and comorbidity burden, beneficiaries with 3 prescribers were less likely to have lipid control than beneficiaries with a single prescriber.

Conclusions:

Multiple prescribers were associated with worse disease control, possibly because patients with more severe diabetes or dyslipidemia have multiple prescribers or because care fragmentation is associated with worse disease control.
Becoming a Baby Friendly Hospital
Authors: Tran Andrea
Published: October 2016

The purpose of the Baby-Friendly hospital initiative is to encourage hospitals to use best practices to support infant feeding, as demonstrated by implementing the Ten Steps to Successful Breastfeeding recommended by the World Health Organization. The journey to becoming a Baby-Friendly designated hospital is challenging but ultimately rewarding. In October 2015, Boulder Community Foothills Hospital, a community hospital with a strong breastfeeding culture and a 98% rate of women who initiate breastfeeding postpartum, became one of the approximately 300 Baby-Friendly designated hospitals in the United States. Significant challenges and how we succeeded each step of the way are included. Even when a hospital is breastfeeding friendly, becoming Baby-Friendly is never a mere formality. Nursing leadership teams in other hospitals may find value in the details of our successful efforts to become a Baby-Friendly designated hospital.
Dynamics of the bacterial community associated withPhaeodactylum tricornutumcultures
Authors: Moejes Fiona Wanjiku , Popa Ovidiu , Succurro Antonella , Maguire Julie , Ebenhöh Oliver
Published: October 2016

The pennate diatomPhaeodactylum tricornutumis a model organism able to synthesise industrially-relevant molecules. Large-scale monocultures are prone to bio-contamination, however, little is known about the identity of the invading organisms. To gain insight into the bacterial community associated with diatoms, we translated the complexity of a natural system into reproducible experiments where we investigated the microbiome ofP. tricornutumcultures. The results revealed a dynamic bacterial community that changed over time and in differing media conditions. We propose a network of putative interactions betweenP. tricornutumand the main bacterial factions, which is translated into a set of ordinary differential equations constituting a computational dynamic model. The proposed mathematical model is able to capture the population dynamics, further supporting the hypothesised interactions. The interdisciplinary approach implemented provides a framework for understanding the dynamics of diatom-associated microbial communities, and provides a foundation for further systematic investigations of host-microbe interactions.
The Coevolution of Social Learning and Sensitivity to Changing Environments
Authors: McElreath Richard
Published: October 2016

Abstract

There is widespread agreement that social and individual learning are adaptations to varying environments. However, existing theory assumes that organisms cannot detect changes in the environment and instead adapt to averages. This paper develops the first analytical model that allows for the simultaneous coevolution of socially learned traditions, reliance on social learning, and signal detection for environmental change. There are numerous conditions under which detection can be stable once common but cannot invade the population when rare. When signal detection is maintained by selection, it always leads to pure separating equilibria at which organisms always learn individually when they believe the environment has recently changed and otherwise always learn socially. Detection can increase mean fitness at equilibrium, but it may also reduce it.
Proteus: A Random Forest Classifier to Predict Disorder-to-Order Transitioning Binding Regions in Intrinsically Disordered Proteins
Authors: Basu Sankar , Söderquist Fredrik , Wallner Björn
Published: October 2016

The focus of the computational structural biology community has taken a dramatic shift over the past one-and-a-half decades from the classical protein structure prediction problem to the possible understanding of intrinsically disordered proteins (IDP) or proteins containing regions of disorder (IDPR). The current interest lies in the unraveling of a disorder-to-order transitioning code embedded in the amino acid sequences of IDPs / IDPRs. Disordered proteins are characterized by an enormous amount of structural plasticity which makes them promiscuous in binding to different partners, multi-functional in cellular activity and atypical in folding energy landscapes resembling partially folded molten globules. Also, their involvement in several deadly human diseases (e.g. cancer, cardiovascular and neurodegenerative diseases) makes them attractive drug targets, and important for a biochemical understanding of the disease(s). The study of the structural ensemble of IDPs is rather difficult, in particular for transient interactions. When bound to a structured partner, an IDPR adapts an ordered conformation in the complex. The residues that undergo this disorder-to-order transition are called protean residues, generally found in short contiguous stretches and the first step in understanding the modus operandi of an IDP / IDPR would be to predict these residues. There are a few available methods which predict these protean segments from their amino acid sequences; however, their performance reported in the literature leaves clear room for improvement. With this background, the current study presents 'Proteus', a random forest classifier that predicts the likelihood of a residue undergoing a disorder-to-order transition upon binding to a potential partner protein. The prediction is based on features that can be calculated using the amino acid sequence alone. Proteus compares favorably with existing methods predicting twice as many true positives as the second best method (55% vs. 27%) with a much higher precision on an independent data set. The current study also sheds some light on a possible 'disorder-to-order' transitioning consensus, untangled, yet embedded in the amino acid sequence of IDPs. Some guidelines have also been suggested for proceeding with a real-life structural modeling involving an IDPR using Proteus.

Software Availability

https://github.com/bjornwallner/proteus
Conservation of EMT transcription factor function in controlling pluripotent adult stem cell migrationin vivoin planarians
Authors: Abnave Prasad , Aboukhatwa Ellen , Kosaka Nobuyoshi , Thompson James , Hill Mark A. , Aziz Aboobaker A.
Published: October 2016

Migration of stem cells underpins the physiology of metazoan animals. For tissues to be maintained, stem cells and their progeny must migrate and differentiate in the correct positions. This need is even more acute after tissue damage by wounding or pathogenic infections. Inappropriate migration also underpins the formation of metastasis. Despite this, few mechanistic studies address stem cell migration during repair or homeostasis in adult tissues. Here, we present a shielded X-ray irradiation assay that allows us to follow stem cell migration in the planarians. We demonstrate that we can use this system to study the molecular control of stem cell migration and show thatsnailandzeb-1EMT transcription factors homologs are necessary for cell migration to wound sites and for the establishment of migratory cell morphology. Our work establishes planarians as a suitable model for further in depth study of the processes controlling stem cell migration in vivo.
A cryptography-based approach for movement decoding
Authors: Dyer Eva L. , Azar Mohammad Gheshlaghi , Fernandes Hugo L. , Perich Matthew G. , Naufel Stephanie , Miller Lee , Körding Konrad P.
Published: October 2016

Brain decoders use neural recordings to infer a user’s activity or intent. To train a decoder, we generally need infer the variables of interest (covariates) using simultaneously measured neural activity. However, there are many cases where this approach is not possible. Here we overcome this problem by introducing a fundamentally new approach for decoding called distribution alignment decoding (DAD). We use the statistics of movement, much like cryptographers use the statistics of language, to find a mapping between neural activity and motor variables. DAD learns a linear decoder which aligns the distribution of its output with the typical distribution of motor outputs by minimizing their KL-divergence. We apply our approach to a two datasets collected from the motor cortex of non-human primates (NHPs): a reaching task and an isometric force production task. We study the performance of DAD and find regimes where DAD provides comparable and in some cases, better performance than a typical supervised decoder. As DAD does not rely on the ability to record motor-related outputs, it promises to broaden the set of potential applications of brain decoding.
Mcmdc2, a minichromosome maintenance (MCM) paralog, is required for repair of meiotic DNA breaks and homolog pairing in mouse meiosis
Authors: McNairn Adrian J. , Rinaldi Vera D. , Schimenti John C.
Published: October 2016

The mammalianMcm-domain containing 2(Mcmdc2) gene encodes a protein of unknown function that is homologous to the mini-chromosome maintenance family of DNA replication licensing and helicase factors.Drosophila melanogastercontains two separate genes, the “Mei-MCMs,” that appear to have arisen from a single ancestralMcmdc2gene. The Mei-MCMs are involved in promoting meiotic crossovers by blocking the anti-crossover activity of BLM helicase, a function performed by MSH4 and MSH5 in metazoans. Here, we report that MCMDC2-deficient mice of both sexes are viable but sterile. Males fail to produce spermatozoa, and formation of primordial follicles is disrupted in females. Histology and immunocytological analyses of mutant testes revealed that meiosis is arrested in Prophase I, and is characterized by persistent meiotic double-stranded DNA breaks (DSBs), failure of homologous chromosome synapsis and XY body formation, and an absence of crossing over. These phenotypes essentially phenocopy those of MSH4/5 deficient meiocytes. The data indicate that MCMDC2 is essential for invasion of homologous sequences by RAD51- and DMC1-coated ssDNA filaments, or stabilization of recombination intermediates following strand invasion, both of which are needed to drive stable homolog pairing and DSB repair via recombination in mice.
Measurements of morphological and biochemical alterations in individual neuron cells associated with early neurotoxic effects in Parkinson’s disease
Authors: Yang Su-A , Yoon Jonghee , Kim Kyoohyun , Park YongKeun
Published: October 2016

Parkinson’s disease (PD) is a common neurodegenerative disease. However, therapeutic methods of PD are still limited due to complex pathophysiology in PD. Here, we present optical measurements of individual neurons fromin vitroPD model using optical diffraction tomography (ODT). By measuring 3-D refractive index distribution of neurons, morphological and biochemical alterations inin-vitroPD model are quantitatively investigated. We found that neurons show apoptotic features in early PD progression. The present approach will open up new opportunities for quantitative investigation of the pathophysiology of various neurodegenerative diseases.
Grow with the flow: a latitudinal cline in physiology is associated with more variable precipitation inErythranthe cardinalis
Authors: Muir Christopher D. , Angert Amy L.
Published: October 2016

Local adaptation is commonly observed in nature: organisms perform well in their natal environment, but poorly outside it. Correlations between traits and latitude, or latitudinal clines, are among the most common pieces of evidence for local adaptation, but identifying the traits under selection and the selective agents is challenging. Here, we investigated a latitudinal cline in growth and photosynthesis across 16 populations of the perennial herbErythranthe cardinalis(Phrymaceae). Using machine learning methods, we identify interannual variation in precipitation as a likely selective agent: Southern populations from more variable environments had higher photosynthetic rates and grew faster. We hypothesize that selection may favor a more annualized life history – grow now rather than save for next year – in environments where severe droughts occur more often. Thus our study provides insight into how species may adapt if Mediterranean climates become more variable due to climate change.
Rapid and consistent evolution of colistin resistance inPseudomonas aeruginosaduring morbidostat culture
Authors: Regenbogen Bianca , Willmann Matthias , Steglich Matthias , Bunk Boyke , Nübel Ulrich , Peter Silke , Neher Richard A.
Published: October 2016

Colistin is a last resort antibiotic commonly used against multidrug-resistant strains ofPseudomonas aeruginosa. To investigate the potential forin-situevolution of resistance against colistin and map the molecular targets of colistin resistance, we exposed twoP. aeruginosaisolates to colistin using a continuous culture device known as morbidostat. Colistin resistance emerged within two weeks along with highly stereotypic yet strain specific mutation patterns. The majority of mutations hit theprmABtwo component signaling system and genes involved in lipopolysaccharide synthesis, includinglpxC,pmrE, andmigA. In seven out of 18 cultures, we observed mutations inmutSalong with a mutator phenotype that seemed to facilitate resistance evolution.
Benchmarking substrate-based kinase activity inference using phosphoproteomic data
Authors: Hernandez-Armenta Claudia , Ochoa David , Gonçalves Emanuel , Saez-Rodriguez Julio , Beltrao Pedro
Published: October 2016

Motivation

Phosphoproteomic experiments are increasingly used to study the changes in signalling occurring across different conditions. It has been proposed that changes in phosphorylation of kinase target sites can be used to infer when a kinase activity is under regulation. However, these approaches have not yet been benchmarked due to a lack of appropriate benchmarking strategies.

Results

We curated public phosphoproteomic experiments to identify a gold standard dataset containing a total of 184 kinase-condition pairs where regulation is expected to occur. A list of kinase substrates was compiled and used to estimate changes in kinase activities using the following methods: Z-test, Kolmogorov Smirnov test, Wilcoxon rank sum test, gene set enrichment analysis (GSEA), and a multiple linear regression model (MLR). We also tested weighted variants of the Z-test, and GSEA that include information on kinase sequence specificity as proxy for affinity. Finally, we tested how the number of known substrates and the type of evidence(in vivo, in vitroorin silico)supporting these influence the predictions.

Conclusions

Most models performed well with the Z-test and the GSEA performing best as determined by the area under the ROc curve (Mean AUC=0.722). Weighting kinase targets by the kinase target sequence preference improves the results only marginally. However, the number of known substrates and the evidence supporting the interactions has a strong effect on the predictions.
Low plastic ingestion rate in Atlantic Cod (Gadus morhua) from Newfoundland destined for human consumption collected through citizen science methods
Authors: Liboiron Max , Liboiron France , Wells Emily , Richárd Natalie , Zahara Alexander , Mather Charles , Bradshaw Hillary , Murichi Judyannet
Published: October 2016

Marine microplastics are a contaminant of concern because their small size allows ingestion by a wide range of marine life. Using citizen science during the Newfoundland recreational cod fishery, we sampled 205 Atlantic cod (Gadus morhua) destined for human consumption and found that 5 had eaten plastic, an ingestion prevalence rate of 2.4%. This ingestion rate for Atlantic cod is the second lowest recorded rate in the reviewed published literature (the lowest is 1.4%), and the lowest for any fish in the North Atlantic. This is the first report for plastic ingestion in fish in Newfoundland, Canada, a province dependent on fish for sustenance and livelihoods.

Highlights (3–5 points, 85 char max including spaces)

Plastic ingestion rate of 2.4% for Atlantic Cod (n=205)

First recorded baseline for fish in Newfoundland, Canada

This plastic ingestion prevalence rate is among the lowest recorded to date

Used citizen science to collect GI tracts from fish destined for human consumption
High precision registration between zebrafish brain atlases using symmetric diffeomorphic normalization
Authors: Marquart Gregory D. , Tabor Kathryn M. , Horstick Eric J. , Brown Mary , Burgess Harold A.
Published: October 2016

Atlases provide a framework for information from diverse sources to be spatially mapped and integrated into a common reference space. In particular, brain atlases allow regional annotation of gene expression, cell morphology, connectivity and activity. In larval zebrafish, advances in genetics, imaging and computational methods have enabled the collection of large datasets providing such information on a whole-brain scale. However, datasets from different sources may not be aligned to the same spatial coordinate system, because technical considerations may necessitate use of different reference templates. Two recent brain atlases for larval zebrafish exemplify this problem. The Z-Brain atlas contains information on gene expression, neural activity and neuroanatomical segmentation acquired using immunohistochemical staining of fixed tissue. In contrast, the Zebrafish Brain Browser (ZBB) atlas was constructed from live scans of fluorescent reporter genes in transgenic larvae. Although different reference brains were used, the two atlases included several transgene patterns in common that provided potential 'bridges' for transforming each into the other’s coordinate space. We therefore tested multiple bridging channels and registration algorithms. The symmetric diffeomorphic normalization (SyN) algorithm in ANTs improved the precision of live brain registration while better preserving cell morphology than the previously used B-spline elastic registration algorithm. SyN could also be calibrated to correct for tissue distortion introduced during fixation and permeabilization. Finally, multi-reference channel optimization provided a transformation matrix that enabled Z-Brain and ZBB to be co-aligned with acceptable precision and minimal perturbation of cell and tissue morphology. This study demonstrates the feasibility of integrating whole brain datasets, despite disparate acquisition protocols and reference templates, when sufficient information is present for bridging.

Anatomical abbreviations

ac

anterior commissure

DT

Thalamus

GT

Griseum tectale

Ha

Habenula

Hc

Hypothalamus caudal zone

Hi

Hypothalamus intermediate zone

MO

Medulla oblongata

NXm

Vagus motor neurons

OB

Olfactory bulb

OE

Olfactory epithelium

IO

Inferior olive

LC

Locus coeruleus

MN

Mauthner neuron

MO

Medulla oblongata

Pal

Pallium

pc

posterior commissure

Pr

Pretectum

SR

Superior raphe

Teg

Tegmentum

TeOn

Optic tectum neuropil

TG

Trigeminal ganglion

TL

Torus longitudinalis
Discovering event structure in continuous narrative perception and memory
Authors: Baldassano Christopher , Chen Janice , Zadbood Asieh , Pillow Jonathan W , Hasson Uri , Norman Kenneth A
Published: October 2016

During realistic, continuous perception, humans automatically segment experiences into discrete events. Using a novel model of neural event dynamics, we investigate how cortical structures generate event representations during continuous narratives, and how these events are stored and retrieved from long-term memory. Our data-driven approach enables identification of event boundaries and event correspondences across datasets without human-generated stimulus annotations, and reveals that different regions segment narratives at different timescales. We also provide the first direct evidence that narrative event boundaries in high-order areas (overlapping the default mode network) trigger encoding processes in the hippocampus, and that this encoding activity predicts pattern reinstatement during recall. Finally, we demonstrate that these areas represent abstract, multimodal situation models, and show anticipatory event reinstatement as subjects listen to a familiar narrative. Our results provide strong evidence that brain activity is naturally structured into semantically meaningful events, which are stored in and retrieved from long-term memory.
BioBlocks: Programming protocols in biology made easier
Authors: Gupta Vishal , Irimia Jesus , Pau Ivan , Rodriguez-Paton Alfonso
Published: October 2016

The methods to execute biological experiments are evolving. Affordable fluid handling robots and on-demand biology enterprises are making automating entire experiments a reality. Automation offers the benefit of high-throughput experimentation, rapid prototyping and improved reproducibility of results. However, learning to automate and codify experiments is a difficult task as it requires programming expertise. Here, we present a web-based visual development environment called BioBlocks for describing experimental protocols in biology. It is based on Google's Blockly and Scratch, and requires little or no experience in computer programming to automate the execution of experiments. The experiments can be specified, saved, modified and shared between multiple users in an easy manner. BioBlocks is open-source and can be customized to execute protocols on local robotic platforms or remotely i.e. in the cloud. It aims to serve as a 'de facto' open standard for programming protocols in Biology.
Putting bandits into context: How function learning supports decision making
Authors: Schulz Eric , Konstantinidis Emmanouil , Speekenbrink Maarten
Published: October 2016

We introduce the contextual multi-armed bandit task as a framework to investigate learning and decision making in uncertain environments. In this novel paradigm, participants repeatedly choose between multiple options in order to maximise their rewards. The options are described by a number of contextual features which are predictive of the rewards through initially unknown functions. From their experience with choosing options and observing the consequences of their decisions, participants can learn about the functional relation between contexts and rewards and improve their decision strategy over time. In three experiments, we explore participants’ behaviour in such learning environments. We predict participants’ behaviour by context-blind (mean-tracking, Kalman filter) and contextual (Gaussian process and linear regression) learning approaches combined with different choice strategies. Participants are mostly able to learn about the context-reward functions and their behaviour is best described by a Gaussian process learning strategy which generalizes previous experience to similar instances. In a relatively simple task with binary features, they seem to combine this learning with a “probability of improvement” decision strategy which focuses on alternatives that are expected to lead to an improvement upon a current favourite option. In a task with continuous features that are linearly related to the rewards, participants seem to more explicitly balance exploration and exploitation. Finally, in a difficult learning environment where the relation between features and rewards is non-linear, some participants are again well-described by a Gaussian process learning strategy, whereas others revert to context-blind strategies.
Motivational, proteostatic and transcriptional deficits precede synapse loss, gliosis and neurodegeneration in the B6.HttQ111/+model of Huntington’s disease
Authors: Bragg Robert M. , Coffey Sydney R. , Weston Rory M. , Ament Seth A. , Cantle Jeffrey P. , Minnig Shawn , Funk Cory C. , Shuttleworth Dominic D. , Woods Emily L. , Sullivan Bonnie R. , Jones Lindsey , Glickenhaus Anne , Anderson John S. , Anderson Michael D. , Dunnett Stephen B. , Wheeler Vanessa C. , MacDonald Marcy E. , Brooks Simon P. , Price Nathan D. , Carroll Jeffrey B.
Published: October 2016

We investigated the appearance and progression of disease-relevant signs in the B6.HttQ111/+mouse, a genetically precise model of the mutation that causes Huntington’s disease (HD). We find that B6.HttQ111/+mice are healthy, show no overt signs of central or peripheral inflammation, and no gross motor impairment as late as 12 months of age. Behaviorally, we find that 4-9 month old B6.HttQ111/+mice have normal activity levels and show no clear signs of anxiety or depression, but do show clear signs of reduced motivation. The neuronal density, neuronal size, synaptic density and number of glia is normal in B6.HttQ111/+striatum, the most vulnerable brain region in HD, up to 12 months of age. Despite this preservation of the synaptic and cellular composition of the striatum, we observe clear progressive, striatal-specific, transcriptional dysregulation and accumulation of neuronal intranuclear inclusions (NIIs). Simulation studies suggest these molecular endpoints are sufficiently robust for future preclinical studies, and that B6.HttQ111/+mice are a useful tool for modeling disease-modifying or neuroprotective strategies for disease processes before the onset of overt phenotypes.
Maintaining tiger connectivity and minimizing extinction into the next century: Insights from landscape genetics and spatially-explicit simulations
Authors: Thatte Prachi , Joshi Aditya , Vaidyanathan Srinivas , Landguth Erin , Ramakrishnan Uma
Published: October 2016

Habitat loss is the greatest threat to large carnivores around the world. Maintenance of functional connectivity in fragmented landscapes will be important for long-term species persistence. Here, we merge landscape genetics analyses and spatially-explicit simulations to understand future persistence and extinction of tigers (Panthera tigris) in Central India. Tigers in this landscape are restricted to Protected Areas (PAs) and forest fragments embedded within a mosaic of agricultural fields and human settlements. We examined current population connectivity of tigers across nine reserves (using 116 non-invasively sampled individuals and 12 microsatellites). Genetic data was used to infer resistance-to-movement. Our results suggest that dense human settlements and roads with high traffic are detrimental to tiger movement. We used landscape genetic simulations to model 86 different scenarios that incorporated impacts of future land-use change on inferred population connectivity and extinction. Our results confirm that genetic variability (heterozygosity) will decrease in the future and small and/or isolated PAs will have a high risk of local extinction. The average extinction risk of small PAs reduced by 23-70% on adding a 5 km buffer around exiting boundaries. Unplanned development results in 35% lower heterozygosity and 56% higher average extinction probability for tigers even within protected areas. Increasing tiger numbers in such a scenario decreases extinction probability just by 12 % (from 56% to 44%). Scenarios where habitat connectivity was enhanced and maintained, stepping-stone populations were introduced/maintained, and tiger numbers were increased, led to low overall extinction probability (between 3-21%). Our simulations provide a means to quantitatively evaluate the effects of different land-use change scenarios on connectivity and extinction, linking basic science to land-use change policy and planned infrastructure development.
Inferring Synaptic Excitation/Inhibition Balance from Field Potentials
Authors: Gao Richard D. , Peterson Erik J. , Voytek Bradley
Published: October 2016

Neural circuits sit in a dynamic balance between excitation (E) and inhibition (I). Fluctuations in this E:I balance have been shown to influence neural computation, working memory, and information processing. While more drastic shifts and aberrant E:I patterns are implicated in numerous neurological and psychiatric disorders, current methods for measuring E:I dynamics require invasive procedures that are difficult to perform in behaving animals, and nearly impossible in humans. This has limited the ability to examine the full impact that E:I shifts have in neural computation and disease. In this study, we develop a computational model to show that E:I ratio can be estimated from the power law exponent (slope) of the electrophysiological power spectrum, and validate this relationship using previously published datasets from two species (rat local field potential and macaque electrocorticography). This simple method--one that can be applied retrospectively to existing data--removes a major hurdle in understanding a currently difficult to measure, yet fundamental, aspect of neural computation.
Discordant inheritance of chromosomal and extrachromosomal DNA elements contributes to dynamic disease evolution in glioblastoma
Authors: deCarvalho Ana C. , Kim Hoon , Poisson Laila M. , Winn Mary E. , Mueller Claudius , Cherba David , Koeman Julie , Seth Sahil , Protopopov Alexei , Felicella Michelle , Zheng Siyuan , Multani Asha , Jiang Yongying , Zhang Jianhua , Nam Do-Hyun , Petricoin Emanuel F. , Chin Lynda , Mikkelsen Tom , Verhaak Roel G.W.
Published: October 2016

To understand how genomic heterogeneity of glioblastoma (GBM) contributes to the poor response to therapy, which is characteristic of this disease, we performed DNA and RNA sequencing on GBM tumor samples and the neurospheres and orthotopic xenograft models derived from them. We used the resulting data set to show that somatic driver alterations including single nucleotide variants, focal DNA alterations, and oncogene amplification in extrachromosomal DNA (ecDNA) elements were in majority propagated from tumor to model systems. In several instances, ecDNAs and chromosomal alterations demonstrated divergent inheritance patterns and clonal selection dynamics during cell culture and xenografting. Longitudinal patient tumor profiling showed that oncogenic ecDNAs are frequently retained after disease recurrence. Our analysis shows that extrachromosomal elements increase the genomic heterogeneity during tumor evolution of glioblastoma, independent of chromosomal DNA alterations.
Systemizing and empathy in forensic ASD talk
Authors: Dobbinson Sushie Jayne
Published: October 2016

Purpose

Since often missed in forensic care settings, little is known about how the autism spectrum disorder (ASD) social and communication deficit impacts on rehabilitation work, particularly when accompanied by intellectual disability. The purpose of this paper is to show how Baron-Cohen’s empathizing – systemizing theory can elucidate common processes in the interaction-based risk-reduction work carried on between ASD forensic patients and their clinicians.

Design/methodology/approach

Conversation analysis (CA) is used to analyse the talk of two ASD men engaged in risk reduction work with their clinicians on a forensic intellectual disability ward in a medium secure psychiatric hospital in the UK. The clinicians include two forensic nurses and a speech and language therapist.

Findings

Clinicians adapt to their patients’ systematic processes particularly with regard to helping them understand complex social phenomena such as others’ emotional displays and their understanding of empathy.

Practical implications

Since ASD in forensic care is poorly researched, clinicians have little in the way of guidance about the interactive strengths and weaknesses of their ASD patients, despite risk reduction work being carried out by means of conversational interactions. This paper demonstrates some key aspects of ASD clinical interactions which may be used to inform treatment strategies elsewhere in the forensic establishment.

Originality/value

By using Baron-Cohen’s empathizing systemizing theory in combination with CA, this paper aims to bring understanding of ASD interaction up to date. This is of particular importance for this poorly researched patient group, who, because of the way in which they differ to standard psychiatric patients, are at risk of being detained for lengthy periods where treatment strategies are not designed to fit their social and communicative profiles.
The prevalence of autistic spectrum conditions in a community offender sample
Authors: Bates Andrew
Published: October 2016

Purpose

Previous prevalence studies of likely autistic spectrum condition (ASC) within criminal justice settings have focussed on specialist forensic mental health settings. The purpose of this paper is to examine prevalence of autism in a general community forensic sample.

Design/methodology/approach

In total, 336 offenders managed by a probation office were administered with a recognised screening tool to identify likely autism (AQ-10). Screenings were scored and those above the threshold were identified, where possible further diagnostic information was sought on positive-screened cases.

Findings

In total, 4.5 per cent (15 offenders) of the caseload screened positive for autism. Descriptive demographic information such as gender, age and offence type is provided for this group. Further diagnostic information was available on eight of the cases. Three already had an autism diagnosis and further psychometric assessment indicated that a further three cases were 80 per cent likely to be diagnosable with autism.

Research limitations/implications

Demographic information on the sample could not be compared with norms across the whole probation caseload due to limitation of resources for the project. No further diagnostic information was available on six offenders who screened positive for autism.

Practical implications

The research indicates that autism is not substantially over-represented in a large community offender sample although further research is required to identify the full degree of representation.

Social implications

Different kinds of offences are observed to be committed by offenders who do exhibit autism. It would be useful for criminal justice staff to have a general knowledge about autism, also how people with autism might offend and how they might best be supervised by probation services.

Originality/value

This is the first study of its kind internationally to examine prevalence of autism in a general community forensic sample.
Evaluation of automation levels for construction change management
Authors: Karimidorabati Shahin , Haas Carl T. , Gray Joel
Published: October 2016

Purpose

Current processes to manage changes are subject to failure since they are heavily dependent on human discipline. The purpose of this paper is to evaluate and quantify the difference between levels of automation of change management processes and to provide input for determining the use of automation systems for change management.

Design/methodology/approach

Three generations of change management processes are defined to represent progressive practices used in major capital projects over the past few decades. Discrete event simulation was used to model these processes to capture their behavior and compare their performance according to time and compliance metrics. An oil and gas megaproject served to validate the findings of this modeling and analysis.

Findings

The results showed that automated processes can bring more compliance and real-time traceability, but not a significant time reduction in the change process. This contributes to the understanding of the impact of workflow-based automation on construction process performance. The validity of the conclusions are limited by the breadth of sectors studied and the inability to capture off-line time allocations of the personnel involved. Future research may build on the work presented here by studying additional processes such as requests for information, project change notices, requests for scaffolding, and interface management in various industry sectors.

Originality/value

A new approach for modeling and evaluating construction management process automation is contributed and the specific results of the paper indicate that automated workflow-based change management processes should be implemented in megaprojects.