bluuebunny/crossref_metadata_2025 huggingface dataset:
RETINAL DETACHMENT ASSOCIATED WITH PERIPHERAL TEAR OF THE RETINAL PIGMENT EPITHELIUM IN PACHYCHOROID SPECTRUM DISEASE
Authors: Mikhail Mikel , Nofal Nour , Sebag Mikael
Published: September 2016

Purpose:

To describe a rare case of an exudative retinal detachment associated with a peripheral tear of the retinal pigment epithelium in a young myopic pachychoroid eye.

Methods:

Clinical case report and literature review. Imaging was obtained with color fundus photography, spectral domain optical coherence tomography, fluorescein angiography, and fluorescein angiography.

Results:

A 33-year-old white man presented with an exudative choroidopathy resulting in an exudative neurosensory detachment, associated with peripheral retinal pigment epithelium tears. Spectral domain optical coherence tomography demonstrated a pachychoroid (628 μm) with subfoveal fluid. Despite a secondary pars-plana vitrectomy with silicone oil and later, Densiron-68 (Labtician Ophthalmics Inc) endotamponade, there was an area of persistent subretinal fluid inferiorly. A previously placed scleral buckle was removed, and scleral window surgery performed, with complete resolution of fluid and restoration of vision. Choroidal thickness improved to 333 μm postoperatively.

Conclusion:

Peripheral retinal pigment epithelium tear–associated retinal detachment can be seen in patients with pachychoroid spectrum disease. Scleral window surgery may be considered in the management of these retinal detachments.
YOUNGEST REPORTED CASE OF MACULAR TELANGIECTASIA (MAC TEL) TYPE 2
Authors: Rajesh Bindu , Giridhar Anantharaman
Published: September 2016

Purpose:

To report the occurrence of macular telangiectasia (Mac Tel) Type 2 in a 28-year-old lady.

Methods:

Retrospective case report.

Results:

A 28-year-old obese diabetic lady presented with mild blurring of vision and reading difficulty for 2 months. Clinical examination revealed the presence of myopic refraction and features suggestive of macular telangiectasia Type 2 on fundus evaluation. Fundus fluorescein angiography and optical coherence tomography confirmed the diagnosis of Mac Tel Type 2, Stage 3. As there was no evidence of subretinal neovascular membrane, she was advised to follow-up regularly.

Conclusion:

Mac Tel Type 2 or idiopathic juxtafoveal telangiectasia is a condition commonly reported in middle age or elderly people. Presentation in a young individual alerts us to the possibility of this condition occurring at an early age and also stresses on the need for meticulous examination to detect subtle signs of the condition in the young.
The Effect of Right Colon Retroflexion on Adenoma Detection
Authors: Cohen Jonah , Grunwald Douglas , Grossberg Laurie B. , Sawhney Mandeep S.
Published: September 2016

Background:

Although colonoscopy with polypectomy can prevent up to 80% of colorectal cancers, a significant adenoma miss rate still exists, particularly in the right colon. Previous studies addressing right colon retroflexion have revealed discordant evidence regarding the benefit of this maneuver on adenoma detection with concomitant concerns about safety and rates of maneuver success. In this meta-analysis, we sought to determine the effect of right colon retroflexion on improving adenoma detection compared with conventional colonoscopy without retroflexion, as well as determine the rates of retroflexion maneuver success and adverse events.

Methods:

Multiple databases including MEDLINE, Embase, and Web of Science were searched for studies on right colon retroflexion and its impact on adenoma detection compared with conventional colonoscopy. Pooled analyses of adenoma detection and retroflexion success were based on mixed-effects and random-effects models with heterogeneity analyses.

Results:

Eight studies met the inclusion criteria (N=3660). The primary analysis comparing colonoscopy with right-sided retroflexion versus conventional colonoscopy to determine the per-adenoma miss rate in the right colon was 16.9% (95% confidence interval, 12.5%-22.5%). The overall rate of successful retroflexion was 91.9% (95% confidence interval, 86%-95%) and rate of adverse events was 0.03%.

Conclusions:

Colonoscopy with right-sided retroflexion significantly increases the detection of adenomas in the right colon compared with conventional colonoscopy with a high rate of maneuver success and small risk of adverse events. Thus, reexamination of the right colon in retroflexed view should be strongly considered in future standard of care colonoscopy guidelines for quality improvement in colon cancer prevention.
Oocyte cryopreservation for fertility preservation in women with cancer
Authors: Domingo Javier , Garcia-Velasco Juan A.
Published: September 2016

Purpose of review

It is necessary to clarify the fertility preservation-related points of concern that often frighten patients or physicians when it comes to deciding about oocyte cryopreservation for fertility preservation, which are often perceived as procedure limitations, are sometimes real and often theoretical and may make the prognosis worse.

Recent findings

Letrozole added to gonadotrophins for controlled ovarian stimulation is safe when applied to hormone-sensitive cancer patients as it avoids associated high estradiol levels. This benefit is only for estrogens, but not for progesterone. Triggering ovulation with gonadotropin releasing hormone agonist bolus and adding the gonadotropin releasing hormone antagonist after oocyte retrieval help minimize its effect. A random start is currently widespread as neither results nor offspring are compromised, and it avoids waiting for menstruation and, therefore, delaying treatment.

The cumulative live birth rate is conditioned by the number of available oocytes and patient's age. Assisted reproductive technologies may help cancer patients to achieve pregnancy with good obstetric outcomes and apparent oncological safety. Although counseling should be provided on an individual basis, fertility preservation in cancer patients and later pregnancy in survivors after adequate treatment and follow-up should not be discouraged.
Knee rotationplasty: motion of the body centre of mass during walking
Authors: Rota Viviana , Benedetti Maria Grazia , Okita Yusuke , Manfrini Marco , Tesio Luigi
Published: September 2016

Knee rotationplasty (KRP) is a type of surgery in which the rotated ankle serves as a new knee after being removed for bone tumor. Although this limb salvage surgery is rarely indicated in properly selected patients, it may offer functional advantages over transfemoral amputation, and more durable results compared with a prosthesis. The walking mechanics of adult patients after KRP is believed to be close to that of below-knee amputees. In this study, we evaluated steady-state walking of KRP patients from the viewpoint of the overall muscle power needed to keep the body centre of mass in motion. Three adult patients after KRP, all athletes, were evaluated. Ground reactions during walking were recorded during six subsequent strides on a force treadmill. The positive mechanical work and power sustaining the motion of the centre of mass and the recovery of muscle energy due to the pendulum-like mechanism of walking were computed and compared with those obtained in previous studies from above-knee, below-knee amputees and healthy individuals. In KRP patients, walking was sustained by a muscle power output which was 1.4–3.6 times lower during the step performed on the rotated limb than on the subsequent step. The recovery of muscle energy was slightly lower (0.9) or higher (1.3–1.4 times) on the affected side. In two out of the three KRP patients, our findings were more similar to those from above-knee amputees than to those from below-knee amputees. After KRP, the rotated limb does not necessarily provide the same power provided by below-knee amputation. This may have a relevance for the paralympic classification of KRP athletes.
Primary Ovarian Malignant PEComa: A Case Report
Authors: Westaby Joseph D. , Magdy Nesreen , Fisher Cyril , El-Bahrawy Mona
Published: September 2016

Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm characterized by expression of both melanocytic and smooth muscle markers. PEComas are rarely encountered in the female genital tract. We report a case of malignant primary PEComa of the ovary, and discuss the differential diagnosis. This represents the first case of primary typical malignant PEComa of the ovary.
Local Health Departments' Partners and Challenges in Electronic Exchange of Health Information
Authors: Shah Gulzar H. , Vest Joshua R. , Lovelace Kay , McCullough J. Mac
Published: September 2016

Background:

Unprecedented amounts of data are produced by the health care and other sectors, presenting opportunities for local health departments (LHDs) to access these data. LHDs will need to participate in health information exchange (HIE) with a number of partners in order to benefit from these data resources. LHDs' participation in HIEs with specific partners has not been studied.

Objectives:

To describe the level of and challenges in LHD participation in HIE with other partners, and variation by LHD population size and governance type.

Data and Methods:

This research uses data from the 2015 Informatics Capacity and Needs Assessment Survey, with a target population of all LHDs in the United States. A representative sample of 650 LHDs was drawn using a stratified random sampling design. A total of 324 completed responses were received with a 50% response rate. Survey data were cleaned, and bivariate comparisons were conducted using χ2 and Somer's D.

Results:

Substantial variation existed in LHDs' participation in HIE by type of exchange partner. Although 71% participated in HIE with the state departments of health, only 12% with jail/correctional health, 14% with health or county-based purchasing plans, and 15% with home health agencies. Compared with large LHDs (jurisdiction populations of ≥500 000), smaller LHDs were more likely to participate in HIE with state departments of health, but less likely with other exchange partners. The challenges to HIE participation were technological, and organizational/interorganizational in nature and variation existed by LHDs' population size and governance structure with respect to state authority.

Conclusions:

Local public health agencies more commonly participate in HIE with some partners, but may need to improve HIE with many others. National strategies targeting an increase in HIE of LHDs may use our findings to focus those initiatives.
Clinical Data Systems to Support Public Health Practice: A National Survey of Software and Storage Systems Among Local Health Departments
Authors: McCullough J. Mac , Goodin Kate
Published: September 2016

Context:

Numerous software and data storage systems are employed by local health departments (LHDs) to manage clinical and nonclinical data needs. Leveraging electronic systems may yield improvements in public health practice. However, information is lacking regarding current usage patterns among LHDs.

Objective:

To analyze clinical and nonclinical data storage and software types by LHDs.

Design:

Data came from the 2015 Informatics Capacity and Needs Assessment Survey, conducted by Georgia Southern University in collaboration with the National Association of County and City Health Officials.

Participants:

A total of 324 LHDs from all 50 states completed the survey (response rate: 50%).

Main Outcome Measures:

Outcome measures included LHD's primary clinical service data system, nonclinical data system(s) used, and plans to adopt electronic clinical data system (if not already in use). Predictors of interest included jurisdiction size and governance type, and other informatics capacities within the LHD. Bivariate analyses were performed using χ2 and t tests.

Results:

Up to 38.4% of LHDs reported using an electronic health record (EHR). Usage was common especially among LHDs that provide primary care and/or dental services. LHDs serving smaller populations and those with state-level governance were both less likely to use an EHR. Paper records were a common data storage approach for both clinical data (28.9%) and nonclinical data (59.4%). Among LHDs without an EHR, 84.7% reported implementation plans.

Conclusions:

Our findings suggest that LHDs are increasingly using EHRs as a clinical data storage solution and that more LHDs are likely to adopt EHRs in the foreseeable future. Yet use of paper records remains common. Correlates of electronic system usage emerged across a range of factors. Program- or system-specific needs may be barriers or facilitators to EHR adoption. Policy makers can tailor resources to address barriers specific to LHD size, governance, service portfolio, existing informatics capabilities, and other pertinent characteristics.
An Iterative, Low-Cost Strategy to Building Information Systems Allows a Small Jurisdiction Local Health Department to Increase Efficiencies and Expand Services
Authors: Lovelace Kay A. , Shah Gulzar H.
Published: September 2016

Objective and Methods:

The objective of this case study was to describe the process and outcomes of a small local health department's (LHD's) strategy to build and use information systems. The case study is based on a review of documents and semi-structured interviews with key informants in the Pomperaug District Health Department. Interviews were recorded, transcribed, coded, and analyzed.

Results and Conclusions:

The case study here suggests that small LHDs can use a low-resource, incremental strategy to build information systems for improving departmental effectiveness and efficiency. Specifically, we suggest that the elements for this department's success were simple information systems, clear vision, consistent leadership, and the involvement, training, and support of staff.
Using Information Systems to Improve a Mid-Sized Local Health Department's Effectiveness in a Time of Rapid Change
Authors: Lovelace Kay , Shah Gulzar H.
Published: September 2016

Background:

Informatics capacity building is resource and personnel intensive. Many local health departments (LHDs) face tradeoffs between using their resources to carry out existing mandates and using resources to build their capacity, for example, through informatics, to deliver essential services in a more effective and efficient manner.

Objective:

The purpose of this case study is to describe how a mid-sized LHD built and used information systems to support its strategic objectives, clinical services, and surveillance.

Methods:

The mid-sized LHD described here was chosen for its “best practices” in informatics capacity building and use by NACCHO's study advisory committee. To conduct the case study, authors reviewed departmental documents and conducted semistructured interviews with key informants in the agency. Interviews were recorded, transcribed, thematically coded, and analyzed.

Results and Conclusions:

Findings from the case study suggest that including capacity building in informatics as a strategic priority is one of the most effective ways to ensure that informatics are assessed, updated, and included in resource decisions. Leadership at all levels is critical to the successful implementation of informatics as is proactive partnership with community partners who have overlapping goals. The efficiency and effectiveness of LHDs rely on informatics capacity, especially when resources are challenged.
Electronic Health Records and Meaningful Use in Local Health Departments: Updates From the 2015 NACCHO Informatics Assessment Survey
Authors: Williams Karmen S. , Shah Gulzar H.
Published: September 2016

Background:

Electronic health records (EHRs) are evolving the scope of operations, practices, and outcomes of population health in the United States. Local health departments (LHDs) need adequate health informatics capacities to handle the quantity and quality of population health data.

Purpose:

The purpose of this study was to gain an updated view using the most recent data to identify the primary storage of clinical data, status of data for meaningful use, and characteristics associated with the implementation of EHRs in LHDs.

Methods:

Data were drawn from the 2015 Informatics Capacity and Needs Assessment Survey, which used a stratified random sampling design of LHD populations. Oversampling of larger LHDs was conducted and sampling weights were applied. Data were analyzed using descriptive statistics and logistic regression in SPSS.

Results:

Forty-two percent of LHDs indicated the use of an EHR system compared with 58% that use a non-EHR system for the storage of primary health data. Seventy-one percent of LHDs had reviewed some or all of the current systems to determine whether they needed to be improved or replaced, whereas only 6% formally conducted a readiness assessment for health information exchange. Twenty-seven percent of the LHDs had conducted informatics training within the past 12 months. LHD characteristics statistically associated with having an EHR system were having state or centralized governance, not having created a strategic plan related to informatics within the past 2 years throughout LHDs, provided informatics training in the past 12 months, and various levels of control over decisions regarding hardware allocation or acquisition, software selection, software support, and information technology budget allocation.

Conclusion:

A focus on EHR implementation in public health is pertinent to examining the impact of public health programming and interventions for the positive change in population health.
Investigating Informatics Activity, Control, and Training Needs in Large, Medium, and Small Health Departments
Authors: Bakota Eric , Arnold Ryan , Yang Biru
Published: September 2016

Introduction:

A recent National Association of City & County Health Officials survey shed light on informatics workforce development needs. Local health departments (LHDs) of various jurisdictional sizes and control over informatics may differ on training needs and activity. Understanding the precise nature of this variation will allow stakeholders to appropriately develop workforce development tools to advance the field.

Objective:

To understand the informatics training needs for LHDs of different jurisdictional sizes.

Methods:

Survey responses were analyzed by comparing training needs and LHD population size.

Results:

Larger health departments consistently reported having greater informatics-related capacity and informatics-related training needs. Quantitative data analysis was identified as a primary need for large LHDs. In addition, LHDs that report higher control of informatics/information technology were able to engage in more informatics activities.

Conclusion:

Smaller LHDs need additional resources to improve informatics-related capacity and engagement with the field.
Does physical exercise improve quality of life of advanced cancer patients?
Authors: Navigante Alfredo , Morgado Pablo Cresta
Published: September 2016

Purpose of review

We discuss the principal issues about physical activity in advanced cancer patients through the analyses of the last articles and our experience in this field.

Recent findings

The efficacy of exercise training intervention could improve quality of life (QOL), fatigue and well being in advanced cancer patients. Several published studies have included, nevertheless, patients with early stage of disease and more recently, populations of patients with local advanced tumors of the breast, rectum and lung, who are undergoing neoadjuvant therapy. Despite the insufficient sample of patients in these studies, physical exercise is considered to improve both cardiopulmonary function and physical muscle fitness. Cancer-related fatigue is a devastating symptom in advanced cancer patients that implies loss of mobility and independence.

Physical exercise could be a treatment to increase skeletal muscle endurance and improve well being. In palliative medicine, physical activity could be applied to medical assistance or to design prospective and controlled trials so as to evaluate possible usefulness.
PT-symmetric graphene under a magnetic field
Authors: Bagarello Fabio , Hatano Naomichi
Published: September 2016

We propose a

P
T

-symmetrically deformed version of the graphene tight-binding model under a magnetic field. We analyse the structure of the spectra and the eigenvectors of the Hamiltonians around the
K
and
K
′ points, both in the

P
T

-symmetric and

P
T

-broken regions. In particular, we show that the presence of the deformation parameter
V
produces several interesting consequences, including the asymmetry of the zero-energy states of the Hamiltonians and the breakdown of the completeness of the eigenvector sets. We also discuss the biorthogonality of the eigenvectors, which turns out to be different in the

P
T

-symmetric and

P
T

-broken regions.
Pipette aspiration testing of soft tissues: the elastic half-space model revisited
Authors: Argatov Ivan , Mishuris Gennady
Published: September 2016

The pipette aspiration testing technique is considered, and the elastic half-space model, which was originally introduced in the isotropic incompressible case, is revisited and generalized for the case of transverse isotropy. Asymptotic solutions are obtained in the two limiting cases of a wide and a narrow pipette.
A shotgun approach to identify mechanical nociception genes
Authors: Christianson Melissa G. , Mauthner Stephanie E. , Tracey W. Daniel
Published: September 2016

The molecular mechanisms of sensing noxious mechanical force by nociceptive sensory neurons remain poorly understood. Traditional methods for probing mechanical nociception behavioral responses are labor intensive and involve the testing of one animal at a time. This time consuming process of behavioral testing has largely precluded large scale analyses. Indeed, large scale genetic screens that have been performed thus far have been largely restricted to the investigation of ion channel genes [1]. Here we describe a new behavioral assay for mechanical nociception in which tens of animals can be stimulated simultaneously. In this assay, third instar larvae of the genetically tractable organismDrosophila melanogasterare mechanically stimulated with tungsten particles that are fired from a gun. We have used the new assay to carry out a genetic screen in which we investigated the function of 231 nociceptor enriched genes with tissue-specific RNA interference. Targeting of 21 genes resulted in mechanically insensitive phenotypes and targeting of a single gene resulted in a hypersensitive mechanical nociception phenotype. Six of the identified genes were previously uncharacterized and these were named after famed Roman gladiators (Spartacus (CG14186),Commodus (CG1311), Flamma (CG10914), Crixus(CG6685), Spiculus (CG10932),andVerus (CG31324)).
Actomyosin Contractility Drives Bile Regurgitation as an Early Homeostatic Response to Increased Biliary Pressure in Obstructive Cholestasis
Authors: Gupta Kapish , Li Qiushi , Fan Jun Jun , Shan Fong Eliza Li , Song Ziwei , Mo Shupei , Tang Haoyu , Ng Inn Chuan , Ng Chan Way , Pawijit Pornteera , Zhuo Shuangmu , Dong Chen-Yuan , Low Boon Chuan , Wee Aileen , Dan Yock Young , Kanchanawong Pakorn , So Peter , Viasnoff Virgile , Yu Hanry
Published: September 2016

A wide range of liver diseases manifest as biliary obstruction, or cholestasis. However, the sequence of molecular events triggered as part of the early hepatocellular homeostatic response to abnormal elevations in biliary pressure remains poorly elucidated. Bile canaliculi are dynamic luminal structures that undergo actomyosin-mediated periodic contractions to propel secreted bile. Additionally, pericanalicular actin is accumulated during obstructive cholestasis. Therefore, we hypothesize that the pericanalicular actin cortex undergoes significant remodeling as a regulatory response against increased biliary pressure. Here, we report that, actomyosin contractility induces transient deformations along the canalicular membrane, a process we have termed inward blebbing. We show that these membrane intrusions are initiated by local ruptures in the pericanalicular actin cortex, and they typically retract following repair by actin polymerization and actomyosin contraction. However, above a certain osmotic pressure threshold, these inward blebs pinch away from the canalicular membrane into the hepatocyte cytoplasm as large vesicles (2-8 µm). Importantly, we show that these vesicles aid in the regurgitation of bile from the canalicular system. Conclusion: Actomyosin contractility induces the formation of bile-regurgitative vesicles, thus serving as an early homeostatic mechanism against increased biliary pressure during cholestasis.
An International Inter-Laboratory Digital PCR Study Demonstrates High Reproducibility for the Measurement of a Rare Sequence Variant
Authors: Whale Alexandra S. , Devonshire Alison S. , Karlin-Neumann George , Regan Jack , Javier Leanne , Cowen Simon , Fernandez-Gonzalez Ana , Jones Gerwyn M. , Redshaw Nicholas , Beck Julia , Berger Andreas W. , Combaret Valérie , Kjersgaard Nina Dahl , Davis Lisa , Fina Frederic , Forshew Tim , Andersen Rikke Fredslund , Galbiati Silvia , Hernández Álvaro González , Haynes Charles A. , Janku Filip , Lacave Roger , Lee Justin , Mistry Vilas , Pender Alexandra , Pradines Anne , Proudhon Charlotte , Saal Lao , Stieglitz Elliot , Ulrich Bryan , Foy Carole A. , Parkes Helen , Tzonev Svilen , Huggett Jim F.
Published: September 2016

This study tested the claim that digital PCR (dPCR) can offer highly reproducible quantitative measurements in disparate labs. Twenty-one laboratories measured four blinded samples containing different quantities of aKRASfragment encoding G12D, an important genetic marker for guiding therapy of certain cancers. This marker is challenging to quantify reproducibly using qPCR or NGS due to the presence of competing wild type sequences and the need for calibration. Using dPCR, eighteen laboratories were able to quantify the G12D marker within 12% of each other in all samples. Three laboratories appeared to measure consistently outlying results; however, proper application of a follow-up analysis recommendation rectified their data. Our findings show that dPCR has demonstrable reproducibility across a large number of laboratories without calibration and could enable the reproducible application of molecular stratification to guide therapy, and potentially for molecular diagnostics.

SIGNIFICANCE STATEMENT

The poor reproducibility of molecular diagnostic methods limits their application in part due to the challenges associated with calibration of what are relative measurement approaches. In this study we investigate the performance of one of the only absolute measurement methods available today, digital PCR (dPCR), and demonstrated that when compared across twenty-one laboratories, dPCR has unprecedented reproducibility. These results were achieved when measuring a challenging single nucleotide variant and without calibration to any reference samples. This opens the possibility for dPCR to offer a method to transform reproducibility in the molecular diagnostic field, both by direct use as well as in support of other currently used clinical methods.
Blockwise Site Frequency Spectra for Inferring Complex Population Histories and Recombination
Authors: Beeravolu Champak R. , Hickerson Michael J. , Frantz Laurent A.F. , Lohse Konrad
Published: September 2016

We introduce ABLE (Approximate Blockwise Likelihood Estimation), a novel composite likelihood framework based on a recently introduced summary of sequence variation: the blockwise site frequency spectrum (bSFS). This simulation-based framework uses the the frequencies of bSFS configurations to jointly model demographic history and recombination and is explicitly designed to make inference using multiple whole genomes or genome-wide multi-locus data (e.g.RADSeq) catering to the needs of researchers studying model or non-model organisms respectively. The flexible nature of our method further allows for arbitrarily complex population histories using unphased and unpolarized whole genome sequences.In silicoexperiments demonstrate accurate parameter estimates across a range of divergence models with increasing complexity, and as a proof of principle, we infer the demographic history of the two species of orangutan from multiple genome sequences (over 160 Mbp in length) from each species. Our results indicate that the two orangutan species split approximately 650-950 thousand years ago but experienced a pulse of secondary contact much more recently, most likely during a period of low sea-level South East Asia (∼300,000 years ago). Unlike previous analyses we can reject a history of continuous gene flow and co-estimate genome-wide recombination. ABLE is available for download athttps://github.com/champost/ABLE.
Proper modelling of ligand binding requires an ensemble of bound and unbound states
Authors: Pearce Nicholas M , von Delft Frank
Published: September 2016

Synopsis

We emphasise and demonstrate the importance of modelling the superpositions of ligand-bound and unbound states that commonly occur in crystallographic datasets. Generation of an ensemble that describes not only the dominant state in the crystal is important for the high-quality refinement of low-occupancy ligands, as well as to present a model that explains all of the observed density.

Small molecules bind to only a fraction of the proteins in the crystal lattice, but occupancy refinement of ligands is often avoided by convention; occupancies are set to unity, assuming that the error will be adequately modelled by the B-factors, and weak ligand density is generally ignored or attributed to disorder. Where occupancy refinementisperformed, the superposed atomic state is rarely modelled. We show here that these modelling approaches lead to a degradation of the quality of the ligand model, and potentially affect the interpretation of the interactions between the bound ligand and the protein. Instead, superior accuracy is achieved by modelling the ligand as partially occupied and superposed on a ligand-free “ground-state” solvent model. Explicit modelling of the superposed unbound fraction of the crystal using a reference dataset allows constrained refinement of the occupancy of the ligand with minimal fear of over-fitting. Better representation of the crystal also leads to more meaningful refined atomic parameters such as the B-factor, allowing more insight into dynamics in the crystal. We present a simple approach and simple guidelines for generating the ensemble of bound and unbound states, assuming that datasets representing the unbound states (the ground state) are available. Judged by various electron density metrics, ensemble models are consistently better than corresponding single-state models. Furthermore, local modelling of the superposed ground state is found to be generally more important for the quality of the ligand model than convergence of the overall phases.
Evolutionary and Functional Implications of Hypervariable Loci Within the Skin Virome
Authors: Hannigan Geoffrey D. , Zheng Qi , Meisel Jacquelyn S. , Minot Samuel , Bushman Frederick D. , Grice Elizabeth A.
Published: September 2016

Localized genomic variability is crucial for the ongoing conflicts between infectious microbes and their hosts. An understanding of evolutionary and adaptive patterns associated with genomic variability will help guide development of vaccines and anti-microbial agents. While most analyses of the human microbiome have focused on taxonomic classification and gene annotation, we investigated genomic variation of skin-associated viral communities. We evaluated patterns of viral genomic variation across 16 healthy human volunteers. HPV andStaphylococcusphages contained 106 and 465 regions of diversification, or hypervariable loci, respectively.Propionibacteriumphage genomes were minimally divergent and contained no hypervariable loci. Genes containing hypervariable loci were involved in functions including host tropism and immune evasion. HPV andStaphylococcusphage hypervariable loci were associated with purifying selection. Amino acid substitution patterns were virus dependent, as were predictions of their phenotypic effects. We identified diversity generating retroelements as one likely mechanism driving hypervariability. We validated these findings in an independently collected skin metagenomic sequence dataset, suggesting that these features of skin virome genomic variability are widespread. Our results highlight the genomic variation landscape of the skin virome and provide a foundation for better understanding community viral evolution and the functional implications of genomic diversification of skin viruses.
Protein Kinase C and the stress response pathways are required for kinetochore homeostasis
Authors: Ledesma-Fernández Elena , Herrero Eva , Ólafsson Guðjón , Thorpe Peter H
Published: September 2016

Kinetochores serve both a structural role linking chromosomes to the mitotic spindle and a regulatory role, controlling the timing of mitosis via the spindle assembly checkpoint. To identify proteins that regulate the kinetochore we used a genome-wide fluorescence microscopy approach. We combined an array of mutants of either non-essential gene deletions or essential temperature-sensitive alleles with fluorescently tagged spindle pole bodies (centrosome) and outer kinetochores. Quantitative and qualitative analysis revealed mutants that affect the levels and distribution of kinetochores respectively. These mutants are enriched for those involved in mRNA processing, chromatin organization, DNA replication/repair and mitosis. Our data show that the Pkc1 kinase maintains the kinetochore focus via its ability to prevent cell stress and this phenotype is rescued by an osmotic stabilizer. These data support the notion that kinetochore and microtubule homeostasis are perturbed by the stress response pathways. Hence this observation provides a candidate mechanism for extracellular stress leading to chromosome segregation defects.
Assessing the Relationship Between Vegetation Structure and Harvestmen Assemblage in an Amazonian Upland Forest
Authors: Colmenares Pío , Baccaro Fabrício B. , Tourinho Ana Lúcia
Published: September 2016

1. Arthropod diversity and non-flying arthropod food web are strongly influenced by habitat components related to plant architecture and habitat structural complexity. However, we still poorly understand the relationship between arthropod diversity and the vegetation structure at different spatial scales. Here, we examined how harvestmen assemblages are distributed across six local scale habitats (trees, dead trunks, palms, bushes, herbs and litter), and along three proxies of vegetation structure (number of palms, number of trees and litter depth) at mesoscale.

2. We collected harvestmen using cryptic manual search in 30 permanent plots of 250 m at Reserva Ducke, Amazonas, Brazil. The 30 plots cover approximately 25 km2of upland forests. At a local scale, harvestmen were most diverse and abundant on trees. The likely preference of trees by harvestmen may be related to the variety of local microhabitats offered by large trees. However, despite the strong link between number of harvestman species and individuals with large trees, only harvestmen assemblages composition were related with number of trees and with number of palms, at mesoscale.

3. Harvestman richness and abundance were not related with any vegetation structure predictor at mesoscale. Therefore, areas ofuplandforest in the central Amazon with large trees and palms do not harbor more harvestman species nor individuals, but are suitable to maintain different harvestmen assemblages.
A phylogenetic codon substitution model for antibody lineages
Authors: Hoehn Kenneth B , Lunter Gerton , Pybus Oliver G
Published: September 2016

Phylogenetic methods have shown promise in understanding the development of broadly neutralizing antibody lineages (bNAbs). However, the mutational process that generates these lineages – somatic hypermutation (SHM) – is biased by hotspot motifs, which violates important assumptions in most phylogenetic substitution models. Here, we develop a modified GY94-type substitution model that partially accounts for this context-dependency while preserving independence of sites during calculation. This model shows a substantially better fit to three well-characterized bNAb lineages than the standard GY94 model. We show through simulations that accounting for hotspot motifs can lead to reduced bias of other substitution parameters, and more accurate ancestral state reconstructions. We also demonstrate how our model can be used to test hypotheses concerning the roles of different hotspot and coldspot motifs in the evolution of B-cell lineages. Further, we explore the consequences of the idea that the number of hotspot motifs – and perhaps the mutation rate in general – is expected to decay over time in individual bNAb lineages.
Orientations – perfectly colored
Authors: Nolze G. , Hielscher R.
Published: September 2016

The inverse pole figure (IPF) coloring for a suitable evaluation of crystal orientation data is discussed. The major goal is a high correlation between encoding color and crystal orientation. Revised color distributions of the fundamental sectors are introduced which have the advantages of (1) being applicable for all point groups, (2) not causing color discontinuities within grains, (3) featuring carefully balanced regions for red, cyan, blue, magenta, green and yellow, and (4) an enlarged gray center in opposition to a tiny white center. A new set of IPF color keys is proposed which is the result of a thorough analysis of the colorization problem. The discussion considers several topics: (a) the majority of presently applied IPF color keys generate color discontinuities for specifically oriented grains; (b) if a unique correlation between crystal direction and color is requested, discontinuity-preventing keys are possible for all point groups, except for {\overline 4}, {\overline 3} and {\overline 1}; (c) for a specific symmetry group several IPF color keys are available, visualizing different features of a microstructure; and (d) for higher symmetries a simultaneous IPF mapping of two or three standard reference directions is insufficient for an unequivocal orientation assignment. All color keys are available inMTEX, a freely available MATLAB toolbox.
New insights into BaTi1–x
Sn
x
O3 (0 ≤ x ≤ 0.20) phase diagram from neutron diffraction data
Authors: Veselinović Ljiljana , Mitrić Miodrag , Avdeev Maxim , Marković Smilja , Uskoković Dragan
Published: September 2016

Neutron powder diffraction (NPD) was employed to further investigate the BaTi1−x
Sn
x
O3 (BTS) system previously studied by X-ray diffraction. The room-temperature phase compositions and crystal structures of BTS samples with x = 0, 0.025, 0.05, 0.07, 0.10, 0.12, 0.15 and 0.20 were refined by the Rietveld method using NPD data. It is well known that barium titanate powder (x = 0) crystallizes in the tetragonal P4mm space group. The crystal structures of the samples with 0.025 ≤ x ≤ 0.07 were refined as mixtures of P4mm and Amm2 phases; those with x = 0.1 and 0.12 show the coexistence of rhombohedral R3m and cubic phases, while the samples with x = 0.15 and 0.20 crystallize in a single cubic Pm{\overline 3}m phase. Temperature-dependent NPD was used to characterize the BaTi0.95Sn0.05O3 sample at 273, 333 and 373 K, and it was found to form single-phase Amm2, P4mm and Pm{\overline 3}m structures at these respective temperatures. The NPD results are in agreement with data obtained by differential scanning calorimetry and dielectric permittivity measurements, which show a paraelectric–ferroelectric transition (associated with structural transition) from Pm{\overline 3}m to P4mm at about 353 K followed by a P4mm to Amm2 phase transition at about 303 K.
Alignment of governance and senior executive perceptions of culture
Authors: Looi Evelyn Suk Yi , Greatbanks Richard , Everett André M.
Published: September 2016

Purpose

The purpose of this paper is to examine the alignment of perceived organizational culture between Health Board chairs and Board members with that of their respective senior executive teams. It compares the degree of alignment between these two groups, and analyses them against District Health Board (DHB) performance using the New Zealand Ministry of Health’s national measure “shorter stays in Emergency Departments.”

Design/methodology/approach

Primary survey data were collected across eight DHBs using a modified version of the Organizational Culture Assessment Instrument and utilizes a sample of both higher and lower performing DHBs as defined by the “shorter stays” measure.

Findings

Many health organizations cite Ovseiko and Buchan’s (2012) preferred culture as an ideal model. However, this study’s findings indicate that most DHBs scored higher than the preferred score for “Hierarchical” and “Rational” cultures, and lower for “Clan” and “Developmental” cultures, and therefore calls into question the validity of this organizational profile as the “preferred” cultural state.

Research limitations/implications

This research considers perceived organizational culture from the perspective of the Board members and their respective senior executive teams. It uses a relatively small sample size and excludes potential interactions of national culture.

Practical implications

The findings indicate that healthcare organizations should de-emphasize the dominant “Hierarchical” and “Rational” cultures, and promote “Clan” and “Developmental” cultures within their organizations as a means of potentially improving healthcare performance.

Originality/value

Organizational culture has been highlighted as a major component of performance within healthcare organizations, yet very few studies examine how organizational culture is perceived by governance and executive groups. This study empirically counters prevailing knowledge regarding the most appropriate organizational cultures for healthcare organizations.
Measuring distributed leadership agency in a hospital context
Authors: Jønsson Thomas , Unterrainer Christine , Jeppesen Hans-Jeppe , Jain Ajay Kumar
Published: September 2016

Purpose

The purpose of this paper is to develop and validate an instrument that can measure distributed leadership (DL) as employees’ active participation in DL tasks. The authors designate this as the distributed leadership agency (DLA).

Design/methodology/approach

Data were collected throughout all departments and occupational groups at a merged centralized hospital setting in Denmark. A total of 1,774 employees from 24 hospital departments and 16 occupational groups completed our survey. Structural equation model and confirmatory factor analyses were applied to identify appropriate items and a test for measurement invariance, predictive, discriminant and convergent validity, and ANOVAs were applied to analyse group differences in DLA.

Findings

The identified unidimensional questionnaire consists of seven items, as it is different from, but associated with, empowering leadership, organizational influence, attitude to participation and trust in management. As theoretically predicted, DLA is positively related to self-efficacy, job satisfaction and innovative behaviour. Chief physicians, permanent employees and employee representatives scored higher on the scale than the rest of their respective counterparts.

Practical implications

The survey offers a method to assess a distribution of leadership agency in hospital organizations. Such assessment may provide a basis for organizational and leadership development.

Originality/value

The present study provides a reliable and valid quantitative instrument that measures how much employees at all hierarchical levels are involved in concrete leadership activities in the hospital context. Taking a normative perspective the authors could show that DL – measured with the DLA-questionnaire – has positive effects on employees’ behaviour.
Process redesign for time-based emergency admission targets
Authors: G. Leggat Sandra , Gough Richard , Bartram Timothy , Stanton Pauline , Bamber Greg J. , Ballardie Ruth , Sohal Amrik
Published: September 2016

Purpose

Hospitals have used process redesign to increase the efficiency of the emergency department (ED) to cope with increasing demand. While there are published studies suggesting a positive outcome, recent reviews have reported that it is difficult to conclude that these approaches are effective as a result of substandard research methodology. The purpose of this paper is to explore the perceptions of hospital staff on the impact of a process redesign initiative on quality of care.

Design/methodology/approach

A retrospective qualitative case study examining a Lean Six Sigma (LSS) initiative in a large metropolitan hospital from 2009 to 2010. Non-probability sampling identified interview subjects who, through their participation in the redesign initiative, had a detailed understanding of the implementation and outcomes of the initiative. Between April 2012 and January 2013 26 in-depth semi-structured interviews were conducted and analysed with thematic content analysis.

Findings

There were four important findings. First, when asked to comment on the impact of the LSS implementation, without prompting the staff spoke of quality of care. Second, there was little agreement among the participants as to whether the project had been successful. Third, despite the recognition of the need for a coordinated effort across the hospital to improve ED access, the redesign process was not successful in reducing existing divides among clinicians and among managers and clinicians. Finally, staff expressed tension between production processes to move patients more quickly and their duty of care to their patients as individuals.

Originality/value

One of the first studies to explore the impact of process redesign through in-depth interviews with participating staff, this study adds further evidence that organisations implementing process redesign must ensure the supporting management practices are in place.
What factors determine the choice of public engagement undertaken by health technology assessment decision-making organizations?
Authors: Wortley Sally , Street Jackie , Lipworth Wendy , Howard Kirsten
Published: September 2016

Purpose

Public engagement in health technology assessment (HTA) is increasingly considered crucial for good decision making. Determining the “right” type of engagement activity is key in achieving the appropriate consideration of public values. Little is known about the factors that determine how HTA organizations (HTAOs) decide on their method of public engagement, and there are a number of possible factors that might shape these decisions. The purpose of this paper is to understand the potential drivers of public engagement from an organizational perspective.

Design/methodology/approach

The published HTA literature is reviewed alongside existing frameworks of public engagement in order to elucidate key factors influencing the choice of public engagement process undertaken by HTAOs. A conceptual framework is then developed to illustrate the factors identified from the literature that appear to influence public engagement choice.

Findings

Determining the type of public engagement undertaken in HTA is based on multiple factors, some of which are not always explicitly acknowledged. These factors included the: perceived complexity of the policy-making issue, perceived impact of the decision, transparency and opportunities for public involvement in governance, as well as time and resource constraints. The influences of these factors vary depending on the context, indicating that a one size fits all approach to public engagement may not be effective.

Originality/value

Awareness of the various factors that might influence the type of public engagement undertaken would enable decision makers to reflect on their choices and be more accountable and transparent about their choice of engagement process in eliciting public values and preferences in a HTAO.