bluuebunny/crossref_metadata_2025 huggingface dataset:
OsMADS25 regulates root system development via auxin signalling in rice
Authors: Zhang Guopeng , Xu Ning , Chen Hongli , Wang Guixue , Huang Junli
Published: June 2018

The phytohormone auxin is essential for root development in plants. OsMADS25 is a homologue of the AGL17‐clade MADS‐box genes in rice. Despite recent progress, the molecular mechanisms underlying the regulation of root development by OsMADS25 are not well known. It is unclear whether OsMADS25 regulates root development via auxin signalling. In this study, we examined the role of OsMADS25 in root development and characterized the signalling pathway through which OsMADS25 regulates root system development in rice. OsMADS25 overexpression significantly increased, but RNAi gene silencing repressed primary root (PR) length and lateral root (LR) density. Moreover, OsMADS25 promoted LR development in response to NO3−. Further study showed that OsMADS25 increased auxin accumulation in the root system by enhancing auxin biosynthesis and transport, while also reducing auxin degradation, therefore stimulating root development. More importantly, OsMADS25 was found to regulate OsIAA14 expression directly by binding to the CArG‐box in the promoter region of OsIAA14, which encodes an Aux/indole acetic acid (IAA) transcriptional repressor of auxin signalling. Elevated auxin levels and decreased OsIAA14 expression might lead to reduced OsIAA14 protein accumulation, as a mechanism to regulate auxin signalling. Therefore, our findings reveal a molecular mechanism by which OsMADS25 modulates root system growth and development in rice, at least partilly, via Aux/IAA‐based auxin signalling.
Magnetic resonance imaging of a giant frontal hemorrhagic mucocele with intracranial extension in a cat
Authors: Vandenberghe Hélène , Thibaud Jean‐Laurent , Moissonnier Pierre , Blot Stéphane
Published: June 2018

A 6‐year‐old domestic short‐haired cat was presented with an acute onset of right cortical encephalopathy. Magnetic resonance imaging (MRI) performed 4 days after the onset of clinical signs revealed a lesion originating from the right frontal sinus with intracranial extension and compression of the right frontal lobe. The lesion was T1‐weighted hypointense and T2‐weighted and fluid‐attenuated inversion recovery hyperintense. Signal voids within the lesion were observed on T2* images, consistent with hemorrhage. Peripheral ring enhancement was visible on postcontrast sequences. These features were consistent with a giant hemorrhagic mucocele. To the authors’ knowledge, this is the first report of MRI characteristics of this lesion in a cat.
Human mesenchymal‐stem‐cells‐derived exosomes are important in enhancing porcine islet resistance to hypoxia
Authors: Nie Wei , Ma Xiaoqian , Yang Cejun , Chen Zeyi , Rong Pengfei , Wu Minghua , Jiang Jianhui , Tan Mengqun , Yi Shounan , Wang Wei
Published: June 2018

Background

Hypoxia‐induced damage is one of the key factors associated with islet graft dysfunction. Mesenchymal stem cells (MSCs) could be used to enhance the therapeutic effect of islet transplantation due to their paracrine potential such as exosomes. In this study, we investigated whether exosomes from human umbilical cord‐derived MSC‐conditioned medium (hu‐MSC‐CM) could increase the survival and function of neonatal porcine islet cell clusters (NICCs) exposed to hypoxia.

Methods

Neonatal porcine islet cell clusters were cultured with hu‐MSC‐CM, with or without exosomes, and native medium RPMI‐1640 (Control) under hypoxic conditions (1% O2). The effects of exosomes on NICCs viability and function in vitro were examined by FACS, the Loops system, and the Extracellular Flux assay, respectively.

Results

Compared with NICCs cultured in RPMI‐1640 medium and hu‐MSC‐CM without exosomes, the survival ratio, viability, and function increased in NICCs cultured in hu‐MSC‐CM with exosomes.

Conclusions

This study found that hu‐MSC‐CM could protect NICCs from hypoxia‐induced dysfunction, and exosomes played an important role in hypoxic resistance, suggesting a potential strategy to improve islet transplantation outcomes.
Glycosphingolipids of porcine, bovine, and equine pericardia as potential immune targets in bioprosthetic heart valve grafts
Authors: Barone Angela , Benktander John , Whiddon Christy , Jin Chunsheng , Galli Cesare , Teneberg Susann , Breimer Michael. E.
Published: June 2018

Background

Pericardial tissue from various animal species is utilized for the production of the bioprosthetic heart valves (BHV) used clinically. Experimental data show that the eventual breakdown of BHV is partly due to immunological interactions with carbohydrate tissue antigens. To understand these processes, we have examined the glycolipid‐based carbohydrate antigens in naïve porcine, bovine, and equine pericardia.

Experimental

Total non‐acid and acid glycosphingolipid fractions were isolated from porcine, bovine, and equine pericardia, and individual glycolipid compounds were characterized by thin‐layer chromatography, mass spectrometry, and binding of monoclonal antibodies, lectins and bacteria in chromatogram binding assays.

Results

The non‐acid glycolipid fractions from all species contained glycosphingolipids based on the globo‐ and neolacto‐series, including pentaglycosylceramides with terminal Galα3 determinants. Terminal blood group A and H (O) structures based on type 2 core chains were present in porcine pericardium, while the Forssman pentaosylceramide was found in equine pericardium. All acid glycolipid fractions contained sulfatide and several gangliosides with both N‐acetyl‐ and N‐glycolyl‐neuraminic acid as terminal saccharide chain determinants.

Conclusion

Several carbohydrate antigens which are potential targets for the human immune system have been identified in the animal pericardial tissues used for the production of BHV. Which of these antigens are left in the tissues after industrial BHV production processes, as well as their potential role in eventual BHV degradation, remains to be elucidated.
Evolution of sialic acids: Implications in xenotransplant biology
Authors: Paul Anu , Padler‐Karavani Vered
Published: June 2018

All living cells are covered with a dense “sugar‐coat” of carbohydrate chains (glycans) conjugated to proteins and lipids. The cell surface glycome is determined by a non‐template driven process related to the collection of enzymes that assemble glycans in a sequential manner. In mammals, many of these glycans are topped with sialic acids (Sia), a large family of acidic sugars. The “Sialome” is highly diverse owing to various Sia types, linkage to underlying glycans, range of carriers, and complex spatial organization. Presented at the front of cells, Sia play a major role in immunity and recognition of “self” versus “non‐self,” largely mediated by the siglecs family of Sia‐binding host receptors. Albeit many mammalian pathogens have evolved to hijack this recognition system to avoid host immune attack, presenting a fascinating host‐pathogen evolutionary arms race. Similarly, cancer cells exploit Sia for their own survival and propagation. As part of this ongoing fitness, humans lost the ability to synthesize the Sia type N‐glycolylneuraminic acid (Neu5Gc), in contrast to other mammals. While this loss had provided an advantage against certain pathogens, humans are continuously exposed to Neu5Gc through mammalian‐derived diet (eg, red meat), consequently generating a complex immune response against it. Circulating anti‐Neu5Gc antibodies together with Neu5Gc on some human tissues mediate chronic inflammation “xenosialitis” that exacerbate various human diseases (eg, cancer and atherosclerosis). Similarly, Neu5Gc‐containing xenografts are exposed to human anti‐Neu5Gc antibodies with implications to sustainability. This review aimed to provide a glimpse into the evolution of Sia and their implications to xenotransplantation.
Determinants of stakeholders’ attitudes to xenotransplantation
Authors: Amin Latifah , Hashim Hasrizul , Mahadi Zurina , Che Ngah Anisah , Ismail Khaidzir
Published: June 2018

Background

Advances in xenotransplantation have the potential to resolve the issue of organ shortages. Despite this, the procedure is expected to meet with a degree of resistance from the public. The purpose of this study was to identify the relevant factors influencing stakeholders’ attitudes towards xenotransplantation.

Methods

A multidimensional survey instrument measuring attitudes to xenotransplantation, including the factors that predict such attitudes, was developed based on earlier studies and validated. It was then completed by 469 respondents who were stratified in accordance with stakeholder groups in Malaysia. A single‐step SEM analysis was then conducted to estimate the measurement and create a structural model using IBM SPSS Amos version 20 with a maximum‐likelihood function.

Results

The attitudes of Malaysian stakeholders towards xenotransplantation were moderately positive (mean score of 4.20). The most important direct predictor of attitude to xenotransplantation was perceived benefit (β = 0.59, P < .001) followed by perceived moral concern (β = −0.32, P < .001). Perceived risk had a strong positive association with moral concern (β = 0.65, P < .001), while attitude to nature had a positive association with perceived benefit (β = 0.16, P < .01) and a negative association with perceived risk (β = −0.19, P < .01). Religiosity had a positive relationship with perceived risk (β = 0.13, P < .05) while engagement with biotechnology had a positive relationship with perceived benefits (β = 0.26, P < .001) and a negative association with risks (β = −0.15, P < .05) and moral issues (β = −0.11, P < .05).

Conclusion

The Malaysian stakeholders were cautious about xenotransplantation. This study showed that their views regarding the application are complex and multifaceted.
Observation of Poiseuille flow of phonons in black phosphorus
Authors: Machida Yo , Subedi Alaska , Akiba Kazuto , Miyake Atsushi , Tokunaga Masashi , Akahama Yuichi , Izawa Koichi , Behnia Kamran
Published: June 2018

Hydrodynamic flow of phonons, previously detected only in a handful of solids, is observed in black phosphorus.
Combination of Amino Acid Substitutions Leading to CTX-M-15-Mediated Resistance to the Ceftazidime-Avibactam Combination
Authors: Compain Fabrice , Dorchène Delphine , Arthur Michel
Published: June 2018

Single amino acid substitutions in the Ω loop of KPC β-lactamases are known to lead to resistance to the ceftazidime-avibactam combination. Here, we investigate this mechanism of resistance in CTX-M enzymes, which are the most widely spread extended-spectrum β-lactamases worldwide.
Geological characterization and assessment of confining layer potential of the Upper Ordovician Utica Shale, Michigan Basin, USA
Authors: Sattler Frank R. , Barnes David A.
Published: June 2018

The objective of this study was to investigate the geological controls on stratigraphic and lithologic variability in the Ordovician Utica Shale and related Collingwood Member in the Michigan Basin in order to assess CO2 sequestration cap rock (seal) potential, including petrophysical properties and mechanical fracture responses. Twelve conventional cores and hundreds of modern well logs from the Michigan Basin were analyzed to correlate and calibrate wireline log signatures with whole-rock mineral composition (from X-ray diffraction analysis) and mechanical properties (from core analysis) to identify brittle, fracture-prone zones, and to validate the Utica Shale as a regional geologic seal. Analysis using scanning electron microscopy with Quantitative Evaluation of Minerals by Scanning Electron Microscope (QEMSCAN®) software was employed to image pores and for quantitative analysis of mineralogy, texture, and porosity. Mercury injection capillary pressure and triaxial strength testing was conducted to assess petrophysical properties and mechanical responses. The results suggest the Utica Shale could reliably contain upwards of 1500 m of buoyant, supercritical CO2 stored in underlying Cambrian and Ordovician reservoirs.
A new sequence stratigraphic model for the Silurian A-1 Carbonate (Ruff Formation) of the Michigan Basin
Authors: Rine Matthew J. , Kaczmarek Stephen E. , Garrett Jonathan D.
Published: June 2018

The A-1 Carbonate is the primary hydrocarbon source rock and an important reservoir component of the Silurian (Niagaran) pinnacle reef complexes in the Michigan Basin. The geology of the A-1 Carbonate, however, is not widely known because the majority of published research about this hydrocarbon system focuses on the pinnacle reefs. To gain a better understanding of the sedimentology and stratigraphy of the A-1 Carbonate, we integrated data from slabbed core, thin section petrography, gamma-ray logs, and energy-dispersive X-ray fluorescence spectrometry (ED-XRF). Thirteen distinct lithofacies within the A-1 Carbonate are recognized, with inferred depositional environments ranging from intertidal-sabkha to deep basin. The recognition of deep-water lithofacies contrasts significantly with previous interpretations of the A-1 Carbonate as a shallow, peritidal deposit.

Lithofacies stacking patterns and ED-XRF elemental trends within the A-1 Carbonate are consistent with basinwide sea-level fluctuations that resulted in deposition of three major stratigraphic units, called the Lower A-1 Carbonate, Rabbit Ear Anhydrite, and Upper A-1 Carbonate. The basal part of the Lower A-1 Carbonate was deposited during a basinwide transgression, as evidenced by deep-water pelagic carbonate accumulation in the basin center, lithofacies that become progressively muddier from bottom to top, and higher concentrations of Si, Al, and K upward, which are interpreted to reflect the influx of continental sediments. The subsequent highstand deposits of the upper part of the Lower A-1 Carbonate are characterized by a decrease in Si, Al, and K, coupled with a shallowing-upward facies succession consistent with increased carbonate production rates. The Rabbit Ear Anhydrite, which bifurcates the Upper and Lower A-1 Carbonate units, exhibits a variety of anhydrite fabrics across a wide range of paleotopographic settings within the basin. The Rabbit Ear Anhydrite is interpreted to reflect a time-correlative sea-level drawdown, which caused basin restriction, gypsum deposition, and elevated concentrations of redox-sensitive elements, such as Mo and Ni. The Upper A-1 Carbonate represents sedimentation during another major basinwide transgression that culminated in the deposition of shallow-water microbialites on the crests of previously exposed Niagara reef complexes. Similar to the Lower A-1 Carbonate, the base of the Upper A-1 Carbonate exhibits elemental signatures indicative of continental influence, whereas the overlying highstand deposits are characterized by more normal marine conditions and lower concentrations of Si, Al, and K.
Regional reservoir characterization of the Ordovician Upper St. Peter Sandstone, Michigan Basin, USA
Authors: Stephen Zdan , Barnes David A.
Published: June 2018

The Middle Ordovician St. Peter Sandstone in the Michigan Basin is a target for hydrocarbon exploration/production, and carbon sequestration and geologic storage. The St. Peter Sandstone is predominantly a marine sandstone with four dominant lithologic facies. The uppermost facies contains zones of porosity and good reservoir quality. Because of the mostly uniform, quartzose detrital grain composition, diagenesis played a dominant role in reservoir quality development. The distribution of diagenetic alteration is believed to result from variations in depositional setting and related geologic processes, including variations in sediment accumulation rate. Early marine carbonate cements preserved precompaction intergranular space available for late diagenetic processes, including the inhibition of quartz overgrowth and decementation. Data from conventional cores, petrographic/petrologic techniques, and wireline logs were used to assess stratigraphic and sedimentologic controls on vertical and horizontal variability of reservoir quality. Evidence for early marine cements and related enhanced reservoir quality is associated with thin shale beds (interpreted as flooding surfaces), which are regionally correlative across the basin.
Utilization of modern and ancient analogs to constrain 3-D geostatistical models, Devonian of South Buckeye field, Michigan Basin
Authors: McCloskey Shawn M. , Grammer G. Michael
Published: June 2018

Middle Devonian Dundee Formation carbonates are prolific hydrocarbon reservoirs throughout the Michigan Basin that have produced in excess of 375 million barrels of oil from more than 100 fields. There is limited fundamental understanding of the complex facies mosaics and stratigraphic architecture in this interval. This stratigraphic complexity is likely controlling the reservoir architecture in both lateral and vertical dimensions. The primary goal of this study was to develop a more detailed understanding of the stratigraphic architecture of the Dundee Formation in the South Buckeye field through utilization of closely spaced subsurface cores and accompanying wireline logs. Data on facies types, vertical stacking patterns, and variability within the field were then combined with modern and ancient analogs to develop the parameters to populate a series of three-dimensional (3-D) static geostatistical models. A fundamental question was to determine if the geographic distribution of patch reefs in the South Buckeye field could be accurately modeled with industry-standard geostatistical software (Schlumberger’s Petrel) based on core and wireline log data without a tie to 3-D seismic data. This study used geometrical data from multiple modern and ancient depositional analogs to constrain the geostatistical models. The geographic distribution and internal architecture of patch reefs were defined through the integration of petrophysical and high-density petrographic analyses from the subsurface core data.

Based on core, wireline log analysis, and depositional analogs, three end-member interpretations were modeled geostatistically and used to define the distribution and scale of the patch reef reservoirs in the South Buckeye field. As with many carbonate reservoirs, a 3-D static reservoir model is a critical step in the workflow for efficient hydrocarbon extraction, natural gas storage, and CO2 sequestration, and this study provides insight into the Michigan Basin Dundee Formation patch reefs as well as possibly other Devonian carbonates and reef trends around the world.
Controls on stratigraphy and sedimentation of the Mississippian Marshall Formation, Michigan Basin, USA
Authors: Adducci Joseph G. , Barnes David A.
Published: June 2018

An understanding of regional orogenic, climatic, and eustatic processes is critical to interbasinal correlation of Paleozoic strata in eastern North America. Tectonic activity associated with the culmination of Appalachian orogenic events has been shown to have regional influence on paleostructure and sediment dispersal in the Appalachian foreland basin and adjacent intracratonic Illinois and Michigan Basins. The culmination of the Acadian orogeny at the end of the Devonian represents the beginning of a period of general tectonic quiescence extending throughout the early and middle Mississippian in eastern North America. Early Mississippian strata in the Michigan Basin are distinctive and mark the transition from marine shale and carbonate-dominated sedimentation during much of the Late Ordovician through Late Devonian to siliciclastic-dominated deposition throughout much of the Carboniferous. The Osagean Stage Marshall Formation constitutes an important coarse-grained siliciclastic formation in the Michigan Basin. Despite numerous outcrop studies and early subsurface investigations, the Marshall Formation remains poorly understood in terms of depositional controls and stratigraphic relationships to related Mississippian strata in Michigan and correlative strata in adjacent basins.

This work documents sedimentological and sequence stratigraphic relationships in early–middle Mississippian, generally clastic-dominated strata of the Marshall and lower Michigan Formations (as described in previous literature). Utilizing 535 well logs and core-to-log calibration in conjunction with detailed descriptions of seven cored intervals spanning the Michigan Basin, new stratigraphic relationships are presented suggesting the Marshall Formation and informal stray sandstone units are genetically related and reflect tectonic, eustatic, and climatic processes that occurred in the Michigan Basin during the early Carboniferous.
Pennsylvanian Pewamo Formation and Haybridge strata of central Michigan: The youngest rocks of the Michigan Basin?
Authors: Benison Kathleen C.
Published: June 2018

Pennsylvanian red beds are the youngest known rocks in the Michigan Basin. Two new formation-level units, the Pewamo Formation and the Haybridge strata, have recently been described. The Pewamo Formation, composed of Pennsylvanian red sandstones and minor laminated mudstones, is known from outcrops, abandoned quarries, and one core in Ionia County. The Haybridge unit is located in the shallow subsurface and in coal mine tailing piles in Shiawassee County. It consists of red sandstone, red mudstone, coal, and gray mudstone, all hosting Pennsylvanian macroscopic plant fossils. Neither the Pewamo nor the Haybridge rocks have any demonstrated relationship to red core cuttings reported as Jurassic from the central Lower Peninsula of Michigan. No firm evidence exists for Jurassic, or any other post-Pennsylvanian rocks in the Michigan Basin. The red core cuttings may be glacial sediments with reworked palynomorphs from rocks transported from elsewhere. A shallow coring project, followed by detailed sedimentologic, petrographic, mineralogic, and paleontologic studies, is necessary to: (1) refine the vertical and lateral stratigraphy of the Pennsylvanian rocks in Michigan; (2) solve the “Jurassic red bed problem”; and (3) understand the late Pennsylvanian–Pleistocene history of the Michigan Basin.
Fifteen-minute consultation: Preseptal and orbital cellulitis
Authors: Adamson Jonathan , Waterfield Thomas
Published: June 2018

‘It is midnight and you are called to see a thirteen-year-old boy who has been brought to the paediatric emergency department with a 24-hour history of swelling and redness of his left eye. He has had a ‘runny nose’ for a couple of days. He is systemically well. His upper and lower lids are red and swollen such that his eye is not open fully, though you elicit normal eye movements when you open his eye. Pupils are equal and reactive with no afferent pupillary defect. Visual acuity and colour vision are normal on examination.’ In this article, we consider the approach to preseptal and orbital cellulitis in children including the initial assessment and management options.
Impact of exercise on articular cartilage in people at risk of, or with established, knee osteoarthritis: a systematic review of randomised controlled trials
Authors: Bricca Alessio , Juhl Carsten B , Steultjens Martijn , Wirth Wolfgang , Roos Ewa M
Published: June 2018

Objective

To investigate the impact of knee joint loading exercise on articular cartilage in people at risk of, or with established, knee osteoarthritis (OA) by conducting a systematic review of randomised controlled trials (RCTs).

Design

We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.

Data sources

We performed a literature search with no restriction on publication year or language in MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials and Web of Science up to September 2017.

Eligibility criteria

RCTs investigating the impact of exercise on MRI-assessed articular cartilage in people over 18 years of age.

Results

We included nine trials, including a total of 14 comparisons of cartilage morphometry, morphology and composition outcomes, of which two included participants at increased risk of knee OA and 12 included participants with knee OA. In participants at increased risk, one study comparison reported no effect on cartilage defects and one had positive effects on glycosaminoglycans (GAG). In participants with OA, six study comparisons reported no effect on cartilage thickness, volume or defects; one reported a negative effect and one no effect on GAG; two reported a positive effect and two no effect on collagen.

Conclusions

Knee joint loading exercise seems to not be harmful for articular cartilage in people at increased risk of, or with, knee OA. However, the quality of evidence was low, including some interventions studying activities considered outside the therapeutic loading spectrum to promote cartilage health.
Effect of Baduanjin exercise on cognitive function in patients with post-stroke cognitive impairment: study protocol for a randomised controlled trial
Authors: Zheng Guohua , Zheng Yuhui , Xiong Zhenyu , Ye Bingzhao , Tao Jing , Chen Lidian
Published: June 2018

Introduction

Poststroke cognitive impairment is one of the most common complications in stroke survivors, and >65% of these patients suffer from cognitive impairment at 12 months following onset, which strongly affects the rehabilitation of their motor function and quality of life. Therefore, it is important to improve the cognitive ability of stroke survivors. As an important component of traditional Chinese Qigong exercises, characterised by the coordination of mind and body with a low exercise intensity, Baduanjin has the potential benefit of improving cognitive ability for patients who had a stroke with cognitive impairment. The primary purpose of this study is to investigate the effectiveness and safety of Baduanjin training on the cognitive function of stroke survivors.

Method and analysis

This study is designed as a randomised, two-arm parallel controlled trial with allocation concealment and assessors blinding. A total of 48 participants will be recruited and randomly allocated into the Baduanjin exercise intervention or control group. Baduanjin intervention will last 24 weeks with a frequency of 3 days a week and 40 min a day. Global cognitive function and the specific domains of cognition (ie, memory, processing speed, execution, attention and visuospatial ability) will be measured at baseline, 8, 16 and, 24 weeks after intervention and after an additional 4-week follow-up period, while the motor function and quality of life will be measured at baseline, 24 weeks after intervention and after an additional 4-week follow-up period.

Ethics and dissemination

Ethics approval was obtained from the Ethics Committee of Fujian University of Traditional Chinese Medicine Subsidiary Rehabilitation Hospital (approval number: 2016KY-022–01). The findings will be disseminated through peer-reviewed publications and at scientific conferences.

Trial registration number

ChiCTR-INR-16009364; Pre-results.
Community-based parent-delivered early detection and intervention programme for infants at high risk of cerebral palsy in a low-resource country (Learning through Everyday Activities with Parents (LEAP-CP): protocol for a randomised controlled trial
Authors: Benfer Katherine A , Novak Iona , Morgan Catherine , Whittingham Koa , Khan Naila Zaman , Ware Robert S , Bell Kristie L , Bandaranayake Sasaka , Salt Alison , Ghosh Asis Kumar , Bhattacharya Anjan , Samanta Sandip , Moula Golam , Bose Dilip , Tripathi Santanu , Boyd Roslyn N
Published: June 2018

Introduction

Cerebral palsy (CP) is the most common childhood physical disability, with 80% estimated to be in low-middle-income countries. This study aims to (1) determine the accuracy of General Movements (GMs)/Hammersmith Infant Neurological Examination (HINE) for detecting CP at 18 months corrected age (CA); (2) determine the effectiveness of a community-based parent-delivered early intervention for infants at high risk of CP in West Bengal, India (Learning through Everyday Activities with Parents for infants with CP; LEAP-CP).

Methods

This study comprises two substudies: (1) a study of the predictive validity of the GMs and HINE for detecting CP; (2) randomised, double-blinded controlled trial of a novel intervention delivered through peer trainers (Community Disability Workers, CDW) compared with health advice (15 fortnightly visits). 142 infants at high risk of CP (‘absent fidgety’ GMs; ‘high risk score’ on HINE) aged 12–40 weeks CA will be recruited to the intervention substudy, with infants randomised based on a computer-generated sequence. Researchers will be masked to group allocation, and caregivers and CDWs naïve to intervention status. Visits will include therapeutic modules (goal-directed active motor/cognitive strategies and LEAP-CP games) and parent education. Health advice is based on the Integrated Management of Childhood Illness, WHO. Infants will be evaluated at baseline, post intervention and 18 months CA. The primary hypothesis is that infants receiving LEAP-CP will have greater scaled scores on the Pediatric Evaluation of Disability Inventory—Computer Adaptive Test (mobility domain) at 18 months compared with health advice. Secondary outcomes include infant functional motor, cognitive, visual and communication development; infant growth; maternal mental health.

Ethics and dissemination

This study is approved through appropriate Australian and Indian ethics committees (see in text) with families providing written informed consent. Findings from this trial will be disseminated through peer-reviewed journal publications and conference presentations.

Trial registration number

12616000653460p; Pre-results.
Older kidney transplantation candidates’ expectations of improvement in life and health following kidney transplantation: semistructured interviews with enlisted dialysis patients aged 65 years and older
Authors: Lønning Kjersti , Midtvedt Karsten , Heldal Kristian , Andersen Marit Helen
Published: June 2018

Objective

The aim was to study the expectations of improvement in life and health following kidney transplantation (KTx) in a population of wait-listed patients ≥65 years with end-stage kidney disease.

Design

Qualitative research with individual in-depth interviews.

Setting

Patients on dialysis enlisted for a KTx from a deceased donor were included from an ongoing study of older patients’ perspectives on KTx. Qualitative face-to-face interviews were conducted in a safe and familiar setting, and were analysed thematically using the theoretical framework of lifespan.

Informants

Fifteen patients (median age 70 years, range 65–82) from all parts of Norway were interviewed. Informants were included consecutively until no new information was gained.

Results

Two main themes were evident: receiving a kidney is getting life back and grasp the chance. In addition, the themes ‘hard to loose capacity and strength’, ‘reduced freedom’ and ‘life on hold’ described the actual situation and thereby illuminated the informants’ expectations. The informants tried to balance positive expectations and realism towards KTx, and they were hoping to become free from dialysis and to live a normal life.

Conclusion

This study shows that older KTx candidates comprise a heterogeneous group of patients who take individual approaches that allow them to maintain autonomy and control while waiting for a transplant. This study provides new knowledge about the older KTx candidates relevant for clinicians, patients and researchers.
Validation of EGFL6 expression as a prognostic marker in patients with lung adenocarcinoma in Taiwan: a retrospective study
Authors: Chang Chun-Chi , Sung Wen-Wei , Hsu Hui-Ting , Yeh Chung-Min , Lee Chien-Hsun , Chen Ya-Ling , Liu Ta-Chih , Yeh Kun-Tu
Published: June 2018

Objective

Lung adenocarcinoma is a non-small cell lung cancer, a common cancer in both genders, and has poor clinical outcome. Our aim was to evaluate the role of epidermal growth factor (EGF)-like domain multiple 6 (EGFL6) and its prognostic significance in lung adenocarcinoma.

Methods

EGFL6 expression was studied by immunohistochemical staining of specimens from 150 patients with lung adenocarcinoma. The correlation between clinicopathological features and EGFL6 expression was quantitatively analysed. We used Kaplan-Meier analysis and Cox proportional hazard models to examine the prognostic value of EGFL6 in terms of overall survival.

Results

No significant correlation was found between EGFL6 expression and clinical parameters. However, patients with high levels of EGFL6 expression showed a tendency towards poor prognosis, with borderline statistical significance. Grouping the patients according to a medium age value revealed a significant association between high EGFL6 expression and poor clinical outcome in young patients. This finding was further confirmed by grouping the patients into three groups according to age. HR in patients with high EGFL6 expression was higher in younger patients than in older patients.

Conclusion

High EGFL6 expression may serve as a marker for poor prognosis of lung adenocarcinoma, especially in younger patients.
Lactobacillus rhamnosusGG protects the intestinal epithelium from radiation injury through release of lipoteichoic acid, macrophage activation and the migration of mesenchymal stem cells
Authors: Riehl Terrence E , Alvarado David , Ee Xueping , Zuckerman Aaron , Foster Lynn , Kapoor Vaishali , Thotala Dinesh , Ciorba Matthew A , Stenson William F
Published: June 2018

Objective

Lactobacillus rhamnosusGG (LGG), a probiotic, given by gavage is radioprotective of the mouse intestine. LGG-induced radioprotection is toll-like receptor 2 (TLR2) and cyclooxygenase-2 (COX-2)-dependent and is associated with the migration of COX-2+mesenchymal stem cells (MSCs) from the lamina propria of the villus to the lamina propria near the crypt epithelial stem cells. Our goals were to define the mechanism of LGG radioprotection including identification of the TLR2 agonist, and the mechanism of the MSC migration and to determine the safety and efficacy of this approach in models relevant to clinical radiation therapy.

Design

Intestinal radioprotection was modelled in vitro with cell lines and enteroids as well as in vivo by assaying clinical outcomes and crypt survival. Fractionated abdominal and single dose radiation were used along with syngeneic CT26 colon tumour grafts to assess tumour radioprotection.

Results

LGG with a mutation in the processing of lipoteichoic acid (LTA), a TLR2 agonist, was not radioprotective, while LTA agonist and native LGG were. An agonist of CXCR4 blocked LGG-induced MSC migration and LGG-induced radioprotection. LGG given by gavage induced expression of CXCL12, a CXCR4 agonist, in pericryptal macrophages and depletion of macrophages by clodronate liposomes blocked LGG-induced MSC migration and radioprotection. LTA effectively protected the normal intestinal crypt, but not tumours in fractionated radiation regimens.

Conclusions

LGG acts as a ‘time-release capsule’ releasing radioprotective LTA. LTA then primes the epithelial stem cell niche to protect epithelial stem cells by triggering a multicellular, adaptive immune signalling cascade involving macrophages and PGE2 secreting MSCs.

Trial registration number

NCT01790035; Pre-results.
Use of registered donkeys on the areas of natural constraint scheme in Ireland
Authors: Collins Joseph A , Wall Patrick G , Duggan Vivienne E
Published: June 2018

Data concerning the numbers, locations and types of donkeys being officially registered (passported) in Ireland (32 counties) via horse passport issuing organisations were gathered. The numbers of agricultural area aid scheme (Areas of Natural Constraint (ANC)) applicants registering passported donkeys (as compared with horses) as livestock units (LUs), the numbers of donkeys they registered and the value of payments that thus accrued to the applicants are also reported for each of 26 counties for the years 2012 to 2014 inclusive. Equids have not been eligible for equivalent agricultural schemes in the six counties of Northern Ireland. Horse Sport Ireland registration data shows that two‐thirds of almost 8000 donkey passport applicants over a 10‐year period came from counties Galway and Mayo and that only one‐third of donkeys registered were male. As per ANC figures reported here for 2014, there were over 2500 donkeys registered as LUs on ANC, at a payment value to their keepers (in the 26 counties) of almost €1.6M. Future iterations of the ANC scheme are currently under review with regard to limiting donkey eligibility criteria, for example, to females and neutered males. The future monetary value of (some) donkeys could be adversely affected by restrictions in eligibility and by the uncertainty engendered by the prospect of change with the potential for unintended consequences.
Complete MDP convolutional codes
Authors: Lieb Julia
Published: June 2018

Maximum distance profile (MDP) convolutional codes have the property that their column distances are as large as possible. It has been shown that, transmitting over an erasure channel, these codes have optimal recovery rate for windows of a certain length. Reverse MDP convolutional codes have the additional advantage that they are suitable for forward and backward decoding algorithms. Beyond that the subclass of complete MDP convolutional codes has the ability to reduce the waiting time during decoding. The first main result of this paper is to show the existence and genericity of [Formula: see text] complete MDP convolutional codes for all code parameters with [Formula: see text] as well as that complete MDP convolutional codes cannot exist if [Formula: see text]. The second main contribution is the presentation of two concrete construction techniques to obtain complete MDP convolutional codes. These constructions work for all code parameters with [Formula: see text] but require that the size of the underlying base field is (sufficiently) large.
The Old Red Group (Devonian) – Rotliegend Group (Permian) Unconformity in the Inner Moray Firth
Authors: Marshall J. E. A. , Glennie K. W. , Astin T. R. , Hewett A. J.
Published: June 2018

A major stratigraphical problem in the offshore Paleozoic of the Inner Moray Firth is the identification of the top of the Devonian Old Red Sandstone Group beneath the lithologically similar Permian Rotliegend Group. Wireline log criteria for a revised Old Red Group to Permian boundary are given for the Inner Moray Firth. Section lines drawn using these criteria and flattened on the overlying Triassic Smith Bank or Permian Kupferschiefer formations show a relatively thin development of Rotliegend with two depocentres. The underlying Devonian when flattened on the Eday Marl shows a systematic subcrop pattern. There is currently no exposed onshore Old Red to Rotliegend boundary, but the possibility remains that a Permian section is present in the ‘Upper Old Red Sandstone’ of Tarbat in Easter Ross. An exposed Permian–Devonian boundary is present in East Greenland and provides an analogue for the Inner Moray Firth.
Automatically Distributing Eulerian and Hybrid Fluid Simulations in the Cloud
Authors: Mashayekhi Omid , Shah Chinmayee , Qu Hang , Lim Andrew , Levis Philip
Published: June 2018

Distributing a simulation across many machines can drastically speed up computations and increase detail. The computing cloud provides tremendous computing resources, but weak service guarantees force programs to manage significant system complexity: nodes, networks, and storage occasionally perform poorly or fail.

We describe Nimbus, a system that automatically distributes grid-based and hybrid simulations across cloud computing nodes. The main simulation loop is sequential code and launches distributed computations across many cores. The simulation on each core runs as if it is stand-alone: Nimbus automatically stitches these simulations into a single, larger one. To do this efficiently, Nimbus introduces a four-layer data model that translates between the contiguous, geometric objects used by simulation libraries and the replicated, fine-grain objects managed by its underlying cloud computing runtime.

Using PhysBAM particle-level set fluid simulations, we demonstrate that Nimbus can run higher detail simulations faster, distribute simulations on up to 512 cores, and run enormous simulations (1024
3
cells). Nimbus automatically manages these distributed simulations, balancing load across nodes and recovering from failures. Implementations of PhysBAM water and smoke simulations as well as an open source heat-diffusion simulation show that Nimbus is general and can support complex simulations.

Nimbus can be downloaded from https://nimbus.stanford.edu.
The Effect of Pets on Happiness
Authors: Peng Xuefeng , Chi Li-Kai , Luo Jiebo
Published: June 2018

From reducing stress and loneliness, to boosting productivity and overall well-being, pets are believed to play a significant role in people’s daily lives. Many traditional studies have identified that frequent interactions with pets could make individuals become healthier and more optimistic, and ultimately enjoy a happier life. However, most of those studies are not only restricted in scale, but also may carry biases by using subjective self-reports, interviews, and questionnaires as the major approaches. In this article, we leverage large-scale data collected from social media and the state-of-the-art deep learning technologies to study this phenomenon in depth and breadth. Our study includes five major steps: (1) collecting timeline posts from around 20,000 Instagram users; (2) using face detection and recognition on 2 million photos to infer users’ demographics, relationship status, and whether having children, (3) analyzing a user’s degree of happiness based on images and captions via smiling classification and textual sentiment analysis; (4) applying transfer learning techniques to retrain the final layer of the Inception v3 model for pet classification; and (5) analyzing the effects of pets on happiness in terms of multiple factors of user demographics. Our main results have demonstrated the efficacy of our proposed method with many new insights. We believe this method is also applicable to other domains as a scalable, efficient, and effective methodology for modeling and analyzing social behaviors and psychological well-being. In addition, to facilitate the research involving human faces, we also release our dataset of 700K analyzed faces.
How to make dull information exciting
Authors: Yaffe Philip
Published: June 2018

Each "Communication Corner" essay is self-contained; however, they build on each other. For best results, before reading this essay and doing the exercise, go to the first essay "How an Ugly Duckling Became a Swan," then read each succeeding essay.

In this installment, Philip Yaffe explains how to give the reader what they want.
Chronic atorvastatin and exercise can partially reverse established skeletal muscle microvasculopathy in metabolic syndrome
Authors: Lemaster Kent A. , Frisbee Stephanie J. , Dubois Luc , Tzemos Nikolaos , Wu Fan , Lewis Matthew T. , Wiseman Robert W. , Frisbee Jefferson C.
Published: June 2018

It has long been known that chronic metabolic disease is associated with a parallel increase in the risk for developing peripheral vascular disease. Although more clinically relevant, our understanding about reversing established vasculopathy is limited compared with our understanding of the mechanisms and development of impaired vascular structure/function under these conditions. Using the 13-wk-old obese Zucker rat (OZR) model of metabolic syndrome, where microvascular dysfunction is sufficiently established to contribute to impaired skeletal muscle function, we imposed a 7-wk intervention of chronic atorvastatin treatment, chronic treadmill exercise, or both. By 20 wk of age, untreated OZRs manifested a diverse vasculopathy that was a central contributor to poor muscle performance, perfusion, and impaired O2 exchange. Atorvastatin or exercise, with the combination being most effective, improved skeletal muscle vascular metabolite profiles (i.e., nitric oxide, PGI2, and thromboxane A2 bioavailability), reactivity, and perfusion distribution at both individual bifurcations and within the entire microvascular network versus responses in untreated OZRs. However, improvements to microvascular structure (i.e., wall mechanics and microvascular density) were less robust. The combination of the above improvements to vascular function with interventions resulted in an improved muscle performance and O2 transport and exchange versus untreated OZRs, especially at moderate metabolic rates (3-Hz twitch contraction). These results suggest that specific interventions can improve specific indexes of function from established vasculopathy, but either this process was incomplete after 7-wk duration or measures of vascular structure are either resistant to reversal or require better-targeted interventions.

NEW & NOTEWORTHY We used atorvastatin and/or chronic exercise to reverse established microvasculopathy in skeletal muscle of rats with metabolic syndrome. With established vasculopathy, atorvastatin and exercise had moderate abilities to reverse dysfunction, and the combined application of both was more effective at restoring function. However, increased vascular wall stiffness and reduced microvessel density were more resistant to reversal.

Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/reversal-of-microvascular-dysfunction/ .
CaMKII-dependent late Na+current increases electrical dispersion and arrhythmia in ischemia-reperfusion
Authors: Howard Taylor , Greer-Short Amara , Satroplus Tony , Patel Nehal , Nassal Drew , Mohler Peter J. , Hund Thomas J.
Published: June 2018

The mechanisms underlying Ca2+/calmodulin-dependent protein kinase II (CaMKII)-induced arrhythmias in ischemia-reperfusion (I/R) are not fully understood. We tested the hypothesis that CaMKII increases late Na+current ( INa,L) via phosphorylation of Nav1.5 at Ser571during I/R, thereby increasing arrhythmia susceptibility. To test our hypothesis, we studied isolated, Langendorff-perfused hearts from wild-type (WT) mice and mice expressing Navchannel variants Nav1.5-Ser571E (S571E) and Nav1.5-Ser571A (S571A). WT hearts showed a significant increase in the levels of phosphorylated CaMKII and Nav1.5 at Ser571[p-Nav1.5(S571)] after 15 min of global ischemia (just before the onset of reperfusion). Optical mapping experiments revealed an increase in action potential duration (APD) and APD dispersion without changes in conduction velocity during I/R in WT and S571E compared with S571A hearts. At the same time, WT and S571E hearts showed an increase in spontaneous arrhythmia events (e.g., premature ventricular contractions) and an increase in the inducibility of reentrant arrhythmias during reperfusion. Pretreatment of WT hearts with the Na+channel blocker mexiletine (10 μM) normalized APD dispersion and reduced arrhythmia susceptibility during I/R. We conclude that CaMKII-dependent phosphorylation of Nav1.5 is a crucial driver for increased INa,L,arrhythmia triggers, and substrate during I/R. Selective targeting of this CaMKII-dependent pathway may have therapeutic potential for reducing arrhythmias in the setting of I/R.

NEW & NOTEWORTHY Ca2+/calmodulin-dependent protein kinase II (CaMKII) phosphorylation of Nav1.5 at Ser571leads to a prolongation of action potential duration (APD), increased APD dispersion, and increased arrhythmia susceptibility after ischemia-reperfusion in isolated mouse hearts. Genetic ablation of the CaMKII-dependent phosphorylation site Ser571on Nav1.5 or low-dose mexiletine (to inhibit late Na+current) reduced APD dispersion, arrhythmia triggers, and ventricular tachycardia inducibility.