bluuebunny/crossref_metadata_2025 huggingface dataset:
Nontypeable Haemophilus influenzae Lipooligosaccharide Expresses a Terminal Ketodeoxyoctanoate
In Vivo
, Which Can Be Used as a Target for Bactericidal Antibody
Authors: Apicella Michael A. , Coffin Jeremy , Ketterer Margaret , Post Deborah M. B. , Day Christopher J. , Jen Freda E.-C. , Jennings Michael P.
Published: July 2018

Nontypeable
Haemophilus influenzae
(NTHi) is an important pathogen in individuals of all ages. The lipooligosaccharide (LOS) of NTHi has evolved a complex structure that can be attributed to a multiplicity of glycosyltransferases, the random switching of glycosyltransferase gene expression via phase variation, and the complex structure of its core region with multiple glycoform branch points. This article adds to that complexity by describing a multifunctional enzyme (LsgB) which optimally functions when the species is grown on a solid surface and which can add either a ketodeoxyoctanoate (KDO) or an
N
-acetylneuramic acid (Neu5Ac) moiety to a terminal
N-
acetyllactosamine structure of LOS. Our studies show that expression of
lsgB
is reduced four- to sixfold when NTHi is grown in broth. The substrate that the enzyme utilizes is dependent upon the concentration of free Neu5Ac (between 1 and 10 µg/ml) in the environment. In environments in which Neu5Ac is below that level, the enzyme utilizes endogenous CMP-KDO as the substrate. Our studies show that during
in vivo
growth in an NTHi biofilm, the KDO moiety is expressed by the organism. Monoclonal antibody 6E4, which binds KDO, is bactericidal for NTHi strains that express the KDO epitope at high levels. In a survey of 33 NTHi strains isolated from healthy and diseased individuals, the antibody was bactericidal (>90% kill) for 12 strains (36%). These studies open up the possibility of using a KDO-based glycoconjugate vaccine as part of a multicomponent vaccine against NTHi.

IMPORTANCE
Nontypeable
Haemophilus influenzae
is an important pathogen in middle ear infections in children, sinusitis in adults, and acute bronchitis in individuals with chronic obstructive lung disease. The organism is very well adapted to the human host environment, and this has hindered successful development of an effective vaccine. In this article, we describe a mechanism by which the bacteria decorates its surface lipooligosaccharide with a sugar unique to Gram-negative bacteria, ketodeoxyoctanoate (KDO). This sugar decoration is present during active infection and we have shown that an antibody directed against this sugar can result in killing of the organism. These data demonstrate that the lipooligosaccharide ketodeoxyoctanoate epitope may be a novel NTHi
-
specific candidate vaccine antigen.
Combinatorial Approaches to Viral Attenuation
Authors: Paff Matthew L. , Jack Benjamin R. , Smith Bartram L. , Bull James J. , Wilke Claus O.
Published: July 2018

Live viral vaccines rely on attenuated viruses that can successfully infect their host but have reduced fitness or virulence. Such attenuated viruses were originally developed through trial and error, typically by adaptation of the wild-type virus to novel conditions. That method was haphazard, with no way of controlling the degree of attenuation or the number of attenuating mutations or preventing evolutionary reversion. Synthetic biology now enables rational design and engineering of viral attenuation, but rational design must be informed by biological principles to achieve stable, quantitative attenuation. This work shows that in a model system for viral attenuation, bacteriophage T7, attenuation can be obtained from rational design principles, and multiple different attenuation approaches can be combined for enhanced overall effect.
Hidradenoma papilliferum: an unusual benign perianal tumour
Authors: Cheong Ju Yong , Lee Cheok Soon , Young Christopher John
Published: July 2018

Hidradenoma papilliferum is an uncommon benign tumour that is located in the anogenital region of middle-aged women. They are usually only diagnosed after excision and are thought to arise from anogenital mammary-like glands. We present the case of a young woman who noticed a slow growing perianal lump which caused minimal symptoms.
Three-year outcomes of small incision lenticule extraction (SMILE) and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) for myopia and myopic astigmatism
Authors: Han Tian , Xu Ye , Han Xiao , Zeng Li , Shang Jianmin , Chen Xun , Zhou Xingtao
Published: July 2018

Aims

To compare long-term clinical outcomes following small incision lenticule extraction (SMILE) and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) for myopia and myopic astigmatism correction.

Methods

In this retrospective study, we enrolled a total of 101 patients (101 eyes) who underwent SMILE or FS-LASIK 3 years prior. Measured parameters included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), manifest refraction and corneal wavefront aberrations.

Results

No significant differences in patient characteristics were found between the two groups. At the 3-year follow-up, UDVA was better than or equal to 20/20 in 90% and 85% (p=0.540) of the eyes; the efficacy indexes were 1.05±0.19 and 1.01±0.21 in the SMILE and FS-LASIK groups, respectively (p=0.352). Safety indexes were 1.19±0.17 and 1.15±0.20 in the SMILE and FS-LASIK groups, respectively (p=0.307). Eighty per cent and 65% of eyes were within ±0.50 D of the attempted spherical equivalent correction after SMILE and FS-LASIK, respectively (p=0.164). Vector analysis revealed no significant differences in astigmatic correction between the two groups (p>0.05). Surgically induced spherical aberration was higher in the FS-LASIK group than in the SMILE group (p<0.001).

Conclusion

Long-term follow-up analysis suggested that both SMILE and FS-LASIK were safe and equally effective for myopic and astigmatic correction.
Protocol for a phase II, monocentre, double-blind, placebo-controlled, cross-over trial to assess efficacy of pyridostigmine in patients with spinal muscular atrophy types 2–4 (SPACE trial)
Authors: Stam Marloes , Wadman Renske I , Wijngaarde Camiel A , Bartels Bart , Asselman Fay-Lynn , Otto Louise A M , Goedee H Stephan , Habets Laura E , de Groot Janke F , Schoenmakers Marja A G C , Cuppen Inge , van den Berg Leonard H , van der Pol W Ludo
Published: July 2018

Introduction

Hereditary proximal spinal muscular atrophy (SMA) is caused by homozygous loss of function of the survival motor neuron 1 gene. The main characteristic of SMA is degeneration of alpha motor neurons in the anterior horn of the spinal cord, but recent studies in animal models and patients have shown additional anatomical abnormalities and dysfunction of the neuromuscular junction (NMJ). NMJ dysfunction could contribute to symptoms of weakness and fatigability in patients with SMA. We hypothesise that pyridostigmine, an acetylcholinesterase inhibitor that improves neuromuscular transmission, could improve NMJ function and thereby muscle strength and fatigability in patients with SMA.

Methods and analysis

We designed a monocentre, placebo-controlled, double-blind cross-over trial with pyridostigmine and placebo to investigate the effect and efficacy of pyridostigmine on muscle strength and fatigability in patients with genetically confirmed SMA. We aim to include 45 patients with SMA types 2–4, aged 12 years and older in the Netherlands. Participants receive 8 weeks of treatment with pyridostigmine and 8 weeks of treatment with placebo in a random order separated by a washout period of 1 week. Treatment allocation is double blinded. Treatment dose will gradually be increased from 2 mg/kg/day to the maximum dose of 6 mg/kg/day in four daily doses, in the first week of each treatment period. The primary outcome measures are a change in the Motor Function Measure and repeated nine-hole peg test before and after treatment. Secondary outcome measures are changes in recently developed endurance tests, that is, the endurance shuttle nine-hole peg test, the endurance shuttle box and block test and the endurance shuttle walk test, muscle strength, level of daily functioning, quality of and activity in life, perceived fatigue and fatigability, presence of decrement on repetitive nerve stimulation and adverse events.

Ethics and dissemination

The protocol is approved by the local medical ethical review committee at the University Medical Center Utrecht and by the national Central Committee on Research Involving Human Subjects. Findings will be shared with the academic and medical community, funding and patient organisations in order to contribute to optimisation of medical care and quality of life for patients with SMA.

Trial registration number

NCT02941328.
Consensus study to define appropriate inaction and inappropriate inertia in the management of patients with hypertension in primary care
Authors: Lebeau Jean-Pierre , Biogeau Julie , Carré Maxime , Mercier Alain , Aubin-Auger Isabelle , Rusch Emmanuel , Remmen Roy , Vermeire Etienne , Hendrickx Kristin
Published: July 2018

Objectives

To elaborate and validate operational definitions for appropriate inaction and for inappropriate inertia in the management of patients with hypertension in primary care.

Design

A two-step approach was used to reach a definition consensus. First, nominal groups provided practice-based information on the two concepts. Second, a Delphi procedure was used to modify and validate the two definitions created from the nominal groups results.

Participants

14 French practicing general practitioners participated in each of the two nominal groups, held in two different areas in France. For the Delphi procedure, 30 academics, international experts in the field, were contacted; 20 agreed to participate and 19 completed the procedure.

Results

Inappropriate inertia was defined as: to not initiate or intensify an antihypertensive treatment for a patient who is not at the blood pressure goals defined for this patient in the guidelines when all following conditions are fulfilled: (1) elevated blood pressure has been confirmed by self-measurement or ambulatory blood pressure monitoring, (2) there is no legitimate doubt on the reliability of the measurements, (3) there is no observance issue regarding pharmacological treatment, (4) there is no specific iatrogenic risk (which alters the risk-benefit balance of treatment for this patient), in particular orthostatic hypotension in the elderly, (5) there is no other medical priority more important and more urgent, and (6) access to treatment is not difficult. Appropriate inaction was defined as the exact mirror, that is, when at least one of the above conditions is not met.

Conclusion

Definitions of appropriate inaction and inappropriate inertia in the management of patients with hypertension have been established from empirical practice-based data and validated by an international panel of academics as useful for practice and research.
Association of resilience with health-related quality of life and depression in multiple myeloma and its precursors: results of a German cross-sectional study
Authors: Maatouk Imad , He Susanne , Becker Natalia , Hummel Manuela , Hemmer Stefan , Hillengass Michaela , Goldschmidt Hartmut , Hartmann Mechthild , Schellberg Dieter , Herzog Wolfgang , Hillengass Jens
Published: July 2018

Objectives

To investigate the relation between resilience, health-related quality of life (HRQOL) and depression in multiple myeloma (MM) and its premalignant stages. MM is one of the most frequent haematological disorders. It is regularly preceded by asymptomatic stages of the disease namely monoclonal gammopathy of undetermined significance (MGUS) and smouldering multiple myeloma (SMM). Survivors have to cope with mental and physical impairment in terms of HRQOL and depression. The concept of resilience refers to a person’s ability to adapt to adversity.

Design

Cross-sectional study.

Setting

MM outpatient department at a University Hospital in Germany (tertiary care).

Participants

292 consecutive patients from our MM outpatient department.

Outcome measures

HRQOL, depression and psychological resilience were assessed with validated questionnaires.

Results

Regression analyses were performed to determine associations between resilience, HRQOL and depression. 98 patients (33.6%) had a new diagnosis of active MM, 106 patients (36.3%) were already treated for MM and 88 patients had the diagnosis of a precursor (MGUS or SMM; 30.1%) of MM. Multivariate linear regression analyses revealed a strong positive impact of resilience on physical (b 7.20; 95% CI 4.43 to 9.98; p<0.001) and mental (b 12.12; 95% CI 9.36 to 14.87; p<0.001) HRQOL. Ordered logistic regression analysis showed that the odds for higher depression severity were lowered for individuals with a high level of resilience in comparison to the individuals with a low level of resilience (OR 0.11; 95% CI 0.06 to 0.19; p<0.001).

Conclusions

Resilience may be a protective factor in the disease trajectory of MM and its precursors. As a next step, future research should focus on longitudinal assessments at various time points to elucidate the role of resilience in one of the most frequent haematological malignancies.
Gender differences in the mental health of unaccompanied refugee minors in Europe: a systematic review
Authors: Mohwinkel Lea-Marie , Nowak Anna Christina , Kasper Anne , Razum Oliver
Published: July 2018

Objectives

Our aim was to summarise the current evidence regarding gender differences in the mental health of unaccompanied refugee minors (URM) and to identify gaps in research.

Setting

We focused on quantitative studies presenting primary data from Organisation for Economic Co-Operation and Development(OECD)countries. Language was restricted to English or German.

Participants

To be eligible, a study had to involve (former) URM who immigrated to an OECD country.

Design

We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The databases MEDLINE, CINAHL, LIVIVO, PSYNDEX and PsycINFO were searched from 1990 to 2017. Studies were judged for eligibility by two independent reviewers each. We narratively summarised our results.

Results

9 primary studies, all from Europe, examined gender differences in the mental health of URM. The majority of the included studies found female URM to be more often affected by post-traumatic or depressive symptoms than their male counterparts. There is only weak evidence regarding other mental health outcomes. Two studies each conducted gender-specific analyses on anxiety and externalising behaviour, but no statistically significant differences between female and male URM were detected.

Conclusions

Female gender is associated with a higher vulnerability towards certain mental health problems among URM residing in Europe. However, the lack of representative studies using reliable diagnostic methods indicates that the findings so far should be treated with caution. Further research is needed to clarify the role of gender for mental health in URM and to examine underlying mechanisms.
Public reporting of antipsychotic prescribing in nursing homes: population-based interrupted time series analyses
Authors: Ivers Noah M , Taljaard Monica , Giannakeas Vasily , Reis Catherine , Williams Evelyn , Bronskill Susan
Published: July 2018

Background

Although sometimes appropriate, antipsychotic medications are associated with increased risk of significant adverse events. In 2014, a series of newspaper articles describing high prescribing rates in nursing homes in Ontario, Canada, garnered substantial interest. Subsequently, an online public reporting initiative with home-level data was launched. We examined the impact of these public reporting interventions on antipsychotic prescribing in nursing homes.

Methods

Time series analysis of all nursing home residents in Ontario, Canada, between 1 October 2013 and 31 March 2016. The primary outcome was the proportion of residents prescribed antipsychotics each month. Balance measures were prescriptions for common alternative sedating agents (benzodiazepines and/or trazodone). We used segmented regression to assess the effects on prescription trends of the newspaper articles and the online home-level public reporting initiative.

Results

We included 120 009 nursing home resident admissions across 636 nursing homes. Following the newspaper articles, the proportion of residents prescribed an antipsychotic decreased by 1.28% (95% CI 1.08% to 1.48%) and continued to decrease at a rate of 0.2% per month (95% CI 0.16% to 0.24%). The online public reporting initiative did not alter this trend. Over 3 years, there was a net absolute reduction in antipsychotic prescribing of 6.0% (95% CI 5.1% to 6.9%). Trends for benzodiazepine prescribing did not change as substantially during the period of observation. Trazodone use has been gradually increasing, but its use did not change abruptly at the time of the mass media report or the public reporting initiative.

Interpretation

The rapid impact of mass media on prescribing suggests both an opportunity to use this approach to invoke change and a warning to ensure that such reporting occurs responsibly.
Oral direct-acting antivirals and the incidence or recurrence of hepatocellular carcinoma: a systematic review and meta-analysis
Authors: Singh Sonal , Nautiyal Amit , Loke Yoon K
Published: July 2018

Background

The influence of direct-acting antiviral (DAA) therapy for chronic hepatitis C virus on the risk of hepatocellular carcinoma (HCC) is conflicting.

Methods

We conducted a systematic review and meta-analysis to determine the incidence or recurrence of HCC associated with oral DAA therapy. We searched PubMed, Scopus, Embase from inception to August 2017 to identify observational studies reporting on HCC among patients treated with DAAs. Two independent reviewers extracted data and assessed the risk of bias. Data were pooled by random-effects model. The primary outcome was the proportion of participants with incidence or recurrence of HCC (PROSPERO number CRD42017057040).

Results

After reviewing 2080 citations, we included 8 controlled studies and 36 uncontrolled studies. The pooled proportion for incident HCC was 1.5 % (95% CI 1.0% to 2.1%; I2=90.1%; n= 542/39 145) from 18 uncontrolled studies and 3.3% (95% CI 1.2% to 9%; I2=96%; n=109/6909) from 5 controlled studies, respectively. The pooled proportion for recurrent HCC was 16.7% (95% CI 10.2% to 26%; I2=84.8%; n=136/867) from 12 uncontrolled studies and 20.1% (95% CI 5.5% to 52.1%; I2=87.5%; n=36/225) from 3 controlled studies, respectively. There was no statistically significant effect on the risk of recurrent HCC (OR 0.50, 95%CI 0.16 to 1.59; I2=73.4%) in a meta-analysis of three studies.

Conclusions

Our findings show low proportion of incident HCC, but high proportion of recurrent HCC on treatment with DAAs. Continued active surveillance for HCC after treatment with DAAs remains prudent.
Chocolate consumption and risk of cardiovascular diseases: a meta-analysis of prospective studies
Authors: Ren Yongcheng , Liu Yu , Sun Xi-Zhuo , Wang Bing-Yuan , Zhao Yang , Liu De-Chen , Zhang Dong-Dong , Liu Xue-Jiao , Zhang Rui-Yuan , Sun Hao-Hang , Liu Fei-Yan , Chen Xu , Cheng Cheng , Liu Lei-Lei , Zhou Qiong-Gui , Zhang Ming , Hu Dong-Sheng
Published: July 2018

Objective

Studies investigating the impact of chocolate consumption on cardiovascular disease (CVD) have reached inconsistent conclusions. As such, a quantitative assessment of the dose–response association between chocolate consumption and incident CVD has not been reported. We performed a systematic review and meta-analysis of studies assessing the risk of CVD with chocolate consumption.

Methods

PubMed and EMBASE databases were searched for articles published up to 6 June 2018. Restricted cubic splines were used to model the dose–response association.

Results

Fourteen publications (23 studies including 405 304 participants and 35 093 cases of CVD) were included in the meta-analysis. The summary of relative risk (RR) per 20 g/week increase in chocolate consumption was 0.982 (95% CI 0.972 to 0.992, I2=50.4%, n=18) for CVD (heart failure: 0.995 (0.981 to 1.010, I2=36.3%, n=5); total stroke: 0.956 (0.932 to 0.980, I2=25.5%, n=7); cerebral infarction: 0.952 (0.917 to 0.988, I2=0.0%, n=4); haemorrhagic stroke: 0.931 (0.871 to 0.994, I2=0.0%, n=4); myocardial infarction: 0.981 (0.964 to 0.997, I2=0.0%, n=3); coronary heart disease: 0.986 (0.973 to 0.999, n=1)). A non-linear dose–response (pnon-linearity=0.001) indicated that the most appropriate dose of chocolate consumption for reducing risk of CVD was 45 g/week (RR 0.890;95%CI 0.849 to 0.932).

Conclusions

Chocolate consumption may be associated with reduced risk of CVD at <100 g/week consumption. Higher levels may negate the health benefits and induce adverse effects associated with high sugar consumption.
Political views of doctors in the UK: a cross-sectional study
Authors: Mandeville Kate L , Satherley Rose-Marie , Hall Jennifer A , Sutaria Shailen , Willott Chris , Yarrow Kielan , Mohan Keerthi , Wolfe Ingrid , Devakumar Delan
Published: July 2018

Background

Little is known about the political views of doctors in the UK despite doctors' importance in the functioning of the National Health Service (NHS).

Methods

This is a survey-based, cross-sectional study in which we asked questions about voting behaviour in 2015 and 2017 UK general elections and 2016 referendum on leaving the European Union (EU) (Brexit), and questions relating to recent health policies.

Results

1172 doctors (45.1% women) from 1295 responded to an online survey. 60.5% described their political views as ‘left-wing’ and 62.2% described themselves as ‘liberal’. 79.4% of respondents voted to remain in the EU in the 2016 referendum compared with 48.1% of voters as a whole (χ2=819.8, p<0.001). 98.6% of respondents agreed that EU nationals working in the NHS should be able to remain in the UK after Brexit. The median score for the impact of Brexit on the NHS on a scale of 0 (worst impact) to 10 (best impact) was 2 (IQR=1–4). Most respondents agreed with the introduction of minimum alcohol pricing in the UK (73.9%), charging patients who are not eligible for NHS treatment for non-urgent care (70.6%) and protecting a portion of national spending for the NHS (87.1%). 65.8% thought there was too much use of NHS-funded private sector provision in their medical practice. Specialty, income and grade were associated with divergent opinions.

Conclusions

UK doctors are left-leaning and liberal in general, which is reflected in their opinions on topical health policy issues. Doctors in the UK voted differently from the general electorate in recent polls.
Mutations in IRS4 are associated with central hypothyroidism
Authors: Heinen Charlotte A , de Vries Emmely M , Alders Mariëlle , Bikker Hennie , Zwaveling-Soonawala Nitash , van den Akker Erica L T , Bakker Boudewijn , Hoorweg-Nijman Gera , Roelfsema Ferdinand , Hennekam Raoul C , Boelen Anita , van Trotsenburg A S Paul , Fliers Eric
Published: July 2018

Background

Four genetic causes of isolated congenital central hypothyroidism (CeH) have been identified, but many cases remain unexplained. We hypothesised the existence of other genetic causes of CeH with a Mendelian inheritance pattern.

Methods

We performed exome sequencing in two families with unexplained isolated CeH and subsequently Sanger sequenced unrelated idiopathic CeH cases. We performed clinical and biochemical characterisation of the probands and carriers identified by family screening. We investigated IRS4 mRNA expression in human hypothalamus and pituitary tissue, and measured serum thyroid hormones and Trh and Tshb mRNA expression in hypothalamus and pituitary tissue of Irs4 knockout mice.

Results

We found mutations in the insulin receptor substrate 4 (IRS4) gene in two pairs of brothers with CeH (one nonsense, one frameshift). Sequencing of IRS4 in 12 unrelated CeH cases negative for variants in known genes yielded three frameshift mutations (two novel) in three patients and one male sibling. All male carriers (n=8) had CeH with plasma free thyroxine concentrations below the reference interval. MRI of the hypothalamus and pituitary showed no structural abnormalities (n=12). 24-hour thyroid-stimulating hormone (TSH) secretion profiles in two adult male patients showed decreased basal, pulsatile and total TSH secretion. IRS4 mRNA was expressed in human hypothalamic nuclei, including the paraventricular nucleus, and in the pituitary gland. Female knockout mice showed decreased pituitary Tshb mRNA levels but had unchanged serum thyroid hormone concentrations.

Conclusions

Mutations in IRS4 are associated with isolated CeH in male carriers. As IRS4 is involved in leptin signalling, the phenotype may be related to disrupted leptin signalling.
The LUNA aneurysm embolization system for intracranial aneurysm treatment: short-term, mid-term and long-term clinical and angiographic results
Authors: Piotin Michel , Biondi Alessandra , Sourour Nader , Mounayer Charbel , Jaworski Maciej , Mangiafico Salvatore , Andersson Tommy , Söderman Michael , Goffette Pierre , Anxionnat René , Blanc Raphaël
Published: July 2018

Background and purpose

Intrasaccular aneurysm flow disruption represents an emerging endovascular approach to treat intracranial aneurysms. The purpose of this study was to determine the clinical and angiographic outcomes of using the LUNA aneurysm embolization system (AES) for treatment of intracranial aneurysms.

Materials and methods

The LUNA AES Post-Market Clinical Follow-Up study is a prospective, multicenter, single-arm study that was designed to evaluate device safety and efficacy. Bifurcation and sidewall aneurysms were included. Aneurysm occlusion was assessed using the Raymond-Roy classification scale. Disability was assessed using the Modified Rankin Scale (mRS). Morbidity was defined as mRS >2 if baseline mRS ≤2, increase in mRS of 1 or more if baseline mRS >2, or mRS >2 if aneurysm was ruptured at baseline. Clinical and angiographic follow-up was conducted at 6, 12 and 36 months.

Results

Sixty-three subjects with 64 aneurysms were enrolled. Most aneurysms were unruptured (60/63 (95.2%)); 49 were bifurcation or terminal (49/64 (76.6%)). Mean aneurysm size was 5.6±1.8 mm (range, 3.6–14.9 mm), and mean neck size was 3.8±1.0 mm (range, 1.9–8.7 mm). Though immediate postoperative adequate occlusion was low (11/63, 18%), adequate occlusion was achieved in 78.0% (46/59) and 79.2% (42/53) of the aneurysms at 12 months and 36 months, respectively. Four patients were retreated by the 12-month follow-up (4/63 (6.3%)) and three patients were retreated by the 36-month follow-up (3/63 (4.8%)). There were two major strokes (2/63 (3.2%)), one minor stroke (1/63 (1.6%)) and three incidents of intracranial hemorrhage in two subjects (2/63 (3.2%)) prior to the 12-month follow-up. There was one instance of mortality (1/63, 1.6%). Morbidity was 0% (0/63) and 1.8% (1/63) at the 12-month and 36-month follow-ups, respectively.

Conclusions

LUNA AES is safe and effective for the treatment of bifurcation and sidewall aneurysms.

Clinical trial registration

ISRCTN72343080; Results.
Exposure to disinfectant by-products and the risk of stillbirth in Massachusetts
Authors: Rivera-Núñez Zorimar , Wright J Michael , Meyer Amy
Published: July 2018

Objectives

We examined stillbirths in relation to disinfection by-product (DBP) exposures including chloroform, bromodichloromethane (BDCM), dibromochloromethane, bromoform, trichloroacetic acid, dichloroacetic acid (DCAA), monobromoacetic acid and summary DBP measures (trihalomethanes (THM4), haloacetic acids (HAA5), THMBr (brominated trihalomethanes) and DBP9 (sum of THM4 and HAA5)).

Methods

We randomly selected 10 controls for each of the 2460 stillbirth cases with complete quarterly 1997–2004 THM4 and HAA5 town-level drinking water data. Adjusted (aORs) were calculated based on weight-averaged second-trimester DBP exposures.

Results

We detected statistically significant associations for stillbirths and the upper DCAA quartiles (aOR range: 1.50–1.71). We also found positive associations for the upper four HAA5 quintiles and different stillbirth cause of death categories that were examined including unexplained stillbirth (aOR range: 1.24–1.72), compression of umbilical cord (aOR range: 1.08–1.94), prematurity (aOR range: 1.37–2.88), placental separation and haemorrhage (aOR range: 1.44–2.01) and asphyxia/hypoxia (aOR range: 1.52–1.97). Additionally, we found positive associations between stillbirths and chloroform exposure (aOR range: 1.29 – 1.36) and unexplained stillbirths and BDCM exposure (aOR range: 1.51 – 1.78). We saw no evidence of exposure–response relationships for any categorical DBP metrics.

Conclusions

Consistent with some previous studies, we found associations between stillbirths and chloroform and unexplained stillbirth and BDCM exposures. These findings strengthen existing evidence of prenatal THM exposures increasing the risk of stillbirth. Additionally, we saw statistically significant associations between DCAA and stillbirth. Future research should examine cause-specific stillbirths in relation to narrower critical windows and additional DBP exposure metrics beyond trihalomethanes and haloacetic acids.
Applying the ordinal model of atherosclerosis to imaging science: a brief review
Authors: Groenendyk Jacob W , Mehta Nehal N
Published: July 2018

Atherogenesis has been well demonstrated to proceed in an ordinal fashion. Imaging technologies have advanced substantially in recent decades, enabling early detection of atherosclerosis. Some modalities, such as coronary CT, have seen broad clinical adaptation. In contrast, others, such as flow-mediated dilatation, remain predominantly research-based. Optimal and appropriate usage of these technologies remains an area of active investigation. We hypothesise that investigators ought to consider which stage of atherosclerosis is under investigation when choosing imaging modalities. Additionally, when assessing the efficacy of a particular treatment, some imaging modalities may be more appropriate than others. We review the most important available imaging modalities and suggest stages at which each may or may not be well used. Conceptual application of the classic stages of atherosclerosis model to the variety of modern imaging modalities available will result in more effective investigation and treatment of cardiovascular disease.
Sustainable production and use of cleaner fish for the biological control of sea lice: recent advances and current challenges
Authors: Brooker Adam J , Papadopoulou Athina , Gutierrez Carolina , Rey Sonia , Davie Andrew , Migaud Herve
Published: July 2018

Currently, cleaner fish are one of the most widely used sea lice control strategies in Atlantic salmon aquaculture. Two species are currently being farmed in North Atlantic countries, ballan wrasse (Labrus bergylta) and lumpfish (Cyclopterus lumpus), and the sector in most countries is rapidly expanding towards self‐sufficiency. The species are very different both in terms of their biology and life histories and, consequently, production and husbandry methods must be tailored to each species. There are numerous health challenges currently experienced in both species, with bacterial and parasitic diseases being the most prevalent, and cohabitation with salmon may increase the risk of disease. Good husbandry and routine health monitoring are essential, although treatment is often required when disease outbreaks occur. Ballan wrasse and lumpfish are both proven to be effective salmon delousers, although delousing efficacy can be variable in farmed fish; the provision of suitable habitat and acclimation to net‐pen conditions may encourage natural behaviours, including delousing, and the use of operational welfare indicators can highlight potential welfare issues. Cleaner fish research is progressing rapidly, although much of the basic knowledge regarding the species’ biology remains unknown. The simultaneous domestication of two new marine aquaculture species is a significant challenge demanding sustained effort and funding over a prolonged period of time. Research must focus on enhancing the robustness of the farmed stocks and increasing hatchery outputs to meet the urgent demands from the salmon sector and protect wild stocks from overfishing.
Effect of carbohydrate beverage ingestion on central versus peripheral fatigue: a placebo-controlled, randomized trial in cyclists
Authors: Glace Beth W. , Kremenic Ian J. , McHugh Malachy P.
Published: July 2018

We investigated whether carbohydrate ingestion delays fatigue in endurance-trained cyclists via peripheral or central mechanisms. Ten men (35 ± 9 years of age) and 10 women (42 ± 7 years of age) were assigned, in a double-blind, crossover design, to a sports drink (CHO) or to a placebo (PL). The following strength measures were made 3 times (before exercise, after a time trial (TT), and after a ride to exhaustion): (i) maximal voluntary contraction (MVC); (ii) MVC with superimposed femoral nerve magnetic stimulation to measure central activation ratio (CAR); and (iii) femoral nerve stimulation in a 3-s pulse train on relaxed muscle. The subjects cycled for 2 h at approximately 65% of peak oxygen consumption, with five 1-min sprints interspersed, followed by a 3-km TT. After strength testing, the cyclists remounted their bikes, performed a brief warm-up, and pedaled at approximately 85% peak oxygen consumption until unable to maintain workload. Changes in metabolic and strength measurements were analyzed with repeated-measures ANOVA. From before exercise to after the TT, MVC declined in men (17%) and women (18%) (p = 0.004), with no effect of beverage (p > 0.193); CAR decreased in both sexes with PL (p = 0.009), and the decline was attenuated by CHO in men only (time × treatment, p = 0.022); and there was no evidence of peripheral fatigue in either sex with either beverage (p > 0.122). Men rode faster in the TT with CHO (p = 0.005) but did not improve performance in the ride to exhaustion (p = 0.080). In women, CHO did not improve performance in the TT (p = 0.173) or in the ride to exhaustion (p = 0.930). We concluded that carbohydrate ingestion preserved central activation and performance in men, but not in women, during long-duration cycling.
Time of day, but not sleep restriction, affects markers of hemostasis following heavy exercise
Authors: Roberson Paul A. , Chase John D. , Bigman Matthew B. , Saunders Michael J. , Luden Nicholas D. , Womack Christopher J.
Published: July 2018

We sought to determine the effects of sleep restriction on markers of hemostasis the morning after an exercise session. Seven subjects performed evening exercise followed by an exercise session the next morning, both with and without sleep restriction. Evening exercise included a 20-min submaximal cycling trial (10 min at 50% maximal power (Wmax), 10 min at 60% Wmax), a 3-km cycling time trial, 60 min of cycling intervals, and 3 sets of leg press. Subsequent morning exercise was the same, excluding intervals and leg press. Blood samples were collected at rest and following the 20-min submaximal trial for factor VIII antigen, tissue plasminogen activator (tPA) activity, and plasminogen activator inhibitor-1 (PAI-1) activity. Sleep restriction had no effect on the variables. Factor VIII antigen was higher and tPA activity lower in the morning versus evening, respectively (P < 0.05). There were larger (P < 0.05) exercise responses for tPA activity in the evening (pre-exercise = 0.32 ± 0.14, postexercise = 1.89 ± 0.60 AU/mL) versus morning (pre-exercise = 0.27 ± 0.13 AU/mL, postexercise = 0.69 ± 0.18 AU/mL). PAI-1 exhibited lower (P < 0.05) responses in the evening (pre-exercise = 0.78 ± 0.26 AU/mL, postexercise = 0.69 ± 0.29 AU/mL) versus morning (pre-exercise = 7.06 ± 2.66, postexercise = 5.40 ± 2.31 AU/mL). Although a prothrombotic environment was observed the morning following an evening exercise session, it was not exacerbated by sleep restriction.
Unrestrictive identification of post-translational modifications inHevea brasiliensislatex
Authors: Habib Mohd Afiq Hazlami , Gan Chee-Yuen , Abdul Latiff Aishah , Ismail Mohd Nazri
Published: July 2018

The natural rubber latex extracted from the bark of Hevea brasiliensis plays various important roles in modern society. Post-translational modifications (PTMs) of the latex proteins are important for the stability and functionality of the proteins. In this study, latex proteins were acquired from the C-serum, lutoids, and rubber particle layers of latex without using prior enrichment steps; they were fragmented using collision-induced dissociation (CID), higher-energy collisional dissociation (HCD), and electron-transfer dissociation (ETD) activation methods. PEAKS 7 were used to search for unspecified PTMs, followed by analysis through PTM prediction tools to crosscheck both results. There were 73 peptides in 47 proteins from H. brasiliensis protein sequences derived from UniProtKB were identified and predicted to be post-translationally modified. The peptides with PTMs identified include phosphorylation, lysine acetylation, N-terminal acetylation, hydroxylation, and ubiquitination. Most of the PTMs discovered have yet to be reported in UniProt, which would provide great assistance in the research of the functional properties of H. brasiliensis latex proteins, as well as being useful biomarkers. The data are available via the MassIVE repository with identifier MSV000082419.
Comparative analysis of the bioenergetics of human adenocarcinoma Caco-2 cell line and postoperative tissue samples from colorectal cancer patients
Authors: Ounpuu Lyudmila , Truu Laura , Shevchuk Igor , Chekulayev Vladimir , Klepinin Aleksandr , Koit Andre , Tepp Kersti , Puurand Marju , Rebane-Klemm Egle , Käämbre Tuuli
Published: July 2018

The aim of this work was to explore the key bioenergetic properties for mitochondrial respiration in the widely-used Caco-2 cell line and in human colorectal cancer (HCC) postoperational tissue samples. Oxygraphy and metabolic control analysis (MCA) were applied to estimate the function of oxidative phosphorylation in cultured Caco-2 cells and HCC tissue samples. The mitochondria of Caco-2 cells and HCC tissues displayed larger functional activity of respiratory complex (C)II compared with CI, whereas in normal colon tissue an inverse pattern in the ratio of CI to CII activity was observed. MCA showed that the respiration in Caco-2 and HCC tissue cells is regulated by different parts of electron transport chain. In HCC tissues, this control is performed essentially at the level of respiratory chain complexes I–IV, whereas in Caco-2 cells at the level of CIV (cytochrome c oxidase) and the ATP synthasome. The differences we found in the regulation of respiratory chain activity and glycose index could represent an adaptive response to distinct growth conditions; this highlights the importance of proper validation of results obtained from in-vitro models before their extrapolation to the more complex in-vivo systems.
Constitutive model to simulate full deformation and failure process for rocks considering initial compression and residual strength behaviors
Authors: Cao Wengui , Tan Xin , Zhang Chao , He Min
Published: July 2018

A constitutive model with capacity to simulate the full deformation and failure process for rocks considering initial compression and residual strength behaviors is discussed in this paper. The rock was assumed to consist of the initial voids portion and the solid skeleton portion. The full deformation model of rocks can be established by the consideration of the macroscopic deformation of rocks and the microscopic deformations of the two different portions based on the statistical damage theory. Comparisons between the experimental data from triaxial compression tests and calculated results show that the proposed constitutive model provided a good prediction of the full deformation and failure process, including the effects of initial void compression, stiffness degradation, strain hardening–softening, and residual strength.
Case study application of prevention through design to enhance workplace safety and health in Manitoba heavy construction projects
Authors: Ezisi Uzo , Issa Mohamed H.
Published: July 2018

This research aimed to develop a method to facilitate the implementation of prevention through design and apply it to a pump station case study in Manitoba, Canada. The method used, in part, failure mode and effects analysis and involved tasking experts with analyzing the project’s design documents to identify potential occupational health and safety failures that could occur throughout construction. It also entailed analyzing the project’s construction documents to determine actual, design-related, occupational health and safety failures observed throughout construction. The application of the method to that project identified 42 potential failure modes in the design, 38% of which were deemed high-risk. A total of 18 failures were detected throughout construction. Of these, 89% were predicted using failure mode and effects analysis and thus deemed preventable by design, indicating the potential effectiveness of the method. Future research should reapply it to other projects to validate these findings.
Integration of optimization methodology to evaluate pavement maintenance strategies for deteriorated low-volume roads
Authors: Hafez Marwan , Ksaibati Khaled , Atadero Rebecca
Published: July 2018

Low-volume roads (LVRs) are restricted with limited maintenance funding due to the recent national economic downturn. Only few selected LVRs with deteriorated pavements are typically rehabilitated in which poor LVRs are expected to continue deteriorating to extreme levels of distress. Colorado Department of Transportation (CDOT) is evaluating pavement treatments on LVRs to find the most cost-effective maintenance strategies. As part of these efforts, a comprehensive optimization analysis is adopted in this paper to investigate alternative maintenance strategies and define the capital improvement plans for deteriorated LVRs with marginal pavement conditions. A proposed strategy was found to enhance the effectiveness of current policies followed by CDOT. However, the results emphasize the need for additional resources at network level for dealing with deteriorated LVRs. The optimization procedure described in this paper can be followed by other agencies nationwide to identify strategies and establish funding needs that secure higher funding from decision makers.
Heritability estimation via molecular pedigree reconstruction in a wild fish population reveals substantial evolutionary potential for sea age at maturity, but not size within age classes
Authors: Reed Thomas E. , Prodöhl Paulo , Bradley Caroline , Gilbey John , McGinnity Philip , Primmer Craig R. , Bacon Philip J.
Published: July 2018

While evolutionary responses require heritable variation, estimates of heritability (h2) from wild fish populations remain rare. A 20-year molecular pedigree for a wild Scottish population of Atlantic salmon (Salmo salar) was used to investigate genetic contributions to (co)variation in two important, correlated, phenotypic traits: “sea age” (number of winters spent at sea prior to spawning) and size-at-maturity (body length just prior to spawning). Sea age was strongly heritable (h2= 0.51) and size exhibited moderate heritability (h2= 0.27). A very strong genetic correlation (rG= 0.96) between these traits implied the same functional loci must underpin variation in each. Indeed, body size within sea ages had much lower heritability that did not differ significantly from zero. Thus, within wild S. salar populations, temporal changes in sea age composition could reflect evolutionary responses, whereas rapid changes of body size within sea ages are more likely due to phenotypic plasticity. These inheritance patterns will influence the scope of evolutionary responses to factors such as harvest or climate change and, hence, have management implications for salmonid populations comprising a mix of sea ages.
Aggregating microsegments into harvest blocks by using spatial optimization and proximity objectives
Authors: Heinonen Tero , Mäkinen Antti , Rasinmäki Jussi , Pukkala Timo
Published: July 2018

This study analyzed the performance of distance-based objective variables as an alternative to adjacency-based variables in spatial optimization when the aim is to aggregate small forest segments into harvest blocks. Distance-based objective variables maximized harvested volume within a certain distance from a harvested segment. Segments that constituted a harvest block did not have to be adjacent. It was hypothesized that it is more profitable to aggregate harvest blocks by using distance-based objective variables instead of adjacency-based objectives. It was also assumed that distance-based objectives result in harvest areas that correspond better to the harvest blocks of forestry practice. Distance-based objectives were tested with four maximum distances of uncut forest between two segments of the same harvest block. The tested distances were 0, 25, 100, and 300 m. A zero distance means that only adjacent segments form harvest blocks. The results showed that distance-based cutting aggregations improved net present value, as compared with adjacency-based cutting aggregation. Distance-based objective variables also resulted in larger harvest block size than adjacency-based objectives, if the maximum allowed distance of uncut forest between two harvested segments of the same harvest block was 25 m or longer and the average removal of a harvest block was 300 m3 or more. Requirement for adjacency led to small and compact harvest blocks.
Pellets derived from Eucalyptus nitens residue: physical, chemical, and thermal characterization for a clean combustion product made in Chile
Authors: Oliveira Patricia E. , Leal Paola , Pichara Cristian
Published: July 2018

As the southernmost country in Latin America, Chile has more than 12 cities on alert for particle pollution. These warnings are issued according to the air quality index, which is partly based on the concentration of coarse and fine particles. Coupled with this, there is also a significant need to use renewable energy for heating. This study describes the production of pellets using Eucalyptus nitens (H. Deane & Maiden) Maiden sawdust for use as a heating fuel. Pinus radiata D. Don was also included to produce the profile that is required for commercial-grade fuel pellets. Finally, we also suggest the use of sodium lignosulfonate as a natural binder to complement the low adhesiveness of the main raw material (E. nitens), as well as enhance the calorific value of the mixture. The results reveal that the different mixtures of eucalyptus and pine were all satisfactory, regardless of their proportions. The pellets made with sodium lignosulfonate proved to have a high calorific value, making them an attractive product; however, the formulations also had a high level of ash content (1.15% to 1.85%), which is close to the limit allowed by international standards.
Accurate study on the properties of spectral lines for Na-like Cr13+
Authors: Singh A.K. , Dimri Mayank , Dawra Dishu , Jha Alok K.S. , Mohan Man
Published: July 2018

An extended calculation of energy levels, radiative rates, and lifetimes are reported for sodium-like chromium. Extensive configuration interaction calculations have been performed using general-purpose relativistic atomic structure package (GRASP). The radiative rates, oscillator strengths, and line strengths are listed for all electric dipole (E1) transitions. However, for magnetic dipole (M1), electric quadrupole (E2), and magnetic quadrupole (M2) transitions, only radiative rates are listed. The importance of valence–valence (VV) and core–valence (CV) correlation effects in the calculation of energy levels have also been shown. To confirm the accuracy of the present results for energy levels by GRASP, independent calculations have been performed by using Flexible Atomic Code (FAC) and configuration interaction method (CIV3). The accuracy of the present levels, wavelengths, transition rates, and lifetimes are assessed by comparing them to available experimental and other theoretical results. We believe that our extensive results may be beneficial in fusion plasma research and astrophysical investigations and applications.