bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational Intelligence Nonmodel-Based Calibration Approach for Internal Combustion Engines
Authors: Ma He , Li Ziyang , Tayarani Mohammad , Lu Guoxiang , Xu Hongming , Yao Xin
Published: September 2017

Over the past 20 years, with the increase in the complexity of engines, and the combinatorial explosion of engine variables space, the engine calibration process has become more complex, costly, and time consuming. As a result, an efficient and economic approach is desired. For this purpose, many engine calibration methods are under development in original equipment manufacturers and universities. The state-of-the-art model-based steady-state design of experiments (DOE) technique is mature and is used widely. However, it is very difficult to further reduce the measurement time. Additionally, the increasingly high requirements of engine model accuracy and robust testing process with high data quality by high-quality testing facility also constrain the further development of model-based DOE engine calibration. This paper introduces a new computational intelligence approach to calibrate internal combustion engine without the need for an engine model. The strength Pareto evolutionary algorithm 2 (SPEA2) is applied to this automatic engine calibration process. In order to implement the approach on a V6 gasoline direct injection (GDI) engine test bench, a simulink real-time based embedded system was developed and implemented to engine electronic control unit (ECU) through rapid control prototyping (RCP) and external ECU bypass technology. Experimental validations prove that the developed engine calibration approach is capable of automatically finding the optimal engine variable set which can provide the best fuel consumption and particulate matter (PM) emissions, with good accuracy and high efficiency. The introduced engine calibration approach does not rely on either the engine model or the massive test bench experimental data. It has great potential to improve the engine calibration process for industries.
Effect of Integral Feedback on a Class of Uncertain Nonlinear Systems: Stability and Induced Limit Cycles
Authors: Abeysiriwardena Singith , Das Tuhin
Published: September 2017

The theoretical problem addressed in the present work involves the effect of integral feedback on a class of uncertain nonlinear systems. The intriguing aspects of the problem arise as a result of transient constraints combined with the presence of parametric uncertainty and an unknown nonlinearity. The motivational problem was the state-of-charge (SOC) control strategy for load-following in solid oxide fuel cells (SOFCs) hybridized with an ultracapacitor. In the absence of parametric uncertainty, our prior work established asymptotic stability of the equilibrium if the unknown nonlinearity is a passive memoryless function. In contrast, this paper addresses the realistic scenario with parametric uncertainty. Here, an integral feedback/parameter adaption approach is taken to incorporate robustness. The integral action, which results in a higher-order system, imposes further restriction on the nonlinearity for guaranteeing asymptotic stability. Furthermore, it induces a limit cycle behavior under additional conditions. The system is studied as a Lure problem, which yields a stability criterion. Subsequently, the describing function method yields a necessary condition for half-wave symmetric periodic solution (induced limit cycle).
Polarization recovery through scattering media
Authors: de Aguiar Hilton B. , Gigan Sylvain , Brasselet Sophie
Published: September 2017

The lost polarization state purity of light is now shown to be recovered, after propagating in a strongly scattering environment.
Intracellular spectral recompositioning of light enhances algal photosynthetic efficiency
Authors: Fu Weiqi , Chaiboonchoe Amphun , Khraiwesh Basel , Sultana Mehar , Jaiswal Ashish , Jijakli Kenan , Nelson David R. , Al-Hrout Ala’a , Baig Badriya , Amin Amr , Salehi-Ashtiani Kourosh
Published: September 2017

Spectral conversion of light enhances algal photosynthesis and enables technologies for sustainable energy and food production.
Low-energy transmission electron diffraction and imaging of large-area graphene
Authors: Zhao Wei , Xia Bingyu , Lin Li , Xiao Xiaoyang , Liu Peng , Lin Xiaoyang , Peng Hailin , Zhu Yuanmin , Yu Rong , Lei Peng , Wang Jiangtao , Zhang Lina , Xu Yong , Zhao Mingwen , Peng Lianmao , Li Qunqing , Duan Wenhui , Liu Zhongfan , Fan Shoushan , Jiang Kaili
Published: September 2017

Crystalline characterization of large-area graphene and study of adsorbates on it can be realized with low-energy electron beam.
Cardiolipin mediates membrane and channel interactions of the mitochondrial TIM23 protein import complex receptor Tim50
Authors: Malhotra Ketan , Modak Arnab , Nangia Shivangi , Daman Tyler H. , Gunsel Umut , Robinson Victoria L. , Mokranjac Dejana , May Eric R. , Alder Nathan N.
Published: September 2017

Cardiolipin mediates dynamic receptor-channel interactions within the mitochondrial TIM23 protein import complex.
Mechanistic basis for the recognition of laminin-511 by α6β1 integrin
Authors: Takizawa Mamoru , Arimori Takao , Taniguchi Yukimasa , Kitago Yu , Yamashita Erika , Takagi Junichi , Sekiguchi Kiyotoshi
Published: September 2017

The Glu residue in the laminin γ-tail forms a bipartite integrin binding site with three globular domains of the α chain.
An immune clock of human pregnancy
Authors: Aghaeepour Nima , Ganio Edward A. , Mcilwain David , Tsai Amy S. , Tingle Martha , Van Gassen Sofie , Gaudilliere Dyani K. , Baca Quentin , McNeil Leslie , Okada Robin , Ghaemi Mohammad S. , Furman David , Wong Ronald J. , Winn Virginia D. , Druzin Maurice L. , El-Sayed Yaser Y. , Quaintance Cecele , Gibbs Ronald , Darmstadt Gary L. , Shaw Gary M. , Stevenson David K. , Tibshirani Robert , Nolan Garry P. , Lewis David B. , Angst Martin S. , Gaudilliere Brice
Published: September 2017

High-dimensional analysis reveals the chronology of immunological adaptations during the course of human pregnancies.
A recycling program that keeps PD-L1 out of the cancer cell's junkyard
Authors: Griffin Gabriel K.
Published: September 2017

CMTM6 limits antitumor immunity by ensuring efficient recycling of endocytosed PD-L1 protein.
CRISPR-Cas9
D10A
Nickase-Assisted Genome Editing in Lactobacillus casei
Authors: Song Xin , Huang He , Xiong Zhiqiang , Ai Lianzhong , Yang Sheng
Published: September 2017

Lactobacillus casei
has drawn increasing attention as a health-promoting probiotic, while effective genetic manipulation tools are often not available, e.g., the single-gene knockout in
L. casei
still depends on the classic homologous recombination-dependent double-crossover strategy, which is quite labor-intensive and time-consuming. In the present study, a rapid and precise genome editing plasmid, pLCNICK, was established for
L. casei
genome engineering based on CRISPR-Cas9
D10A
. In addition to the P
23
-Cas9
D10A
and P
ldh
-sgRNA (single guide RNA) expression cassettes, pLCNICK includes the homologous arms of the target gene as repair templates. The ability and efficiency of chromosomal engineering using pLCNICK were evaluated by in-frame deletions of four independent genes and chromosomal insertion of an enhanced green fluorescent protein (eGFP) expression cassette at the
LC2W_1628
locus. The efficiencies associated with in-frame deletions and chromosomal insertion is 25 to 62%. pLCNICK has been proved to be an effective, rapid, and precise tool for genome editing in
L. casei
, and its potential application in other lactic acid bacteria (LAB) is also discussed in this study.

IMPORTANCE
The lack of efficient genetic tools has limited the investigation and biotechnological application of many LAB. The CRISPR-Cas9
D10A
nickase-based genome editing in
Lactobacillus casei
, an important food industrial microorganism, was demonstrated in this study. This genetic tool allows efficient single-gene deletion and insertion to be accomplished by one-step transformation, and the cycle time is reduced to 9 days. It facilitates a rapid and precise chromosomal manipulation in
L. casei
and overcomes some limitations of previous methods. This editing system can serve as a basic technological platform and offers the possibility to start a comprehensive investigation on
L. casei
. As a broad-host-range plasmid, pLCNICK has the potential to be adapted to other
Lactobacillus
species for genome editing.
Exogenous Polyunsaturated Fatty Acids Impact Membrane Remodeling and Affect Virulence Phenotypes among Pathogenic Vibrio Species
Authors: Moravec Anna R. , Siv Andrew W. , Hobby Chelsea R. , Lindsay Emily N. , Norbash Layla V. , Shults Daniel J. , Symes Steven J. K. , Giles David K.
Published: September 2017

The pathogenic
Vibrio
species (
V. cholerae
,
V. parahaemolyticus
, and
V. vulnificus
) represent a constant threat to human health, causing foodborne and skin wound infections as a result of ingestion of or exposure to contaminated water and seafood. Recent studies have highlighted
Vibrio
's ability to acquire fatty acids from environmental sources and assimilate them into cell membranes. The possession and conservation of such machinery provokes consideration of fatty acids as important factors in the pathogenic lifestyle of
Vibrio
species. The findings here link exogenous fatty acid exposure to changes in bacterial membrane phospholipid structure, permeability, phenotypes associated with virulence, and consequent stress responses that may impact survival and persistence of pathogenic
Vibrio
species. Polyunsaturated fatty acids (PUFAs) (ranging in carbon length and unsaturation) supplied in growth medium were assimilated into bacterial phospholipids, as determined by thin-layer chromatography and liquid chromatography-mass spectrometry. The incorporation of fatty acids variably affected membrane permeability, as judged by uptake of the hydrophobic compound crystal violet. For each species, certain fatty acids were identified as affecting resistance to antimicrobial peptide treatment. Significant fluctuations were observed with regard to both motility and biofilm formation following growth in the presence of individual PUFAs. Our results illustrate the important and complex roles of exogenous fatty acids in the membrane physiology and virulence of a bacterial genus that inhabits aquatic and host environments containing an abundance of diverse fatty acids.

IMPORTANCE
Bacterial responses to fatty acids include, but are not limited to, degradation for metabolic gain, modification of membrane lipids, alteration of protein function, and regulation of gene expression.
Vibrio
species exhibit significant diversity with regard to the machinery known to participate in the uptake and incorporation of fatty acids into their membranes. Both aquatic and host niches occupied by
Vibrio
are rife with various free fatty acids and fatty acid-containing lipids. The roles of fatty acids in the environmental survival and pathogenesis of bacteria have begun to emerge and are expected to expand significantly. The current study demonstrates the responsiveness of
V. cholerae
,
V. parahaemolyticus
, and
V. vulnificus
to exogenous PUFAs. In addition to phospholipid remodeling, PUFA assimilation impacts membrane permeability, motility, biofilm formation, and resistance to polymyxin B.
Chemical Pretreatment-Independent Saccharifications of Xylan and Cellulose of Rice Straw by Bacterial Weak Lignin-Binding Xylanolytic and Cellulolytic Enzymes
Authors: Teeravivattanakit Thitiporn , Baramee Sirilak , Phitsuwan Paripok , Sornyotha Somphit , Waeonukul Rattiya , Pason Patthra , Tachaapaikoon Chakrit , Poomputsa Kanokwan , Kosugi Akihiko , Sakka Kazuo , Ratanakhanokchai Khanok
Published: September 2017

Complete utilization of carbohydrate fractions is one of the prerequisites for obtaining economically favorable lignocellulosic biomass conversion. This study shows that xylan in untreated rice straw was saccharified to xylose in one step without chemical pretreatment, yielding 58.2% of the theoretically maximum value by
Paenibacillus curdlanolyticus
B-6 PcAxy43A, a weak lignin-binding trifunctional xylanolytic enzyme, endoxylanase/β-xylosidase/arabinoxylan arabinofuranohydrolase. Moreover, xylose yield from untreated rice straw was enhanced to 78.9% by adding endoxylanases PcXyn10C and PcXyn11A from the same bacterium, resulting in improvement of cellulose accessibility to cellulolytic enzyme. After autoclaving the xylanolytic enzyme-treated rice straw, it was subjected to subsequent saccharification by a combination of the
Clostridium thermocellum
endoglucanase CtCel9R and
Thermoanaerobacter brockii
β-glucosidase TbCglT, yielding 88.5% of the maximum glucose yield, which was higher than the glucose yield obtained from ammonia-treated rice straw saccharification (59.6%). Moreover, this work presents a new environment-friendly xylanolytic enzyme pretreatment for beneficial hydrolysis of xylan in various agricultural residues, such as rice straw and corn hull. It not only could improve cellulose saccharification but also produced xylose, leading to an improvement of the overall fermentable sugar yields without chemical pretreatment.

IMPORTANCE
Ongoing research is focused on improving “green” pretreatment technologies in order to reduce energy demands and environmental impact and to develop an economically feasible biorefinery. The present study showed that PcAxy43A, a weak lignin-binding trifunctional xylanolytic enzyme, endoxylanase/β-xylosidase/arabinoxylan arabinofuranohydrolase from
P. curdlanolyticus
B-6, was capable of conversion of xylan in lignocellulosic biomass such as untreated rice straw to xylose in one step without chemical pretreatment. It demonstrates efficient synergism with endoxylanases PcXyn10C and PcXyn11A to depolymerize xylan in untreated rice straw and enhanced the xylose production and improved cellulose hydrolysis. Therefore, it can be considered an enzymatic pretreatment. Furthermore, the studies here show that glucose yield released from steam- and xylanolytic enzyme-treated rice straw by the combination of CtCel9R and TbCglT was higher than the glucose yield obtained from ammonia-treated rice straw saccharification. This work presents a novel environment-friendly xylanolytic enzyme pretreatment not only as a green pretreatment but also as an economically feasible biorefinery method.
Cupriavidus necator H16 Uses Flavocytochrome
c
Sulfide Dehydrogenase To Oxidize Self-Produced and Added Sulfide
Authors: Lü Chuanjuan , Xia Yongzhen , Liu Daixi , Zhao Rui , Gao Rui , Liu Honglei , Xun Luying
Published: September 2017

Production of sulfide (H
2
S, HS
−
, and S
2−
) by heterotrophic bacteria during aerobic growth is a common phenomenon. Some bacteria with sulfide:quinone oxidoreductase (SQR) and persulfide dioxygenase (PDO) can oxidize self-produced sulfide to sulfite and thiosulfate, but other bacteria without these enzymes release sulfide into the medium, from which H
2
S can volatilize into the gas phase. Here, we report that
Cupriavidus necator
H16, with the
fccA
and
fccB
genes encoding flavocytochrome
c
sulfide dehydrogenases (FCSDs), also oxidized self-produced H
2
S. A mutant in which
fccA
and
fccB
were deleted accumulated and released H
2
S. When
fccA
and
fccB
were expressed in
Pseudomonas aeruginosa
strain Pa3K with deletions of its
sqr
and
pdo
genes, the recombinant rapidly oxidized sulfide to sulfane sulfur. When PDO was also cloned into the recombinant, the recombinant with both FCSD and PDO oxidized sulfide to sulfite and thiosulfate. Thus, the proposed pathway is similar to the pathway catalyzed by SQR and PDO, in which FCSD oxidizes sulfide to polysulfide, polysulfide spontaneously reacts with reduced glutathione (GSH) to produce glutathione persulfide (GSSH), and PDO oxidizes GSSH to sulfite, which chemically reacts with polysulfide to produce thiosulfate. About 20.6% of sequenced bacterial genomes contain SQR, and only 3.9% contain FCSD. This is not a surprise, since SQR is more efficient in conserving energy because it passes electrons from sulfide oxidation into the electron transport chain at the quinone level, while FCSD passes electrons to cytochrome
c
. The transport of electrons from the latter to O
2
conserves less energy. FCSDs are grouped into three subgroups, well conserved at the taxonomic level. Thus, our data show the diversity in sulfide oxidation by heterotrophic bacteria.

IMPORTANCE
Heterotrophic bacteria with SQR and PDO can oxidize self-produced sulfide and do not release H
2
S into the gas phase.
C. necator
H16 has FCSD but not SQR, and it does not release H
2
S. We confirmed that the bacterium used FCSD for the oxidation of self-produced sulfide. The bacterium also oxidized added sulfide. The common presence of SQRs, FCSDs, and PDOs in heterotrophic bacteria suggests the significant role of heterotrophic bacteria in sulfide oxidation, participating in sulfur biogeochemical cycling. Further, FCSDs have been identified in anaerobic photosynthetic bacteria and chemolithotrophic bacteria, but their physiological roles are unknown. We showed that heterotrophic bacteria use FCSDs to oxidize self-produced sulfide and extraneous sulfide, and they may be used for H
2
S bioremediation.
Correlates of second-line type 2 diabetes medication selection in the USA
Authors: Ackermann Ronald T , Wallia Amisha , O'Brien Matthew J , Kang Raymond , Cooper Andrew , Moran Margaret R , Liss David T
Published: September 2017

Objective

Past research provides insufficient evidence to inform second-line diabetes medication prescribing when metformin is no longer sufficient. We evaluated patient, prescriber, and health plan characteristics associated with selection of second-line diabetes medications in the USA.

Research design and methods

We used a multiple case-comparison study design to identify characteristics associated with the probability of starting each of six second-line diabetes medication alternatives within 77 744 adults enrolled in commercial or Medicare Advantage health plans from 2011 to 2015. National administrative data were provided by a large commercial health payer. Multinomial logistic regression models were used to identify characteristics independently associated with selecting each diabetes drug class.

Results

From 2011 to 2015, sulfonylureas still represented 47% of all second-line drug starts, with proportionately higher use in patients ≥75 years of age (63% of drug starts). Basal insulin was more likely to be selected when a past A1c test result was >10% (13.0% vs 4.5% for those with A1c <8%; p<0.001). Initiation of a glucagon-like peptide-1 receptor agonist was associated with being female (10.1% vs 6.0% for male; p<0.001) and having a diagnosis code for obesity (10.8% vs 6.9% for no diagnosis; p<0.001). For all drug classes, the recent prescribing behavior of the provider was a strong correlate of subsequent second-line drug selection.

Conclusions

Sulfonylureas continue to represent almost half of second-line diabetes medication starts in the USA. This could reflect overuse for some groups such as older adults, for whom some alternatives may be safer, although more costly and potentially less effective. Future research should compare outcomes of medication choices and conditions under which particular classes are most effective.
Suicide and all-cause mortality in Swedish deployed military veterans: a population-based matched cohort study
Authors: Pethrus Carl-Martin , Johansson Kari , Neovius Kristian , Reutfors Johan , Sundström Johan , Neovius Martin
Published: September 2017

Objective

To investigate suicide and mortality risk in deployed military veterans versus non-deployed comparators who had gone through military conscription testing.

Design

Population-based matched cohort study.

Setting

Sweden.

Participants

Participants were identified from the Military Service Conscription Register and deployment status from the Swedish Military Information Personnel Register. Of 1.9 million conscripts, 21 721 had deployed at some time between 1990 and 2013 (deployed military veterans). Non-deployed comparators were matched to deployed military veterans in two ways: (1) by cognitive ability, psychological assessment, mental health, body mass index, sex, birth-year and conscription-year (carefully matched), with further adjustment for exercise capacity and suicide attempt history; and (2) by sex, birth-year and conscription-year (age- and sex-matched).

Main outcome

Suicide retrieved from the Swedish National Patient and Causes of Death Register until 31 December 2013.

Results

During a median follow-up of 12 years, 39 and 211 deaths by suicide occurred in deployed military veterans (n=21 627) and carefully matched non-deployed comparators (n=107 284), respectively (15 vs 16/100 000 person-years; adjusted HR (aHR) 1.07; 95% CI 0.75 to 1.52; p=0.72) and 329 in age- and sex-matched non-deployed comparators (n=108 140; 25/100 000 person-years; aHR 0.59; 95% CI 0.42 to 0.82; p=0.002). There were 284 and 1444 deaths by suicide or attempted suicides in deployed military veterans and carefully matched non-deployed comparators, respectively (109 vs 112; aHR 0.99; 95% CI 0.88 to 1.13; p=0.93) and 2061 in age- and sex-matched non-deployed comparators (158; aHR 0.69; 95% CI 0.61 to 0.79; p<0.001). The corresponding figures for all-cause mortality for carefully matched non-deployed comparators were 159 and 820 (61 vs 63/100 000 person-years; aHR 0.97; 95% CI 0.82 to 1.15; p=0.71) and 1289 for age- and sex-matched non-deployed comparators (98/100 000 person-years; aHR 0.62; 95% CI 0.52 to 0.73; p<0.001).

Conclusion

Deployed military veterans had similar suicide and mortality risk as non-deployed comparators after accounting for psychological, psychiatric and physical factors. Studies of mental health in deployed veterans need to adjust for more factors than age and sex for comparisons to be meaningful.
Suicide and self-harm trends in recent immigrant youth in Ontario, 1996-2012: a population-based longitudinal cohort study
Authors: Saunders Natasha Ruth , Lebenbaum Michael , Stukel Therese A , Lu Hong , Urquia Marcelo L , Kurdyak Paul , Guttmann Astrid
Published: September 2017

Objective

To describe the trends in suicide and emergency department (ED) visits for self-harm in youth by immigration status and immigrant characteristics.

Design

Population-based longitudinal cohort study from 1996 to 2012 using linked health and administrative datasets.

Setting

Ontario, Canada.

Participants

Youth 10 to 24 years, living in Ontario, Canada.

Exposure

The main exposure was immigrant status (recent immigrant (RI) versus long-term residents (LTR)). Secondary exposures included region of birth, duration or residence, and refugee status.

Main outcome measure

Trends over time in suicide and ED self-harm were modelled within consecutive 3-year time periods. Rate ratios were estimated using Poisson regression models.

Results

2.5 to 2.9 million individuals were included per cohort period. LTR suicide rates ranged from 7.4 to 9.4/100 000 male person-years versus 2.2–3.4/100 000 females. RI’s suicide rates were 2.7–7.2/100,000 male versus 1.9–2.7/100 000 female person-years. Suicide rates were lower among RI compared with LTR (adjusted relative rate (aRR)=0.70, 95% CI=0.57 to 0.85) with different mechanisms of suicide. No significant time trend in suicide rates was observed (p=0.40). ED self-harm rates for LTR and RI were highest in females (2.6–3.4/1000 LTR females versus 1.1–1.5/1000 males, 1.2–1.8/1000 RI females versus 0.4–0.6/1000 males). RI had lower rates of self-harm compared with LTR (aRR=0.60, 95% CI=0.56 to 0.65). Stratum-specific rates showed a steeper decline per period in RI compared with LTR (RI: aRR=0.85, 95% CI=0.81 to 0.89; LTR: aRR=0.91, 95% CI=0.90 to 0.93). Observed trends were not universal across region of origin and by refugee status.

Interpretation

Suicide rates have been stable and ED self-harm rates are declining over time among RI youth. These trends by important subgroups should continue to be monitored to allow for early identification of subpopulations of immigrant youth in need of targeted and culturally appropriate public health interventions.
Efficacy and safety of renal denervation for Chinese patients with resistant hypertension using a microirrigated catheter: study design and protocol for a prospective multicentre randomised controlled trial
Authors: Liu Zongjun , Shen Li , Huang Weijian , Zhao Xianxian , Fang Weiyi , Wang Changqian , Yin Zhaofang , Wang Jianan , Fu Guosheng , Liu Xuebo , Jiang Jianjun , Zhang Zhihui , Li Jingbo , Lu Yingmin , Ge Junbo
Published: September 2017

Introduction

Available data show that approximately 8%–18% of patients with primary hypertension will develop resistant hypertension. In recent years, catheter-based renal denervation (RDN) has emerged as a potential treatment option for resistant hypertension. A number of observational studies and randomised controlled trials among non-Chinese patients have demonstrated its potential safety and efficacy.

Methods and analysis

This is a multicentre, randomised, open-label, parallel-group, active controlled trial that will investigate the efficacy and safety of a 5F saline-irrigated radiofrequency ablation (RFA) used for RDN in the treatment of Chinese patients with resistant hypertension. A total of 254 patients who have failed pharmacological therapy will be enrolled. Eligible subjects will be randomised in a 1:1 ratio to undergo RDN using the RFA plus antihypertensive medication or to receive treatment with antihypertensive medication alone. The primary outcome measure is the change in 24 hours average ambulatory systolic blood pressure from baseline to 3 months, comparing the RDN-plus-medication group with the medication-alone group. Important secondary endpoints include the change in office blood pressure from baseline to 6 months after randomisation. Safety endpoints such as changes in renal function will also be evaluated. The full analysis set, according to the intent-to-treat principle, will be established as the primary analysis population.

Ethics and dissemination

All participants will provide informed consent; the study protocol has been approved by the Independent Ethics Committee for each site. This study is designed to investigate the efficacy and safety of RDN using a 5F saline microirrigated RFA. Findings will be shared with participating hospitals, policymakers and the academic community to promote the clinical management of resistant hypertension in China.

Trial registration

ClinicalTrials.gov ID:NCT02900729; pre-results.
Ablation with irreversible electroporation in patients with advanced perihilar cholangiocarcinoma (ALPACA): a multicentre phase I/II feasibility study protocol
Authors: Coelen Robert J S , Vogel Jantien A , Vroomen Laurien G P H , Roos Eva , Busch Olivier R C , van Delden Otto M , Delft Foke van , Heger Michal , van Hooft Jeanin E , Kazemier Geert , Klümpen Heinz-Josef , van Lienden Krijn P , Rauws Erik A J , Scheffer Hester J , Verheul Henk M , Vries Jan de , Wilmink Johanna W , Zonderhuis Barbara M , Besselink Marc G , van Gulik Thomas M , Meijerink Martijn R
Published: September 2017

Introduction

The majority of patients with perihilar cholangiocarcinoma (PHC) has locally advanced disease or distant lymph node metastases on presentation or exploratory laparotomy, which makes them not eligible for resection. As the prognosis of patients with locally advanced PHC or lymph node metastases in the palliative setting is significantly better compared with patients with organ metastases, ablative therapies may be beneficial. Unfortunately, current ablative options are limited. Photodynamic therapy causes skin phototoxicity and thermal ablative methods, such as stereotactic body radiation therapy and radiofrequency ablation, which are affected by a heat/cold-sink effect when tumours are located close to vascular structures, such as the liver hilum. These limitations may be overcome by irreversible electroporation (IRE), a relatively new ablative method that is currently being studied in several other soft tissue tumours, such as hepatic and pancreatic tumours.

Methods and analysis

In this multicentre phase I/II safety and feasibility study, 20 patients with unresectable PHC due to vascular or distant lymph node involvement will undergo IRE. Ten patients who present with unresectable PHC will undergo CT-guided percutaneous IRE, whereas ultrasound-guided IRE will be performed in 10 patients with unresectable tumours detected at exploratory laparotomy. The primary outcome is the total number of clinically relevant complications (Common Terminology Criteria for Adverse Events, score of≥3) within 90 days. Secondary outcomes include quality of life, tumour response, metal stent patency and survival. Follow-up will be 2 years.

Ethics and dissemination

The protocol has been approved by the local ethics committees. Data and results will be submitted to a peer-reviewed journal.

Conclusion

The Ablation with irreversible eLectroportation in Patients with Advanced perihilar CholangiocarcinomA (ALPACA) study is designed to assess the feasibility of IRE for advanced PHC. The main purpose is to inform whether a follow-up trial to evaluate safety and effectiveness in a larger cohort would be feasible.
Labtracker+, a medical smartphone app for the interpretation of consecutive laboratory results: an external validation study
Authors: Hilderink Judith M , Rennenberg Roger J M W , Vanmolkot Floris H M , Bekers Otto , Koopmans Richard P , Meex Steven J R
Published: September 2017

Objectives

When monitoring patients over time, clinicians may struggle to distinguish ‘real changes’ in consecutive blood parameters from so-called natural fluctuations. In practice, they have to do so by relying on their clinical experience and intuition. We developedLabtracker+, a medical app that calculates the probability that an increase or decrease over time in a specific blood parameter is real, given the time between measurements.

Design

We presented patient cases to 135 participants to examine whether there is a difference between medical students, residents and experienced clinicians when it comes to interpreting changes between consecutive laboratory results. Participants were asked to interpret if changes in consecutive laboratory values were likely to be ‘real’ or rather due to natural fluctuations. The answers of the study participants were compared with the calculated probabilities by the appLabtracker+and the concordance rates were assessed.

Setting and participants

Medical students (n=92), medical residents from the department of internal medicine (n=19) and internists (n=24) at a Dutch University Medical Centre.

Primary and secondary outcome measures

Concordance rates between the study participants and the calculated probabilities by the appLabtracker+were compared. Besides, we tested whether physicians with clinical experience scored better concordance rates with the appLabtracker+than inexperienced clinicians.

Results

Medical residents and internists showed significantly better concordance rates with the calculated probabilities by the appLabtracker+than medical students, regarding their interpretation of differences between consecutive laboratory results (p=0.009 and p<0.001, respectively).

Conclusion

The appLabtracker+could serve as a clinical decision tool in the interpretation of consecutive laboratory test results and could contribute to rapid recognition of parameter changes by physicians.
Estimating the prevalence of heterozygous familial hypercholesterolaemia: a systematic review and meta-analysis
Authors: Akioyamen Leo E , Genest Jacques , Shan Shubham D , Reel Rachel L , Albaum Jordan M , Chu Anna , Tu Jack V
Published: September 2017

Objectives

Heterozygous familial hypercholesterolaemia (FH) confers a significant risk for premature cardiovascular disease (CVD). However, the estimated prevalence of FH varies substantially among studies. We aimed to provide a summary estimate of FH prevalence in the general population and assess variations in frequency across different sociodemographic characteristics.

Setting, participants and outcome measures

We searched MEDLINE, EMBASE, Global Health, the Cochrane Library, PsycINFO and PubMed for peer-reviewed literature using validated strategies. Results were limited to studies published in English between January 1990 and January 2017. Studies were eligible if they determined FH prevalence using clinical criteria or DNA-based analyses. We determined a pooled point prevalence of FH in adults and children and assessed the variation of the pooled frequency by age, sex, geographical location, diagnostic method, study quality and year of publication. Estimates were pooled using random-effects meta-analysis. Differences by study-level characteristics were investigated through subgroups, meta-regression and sensitivity analyses.

Results

The pooled prevalence of FH from 19 studies including 2 458 456 unique individuals was 0.40% (95% CI 0.29% to 0.52%) which corresponds to a frequency of 1 in 250 individuals. FH prevalence was found to vary by age and geographical location but not by any other covariates. Results were consistent in sensitivity analyses.

Conclusions

Our systematic review suggests that FH is a common disorder, affecting 1 in 250 individuals. These findings underscore the need for early detection and management to decrease CVD risk.
Development and validation of the Fracture Risk Scale (FRS) that predicts fracture over a 1-year time period in institutionalised frail older people living in Canada: an electronic record-linked longitudinal cohort study
Authors: Ioannidis George , Jantzi Micaela , Bucek Jenn , Adachi Jonathan D , Giangregorio Lora , Hirdes John , Pickard Laura , Papaioannou Alexandra
Published: September 2017

Objectives

To develop and validate our Fracture Risk Scale (FRS) over a 1-year time period, using the long-term care (LTC) Resident Assessment Instrument Minimum Data Set Version 2.0 (RAI-MDS 2.0).

Design

A retrospective cohort study.

Setting

LTC homes in Ontario, Canada.

Participants

Older adults who were admitted to LTC and received a RAI-MDS 2.0 admission assessment between 2006 and 2010.

Results

A total of 29 848 LTC residents were enrolled in the study. Of these 22 386 were included in the derivation dataset and 7462 individual were included in the validation dataset. Approximately 2/3 of the entire sample were women and 45% were 85 years of age or older. A total of 1553 (5.2%) fractures were reported over the 1-year time period. Of these, 959 (61.8%) were hip fractures. Following a hip fracture, 6.3% of individuals died in the emergency department or as an inpatient admission and did not return to their LTC home. Using decision tree analysis, our final outcome scale had eight risk levels of differentiation. The percentage of individuals with a hip fracture ranged from 0.6% (lowest risk level) to 12.6% (highest risk level). The area under the curve of the outcome scale was similar for the derivation (0.67) and validation (0.69) samples, and the scale exhibited a good level of consistency.

Conclusions

Our FRS predicts hip fracture over a 1-year time period and should be used as an aid to support clinical decisions in the care planning of LTC residents. Future research should focus on the transformation of our scale to a Clinical Assessment Protocol and to assess the FRS in other healthcare settings.
Psychological distress and quality of life: rationale and protocol of a prospective cohort study in a rural district in Bangaladesh
Authors: Uddin Mohammed Nazim , Bhar Sunil , Al Mahmud Abdullah , Islam Fakir M Amirul
Published: September 2017

Introduction

A significant proportion of the global burden of disease has been attributed to mental and behavioural disorders. People with mental disorders (MDs) have lower levels of health-related quality of life than those without MDs. Several studies have shown that in low-resource countries, a range of social determinants including poor health literacy is critical in the epidemiological transition of disease outcome. There is a lack of evidence of MDs literacy, the prevalence and risk factors of common mental health conditions, or any validated instruments to measure psychological distress or evaluate the quality of life in rural areas of Bangladesh.

Aims

The aims of this study are: (1) report the awareness, knowledge, attitudes and practice (KAP) of MDs; (2) estimate the prevalence of and risk factors for psychological distress; (3) measure association of psychological distress and other socio-demographic factors with quality of life and (4) test the feasibility to use Kessler 10-item (K10) and WHO Quality Of Life-BREF (WHOQOL-BREF) questionnaires in rural Bangladesh for measuring psychological distress and quality of life.

Methods and analysis

A sample of 1500 adults aged 18–59 years and 1200 older adults aged 60–90 years will be interviewed from a multistage cluster random sample. Each participant will go through a face-to-face interview to assess their awareness and KAP of MDs. Information about the participant’s sociodemographic and socioeconomic status will be collected along with the psychological distress (K10) and quality of life (WHOQOL-BREF) questionnaires. Internal consistency, validity, reliability and item discrimination of K10 and WHOQOL-BREF instruments will be determined by using Rasch analysis and regression techniques.

Ethics and dissemination

Human Ethics Approval was received from the Swinburne University of Technology Human Ethics Committee. Results of this research will be disseminated via scientific forums including peer-reviewed publications and presentations at national and international conferences.
Design and validation of a clinical scale for prehospital stroke recognition, severity grading and prediction of large vessel occlusion: the shortened NIH Stroke Scale for emergency medical services
Authors: Purrucker Jan Christoph , Härtig Florian , Richter Hardy , Engelbrecht Andreas , Hartmann Johannes , Auer Jonas , Hametner Christian , Popp Erik , Ringleb Peter Arthur , Nagel Simon , Poli Sven
Published: September 2017

Objective

To develop an NIH Stroke Scale (NIHSS)-compatible, all-in-one scale for rapid and comprehensive prehospital stroke assessment including stroke recognition, severity grading and progression monitoring as well as prediction of large vessel occlusion (LVO).

Methods

Emergency medical services (EMS) personnel and stroke physicians (n=326) rated each item of the NIHSS regarding suitability for prehospital use; best rated items were included. Stroke recognition was evaluated retrospectively in 689 consecutive patients with acute stroke or stroke mimics, prediction of LVO in 741 consecutive patients with ischaemic stroke with acute vessel imaging independent of admission NIHSS score.

Results

Nine of the NIHSS items were rated as ‘suitable for prehospital use.’ After excluding two items in order to increase specificity, the final scale (termed shortened NIHSS for EMS, sNIHSS-EMS) consists of ‘level of consciousness’, ‘facial palsy’, ‘motor arm/leg’, ‘sensory’, ‘language’ and ‘dysarthria’. Sensitivity for stroke recognition of the sNIHSS-EMS is 91% (95% CI 86 to 94), specificity 52% (95% CI 47 to 56). Receiver operating curve analysis revealed an optimal cut-off point for LVO prediction of ≥6 (sensitivity 70% (95% CI 65 to 76), specificity 81% (95% CI 76 to 84), positive predictive value 70 (95% CI 65 to 75), area under the curve 0.81 (95% CI 0.78 to 0.84)). Test characteristics were non-inferior to non-comprehensive scales.

Conclusions

The sNIHSS-EMS may overcome the sequential use of multiple emergency stroke scales by permitting parallel stroke recognition, severity grading and LVO prediction. Full NIHSS-item compatibility allows for evaluation of stroke progression starting at the prehospital phase.
Admission to psychiatric hospital for mental illnesses 2 years prechildbirth and postchildbirth in Scotland: a health informatics approach to assessing mother and child outcomes
Authors: Martin Julie Langan , McLean Gary , Martin Daniel , Cantwell Roch , Smith Daniel J
Published: September 2017

Objective

To identify factors associated with: admission to a specialist mother and baby unit (MBU) and the impact of perinatal mental illness on early childhood development using a data linkage approach in the 2 years prechildbirth and postchildbirth.

Methods

Scottish maternity records (SMR02) were linked to psychiatric hospital admissions (SMR04). 3290 pregnancy-related psychiatric admissions for 1730 women were assessed. To investigate factors associated with MBU admission, the group of mothers admitted to an MBU were compared with those admitted to general psychiatric wards. To assess the impact of perinatal mental illness on early child development, a pragmatic indicator for ‘at potential risk of adversity’, defined as a child who was recorded as requiring intensive treatment at any time under the health plan indicators (HPI) and/or who had no record of completing three doses of the 5-in-1 vaccine by 12 months was generated. Logistic regression models were used to describe the association between each variable and the risk of admission between those with a history of prior psychiatric admission and those without.

Results

Women admitted to an MBU were significantly more likely to be admitted with non-affective psychosis (OR=1.97, 95% CI 1.22 to 3.18), affective psychosis (OR=2.44, 95% CI 1.37 to 4.33) and non-psychotic depressive episodes (OR=1.93, 95% CI 1.42 to 2.63). They were less likely to come from deprived areas (OR=0.68 95% CI 0.49 to 0.93). Women with a previous history of psychiatric admission were significantly more likely to be located in the two most deprived quintiles. Almost one-third (29%) of children born to mothers with a pregnancy-related psychiatric admission were assessed as ‘at potential risk of adversity.’

Conclusions

A health informatics approach has potential for improving understanding of social and clinical factors, which contribute to the outcomes of perinatal mental illness, as well as potential adverse developmental outcomes for offspring.
A protocol for a randomised controlled trial of the bone response to impact loading or resistance training in young women with lower than average bone mass: the OPTIMA-Ex trial
Authors: Lambert Conor , Beck Belinda R , Harding Amy T , Watson Steven L , Weeks Benjamin K
Published: September 2017

Introduction

The aim of the Osteoporosis Prevention Through Impact and Muscle-loading Approaches to Exercise trial is to compare the bone response to two known osteogenic stimuli — impact loading exercise and resistance training. Specifically, we will examine the effect of a 10-month, twice-weekly, high-intensity impact loading exercise intervention and a 10-month, twice-weekly, high-intensity resistance training intervention on bone mass and strength at clinically important skeletal sites. The intervention groups will be compared against a home-based ‘positive’ control group. Safety and acceptability of each exercise modality will also be determined.

Methods and analysis

Sedentary otherwise healthy young women aged 18–30 years with bone mineral density (BMD) T-scores less than or equal to 0 at the hip and lumbar spine, screened for conditions and medications that influence bone and physical function, will be recruited. Eligible participants are randomised to 10-month, twice-weekly, either supervised high-intensity impact training, high-intensity resistance training or a home-based ‘positive’ control group. The primary outcome measure will be lumbar spine areal BMD, while secondary outcome measures will include: whole body, femoral neck and regional measures (upper and lower limb) of bone, muscle and fat; anthropometrics; muscle strength and power; quality of life and exercise safety, enjoyment and acceptability. All outcome measures will be conducted at baseline (T0) and 10 months (T10) and will be analysed according to the intention-to-treat principle and per protocol.

Ethics and dissemination

The study has been granted ethical approval from the Griffith University Human Research Ethics Committee (GU Ref: 2015/775). Standard scientific reporting practices will occur, including publication in peer-reviewed journals. Participant confidentiality will be maintained in all forms of reporting.

Trial registration number

ACTRN12616001444471.
How can primary care enhance end-of-life care for liver disease? Qualitative study of general practitioners’ perceptions and experiences
Authors: Standing Holly , Jarvis Helen , Orr James , Exley Catherine , Hudson Mark , Kaner Eileen , Hanratty Barbara
Published: September 2017

Background

Liver disease is the third most common cause of premature death in the UK. The symptoms of terminal liver disease are often difficult to treat, but very few patients see a palliative care specialist and a high proportion die in hospital. Primary care has been identified as a setting where knowledge and awareness of liver disease is poor. Little is known about general practitioners’ (GPs) perceptions of their role in managing end-stage liver disease.

Objective

To explore GPs’ experiences and perceptions of how primary care can enhance end-of-life care for patients with liver disease.

Design

Qualitative interview study, thematic analysis.

Participants

Purposive sample of 25 GPs from five regions of England.

Results

GPs expressed a desire to be more closely involved in end-of-life care for patients with liver disease but identified a number of factors that constrained their ability to contribute. These fell into three main areas; those relating directly to the condition, (symptom management and the need to combine a palliative care approach with ongoing medical interventions); issues arising from patients’ social circumstances (stigma, social isolation and the social consequences of liver disease) and deficiencies in the organisation and delivery of services. Collaborative working with support from specialist hospital clinicians was regarded as essential, with GPs acknowledging their lack of experience and expertise in this area.

Conclusions

End-of-life care for patients with liver disease merits attention from both primary and secondary care services. Development of care pathways and equitable access to symptom relief should be a priority.