bluuebunny/crossref_metadata_2025 huggingface dataset:
A cluster robustness score for identifying cell subpopulations in single cell gene expression datasets from heterogeneous tissues and tumors
Authors: Kanter Itamar , Dalerba Piero , Kalisky Tomer
Published: August 2018

Motivation

A major aim of single cell biology is to identify important cell types such as stem cells in heterogeneous tissues and tumors. This is typically done by isolating hundreds of individual cells and measuring expression levels of multiple genes simultaneously from each cell. Then, clustering algorithms are used to group together similar single-cell expression profiles into clusters, each representing a distinct cell type. However, many of these clusters result from overfitting, meaning that rather than representing biologically meaningful cell types, they describe the intrinsic ‘noise’ in gene expression levels due to limitations in experimental precision or the intrinsic randomness of biochemical cellular processes. Consequentially, these non-meaningful clusters are most sensitive to noise: a slight shift in gene expression levels due to a repeated measurement will rearrange the grouping of data points such that these clusters break up.

Results

To identify the biologically meaningful clusters we propose a ‘cluster robustness score’: We add increasing amounts of noise (zero mean and increasing variance) and check which clusters are most robust in the sense that they do not mix with their neighbors up to high levels of noise. We show that biologically meaningful cell clusters that were manually identified in previously published single cell expression datasets have high robustness scores. These scores are higher than what would be expected in corresponding randomized homogeneous datasets having the same expression level statistics. We believe that this scoring system provides a more automated way to identify cell types in heterogeneous tissues and tumors.

Supplementary information

Supplementary data are available at Bioinformatics online.
MOLGENIS research: advanced bioinformatics data software for non-bioinformaticians
Authors: van der Velde K Joeri , Imhann Floris , Charbon Bart , Pang Chao , van Enckevort David , Slofstra Mariska , Barbieri Ruggero , Alberts Rudi , Hendriksen Dennis , Kelpin Fleur , de Haan Mark , de Boer Tommy , Haakma Sido , Stroomberg Connor , Scholtens Salome , van de Geijn Gert-Jan , Festen Eleonora A M , Weersma Rinse K , Swertz Morris A
Published: August 2018

Motivation

The volume and complexity of biological data increases rapidly. Many clinical professionals and biomedical researchers without a bioinformatics background are generating big ’-omics’ data, but do not always have the tools to manage, process or publicly share these data.

Results

Here we present MOLGENIS Research, an open-source web-application to collect, manage, analyze, visualize and share large and complex biomedical datasets, without the need for advanced bioinformatics skills.

Availability and implementation

MOLGENIS Research is freely available (open source software). It can be installed from source code (see http://github.com/molgenis), downloaded as a precompiled WAR file (for your own server), setup inside a Docker container (see http://molgenis.github.io), or requested as a Software-as-a-Service subscription. For a public demo instance and complete installation instructions see http://molgenis.org/research.
Pharmacodynamic Analysis of Daptomycin-treated Enterococcal Bacteremia: It Is Time to Change the Breakpoint
Authors: Avery Lindsay M , Kuti Joseph L , Weisser Maja , Egli Adrian , Rybak Michael J , Zasowski Evan J , Arias Cesar A , Contreras German A , Chong Pearlie P , Aitken Samuel L , DiPippo Adam J , Wang Jann-Tay , Britt Nicholas S , Nicolau David P
Published: August 2018

Background

Currently, there is debate over whether the daptomycin susceptibility breakpoint for enterococci (ie, minimum inhibitory concentration [MIC] ≤4 mg/L) is appropriate. In bacteremia, observational data support prescription of high doses (>8 mg/kg). However, pharmacodynamic targets associated with positive patient outcomes are undefined.

Methods

Data were pooled from observational studies that assessed outcomes in daptomycin-treated enterococcal bacteremia. Patients who received an additional antienterococcal antibiotic and/or a β-lactam antibiotic at any time during treatment were excluded. Daptomycin exposures were calculated using a published population pharmacokinetic model. The free drug area under the concentration-time curve to MIC ratio (fAUC/MIC) threshold predictive of survival at 30 days was identified by classification and regression tree analysis and confirmed with multivariable logistic regression. Monte Carlo simulations determined the probability of target attainment (PTA) at clinically relevant MICs.

Results

Of 114 patients who received daptomycin monotherapy, 67 (58.8%) were alive at 30 days. A fAUC/MIC >27.43 was associated with survival in low-acuity (n = 77) patients (68.9 vs 37.5%, P = .006), which remained significant after adjusting for infection source and immunosuppression (P = .026). The PTA for a 6-mg/kg/day (every 24 hours) dose was 1.5%–5.5% when the MIC was 4 mg/L (ie, daptomycin-susceptible) and 91.0%–97.9% when the MIC was 1 mg/L.

Conclusions

For enterococcal bacteremia, a daptomycin fAUC/MIC >27.43 was associated with 30-day survival among low-acuity patients. As pharmacodynamics for the approved dose are optimized only when MIC ≤1 mg/L, these data continue to stress the importance of reevaluation of the susceptibility breakpoint.
Depressive Symptoms and the Buffering Effect of Resilience on Widowhood by Gender
Authors: King Brittany M , Carr Dawn C , Taylor Miles G
Published: August 2018

Background and Objectives

Spousal loss is a stressful life event that often results in significant depressive symptoms, with men often experiencing more significant depressive symptoms than women. Recent research suggests that psychological resilience may play a role in shaping how well people recover from the loss of a spouse. This study examined the moderating effect of resilience on widowhood in relation to changes in depressive symptoms for men and women.

Research Design and Methods

This study used data from the Health and Retirement Study to examine a change in depressive symptoms for men and women who experience spousal loss compared to those who remain continuously married (N = 5,626). We used the Simplified Resilience Score, which is based on measures drawn from the psychosocial and lifestyle questionnaire. Ordinary least squares regression was used to assess depression following reported spousal loss for widows relative to their continuously married counterparts.

Results

Results show resilience moderated depressive symptoms following spousal loss, but these effects varied by gender. Resilience was significantly and negatively associated with depressive symptoms for married but not for widowed women. However, for widowed men, resilience was significantly and negatively associated with depressive symptoms, and a high resilience score buffered the effect of widowhood.

Discussion and Implications

Our study suggests that having high levels of resilience prior to spousal loss may help offset persistent depressive symptoms, especially for men. Implications for future research and clinical practice are discussed.
Participatory management in a high value small-scale fishery in the Mediterranean Sea
Authors: Maravelias Christos D , Vasilakopoulos Paraskevas , Kalogirou Stefanos
Published: August 2018

In the Mediterranean Sea, the dominant type of fisheries is small-scale. Coastal communities remain dependent on fisheries for their income, some of them with limited potential for economic diversification. The top-down micro-management regime has proven ineffective to secure ecological and social sustainability as it lacks flexibility and adaptation to local and regional conditions. This paper explores the advantages of using a participatory approach and a bio-economic model to develop management scenarios in a high value small-scale shrimp trap fishery in Greece. Seeking active stakeholder involvement throughout the management process advanced the identification of management measures aiming at MSY, with high levels of acceptance from stakeholders. It also increased transparency and legitimacy of the proposed management measures and could be considered as a first step towards co-management and regionalization. The participatory approach undertaken could promote compliance and facilitate the transition to sustainable fishing, ensuring the viability of coastal communities and, thus, social sustainability.
Patient perspectives on medication self-management in rural Kenya: a cross-sectional survey
Authors: Kim Erika , Ndege Peter K , Jackson Elizabeth , Clauw Daniel J , Ellingrod Vicki L
Published: August 2018

Objectives

The presence of HIV, tuberculosis and non-communicable diseases result in a double burden of disease in the East African community. Most studies have focused on urban Nairobi and western Kenya, leading to a lack of information on rural regions that make up 75% of the population. This study determined baseline rates and barriers to medication self-management in rural Meru County.

Design

A cross-sectional, descriptive community survey focused on Meru, Kenya.

Setting

Participants were surveyed at a local Kithoka dispensary and the government operated Meru Level 5 Hospital.

Participants

Seventy-five chronic illness patients between June 2016 and July 2016.

Intervention

Twelve-question Measures of Drug Self-Management Scale (MeDS).

Main Outcome Measure

Baseline rates of medication self-management. A score of 10 or more defined ‘adequate’ medication drug self-management.

Results

The average MeDS score was 8.16 ± 2.4, indicating inadequate medication self-management. There was no significant difference across age (P = 0.75), and between the scores of males and females (8.1 ± 2.4 and 8.2 ± 2.5, respectively, P = 0.89). Minor side effects and the idea that taking medicines disrupt life were highly associated with inadequate drug self-management (r = 0.58). Forgetfulness and non-adherence had the highest correlation (r = 0.64). Cost is a large barrier, with 64% agreeing that they have a hard time paying for their medicines.

Conclusions

All questions on the MeDS survey had statistically significant correlations with the overall score, while gender and age did not. The MeDS questionnaire showed to be an effective tool to evaluate risk of long-term non-adherence globally in rural populations.
Elite-Citizen Linkages and Issue Congruency under Competitive Authoritarianism
Authors: Shalaby Marwa , Aydogan Abdullah
Published: August 2018

To what extent, if any, do the issue priorities of elites overlap with that of the public under competitive authoritarianism? While previous studies examined the overlap of the priorities of elites and ordinary citizens in democracies, our knowledge is still limited when we move beyond these contexts. This article aims to contribute to the democratisation and legislative politics literature by testing congruence of issue priorities under competitive authoritarianism. Analysing more than 10,000 legislative texts from the 2012 Moroccan parliament, we found high levels of congruence between the issue priorities of legislators and citizens, especially in non-legislative activities (i.e. parliamentary questions). Moreover, contrary to earlier studies on clientelism and citizen-elite linkage in the Middle East and North Africa (MENA) region, our results demonstrate a higher correlation between the priorities of the two largest political parties and the mass public, when compared with those parties’ core supporters.
Transcriptomics of Epichloë-Grass Symbioses in Host Vegetative and Reproductive Stages
Authors: Nagabhyru Padmaja , Dinkins Randy D. , Schardl Christopher L.
Published: August 2018

Epichloë species are fungal symbionts (endophytes) of cool-season grasses that transmit vertically via inflorescence primordia (IP), ovaries (OV), and ultimately, embryos. Epichloë coenophiala, an endophyte of tall fescue (Schedonorus arundinaceus), provides multiple protective benefits to the grass. We conducted transcriptome analysis of the tall fescue–E. coenophiala symbiosis, comparing IP, OV, vegetative pseudostems (PS), and the lemma and palea (LP) (bracts) of the young floret. Transcriptomes of host OV and PS exhibited almost no significant differences attributable to endophyte presence or absence. Comparison of endophyte gene expression in different plant parts revealed numerous differentially expressed genes (DEGs). The 150 endophyte DEGs significantly higher in PS over OV included genes for alkaloid biosynthesis and sugar or amino acid transport. The 277 endophyte DEGs significantly higher in OV over PS included genes for protein chaperones (including most heat-shock proteins), trehalose synthesis complex, a bax inhibitor-1 protein homolog, the CLC chloride ion channel, catalase, and superoxide dismutase. Similar trends were apparent in the Brachypodium sylvaticum–Epichloë sylvatica symbiosis. Gene expression profiles in tall fescue IP and LP indicated that the endophyte transcriptome shift began early in host floral development. We discuss possible roles of the endophyte DEGs in colonization of reproductive grass tissues.
Cryptic Speciation in Western North America and Eastern Eurasia of the Pathogens Responsible for Laminated Root Rot
Authors: Leal I. , Bergeron M.-J. , Feau N. , Tsui C. K. M. , Foord B. , Pellow K. , Hamelin R. C. , Sturrock R. N.
Published: August 2018

Coniferiporia sulphurascens is a facultative fungal pathogen that causes laminated root rot (LRR) in commercially important coniferous species worldwide. This fungus spreads primarily by way of vegetative mycelium transferring at points of contact between infected and healthy roots. Successful intervention to control LRR requires a better understanding of the population structure and genetic variability of C. sulphurascens. In this study, we investigated the population genetic structure and origin of C. sulphurascens populations in western North America and eastern Eurasia collected from multiple coniferous hosts. By analyzing the small and large mitochondrial ribosomal RNA subunit genes combined with six nuclear loci (internal transcribed spacer region, actin, RNA polymerase II largest subunit, RNA polymerase II second-largest subunit, laccase-like multicopper oxidase, and translation elongation factor 1-α), we observed that none of the alleles among the loci were shared between North American (NA) and Eurasian C. sulphurascens populations. In total, 55 multilocus genotypes (MLGs) were retrieved in C. sulphurascens isolates occurring in these two continental regions. Of these, 41 MLGs were observed among 58 isolates collected from widespread locations in British Columbia (Canada) and the northwestern United States, while 14 MLGs were observed among 16 isolates sampled in Siberia and Japan. Our data showed that the levels of genetic differentiation between the NA and Eurasian populations are much greater than the populations from within each continental region; the two continental populations formed clearly divergent phylogenetic clades or lineages since they were separated approximately 7.5 million years ago. Moreover, the Eurasian population could be the source of the NA population. Our study indicates the existence of cryptic diversity in this pathogen species, and strongly suggests that the NA and Eurasian populations represent two lineages, which have progressively diverged from each other in allopatry.
Evolution of a TAVR Program
Authors: Berger Diane
Published: August 2018

Transcatheter aortic valve replacement (TAVR) is quickly becoming the new standard of care for high- and intermediate-risk patients requiring aortic valve replacement. From May 2012 through April 2018, 1850 patients were evaluated for severe aortic valve stenosis, and over 900 TAVR procedures were performed at the author's institution, Allegheny General Hospital, Pittsburgh. Efficient screening processes, comprehensive review of data, and the less invasive delivery of care have made the TAVR program a viable and sustainable treatment option for patients with severe symptomatic aortic valve stenosis. Developing an efficient and dedicated process for patient evaluation and delivery of care with reevaluation for leaner processes ensures the efficacy and good patient outcomes of a TAVR program.
PERSISTENT PLACOID MACULOPATHY
Authors: Kolomeyer Anton M. , Brucker Alexander J.
Published: August 2018

Purpose:

To review the literature on persistent placoid maculopathy.

Methods:

Several databases were searched for all years for “persistent placoid maculopathy.”

Results:

A total of 21 unique patients were identified (most commonly Caucasian men in their 50s and 60s). Mean ± SD age at time of presentation was 58.6 ± 6.9 years of age, and follow-up time was 29.2 ± 51.9 months. Thirty-three (79%) eyes had subjective symptoms on presentation. Five (24%) patients presented with a prodrome, and four (19%) patients had vitreous cell. Mean ± SD logarithm of minimal angle of resolution presenting versus final vision was 0.48 ± 0.50 (Snellen equivalent, 20/60) versus 0.63 ± 0.52 (Snellen equivalent, 20/84). Systemic inflammation and autoimmune disease were associated with worse presenting and final vision. Persistent placoid maculopathy characteristic imaging features that aid in diagnosing this rare clinical entity include the following: 1) plaque-like hypopigmented, white/yellowish foveal/perifoveal lesions on color fundus photography; 2) early hypofluorescence and late “fill-in” or staining on fluorescein angiography; 3) persistent hypocyanescence on indocyanine green angiography; and 4) choriocapillaris hyposignal on optical coherence tomography angiography. Choroidal neovascularization was present in 50% of eyes, with 62% diagnosed at presentation. Although choroidal neovascularization is typically responsive to anti–vascular endothelial growth factor injections, it is associated with poor visual outcome. Systemic steroids are generally used as first-line agents with addition of other immunomodulatory medications if the disease is refractory or recurrent.

Conclusion:

Precise disease pathophysiology of persistent placoid maculopathy has not been elucidated but most probably relates to selective choriocapillaris hypoperfusion/ischemia/vasculitis. Combination of anti–vascular endothelial growth factor injections and immunosuppressive medications may be effective in controlling disease activity and limiting development of sight-threatening complications.
INCREASED COMPLEMENT LEVELS IN HUMAN VITREOUS ASPIRATES OF PROLIFERATIVE DIABETIC RETINOPATHY AND RETINAL DETACHMENT EYES
Authors: Manoharan Niranjan , Patnaik Jennifer L. , Olson Jeffrey L.
Published: August 2018

Purpose:

To evaluate levels of complement factors in human vitreous of eyes with retinal detachments (RDs) and proliferative diabetic retinopathy (PDR) eyes.

Methods:

Human vitreous samples were collected from eyes undergoing routine vitrectomy at the University of Colorado Health Eye Center (Aurora, CO). Complement factor D, component C5/C5a, and component C9 levels were measured using enzyme-linked immunosorbent assay and multiplex assays. Retinal detachment and PDR eyes were compared with controls, which were defined as eyes with macular holes or epiretinal membranes.

Results:

The levels of complement factor D in PDR (mean = 2,110.0 ng/mL, P = 0.001) and RD (mean = 660.9 ng/mL, P = 0.03) eyes were statistically significantly higher than controls (mean = 290.5 ng/mL). The levels of complement component C9 were also more elevated in PDR (P = 0.004) compared with control but not in RD eyes.

Conclusion:

Elevated complement factors, particularly of the alternative pathway, were noted in PDR and RD eyes compared with controls. One potential explanation for this is that the oxidative stress in RD and PDR eyes leads to complement dysregulation and alternative complement upregulation.
Prophylactic Extended-Field Irradiation for Patients With Cervical Cancer Treated With Concurrent Chemoradiotherapy: A Propensity-Score Matching Analysis
Authors: Wang Weiping , Liu Xiaoliang , Meng Qingyu , Zhang Fuquan , Hu Ke
Published: August 2018

Objective

The aim of the study was to evaluate the efficacy and toxicity of prophylactic extended-field radiation therapy (RT) for cervical cancer patients treated with concurrent chemoradiotherapy (CCRT).

Methods

Records of patients with cervical cancer without para-aortic metastatic lymph nodes who were treated with definitive RT or CCRT between January 2011 and December 2014 were reviewed. Patients were classified into the pelvic RT and extended-field RT groups. An additional dose of 50.4 Gy in 28 fractions was delivered to para-aortic lymph node regions for patients in the extended-field RT group. Cox regression and propensity-score matching (1:1) were used to compare the overall survival (OS), disease-free survival (DFS), distant failure, and para-aortic lymph node failure (PALNF) between the pelvic RT and extended-field RT groups.

Results

A total of 778 patients were analyzed. Of them, 624 patients were treated with pelvic RT and 154 patients received extended-field RT. The median follow-up period was 37.5 months. In multivariate analysis, extended-field RT was an independent prognostic factor of distant failure (hazard ratio [HR] = 0.49, 95% confidence interval [CI] = 0.26–0.90,P= 0.023) and PALNF (HR = 0.012, 95% CI = 0.00–0.49,P= 0.019). However, it was not significant in predicting OS (P= 0.546) and DFS (P= 0.187). With propensity-score matching, 108 pairs of patients were selected. The 3-year OS, DFS, local control, distant failure, and PALNF rates in the pelvic RT and extended-field RT groups were 87.1% and 85.7% (P= 0.681), 71.0% and 80.6% (P= 0.199), 86.6% and 85.0% (P= 0.695), 21.7% and 7.0% (P= 0.016), and 6.6% and 0% (P= 0.014), respectively. The incidences of grade 3 or greater chronic toxicities were 3.5% and 6.5% in the pelvic RT and extended-field RT groups, respectively (P= 0.097).

Conclusions

Prophylactic extended-field RT was associated with decreased distant failure and PALNF and showed a trend in improving DFS in patients with cervical cancer treated with CCRT.
Conjunctival Retention Cysts: Outcomes of Aspiration and Sclerotherapy With Sodium Tetradecyl Sulfate
Authors: Dave Tarjani , Taneja Shikha , Tiple Sweety , Basu Sayan , Naik Milind N.
Published: August 2018

Purpose:

To assess the outcome of aspiration and sclerotherapy with sodium tetradecyl sulfate in the management of conjunctival inclusion cysts.

Methods:

Retrospective interventional case series of 6 patients with clinical diagnosis of conjunctival inclusion cysts treated with cyst aspiration and foam sclerotherapy with 3% sodium tetradecyl sulfate. The volume of the sclerosant was 20% of the aspirated cyst volume.

Results:

Four patients had an inclusion cyst in anophthalmic sockets and 2 patients in sighted eyes. Average time lag between primary surgery and cyst formation was 14.6 months (range 2–30 months). Average amount of fluid aspirated from cyst was 3.07 ml (range 1–9 ml). Average volume of sclerosant injected was (20% of the aspirated volume) 0.55 ml (range 0.2–1.1 ml). All 6 patients showed complete resolution of cyst at a mean follow-up period of 15.6 months (range 9–24 months). All but one showed complete resolution of cyst with single injection sclerosant. Only 1 patient required a second sclerosant injection. There was no ocular surface or implant-related complications in this cohort.

Conclusions:

Cyst aspiration and sodium tetradecyl sulfate foam sclerotherapy is a minimally invasive procedure for the management of conjunctival inclusion cysts in anophthalmic sockets and sighted eyes. The injection of sodium tetradecyl sulfate in a dose of 20% of the aspirate is effective in the management of conjunctival inclusion cysts over a follow-up period of 13 months. The procedure is safe, with insignificant inflammation and without ocular surface or implant complications.
Evolving management considerations in active surveillance for micropapillary thyroid carcinoma
Authors: Ho Allen S. , Chen Irene , Melany Michelle , Sacks Wendy L.
Published: August 2018

Purpose of review

To summarize developments on active surveillance for micropapillary thyroid cancers, with a focus on strategies for optimal risk stratification and caveats that currently limit adoption.

Recent findings

Observational trials encompassing thousands of active surveillance patients worldwide have increasingly demonstrated the viability of active surveillance for small, low-risk thyroid cancers. Collectively, these data have established that with proper patient selection and strict monitoring, more than 85% of such cases remain indolent no meaningful clinical growth over at least 10 years. Moreover, to date no cases of symptomatic progression or distant metastasis have been reported, and that delayed treatment when needed has not led to unresectable disease or higher risk of complications. Deeper investigation to better predict clinical progression is necessary to improve patient selection, given concerns regarding patient anxiety, age eligibility, and underestimation of true disease extent.

Compelling data from ongoing trials support active surveillance as a first-line management option for micropapillary thyroid carcinomas. Proper risk stratification and strict monitoring protocols will be necessary to sustain the excellent results achieved to date. Broad adoption of active surveillance will require further education, collaboration, and equipoise between physicians and patients to optimize such individualized treatment plans.
Characterization of the Neuroendocrine Tumor Immune Microenvironment
Authors: da Silva Annacarolina , Bowden Michaela , Zhang Sui , Masugi Yohei , Thorner Aaron R. , Herbert Zachary T. , Zhou Chensheng Willa , Brais Lauren , Chan Jennifer A. , Hodi F. Stephen , Rodig Scott , Ogino Shuji , Kulke Matthew H.
Published: August 2018

Objectives

The immune environment and the potential for neuroendocrine tumors (NETs) to respond to immune checkpoint inhibitors remain largely unexplored. We assessed immune checkpoint marker expression, lymphocytic infiltrate, and associated mutational profiles in a cohort of small intestine and pancreatic NETs.

Methods

We assessed expression of PDCD1 (PD-1), CD274 (PD-L1), and PDCD1LG2 (PD-L2) in archival tissue from 64 small intestine (SINETs) and 31 pancreatic NETs (pNET). We additionally assessed T-cell infiltrates, categorizing T-cell subsets based on expression of the T-cell markers CD3, CD8, CD45RO (PTPRC), or FOXP3. Finally, we explored associations between immune checkpoint marker expression, lymphocytic infiltrate, and tumor mutational profiles.

Results

Expression of PD-1 or PD-L1 in small intestine or pancreatic NET was rare, whereas expression of PD-L2 was common in both NET subtypes. T-cell infiltrates were more abundant in pNET than in SINET. We found no clear associations between immune checkpoint marker expression, immune infiltrates, and specific mutational profile within each tumor type.

Conclusions

Our findings provide an initial assessment of the immune environment of well-differentiated NETs. Further studies to define the immunologic differences between pNET and SINET, as well as the role of PD-L2 in these tumors, are warranted.
Effectiveness of the Apple iPad as a Spot-reading Magnifier
Authors: Wittich Walter , Jarry Jonathan , Morrice Elliott , Johnson Aaron
Published: August 2018

SIGNIFICANCE

There are no data available comparing the iPad as a portable magnification device with a portable video magnifier. Our study supports the use and integration of mainstream tablet computers into vision rehabilitation to overcome potential barriers to device uptake due to the stigma attached to traditional devices.

PURPOSE

Portable personal tablet computers have taken on an important role as assistive devices for individuals with visual impairment; however, their use is rarely supported by independent data. Our study aims to contribute to evidence-based practice by comparing a tablet computer with a portable video magnifier in their use as spot-reading devices.

METHODS

We compared the Optelec Compact 5 HD portable video magnifier (Optelec, Longueuil, Canada) and the Apple iPad Air tablet computer (Apple Inc, Cupertino, CA) using the SuperVision+ Magnifier app by asking 60 adults with low vision (age range, 19 to 97 years; mean visual acuity, 20/136) to spot read information on a bill, a medication box, and a food label. Their ability to complete each task was timed; they completed the Quebec User Evaluation of Satisfaction with assistive Technology questionnaire and indicated their preferred device.

RESULTS

Performance speed indicated that easier tasks were completed faster; however, there were no statistically significant differences in performance between the two device conditions. The highest satisfaction scores for both devices were identical: dimensions, ease of use, and effectiveness. Preference between the two devices was split at 25 for iPad, 33 for the portable closed-circuit television, and 2 for undecided.

CONCLUSIONS

The results indicate that performance speed on our spot-reading tasks was comparable across the two devices. In addition, subjective judgment of the device features and personal preferences lead us to conclude that both the iPad and the portable magnifier may have certain equivalence in their functionality, depending on the user and the task for which they are used.
Test-retest Variability of a Standardized Low Vision Lighting Assessment
Authors: Wittich Walter , St. Amour Lorie , Jarry Jonathan , Seiple William
Published: August 2018

SIGNIFICANCE

Systematic lighting assessments should be part of low vision evaluations. The LuxIQ has gained popularity as an assessment tool, but its reliability has not been examined independently and is necessary for evidence-based vision rehabilitation.

PURPOSE

Besides magnification, improved lighting levels are a common intervention in reading rehabilitation for individuals with low vision. Determining the appropriate lighting can be a complex and time-consuming task. The LuxIQ is a portable lighting assessment tool that can be used to systematically measure lighting preferences; however, there is little independent evidence to support its reliability in low vision rehabilitation.

METHODS

One hundred nine control subjects (age, 18 to 85 years) and 64 individuals with low vision (age, 27 to 99 years) adjusted both the luminance and color temperature parameters on the LuxIQ while viewing a sentence on the MNREAD at their preferred print size for continuous reading. After 30 minutes, they were asked to repeat the same measurements.

RESULTS

Using Bland-Altman plots, test-retest variability was calculated using the limits of agreement (LOAs). For illuminance, the LOA width was 2806 lux for control subjects and 2657 lux for visually impaired participants. For color temperature, the LOA width was 2807 K for control subjects and 2364 K for those with a visual impairment. Difference scores were centered near zero, indicating overall accuracy.

CONCLUSIONS

The measurement of lighting preference lacks the precision necessary for clinical utility, given that the LOA for luminance ranged more than 2600 lux, with normally sighted and low vision participants. Such variability translates into a range of approximately ±40 or 50 W in an incandescent light bulb, depending on the luminance level, making it clinically difficult to narrow down the options for evidence-based lighting recommendations. Next steps are to examine whether the reading behavior of low vision clients is positively affected by interventions that are based on LuxIQ recommendations.
Impact of HIV Self-Test Distribution to Male Partners of ANC Clients: Results of a Randomized Controlled Trial in Kenya
Authors: Gichangi Anthony , Wambua Jonesmus , Mutwiwa Stephen , Njogu Rosemary , Bazant Eva , Wamicwe Joyce , Wafula Rose , Vrana Caroline J. , Stevens Danielle R. , Mudany Mildred , Korte Jeffrey E.
Published: August 2018

Background:

In Kenya, HIV testing during first antenatal care (ANC) visit is a standard practice for pregnant women. Despite a policy promoting male partner testing in ANC, few male partners accompany their partners for HIV testing. We evaluated the impact of using oral HIV self-testing on HIV couples testing among ANC clients in Kenya and their male partners.

Methods:

In a 3-arm randomized control study in eastern and central Kenya, consenting women attending the first ANC visit were randomized to receive: (1) standard-of-care and a standard information card; (2) an improved card stating the importance of male HIV testing; and (3) 2 oral HIV self-test kits and HIV testing information. Women completed a baseline and endline questionnaire, and consenting male partners were surveyed 3 months after enrolling female ANC clients. The primary outcome was HIV couples testing as reported by the female partners.

Results:

We randomized 1410 women at their first ANC visit of which 1215 were successfully followed up. One thousand one hundred thirty-three male partners consented to the survey. In the self-testing study arm 3, 79.1% (334/422) of the women reported that their partner tested for HIV as part of a couple, compared with 27% (110/406) and 35.1% (136/387) in study arm 1 and study arm 2, respectively. More than 90% of male partners who used the oral HIV self-test kits reported that it was easy to take sample and read the test results.

Conclusions:

The study demonstrates that the ANC platform offers a unique opportunity to increase HIV couples testing among men using self-testing through distribution by their female partners.
Tertiary Hyperparathyroidism With Renal Osteodystrophy on 18F-Fluorocholine PET/CT
Authors: Broos Wouter A.M. , Wondergem Maurits , van der Zant Friso M. , Knol Remco J.J.
Published: August 2018

A 27-year-old man, with a history of chronic renal failure due to obstructive uropathy, treated with hemodialysis and awaiting kidney transplantation, presented with tertiary hyperparathyroidism. Despite regulation of phosphate and calcium and treatment with cinacalcet, the serum parathyroid hormone levels remained elevated. The patient was referred for parathyroidectomy, and a 18F-fluorocholine PET/CT was acquired for preoperative planning. Besides visualization of the hyperfunctioning parathyroid glands, the scan also showed a typical picture of renal osteodystrophy, a finding on 18F-fluorocholine PET/CT that has not been reported before.
Scintigraphic Findings Beyond Ejection Fraction on Hepatobiliary Scintigraphy
Authors: Christensen Chad T. , Peacock Justin G. , Vroman Penny J. , Banks Kevin P.
Published: August 2018

Objective

To determine if classically reported findings associated with chronic cholecystitis on hepatobiliary scintigraphy (HBS), such as delayed small bowel (SB) transit, slow gallbladder (GB) filling, and reversal of the normal GB and SB transit, are associated with a depressed GB ejection fraction (GBEF). The secondary objectives were to determine whether GBEF is correlated with the time of GB filling, time of SB transit, or reversal of normal GB/SB filling sequence. We hypothesize that an association between a depressed GBEF and these classical HBS findings could validate them as surrogate markers for chronic GB disease.

Patients and Methods

We reviewed all HBS exams over a retrospective 16-month period. Data from 221 patients (mean age, 45.3 ± 15.2 years; 152 female and 69 male subjects) who underwent HBS with GBEF determination for evaluation of chronic symptoms concerning for biliary etiology met inclusion criteria. Classically reported findings for cholecystitis were recorded for each patient. Comparisons were made using t test and Fisher test analysis.

Results

Comparing exams with normal and abnormal GBEF values, there were no significant differences based on age, sex, GB fill time, normal versus delayed SB transit, and reversal of normal GB/SB filling sequence. Additionally, we did not see a correlation between the measured GBEF and GB fill time, SB transit time, or reversal of normal GB/SB filling sequence.

Conclusions

Delayed SB transit, slow GB filling time, and reversal of the normal GB and SB filling sequence on HBS imaging are not associated with the measured GBEF and not predictive of chronic GB disease.
Cervical Cancer Presenting as an Omental Cake
Authors: Canbaz Fevziye , Celik Handan , Kefeli Mehmet , Tosun Migraci
Published: August 2018

In women, peritoneal carcinomatosis usually originates from primary ovarian cancer. We report a case of omental cake as the initial presentation of a cervical cancer, which is extremely rare for this disease. 18F-FDG PET/CT imaging demonstrated diffuse hypermetabolic abdominopelvic peritoneal carcinomatosis originating from cervical cancer that was confirmed by histopathologically.
18F-FDG PET/CT and Bone Scintigraphy Findings in Tietze Syndrome
Authors: Oh Jeong Hee , Park Soo Bin , Oh Hong Chul
Published: August 2018

We present an interesting image of a 62-year-old woman revealed with Tietze syndrome by 18F-FDG PET/CT and bone scintigraphy. She presented with right upper chest wall pain with a hard, palpable mass. However, chest radiograph and CT were unrevealing. On PET/CT, intense FDG uptake was noted at the anterior aspect of the right second costal cartilage with dense calcification, which was the correct symptomatic lesion. Bone scan showed increased radioactive uptake at the FDG uptake lesion, but mild uptake was also seen in the asymptomatic lesion.
Nerve ultrasound and magnetic resonance imaging in the diagnosis of neuropathy
Authors: Goedee H. Stephan , van der Pol W. Ludo , Hendrikse Jeroen , van den Berg Leonard H.
Published: August 2018

Purpose of review

This review summarizes the most relevant developments in the fields of nerve ultrasound and MRI in the diagnosis of treatable inflammatory neuropathies over the last 18 months.

Recent findings

MRI and nerve ultrasound can accurately identify potentially treatable neuropathies and thereby help to improve diagnosis. Advanced MRI techniques also show potential to dissect pathophysiology. The apparent mismatch between nerve function and morphology is not surprising and reflects different dimensions of the disease process in neuropathies.

MRI and nerve ultrasound have become useful tools in the diagnosis of inflammatory neuropathies.

Video Abstract

http://links.lww.com/CONR/A45
Richard Nelson Perham. 27 April 1937—14 February 2015
Authors: Berry Alan , Radford Sheena E.
Published: August 2018

Richard Nelson Perham, FRS, FMedSci, FRSA, was a British professor of structural biochemistry. He undertook his academic career at the University of Cambridge, holding positions as lecturer, reader, chair and head of the Department of Biochemistry, as well as becoming Master of St John's College. Perham published close to 300 scientific papers on protein structure and function, with a focus on mechanistic enzymology, particularly how large multienzyme complexes and flavin-containing enzymes work. He is most renowned for determining how reactive intermediates are transferred between enzyme active sites, for alterations of coenzyme and substrate specificity by his pioneering use of protein engineering and for developing protein display methodologies. Married to Nancy Lane-Perham, and with their two children, Perham enjoyed a full and active life in Cambridge and St John's College. He was a keen participator and supporter of sport and enjoyed art, literature, theatre and music. Perham was a vocal and active champion of equal opportunity in education. His legacy to science is a greater understanding of how enzymes work. His legacy to scientists is as a role model of how to attain the highest levels of achievement while maintaining a sense of personal modesty and a keen support for others.
Replicative cellular age distributions in compartmentalized tissues
Authors: Böttcher Marvin A. , Dingli David , Werner Benjamin , Traulsen Arne
Published: August 2018

The cellular age distribution of hierarchically organized tissues can reveal important insights into the dynamics of cell differentiation and self-renewal and associated cancer risks. Here, we examine the effect of progenitor compartments with varying differentiation and self-renewal capacities on the resulting observable distributions of replicative cellular ages. We find that strongly amplifying progenitor compartments, i.e. compartments with high self-renewal capacities, substantially broaden the age distributions which become skewed towards younger cells with a long tail of few old cells. For several of these strongly amplifying compartments, the age distribution becomes virtually independent of the influx from the stem cell compartment. By contrast, if tissues are organized into many downstream compartments with low self-renewal capacity, the shape of the replicative cell distribution in more differentiated compartments is dominated by stem cell dynamics with little added variation. In the limiting case of a strict binary differentiation tree without self-renewal, the shape of the output distribution becomes indistinguishable from that of the input distribution. Our results suggest that a comparison of cellular age distributions between healthy and cancerous tissues may inform about dynamical changes within the hierarchical tissue structure, i.e. an acquired increased self-renewal capacity in certain tumours. Furthermore, we compare our theoretical results to telomere length distributions in granulocyte populations of 10 healthy individuals across different ages, highlighting that our theoretical expectations agree with experimental observations.
Sensory processing by motoneurons: a numerical model for low-level flight control in flies
Authors: Bartussek Jan , Lehmann Fritz-Olaf
Published: August 2018

Rhythmic locomotor behaviour in animals requires exact timing of muscle activation within the locomotor cycle. In rapidly oscillating motor systems, conventional control strategies may be affected by neural delays, making these strategies inappropriate for precise timing control. In flies, wing control thus requires sensory processing within the peripheral nervous system, circumventing the central brain. The underlying mechanism, with which flies integrate graded depolarization of visual interneurons and spiking proprioceptive feedback for precise muscle activation, is under debate. Based on physiological parameters, we developed a numerical model of spike initiation in flight muscles of a blowfly. The simulated Hodgkin–Huxley neuron reproduces multiple experimental findings and explains on the cellular level how vision might control wing kinematics. Sensory processing by single motoneurons appears to be sufficient for control of muscle power during flight in flies and potentially other flying insects, reducing computational load on the central brain during body posture reflexes and manoeuvring flight.
Neural circuit basis of aversive odour processing in Drosophila from sensory input to descending output
Authors: Huoviala Paavo , Dolan Michael-John , Love Fiona M. , Myers Philip , Frechter Shahar , Namiki Shigehiro , Pettersson Lovisa , Roberts Ruairí J.V. , Turnbull Robert , Mitrevica Zane , Breads Patrick , Schlegel Philipp , Bates Alexander Shakeel , Rodrigues Tiago , Aso Yoshinori , Bock Davi , Rubin Gerald M. , Stensmyr Marcus , Card Gwyneth , Costa Marta , Jefferis Gregory S.X.E.
Published: August 2018

Evolution has shaped nervous systems to produce stereotyped behavioural responses to ethologically relevant stimuli. For example when laying eggs, female Drosophila avoid geosmin, an odorant produced by toxic moulds. Here we identify second, third, and fourth order neurons required for this innate olfactory aversion. Connectomics data place these neurons in a complete synaptic circuit from sensory input to descending output. We find multiple levels of valence-specific convergence, including a novel form of axo-axonic input onto second order neurons conveying another danger signal, the pheromone of parasitoid wasps. However, we also observe extensive divergence: second order geosmin neurons connect with a diverse array of 80 third order cell types. We find a pattern of convergence of aversive odour channels at this level. Crossing one more synaptic layer, we identified descending neurons critical for egg-laying aversion. Our data suggest a transition from a labelled line organisation in the periphery to a highly distributed central brain representation that is then coupled to distinct descending pathways.
A new insight into underlying disease mechanism through semi-parametric latent differential network model
Authors: He Yong , Ji Jiadong , Xie Lei , Zhang Xinsheng , Xue Fuzhong
Published: August 2018

Background

In genomic studies, to investigate how the structure of a genetic network differs between two experiment conditions is a very interesting but challenging problem, especially in high-dimensional setting. Existing literatures mostly focus on differential network modelling for continuous data. However, in real application, we may encounter discrete data or mixed data, which urges us to propose a unified differential network modelling for various data types.

Results

We propose a unified latent Gaussian copula differential network model which provides deeper understanding of the unknown mechanism than that among the observed variables. Adaptive rank-based estimation approaches are proposed with the assumption that the true differential network is sparse. The adaptive estimation approaches do not require precision matrices to be sparse, and thus can allow the individual networks to contain hub nodes. Theoretical analysis shows that the proposed methods achieve the same parametric convergence rate for both the difference of the precision matrices estimation and differential structure recovery, which means that the extra modeling flexibility comes at almost no cost of statistical efficiency. Besides theoretical analysis, thorough numerical simulations are conducted to compare the empirical performance of the proposed methods with some other state-of-the-art methods. The result shows that the proposed methods work quite well for various data types. The proposed method is then applied on gene expression data associated with lung cancer to illustrate its empirical usefulness.

Conclusions

The proposed latent variable differential network models allows for various data-types and thus are more flexible, which also provide deeper understanding of the unknown mechanism than that among the observed variables. Theoretical analysis, numerical simulation and real application all demonstrate the great advantages of the latent differential network modelling and thus are highly recommended.