bluuebunny/crossref_metadata_2025 huggingface dataset:
Elemental fingerprint as a cerebrospinal fluid biomarker for the diagnosis of Parkinson's disease
Authors: Maass Fabian , Michalke Bernhard , Leha Andreas , Boerger Matthias , Zerr Inga , Koch Jan‐Christoph , Tönges Lars , Bähr Mathias , Lingor Paul
Published: February 2018

The diagnosis of Parkinson's disease (PD) still lacks objective diagnostic markers independent of clinical criteria. Cerebrospinal fluid (CSF) samples from 36 PD and 42 age‐matched control patients were subjected to inductively coupled plasma‐sector field mass spectrometry and a total of 28 different elements were quantified. Different machine learning algorithms were applied to the dataset to identify a discriminating set of elements yielding a novel biomarker signature. Using 19 stably detected elements, the extreme gradient tree boosting model showed the best performance in the discrimination of PD and control patients with high specificity and sensitivity (78.6% and 83.3%, respectively), re‐classifying the training data to 100%. The 10 times 10‐fold cross‐validation yielded a good area under the receiver operating characteristic curve of 0.83. Arsenic, magnesium, and selenium all showed significantly higher mean CSF levels in the PD group compared to the control group (p = 0.01, p = 0.04, and p = 0.03). Reducing the number of elements to a discriminating minimum, we identified an elemental cluster (Se, Fe, As, Ni, Mg, Sr), which most importantly contributed to the sample discrimination. Selenium was identified as the element with the highest impact within this cluster directly followed by iron. After prospective validation, this elemental fingerprint in the CSF could have the potential to be used as independent biomarker for the diagnosis of PD. Next to their value as a biomarker, these data also argue for a prominent role of these highly discriminating six elements in the pathogenesis of PD.

image
FACT‐Hep increases the accuracy of survival prediction in HCC patients when added to ECOG Performance Status
Authors: Gmür Andrea , Kolly Philippe , Knöpfli Marina , Dufour Jean‐François
Published: February 2018

Background and aim

The Eastern Cooperative Oncology Group Performance Status (ECOG PS) is a strong predictor of survival for patients with hepatocellular carcinoma (HCC), and is used with liver function and tumour burden in the Barcelona Clinic Liver Cancer (BCLC) staging system. This work assesses whether the health‐related quality of life (HRQL), measured by the Functional Assessment of Cancer Therapy‐Hepatobiliary (FACT‐Hep) questionnaire, discriminates HCC patients in terms of survival and adds prognostic information to ECOG PS.

Methods

A total of 242 patients participating in the prospective Bern HCC Cohort at the University Hospital Bern were analysed. The relationship between FACT‐Hep and sociodemographic and clinical factors, including survival, were assessed. An analysis on treatment subgroups was performed using Kaplan‐Meier curves and Long‐Rank test. Additionally, the ability to predict overall survival was compared between the ECOG PS and FACT‐Hep total and subscales using Nagelkerke pseudo‐R2.

Results

FACT‐Hep subscales were significantly worse in females and in patients with limited liver function. FACT‐Hep total and all subscales, except the social/family well‐being subscale showed significant differences between ECOG PS groups and were significant predictors of survival. ECOG PS groups, followed by the functional well‐being subscale, were the best at predicting survival. In the resection subgroup, significant differences in OS regarding to HRQL were found. When adding the functional well‐being subscale to ECOG PS, the accuracy of the survival prediction was significantly increased.

Conclusion

HRQL assessed by the FACT‐Hep questionnaire is a reliable prognostic predictor of survival for patients with HCC and it adds prognostic information to the ECOG PS.
Intravesicular cidofovir for BK hemorrhagic cystitis in pediatric patients after hematopoietic stem cell transplant
Authors: Foster Jennifer H. , Cheng W. Susan , Nguyen Ngoc‐Yen , Krance Robert , Martinez Caridad
Published: February 2018

BK virus hemorrhagic cystitis is a complication of HCST. Response to IV cidofovir is unpredictable, and treatment carries risk of toxicity. We report the largest series of pediatric patients with BKHC after HSCT successfully treated with intravesicular cidofovir. There was no significant decrease in urine or plasma BK PCR. There was significant decrease in pain score on days 3 and 7, with associated decrease in morphine use. No patients experienced toxicities associated with IV cidofovir. Intravesicular cidofovir appears to be safe and effective for symptomatic treatment of BKHC in pediatric patients after HSCT.
Comparison of tuberculin skin test and interferon gamma release assay for diagnosis of latent tuberculosis infection in pediatric candidates of renal transplantation
Authors: Sayyahfar Shirin , Davoodzadeh Faranak , Hoseini Rozita , Rahimzadeh Nahid , Otukesh Hasan
Published: February 2018

IGRA has been approved as an alternative in vitro test to diagnose Mycobacterium TB infection. This study aimed to assess the diagnostic value of TST in comparison with QFT assay to detect LTBI among Iranian children candidate for renal transplantation. This cross‐sectional study was performed on 31 children who were candidate for renal transplantation admitted to Ali Asghar Children's Hospital and Rasoul Akram Hospital, Tehran, Iran, from 2013 to 2014. TST and QFT were performed for all patients. QFT was negative in all patients, while TST was positive only in one case. Both tests results were negative in 30 patients, yielding an accuracy rate of 96.7% for TST to diagnose LTBI when compared to QFT. In conclusion, compared to QFT, TST is still a valuable diagnostic tool with high accuracy rate for diagnosis of LTBI in children candidates for renal transplantation and can still be used as an accurate test for screening Mycobacterium TB infection.
Disseminated fungal infection by Aureobasidium pullulans in a renal transplant recipient
Authors: Nalcacioglu Hulya , Yakupoglu Y. Kamil , Genc Gurkan , Belet Nursen , Sensoy Sema Gulnar , Birinci Asuman , Ozkaya Ozan
Published: February 2018

Renal transplant recipients are on long‐term potent immunosuppressive therapy, which makes them highly vulnerable to opportunistic fungal infections. Dematiaceous, or dark‐pigmented saprophytic fungi, are being increasingly seen as opportunistic pathogens of mycoses in immunosuppressed patients. One of these is Aureobasidium pullulans, which is a black yeast‐like dematiaceous fungus found ubiquitously in the environment that can cause various opportunistic human infections. Most infections occur by traumatic inoculation, such as keratitis and cutaneous lesions; disseminated mycoses are very rare and occur only in severely immunocompromised patients. We report a case of disseminated fungal infection due to A. pullulans in a pediatric patient who underwent renal transplant. The use of voriconazole and vacuum‐assisted closure along with surgical drainage most likely contributed to the patient's positive outcome.
The effect of peri‐transplant plasmapheresis in the prevention of recurrent FSGS
Authors: Verghese P. S. , Rheault M. N. , Jackson S. , Matas A. J. , Chinnakotla S. , Chavers B.
Published: February 2018

Many pediatric centers utilize a variety of protocols including preemptive plasmapheresis to prevent the recurrence of FSGS post‐transplant. But the effectiveness of this expensive, time‐consuming process of plasmapheresis in the prevention of FSGS recurrence is still unclear. We retrospectively reviewed all pediatric cases of FSGS in our center that received a kidney transplant and compared the transplant and patient outcomes of those transplanted after 2006 who received pretransplant plasmapheresis to those prior to 2006 who did not. Of the 57 children with FSGS, 31 and 26 were transplanted before and after 2006, respectively. The cohorts differed significantly in keeping with the center immunosuppression protocol changes, and prior to 2006, the recipients were significantly younger. All children with FSGS transplanted after 2006 underwent three and one sessions of 1.0 plasma volume/exchange plasmapheresis with fresh frozen plasma replacement prior to the transplant in living and deceased donors, respectively, in addition to five sessions of every other day post‐transplant pheresis. The incidence (27% vs 26%, P = 1.0) and time to recurrence of FSGS in the kidney allograft (P = .22) were not significantly different in patients that did and did not undergo prophylactic plasmapheresis. We need to re‐evaluate the role of preemptive plasmapheresis in the prevention of FSGS recurrence in a prospective multicenter study.
Ecosystem‐level effects of keystone species reintroduction: a literature review
Authors: Hale Sarah L. , Koprowski John L.
Published: February 2018

The keystone species concept was introduced in 1969 in reference to top‐down regulation of communities by predators, but has expanded to include myriad species at different trophic levels. Keystone species play disproportionately large, important roles in their ecosystems, but human‐wildlife conflicts often drive population declines. Population declines have resulted in the necessity of keystone species reintroduction; however, studies of such reintroductions are rare. We conducted a literature review and found only 30 peer‐reviewed journal articles that assessed reintroduced populations of keystone species, and only 11 of these assessed ecosystem‐level effects following reintroduction. Nine of 11 publications assessing ecosystem‐level effects found evidence of resumption of keystone roles; however, these publications focus on a narrow range of species. We highlight the deficit of peer‐reviewed literature on keystone species reintroductions, and draw attention to the need for assessment of ecosystem‐level effects so that the presence, extent, and rate of ecosystem restoration driven by keystone species can be better understood.
Michelangelo, St Bartholomew, and northern Italy
Authors: Gregory Sharon
Published: February 2018

Since 1925, it has been widely accepted that Michelangelo painted his own self‐portrait into the flayed skin of St Bartholomew in the fresco of the Last Judgement. Interpretations of what this can have been intended to mean differ widely, from representing Michelangelo's desire to be freed from the constraints of the flesh, to the artist's recognition of his own Marsyas‐like audacity. It seems prudent to inquire into the origins of this motif before speculating on its meaning in the context of this fresco. Perhaps thanks to historical assertions of Michelangelo's originality and inherent genius, it is infrequently noted that Michelangelo owed a significant debt to earlier depictions of the Last Judgement. This paper aims to show that St Bartholomew is often depicted by Northern Italian artists as holding or wearing his flayed skin. Michelangelo may have become aware of these images during his northern sojourns, which included two visits to Venice.
Sub‐dimensions of trait emotional intelligence and health: A critical and systematic review of the literature
Authors: Baudry Anne‐Sophie , Grynberg Delphine , Dassonneville Charlotte , Lelorain Sophie , Christophe Véronique
Published: February 2018

Despite a growing number of studies on the role of the multidimensional construct of trait emotional intelligence (EI) in health, most have focused on global EI, without examining the role of the sub‐dimensions. The present systematic review aimed to highlight the current knowledge about self‐reported health associated with trait‐EI sub‐dimensions in general and clinical populations. We searched for the articles including valid self‐report scales of trait‐EI and health (mental or physical or general) in general and clinical samples. Based on 42 studies, the majority of studies was based on mental health with cross‐sectional designs and the TMMS scale, in the general population. Few studies have been focused on physical health and clinical population. The description of studies results revealed that trait‐EI sub‐dimensions are associated to a greater extent with better mental health, rather than with physical and general health. Furthermore, intrapersonal dimensions, and especially emotion regulation, have stronger effects on health than interpersonal dimensions. Finally, patients with a clinical disorder present lower trait‐EI sub‐dimensions than the general population. This review supports the importance of focusing on the sub‐dimensions of trait‐EI to understand better the role of EI in health. The use of scales exclusively based on emotional competences in health contexts is recommended. Developing interventions targeting emotional competences according to the emotional profiles and contexts of individuals could be beneficial to improve health and disease adjustment.
Characterization of a novel HLA‐DRB1*07 allele, DRB1*07:83
Authors: Balas A. , Alenda R. , Moreno‐Hidalgo M. A. , García‐Sánchez F. , Vicario J. L.
Published: February 2018

A new DRB1*07 allele, DRB1*07:83, was described in a Caucasian Spanish donor.
Characterization of the novel HLA‐C*16:116 allele by sequencing‐based typing
Authors: Guidicelli G. , Elsermans V. , Top I. , Ralazamahaleo M. , Visentin J.
Published: February 2018

HLA‐C*16:116 differs from HLA‐C*16:01:01:01 by single‐nucleotide substitution at position 30.
Purification and characterization of Arabidopsis thaliana oligosaccharyltransferase complexes from the native host: a protein super‐expression system for structural studies
Authors: Jeong In Sil , Lee Sangmin , Bonkhofer Florian , Tolley Jordan , Fukudome Akihito , Nagashima Yukihiro , May Kimberly , Rips Stephan , Lee Sang Y. , Gallois Patrick , Russell William K. , Jung Hyun Suk , von Schaewen Antje , Koiwa Hisashi
Published: February 2018

The oligosaccharyltransferase (OT) complex catalyzes N‐glycosylation of nascent secretory polypeptides in the lumen of the endoplasmic reticulum. Despite their importance, little is known about the structure and function of plant OT complexes, mainly due to lack of efficient recombinant protein production systems suitable for studies on large plant protein complexes. Here, we purified Arabidopsis OT complexes using the tandem affinity‐tagged OT subunit STAUROSPORINE AND TEMPERATURE SENSITIVE3a (STT3a) expressed by an Arabidopsis protein super‐expression platform. Mass‐spectrometry analysis of the purified complexes identified three essential OT subunits, OLIGOSACCHARYLTRANSFERASE1 (OST1), HAPLESS6 (HAP6), DEFECTIVE GLYCOSYLATION1 (DGL1), and a number of ribosomal subunits. Transmission‐electron microscopy showed that STT3a becomes incorporated into OT–ribosome super‐complexes formed in vivo, demonstrating that this expression/purification platform is suitable for analysis of large protein complexes. Pairwise in planta interaction analyses of individual OT subunits demonstrated that all subunits identified in animal OT complexes are conserved in Arabidopsis and physically interact with STT3a. Genetic analysis of newly established OT subunit mutants for OST1 and DEFENDER AGAINST APOTOTIC DEATH (DAD) family genes revealed that OST1 and DAD1/2 subunits are essential for the plant life cycle. However, mutations in these individual isoforms produced much milder growth/underglycosylation phenotypes than previously reported for mutations in DGL1, OST3/6 and STT3a.
Cellular distribution of secretory pathway markers in the haploid synergid cells of Arabidopsis thaliana
Authors: Jones Daniel S. , Liu Xunliang , Willoughby Andrew C. , Smith Benjamin E. , Palanivelu Ravishankar , Kessler Sharon A.
Published: February 2018

In flowering plants, cell–cell communication plays a key role in reproductive success, as both pollination and fertilization require pathways that regulate interactions between many different cell types. Some of the most critical of these interactions are those between the pollen tube (PT) and the embryo sac, which ensure the delivery of sperm cells required for double fertilization. Synergid cells function to attract the PT through secretion of small peptides and in PT reception via membrane‐bound proteins associated with the endomembrane system and the cell surface. While many synergid‐expressed components regulating PT attraction and reception have been identified, few tools exist to study the localization of membrane‐bound proteins and the components of the endomembrane system in this cell type. In this study, we describe the localization and distribution of seven fluorescent markers that labelled components of the secretory pathway in synergid cells of Arabidopsis thaliana. These markers were used in co‐localization experiments to investigate the subcellular distribution of the two PT reception components LORELEI, a GPI‐anchored surface protein, and NORTIA, a MILDEW RESISTANCE LOCUS O protein, both found within the endomembrane system of the synergid cell. These secretory markers are useful tools for both reproductive and cell biologists, enabling the analysis of membrane‐associated trafficking within a haploid cell actively involved in polar transport.
Transfusion‐associated circulatory overload in a pediatric intensive care unit: different incidences with different diagnostic criteria
Authors: De Cloedt Lise , Emeriaud Guillaume , Lefebvre Émilie , Kleiber Niina , Robitaille Nancy , Jarlot Christine , Lacroix Jacques , Gauvin France
Published: February 2018

BACKGROUND

The incidence of transfusion‐associated circulatory overload (TACO) is not well known in children, especially in pediatric intensive care unit (PICU) patients.

STUDY DESIGN AND METHODS

All consecutive patients admitted over 1 year to the PICU of CHU Sainte‐Justine were included after they received their first red blood cell transfusion. TACO was diagnosed using the criteria of the International Society of Blood Transfusion, with two different ways of defining abnormal values: 1) using normal pediatric values published in the Nelson Textbook of Pediatrics and 2) by using the patient as its own control and comparing pre‐ and posttransfusion values with either 10 or 20% difference threshold. We monitored for TACO up to 24 hours posttransfusion.

RESULTS

A total of 136 patients were included. Using the “normal pediatric values” definition, we diagnosed 63, 88, and 104 patients with TACO at 6, 12, and 24 hours posttransfusion, respectively. Using the “10% threshold” definition we detected 4, 15, and 27 TACO cases in the same periods, respectively; using the “20% threshold” definition, the number of TACO cases was 2, 6, and 17, respectively. Chest radiograph was the most frequent missing item, especially at 6 and 12 hours posttransfusion. Overall, the incidence of TACO varied from 1.5% to 76% depending on the definition.

CONCLUSION

A more operational definition of TACO is needed in PICU patients. Using a threshold could be more optimal but more studies are needed to confirm the best threshold.
Differential sensitivity of Atriplex patula and Chenopodium album to sugar beet herbicides: a possible cause for the upsurge of A. patula in sugar beet fields
Authors: De Cauwer B , Cardinael A , Claerhout S , Manderyck B , Reheul D
Published: February 2018

In the last decade, the prevalence of Atriplex patula as a weed in the Belgian sugar beet area has increased. Possible reasons for its expansion in sugar beet fields, besides a poor implementation of the low‐dose phenmedipham/activator/soil‐acting herbicide (FAR) system, might be low sensitivity or evolved resistance to one or more herbicides used in sugar beet. Dose–response pot bioassays were conducted in the glasshouse to evaluate the effectiveness of five foliar‐applied sugar beet herbicides (metamitron, phenmedipham, desmedipham, ethofumesate and triallate) and three pre‐plant‐incorporated herbicides (metamitron, lenacil, dimethenamid‐P) for controlling five Belgian A. patula populations. Local metamitron‐susceptible and metamitron‐resistant populations of Chenopodium album were used as reference populations. Effective dosages and resistance indices were calculated. DNA sequence analysis of the photosystem II psbA gene was performed on putative resistant A. patula populations. Overall, A. patula exhibited large intraspecific variation in herbicide sensitivity. In general, A. patula populations were less susceptible to phenmedipham, desmedipham, ethofumesate and triallate relative to C. album populations. Two A. patula populations bear the leucine‐218 to valine mutation on the chloroplast psbA gene conferring low level to high level cross‐resistance to the photosystem II inhibitors phenmedipham, desmedipham, metamitron and lenacil. In order to avoid insufficient A. patula control and further spread, seedlings should preferentially be treated with FAR mixtures containing higher‐than‐standard doses of metamitron and phenmedipham/desmedipham and no later than the cotyledon stage.
Phrenic motor neuron adenosine 2A receptors elicit phrenic motor facilitation
Authors: Seven Yasin B. , Perim Raphael R. , Hobson Orinda R. , Simon Alec K. , Tadjalli Arash , Mitchell Gordon S.
Published: February 2018

Key points

Although adenosine 2A (A2A) receptor activation triggers specific cell signalling cascades, the ensuing physiological outcomes depend on the specific cell type expressing these receptors.

Cervical spinal adenosine 2A (A2A) receptor activation elicits a prolonged facilitation in phrenic nerve activity, which was nearly abolished following intrapleural A2A receptor siRNA injections.

A2A receptor siRNA injections selectively knocked down A2A receptors in cholera toxin B‐subunit‐identified phrenic motor neurons, sparing cervical non‐phrenic motor neurons.

Collectively, our results support the hypothesis that phrenic motor neurons express the A2A receptors relevant to A2A receptor‐induced phrenic motor facilitation.

Upregulation of A2A receptor expression in the phrenic motor neurons per se may potentially be a useful approach to increase phrenic motor neuron excitability in conditions such as spinal cord injury.

Cervical spinal adenosine 2A (A2A) receptor activation elicits a prolonged increase in phrenic nerve activity, an effect known as phrenic motor facilitation (pMF). The specific cervical spinal cells expressing the relevant A2A receptors for pMF are unknown. This is an important question since the physiological outcome of A2A receptor activation is highly cell type specific. Thus, we tested the hypothesis that the relevant A2A receptors for pMF are expressed in phrenic motor neurons per se versus non‐phrenic neurons of the cervical spinal cord. A2A receptor immunostaining significantly colocalized with NeuN‐positive neurons (89 ± 2%). Intrapleural siRNA injections were used to selectively knock down A2A receptors in cholera toxin B‐subunit‐labelled phrenic motor neurons. A2A receptor knock‐down was verified by a ∼45% decrease in A2A receptor immunoreactivity within phrenic motor neurons versus non‐targeting siRNAs (siNT; P < 0.05). There was no evidence for knock‐down in cervical non‐phrenic motor neurons. In rats that were anaesthetized, subjected to neuromuscular blockade and ventilated, pMF induced by cervical (C3–4) intrathecal injections of the A2A receptor agonist CGS21680 was greatly attenuated in siA2A (21%) versus siNT treated rats (147%; P < 0.01). There were no significant effects of siA2A on phrenic burst frequency. Collectively, our results support the hypothesis that phrenic motor neurons express the A2A receptors relevant to A2A receptor‐induced pMF.
One-Dimensional Constrained Blister Test to Measure Thin Film Adhesion
Authors: Zhu Tingting , Müftü Sinan , Wan Kai-tak
Published: February 2018

A rectangular film is clamped at the opposite ends before being inflated into a blister by an external pressure, p. The bulging film adheres to a constraining plate with distance, w0, above. Increasing pressure expands the contact area of length, 2c. Depressurization shrinks the contact area and ultimate detaches the film. The relation of (p, w0, c) is established for a fixed interfacial adhesion energy.
Effects of Plastic Anisotropy and Void Shape on Full Three-Dimensional Void Growth
Authors: Legarth Brian Nyvang , Tvergaard Viggo
Published: February 2018

Void growth in an anisotropic ductile solid is studied by numerical analyses for three-dimensional (3D) unit cells initially containing a void. The effect of plastic anisotropy on void growth is the main focus, but the studies include the effects of different void shapes, including oblate, prolate, or general ellipsoidal voids. Also, other 3D effects such as those of different spacings of voids in different material directions and the effects of different macroscopic principal stresses in three directions are accounted for. It is found that the presence of plastic anisotropy amplifies the differences between predictions obtained for different initial void shapes. Also, differences between principal transverse stresses show a strong interaction with the plastic anisotropy, such that the response is very different for different anisotropies. The studies are carried out for one particular choice of void volume fraction and stress triaxiality.
Early Acoustic Warning for the Onset of Acute Chest Syndrome in Sickle Cell Patients
Authors: Henry Brian , Yost Gardner , Molokie Robert , Royston Thomas J.
Published: February 2018

Acute chest syndrome (ACS) is a leading cause of death for those with sickle cell disease (SCD). ACS is defined by the development of a new pulmonary infiltrate on chest X-ray, with fever and respiratory symptoms. Efforts have been made to apply various technologies in the hospital setting to provide earlier detection of ACS than X-ray, but they are expensive, increase radiation exposure to the patient, and are not technologies that are easily transferrable for home use to help with early diagnosis. We present preliminary studies on patients suggesting that acoustical measurements recorded quantitatively with contact sensors (electronic stethoscopes) and analyzed using advanced computational analysis methods may provide an earlier diagnostic indicator of the onset of ACS than is possible with current clinical practice. Novel in silico models of respiratory acoustics utilizing image-based and algorithmically developed lungs with full conducting airway trees support and help explain measured acoustic trends and provide guidance on the next steps in developing and translating a diagnostic approach. More broadly, the experimental and computational techniques introduced herein, while focused on monitoring and predicting the onset of ACS, could catalyze further advances in mobile health (mhealth)-enabled, computer-based auscultative diagnoses for a wide range of cardiopulmonary pathologies.
NASA seeks to revive lost probe that traced solar storms
Authors: Voosen Paul
Published: February 2018

Amateur found IMAGE while looking for spy satellite.
Climate, ecosystems, and planetary futures: The challenge to predict life in Earth system models
Authors: Bonan Gordon B. , Doney Scott C.
Published: February 2018

Integrating the biosphere into climate models

High-quality climate predictions are crucial for understanding the impacts of different greenhouse gas emission scenarios and for mitigating and adapting to the resulting climatic changes. Bonan and Doney review advances in Earth system models that include the terrestrial and marine biosphere. Such models capture interactions between physical and biological aspects of the Earth system. This provides insight into climate impacts of societal importance, such as altered crop yields, wildfire risk, and water availability. Further research is needed to better understand model uncertainties, some of which may be unavoidable, and to better translate observations into abstract model representations.

Science
, this issue p.
eaam8328
A Novel Dual-
cre
Motif Enables Two-Way Autoregulation of CcpA in Clostridium acetobutylicum
Authors: Zhang Lu , Liu Yanqiang , Yang Yunpeng , Jiang Weihong , Gu Yang
Published: February 2018

The master regulator CcpA (catabolite control protein A) manages a large and complex regulatory network that is essential for cellular physiology and metabolism in Gram-positive bacteria. Although CcpA can affect the expression of target genes by binding to a
cis
-acting catabolite-responsive element (
cre
), whether and how the expression of CcpA is regulated remain poorly explored. Here, we report a novel dual-
cre
motif that is employed by the CcpA in
Clostridium acetobutylicum
, a typical solventogenic
Clostridium
species, for autoregulation. Two
cre
sites are involved in CcpA autoregulation, and they reside in the promoter and coding regions of CcpA. In this dual-
cre
motif,
cre
P
, in the promoter region, positively regulates
ccpA
transcription, whereas
cre
ORF
, in the coding region, negatively regulates this transcription, thus enabling two-way autoregulation of CcpA. Although CcpA bound
cre
P
more strongly than
cre
ORF
in vitro
, the
in vivo
assay showed that
cre
ORF
-based repression dominates CcpA autoregulation during the entire fermentation. Finally, a synonymous mutation of
cre
ORF
was made within the coding region, achieving an increased intracellular CcpA expression and improved cellular performance. This study provides new insights into the regulatory role of CcpA in
C. acetobutylicum
and, moreover, contributes a new engineering strategy for this industrial strain.

IMPORTANCE
CcpA is known to be a key transcription factor in Gram-positive bacteria. However, it is still unclear whether and how the intracellular CcpA level is regulated, which may be essential for maintaining normal cell physiology and metabolism. We discovered here that CcpA employs a dual-
cre
motif to autoregulate, enabling dynamic control of its own expression level during the entire fermentation process. This finding answers the questions above and fills a void in our understanding of the regulatory network of CcpA. Interference in CcpA autoregulation leads to improved cellular performance, providing a new useful strategy in genetic engineering of
C. acetobutylicum
. Since CcpA is widespread in Gram-positive bacteria, including pathogens, this dual-
cre
-based CcpA autoregulation would be valuable for increasing our understanding of CcpA-based global regulation in bacteria.
Social and structural conditions for the avoidance of advance care planning in neuro-oncology: a qualitative study
Authors: Llewellyn Henry , Neerkin Jane , Thorne Lewis , Wilson Elena , Jones Louise , Sampson Elizabeth L , Townsley Emma , Low Joseph T S
Published: February 2018

Background

Primary brain tumours newly affect >260 000 people each year worldwide. In the UK, every year >10 000 people are diagnosed with a brain tumour while >5000 die annually from the disease. Prognoses are poor, cognitive deterioration common and patients have prolonged palliative needs. Advance care planning (ACP) may enable early discussion of future care decisions. Although a core commitment in the UK healthcare strategy, and the shared responsibility of clinical teams, ACP appears uncommon in practice. Evidence around ACP practice in neuro-oncology is limited.

Objectives

We aimed to elicit keysocial and structural conditionscontributing to the avoidance of ACP in neuro-oncology.

Design

A cross-sectional qualitative study design was used.

Setting

One tertiary care hospital in the UK.

Participants

Fifteen healthcare professionals working in neuro-oncology participated in this study, including neuro-oncologists, neurosurgeons, clinical nurse specialists, allied healthcare professionals and a neurologist.

Method

Semi-structured interviews were conducted with participants to explore their assumptions and experiences of ACP. Data were analysed thematically using the well-established framework method.

Results

Participants recognised the importance of ACP but few had ever completed formal ACP documentation. We identified eight key factors, which we suggest comprise three main conditions for avoidance: (1) difficulties being a highly emotive, time-intensive practice requiring the right ‘window of opportunity’ and (2) presence and availability of others; (3) ambiguities in ACP definition, purpose and practice. Combined, these created a ‘culture of shared avoidance’.

Conclusion

In busy clinical environments, ‘shared responsibility’ is interpreted as ‘others’ responsibility’ laying the basis for a culture of avoidance. To address this, we suggest a ‘generalists and specialists’ model of ACP, wherein healthcare professionals undertake particular responsibilities. Healthcare professionals are already adopting this model informally, but without formalised structure it is likely to fail given a tendency for people to assume a generalist role.
Investigation of the conditions affecting the joining of Hungarian hospitals to an accreditation programme: a cross-sectional study
Authors: Dombrádi Viktor , Margitai Barnabás , Dózsa Csaba , Bárdos-Csenteri Orsolya Karola , Sándor János , Gáll Tibor , Gődény Sándor
Published: February 2018

Objective

Quantitative studies have shown the various benefits for having accreditation in hospitals. However, neither of these explored the general conditions before applying for an accreditation. To close this gap, this study aimed to investigate the possible association between joining an accreditation programme with various hospital characteristics.

Design

A cross-sectional study was implemented using the databases of the 2013 Hungarian hospital survey and of the Hungarian State Treasury.

Setting

Public general hospitals in Hungary.

Participants

The analysis involved 44 public general hospitals, 14 of which joined the preparatory project for a newly developed accreditation programme.

Main outcome measures

The outcomes included the percentage of compliance in quality management, patient information and identification, internal professional regulation, safe surgery, pressure sore prevention, infection control, the opinions of the heads of quality management regarding the usefulness of quality management and clinical audits, and finally, the total debt of the hospital per bed and per discharged patient.

Results

According to our findings, the general hospitals joining the preparatory project of the accreditation programme performed better in four of the six investigated activities, the head of quality management had a better opinion on the usefulness of quality management, and both the debt per bed number and the debt per discharged patient were lower than those who did not join. However, no statistically significant differences between the two groups were found in any of the examined outcomes.

Conclusions

The findings suggest that hospitals applying for an accreditation programme do not differ significantly in characteristics from those which did not apply. This means that if in the future the accredited hospitals become better than other hospitals, then the improvement could be solely contributed to the accreditation.
Predicting prostate cancer progression: protocol for a retrospective cohort study to identify prognostic factors for prostate cancer outcomes using routine primary care data
Authors: Merriel Samuel W D , May Margaret T , Martin Richard M
Published: February 2018

Introduction

Prostate cancer is the most common cancer in men in the UK, with nearly 40 000 diagnosed in 2014; and it is the second most common cause of male cancer-related mortality. The clinical conundrum is that most men live with prostate cancer rather than die from it, while existing treatments have significant associated morbidity. Recent studies have shown very low mortality rates (1% after a median of 10-year follow-up) and no treatment-related reductions in mortality, in men with localised prostate cancer. This study will identify prognostic factors associated with prostate cancer progression to help differentiate aggressive from more indolent tumours in men with localised disease at diagnosis, and so inform the decision to adopt conservative (active surveillance) or radical (surgery or radiotherapy) management strategies.

Methods and analysis

The Clinical Practice Research Datalink (CPRD) contains 57 318 men who were diagnosed with prostate cancer between 1 January 1987 and 31 December 2016. These men will be linked to the Office for National Statistics (ONS) and the National Cancer Registration and Analysis Service registry databases for mortality, TNM stage, Gleason grade and treatment data. Men with a diagnosis date prior to 1 January 1987 and men with lymph node or distant metastases at diagnosis will be excluded. A priori determined prognostic factors potentially associated with prostate cancer mortality, the end point of cancer progression, will be measured at baseline, and the participants followed through to development of cancer progression, death or the end of the follow-up period (31 December 2016). Cox proportional hazards regression will be used to estimate crude and mutually adjusted HRs. Mortality risk will be predicted using flexible parametric survival models that can accurately fit the shape of the hazard function.

Ethics and dissemination

This study protocol has approval from the Independent Scientific Advisory Committee for the UK Medicines and Healthcare products Regulatory Agency Database Research (protocol 17_041). The findings will be presented in peer-reviewed journals and local CPRD researcher meetings.
Do police officers and firefighters have a higher risk of disease than other public officers? A 13-year nationwide cohort study in South Korea
Authors: Han Minkyung , Park Sohee , Park Jong Heon , Hwang Seung-sik , Kim Inah
Published: February 2018

Objectives

The work of public officers involves repeated and long-term exposure to heavy workloads, high job strain and workplace violence, all of which negatively impact physical and mental health. This study aimed to evaluate and compare the incidences of diseases among different categories of public officers in Korea, in order to further understand the health risks associated with these occupations.

Design

A cohort study using the National Health Insurance data.

Participants

We collated claims data between 2002 and 2014 for 860 221 public officers.

Primary and secondary outcome measures

Age-standardised rates were calculated using the direct standardisation method, and HRs were calculated using the Cox proportional hazard regression models.

Results

Overall, we found that police officers and firefighters had a higher incidence of a range of diseases when compared with national and regional government officers (NRG). The most prominent HRs were observed among police officers for angina pectoris (HR: 1.52, 95% CI 1.49 to 1.54), acute myocardial infarction (HR: 1.84, 95% CI 1.77 to 1.92) and cerebrovascular disease (HR: 1.36, 95% CI 1.31 to 1.40). Firefighters were more susceptible to physical ailments and were at a significantly higher risk for traumatic stress disorders (HR: 1.40, 95% CI 1.26 to 1.56) than NRGs.

Conclusion

Compared withNRGs, police officers had higher HRs for all measured diseases, except for traumatic stress disorders. While firefighters had higher HRs for almost all diseases examined, public education officers had a higher HR for traumatic stress disorders, when compared with NRGs.
Long-term follow-up of the use of maintenance antibiotic therapy for chronic antibiotic-dependent pouchitis
Authors: Segal Jonathan P , Poo Stephanie X , McLaughlin Simon D , Faiz Omar D , Clark Susan K , Hart Ailsa L
Published: February 2018

Objective

Restorative proctolectomy is considered the procedure of choice in patients with ulcerative colitis who have failed medical therapy. Chronic pouchitis occurs in 10%–15% of patients, which often require long-term antibiotics to alleviate symptoms. Safety and efficacy of long-term maintenance antibiotics for chronic pouchitis has yet to be established. We aimed to assess the long-term safety and efficacy of maintenance antibiotic therapy for chronic pouchitis.

Design

This was an observational study. We followed up patients who were diagnosed with chronic antibiotic-dependent pouchitis.

Setting

Data were collected from our single specialist pouch centre.

Patients

Patients with chronic antibiotic-dependent pouchitis who had been maintained on antibiotics continuously for at least 1 year with a least one follow-up visit.

Main outcome measure

Development of pouch failure defined by the need for an ileostomy, patient-reported side effects of antibiotics and development of antibiotic resistance found on stool coliform testing.

Results

Long-term use of antibiotics achieve remission in 21% of patients over a median follow-up of 102 (range 9–125). Pouch failure in association with chronic pouchitis after a median follow-up of 8.5 years occurred in 18%. Side effects of long-term antibiotic use occurred in 28% of patients, with resistance to antibiotics from at least one stool sample occurring in 78% patients.

Conclusions

Although the use of antibiotics in chronic pouchitis may be justified, the use of long-term antibiotics must be weighed against potential complications associated with pouchitis and antibiotics.
Production of Jiggs bermudagrass and the impact of quality milk production and quality of Holstein dairy cows under an intermittent grazing system
Authors: Brandstetter E.V. , Costa K.A.P. , da Silva M.A.P. , Araújo Neto F.R. , da Silva V.R. , Neves R.B.S. , de Souza W.F. , de Oliveira I.P.
Published: February 2018

Dairy production plays a fundamental role in the Brazilian economy and high-quality forage is necessary for ruminants to produce satisfactory milk levels. The aim of the present study was to evaluate the production and quality of Jiggs bermudagrass and its effects on the production and quality parameters of milk from Holstein cows under an intermittent grazing system throughout the year. The experiment was conducted in a randomized design with the four seasons as treatments, replicated five times. The season had a significant effect on the production and nutritional parameters of Jiggs bermudagrass with the highest total dry matter production observed during summer, followed by spring and fall. The neutral detergent fiber and acid detergent fiber contents were significantly higher in winter. The in vitro dry matter digestibility was significantly higher in summer, spring, and fall. Jiggs bermudagrass is a promising forage for the enhancement of milk production under intermittent stocking. However, its effects vary seasonally which exerts a greater influence during the winter, even with irrigation, because it directly affects the milk production and quality. The correlation results demonstrated the importance of better quality forage for increasing milk production without compromising the levels of milk solids.
Analytical bound-state solutions of the Schrödinger equation for the Manning–Rosen plus Hulthén potential within SUSY quantum mechanics
Authors: Ahmadov A. I. , Naeem Maria , Qocayeva M. V. , Tarverdiyeva V. A.
Published: February 2018

In this paper, the bound-state solution of the modified radial Schrödinger equation is obtained for the Manning–Rosen plus Hulthén potential by using new developed scheme to overcome the centrifugal part. The energy eigenvalues and corresponding radial wave functions are defined for any [Formula: see text] angular momentum case via the Nikiforov–Uvarov (NU) and supersymmetric quantum mechanics (SUSY QM) methods. Thanks to both methods, equivalent expressions are obtained for the energy eigenvalues, and the expression of radial wave functions transformations to each other is presented. The energy levels and the corresponding normalized eigenfunctions are represented in terms of the Jacobi polynomials for arbitrary [Formula: see text] states. A closed form of the normalization constant of the wave functions is also found. It is shown that, the energy eigenvalues and eigenfunctions are sensitive to [Formula: see text] radial and [Formula: see text] orbital quantum numbers.
Thermodynamics and phase transition of charged AdS black holes with a global monopole
Authors: Deng Gao-Ming , Fan Jinbo , Li Xinfei , Huang Yong-Chang
Published: February 2018

Thermodynamical properties of charged AdS black holes with a global monopole still remain obscure. In this paper, we investigate the thermodynamics and phase transition of the black holes in the extended phase space. It is shown that thermodynamical quantities of the black holes exhibit an interesting dependence on the internal global monopole, and they perfectly satisfy both the first law of thermodynamics and Smarr relation. Furthermore, analysis of the local and the global thermodynamical stability manifests that the charged AdS black hole undergoes an elegant phase transition at critical point. Of special interest, critical behaviors of the black holes resemble a Van der Waals liquid–gas system. Our results not only reveal the effect of a global monopole on thermodynamics of AdS black holes, but also further support that Van der Waals-like behavior of the black holes is a universal phenomenon.
Dynamical analysis of an n−H−T cosmological quintessence real gas model with a general equation of state
Authors: Ivanov Rossen I. , Prodanov Emil M.
Published: February 2018

The cosmological dynamics of a quintessence model based on real gas with general equation of state is presented within the framework of a three-dimensional dynamical system describing the time evolution of the number density, the Hubble parameter and the temperature. Two global first integrals are found and examples for gas with virial expansion and van der Waals gas are presented. The van der Waals system is completely integrable. In addition to the unbounded trajectories, stemming from the presence of the conserved quantities, stable periodic solutions (closed orbits) also exist under certain conditions and these represent models of a cyclic Universe. The cyclic solutions exhibit regions characterized by inflation and deflation, while the open trajectories are characterized by inflation in a “fly-by” near an unstable critical point.
Adaptive Fuzzy Tracking Control for Stochastic Nonlinear Systems with Time-Varying Input Delays Using the Quadratic Functions
Authors: Yue Hongyun , Li Junmin , Shi Jiarong , Yang Wei
Published: February 2018

In this paper, for the stochastic nonlinear systems the adaptive fuzzy tracking controllers are constructed by using the fuzzy logic systems (FLS) and the classical quadratic functions. Compared with the existing results for adaptive fuzzy control, the stochastic nonlinear systems investigated in this paper are much more complex since the systems not only have distributed state time-varying delays in the noise jamming intensity terms but also have the time-varying delays in the input signals. During the controller design procedure, through appropriate assumptions and a state transformation the system with time-varying input delay can be easily transformed into a system without input delay. The other main advantage is that quadratic functions are used as Lyapunov functions to analyze the stability of systems, other than the fourth moment approach proposed by H. Deng and M. Krstic, and the hyperbolic tangent functions are introduced to deal with the Hessian terms. The proposed adaptive fuzzy controller guarantees that all the signals in the closed-loop system are bounded in probability and the tracking error can converge to a small residual set around the origin in the mean square sense.
Wipro Ltd.: The Demerger of Wipro Enterprises
Authors: Haldipur Rajesh , Narapareddy Vijaya , Vishwanath S. R.
Published: February 2018

In November 2012, Wipro Ltd., a NYSE listed IT Services company, announced its plan to demerge the non-IT businesses into an unlisted entity — Wipro Enterprises. The case highlights the governance, valuation, and ethical issues surrounding the demerger. Shareholders were given three options to choose from. But, in reality, they had no choice but to exchange Wipro Enterprises shares that they would receive after the demerger with Wipro Ltd shares because Wipro Enterprises would remain unlisted. The case asks the student to analyze the restructuring from an investor’s perspective. The case is especially interesting in that it provides a platform to discuss governance issues in the context of a familyowned public firm. It demonstrates how the preferences of majority shareholders can affect the wealth of minority shareholders.