bluuebunny/crossref_metadata_2025 huggingface dataset:
Does host outcrossing disrupt compatibility with heritable symbionts?
Authors: Sneck Michelle E. , Rudgers Jennifer A. , Young Carolyn A. , Miller Tom E. X.
Published: January 2019

Vertically transmitted microbes are common in macro‐organisms and can enhance host defense against environmental stress. Because vertical transmission couples host and symbiont lineages, symbionts may become specialized to host species or genotypes. Specialization and contrasting reproductive modes of symbiotic partners could create incompatibilities between inherited symbionts and novel host genotypes when hosts outcross or hybridize. Such incompatibilities could manifest as failed colonization or poor symbiont growth in host offspring that are genetically dissimilar from their maternal host. Moreover, outcrossing between host species could influence both host and symbiont reproductive performance. We tested these hypotheses by manipulating outcrossing between populations and species of two grasses, Elymus virginicus and E. canadensis, that host vertically transmitted fungal endophytes (genus Epichloё). In both greenhouse and field settings, we found that host–symbiont compatibility was robust to variation in host genetic background, spanning within‐population, between‐population and between‐species crosses. Symbiont transmission into the F1 generation was generally high and weakly affected by host outcrossing. Furthermore, endophytes grew equally well in planta regardless of host genetic background and transmitted at high frequencies into the F2 generation. However, outcrossing, especially inter‐specific hybridization, reduced reproductive fitness of the host, and thereby the symbiont. Our results challenge the hypothesis that host genetic recombination, which typically exceeds that of symbionts, is a disruptive force in heritable symbioses. Instead, symbionts may be sufficiently generalized to tolerate ecologically realistic variation in host outcrossing.
Unsupervised trajectories of respiratory/allergic symptoms throughout childhood in the PARIS cohort
Authors: Bougas Nicolas , Just Jocelyne , Beydon Nicole , De Blic Jacques , Gabet Stephan , Lezmi Guillaume , Amat Flore , Rancière Fanny , Momas Isabelle
Published: January 2019

Background

Natural course and co‐occurrence of asthma, eczema, and allergic rhinitis through childhood are still not fully documented. We aim to identify and characterize profiles based on the time course, severity, and apparent triggers of respiratory/allergy symptoms in school‐aged children.

Methods

Data on occurrence, severity, and triggers of asthma, rhinitis, and dermatitis symptoms were collected annually during the follow‐up of the PARIS birth cohort. Children with similar symptom trajectories until 8‐9 years were grouped into profiles using multidimensional (all symptoms considered simultaneously) cluster analysis. Associations between profiles and different health outcomes were analyzed using logistic or linear regression models.

Results

Six distinct symptomatic profiles were identified. A profile was defined by persistent dermatitis symptoms, associated with sensitization to food and aeroallergens. Two profiles were characterized by wheezing: one with early transient wheezing and the other with persistent wheezing related to doctor‐diagnosed asthma, airway obstruction, and perennial aeroallergen sensitization. Three profiles were characterized by rhinitis symptoms: one non‐allergic and two allergic, either with persistent rhinitis symptoms related to allergic multimorbidity and sensitization to perennial aeroallergens, or with late‐onset symptoms, related to both pollen and perennial aeroallergens sensitization as well as low lung function.

Conclusion

This study brings further insights into the developmental profiles of respiratory/allergic outcomes from birth to school age. The identified profiles clearly differed regarding objective features such as diagnosed morbidity, sensitization, or lung function measurements, thus highlighting their biologic and clinical relevance. Allergic rhinitis profiles deserve particular attention, since they were likely to be involved in multimorbidity patterns.
Risk factors of multidrug‐resistant tuberculosis in China: A meta‐analysis
Authors: Feng Mei , Xu YuanGao , Zhang XiangYan , Qiu Qian , Lei ShiGuang , Li JinLan , Yuan Wei , Song QunFeng , Xu JinHong
Published: January 2019

Background

Multidrug‐resistant tuberculosis (MDR‐TB) brings major challenges to the health care workers (HCWs). This study is to determine the risk factors for MDR‐TB, latent tuberculosis infection (LTBI), and tuberculosis (TB) disease among HCWs in China.

Methods

A meta‐analysis was conducted to evaluate the risk factors for MDR‐TB, LTBI, and TB disease among HCWs using a random‐effects model, and the pooled odds ratios (ORs) with 95% confidence interval (CI) were used as effect indicators.

Results

We identified 46 eligible studies and found eight factors were associated with MDR. The ORs with 95% CI are migrant population 1.96 (95% CI, 1.50–2.57), low family income 2.23 (95% CI, 1.74–2.85), retreatment 7.22 (95% CI, 5.63–9.26), anti‐TB treatment history 5.65 (95% CI, 4.80–6.65), multiple episodes of treatment 3.28 (95% CI, 2.60–4.13), adverse reactions 3.48 (95% CI, 2.54–4.76), interrupted treatment 3.18 (95% CI, 2.60–3.89), and lung cavities 1.42 (95% CI, 1.14–1.77). Work duration as a HCW for 5 years and above increased the risk of LTBI and TB. HCWs aged 30 years and above were more susceptible to TB (OR = 1.70, 95% CI: 1.37–2.09).

Conclusion

The risk factors for MDR‐TB in China are possibly migrant population, low family income, retreatment, anti‐TB treatment history, adverse reactions, interrupted treatment, and lung cavities. Longer work duration and greater age are risk factors for LTBI and TB among HCWs.
Deflationism, Creeping Minimalism, and Explanations of Content
Authors: Taylor David E.
Published: January 2019

Metaethics, like many areas of philosophy, has for some time now been experiencing a trend toward deflationary conceptions of truth. This is owing both to a general skepticism about the prospects of any substantial account of truth and also to the “accommodationist” strategies of metaethical expressivists. But I'm skeptical of this trend toward deflationism. The main source of my skepticism, and what I explore in this paper, is the simple fact that deflationism has consequences—consequences that are far‐reaching, controversial, and often underappreciated. I first draw out a number of consequences of deflationism, and then show how certain metaethical positions, despite their explicit acceptance of deflationism, run afoul of these consequences. The consequences of deflationism I have in mind are all consequences to the effect that deflationism is incompatible with one way or another of explaining content. The positions in metaethics I have in mind are all proposed solutions to a certain metaethical problem known as the problem of creeping minimalism. So in the end my claim will be that various proposed solutions to the problem of creeping minimalism both subscribe to deflationism and yet at the same time appeal to explanations of content that are demonstrably incompatible with deflationism.
Colour evolution within orchids depends on whether the pollinator is a bee or a fly
Authors: Shrestha M. , Burd M. , Garcia J. E. , Dorin A. , Dyer A. G.
Published: January 2019

Orchids are a classic angiosperm model for understanding biotic pollination. We studied orchid species within two species‐rich herbaceous communities that are known to have either hymenopteran or dipteran insects as the dominant pollinators, in order to understand how flower colour relates to pollinator visual systems.

We analysed features of the floral reflectance spectra that are significant to pollinator visual systems and used models of dipteran and hymenopteran colour vision to characterise the chromatic signals used by fly‐pollinated and bee‐pollinated orchid species.

In contrast to bee‐pollinated flowers, fly‐pollinated flowers had distinctive points of rapid reflectance change at long wavelengths and a complete absence of such spectral features at short wavelengths. Fly‐pollinated flowers also had significantly more restricted loci than bee‐pollinated flowers in colour space models of fly and bee vision alike.

Globally, bee‐pollinated flowers are known to have distinctive, consistent colour signals. Our findings of different signals for fly pollination is consistent with pollinator‐mediated selection on orchid species that results from the distinctive features of fly visual systems.
The patients have spoken; now it is time for us to listen and move the needle forward
Authors: Lindell Kathleen O.
Published: January 2019

See related Article
The differential impact of HIV and antiretroviral therapy on gender‐specific tuberculosis rates
Authors: Hermans Sabine , Cornell Morna , Middelkoop Keren , Wood Robin
Published: January 2019

Objective

To assess the impact of the HIV epidemic and the rollout of antiretroviral therapy (ART) from 2004 on the gender‐specific TB burden in Cape Town, we investigated temporal changes in TB notification rates, the HIV‐associated relative risk of TB and the population attributable risk fraction (PAF) of HIV by gender.

Methods

Annual TB notifications, mid‐year population and HIV prevalence estimates were used to calculate rates per 100 000 population stratified by gender and HIV. Annual rate ratios (RR) of TB associated with HIV and PAF were calculated by gender.

Results

Pre‐HIV TB notification rates were lower among women than men (146/100 000 vs. 247/100 000). With the onset of the HIV, epidemic rates increased 5.3‐fold in women (to 778/100 000) and 3.7‐fold in men (to 917/100 000) to a peak in 2008, after which they declined by 25% in women (to 634/100 000) and 18% in men (to 755/100 000) by 2014. The HIV‐associated RR of TB was 25% higher in women than in men in 2006 (25 vs. 20), but decreased to the same level in 2014. HIV PAF declined between 2008 and 2014 from 56% to 50% and from 40% to 38% in women and men, respectively.

Conclusions

The HIV epidemic led to greater relative increases in TB rates among women than men. The increased HIV‐associated TB risk in women could be compatible with removal of the biological protection of female gender by HIV infection. The decline in RR and PAF in HIV‐positive women could be explained by increasing ART usage reversing female gender‐related susceptibility.
Blood transfusions, blood storage, and correlation with elevated pulmonary arterial pressures
Authors: Cullison Marilynn , Mahon Richard , McGwin Gerald , McCarron Richard , Browning Robert , Auker Charles
Published: January 2019

BACKGROUND

The aim of this study was to determine if transfusion with RBCs is associated with a rise in mean pulmonary artery pressure (MPAP) and whether such a rise is influenced by the duration of RBC storage.

STUDY DESIGN AND METHODS

A retrospective chart review of intensive care unit patients with pulmonary artery catheters was conducted at two military medical centers.

RESULTS

RBC transfusion is associated with a sustained (≥4 hours) statistically significant 2‐ to 3‐mm Hg rise in MPAP relative to both pretransfusion levels (p < 0.05) and compared to asanguinous fluid infusions (p < 0.05). The magnitude of the rise (all infusions, RBCs, and asanguinous) correlates positively with in‐hospital mortality (p < 0.01) and hospital length of stay (p < 0.01). The duration of RBC storage was not statistically correlated with the magnitude of rise in the population studied. Mean infusion volume was greater for RBC (vs. asanguinous) infusions, but volume adjustment of MPAP values did not alter the pattern or statistical significance of the results.

CONCLUSIONS

Analysis of retrospectively collected data suggests that transfusion of RBC‐containing fluids results in a sustained elevation of MPAP. In the patient population studied, the duration of RBC storage did not correlate with the magnitude of MPAP rise. Future prospective studies of transfusion effects should consider including assessment of MPAP and subpopulation analyses.
Variations in surgical technique for adrenalectomy with caudal vena cava venotomy in 19 dogs
Authors: Knight Rebekah C. , Lamb Christopher R. , Brockman Daniel J. , Lipscomb Victoria J.
Published: January 2019

Objective

To describe surgical techniques, caval occlusion times, and short‐term outcomes in dogs undergoing adrenalectomy with caval venotomy.

Study design

Retrospective case series.

Animals

Dogs undergoing adrenalectomy with caval venotomy between October 1, 2010 and May 31, 2018.

Methods

Medical records of dogs undergoing adrenalectomy with caval venotomy were reviewed for signalment, perioperative management, surgical details, perioperative complications, mortality, and histopathology. Computed tomography images were reviewed to describe tumor morphology and signs of thrombus extension.

Results

Nineteen dogs had adrenal tumor thrombi extending into the prehepatic (14 dogs, 74%), hepatic (3 dogs, 16%), and posthepatic (2 dogs, 11%) caudal vena cava. Tumors occurred in left (11) and right (8) adrenal glands. Median caval occlusion was 6.5 minutes (range, 2–25). Two to six vascular tourniquets were used. Venotomy closure was performed under full caval occlusion in 11 dogs and by using a partial occlusion clamp in 8 dogs. Left ureteronephrectomy was performed in 5 dogs. Perioperative mortality rate was 21% (4 dogs).

Conclusion

Extension of caval tumor thrombus beyond the hepatic hilus did not preclude a good outcome. Longer caval occlusion than has been previously reported was tolerated in some cases. Number of vascular tourniquets used reflected the location of phrenicoabdominal vein insertion on the cava and length of the caval tumor thrombus. Venotomy closure under full occlusion was often required for right adrenal tumors. When required, ureteronephrectomy was left sided.

Clinical significance

Dogs with adrenal tumors extending beyond the hepatic hilus and those requiring a long caval occlusion time can survive adrenalectomy.
Evaluation of a resorbable self‐locking ligation device for performing peripheral lung biopsies in a caprine cadaveric model
Authors: Nylund Adam M. , Chen Chi‐Ya , Höglund Odd V. , Campbell Bonnie G. , Fransson Boel A.
Published: January 2019

Objective

To compare airway leak pressures after sealing peripheral lung biopsy sites with a resorbable ligation device (LigaTie) or thoracoabdominal (TA) staples.

Study design

Ex vivo study.

Animals

Four normal caprine cadavers.

Methods

Twelve lung lobes were harvested from 4 goats immediately after euthanasia. Each lobe was inflated to 20 cm H2O to test for leaks prior to biopsy. Pressure was then maintained at 10 cm H2O. Biopsy samples were obtained 3 cm from the periphery with a resorbable ligation device or a TA stapler (n = 6 per group). After biopsy, inflation pressure was slowly increased to 40 cm H2O while lungs were submerged in water. The pressure at which bubbles were first seen was recorded as the airway leak pressure. The length, width, volume, and weight were recorded for each biopsy sample.

Results

Five of 6 LigaTie biopsy sites sustained the maximum pressure of 40 cm H2O without leaking. One site leaked at 24 cm H2O. The TA‐stapled sites sustained airway pressure to median 25.5 cm H2O (interquartile range, 23.5–26 cm H2O), and none of them reached the maximum pressure (P = .015). There were no differences in biopsy length, volume, or weight between groups.

Conclusion

Biopsy sites sealed with LigaTie withstood higher airway pressure without leaking compared with TA‐stapled biopsy sites in normal cadaveric specimens.

Clinical significance

The LigaTie may be an alternative technique for sealing peripheral lung biopsy sites.
Homes Away from Home
Authors: Wobick-Segev Sarah
Published: January 2019

This book is the first comparative study of Jewish communities in Western, Central, and Eastern Europe. It analyzes how Jews used social and religious spaces to reformulate patterns of fraternity, celebration, and family formation and expressions of self-identification. It suggests that the social patterns that developed between 1890 and the 1930s were formative for the fundamental reshaping of Jewish community and remain essential to our understanding of contemporary Jewish life. Focusing on the social interactions of urban European Jews, this book offers a new perspective on how Jews confronted the challenges of modernity. As membership in the official community was becoming increasingly a matter of individual choice, Jews created spaces to meet new social and emotional needs. Cafés, hotels, and restaurants became places to gather and celebrate festivals and holy days, and summer camps served as sites for the informal education of young children. These places facilitated the option of secular Jewish belonging, marking a clear distinction between Judaism and Jewishness that would have been impossible on a large scale in the pre-emancipation era. By creating new centers for Jewish life, a growing number of historical actors, including women and youth, took the process of community building into their own hands. The contexts of Jewish life expanded beyond the confines of “traditional” Jewish spaces and sometimes challenged the desires of Jewish authorities. The book further argues that these social practices remained vital in reconstructing certain Jewish communities in the wake of the devastation of the Holocaust.
Medical students’ experience of a Teddy Bear Hospital as part of a paediatric curriculum
Authors: Nheu Lilly , Uahwatanasakul Wonie , Gray Amy
Published: January 2019

Introduction: Teddy Bear Hospital is a strategy used to help reduce children’s fears of the healthcare system and teach them about health-related issues. It involves mock consultations where medical students play the role of a “teddy doctor” and children act as the carer of teddy, or another soft toy, requiring consultation. This provides medical students with the opportunity to interact with children and develop communication skills while children are introduced to the medical consultation process. The aim of this study was to evaluate the medical student experience of Teddy Bear Hospital as part of a paediatric curriculum.Methods: We conducted a qualitative observational study using observations and focus group interviews with third-year postgraduate medical students. Strategies for engaging children and medical student behaviours were observed. In focus groups, students discussed their experience and the benefits of involvement they perceive. Inductive content analysis was performed, guided by a phenomenological approach, to identify themes.Results: Three major themes were identified: student discomfort, adapting communication to child temperament and developmental age and how the Teddy Bear Hospital contextimpacts learning. Students experienced discomfort approaching families and through disclosure of medical information. Despite this, students described it as an enjoyable learning experience that taught them to adapt communication to the child. Students also recognised greater challenges in a hospital-based event than one in the community.Conclusions: Participation in Teddy Bear Hospital appears to be a valuable component of the paediatric curriculum for medical students. Through enjoyable experiential learning, students described developing important communication skills with children. While they did experience discomfort in the process, this has potential to deepen learning.
Radiography Student Preferences Regarding Assessments and Feedback
Authors: Oh Audrey , Williams Imelda , Hodgson Yvonne
Published: January 2019

Introduction: Assessment and feedback are important aspects of higher education. In allied health degrees, including radiography, the successful completion of assessments demonstrates that a graduate meets accreditation standards for clinical practice. Feedback within a degree program provides critical information to students on their attainment of these skills. Using a framework of discourse, emotion and identity, this study investigated the preferences of radiography students regarding the assessments and feedback they experienced during their degree program at an Australian university.Method: A survey was administered to all radiography students. Students were asked to rank the assessment tasks and feedback they experienced during their degree program according to what they liked most and learned the most from. Final-year students were asked an additional question about their perceived readiness to meet professional standards.Results: The survey was completed by 129/264 (48.9%) students. The assessment most liked by students was computer-based image analysis (mean 4.99/6.00) while practical assessment was ranked as the assessment that they learned the most from (mean 4.12/6.00). These types of assessments are strongly related to professional identity. Feedback preferences differed depending on the setting—detailed written comments were most preferred on campus (mean 4.88/6.00) while individual verbal feedback was most preferred in the clinical context (mean 4.54/6.00). Discourse is an important aspect of these types of feedback. Final-year students gave positive ratings of their preparedness to meet professional standards.Conclusion: Our findings provide a greater understanding of radiography student preferences in assessment and feedback, which can guide future curriculum design. Students valued and preferred assessments that related to professional identity and real-life radiography skills. Students’ preferred form of feedback was dependent upon the learning environment.
Use of ellipsometry to monitor methane plasma ion implant process
Authors: Bateman Nicholas P. T.
Published: January 2019

Plasma implantation processes, like the Applied Materials PLAD™ ion implant process, directly expose a wafer to plasma. For some plasma chemistries, this exposure leads to both deposition and implant damage. Standard industrial metrologies like thermal wave are only sensitive to implant damage, but device results can depend on other implant metrics, such as implant depth and conformality. Deposition can affect these metrics without affecting the implant damage. Ellipsometry is the ideal industrial technique to measure the deposition left by a plasma implant process. However, it has not been used to evaluate deposition thickness in the presence of implant damage. This paper describes the development of an ellipsometry model that can be used to simultaneously monitor the deposited layer thickness and the implant damage produced by a methane plasma implant process. The extracted thickness of the implanted damage layer tracks thermal wave across a wide range of process parameters, and through an extended “marathon” test. The ellipsometry model is also consistent with a “deposition-only” ellipsometry model that matches scanning electron microscopy thickness measurements when implant damage is absent. For the methane recipe that was studied, ellipsometry can detect process excursions in plasma implantation that cannot be detected with established implant process monitors.
Exploring the source of short-term variations in respiratory data
Authors: Fuchs Susanne , Koenig Laura L. , Petrone Caterina
Published: January 2019

This study explores short-term respiratory volume changes in German oral and nasal stops and discusses to what extent these changes may be explained by laryngeal-oral coordination. It is expected that respiratory volumes decrease more rapidly when the glottis and the vocal tract are open after the release of voiceless aspirated stops. Two experiments were performed using Inductance Plethysmography and acoustics, varying consonantal properties, loudness, and prosodic focus. Results show consistent differences in respiratory slopes between voiceless vs voiced and nasal stops, which are more extreme in a loud or focused position. Thus, respiratory changes can even occur at a local level.
Determining the energetic and informational components of speech-on-speech masking in listeners with sensorineural hearing loss
Authors: Kidd Gerald , Mason Christine R. , Best Virginia , Roverud Elin , Swaminathan Jayaganesh , Jennings Todd , Clayton Kameron , Steven Colburn H.
Published: January 2019

The ability to identify the words spoken by one talker masked by two or four competing talkers was tested in young-adult listeners with sensorineural hearing loss (SNHL). In a reference/baseline condition, masking speech was colocated with target speech, target and masker talkers were female, and the masker was intelligible. Three comparison conditions included replacing female masker talkers with males, time-reversal of masker speech, and spatial separation of sources. All three variables produced significant release from masking. To emulate energetic masking (EM), stimuli were subjected to ideal time-frequency segregation retaining only the time-frequency units where target energy exceeded masker energy. Subjects were then tested with these resynthesized “glimpsed stimuli.” For either two or four maskers, thresholds only varied about 3 dB across conditions suggesting that EM was roughly equal. Compared to normal-hearing listeners from an earlier study [Kidd, Mason, Swaminathan, Roverud, Clayton, and Best, J. Acoust. Soc. Am. 140, 132–144 (2016)], SNHL listeners demonstrated both greater energetic and informational masking as well as higher glimpsed thresholds. Individual differences were correlated across masking release conditions suggesting that listeners could be categorized according to their general ability to solve the task. Overall, both peripheral and central factors appear to contribute to the higher thresholds for SNHL listeners.
Does good perception of vocal characteristics relate to better speech-on-speech intelligibility for cochlear implant users?
Authors: El Boghdady Nawal , Gaudrain Etienne , Başkent Deniz
Published: January 2019

Differences in voice pitch (F0) and vocal tract length (VTL) improve intelligibility of speech masked by a background talker (speech-on-speech; SoS) for normal-hearing (NH) listeners. Cochlear implant (CI) users, who are less sensitive to these two voice cues compared to NH listeners, experience difficulties in SoS perception. Three research questions were addressed: (1) whether increasing the F0 and VTL difference (ΔF0; ΔVTL) between two competing talkers benefits CI users in SoS intelligibility and comprehension, (2) whether this benefit is related to their F0 and VTL sensitivity, and (3) whether their overall SoS intelligibility and comprehension are related to their F0 and VTL sensitivity. Results showed: (1) CI users did not benefit in SoS perception from increasing ΔF0 and ΔVTL; increasing ΔVTL had a slightly detrimental effect on SoS intelligibility and comprehension. Results also showed: (2) the effect from increasing ΔF0 on SoS intelligibility was correlated with F0 sensitivity, while the effect from increasing ΔVTL on SoS comprehension was correlated with VTL sensitivity. Finally, (3) the sensitivity to both F0 and VTL, and not only one of them, was found to be correlated with overall SoS performance, elucidating important aspects of voice perception that should be optimized through future coding strategies.
An enantioconvergent halogenophilic nucleophilic substitution (S
N
2X) reaction
Authors: Zhang Xin , Ren Jingyun , Tan Siu Min , Tan Davin , Lee Richmond , Tan Choon-Hong
Published: January 2019

Attack from the front

Biomolecular substitution reactions are widely applied to compounds with carbon-halogen bonds. Typically, an incoming reactive group will attack the carbon from behind its bond with the halogen, causing the halogen to depart in the opposite direction. Zhang
et al.
now present an asymmetric catalytic substitution reaction that flips the script with an attack on the halogen from the front. Specifically, nitrogen and sulfur nucleophiles stripped bromine from a variety of carbon centers activated by electron-withdrawing groups. A chiral cationic catalyst then directed the carbon fragment back to form a carbon-sulfur or carbon-nitrogen bond enantioselectively.

Science
, this issue p.
400
A regulatory circuit conferring varied flowering response to cold in annual and perennial plants
Authors: Hyun Youbong , Vincent Coral , Tilmes Vicky , Bergonzi Sara , Kiefer Christiane , Richter René , Martinez-Gallegos Rafael , Severing Edouard , Coupland George
Published: January 2019

Diversity in flowering regulation

Annual plants flower for one season and then die, whereas perennials can flower repeatedly year after year. Hyun
et al.
explain how different signaling pathways control such variation in flowering. The perennial pathway requires a floral integrator limited to older shoots. The annual pathway, on the other hand, allows a photoperiodic response to incite flowering on young shoots. Solutions to challenging environments may emerge through evolution as the balance between these regulatory systems shifts.

Science
, this issue p.
409
Distinct molecular programs regulate synapse specificity in cortical inhibitory circuits
Authors: Favuzzi Emilia , Deogracias Rubén , Marques-Smith André , Maeso Patricia , Jezequel Julie , Exposito-Alonso David , Balia Maddalena , Kroon Tim , Hinojosa Antonio J. , F. Maraver Elisa , Rico Beatriz
Published: January 2019

Inhibitory synapse specificity

As neurons build circuits in the developing brain, they select not only what other neurons to connect to but also where on that neuron they will touch base. Working in mice, Favuzzi
et al.
found that gene expression programs that define subsets of interneurons also define where on the postsynaptic partner those interneurons prefer to build a synapse. One class of interneurons prefers to synapse onto the cell body of pyramidal neurons, another class onto the dendrites, and yet another onto the axon initial segment.

Science
, this issue p.
413
Ocean recoveries for tomorrow’s Earth: Hitting a moving target
Authors: Ingeman Kurt E. , Samhouri Jameal F. , Stier Adrian C.
Published: January 2019

Ocean recoveries are moving targets

As the human population has grown, our demands on the ocean have increased rapidly. These demands have similarly increased the pressure we place on these systems, and we now cause considerable damage globally. If we want to maintain healthy ocean ecosystems into the future, we must learn to use ocean resources in a sustainable way and facilitate recovery in regions that have declined. Determining how to make these goals a reality, however, is no small challenge. Ingeman
et al.
review the challenge presented by attempting both to recover and to use ecosystems simultaneously and discuss several approaches for facilitating this essential dual goal.

Science
, this issue p.
eaav1004
Tuning superconductivity in twisted bilayer graphene
Authors: Yankowitz Matthew , Chen Shaowen , Polshyn Hryhoriy , Zhang Yuxuan , Watanabe K. , Taniguchi T. , Graf David , Young Andrea F. , Dean Cory R.
Published: January 2019

Upping the pressure in bilayer graphene

The discovery of superconductivity and exotic insulating phases in twisted bilayer graphene has established this material as a model system of strongly correlated electrons. To achieve superconductivity, the two layers of graphene need to be at a very precise angle with respect to each other. Yankowitz
et al.
now show that another experimental knob, hydrostatic pressure, can be used to tune the phase diagram of twisted bilayer graphene (see the Perspective by Feldman). Applying pressure increased the coupling between the layers, which shifted the superconducting transition to higher angles and somewhat higher temperatures.

Science
, this issue p.
1059
; see also p.
1035
Transport with strong interactions
Authors: Brantut Jean-Philippe
Published: January 2019

Motion of spin and charge is explored with cold-atom quantum simulations
Illustrating nature
Martin Lister and His Remarkable Daughters
Anna Marie Roos
Bodleian Library/University of Oxford, 2019. 224 pp.
Authors: Newman Cathy
Published: January 2019

Art and science interweave in a tale of two talented sisters and their polymath father
Chlorine and Monochloramine Disinfection of
Legionella pneumophila
Colonizing Copper and Polyvinyl Chloride Drinking Water Biofilms
Authors: Buse Helen Y. , J. Morris Brian , Struewing Ian T. , Szabo Jeffrey G.
Published: January 2019

Microbial regrowth within building water systems are promoted by water stagnation, low disinfectant residual, high surface-to-volume ratio, amenable growth temperatures, and colonization of drinking water biofilms. Moreover, biofilms provide protection from environmental stresses, access to higher levels of nutrients, and opportunities for symbiotic interactions with other microbes. Disinfectant efficacy information is historically based on inactivation of pathogens in their planktonic, free-floating forms. However, due to the ecological importance of drinking water biofilms for pathogen survival, this study evaluated the efficacy of two common disinfectants, free chlorine and monochloramine, on
Legionella pneumophila
colonizing mature, drinking water biofilms established on copper and PVC surfaces. Results showed that inactivation was dependent on the disinfectant type and biofilm substratum. Overall, this, and other related research, will provide a better understanding of
Legionella
ecological stability and survival and aid policy makers in the management of exposure risks to water-based pathogens within building water systems.
Identification of a Conserved, Orphan G Protein-Coupled Receptor Required for Efficient Pathogen Clearance in Caenorhabditis elegans
Authors: Anderson Alexandra , Chew Yee Lian , Schafer William , McMullan Rachel
Published: January 2019

G protein-coupled receptors contribute to host defense across the animal kingdom, transducing many signals involved in both vertebrate and invertebrate immune responses. While it has become well established that the nematode worm
Caenorhabditis elegans
triggers innate immune responses following infection with numerous bacterial, fungal, and viral pathogens, the mechanisms by which
C. elegans
recognizes these pathogens have remained somewhat more elusive.
Mechanisms of Resistance to the Contact-Dependent Bacteriocin CdzC/D in
Caulobacter crescentus
Authors: García-Bayona Leonor , Gozzi Kevin , Laub Michael T.
Published: January 2019

Bacteriocins are commonly used by bacteria to kill neighboring cells that compete for resources. Although most bacteriocins are secreted, the aquatic, oligotrophic bacterium
Caulobacter crescentus
produces a two-peptide bacteriocin, CdzC/D, that remains attached to the outer membranes of cells, enabling contact-dependent killing of cells lacking the immunity protein CdzI. The receptor for CdzC/D has not previously been reported. Here, we describe a genetic screen for mutations that confer resistance to CdzC/D. One locus identified,
perA
, encodes a pentapeptide repeat protein that resides in the outer membrane of target cells, where it may act as the direct receptor for CdzC/D. Collectively, our results provide new insight into bacteriocin function and diversity.
Rare Detection of Antiviral Functions of Polyclonal IgA Isolated from Plasma and Breast Milk Compartments in Women Chronically Infected with HIV-1
Authors: Tay Matthew Zirui , Kunz Erika L. , Deal Aaron , Zhang Lu , Seaton Kelly E. , Rountree Wes , Eudailey Joshua A. , Heptinstall Jack , McRaven Michael D. , Matias Edgar , McGuire Erin , Yates Nicole L. , Perez Lautaro G. , Montefiori David C. , Overman R. Glenn , Hope Thomas J. , Shen Xiaoying , Kalilani Linda , Fouda Genevieve G. , Tomaras Georgia D. , Permar Sallie R.
Published: January 2019

Antibodies within the mucosa are part of the first line of defense against mucosal pathogens. Evaluating mucosal antibody isotypes, specificities, and antiviral functions in relationship to the systemic antibody profile can provide insights into whether the antibody response is coordinated in response to mucosal pathogens. In a natural immunity cohort of HIV-infected lactating women, we mapped the fine specificity and function of IgA in breast milk and plasma and compared these with the autologous IgG responses. Antigen specificities and functions differed between IgG and IgA, with antiviral functions (neutralization and phagocytosis) predominantly mediated by the IgG fraction in both milk and plasma. Furthermore, the specificity of milk IgA differed from that of systemic IgA. Our data suggest that milk IgA and systemic IgA should be separately examined as potential correlates of risk. Preventive vaccines may need to employ different strategies to elicit functional antiviral immunity by both antibody isotypes in the mucosa.
GADD45γ Activated Early in the Course of Herpes Simplex Virus 1 Infection Suppresses the Activation of a Network of Innate Immunity Genes
Authors: She Mingmin , Jiang Haifang , Chen Xiaoxiang , Chen Xiaoqing , Liu Xianjie , Zhang Xueyan , Roizman Bernard , Zhou Grace G.
Published: January 2019

Previous studies from our laboratory reported that knockout of some innate immunity genes was associated with increases in the expression of overlapping networks of genes and significant loss of the ability to support the replication of HSV-1; knockout of other genes was associated with decreases in the expression of overlapping networks of genes and had no effect on virus replication. In this report, we document that depletion of GADD45γ reduced virus yields concurrently with significant upregulation of the expression of a cluster of innate immunity genes comprising IFI16, IFIT1, MDA5, and RIG-I. This report differs from the preceding study in an important respect; i.e., the preceding study found no evidence to support the hypothesis that HSV-1 maintained adequate levels of LGP2 or HDAC4 to block upregulation of the cluster of innate immunity genes. We show that HSV-1 causes upregulation of the GADD45γ gene to prevent the upregulation of innate immunity genes.
Multiple foreign bodies in the facial region from a penetrating stab injury
Authors: Etetafia Mabel Okiemute
Published: January 2019

Penetrating injuries can lead to multiple retained foreign bodies. To present a case of a penetrating stab injury on to the right orbital region of a 37-year-old woman which resulted in lacerations on both eyelids, loss of vision in addition to the retention of glass particle and woven artificial hair strands at the anterior end of the floor of the orbit. The woven artificial hair strand, being flexible in nature, was apparently logged in by the penetrating force of the broken glass used as the stab injury object. Under local anaesthesia, a gentle intermittent pull on one hair strand led to the dislodgement of a piece of broken glass particle along with the other end of the hair strand. The resultant wound was repaired. Stab injuries can result in retained multiple foreign bodies. This possibility should be considered during assessment and management of facial injuries to avoid complications of retention.
Progressive cone and cone-rod dystrophies: clinical features, molecular genetics and prospects for therapy
Authors: Gill Jasdeep S , Georgiou Michalis , Kalitzeos Angelos , Moore Anthony T , Michaelides Michel
Published: January 2019

Progressive cone and cone-rod dystrophies are a clinically and genetically heterogeneous group of inherited retinal diseases characterised by cone photoreceptor degeneration, which may be followed by subsequent rod photoreceptor loss. These disorders typically present with progressive loss of central vision, colour vision disturbance and photophobia. Considerable progress has been made in elucidating the molecular genetics and genotype–phenotype correlations associated with these dystrophies, with mutations in at least 30 genes implicated in this group of disorders. We discuss the genetics, and clinical, psychophysical, electrophysiological and retinal imaging characteristics of cone and cone-rod dystrophies, focusing particularly on four of the most common disease-associated genes: GUCA1A, PRPH2, ABCA4 and RPGR. Additionally, we briefly review the current management of these disorders and the prospects for novel therapies.
Three week versus six week immobilisation for stable Weber B type ankle fractures: randomised, multicentre, non-inferiority clinical trial
Authors: Kortekangas Tero , Haapasalo Heidi , Flinkkilä Tapio , Ohtonen Pasi , Nortunen Simo , Laine Heikki-Jussi , Järvinen Teppo LN , Pakarinen Harri
Published: January 2019

Objective

To determine whether treatment of isolated stable Weber B type ankle fractures with a cast or a simple orthotic device for three weeks produces non-inferior outcomes compared with conventional immobilisation in a cast for six weeks.

Design

Randomised, pragmatic, non-inferiority, clinical trial with blinded outcome assessment.

Setting

Two major trauma centres in Finland, 22 December 2012 to 6 June 2016.

Participants

247 skeletally mature patients aged 16 years or older with an isolated Weber B type fibula fracture and congruent ankle mortise in static ankle radiographs.

Interventions

Participants were randomly allocated to conventional six week cast immobilisation (n=84) or three week treatment either in a cast (n=83) or in a simple orthosis (n=80).

Main outcome measures

The primary, non-inferiority, intention-to-treat outcome was the Olerud-Molander Ankle Score at 12 months (OMAS; range 0-100; higher scores indicate better outcomes and fewer symptoms). The predefined non-inferiority margin for the primary outcome was −8.8 points. Secondary outcomes were ankle function, pain, quality of life, ankle motion, and radiographic outcome. Follow-up assessments were performed at 6, 12, and 52 weeks.

Results

212 of 247 randomised participants (86%) completed the study. At 52 weeks, the mean OMAS was 87.6 (SD 18.3) in the six week cast group, 91.7 (SD 12.9) in the three week cast group, and 89.8 (SD 18.4) in the three week orthosis group. The between group difference at 52 weeks for the three week cast versus six week cast was 3.6 points (95% confidence interval −1.9 to 9.1, P=0.20), and for the three week orthosis versus six week cast was 1.7 points (−4.0 to 7.3, P=0.56). In both comparisons, the confidence intervals did not include the predefined inferiority margin of −8.8 points. The only statistically significant between group differences observed in the secondary outcomes and harms in the two primary comparisons were slight improvement in ankle plantar flexion and incidence of deep vein thrombosis, both in the three week orthosis group versus six week cast group.

Conclusion

Immobilisation for three weeks with a cast or orthosis was non-inferior to conventional cast immobilisation for six weeks in the treatment of an isolated stable Weber B type fracture.

Trial registration

ClinicalTrials.govNCT01758835.
Impact and sustainability of centralising acute stroke services in English metropolitan areas: retrospective analysis of hospital episode statistics and stroke national audit data
Authors: Morris Stephen , Ramsay Angus I G , Boaden Ruth J , Hunter Rachael M , McKevitt Christopher , Paley Lizz , Perry Catherine , Rudd Anthony G , Turner Simon J , Tyrrell Pippa J , Wolfe Charles D A , Fulop Naomi J
Published: January 2019

Objectives

To investigate whether further centralisation of acute stroke services in Greater Manchester in 2015 was associated with changes in outcomes and whether the effects of centralisation of acute stroke services in London in 2010 were sustained.

Design

Retrospective analyses of patient level data from the Hospital Episode Statistics (HES) database linked to mortality data from the Office for National Statistics, and the Sentinel Stroke National Audit Programme (SSNAP).

Setting

Acute stroke services in Greater Manchester and London, England.

Participants

509 182 stroke patients in HES living in urban areas admitted between January 2008 and March 2016; 218 120 stroke patients in SSNAP between April 2013 and March 2016.

Interventions

Hub and spoke models for acute stroke care.

Main outcome measures

Mortality at 90 days after hospital admission; length of acute hospital stay; treatment in a hyperacute stroke unit; 19 evidence based clinical interventions.

Results

In Greater Manchester, borderline evidence suggested that risk adjusted mortality at 90 days declined overall; a significant decline in mortality was seen among patients treated at a hyperacute stroke unit (difference-in-differences −1.8% (95% confidence interval −3.4 to −0.2)), indicating 69 fewer deaths per year. A significant decline was seen in risk adjusted length of acute hospital stay overall (−1.5 (−2.5 to −0.4) days; P<0.01), indicating 6750 fewer bed days a year. The number of patients treated in a hyperacute stroke unit increased from 39% in 2010-12 to 86% in 2015/16. In London, the 90 day mortality rate was sustained (P>0.05), length of hospital stay declined (P<0.01), and more than 90% of patients were treated in a hyperacute stroke unit. Achievement of evidence based clinical interventions generally remained constant or improved in both areas.

Conclusions

Centralised models of acute stroke care, in which all stroke patients receive hyperacute care, can reduce mortality and length of acute hospital stay and improve provision of evidence based clinical interventions. Effects can be sustained over time.
Considerations of complexity in rating certainty of evidence in systematic reviews: a primer on using the GRADE approach in global health
Authors: Montgomery Paul , Movsisyan Ani , Grant Sean P , Macdonald Geraldine , Rehfuess Eva Annette
Published: January 2019

Public health interventions and health technologies are commonly described as ‘complex’, as they involve multiple interacting components and outcomes, and their effects are largely influenced by contextual interactions and system-level processes. Systematic reviewers and guideline developers evaluating the effects of these complex interventions and technologies report difficulties in using existing methods and frameworks, such as the Grading of Recommendations Assessment, Development and Evaluation (GRADE). As part of a special series of papers on implications of complexity in the WHO guideline development, this paper serves as a primer on how to consider sources of complexity when using the GRADE approach to rate certainty of evidence. Relevant sources of complexity in systematic reviews, health technology assessments and guidelines of public health are outlined and mapped onto the reported difficulties in rating the estimates of the effect of these interventions. Recommendations on how to address these difficulties are further outlined, and the need for an integrated use of GRADE from the beginning of the review or guideline development is emphasised. The content of this paper is informed by the existing GRADE guidance, an ongoing research project on considering sources of complexity when applying the GRADE approach to rate certainty of evidence in systematic reviews and the review authors’ own experiences with using GRADE.