bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving biofeedback for the treatment of fecal incontinence in women: implementation of a standardized multi‐site manometric biofeedback protocol
Authors: Markland A. D. , Jelovsek J. E. , Whitehead W. E. , Newman D. K. , Andy U. U. , Dyer K. , Harm‐Ernandes I. , Cichowski S. , McCormick J. , Rardin C. , Sutkin G. , Shaffer A. , Meikle S. ,   the Pelvic Floor Disorders Network
Published: July 2016

Background

Standardized training and clinical protocols using biofeedback for the treatment of fecal incontinence (FI) are important for clinical care. Our primary aims were to develop, implement, and evaluate adherence to a standardized protocol for manometric biofeedback to treat FI.

Methods

In a Pelvic Floor Disorders Network (PFDN) trial, participants were enrolled from eight PFDN clinical centers across the United States. A team of clinical and equipment experts developed biofeedback software on a novel tablet computer platform for conducting standardized anorectal manometry with separate manometric biofeedback protocols for improving anorectal muscle strength, sensation, and urge resistance. The training protocol also included education on bowel function, anal sphincter exercises, and bowel diary monitoring. Study interventionists completed online training prior to attending a centralized, standardized certification course. For the certification, expert trainers assessed the ability of the interventionists to perform the protocol components for a paid volunteer who acted as a standardized patient. Postcertification, the trainers audited interventionists during trial implementation to improve protocol adherence.

Key Results

Twenty‐four interventionists attended the in‐person training and certification, including 46% advanced practice registered nurses (11/24), 50% (12/24) physical therapists, and 4% physician assistants (1/24). Trainers performed audio audits for 88% (21/24), representing 84 audited visits. All certified interventionists met or exceeded the prespecified 80% pass rate for the audit process, with an average passing rate of 93%.

Conclusions & Inferences

A biofeedback protocol can be successfully imparted to experienced pelvic floor health care providers from various disciplines. Our process promoted high adherence to a standard protocol and is applicable to many clinical settings.
Cyanide and the human brain: perspectives from a model of food (cassava) poisoning
Authors: Tshala‐Katumbay Desire D. , Ngombe Nadege N. , Okitundu Daniel , David Larry , Westaway Shawn K. , Boivin Michael J. , Mumba Ngoyi D. , Banea Jean‐Pierre
Published: July 2016

Threats by fundamentalist leaders to use chemical weapons have resulted in renewed interest in cyanide toxicity. Relevant insights may be gained from studies on cyanide mass intoxication in populations relying on cyanogenic cassava as the main source of food. In these populations, sublethal concentrations (up to 80 μmol/l) of cyanide in the blood are commonplace and lead to signs of acute toxicity. Long‐term toxicity signs include a distinct and irreversible spastic paralysis, known as konzo, and cognition deficits, mainly in sequential processing (visual–spatial analysis) domains. Toxic culprits include cyanide (mitochondrial toxicant), thiocyanate (AMPA‐receptor chaotropic cyanide metabolite), cyanate (protein‐carbamoylating cyanide metabolite), and 2‐iminothiazolidine‐4‐carboxylic acid (seizure inducer). Factors of susceptibility include younger age, female gender, protein‐deficient diet, and, possibly, the gut functional metagenome. The existence of uniquely exposed and neurologically affected populations offers invaluable research opportunities to develop a comprehensive understanding of cyanide toxicity and test or validate point‐of‐care diagnostic tools and treatment options to be included in preparedness kits in response to cyanide‐related threats.
Neurosteroids for the potential protection of humans against organophosphate toxicity
Authors: Reddy Doodipala Samba
Published: July 2016

This article describes the therapeutic potential of neurosteroids as anticonvulsant antidotes for chemical intoxication caused by organophosphate pesticides and nerve agents or gases like sarin and soman. Toxic manifestations following nerve agent exposure, as evident in chemical attacks in Japan and Syria, include hypersecretion, respiratory distress, tremors, convulsions leading to status epilepticus (SE), and death. Benzodiazepines, such as diazepam, are the current anticonvulsants of choice for controlling nerve agent–induced life‐threatening seizures, SE, and brain injury. Benzodiazepines can control acute seizures when given early, but they are less effective for delayed treatment of SE, which is characterized by rapid desensitization of synaptic GABAA receptors, benzodiazepine resistance, and brain injury. Neurosteroid‐sensitive extrasynaptic GABAA receptors, however, remain unaffected by such events. Thus, anticonvulsant neurosteroids may produce more effective protection than benzodiazepines against a broad spectrum of chemical agents, even when given late after nerve agent exposure.
Activation of the TREM‐1 pathway in human monocytes by periodontal pathogens and oral commensal bacteria
Authors: Varanat M. , Haase E.M. , Kay J.G. , Scannapieco F.A.
Published: July 2016

Periodontitis is a highly prevalent disease caused in part by an aberrant host response to the oral multi‐species biofilm. A balance between the oral bacteria and host immunity is essential for oral health. Imbalances in the oral microbiome lead to an uncontrolled host inflammatory response and subsequent periodontal disease (i.e. gingivitis and periodontitis). TREM‐1 is a signaling receptor present on myeloid cells capable of acting synergistically with other pattern recognition receptors leading to amplification of inflammatory responses. The aim of this study was to investigate the activation of the TREM‐1 pathway in the human monocyte‐like cell line THP‐1 exposed to both oral pathogens and commensals. The relative expression of the genes encoding TREM‐1 and its adapter protein DAP12 were determined by quantitative real‐time polymerase chain reaction. The surface expression of TREM‐1 was determined by flow cytometry. Soluble TREM‐1 and cytokines were measured by enzyme‐linked immunosorbent assay. The results demonstrate that both commensal and pathogenic oral bacteria activate the TREM‐1 pathway, resulting in a proinflammatory TREM‐1 activity‐dependent increase in proinflammatory cytokine production.
Memory responses of jasmonic acid‐associated Arabidopsis genes to a repeated dehydration stress
Authors: Liu Ning , Staswick Paul E. , Avramova Zoya
Published: July 2016

Dehydration stress activates numerous genes co‐regulated by diverse signaling pathways. Upon repeated exposures, however, a subset of these genes does not respond maintaining instead transcription at their initial pre‐stressed levels (‘revised‐response’ genes). Most of these genes are involved in jasmonic acid (JA) biosynthesis, JA‐signaling and JA‐mediated stress responses. How these JA‐associated genes are regulated to provide different responses to similar dehydration stresses is an enigma. Here, we investigate molecular mechanisms that contribute to this transcriptional behavior. The memory‐mechanism is stress‐specific: one exposure to dehydration stress or to abscisic acid (ABA) is required to prevent transcription in the second. Both ABA‐mediated and JA‐mediated pathways are critical for the activation of these genes, but the two signaling pathways interact differently during a single or multiple encounters with dehydration stress. Synthesis of JA during the first (S1) but not the second dehydration stress (S2) accounts for the altered transcriptional responses. We propose a model for these memory responses, wherein lack of MYC2 and of JA synthesis in S2 is responsible for the lack of expression of downstream genes. The similar length of the memory displayed by different memory‐type genes suggests biological relevance for transcriptional memory as a gene‐regulating mechanism during recurring bouts of drought.
Neurobiological findings related to Internet use disorders
Authors: Park Byeongsu , Han Doug Hyun , Roh Sungwon
Published: July 2016

In the last 10 years, numerous neurobiological studies have been conducted on Internet addiction or Internet use disorder. Various neurobiological research methods – such as magnetic resonance imaging; nuclear imaging modalities, including positron emission tomography and single photon emission computed tomography; molecular genetics; and neurophysiologic methods – have made it possible to discover structural or functional impairments in the brains of individuals with Internet use disorder. Specifically, Internet use disorder is associated with structural or functional impairment in the orbitofrontal cortex, dorsolateral prefrontal cortex, anterior cingulate cortex, and posterior cingulate cortex. These regions are associated with the processing of reward, motivation, memory, and cognitive control. Early neurobiological research results in this area indicated that Internet use disorder shares many similarities with substance use disorders, including, to a certain extent, a shared pathophysiology. However, recent studies suggest that differences in biological and psychological markers exist between Internet use disorder and substance use disorders. Further research is required for a better understanding of the pathophysiology of Internet use disorder.
Immunization practices among pediatric transplant hepatologists
Authors: Feldman Amy G. , Kempe Allison , Beaty Brenda L. , Sundaram Shikha S. ,   the Studies of Pediatric Liver Transplantation (SPLIT) Research Group
Published: July 2016

Vaccination of pediatric liver transplant candidates and recipients represents an opportunity to decrease infectious complications following transplant. Although vaccine recommendations exist, studies have shown that many transplant candidates and recipients are under‐immunized. The goals of this study were to assess among pediatric transplant hepatologists: (i) current immunization practices before and after transplantation, (ii) involvement of an ID physician in the transplant evaluation, and (iii) perceptions about vaccine safety and barriers to immunization. An 80‐item e‐mail survey of pediatric transplant hepatologists at centers in the United States and Canada participating in the SPLIT consortium was conducted from December 2014 to March 2015. The overall response rate was 80% (73/91), representing 97% (32/33) of SPLIT centers. Fifty percent of programs routinely involved an ID physician in the transplant evaluation. Administration of palivizumab was routinely considered by 48% of hepatologists pre‐transplant and by 41% post‐transplant. Live vaccines were recommended by 26% of hepatologists after transplant. About 10% of hepatologists reported concern that live vaccines after transplant could induce rejection. There is wide variation in immunization practices among transplant hepatologists. Specific evidence‐based protocols are needed to guide immunization practices in transplant candidates and recipients.
Decomposing mechanisms of abnormal saccade generation in schizophrenia patients: Contributions of volitional initiation, motor preparation, and fixation release
Authors: Reuter Benedikt , Elsner Björn , Möllers David , Kathmann Norbert
Published: July 2016

Clinical and theoretical models suggest deficient volitional initiation of action in schizophrenia patients. Recent research provided an experimental model of testing this assumption using saccade tasks. However, inconsistent findings necessitate a specification of conditions on which the deficit may occur. The present study sought to detect mechanisms that may contribute to poor performance. Sixteen schizophrenia patients and 16 healthy control participants performed visually guided and two types of volitional saccade tasks. All tasks varied as to whether the initial fixation stimulus disappeared (fixation stimulus offset) or continued during saccade initiation, and whether a direction cue allowed motor preparation of the specific saccade. Saccade latencies of the two groups were differentially affected by task type, fixation stimulus offset, and cueing, suggesting abnormal volitional saccade generation, fixation release, and motor preparation in schizophrenia. However, substantial performance deficits may only occur if all affected processes are required in a task.
Three‐dimensional architecture and hydrostratigraphy of cross‐cutting buried valleys using airborne electromagnetics, glaciated Central Lowlands, Nebraska, USA
Authors: Korus Jesse T. , Joeckel R. Matt , Divine Dana P. , Abraham Jared D.
Published: July 2016

Buried valleys are characteristic features of glaciated landscapes, and their deposits host important aquifers worldwide. Understanding the stratigraphic architecture of these deposits is essential for protecting groundwater and interpreting sedimentary processes in subglacial and ice‐marginal environments. The relationships between depositional architecture, topography and hydrostratigraphy in dissected, pre‐Illinoian till sheets is poorly understood. Boreholes alone are inadequate to characterize the complex geology of buried valleys, but airborne electromagnetic surveys have proven useful for this purpose. A key question is whether the sedimentary architecture of buried valleys can be interpreted from airborne electromagnetic profiles. This study employs airborne electromagnetic resistivity profiles to interpret the three‐dimensional sedimentary architecture of cross‐cutting buried valleys in a ca 400 km2 area along the western margin of Laurentide glaciation in North America. A progenitor bedrock valley is succeeded by at least five generations of tunnel valleys that become progressively younger northward. Tunnel‐valley infills are highly variable, reflecting under‐filled and over‐filled conditions. Under‐filled tunnel valleys are expressed on the modern landscape and contain fine sediments that act as hydraulic barriers. Over‐filled tunnel valleys are not recognized in the modern landscape, but where they are present they form hydraulic windows between deep aquifer units and the land surface. The interpretation of tunnel‐valley genesis herein provides evidence of the relationships between depositional processes and glacial landforms in a dissected, pre‐Illinoian till sheet, and contributes to the understanding of the complex physical hydrology of glacial aquifers in general.
Inflammatory bowel disease in pregnancy
Authors: Kapoor Dipanwita , Teahon Kathy , Wallace Suzanne VF
Published: July 2016

Key content

Inflammatory bowel disease is a condition that presents in young adulthood and is increasingly frequently seen in women in pregnancy.

Prepregnancy counselling helps women to optimise pregnancy timing to reduce the risks of complications.

Pregnancy in women with inflammatory bowel disease should be managed in conjunction with gastroenterologists.

Newer therapies have been found to be highly effective in inducing rapid remission of active disease where other medical treatment has failed but experience in pregnancy is still limited.

Delivery decisions can be complex depending on the disease phenotype and where there has been previous complex surgery.

Learning objectives

To understand the issues related to inflammatory bowel disease and pregnancy.

To gain an overview of the management options for women with inflammatory bowel disease in pregnancy.

Ethical issues

Is it appropriate to continue biologic therapies in pregnancy with minimal evidence of safety?

Should all women with previous surgery for inflammatory bowel disease be offered an elective caesarean section to reduce the risks associated with an emergency caesarean section?
Prenatal diagnosis in the modern era
Authors: Fox Caroline E , Kilby Mark D
Published: July 2016

Key content

It may be possible to define pregnancy complication risk in the first trimester by combining biochemical and biophysical markers with obstetric history. This could allow antenatal care to be personalised, with patient and complication‐specific content.

Molecular genetic testing, by both invasive and noninvasive means, can offer examination of the whole genome or exome.

Noninvasive prenatal testing (NIPT) using cell‐free fetal DNA in the maternal circulation can offer screening and diagnosis of aneuploidy and single gene defects.

Ultrasound can be enhanced by magnetic resonance imaging to provide imaging that is not limited by fetal and maternal characteristics, and can be used to assist preoperative planning for fetal surgery.

Learning objectives

To understand how pregnancy care can evolve with NIPT and a more detailed first trimester assessment.

To understand how NIPT is undertaken, its capabilities and current limitations.

Ethical issues

With increasingly detailed cytogenetic testing there is a need to provide families with sufficient pre‐ and post‐test counselling, as well as consider the ramifications for them and the fetus.
Prediction of Contact Area and Frictional Behaviour of Rubber on Rigid Rough Surfaces
Authors: Lind Hagen , Wangenheim Matthias
Published: July 2016

In the tire-road contact friction depends on several influencing variables (e.g. surface texture, real contact area, sliding velocity, normal contact pressure, temperature, tread block geometry, compound and on the existence of a lubrication film). A multi-scale model for prediction of contact area and frictional behaviour of rubber on rigid rough surfaces at different length scales is presented. Within this publication the multi-scale approach is checked regarding convergence. By means of the model influencing parameters like sliding velocity, compound and surface texture on friction and contact area will be investigated.
Ultrasensitive molecular sensor using N-doped graphene through enhanced Raman scattering
Authors: Feng Simin , dos Santos Maria Cristina , Carvalho Bruno R. , Lv Ruitao , Li Qing , Fujisawa Kazunori , Elías Ana Laura , Lei Yu , Perea-López Nestor , Endo Morinobu , Pan Minghu , Pimenta Marcos A. , Terrones Mauricio
Published: July 2016

N-doped graphene can be used as a substrate for different molecules to effectively enhance their Raman scattering signal.
Leveraging Genetic-Background Effects in Saccharomyces cerevisiae To Improve Lignocellulosic Hydrolysate Tolerance
Authors: Sardi Maria , Rovinskiy Nikolay , Zhang Yaoping , Gasch Audrey P.
Published: July 2016

A major obstacle to sustainable lignocellulosic biofuel production is microbe inhibition by the combinatorial stresses in pretreated plant hydrolysate. Chemical biomass pretreatment releases a suite of toxins that interact with other stressors, including high osmolarity and temperature, which together can have poorly understood synergistic effects on cells. Improving tolerance in industrial strains has been hindered, in part because the mechanisms of tolerance reported in the literature often fail to recapitulate in other strain backgrounds. Here, we explored and then exploited variations in stress tolerance, toxin-induced transcriptomic responses, and fitness effects of gene overexpression in differentSaccharomyces cerevisiae(yeast) strains to identify genes and processes linked to tolerance of hydrolysate stressors. Using six differentS. cerevisiaestrains that together maximized phenotypic and genetic diversity, first we explored transcriptomic differences between resistant and sensitive strains to identify common and strain-specific responses. This comparative analysis implicated primary cellular targets of hydrolysate toxins, secondary effects of defective defense strategies, and mechanisms of tolerance. Dissecting the responses to individual hydrolysate components across strains pointed to synergistic interactions between osmolarity, pH, hydrolysate toxins, and nutrient composition. By characterizing the effects of high-copy gene overexpression in three different strains, we revealed the breadth of the background-specific effects of gene fitness contributions in synthetic hydrolysate. Our approach identified new genes for engineering improved stress tolerance in diverse strains while illuminating the effects of genetic background on molecular mechanisms.

IMPORTANCERecent studies on natural variation withinSaccharomyces cerevisiaehave uncovered substantial phenotypic diversity. Here, we took advantage of this diversity, using it as a tool to infer the effects of combinatorial stress found in lignocellulosic hydrolysate. By comparing sensitive and tolerant strains, we implicated primary cellular targets of hydrolysate toxins and elucidated the physiological states of cells when exposed to this stress. We also explored the strain-specific effects of gene overexpression to further identify strain-specific responses to hydrolysate stresses and to identify genes that improve hydrolysate tolerance independent of strain background. This study underscores the importance of studying multiple strains to understand the effects of hydrolysate stress and provides a method to find genes that improve tolerance across strain backgrounds.
Design and Evaluation of Illumina MiSeq-Compatible, 18S rRNA Gene-Specific Primers for Improved Characterization of Mixed Phototrophic Communities
Authors: Bradley Ian M. , Pinto Ameet J. , Guest Jeremy S.
Published: July 2016

The use of high-throughput sequencing technologies with the 16S rRNA gene for characterization of bacterial and archaeal communities has become routine. However, the adoption of sequencing methods for eukaryotes has been slow, despite their significance to natural and engineered systems. There are large variations among the target genes used for amplicon sequencing, and for the 18S rRNA gene, there is no consensus on which hypervariable region provides the most suitable representation of diversity. Additionally, it is unclear how much PCR/sequencing bias affects the depiction of community structure using current primers. The present study amplified the V4 and V8-V9 regions from seven microalgal mock communities as well as eukaryotic communities from freshwater, coastal, and wastewater samples to examine the effect of PCR/sequencing bias on community structure and membership. We found that degeneracies on the 3′ end of the current V4-specific primers impact read length and mean relative abundance. Furthermore, the PCR/sequencing error is markedly higher for GC-rich members than for communities with balanced GC content. Importantly, the V4 region failed to reliably capture 2 of the 12 mock community members, and the V8-V9 hypervariable region more accurately represents mean relative abundance and alpha and beta diversity. Overall, the V4 and V8-V9 regions show similar community representations over freshwater, coastal, and wastewater environments, but specific samples show markedly different communities. These results indicate that multiple primer sets may be advantageous for gaining a more complete understanding of community structure and highlight the importance of including mock communities composed of species of interest.

IMPORTANCE
The quantification of error associated with community representation by amplicon sequencing is a critical challenge that is often ignored. When target genes are amplified using currently available primers, differential amplification efficiencies result in inaccurate estimates of community structure. The extent to which amplification bias affects community representation and the accuracy with which different gene targets represent community structure are not known. As a result, there is no consensus on which region provides the most suitable representation of diversity for eukaryotes. This study determined the accuracy with which commonly used 18S rRNA gene primer sets represent community structure and identified particular biases related to PCR amplification and Illumina MiSeq sequencing in order to more accurately study eukaryotic microbial communities.
Humanized Monoclonal Antibody That Passively Protects Mice against Systemic and Intranasal Ricin Toxin Challenge
Authors: Van Slyke Greta , Sully Erin K. , Bohorova Natasha , Bohorov Ognian , Kim Do , Pauly Michael H. , Whaley Kevin J. , Zeitlin Larry , Mantis Nicholas J.
Published: July 2016

PB10 is a murine monoclonal antibody against an immunodominant epitope on ricin toxin's enzymatic subunit. Here, we characterize a fully humanized version of PB10 IgG1 (hPB10) and demonstrate that it has potent
in vitro
and
in vivo
toxin-neutralizing activities. We also report the minimum serum concentrations of hPB10 required to protect mice against 10 times the 50% lethal dose of ricin when delivered by injection and inhalation.
Pleistocene onset of rapid, punctuated exhumation in the eastern Central Range of the Taiwan orogenic belt
Authors: Hsu Wei-Hao , Byrne Timothy B. , Ouimet William , Lee Yuan-Hsi , Chen Yue-Gau , Soest Matthijs van , Hodges Kip
Published: July 2016

The Taiwan orogenic belt is often treated as a steady, southward-propagating orogenic system with an essentially constant erosion rate of 4–6 mm/yr over the past 5 m.y. We present 4 new age-elevation transects from the Central Range based on 19 new and 86 previously published fission track and (U-Th)/He dates of completely reset detrital zircon and apatite grains. The age-elevation curves and thermal models imply slow cooling prior to ca. 2–1.5 Ma (at exhumation rates of ∼0.1 mm/yr), an increase in exhumation rates from ca. 2–1.5 Ma to ca. 0.5 Ma (2–4 mm/yr), and possibly a further acceleration in exhumation from ca. 0.5 Ma to present (4–8 mm/yr). Three transects from three different latitudes in the eastern Central Range yield similar results, each showing punctuated exhumation with progressively faster rates.
The Thor suture zone: From subduction to intraplate basin setting
Authors: Smit Jeroen , Wees Jan-Diederik van , Cloetingh Sierd
Published: July 2016

The crustal seismic velocity structure of northwestern Europe shows a low P-wave velocity zone (LVZ) in the lower crust along the Caledonian Thor suture zone (TSZ) that cannot be easily attributed to Avalonia or Baltica plates abutting the TSZ. The LVZ appears to correspond to a hitherto unrecognized crustal segment (accretionary complex) that separates Avalonia from Baltica, explaining well the absence of Avalonia further east. Consequently, the northern boundary of Avalonia is shifted ∼150 km southward. Our interpretation, based on analysis of deep seismic profiles, places the LVZ in a consistent crustal domain interpretation. A comparison with present-day examples of the Kuril and Cascadia subduction zones suggests that the LVZ separating Avalonia from Baltica is composed of remnants of the Caledonian accretionary complex. If so, the present-day geometry probably originates from pre-Variscan extension and eduction during Devonian–Carboniferous backarc extension. The reinterpretation of deep crustal zonation provides a crustal framework in which the northern limit of Avalonia corresponds to the southern limit of the deep North German Basin and the northern limit of prolific gas reservoirs and late Mesozoic inversion structures.
Formation of a future supercontinent through plate motion–driven flow coupled with mantle downwelling flow
Authors: Yoshida Masaki
Published: July 2016

Series of high-resolution numerical simulations of three-dimensional mantle convection were performed to examine the interaction between the drifting continental lithospheres and the underlying mantle structure for 250 m.y. from the present, and to predict the configuration of the future supercontinent. The density anomaly of the mantle interior was determined by the seismic velocity anomaly from global seismic tomography data sets, which contain well-resolved subducting slabs. The present-day plate motion was imposed for the first stage of the simulation as a velocity boundary condition at the top surface boundary, instead of a shear stress–free condition. The switching time from the plate motion boundary to shear stress–free conditions was taken as a free parameter. The results revealed that Australia, Eurasia, North America, and Africa will merge together in the Northern Hemisphere to form a new supercontinent within ∼250 m.y. from the present. The continental drift was assumed to be realized by plate-scale mantle flow, rather than large-scale upwelling plumes. That is, continuously moving plates at the surface for the first stage of the simulation are mechanically coupled with the subducting slabs in the mantle; this enhances the underlying mantle downwelling flow. As a result, persistent continental drift can be reproduced for long future time periods even though top surface boundary conditions may switch in response to shear stress–free conditions. The configuration of the numerically reproduced future supercontinent in this study is broadly consistent with the hypothetical model of Amasia as indicated by previous findings from geological correlations and a paleogeographic reconstruction.
Rifting under steam—How rift magmatism triggers methane venting from sedimentary basins
Authors: Berndt C. , Hensen C. , Mortera-Gutierrez C. , Sarkar S. , Geilert S. , Schmidt M. , Liebetrau V. , Kipfer R. , Scholz F. , Doll M. , Muff S. , Karstens J. , Planke S. , Petersen S. , Böttner C. , Chi W.-C. , Moser M. , Behrendt R. , Fiskal A. , Lever M.A. , Su C.-C. , Deng L. , Brennwald M.S. , Lizarralde D.
Published: July 2016

During opening of a new ocean, magma intrudes into the surrounding sedimentary basins. Heat provided by the intrusions matures the host rock, creating metamorphic aureoles potentially releasing large amounts of hydrocarbons. These hydrocarbons may migrate to the seafloor in hydrothermal vent complexes in sufficient volumes to trigger global warming, e.g., during the Paleocene-Eocene Thermal Maximum (PETM). Mound structures at the top of buried hydrothermal vent complexes observed in seismic data off Norway were previously interpreted as sediment volcanoes, and the amount of released hydrocarbon was estimated based on this interpretation. Here, we present new geophysical and geochemical data from the Gulf of California suggesting that such mound structures could in fact be edifices constructed by the growth of black smoker–type chimneys rather than sediment volcanoes. We have evidence for two buried and one active hydrothermal vent systems outside the rift axis. The active vent releases fluids of several hundred degrees Celsius containing abundant methane, mid-ocean ridge basalt–type helium, and precipitating solids up to 300 m high into the water column. Our observations challenge the idea that methane is emitted slowly from rift-related vents. The association of large amounts of methane with hydrothermal fluids that enter the water column at high pressure and temperature provides an efficient mechanism to transport hydrocarbons into the water column and atmosphere, lending support to the hypothesis that rapid climate change such as during the PETM can be triggered by magmatic intrusions into organic-rich sedimentary basins.
Synchronous diversification of Laurentian and Baltic rhynchonelliform brachiopods: Implications for regional versus global triggers of the Great Ordovician Biodiversification Event
Authors: Trubovitz Sarah , Stigall Alycia L.
Published: July 2016

The profound global impact of marine radiations during the Great Ordovician Biodiversification Event (GOBE) is widely appreciated; however, diversification varied among paleocontinents and these individual trajectories are less understood. Here we present a new species-level diversity curve for rhynchonelliform brachiopods from midcontinental Laurentia based on bed-by-bed analysis of the Simpson Group of Oklahoma (USA). Diversity and abundance data span the Dapingian through Sandbian Stages, which encompass the interval of maximum global diversification. A rapid, statistically significant increase in brachiopod diversity was observed in the early Darriwilian Histiodella holodentata Biozone. We interpret this as a biological signal because the increase cannot be explained by sampling intensity, facies types, or position along depositional gradient. Diversifications on Laurentia and Baltica were temporally synchronous at the biozone level, and cumulative diversity curves for the regions show similar patterns, suggesting a global driver for the radiations. The taxonomic composition of the brachiopod faunas, however, differs substantially, highlighting the importance of regional controls on diversification. Thus both global and local factors controlled diversity increase during the GOBE.
Thoracic intramedullary chordoma without bone involvement: a rare clinical entity
Authors: Faheem Mohd , Zeeshan Qazi , Ojha Balkrishna , Agrawal Preeti
Published: July 2016

An 8-year-old boy presented with a 1-year history of low backache, followed by paraparesis and urinary incontinence. MRI of the thoracic spine revealed an intramedullary, intensely contrast-enhancing lesion extending from T11 to L1 vertebral level, consistent with astrocytoma, ependymoma or haemangioblastoma. A diagnosis of intramedullary chordoma was made on tissue biopsy and immunohistochemical study. This is the second report of an intramedullary chordoma without bone involvement in English literature. After 6 months of follow-up, patient showed good clinical outcome in terms of improvement in power in lower limbs and backache.
SCISSOR—Spinal Cord Injury Study on Small molecule-derived Rho inhibition: a clinical study protocol
Authors: Kopp Marcel A , Liebscher Thomas , Watzlawick Ralf , Martus Peter , Laufer Stefan , Blex Christian , Schindler Ralf , Jungehulsing Gerhard J , Knüppel Sven , Kreutzträger Martin , Ekkernkamp Axel , Dirnagl Ulrich , Strittmatter Stephen M , Niedeggen Andreas , Schwab Jan M
Published: July 2016

Introduction

The approved analgesic and anti-inflammatory drugs ibuprofen and indometacin block the small GTPase RhoA, a key enzyme that impedes axonal sprouting after axonal damage. Inhibition of the Rho pathway in a central nervous system-effective manner requires higher dosages compared with orthodox cyclooxygenase-blocking effects. Preclinical studies on spinal cord injury (SCI) imply improved motor recovery after ibuprofen/indometacin-mediated Rho inhibition. This has been reassessed by a meta-analysis of the underlying experimental evidence, which indicates an overall effect size of 20.2% regarding motor outcome achieved after ibuprofen/indometacin treatment compared with vehicle controls. In addition, ibuprofen/indometacin may also limit sickness behaviour, non-neurogenic systemic inflammatory response syndrome (SIRS), neuropathic pain and heterotopic ossifications after SCI. Consequently, ‘small molecule’-mediated Rho inhibition after acute SCI warrants clinical investigation.

Methods and analysis

Protocol of an investigator-initiated clinical open-label pilot trial on high-dose ibuprofen treatment after acute traumatic, motor-complete SCI. A sample of n=12 patients will be enrolled in two cohorts treated with 2400 mg/day ibuprofen for 4 or 12 weeks, respectively. The primary safety end point is an occurrence of serious adverse events, primarily gastroduodenal bleedings. Secondary end points are pharmacokinetics, feasibility and preliminary effects on neurological recovery, neuropathic pain and heterotopic ossifications. The primary safety analysis is based on the incidence of severe gastrointestinal bleedings. Additional analyses will be mainly descriptive and casuistic.

Ethics and dissemination

The clinical trial protocol was approved by the responsible German state Ethics Board, and the Federal Institute for Drugs and Medical Devices. The study complies with the Declaration of Helsinki, the principles of Good Clinical Practice and all further applicable regulations. This safety and pharmacokinetics trial informs the planning of a subsequent randomised controlled trial. Regardless of the result of the primary and secondary outcome assessments, the clinical trial will be reported as a publication in a peer-reviewed journal.

Trial registration number

NCT02096913; Pre-results.
Engaging migrants and other stakeholders to improve communication in cross-cultural consultation in primary care: a theoretically informed participatory study
Authors: Lionis Christos , Papadakaki Maria , Saridaki Aristoula , Dowrick Christopher , O'Donnell Catherine A , Mair Frances S , van den Muijsenbergh Maria , Burns Nicola , de Brún Tomas , O'Reilly de Brún Mary , van Weel-Baumgarten Evelyn , Spiegel Wolfgang , MacFarlane Anne
Published: July 2016

Objectives

Guidelines and training initiatives (G/TIs) are available to support communication in cross-cultural consultations but are rarely implemented in routine practice in primary care. As part of the European Union RESTORE project, our objective was to explore whether the available G/TIs make sense to migrants and other key stakeholders and whether they could collectively choose G/TIs and engage in their implementation in primary care settings.

Setting

As part of a comparative analysis of 5 linked qualitative case studies, we used purposeful and snowball sampling to recruit migrants and other key stakeholders in primary care settings in Austria, England, Greece, Ireland and the Netherlands.

Participants

A total of 78 stakeholders participated in the study (Austria 15, England 9, Ireland 11, Greece 16, Netherlands 27), covering a range of groups (migrants, general practitioners, nurses, administrative staff, interpreters, health service planners).

Primary and secondary outcome measures

We combined Normalisation Process Theory (NPT) and Participatory Learning and Action (PLA) research to conduct a series of PLA style focus groups. Using a standardised protocol, stakeholders' discussions about a set of G/TIs were recorded on PLA commentary charts and their selection process was recorded through a PLA direct-ranking technique. We performed inductive and deductive thematic analysis to investigate sensemaking and engagement with the G/TIs.

Results

The need for new ways of working was strongly endorsed by most stakeholders. Stakeholders considered that they were the right people to drive the work forward and were keen to enrol others to support the implementation work. This was evidenced by the democratic selection by stakeholders in each setting of one G/TI as a local implementation project.

Conclusions

This theoretically informed participatory approach used across 5 countries with diverse healthcare systems could be used in other settings to establish positive conditions for the start of implementation journeys for G/TIs to improve healthcare for migrants.
Characteristics and outcomes of women using emergency medical services for third-trimester pregnancy-related problems in India: a prospective observational study
Authors: Strehlow Matthew C , Newberry Jennifer A , Bills Corey B , Min Hyeyoun (Elise) , Evensen Ann E , Leeman Lawrence , Pirrotta Elizabeth A , Rao G V Ramana , Mahadevan S V
Published: July 2016

Objectives

Characterise the demographics, management and outcomes of obstetric patients transported by emergency medical services (EMS).

Design

Prospective observational study.

Setting

Five Indian states using a centralised EMS agency that transported 3.1 million pregnant women in 2014.

Participants

This study enrolled a convenience sample of 1684 women in third trimester of pregnancy calling with a ‘pregnancy-related’ problem for free-of-charge ambulance transport. Calls were deemed ‘pregnancy related’ if categorised by EMS dispatchers as ‘pregnancy’, ‘childbirth’, ‘miscarriage’ or ‘labour pains’. Interfacility transfers, patients absent on ambulance arrival and patients refusing care were excluded.

Main outcome measures

Emergency medical technician (EMT) interventions, method of delivery and death.

Results

The median age enrolled was 23 years (IQR 21–25). Women were primarily from rural or tribal areas (1550/1684 (92.0%)) and lower economic strata (1177/1684 (69.9%)). Time from initial call to hospital arrival was longer for rural/tribal compared with urban patients (66 min (IQR 51–84) vs 56 min (IQR 42–73), respectively, p<0.0001). EMTs assisted delivery in 44 women, delivering the placenta in 33/44 (75%), performing transabdominal uterine massage in 29/33 (87.9%) and administering oxytocin in none (0%). There were 1411 recorded deliveries. Most women delivered at a hospital (1212/1411 (85.9%)), however 126/1411 (8.9%) delivered at home following hospital discharge. Follow-up rates at 48 hours, 7 days and 42 days were 95.0%, 94.4% and 94.1%, respectively. Four women died, all within 48 hours. The caesarean section rate was 8.2% (116/1411). On multivariate regression analysis, women transported to private hospitals versus government primary health centres were less likely to deliver by caesarean section (OR 0.14 (0.05–0.43))

Conclusions

Pregnant women from vulnerable Indian populations use free-of-charge EMS for impending delivery, making it integral to the healthcare system. Future research and health system planning should focus on strengthening and expanding EMS as a component of emergency obstetric and newborn care (EmONC).
Association of obesity and overweight with the prevalence of insulin resistance, pre-diabetes and clinical–biochemical characteristics among infertile Mexican women with polycystic ovary syndrome: a cross-sectional study
Authors: Reyes-Muñoz Enrique , Ortega-González Carlos , Martínez-Cruz Nayeli , Arce-Sánchez Lidia , Estrada-Gutierrez Guadalupe , Moran Carlos , Sánchez-Serrano Ana Paola , Higareda-Sánchez Rodolfo , de la Jara-Díaz Julio Francisco
Published: July 2016

Objective

To study the association of obesity and overweight with the prevalence of insulin resistance (IR), pre-diabetes and clinical–biochemical characteristics among infertile Mexican women with polycystic ovary syndrome (PCOS).

Design

Retrospective cross-sectional study.

Setting

Level-three medical institution, an infertility clinic in Mexico City.

Participants

We included infertile Mexican women with diagnosis of PCOS according to the Rotterdam criteria: group 1 (n=83), normal weight (body mass index (BMI) 18.5–24.9 kg/m2); group 2 (n=217), overweight (BMI 25–29.9 kg/m2); and group 3 (n=238), obese (BMI≥30 kg/m2).

Primary and secondary outcome measures

IR was determined by homeostatic model assessment (HOMA) >2.5 and pre-diabetes by fasting glucose between 5.6 and 6.9 mmol/L and/or glucose value between 7.8 and 11 mmol/L at 2 hours during an oral glucose tolerance test. We compared clinical–biochemical characteristics among groups.

Results

Prevalence of IR for groups 1, 2 and 3 was 19.3%, 56.2% and 78.2%; overweight and obesity increase the IR OR (CI 95%) to 5.3 (2.9 to 9.8) and 14.9 (8.0 to 28), respectively. Prevalence of pre-diabetes for groups 1, 2 and 3 was 7.2%, 17.5% and 31.5%; overweight and obesity increase the pre-diabetes OR (CI 95%) to 2.7 (1.1 to 6.7) and 5.9 (2.4 to 14), respectively. Acanthosis nigricans was more frequent in group 3 than group 1. Free Androgen Index (FAI) and thyroid-stimulating hormone (TSH) levels were lower in group 1 than in groups 2 and 3. Progesterone and sex hormone-binding globulin (SHBG) levels were higher in group 1 than in groups 2 and 3. Dehydroepiandrosterone sulfate (DHEA-S) was higher in group 1 than group 3.

Conclusions

Obese and overweight infertile Mexican women with PCOS, attending to an infertility clinic, have a higher prevalence of IR and pre-diabetes compared with normal-weight women with PCOS. Therapeutic interventions should include those that improved metabolic functioning prior to attempting pregnancy in these groups of women.
Valsalva using a syringe: pressure and variation
Authors: Thornton Hilary Sarah , Elwan Mohammed H , Reynolds Joseph A , Coats Timothy J
Published: July 2016

Background

The Valsalva manoeuvre is commonly used in EDs to terminate supraventricular tachycardia by the patient blowing into a syringe.

Aim

To identify whether a specific syringe size can be recommended for use in the ED.

Results

20% of syringes ‘stuck’ and required high pressures to move. In the remaining 80% of syringes, a 20 mL syringe was the most appropriate size to achieve the recommended 40 mm Hg. Once ‘released’ plunger position did not make a difference.

Conclusions

Use of a syringe of any size cannot be recommended if a consistent pressure is required.
ARID4B is a good biomarker to predict tumour behaviour and decide WHO grades in gliomas and meningiomas
Authors: Tsai Wen-Chiuan , Hueng Dueng-Yuan , Nieh Shin , Gao Hong-Wei
Published: July 2016

Aims

Although ARID4B is known to promote tumour metastasis in breast cancer and inhibit transformation and progression in leukaemia, the possible effect of ARID4B on primary brain tumours (PBTs) is not well characterised. We tested the hypothesis that expression of ARID4B correlates with WHO grade and survival in patients with PBTs.

Methods

Western blot analysis was performed on protein lysates prepared from normal brain tissue and glioma cell lines (U87MG, LN229, GBM8401 and U118MG). Subsequently, immunohistochemical analysis of ARID4B was performed on 2 tissue microarrays, including 12 normal brain tissues, 63 meningiomas with different subtypes, 232 gliomas of various grades and degrees of differentiation, 8 central neurocytomas and 4 chordomas. The ARID4B immunostaining score was calculated by multiplying the intensity score by the percentage of tumour cells expressing ARID4B.

Results

In vitro, ARID4B protein expression was increased in some glioma cell lines. In addition, the average ARID4B immunostaining score was 38.03, 79.09, 129.76 and 119.32, respectively, in gliomas of WHO grade I, II, III and IV. Higher ARID4B immunostaining score was significantly correlated with more advanced WHO grade of gliomas (p=7.4×10–6) and meningiomas. Finally, higher ARID4B expression tended to the shorter survival rates, but did not reach statistical significance.

Conclusions

ARID4B overexpression presented in most of PBTs, rather than non-neoplastic brain tissue, and correlated with WHO grades in meningiomas and gliomas. Therefore, ARID4B is a satisfactory biomarker to highlight tumour component and predict tumour behaviour in primary brain neoplasms.
Mexico's epidemic of violence and its public health significance on average length of life
Authors: Canudas-Romo Vladimir , Aburto José Manuel , García-Guerrero Victor Manuel , Beltrán-Sánchez Hiram
Published: July 2016

Objectives

A disproportionate number of homicides have caused Mexican life expectancy to stagnate during the new millennium. No efforts currently exist to quantify the harm of violent acts on the lives of the general population. We quantified the impact of perceived vulnerability on life expectancy.

Methods

Three Mexican national surveys on perceptions of public safety, life tables, and crime and vital statistics (2000–2014) were used. Prevalence rates of vulnerability/safety by age and sex were obtained from surveys at 2 different levels: federal state and home. The Sullivan method was used to estimate life expectancy lived with and without vulnerability for Mexican women and men.

Results

Overall life expectancy at age 20 stagnated between 2005 and 2014 for females and males; yet, there was an increase of 40% and 70% in average number of years lived with vulnerability at the state and home levels, respectively. In 2014, female life expectancy at age 20 was 59.5 years (95% CI 59.0 to 60.1); 71% of these years (42.3 years, 41.6 to 43.0) were spent with perceived vulnerability of violence taking place in the state and 26% at the home (15.3 years, 15 to 15.8). For males, life expectancy at age 20 was 54.5 years (53.7 to 55.1); 64% of these years (34.6 years, 34.0 to 35.4) were lived with perceived vulnerability of violence at the state and 20% at the home (11.1 years, 10.8 to 11.5).

Conclusions

The number of years lived with perceived vulnerability among Mexicans has increased by 30.5 million person-years over the last 10 years. If perceived vulnerability remains at its 2014 level, the average Mexican adults would be expected to live a large fraction of his/her life with perceived vulnerability of violence. Acts of violence continue to rise in the country and they should be addressed as a major public health issue before they become endemic.