bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying women veterans with unhealthy alcohol use using gender‐tailored screening
Authors: Hoggatt Katherine J. , Simpson Tracy , Schweizer Catherine A. , Drexler Karen , Yano Elizabeth M.
Published: February 2018

Background and Objectives

To assess the impact of gender‐tailored alcohol screening criteria.

Methods

Among N = 1,349 women, we calculated the proportion screening positive for unhealthy alcohol use with non‐tailored versus gender‐tailored criteria (a gender‐tailored binge‐drinking item, lower screen‐positive threshold, or both).

Results

Three percent more women screened positive with a modified binge‐drinking question, most reporting risky drinking. Fifteen percent more women screened positive with a lower threshold; most did not report risky drinking.

Discussion and Conclusions

Gender‐tailored binge‐drinking questions may improve detection of women's unhealthy alcohol use.

Scientific Significance

These results can inform future efforts to improve alcohol screening for women. (Am J Addict 2018;27:97–100)
Method comparison of two non‐invasive dual‐wavelength spectrophotometric retinal oximeters in healthy young subjects during normoxia
Authors: Told Reinhard , Boltz Agnes , Schmetterer Leopold , Garhöfer Gerhard , Sacu Stefan , Schmidt‐Erfurth Ursula , Pollreisz Andreas
Published: February 2018

Purpose

Spectrophotometric retinal oximetry is a non‐invasive technology for measuring oxygen saturation in arterioles and venules (SaO2, SvO2). We compared two commercially available systems: the Oxymap T1 (Oxymap ehf., Reykjavik, Iceland) and the Dynamic Vessel Analyzer (DVA, Imedos, Jena, Germany).

Methods

Twenty healthy adults were included after giving informed consent. Two measurement cycles 30 min apart, including Oxymap T1, DVA, arterialized capillary blood draw of the earlobe (ScO2) and peripheral oxygen saturation using finger pulse oximetry (SpO2) were scheduled.

Results

SaO2 (p > 0.0004) but not SvO2 (p < 0.05) was statistically significantly different between the retinal oximeters used. Agreement between devices using repeated SO2 measurements resulted in a standard deviation (SD) of differences of 3.5% in retinal arterioles and 4.8% in venules. Bland–Altman plot using the mean of a participant's two measurements from each device showed an average mean difference of 4.4% (95% confidence limits of agreement: −8.6 to 17.4) and −3.3% (95% confidence limits of agreement: −28.8 to 22.2) for SaO2 and SvO2, respectively. Comparison of mean SaO2 and SvO2 with mean ScO2 and SpO2 indicated that SO2 measurements were generally higher in ScO2 and SpO2.

Conclusion

This study shows very good repeatability for both devices, which is consistent with the literature. However, it does not show sufficient concordance between SaO2 measurements from both devices, indicating that patients should be followed by one device only. Differences in absorbance wavelengths used and image post‐processing may explain the differences.
Clinician‐rated and self‐reported psychotic‐like experiences in individuals accessing a specialist Youth Mental Health Service
Authors: Hodgekins Jo , Lower Rebecca , Wilson Jon , Cole Hannah , Ugochukwu Uju , Maxwell Sarah , Fowler David
Published: February 2018

Aim

The prevalence of psychotic‐like experiences (PLEs) was explored in a sample of 14‐ to 25‐year‐olds with non‐psychotic mental health difficulties. Associations between PLEs, psychopathology, functioning, trauma history, and pathways to care were examined.

Methods

Data were collected for 202 young people. Clinicians rated PLEs using the Primary Care Checklist (PCC) and functioning using Global Assessment Scales. Eighty‐three young people completed self‐report assessments of PLEs using the Prodromal Questionnaire (PQ‐16) and measures of social anxiety, depression, trauma history, and pathways to care.

Results

There was a high prevalence of PLEs in the sample. The prevalence of PLEs was higher when young people self‐rated their experiences. Endorsement frequencies for PLEs ranged from 3.5 to 24% on the PCC and 22 to 70% on the PQ‐16. Higher scores on the PQ‐16 were associated with more pathways into care and greater exposure to traumatic life events.

Conclusions

PLEs are common in young people with non‐psychotic mental health difficulties and may reflect increased severity and complexity of mental health difficulties. Routine screening and further assessment of PLEs are important in understanding and responding to such experiences. Screening should include self‐rating of PLEs as well as clinician‐rated scales.

Practitioner Points

Clinical Implications

Psychotic‐like experiences are common in young people with severe non‐psychotic mental health problems and should be routinely screened in mental health services.

Psychotic‐like experiences were found to be more prevalent when using a self‐report screening tool compared to a clinician‐rated measure.

The presence of psychotic‐like experiences may reflect more severe and complex mental health problems and may also cause delays in young people accessing the right kind of support.

;Limitations

This study only assessed the presence or absence of psychotic‐like experiences. Further studies should use more detailed assessments to understand more about the nature of such experiences and how they are appraised and responded to.

This study is cross‐sectional, and therefore, the direction of the relationships between psychotic‐like experiences and depression, anxiety, functioning, and trauma cannot be specified.

Longitudinal studies are needed to examine the impact of psychotic‐like experiences on long‐term outcomes.
Forest resilience to drought varies across biomes
Authors: Gazol Antonio , Camarero Jesus Julio , Vicente‐Serrano Sergio M. , Sánchez‐Salguero Raúl , Gutiérrez Emilia , de Luis Martin , Sangüesa‐Barreda Gabriel , Novak Klemen , Rozas Vicente , Tíscar Pedro A. , Linares Juan C. , Martín‐Hernández Natalia , Martínez del Castillo Edurne , Ribas Montse , García‐González Ignacio , Silla Fernando , Camisón Alvaro , Génova Mar , Olano José M. , Longares Luis A. , Hevia Andrea , Tomás‐Burguera Miquel , Galván J. Diego
Published: February 2018

Forecasted increase drought frequency and severity may drive worldwide declines in forest productivity. Species‐level responses to a drier world are likely to be influenced by their functional traits. Here, we analyse forest resilience to drought using an extensive network of tree‐ring width data and satellite imagery. We compiled proxies of forest growth and productivity (TRWi, absolutely dated ring‐width indices; NDVI, Normalized Difference Vegetation Index) for 11 tree species and 502 forests in Spain corresponding to Mediterranean, temperate, and continental biomes. Four different components of forest resilience to drought were calculated based on TRWi and NDVI data before, during, and after four major droughts (1986, 1994–1995, 1999, and 2005), and pointed out that TRWi data were more sensitive metrics of forest resilience to drought than NDVI data. Resilience was related to both drought severity and forest composition. Evergreen gymnosperms dominating semi‐arid Mediterranean forests showed the lowest resistance to drought, but higher recovery than deciduous angiosperms dominating humid temperate forests. Moreover, semi‐arid gymnosperm forests presented a negative temporal trend in the resistance to drought, but this pattern was absent in continental and temperate forests. Although gymnosperms in dry Mediterranean forests showed a faster recovery after drought, their recovery potential could be constrained if droughts become more frequent. Conversely, angiosperms and gymnosperms inhabiting temperate and continental sites might have problems to recover after more intense droughts since they resist drought but are less able to recover afterwards.
Prospects for research in haemophilia with real‐world data—An analysis of German registry and secondary data
Authors: Schopohl D. , Bidlingmaier C. , Herzig D. , Klamroth R. , Kurnik K. , Rublee D. , Schramm W. , Schwarzkopf L. , Berger K.
Published: February 2018

Introduction and aim

Open questions in haemophilia, such as effectiveness of innovative therapies, clinical and patient‐reported outcomes (PROs), epidemiology and cost, await answers. The aim was to identify data attributes required and investigate the availability, appropriateness and accessibility of real‐world data (RWD) from German registries and secondary databases to answer the aforementioned questions.

Methods

Systematic searches were conducted in BIOSIS, EMBASE and MEDLINE to identify non‐commercial secondary healthcare databases and registries of patients with haemophilia (PWH). Inclusion of German patients, type of patients, data elements—stratified by use in epidemiology, safety, outcomes and health economics research—and accessibility were investigated by desk research.

Results

Screening of 676 hits, identification of four registries [national PWH (DHR), national/international paediatric (GEPARD, PEDNET), international safety monitoring (EUHASS)] and seven national secondary databases. Access was limited to participants in three registries and to employees in one secondary database. One registry asks for PROs. Limitations of secondary databases originate from the ICD‐coding system (missing: severity of haemophilia, presence of inhibitory antibodies), data protection laws and need to monitor reliability.

Conclusion

Rigorous observational analysis of German haemophilia RWD shows that there is potential to supplement current knowledge and begin to address selected policy goals. To improve the value of existing RWD, the following efforts are proposed: ethical, legal and methodological discussions on data linkage across different sources, formulation of transparent governance rules for data access, redefinition of the ICD‐coding, standardized collection of outcome data and implementation of incentives for treatment centres to improve data collection.
Evaluation of chromogenic factor IX assays by automated protocols
Authors: Kershaw G. W. , Dissanayake K. , Chen V. M. , Khoo T.‐L.
Published: February 2018

Introduction

Chromogenic substrate assays (CSA) to measure Factor IX (FIX) have recently become commercially available. However, information on their performance characteristics and use in diagnostic haemostasis laboratories remains limited.

Aim

To evaluate the Hyphen Biomed (Hyphen) and Rossix FIX CSAs on fully automated coagulation analysers and compare them to the FIX one‐stage assay (OSA). This study was conducted in a tertiary referral haemostasis laboratory associated with a haemophilia treatment centre.

Methods

Automated CSA protocols were adapted to the Sysmex CS2500 (CS2500) and Diagnostica Stago STA‐R (STA‐R) analysers. Samples assayed were from healthy volunteers, haemophilia B patients and FIX deficient plasma spiked with either plasma derived, recombinant or extended half‐life FIX products.

Results

Reference intervals for Hyphen and Rossix assays were 73 IU/dL to 164 IU/dL and 73 IU/dL to 168 IU/dL, respectively, on the CS2500 analyser; and 84 IU/dL to 165 IU/dL for the Rossix assay on the STA‐R. Repeatability across all method/analyser combinations resulted in CVs ranging from 0.8% to 5.4%. Between run reproducibility gave CVs <6.7% for all method/analyser combinations. In spiked samples, FIX recoveries were mostly within an acceptable limit of 100 ± 25% for BeneFIX®, Rixubis® and Alprolix® with some differences between CSAs.

Conclusion

Both commercial factor FIX CSA kits can be adapted for Stago and Sysmex automated coagulation analysers. Reagent cost and workflow practices will need to be considered. These assays are potentially more consistent than OSA in measurement of replacement FIX products in haemophilia B patients.
Extraskeletal osteosarcoma: MDM2 and H3K27me3 analysis of 19 cases suggest disease heterogeneity
Authors: Makise Naohiro , Sekimizu Masaya , Kubo Takashi , Wakai Susumu , Watanabe Shun‐ichi , Kato Tomoyasu , Kinoshita Takayuki , Hiraoka Nobuyoshi , Fukayama Masashi , Kawai Akira , Ichikawa Hitoshi , Yoshida Akihiko
Published: February 2018

Aims

Extraskeletal osteosarcoma (ESOS) is a sarcoma in the non‐skeletal tissue that directly produces neoplastic osteoid or bone. De‐differentiated liposarcoma (DDLPS) and malignant peripheral nerve sheath tumour (MPNST) are the two most common types of sarcoma that can harbour heterologous osteosarcomatous differentiation. We aimed to determine the potential relationship of ESOS to DDLPS and MPNST.

Methods and results

We investigated MDM2 and H3K27me3 status in 19 cases of ESOS, two of which contained a low‐grade component. The ESOS affected deep soft tissues (n = 10), superficial soft tissues (n = 3) and organs (n = 6). Among 10 deep soft‐tissue ESOS, six showed MDM2 amplification, four of which also harboured CDK4 co‐amplification. Both ESOS with a low‐grade component showed co‐amplification for MDM2 and CDK4. Among the six organ‐based ESOS three giant cell‐rich ESOS showed an H3K27me3 deficiency (one in primary and two in metastatic sites). Using targeted next generation sequencing, an H3K27me3‐deficient ESOS showed EED homozygous deletion, while none of the three showed alterations in NF1, CDKN2A or SUZ12 genes. During median follow‐up of 20 months, all six patients with MDM2‐amplified ESOS lived for 3–103 months, while two of the three patients with H3K27me3‐deficient ESOS died from this disease in 4 and 20 months, respectively.

Conclusion

We demonstrate that ESOS may include at least two small subsets: an MDM2‐amplified deep soft‐tissue ESOS (which may be related to DDLPS) and an H3K27me3‐deficient organ‐based ESOS (which is probably unrelated to MPNST). Larger studies are required to validate the present observations and investigate the clinical implications of such subcategorisation.
UNIVERSALISM AND THE VALUE OF POLITICAL POWER
Authors: Koh Yumi
Published: February 2018

Although legislatures typically use majority rule to allocate a budget in distributive legislation, unanimous consent over the broad allocation of benefits is pervasive. I develop a game‐theoretic model where members strategically interact in a universal coalition to determine allocations, with noncooperative bargaining as a threat point for the breakdown of cooperation. To quantify the effects of political power on the agreed‐upon allocation, I structurally estimate the model using the “Bridge Bill Capital Budget” in 1992. I find that 16.73% of the budget would be allocated differently if allocations were determined only based on actual needs.
SurvivingICU: Stories of recovery
Authors: Ewens Beverley A. , Hendricks Joyce M. , Sundin Deborah
Published: February 2018

Aim

The aim of this study was to investigate stories of recovery through the lens of intensive care unit (ICU) survivors.

Background

Survival from ICUs is increasing, as are associated physical and psychological complications. Despite the significant impact on survivors, there is inadequate support provision in Australia and world‐wide for this population.

Design

An interpretive biographical approach of intensive care survivors’ experiences of recovery.

Methods

Data were collected during 2014–2015 from diaries, face to face interviews, memos and field notes. Six participants diarized for 3 months commencing 2 months after hospital discharge. At 5 months, participants were interviewed about the content of their diaries and symbols and signifiers in them to create a shared meaning. Analysis of diaries and interviews were undertaken using two frameworks to identify themes throughout participants’ stories and provides a unique portrait of recovery through their individual lens.

Findings

Participants considered their lives had irreparably changed and yet felt unsupported by a healthcare system that had “saved” them. This view through their lens identified turmoil, which existed between their surface and inner worlds as they struggled to conform to what recovery “should be”.

Conclusion

The novel biographical methods provided a safe and creative way to reveal survivors’ inner thoughts and feelings. Participants’ considered creating their stories supported their recovery process and in particular enabled them to reflect on their progress. Findings from this study may lead to increased awareness among health care providers about problems survivors face and improved support services more broadly, based on frameworks appropriate for this population.
On the role of outside options in wage renegotiation
Authors: Chen Fengjiao , Ko Chiu Yu , Li Duozhe
Published: February 2018

We study a game‐theoretic model of wage renegotiation. A worker, after receiving a superior outside offer, initiates a wage renegotiation with his current employer. During the renegotiation, whenever a proposal is rejected, the worker decides whether to opt out. When the two parties are sufficiently patient, any wage level between the outside offer and the entire net surplus can be sustained in equilibrium. Opting out may also arise in equilibrium. This result is in stark contrast to existing studies, in which the outside option is sometimes a credible threat, but is never exercised in equilibrium.
Impact of product name and seasonal context on the sensory evaluation of a seasonally themed beverage
Authors: Morris Cecile
Published: February 2018

Information can have a powerful impact on liking, however, little is known about the effect of product name on consumer perception. Moreover, the influence of season, as a sensory‐relevant context, has never been investigated. The aim of this study was to investigate the effect of naming products with season evoking names and to compare responses between seasons. One hundred fifty‐three consumers took part in either a summer (n = 71) or winter (n = 82) tasting of a drink named “Winter Spice” or “refreshing summer berries.” Within each campaign, a cross‐over design was applied and participants rated the drink for liking and sensory characteristics (check‐all‐that‐apply). Neither the name nor the season had an impact on liking; however, both factors affected attribute description. The drink was described significantly more often as “spice,” “Christmassy,” and “mulled wine” when named “winter spice,” it was described more often as “blackcurrant” and “cherry” during the winter months.

Practical applications

It appears possible to use product names to deliver different sensorial experiences without impacting negatively on liking providing that the names reflect adequately the product intrinsic qualities. Seasons appear to be a sensory‐relevant context, developing a greater understanding of the underpinning mechanisms is critical product development and marketing.
Raiffa Transformed the Field of Negotiation–and Me
Authors: Bazerman Max
Published: February 2018

Howard Raiffa was a role model, friend, and inspiration. He transformed the field of negotiation, and he transformed my career. This brief article provides a recollection of how Howard revolutionized the field of negotiation, and how those insights are now affecting broader areas of the of the social science. Howard received the 1999 Lifetime Achievement Award from the International Association for Conflict Management.
Morphological changes in hair melanosomes by aging
Authors: Itou Takashi
Published: February 2018

Various changes appear in hair by aging, and graying is the most remarkable one. Changes in melanocytes have been well studied as the cause; however, little is known about the change in melanosomes which have a role of carrying melanin pigments into hair shafts. Using pigmented hairs of Japanese females from their age of 4–75, I isolated melanosomes and observed them. As a result, I found a significant change in the morphology of hair melanosomes with age. They were ellipsoidal on the whole and there was no age dependence in the major axis, while the minor axis significantly increased and its frequency distribution broadened with age. The anticipated volume of the melanosome of the oldest person hairs was about twice larger than that of child hairs. This enlargement of melanosome seems to be a cause of the age‐related color change in pigmented hairs from brown to black.
Acting and Believing Under the Guise of Normative Reasons
Authors: Singh Keshav
Published: February 2018

In this paper, I defend an account of the reasons for which we act, believe, and so on for any Ф such that there can be reasons for which we Ф. Such reasons are standardly called motivating reasons. I argue that three dominant views of motivating reasons (psychologism, factualism and disjunctivism) all fail to capture the ordinary concept of a motivating reason. I show this by drawing out three constraints on what motivating reasons must be, and demonstrating how each view fails to satisfy at least one of these constraints. I then propose and defend my own account of motivating reasons, which I call the Guise of Normative Reasons Account. On the account I defend, motivating reasons are propositions. A proposition is the reason for which someone Ф‐s when (a) she represents that proposition as a normative reason to Ф, and (b) her representation explains, in the right way, her Ф‐ing. As I argue, the Guise of Normative Reasons Account satisfies all three constraints on what motivating reasons must be, and weathers several objections that might be leveled against propositionalist views.
Potential for Porphyry Copper Deposits in Northern Tōhoku (or the Exploration Potential for Base and Precious Metal Deposits in Japan 2020)
Authors: Arribas Antonio , Mizuta Toshio
Published: February 2018

There are no known porphyry copper deposits in Japan. Attempts were made in the past to explain this paradox as the Japanese islands sit above a subduction zone of the type widely accepted to give rise to porphyry‐type deposits within subvolcanic magmatic–hydrothermal systems. Is it possible that porphyry copper systems are incompatible with the volcanoplutonic setting of the Japanese islands? In other words, is the established model for the genesis of porphyry copper systems not completely correct, or is it that the elusive Japanese porphyry deposit has not yet been found? We argue that, until proven otherwise, the answer lies in the latter option.

In this article, we focus on Akita Prefecture and the surrounding areas and consider the potential for the existence of porphyry copper deposits mainly from an empirical and practical point of view, in contrast with the obviously important petrogenetic and/or tectonic perspectives. We argue that this region is representative of the Tōhoku province of northern Honshu and that it serves as a proxy for Japan in general. Akita is rich in mineralization styles and deposits, including two main magmatic‐hydrothermal deposit types of Neogene age: (i) middle Miocene submarine stratiform volcanogenic massive sulfide (VMS) deposits (Kuroko) and (ii) late Miocene to Pleistocene Ag–Au‐bearing polymetallic epithermal/subepithermal veins. In particular the Au–Ag‐bearing polymetallic veins, which are comparable to intermediate‐sulfidation epithermal deposits commonly associated with porphyry copper systems, were discovered and mined for several centuries before the first Kuroko deposits were found in the late 1800s. Osarizawa, the last active vein mine, closed in 1978. Kuroko deposits, the main source of metal production in Akita in the 20th century, had peak of production in the 1970s, followed by a rapid decline during the 1980s and complete cessation of all mining by 1995. Not surprisingly, the end of mining in Akita, combined with a series of strategic decisions made by the Government and the Japanese metal mining industry, coincided with a cessation of mineral exploration, both in Akita and throughout Japan, with the exception of VMS deposits offshore and limited exploration for bonanza‐grade, low‐sulfidation epithermal gold deposits in Hokkaido. Our analysis of post‐1945 regional exploration in northern Tōhoku indicates that Kuroko deposits were by far the dominant target and that the number of drill holes in the 1990s accounted for less than 4% of the total completed from the early 1960s to 1995. These data indicate that essentially no mineral exploration has been conducted in Tōhoku for Au–Ag‐bearing polymetallic vein deposits during the past 30+ years. We conclude that exploration stopped too early and certainly before it could have benefited from the significant applicable metallogenic and technological breakthroughs of the last few decades.
High sensitivity Rutherford backscattering spectrometry using multidetector digital pulse processing
Authors: Laricchiuta Grazia , Vandervorst Wilfried , Zyulkov Ivan , Armini Silvia , Meersschaut Johan
Published: February 2018

Rutherford backscattering spectrometry is a primary reference method for the quantity of materials, but has a limit-of-detection (LOD) presently at ∼1015 at/cm2 for analyses with traceable accuracy near 1%. A multidetector assembly is demonstrated which increases the count rate without decreasing the signal/noise due to pulse pile-up. A LOD of 6 × 1012 at/cm2 is achieved with the multidetector assembly and applied to quantify the onset of an atomic layer deposition (ALD) process for an in-depth study of the growth selectivity of ALD Ru on a-C:H and on SiCN. Besides, the spectrometer enables <10 min measurements on a Ru layer of 2.7 nm, permitting wafer mapping.
Multitechnique elemental depth profiling of InAlGaN and InAlN films
Authors: Mazel Yann , Nolot Emmanuel , Barnes Jean-Paul , Charles Matthew , Bouveyron Romain , Mrad Mrad , Tempez Agnès , Legendre Sébastien
Published: February 2018

This work shows the capabilities of the plasma profiling time of flight mass spectrometry (PP-TOFMS) for the determination of elemental composition and distribution in InAlGaN thin films used for high electron mobility transistors. The PP-TOFMS results have been compared with wavelength dispersive x-ray fluorescence analyses for the elemental composition determination and with x-ray photoelectron spectroscopy and time of flight secondary ion mass spectrometry (TOF-SIMS) for elemental distributions. Relative sensitivity factors have been developed for the comparison of PP-TOFMS with TOF-SIMS results. The PP-TOFMS was able to determine the relative composition of In and Al in the thin films with an accuracy of 10 rel. % without calibration. Depth profiles acquired from the PP-TOFMS technique were obtained within a few minutes and exhibited very similar In, Al, and Ga distributions to TOF-SIMS measurements, and thus PP-TOFMS has been shown to be a valuable addition to TOF-SIMS analysis for a fast process development.
A proactive charcoal approach shields the gut microbiome from systemic antibiotics
Authors: Langelier Chaz
Published: February 2018

A new activated charcoal agent protects beneficial gut microbiota from the adverse effects of systemic antibiotic therapy.
Spread of Plasmid-Encoded NDM-1 and GES-5 Carbapenemases among Extensively Drug-Resistant and Pandrug-Resistant Clinical Enterobacteriaceae in Durban, South Africa
Authors: Pedersen Torunn , Sekyere John Osei , Govinden Usha , Moodley Krishnee , Sivertsen Audun , Samuelsen Ørjan , Essack Sabiha Yusuf , Sundsfjord Arnfinn
Published: February 2018

Whole-genome sequence analyses revealed the presence of
bla
NDM-1
(
n
= 31),
bla
GES-5
(
n
= 8),
bla
OXA-232
(
n
= 1), or
bla
NDM-5
(
n
= 1) in extensively drug-resistant and pandrug-resistant
Enterobacteriaceae
organisms isolated from in-patients in 10 private hospitals (2012 to 2013) in Durban, South Africa. Two novel NDM-1-encoding plasmids from
Klebsiella pneumoniae
were circularized by PacBio sequencing. In p19-10_01 [IncFIB(K); 223.434 bp],
bla
NDM-1
was part of a Tn
1548
-like structure (16.276 bp) delineated by IS
26
. The multireplicon plasmid p18-43_01 [IncR_1/IncFIB(pB171)/IncFII(Yp); 212.326 bp] shared an 80-kb region with p19-10_01, not including the
bla
NDM-1
-containing region. The two plasmids were used as references for tracing NDM-1-encoding plasmids in the other genome assemblies. The p19-10_01 sequence was detected in
K. pneumoniae
(
n
= 7) only, whereas p18-43_01 was tracked to
K. pneumoniae
(
n
= 4),
Klebsiella michiganensis
(
n
= 1),
Serratia marcescens
(
n
= 11),
Enterobacter
spp. (
n
= 7), and
Citrobacter freundii
(
n
= 1), revealing horizontal spread of this
bla
NDM-1
-bearing plasmid structure. Global phylogeny showed clustering of the
K. pneumoniae
(18/20) isolates together with closely related carbapenemase-negative ST101 isolates from other geographical origins. The South African isolates were divided into three phylogenetic subbranches, where each group had distinct resistance and replicon profiles, carrying either p19-10_01, p18-10_01, or pCHE-A1 (8,201 bp). The latter plasmid carried
bla
GES-5
and
aacA4
within an integron mobilization unit. Our findings imply independent plasmid acquisition followed by local dissemination. Additionally, we detected
bla
OXA-232
carried by pPKPN4 in
K. pneumoniae
(ST14) and
bla
NDM-5
contained by a pNDM-MGR194-like genetic structure in
Escherichia coli
(ST167), adding even more complexity to the multilayer molecular mechanisms behind nosocomial spread of carbapenem-resistant
Enterobacteriaceae
in Durban, South Africa.
Plant Homeodomain Genes Play Important Roles in Cryptococcal Yeast-Hypha Transition
Authors: Meng Yunfang , Fan Yumeng , Liao Wanqing , Lin Xiaorong
Published: February 2018

Cryptococcus neoformans
is a major opportunistic fungal pathogen. Like many dimorphic fungal pathogens,
C. neoformans
can undergo morphological transition from the yeast form to the hypha form, and its morphotype is tightly linked to its virulence. Although some genetic factors controlling morphogenesis have been identified, little is known about the epigenetic regulation in this process. Proteins with the plant homeodomain (PHD) finger, a structurally conserved domain in eukaryotes, were first identified in plants and are known to be involved in reading and effecting chromatin modification. Here, we investigated the role of the PHD finger family genes in
Cryptococcus
mating and yeast-hypha transition. We found 16 PHD finger domains distributed among 15 genes in the
Cryptococcus
genome, with two genes,
ZNF1
α and
RUM1
α, located in the mating type locus. We deleted these 15 PHD genes and examined the impact of their disruption on cryptococcal morphogenesis. The deletion of five PHD finger genes dramatically affected filamentation. The
rum1
αΔ and
znf1
αΔ mutants showed enhanced ability to initiate filamentation but impaired ability to maintain filamentous growth. The
bye1
Δ and the
phd11
Δ mutants exhibited enhanced filamentation, while the
set302
Δ mutants displayed reduced filamentation. Ectopic overexpression of these five genes in the corresponding null mutants partially or completely restored the defect in filamentation. Furthermore, we demonstrated that Phd11, a suppressor of filamentation, regulates the yeast-hypha transition through the known master regulator Znf2. The findings indicate the importance of epigenetic regulation in controlling dimorphic transition in
C. neoformans
.

IMPORTANCE
Morphotype is known to have a profound impact on cryptococcal interaction with various hosts, including mammalian hosts. The yeast form of
Cryptococcus neoformans
is considered the virulent form, while its hyphal form is attenuated in mammalian models of cryptococcosis. Although some genetic regulators critical for cryptococcal morphogenesis have been identified, little is known about epigenetic regulation in this process. Given that plant homeodomain (PHD) finger proteins are involved in reading and effecting chromatin modification and their functions are unexplored in
C. neoformans
, we investigated the roles of the 15 PHD finger genes in
Cryptococcus
mating and yeast-hypha transition. Five of them profoundly affect filamentation as either a suppressor or an activator. Phd11, a suppressor of filamentation, regulates this process via Znf2, a known master regulator of morphogenesis. Thus, epigenetic regulation, coupled with genetic regulation, controls this yeast-hypha transition event.
Catecholamine-Modulated Novel Surface-Exposed Adhesin LIC20035 of Leptospira spp. Binds Host Extracellular Matrix Components and Is Recognized by the Host during Infection
Authors: Ghosh Karukriti Kaushik , Prakash Aman , Balamurugan Vinayagamurthy , Kumar Manish
Published: February 2018

In this study, the effect of the host stress hormone catecholamine onLeptospiragene transcripts encoding outer membrane proteins was investigated. There was no impact of catecholamine supplementation on thein vitrogrowth pattern ofLeptospira interrogans; however, 7 genes out of 41 were differentially transcribed, and the effect was reversed to the basal level in the presence of the antagonist propranolol. Comprehensive analysis of one of the differentially regulated proteins, LIC20035 (in serovar Copenhageni)/LB047 (in serovar Lai) (due to catecholamine supplementation), revealed immunogenicity and ability to adhere to host extracellular matrices. Protease accessibility assay and phase partition of integral membrane proteins ofLeptospirashowed LIC20035/LB047 to be an outer membrane surface-exposed protein. The recombinant LIC20035 protein can be serologically detected using human/bovine sera positive for leptospirosis. Moreover, the recombinant LIC20035 can bind to diverse host extracellular matrices, with a higher affinity toward collagen and chondroitin sulfate.

IMPORTANCELeptospirosis is a neglected tropical disease of global importance. This study aimed to identify outer membrane proteins of pathogenicLeptospiraresponding to host chemical signals like catecholamines, with the potential to serve as virulence factors, new serodiagnostic antigens, and vaccine candidates. This study mimicked the plausible means by whichLeptospiraduring infection and hormonal stress intercepts host catecholamines to disseminate in host tissues.
Design of a phase IV randomised, double-blind, placebo-controlled trial assessing the ImPact ofResidual Inflammation Detected via Imaging TEchniques,Drug Levels and Patient Characteristics on the Outcome of Dose TaperIng of Adalimumab inClinical Remission Rheumatoid ArThritis (RA) patients (PREDICTRA)
Authors: Emery Paul , Burmester Gerd R , Naredo Esperanza , Zhou Yijie , Hojnik Maja , Conaghan Philip G
Published: February 2018

Introduction

The current American College of Rheumatology and European League Against Rheumatism treatment recommendations advise tapering biological disease-modifying antirheumatic drug (bDMARD) therapy in patients with rheumatoid arthritis (RA) who achieve stable clinical remission while receiving bDMARDs. However, not all patients maintain remission or low disease activity after tapering or discontinuation of bDMARDs. The aim of the ImPact ofResidual Inflammation Detected via Imaging TEchniques,Drug Levels and Patient Characteristics on the Outcome of Dose TaperIng of Adalimumab inClinical Remission Rheumatoid ArThritis (RA) study, or PREDICTRA, is to generate data on patient and disease characteristics that may predict the clinical course of a fixed dose-tapering regimen with the bDMARD adalimumab.

Methods and analysis

PREDICTRA is an ongoing, multicentre, phase IV, randomised, double-blind, parallel-group study of adalimumab dose tapering controlled by withdrawal in participants with RA who achieved stable clinical remission while receiving adalimumab. The study includes a screening period, a 4-week lead-in period with open-label adalimumab 40 mg every other week and a subsequent 36-week double-blind period during which participants are randomised 5:1 to adalimumab 40 mg every 3 weeks (taper arm) or placebo (withdrawal arm). The primary explanatory efficacy variables are lead-in baseline hand and wrist MRI-detected synovitis and bone marrow oedema scores, as well as a composite of both scores; the dependent variable is the occurrence of flare up to week 40. Additional efficacy variables, safety, pharmacokinetics, biomarkers and immunogenicity will also be assessed, and an ultrasound substudy will be conducted.

Ethics and dissemination

The study is conducted in accordance with the International Conference on Harmonisation guidelines, local laws and the ethical principles of the Declaration of Helsinki. All participants are required to sign a written informed consent statement before the start of any study procedures.

Trial registration number

EudraCT 2014-001114-26 andNCT02198651; Pre-results.
Heritability of glaucoma and glaucoma-related endophenotypes: systematic review and meta-analysis protocol
Authors: Asefa Nigus Gebrmedhin , Neustaeter Anna , Jansonius Nomdo M , Snieder Harold
Published: February 2018

Introduction

Glaucoma is the second leading cause of age-related vision loss worldwide; it is an umbrella term that is used to describe a set of complex ocular disorders with a multifactorial aetiology. Both genetic and lifestyle risk factors for glaucoma are well established. Thus far, however, systematic reviews on the heritability of glaucoma have focused on the heritability of primary open-angle glaucoma only. No systematic review has comprehensively reviewed or meta-analysed the heritability of other types of glaucoma, including glaucoma-related endophenotypes. The aim of this study will be to identify relevant scientific literature regarding the heritability of both glaucoma and related endophenotypes and summarise the evidence by performing a systematic review and meta-analysis.

Methods and analysis

This systematic review will follow the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols 2015 checklist, which provides a standardised approach for carrying out systematic reviews. To capture as much literature as possible, a comprehensive step-by-step systematic search will be undertaken in MEDLINE (PubMed), EMBASE, Web of Science and ScienceDirect, and studies published until 31 December 2017 will be included. Two reviewers will independently search the articles for eligibility according to predefined selection criteria. A database will be used for screening of eligible articles. The quality of the included studies will be rated independently by two reviewers, using the National Health Institute Quality Assessment tool for Observational Cohort and Cross-Sectional Studies. A random-effects model will be used for the meta-analysis. This systematic review is registered with the International Prospective Register of Systematic Reviews with a registration number: CRD42017064504.

Ethics and dissemination

We will use secondary data from peer-reviewed published articles, and hence there is no requirement for ethics approval. The results of this systematic review will be disseminated through publication in a peer-reviewed scientific journal.
Summary of latest NHS England Emergency Preparedness Resilience and Response (EPRR) guidance
Authors: Makin Seth , Groves S
Published: February 2018

The National Health Service (NHS) England Emergency Preparedness, Resilience and Response Framework exists to provide a structure by which NHS England and NHS-funded bodies prepare for and respond to a range of emergencies. This framework exists to ensure that in emergencies the NHS retains the capability to deliver appropriate care to patients. Rather than dealing with individual scenarios, the framework aims to maintain the adaptability and capacity to deal with a variety of emergencies, their consequences and guide recovery plans. This paper summarises this guidance and elucidates the reasoning and mechanisms by which this care will be facilitated and delivered.
Dignity and equality in healthcare
Authors: Liu Pengbo
Published: February 2018

This paper critically examines Barclay’s conception of dignity proposed in her ‘Dignitarian Medical Ethics’. According to Barclay, a subject S enjoys dignity if and only if S is reliably treated as having equal social status. I argue that Barclay’s view faces a number of practical and theoretical problems. First, it is not obvious that failing to treat someone as a social equal is incompatible with respecting her dignity. Second, it is not always clear what treating someone as a social equal amounts to in practice. To be more compelling, her conception of dignity needs to be supplemented with a more principled and substantive account of the content of equal treatment.
MiR-378 promotes the cell proliferation of osteosarcoma through down-regulating the expression of Kruppel-like factor 9
Authors: Peng Ningning , Miao Zhigang , Wang Liguo , Liu Binbin , Wang Guijiang , Guo Xu
Published: February 2018

MicroRNAs (miRNAs) are small non-coding RNAs that play important roles in a variety of biological processes. Dysregulation of miRNAs is tightly associated with the malignancy of cancers. Aberrant expression of miR-378 has been observed in human cancers; however, the function of miR-378 in osteosarcoma (OS) remains largely unknown. Here, we showed that miR-378 was highly expressed in human OS tissues and cell lines. Overexpression of miR-378 significantly promoted the cell proliferation of OS cells. Molecular studies identified Kruppel-like factor-9 (KLF9) as a functional downstream target of miR-378. MiR-378 directly bound to the mRNA 3′-UTR region of KLF9 and suppressed the expression of KLF9. Highly expressed KLF9 reversed the promoting effect of miR-378 on the proliferation of OS cells. The expression level of miR-378 was negatively correlated with that of KLF9 in OS tissues. Collectively, our results demonstrated the molecular interaction between miR-378 and KLF9, indicating the therapeutic potential of miR-378 for OS.
Surface interaction effects to a Klein–Gordon particle embedded in a Woods–Saxon potential well in terms of thermodynamic functions,
Authors: Lütfüoğlu B.C.
Published: February 2018

Recently, it has been investigated how the thermodynamic functions vary when the surface interactions are taken into account for a nucleon that is confined in a Woods–Saxon potential well, with a non-relativistic point of view. In this manuscript, the same problem is handled with a relativistic point of view. More precisely, the Klein–Gordon equation is solved in the presence of mixed scalar–vector generalized symmetric Woods–Saxon potential energy that is coupled to momentum and mass. Employing the continuity conditions the bound state energy spectra of an arbitrarily parameterized well are derived. It is observed that, when a term representing the surface effect is taken into account, the character of Helmholtz free energy and entropy versus temperature are modified in a similar fashion as this inclusion is done in the non-relativistic regime. Whereas it is found that this inclusion leads to different characters to internal energy and specific heat functions for relativistic and non-relativistic regimes.
Kinesins and Myosins: Molecular Motors that Coordinate Cellular Functions in Plants
Authors: Nebenführ Andreas , Dixit Ram
Published: February 2018

Kinesins and myosins are motor proteins that can move actively along microtubules and actin filaments, respectively. Plants have evolved a unique set of motors that function as regulators and organizers of the cytoskeleton and as drivers of long-distance transport of various cellular components. Recent progress has established the full complement of motors encoded in plant genomes and has revealed valuable insights into the cellular functions of many kinesin and myosin isoforms. Interestingly, several of the motors were found to functionally connect the two cytoskeletal systems and thereby to coordinate their activities. In this review, we discuss the available genetic, cell biological, and biochemical data for each of the plant kinesin and myosin families from the context of their subcellular mechanism of action as well as their physiological function in the whole plant. We particularly emphasize work that illustrates mechanisms by which kinesins and myosins coordinate the activities of the cytoskeletal system.
Essential Roles of Local Auxin Biosynthesis in Plant Development and in Adaptation to Environmental Changes
Authors: Zhao Yunde
Published: February 2018

It has been a dominant dogma in plant biology that the self-organizing polar auxin transport system is necessary and sufficient to generate auxin maxima and minima that are essential for almost all aspects of plant growth and development. However, in the past few years, it has become clear that local auxin biosynthesis is required for a suite of developmental processes, including embryogenesis, endosperm development, root development, and floral initiation and patterning. Moreover, it was discovered that local auxin biosynthesis maintains optimal plant growth in response to environmental signals, including light, temperature, pathogens, and toxic metals. In this article, I discuss the recent progress in auxin biosynthesis research and the paradigm shift in recognizing the important roles of local auxin biosynthesis in plant biology.
Trends in Global Agricultural Land Use: Implications for Environmental Health and Food Security
Authors: Ramankutty Navin , Mehrabi Zia , Waha Katharina , Jarvis Larissa , Kremen Claire , Herrero Mario , Rieseberg Loren H.
Published: February 2018

The eighteenth-century Malthusian prediction of population growth outstripping food production has not yet come to bear. Unprecedented agricultural land expansions since 1700, and technological innovations that began in the 1930s, have enabled more calorie production per capita than was ever available before in history. This remarkable success, however, has come at a great cost. Agriculture is a major cause of global environmental degradation. Malnutrition persists among large sections of the population, and a new epidemic of obesity is on the rise. We review both the successes and failures of the global food system, addressing ongoing debates on pathways to environmental health and food security. To deal with these challenges, a new coordinated research program blending modern breeding with agro-ecological methods is needed. We call on plant biologists to lead this effort and help steer humanity toward a safe operating space for agriculture.
Cell and Developmental Biology of Plant Mitogen-Activated Protein Kinases
Authors: Komis George , Šamajová Olga , Ovečka Miroslav , Šamaj Jozef
Published: February 2018

Plant mitogen-activated protein kinases (MAPKs) constitute a network of signaling cascades responsible for transducing extracellular stimuli and decoding them to dedicated cellular and developmental responses that shape the plant body. Over the last decade, we have accumulated information about how MAPK modules control the development of reproductive tissues and gametes and the embryogenic and postembryonic development of vegetative organs such as roots, root nodules, shoots, and leaves. Of key importance to understanding how MAPKs participate in developmental and environmental signaling is the characterization of their subcellular localization, their interactions with upstream signal perception mechanisms, and the means by which they target their substrates. In this review, we summarize the roles of MAPK signaling in the regulation of key plant developmental processes, and we survey what is known about the mechanisms guiding the subcellular compartmentalization of MAPK modules.