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Cystic fibrosis (CF) is the most common life-threatening inherited condition in the Caucasian population, where mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene result in a multifactorial syndrome, with pulmonary disease representing the largest contributor to morbidity and mortality. Life expectancy has improved and the recent development of disease-modifying CFTR modulator therapies is likely to further improve survival. However, increasing life expectancy brings new challenges related to the complications of a chronic disease including an increasing prevalence of cystic fibrosis related diabetes (CFRD), itself associated with increased morbidity and early mortality. This review provides an update as regards the underlying mechanisms, investigation and management of CFRD., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Hantavirus cardiopulmonary syndrome (HPS) has gained importance in Latin America as an emerging disease, with reports of about 4000 HPS cases; however, this is probably an underestimate because of limited surveillance programs and diagnostic tools to confirm HPS. In order to address this issue and develop better serosurveillance capability, we evaluated three recombinant peptides from the Necoclí virus (NECV) nucleocapsid in antibody-capture ELISA. We cloned and expressed antigens representing the whole NECV nucleocapsid protein (NECV-rN), the immunodominant domain (NECV-rN100), and a serospecific domain (NECV-rN428), and then we compared these antigens in ELISA to detect IgG antibodies to NECV in human sera. We evaluated human sera collected during two epidemiological studies from the area where NECV was discovered. The first group included 609 sera from healthy individuals, and the second one included 89 samples from patients with undifferentiated febrile illness. In these two groups, hantavirus infection had previously been determined by the presence of IgG to Maciel virus (MCLV), a hantavirus closely related to NECV. The number of IgG-positive sera was higher using the Necoclí ELISA with the rN100 protein, which detected antibodies in a higher percentage of healthy individuals, 129/609 (21.2%), as well as in febrile patients, 11/89 (12.3%). In contrast, using MCLV ELISA, 8 of 609 (1.3%) and 4 of 89 (4.5%) samples from healthy and febrile patients, respectively, were seropositive. The agreement between the NECV and MCLV ELISA assays was ≥ 82.3%; however, the kappa indices were weak but statistically significant for rN (0.251 CI; 0.138-0.365) and rN100rN (0.153 CI; 0.084-0.223). The weak kappa indices were attributed to decreased MCLV ELISA assay sensitivity. These results suggest that NECV rN and rN100 have increased specificity and could be further validated for improved diagnosis of hantavirus infections.

Background: Intimate partner violence (IPV) is highly prevalent and associated with physical and mental health problems. Mentor mother support is a low threshold intervention in family practice consisting of support by non-professionals trained to support mothers experiencing IPV. A mentor mother support study showed reduced exposure to IPV and decreased symptoms of depression., Objectives: Identify factors determining implementation success of mentor mother support in family practice., Methods: Individual interviews were conducted with 12 family physicians, 16 abused mothers and three mentor mothers. Four mentor mothers participated in a focus group. Qualitative content analysis was used to analyse the data., Results: The identification and discussion of abuse is hindered by family physicians' attitudes because they considered mothers experiencing IPV as a difficult target group with a responsibility of their own to break out of their violent situation. Some family physicians doubted the partner's violence because he was known as a patient as well. Acceptance of mentor mother support is related to the readiness for change of mothers experiencing IPV. Mentor mothers facilitate acceptance and completion of their support by connecting as a friend who is equal and less threatening than professionals., Conclusion: To improve successful implementation of mentor mother support in primary care, we should focus on family physicians' attitudes towards IPV. To change these attitudes, we recommend continuous training of family physicians. By being paraprofessional friends, mentor mothers offer low threshold support that is complementary to professional support and should be embedded more widely in primary care. [Box: see text].

Background and Purpose: The Beagley-Gibson (BG) grading system utilizes microtopographical skin changes to generate an individualized, objective estimate of cumulative, lifetime ultraviolet radiation (UVR) exposure. However, predictors of BG grade are ill-defined, particularly in older populations. The aim of this cross-sectional study was to describe the factors associated with skin damage as measured by the BG method in 835 community-dwelling older adults., Methods: Study participants aged 53-83 years had silicone casts taken from the dorsum of both hands and graded by the BG method. Lifetime sun exposure, skin phenotypic traits and smoking status were assessed by questionnaire. 25-hydroxyvitamin D and melanin density were measured using radioimmunoassay and spectrophotometry, respectively. Ordered logistic regression was used to compute a single odds ratio (OR) by taking BG grade as the outcome variable., Results: Higher 25-hydroxyvitamin D was associated with increasing BG grade (OR = 1.39, P = 0.02) in adjusted analysis. Age (OR = 1.14, P < 0.001), occupational sun exposure (OR = 1.62, P < 0.001), ability to tan (OR = 1.40, P < 0.001), melanin density (OR=0.79, P = 0.001), lifetime leisure time sun exposure (OR = 1.21, P = 0.004), current smoking (OR = 1.82, P = 0.007), propensity to sunburn (OR = 1.18, P = 0.016), and waist-hip ratio (OR = 1.10, P = 0.02) were independent predictors of BG grade. Hair colour, number of sunburns, body mass index and gender were not independent predictors of BG grade., Conclusions: Beagley-Gibson skin cast grade is a biologically relevant marker of UVR exposure in older adults influenced by both intrinsic and extrinsic factors., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: In addition to technical expertise, surgical competence requires effective non-technical skills to ensure patient safety and maintenance of standards. Recently the Royal Australasian College of Surgeons implemented a new Surgical Education and Training (SET) curriculum that incorporated non-technical skills considered essential for a competent surgeon. This study sought to compare the non-technical skills of experienced surgeons who completed their training before the introduction of SET with the non-technical skills of more recent trainees., Methods: Surgical trainees and experienced surgeons undertook a simulated scenario designed to challenge their non-technical skills. Scenarios were video recorded and participants were assessed using the Non-Technical Skills for Surgeons (NOTSS) scoring system. Participants were divided into subgroups according to years of experience and their NOTSS scores were compared., Results: For most NOTSS elements, mean scores increased initially, peaking around the time of Fellowship, before decreasing roughly linearly over time. There was a significant downward trend in score with increasing years since being awarded Fellowship for six of the 12 NOTSS elements: considering options (score -0·015 units per year), implementing and reviewing decisions (-0·020 per year), establishing a shared understanding (-0·014 per year), setting and maintaining standards (-0·024 per year), supporting others (-0·031 per year) and coping with pressure (-0·015 per year)., Conclusion: The drop in NOTSS score was unexpected and highlights that even experienced surgeons are not immune to deficiencies in non-technical skills. Consideration should be given to continuing professional development programmes focusing on non-technical skills, regardless of the level of professional experience., (© 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Objectives: To evaluate detectability and quantification of coronary calcifications for CT with a tin filter for spectral shaping., Methods: Phantom inserts with 100 small and 9 large calcifications, and a moving artificial artery with 3 calcifications (speed 0-30 mm/s) were placed in a thorax phantom simulating different patient sizes. The phantom was scanned in high-pitch spiral mode at 100 kVp with tin filter (Sn100 kVp), and at a reference of 120 kVp, with electrocardiographic (ECG) gating. Detectability and quantification of calcifications were analyzed for standard (130 HU) and adapted thresholds., Results: Sn100 kVp yielded lower detectability of calcifications (9 % versus 12 %, p = 0.027) and lower Agatston scores (p < 0.008), irrespective of calcification, patient size and speed. Volume scores of the moving calcifications for Sn100 kVp at speed 10-30 mm/s were lower (p < 0.001), while mass scores were similar (p = 0.131). For Sn100 kVp with adapted threshold of 117 HU, detectability (p = 1.000) and Agatston score (p > 0.206) were similar to 120 kVp. Spectral shaping resulted in median dose reduction of 62.3 % (range 59.0-73.4 %)., Conclusions: Coronary calcium scanning with spectral shaping yields lower detectability of calcifications and lower Agatston scores compared to 120 kVp scanning, for which a HU threshold correction should be developed., Key Points: • Sn100kVp yields lower detectability and lower Agatston scores compared to 120kVp • Adapted HU threshold for Sn100kVp provides Agatston scores comparable to 120kVp • Sn100 kVp considerably reduces dose in calcium scoring versus 120 kVp.

The Tec tyrosine kinase is expressed in many cell types, including hematopoietic cells, and is a member of the Tec kinase family that also includes Btk. Although the role of Btk in B cells has been extensively studied, the role of Tec kinase in B cells remains largely unclear. It was previously shown that Tec kinase has the ability to partly compensate for loss of Btk activity in B cell differentiation, although the underlying mechanism is unknown. In this study, we confirm that Tec kinase is not essential for normal B cell development when Btk is present, but we also found that Tec-deficient mature B cells showed increased activation, proliferation, and survival upon BCR stimulation, even in the presence of Btk. Whereas Tec deficiency did not affect phosphorylation of phospholipase Cγ or Ca 2+ influx, it was associated with significantly increased activation of the intracellular Akt/S6 kinase signaling pathway upon BCR and CD40 stimulation. The increased S6 kinase phosphorylation in Tec-deficient B cells was dependent on Btk kinase activity, as ibrutinib treatment restored pS6 to wild-type levels, although Btk protein and phosphorylation levels were comparable to controls. In Tec-deficient mice in vivo, B cell responses to model Ags and humoral immunity upon influenza infection were enhanced. Moreover, aged mice lacking Tec kinase developed a mild autoimmune phenotype. Taken together, these data indicate that in mature B cells, Tec and Btk may compete for activation of the Akt signaling pathway, whereby the activating capacity of Btk is limited by the presence of Tec kinase., (Copyright © 2017 by The American Association of Immunologists, Inc.)

Background: Between 1991 and 2008, approximately 80 cases of fracture (neck or stem) have been reported. This study aimed at determining factors predisposing to implant fracture., Methods: Clinical, surgical, radiological, and retrieval data were collated. Risk factors associated with fracture were categorized to patient related (weight and activity levels), surgical related (poor medial support, component size, and placement), and anatomic/implant related (head size/offset)., Results: Data was available on 60 patients (32 stem and 28 neck fractures). Mean patient age at fracture was similar for both neck and stem fractures (69 years, 67 years, respectively). Also, 77% neck and 52% stem fractures occurred in men. Mean weight was 107 kg in neck and 96.5 kg in stem fractures with 68% neck and 38% stem fractures either obese or morbidly obese. Mean time to fracture was 78 months (range, 36-144 months) for neck and 76 months (range, 2-155 months) for stem fractures. 44#2 and 44#3 were the most common sizes associated with neck fractures. Stem fractures occurred more commonly (84%) in the smaller sizes (35.5 to 44#1). Elongated femoral heads were used in 69% neck and 14% stem fractures., Conclusion: Neck fractures were most commonly associated with patient-related (increased weight and activity) and implant-related (use of an elongated femoral head) factors. Stem fractures were most commonly associated with correctable surgical-related causes, predominantly secondary to stem undersizing or inadequate medial support (84%)., (Copyright © 2016 Elsevier Inc. All rights reserved.)

To date urinary metabolic profiling has been applied to define a specific metabolic fingerprint of hepatocellular carcinoma on a background of cirrhosis. Its utility for the stratification of other complications of cirrhosis, such as hepatic encephalopathy (HE), remains to be established. Urinary proton nuclear magnetic resonance ( 1 H-NMR) spectra were acquired and NMR data from 52 patients with cirrhosis (35 male; 17 female, median (range) age [60 (18-81) years]) and 17 controls were compared. A sub-set of 45 patients (33 male; 12 female, [60 (18-90) years, median model for end stage liver disease (MELD) score 11 (7-27)]) were fully characterised by West-Haven criteria, Psychometric Hepatic Encephalopathy Score (PHES) and electroencephalogram (EEG), and defined as overt HE (OHE, n = 21), covert HE (cHE, n = 7) or no HE (n = 17). Urinary proton nuclear magnetic resonance ( 1 H-NMR) spectra were analysed by partial-least-squares discriminant analysis (PLS-DA). The results showed good discrimination between patients with cirrhosis (n = 52) and healthy controls (n = 17) (R2X = 0.66, R2Y = 0.47, Q2Y = 0.31, sensitivity-60 %, specificity-100 %) as the cirrhosis group had higher 1-methylnicotinamide with lower hippurate, acetate, phenylacetylglycine and N-methyl nicotinic acid levels. While patients with OHE could be discriminated from those with no HE, with higher histidine, citrate and creatinine levels, the best models lack robust validity (R2X = 0.65, R2Y = 0.48, Q2Y = 0.12, sensitivity-100 %, specificity-64 %) with the sample size used. Urinary 1 H-NMR metabolic profiling did not discriminate patients with cHE from those without HE, nor discriminate subjects on the basis of PHES/EEG result or MELD score. In conclusion, patients with cirrhosis showed different urinary 1 H-NMR metabolic profiles compared to healthy controls and those with OHE may be distinguished from those with no HE although larger studies are required. However, urinary 1 H-NMR metabolic profiling did not discriminate patients with differing grades of HE or according to severity of underlying liver disease.

Background: Human natural killer (NK) cell activity is regulated by a family of killer cell immunoglobulin-like receptors (KIRs) that bind human leukocyte antigen (HLA) class I. Combinations of KIR and HLA genotypes are associated with disease, including susceptibility to viral infection and disorders of pregnancy. KIR2DL1 binds HLA-C alleles of group C2 (Lys 80 ). KIR2DL2 and KIR2DL3 bind HLA-C alleles of group C1 (Asn 80 ). However, this model cannot explain HLA-C allelic effects in disease or the impact of HLA-bound peptides. The goal of this study was to determine the extent to which the endogenous HLA-C peptide repertoire can influence the specific binding of inhibitory KIR to HLA-C allotypes., Results: The impact of HLA-C bound peptide on inhibitory KIR binding was investigated taking advantage of the fact that HLA-C*05:01 (HLA-C group 2, C2) and HLA-C*08:02 (HLA-C group 1, C1) have identical sequences apart from the key KIR specificity determining epitope at residues 77 and 80. Endogenous peptides were eluted from HLA-C*05:01 and used to test the peptide dependence of KIR2DL1 and KIR2DL2/3 binding to HLA-C*05:01 and HLA-C*08:02 and subsequent impact on NK cell function. Specific binding of KIR2DL1 to the C2 allotype occurred with the majority of peptides tested. In contrast, KIR2DL2/3 binding to the C1 allotype occurred with only a subset of peptides. Cross-reactive binding of KIR2DL2/3 with the C2 allotype was restricted to even fewer peptides. Unexpectedly, two peptides promoted binding of the C2 allotype-specific KIR2DL1 to the C1 allotype. We showed that presentation of endogenous peptides or HIV Gag peptides by HLA-C can promote KIR cross-reactive binding., Conclusion: KIR2DL2/3 binding to C1 is more peptide selective than that of KIR2DL1 binding to C2, providing an explanation for KIR2DL3-C1 interactions appearing weaker than KIR2DL1-C2. In addition, cross-reactive binding of KIR is characterized by even higher peptide selectivity. We demonstrate a hierarchy of functional peptide selectivity of KIR-HLA-C interactions with relevance to NK cell biology and human disease associations. This selective peptide sequence-driven binding of KIR provides a potential mechanism for pathogen as well as self-peptide to modulate NK cell activation through altering levels of inhibition.

Objectives: International guidelines recommend revascularisation as the preferred treatment for patients with critical limb ischaemia (CLI). Most contemporary research focuses on the outcome of invasive procedures for CLI, but little is known about the outcome of conservative management. Amputation free survival (AFS) and overall survival (OS) was investigated in patients with CLI who did or did not receive revascularisation, and characteristics associated with clinical outcomes were explored., Methods: This was a retrospective cohort study of consecutive patients with chronic CLI between 2010 and 2014 in a Dutch university hospital. CLI was defined as the presence of ischaemic rest pain or tissue loss in conjunction with an absolute systolic ankle pressure < 50 mmHg or a toe pressure < 30 mmHg. Patients were divided into invasive (revascularisation within 6 weeks), deferred invasive (revascularisation after 6 weeks), or permanently conservative treatment groups. Univariable and multivariable survival analyses were used to identify factors associated with AFS and OS., Results: The majority (66.7%; N = 96) of the identified 144 patients with CLI (mean age 71.2 years; median follow-up 99 weeks) underwent revascularisation within 6 weeks of diagnosis. Deferred invasive treatment was provided in 18.1% (N = 26) patients and 22 patients (15.3%) were treated permanently conservatively. AFS and OS did not differ significantly between the three groups (Breslow-Wilcoxon p = .16 for AFS and p = .09 for OS). Age, chronic obstructive pulmonary disease (COPD), and heart disease were significant independent predictors of AFS. Age, COPD, and hypertension were significant independent predictors of OS. Treatment was not a significant predictor of either AFS or OS., Conclusions: Not all patients with CLI require revascularisation to achieve an AFS that is similar to patients undergoing revascularisation, although the efficacy of conservative versus invasive treatment in CLI patients is still unclear. Further prospective studies should determine subgroups of patients in whom revascularisation may be omitted., (Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Objective: Population studies have shown coronary calcium score to improve risk stratification in subjects suspected for cardiovascular disease. The aim of this work was to assess the validity of multidetector computed tomography (MDCT) for measurement of calibrated mass scores (MS) in a phantom study, and to investigate inter-scanner variability for MS and Agaston score (AS) recorded in a population study on two different high-end MDCT scanners., Materials and Methods: A calcium phantom was scanned by a first (A) and second (B) generation 320-MDCT. MS was measured for each calcium deposit from repeated measurements in each scanner and compared to known physical phantom mass. Random samples of human subjects from the Copenhagen General Population Study were scanned with scanner A (N=254) and scanner B (N=253) where MS and AS distributions of these two groups were compared., Results: The mean total MS of the phantom was 32.9±0.8mg and 33.1±0.9mg (p=0.43) assessed by scanner A and B respectively - the physical calcium mass was 34.0mg. Correlation between measured MS and physical calcium mass was R 2 =0.99 in both scanners. In the population study the median total MS was 16.8mg (interquartile range (IQR): 3.5-81.1) and 15.8mg (IQR: 3.8-63.4) in scanner A and B (p=0.88). The corresponding median total AS were 92 (IQR: 23-471) and 89 (IQR: 40-384) (p=0.64)., Conclusion: Calibrated calcium mass score may be assessed with very high accuracy in a calcium phantom by different generations of 320-MDCT scanners. In population studies, it appears acceptable to pool calcium scores acquired on different 320-MDCT scanners., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Although commonly used to measure health related quality of life in patients with lower limb ischaemia, the measurement properties of the VascuQol and its assumed underlying health dimensions have not been studied in depth. The objective of this study was therefore to evaluate aspects of reliability and validity of the Dutch version of the VascuQol in patients with intermittent claudication (IC) and critical limb ischaemia (CLI)., Methods: Two datasets containing 195 patients with IC and 150 patients with CLI were used. Face validity of the VascuQol was examined in interviews with patients and a survey among health professionals. Homogeneity and structural validity of the VascuQol were assessed using Cronbach's α coefficients and explanatory factor analysis. Furthermore, convergent validity and known group validity were assessed., Results: During the face validity interviews, three items were indicated as less relevant. Homogeneity analysis showed that the α coefficient of the VascuQol was .93, while the symptoms and social domains had α coefficients below the threshold of .70. The original five domains of the VascuQol could not be reproduced. Instead, factor analysis yielded a three factor solution. Moderate correlations were found for the activities, social and emotional VascuQol domains and matching health domains of other patient reported outcome measures (PROMs). Lower convergent correlations were observed for the pain domain and the sumscore of the VascuQol. The VascuQol was able to distinguish between patients' level of HRQL in relation to their disease severity (IC versus CLI patients)., Conclusions: There is room for improvement of the VascuQol questionnaire. Further clinimetric studies should be performed to strengthen clinically relevant findings based on this instrument., (Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

A targeted reversed-phase gradient UPLC-MS/MS assay has been developed for the quantification /monitoring of 66 amino acids and amino-containing compounds in human plasma and serum using precolumn derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AccQTag Ultra). Derivatization of the target amines required minimal sample preparation and resulted in analytes with excellent chromatographic and mass spectrometric detection properties. The resulting method, which requires only 10 μL of sample, provides the reproducible and robust separation of 66 analytes in 7.5 min, including baseline resolution of isomers such as leucine and isoleucine. The assay has been validated for the quantification of 33 amino compounds (predominantly amino acids) over a concentration range from 2 to 20 and 800 μM. Intra- and interday accuracy of between 0.05 and 15.6 and 0.78-13.7% and precision between 0.91 and 16.9% and 2.12-15.9% were obtained. A further 33 biogenic amines can be monitored in samples for relative changes in concentration rather than quantification. Application of the assay to samples derived from healthy controls and patients suffering from acetaminophen (APAP, paracetamol)-induced acute liver failure (ALF) showed significant differences in the amounts of aromatic and branched chain amino acids between the groups as well as a number of other analytes, including the novel observation of increased concentrations of sarcosine in ALF patients. The properties of the developed assay, including short analysis time, make it suitable for high-throughput targeted UPLC-ESI-MS/MS metabonomic analysis in clinical and epidemiological environments.

Endosomolytic peptides are often coupled to drug delivery systems to enhance endosomal escape, which is crucial for the delivery of macromolecular drugs that are vulnerable to degradation in the endolysosomal pathway. Melittin is a 26 amino acid peptide derived from bee venom that has a very high membranolytic activity. However, such lytic peptides also impose a significant safety risk when applied in vivo as they often have similar activity against red blood cells and other nontarget cell membranes. Our aim is to control the membrane-disrupting capacity of these peptides in time and space by physically constraining them to a nanocarrier surface in such a way that they only become activated when delivered inside acidic endosomes. To this end, a variety of chemical approaches for the coupling of lytic peptides to liposomes via functionalized PEG-lipids were explored, including maleimide-thiol chemistry, click-chemistry, and aldehyde-hydrazide chemistry. The latter enables reversible conjugation via a hydrazone bond, allowing for release of the peptide under endosomal conditions. By carefully choosing the conjugation site and by using a pH activated analog of the melittin peptide, lytic activity toward a model membrane is completely inhibited at physiological pH. At endosomal pH the activity is restored by hydrolysis of the acid-labile hydrazone bond, releasing the peptide in its most active, free form. Furthermore, using an analogue containing a nonhydrolyzable bond as a control, it was shown that the activity observed can be completely attributed to release of the peptide, validating dynamic covalent conjugation as a suitable strategy to maintain safety during circulation.

Cell-penetrating peptides (CPPs) enhance the cellular uptake of membrane-impermeable molecules. Most CPPs are highly cationic, potentially increasing the risk of toxic side effects and leading to accumulation in organs such as the liver. As a consequence, there is an unmet need for less cationic CPPs. However, design principles for effective CPPs are still missing. Here, we demonstrate a design principle based on a classification of peptides according to accumulated side-chain polarity and hydrophobicity. We show that in comparison to randomly selected peptides, CPPs cover a distinct parameter space. We designed peptides of only six to nine amino acids with a maximum of three positive charges covering this property space. All peptides were tested for cellular uptake and subcellular distribution. Following an initial round of screening we enriched the collection with short and hydrophobic peptides and introduced d-amino acid substitutions and lactam bridges which increased cell uptake, in particular for long-term incubation. Using a GFP complementation assay, for the most active peptides we demonstrate cytosolic delivery of a biologically active cargo peptide.

Objectives: Shared decision-making (SDM) has been advocated as the preferred method of choosing a suitable treatment option. However, patient involvement in treatment decision-making is not yet common practice in the field of vascular surgery. The aim of this mixed-methods study was to explore patients' decision-making preferences and to investigate which facilitators and barriers patients perceive as important for the application of SDM in vascular surgery., Design and Setting: Patients were invited to participate after visiting the vascular surgical outpatient clinic of an Academic Medical Center in the Netherlands. A treatment decision was made during the consultation for an abdominal aortic aneurysm or peripheral arterial occlusive disease. Patients filled in a number of questionnaires (quantitative part) and a random subgroup of patients participated in an in-depth interview (qualitative part)., Results: A total of 67 patients participated in this study. 58 per cent of them (n=39) indicated that they preferred a shared role in decision-making. In more than half of the patients (55%; n=37) their preferred role was in disagreement with what they had experienced. 31 per cent of the patients (n=21) preferred a more active role in the decision-making process than they had experienced. Patients indicated a good patient-doctor relationship as an important facilitator for the application of SDM., Conclusions: The vast majority of vascular surgical patients preferred, but did not experience a shared role in the decision-making process, although the concept of SDM was insufficiently clear to some patients. This emphasises the importance of explaining the concept of SDM and implementing it in the clinical encounter., Competing Interests: Conflicts of Interest: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Sepsis-associated acute kidney injury is a multifactorial syndrome in which inflammation and renal microcirculatory dysfunction play a profound role. Subsequently, renal tubule mitochondria reprioritize cellular functions to prevent further damage. Here, we investigated the putative protective effects of human recombinant alkaline phosphatase (recAP) during inhibition of mitochondrial respiration in conditionally immortalized human proximal tubule epithelial cells (ciPTEC). Full inhibition of mitochondrial oxygen consumption was obtained after 24h antimycin A treatment, which did not affect cell viability. While recAP did not affect the antimycin A-induced decreased oxygen consumption and increased hypoxia-inducible factor-1α or adrenomedullin gene expression levels, the antimycin A-induced increase of pro-inflammatory cytokines IL-6 and IL-8 was attenuated. Antimycin A tended to induce the release of detrimental purines ATP and ADP, which reached statistical significance when antimycin A was co-incubated with lipopolysaccharide, and were completely converted into cytoprotective adenosine by recAP. As the adenosine A 2A receptor was up-regulated after antimycin A exposure, an adenosine A 2A receptor knockout ciPTEC cell line was generated in which recAP still provided protection. Together, recAP did not affect oxygen consumption but attenuated the inflammatory response during impaired mitochondrial function, an effect suggested to be mediated by dephosphorylating ATP and ADP into adenosine., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In the military or emergency services, operational requirements and/or community expectations often preclude formal prescriptive working time arrangements as a practical means of reducing fatigue-related risk. In these environments, workers sometimes employ adaptive or protective behaviours informally to reduce the risk (i.e. likelihood or consequence) associated with a fatigue-related error. These informal behaviours enable employees to reduce risk while continuing to work while fatigued. In this study, we documented the use of informal protective behaviours in a group of defence aviation personnel including flight crews. Semi-structured interviews were conducted to determine whether and which protective behaviours were used to mitigate fatigue-related error. The 18 participants were from aviation-specific trades and included aircrew (pilots and air-crewman) and aviation maintenance personnel (aeronautical engineers and maintenance personnel). Participants identified 147 ways in which they and/or others act to reduce the likelihood or consequence of a fatigue-related error. These formed seven categories of fatigue-reduction strategies. The two most novel categories are discussed in this paper: task-related and behaviour-based strategies. Broadly speaking, these results indicate that fatigued military flight and maintenance crews use protective 'fatigue-proofing' behaviours to reduce the likelihood and/or consequence of fatigue-related error and were aware of the potential benefits. It is also important to note that these behaviours are not typically part of the formal safety management system. Rather, they have evolved spontaneously as part of the culture around protecting team performance under adverse operating conditions. When compared with previous similar studies, aviation personnel were more readily able to understand the idea of fatigue proofing than those from a fire-fighting background. These differences were thought to reflect different cultural attitudes toward error and formal training using principles of Crew Resource Management and Threat and Error Management., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The presence of overt hepatic encephalopathy (HE) is associated with structural, metabolic and functional changes in the brain discernible by use of a variety of magnetic resonance (MR) techniques. The changes in patients with minimal HE are less well documented. Twenty-two patients with well-compensated cirrhosis, seven of whom had minimal HE, were examined with cerebral 3 Tesla MR techniques, including T 1 - and T 2 -weighted, magnetization transfer and diffusion-weighted imaging and proton magnetic resonance spectroscopy sequences. Studies were repeated after a 4-week course of oral L-ornithine L-aspartate (LOLA). Results were compared with data obtained from 22 aged-matched healthy controls. There was no difference in mean total brain volume between patients and controls at baseline. Mean cerebral magnetization transfer ratios were significantly reduced in the globus pallidus and thalamus in the patients with cirrhosis irrespective of neuropsychiatric status; the mean ratio was significantly reduced in the frontal white matter in patients with minimal HE compared with healthy controls but not when compared with their unimpaired counterparts. There were no significant differences in either the median apparent diffusion coefficients or the mean fractional anisotropy, calculated from the diffusion-weighted imaging, or in the mean basal ganglia metabolite ratios between patients and controls. Psychometric performance improved in 50 % of patients with minimal HE following LOLA, but no significant changes were observed in brain volumes, cerebral magnetization transfer ratios, the diffusion weighted imaging variables or the cerebral metabolite ratios. MR variables, as applied in this study, do not identify patients with minimal HE, nor do they reflect changes in psychometric performance following LOLA.

Background: The profound hemodynamic changes seen in acute liver failure (ALF) resemble the hyperdynamic state found in the later stages of septic shock. Vasopressor support frequently is required after initial volume therapy. Markers of preload dependency have not been studied in this patient group. Dynamic maneuvers such as passive leg raising or end-expiratory hold, which have shown good predictive accuracy in a general intensive care unit population, cannot be considered safe in this cohort because of the concerns of intracranial hypertension., Methods: Mechanically ventilated patients with ALF admitted to a tertiary specialist intensive care unit in shock and multiorgan failure were enrolled. Markers of fluid responsiveness derived from transpulmonary thermodilution, pulse contour analysis, and echocardiography were compared between responders (cardiac index ≥15%) and nonresponders to a colloid fluid challenge (5 mL/kg predicted body weight). The ability to predict fluid responsiveness of stroke volume variation, pulse pressure variation (PPV), and respiratory change in peak (delta V peak) left ventricular outflow tract velocity for preload dependency were analyzed., Results: Thirty-five patients (mean ± SD age, 38 [14] years, 13 male, 22 female]) were assessed after a single fluid challenge. Ten patients (29%) were fluid responders. Changes in cardiac index and stroke volume index in the cohort of 35 patients were correlated (R = 0.726 [99% confidence interval, 0.401-0.910]; P < .001). PPV predicted fluid responsiveness (area under the receiver operating characteristic curve [AUROC], 0.752 [95% confidence interval, 0.565-0.889]; P = .005; cutoff >9%). The AUROC for stroke volume variation was 0.678 ([95% confidence interval, 0.499-0.825]; P = .084; cutoff >11%). The AUROC for [delta] V peak before fluid bolus was 0.637 (95% confidence interval, 0.413-0.825; P = .322)., Conclusions: PPV based on pulse contour analysis predicted fluid responsiveness in ALF.

Aims: We present the clinical and radiological results at a minimum follow-up of five years for patients who have undergone multiple cement-in-cement revisions of their femoral component at revision total hip arthroplasty (THA)., Patients and Methods: We reviewed the outcome on a consecutive series of 24 patients (10 men, 14 women) (51 procedures) who underwent more than one cement-in-cement revision of the same femoral component. The mean age of the patients was 67.5 years (36 to 92) at final follow-up. Function was assessed using the original Harris hip score (HHS), Oxford Hip Score (OHS) and the Merle D'Aubigné Postel score (MDP)., Results: The mean length of follow-up was 81.7 months (64 to 240). A total of 41 isolated acetabular revisions were performed in which stem removal facilitated access to the acetabulum, six revisions were conducted for loosening of both components and two were isolated stem revisions (each of these patients had undergone at least two revisions). There was significant improvement in the OHS (p = 0.041), HHS (p = 0.019) and MDP (p = 0.042) scores at final follow-up There were no stem revisions for aseptic loosening. Survival of the femoral component was 91.9% (95% confidence intervals (CI) 71.5 to 97.9) at five years and 91.7% (95% CI 70 to 97) at ten years (number at risk 13), with stem revision for all causes as the endpoint., Conclusion: Cement-in-cement revision is a viable technique for performing multiple revisions of the well cemented femoral component during revision total hip arthroplasty at a minimum of five years follow-up. Cite this article: Bone Joint J 2017;99-B:199-203., (©2017 The British Editorial Society of Bone & Joint Surgery.)

Partial life histories from Kenya or Tanzania are presented for Metisella midas midas (Butler), M. medea medea Evans, M. orientalis orientalis Aurivillius, M. quadrisignatus nanda Evans, M. congdoni De Jong & Kielland and M. willemi Wallengren. The ovum of Metisella formosus linda Evans is also illustrated from Zambia. All feed on species of grasses (Poaceae). The convergence of the biology of the grass-feeding skippers, particularly Heteropterinae and Hesperiinae, Baorini is discussed.

We report the discovery of two new invariants for three-qubit states which, similarly to the three-tangle, are invariant under local unitary transformations and permutations of the parties. These quantities have a direct interpretation in terms of the anisotropy of pairwise spin correlations. Applications include a universal ordering of pairwise quantum correlation measures for pure three-qubit states; trade-off relations for anisotropy, three-tangle and Bell nonlocality; strong monogamy relations for Bell inequalities, Einstein-Podolsky-Rosen steering inequalities, geometric discord and fidelity of remote state preparation (including results for arbitrary three-party states); and a statistical and reference-frame-independent form of quantum secret sharing.

Introduction: This case study reports a range of physiological characteristics in a two-time Tour de France champion., Methods: After body composition assessment (dual-energy x-ray absorptiometry), two submaximal cycling step tests were performed in ambient (20°C, 40%) and hot and humid (30°C, 60% [HH]) conditions from which measures of gross efficiency (GE), lactate-power landmarks, and heart rate responses were calculated. In addition, thermoregulatory and sweat responses were collected throughout. V˙O2peak and peak power output (PPO) were also identified after a separate ramp test to exhaustion., Results: V˙O2peak and PPO were 5.91 L·min (84 mL·kg·min) and 525 W, respectively, whereas mean GE values were 23.0% and 23.6% for ambient and HH conditions, respectively. In addition to superior GE, power output at 4 mmol·L lactate was higher in HH versus ambient conditions (429.6 vs 419.0 W) supporting anecdotal reports from the participant of good performance in the heat. Peak core and skin temperature, sweat rate, and electrolyte content were higher in HH conditions. Body fat percentage was 9.5%, whereas total fat mass, lean mass, and bone mineral content were 6.7, 61.5, and 2.8 kg, respectively., Conclusion: The aerobic physiology and PPO values indentified are among the highest reported for professional road cyclists. Notably, the participant displayed both a high V˙O2peak and GE, which is uncommon among elite cyclists and may be a contributing factor to their success in elite cycling. In addition, performance in HH conditions was strong, suggesting effective thermoregulatory physiology. In summary, this is the first study to report physiological characteristics of a multiple Tour de France champion in close to peak condition and suggests what may be the prerequisite physiological and thermoregulatory capacities for success at this level.

The CRISPR-Cas9 gene editing system has taken the biomedical science field by storm, initiating rumors about future Nobel Prizes and heating up a fierce patent war, but also making significant scientific impact. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), together with CRISPR-associated proteins (Cas) are a part of the prokaryotic adaptive immune system and have successfully been repurposed for genome editing in mammalian cells. The CRISPR-Cas9 system has been used to correct genetic mutations and for replacing entire genes, opening up a world of possibilities for the treatment of genetic diseases. In addition, recently some new CRISPR-Cas systems have been discovered with interesting mechanistic variations. Despite these promising developments, many challenges have to be overcome before the system can be applied therapeutically in human patients and enabling delivery technology is one of the key challenges. Furthermore, the relatively high off-target effect of the system in its current form prevents it from being safely applied directly in the human body. In this review, the transformation of the CRISPR-Cas gene editing systems into a therapeutic modality will be discussed and the currently most realistic in vivo applications will be highlighted., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Allergic disease originates in early life and polymorphisms in interleukin-33 gene (IL33) and IL1RL1, coding for IL-33R and decoy receptor sST2, confer allergy risk. Early life T helper 2 (Th2) cell skewing and allergy susceptibility are often seen as remnants of feto-maternal symbiosis. Here we report that shortly after birth, innate lymphoid type 2 cells (ILC2s), eosinophils, basophils, and mast cells spontaneously accumulated in developing lungs in an IL-33-dependent manner. During the phase of postnatal lung alveolarization, house dust mite exposure further increased IL-33, which boosted cytokine production in ILC2s and activated CD11b + dendritic cells (DCs). IL-33 suppressed IL-12p35 and induced OX40L in neonatal DCs, thus promoting Th2 cell skewing. Decoy sST2 had a strong preventive effect on asthma in the neonatal period, less so in adulthood. Thus, enhanced neonatal Th2 cell skewing to inhaled allergens results from postnatal hyperactivity of the IL-33 axis during a period of maximal lung remodeling., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The goal of the present study was to examine whether frontal alpha asymmetry and delta-beta cross-frequency correlation during resting state, anticipation, and recovery are electroencephalographic (EEG) measures of social anxiety. For the first time, we jointly examined frontal alpha asymmetry and delta-beta correlation during resting state and during a social performance task in high (HSA) versus low (LSA) socially anxious females. Participants performed a social performance task in which they first watched and evaluated a video of a peer, and then prepared their own speech. They believed that their speech would be videotaped and evaluated by a peer. We found that HSA participants showed significant negative delta-beta correlation as compared to LSA participants during both anticipation of and recovery from the stressful social situation. This negative delta-beta correlation might reflect increased activity in subcortical brain regions and decreased activity in cortical brain regions. As we hypothesized, no group differences in delta-beta correlation were found during the resting state. This could indicate that a certain level of stress is needed to find EEG measures of social anxiety. As for frontal alpha asymmetry, we did not find any group differences. The present frontal alpha asymmetry results are discussed in relation to the evident inconsistencies in the frontal alpha asymmetry literature. Together, our results suggest that delta-beta correlation is a putative EEG measure of social anxiety.

Background Low-literate patients are at risk to misinterpret written drug information. For the (co-) design of targeted patient information, it is key to involve this group in determining their communication barriers and information needs. Objective To gain insight into how people with low literacy use and evaluate written drug information, and to identify ways in which they feel the patient leaflet can be improved, and in particular how images could be used. Setting Food banks and an education institution for Dutch language training in the Netherlands. Method Semi-structured focus groups and individual interviews were held with low-literate participants (n = 45). The thematic framework approach was used for analysis to identify themes in the data. Main outcome measure Low-literate people's experience with patient information leaflets, ideas for improvements, and perceptions on possible uses for visuals. Results Patient information leaflets were considered discouraging to use, and information difficult to find and understand. Many rely on alternative information sources. The leaflet should be shorter, and improved in terms of organisation, legibility and readability. Participants thought images could increase the leaflet's appeal, help ask questions, provide an overview, help understand textual information, aid recall, reassure, and even lead to increased confidence, empowerment and feeling of safety. Conclusion Already at the stages of paying attention to the leaflet and maintaining interest in the message, low-literate patients experience barriers in the communication process through written drug information. Short, structured, visual/textual explanations can lower the motivational threshold to use the leaflet, improve understanding, and empower the low-literate target group., Competing Interests: All authors declare that they have no conflict of interest.

Background: Patients with peripheral artery disease (PAD) are at increased risk of secondary events, which is exaggerated in the presence of type 2 diabetes mellitus. Diabetes is associated with a systemic pro-inflammatory state. We therefore investigated the cumulative impact of PAD and type 2 diabetes on carotid arterial wall inflammation. As recent data suggest a detrimental role of exogenous insulin on cardiovascular disease, we also included a group of insulin users., Results: 18 F-fluorodeoxyglucose positron emission tomography with computed tomography ( 18 F-FDG PET/CT) imaging showed increased carotid arterial wall inflammation, assessed as target-to-background ratio (TBR), in PAD patients without diabetes (PAD-only: n = 11, 1.97 ± 0.57) compared with matched controls (n = 12, 1.49 ± 0.57; p = 0.009), with a significant further TBR increase in PAD patients with type 2 diabetes (PAD-DM, n = 23, 2.90 ± 1, p = 0.033 vs PAD-only). TBR of insulin users (n = 12, 3.31 ± 1.14) was higher compared with patients on oral medication only (n = 11, 2.44 ± 0.76, p = 0.035), despite comparable PAD severity (Fontaine stages), BMI and CRP. Multivariate regression analysis showed that Hba1c and plasma insulin levels, but not dose of exogenous insulin, correlated with TBR., Conclusions: Concurrent diabetes significantly augments carotid arterial wall inflammation in PAD patients. A further increase in those requiring insulin was observed, which was associated with diabetes severity, rather than with the use of exogenous insulin itself.

Background: Dislocation following primary total hip arthroplasty (THA) is a complication with an incidence of 2%-5%. This study examines the clinical and radiological outcome of a constrained acetabular implant used in primary THA in high-risk patients to prevent dislocation., Methods: 54 patients with 55 constrained implants for primary THA were reviewed clinically and radiologically. Oxford, Harris Hip and Charlson scores were recorded., Results: 54 patients, with an average age of 83.2 years, were followed up at a mean of 44.9 (20-74) months. 38 had an hydroxyapatite- (HA) coated acetabular shell with a constrained insert and 17 had a cemented constrained implant. The median Charlson score at surgery was 5 (4-10). There were significant improvements in Oxford, Harris hip pain and function scores and Charnley pain after surgery.2 patients had radiolucent lines on the most recent radiograph. Neither was symptomatic and the acetabular components had not migrated.3 patients developed postoperative infection, 1 deep requiring a 2-stage revision.Of the 29 patients who died, 1 required revision 2 months following surgery for dislocation of the constrained liner. This patient died 26 months later from unrelated causes having had no further complications from her surgery. There have been no further revisions or reoperations for dislocation in any of the other cases., Conclusions: The use of a constrained acetabular liner at primary THA in high risk patients for dislocation can successfully prevent this complication without increasing component loosening. In this series of 55 constrained implants we have a postoperative dislocation rate of 1.8%.

Monoallelic PMS2 germline mutations cause 5%-15% of Lynch syndrome, a midlife cancer predisposition, whereas biallelic PMS2 mutations cause approximately 60% of constitutional mismatch repair deficiency (CMMRD), a rare childhood cancer syndrome. Recently improved DNA- and RNA-based strategies are applied to overcome problematic PMS2 mutation analysis due to the presence of pseudogenes and frequent gene conversion events. Here, we determined PMS2 mutation detection yield and mutation spectrum in a nationwide cohort of 396 probands. Furthermore, we studied concordance between tumor IHC/MSI (immunohistochemistry/microsatellite instability) profile and mutation carrier state. Overall, we found 52 different pathogenic PMS2 variants explaining 121 Lynch syndrome and nine CMMRD patients. In vitro mismatch repair assays suggested pathogenicity for three missense variants. Ninety-one PMS2 mutation carriers (70%) showed isolated loss of PMS2 in their tumors, for 31 (24%) no or inconclusive IHC was available, and eight carriers (6%) showed discordant IHC (presence of PMS2 or loss of both MLH1 and PMS2). Ten cases with isolated PMS2 loss (10%; 10/97) harbored MLH1 mutations. We confirmed that recently improved mutation analysis provides a high yield of PMS2 mutations in patients with isolated loss of PMS2 expression. Application of universal tumor prescreening methods will however miss some PMS2 germline mutation carriers., (© 2016 WILEY PERIODICALS, INC.)

Aims: We present a minimum 20-year follow-up study of 382 cemented Exeter Universal total hip arthroplasties (350 patients) operated on at a mean age of 66.3 years (17 to 94)., Patients and Methods: All patients received the same design of femoral component, regardless of the original diagnosis. Previous surgery had been undertaken for 33 hips (8.6%). During the study period 218 patients with 236 hips (62%) died, 42 hips (11%) were revised and 110 hips (29%) in 96 patients were available for review. The acetabular components were varied and some designs are now obsolete, however they were all cemented., Results: With an endpoint of revision for aseptic loosening or lysis, survivorship of the stem at 22.8 years was 99.0% (95% confidence interval (CI) 97.0 to 100). One stem was revised 21 years post-operatively in a patient with Gaucher's disease and proximal femoral osteolysis. Survivorship with aseptic loosening or lysis of the acetabular component or stem as the endpoint at 22.8 years was 89.3% (95% CI 84.8 to 93.8). With an endpoint of revision for any reason, overall survivorship was 82.9% (95% CI 77.4 to 88.4) at 22.8 years. Radiological review showed excellent preservation of bone stock at 20 to 25 years, and no impending failures of the stem., Conclusion: The Exeter femoral stem continues to perform well beyond 20 years. Cite this article: Bone Joint J 2016;98-B:1441-9., (©2016 The British Editorial Society of Bone & Joint Surgery.)

Partial life histories are presented for Spialia kituina (Karsch), S. spio (Linnaeus), S. diomus (Hopffer), S. colotes transvaaliae (Trimen), S. dromus (Plötz), S. ploetzi (Aurivillius), S. zebra bifida Higgins and Gomalia elma elma (Trimen). All feed on species of Malvaceae. An earlier record from Kenya of Melhania velutina as the food plant of S. depauperata depauperata (Strand) was based on a misidentification and there are no known records of the food plant of this subspecies. Spialia ferax (Wallengren) stat. rev. is considered a valid species rather than a subspecies of S. diomus, based on significant differences in wing patterns, the shape of the valves, a zone where neither occurs, no signs that a cline is involved, and differences in the colouring and markings of the caterpillars. The convergence of the biology of the chequered skippers of the tribes Carcharodini, Pyrgini and Celaenorrhini is discussed.

Objectives: Biomechanical characteristics, such as wall stress, are important in the pathogenesis of abdominal aortic aneurysms (AAA) and can be visualised and quantified using imaging techniques. This systematic review aims to present an overview of all biomechanical imaging markers that have been studied in relation to AAA growth and rupture., Methods: This systematic review followed the PRISMA guidelines. A search in Medline, Embase, and the Cochrane Library identified 1503 potentially relevant articles. Studies were included if they assessed biomechanical imaging markers and their potential association with growth or rupture., Results: Twenty-seven articles comprising 1730 patients met the inclusion criteria. Eighteen studies performed wall stress analysis using finite element analysis (FEA), 13 of which used peak wall stress (PWS) to quantify wall stress. Ten of 13 case control FEA studies reported a significantly higher PWS for symptomatic or ruptured AAAs than for intact AAAs. However, in some studies there was confounding bias because of baseline differences in aneurysm diameter between groups. Clinical heterogeneity in methodology obstructed a meaningful meta-analysis of PWS. Three of five FEA studies reported a significant positive association between several wall stress markers, such as PWS and 99th percentile stress, and growth. One study reported a significant negative association and one other study reported no significant association. Studies assessing wall compliance, the augmentation index and wall stress analysis using Laplace's law, computational fluid dynamics and fluid structure interaction were also included in this systematic review., Conclusions: Although PWS is significantly higher in symptomatic or ruptured AAAs in most FEA studies, confounding bias, clinical heterogeneity, and lack of standardisation limit the interpretation and generalisability of the results. Also, there is conflicting evidence on whether increased wall stress is associated with growth., (Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

The effects of neuroticism and depressive symptoms on psychophysiological responses in a social judgment task were examined in a sample of 101 healthy young adults. Participants performed a social judgment task in which they had to predict whether or not a virtual peer presented on a computer screen liked them. After the prediction, the actual judgment was shown, and behavioral, electrocortical, and cardiac responses to this judgment were measured. The feedback-related negativity (FRN) was largest after unexpected feedback. The largest P3 was found after the expected "like" judgments, and cardiac deceleration was largest following unexpected "do not like" judgments. Both the P3 and cardiac deceleration were affected by gender-that is, only males showed differential P3 responses to social judgments, and males showed stronger cardiac decelerations. Time-frequency analyses were performed to explore theta and delta oscillations. Theta oscillations were largest following unexpected outcomes and correlated with FRN amplitudes. Delta oscillations were largest following expected "like" judgments and correlated with P3 amplitudes. Self-reported trait neuroticism was significantly related to social evaluative predictions and cardiac reactivity to social feedback, but not to the electrocortical responses. That is, higher neuroticism scores were associated with a more negative prediction bias and with smaller cardiac responses to judgments for which a positive outcome was predicted. Depressive symptoms did not affect the behavioral and psychophysiological responses in this study. The results confirmed the differential sensitivities of various outcome measures to different psychological processes, but the found individual differences could only partly be ascribed to the collected subjective measures.

Purpose: To develop feature tracking (FT) software to perform strain analysis on conventional (nontagged) cardiac magnetic resonance imaging (MRI) function images. With the advent of MRI-conditional pacemaker systems, effects of cardiac pacing on myocardial strain can be studied using MR. In this study the impact of pacing on left ventricular (LV) strain was investigated using MR-FT in patients with an MRI-conditional cardiac implantable electronic device (CIED)., Materials and Methods: FT was performed on 32 1.5T MR studies (16 patients with an MRI-conditional CIED and 16 control patients with normal scans). Short- and long-axis steady state free precession (SSFP) cines were used for the FT analysis. Strain was assessed using CVI(42) software (Circle Cardiovascular Imaging, Alberta, Canada). In addition, the intra- and interobserver variability was determined using the intraclass correlation coefficient., Results: Of the 16 patients with an MRI-conditional CIED, five patients were paced during the MRI exam. Despite the occasional presence of susceptibility artifacts induced by the CIED, radial, circumferential, and longitudinal strain parameters could be derived for all patients. Peak radial strain and peak circumferential strain were reduced during pacing when compared to the control group; for radial strain: 20.1 ± 4.7% vs. 33.1 ± 6.9%, P < 0.001, and for circumferential strain -7.5 ± 3.5% vs. -14.9 ± 3.2%, P < 0.05. Peak strain parameters were reproducible on an intra- and interobserver level., Conclusion: MR-FT is feasible in patients with an MRI-conditional CIED and can be used to quantify regional wall motion. J. MAGN. RESON. IMAGING 2016;44:964-971., (© 2016 International Society for Magnetic Resonance in Medicine.)

Atlantic sturgeon Acipenser oxyrinchus aggregate to feed from May to October in Minas Basin (45° N; 64° W), a large, cul-de-sac embayment of the inner Bay of Fundy. The aggregation consists mainly of migrants from the Saint John, NB and Kennebec Rivers, ME (99%). During 2004-2015, 4393 A. oxyrinchus were taken as by-catch by commercial fish trawlers or at intertidal fishing weirs, and 1453 were marked and/or sampled and released. Fork length (L F ) ranged from 458 to 2670 mm, but 72·5% were <1500 mm. Mass (M) ranged from 0·5 to 58·0 kg. The mass-length relationship for fish ≤50 kg was log 10 M = 3·32log 10 L F - 5·71. Observed growth of unsexed A. oxyrinchus recaptured after 1-8 years indicated fish of 90-179 cm L F grew c. 2-4 cm a year. Ages obtained from pectoral spines were from 4 to 54 years. The Von Bertalanffy growth model predicted K = 0·01 and L ∞ = 5209 mm L F . Estimated annual mortality was 9·5-10·9%. Aggregation sizes in 2008 and 2013 were 8804 and 9244 individuals, respectively. Fish exhibited high fidelity for yearly return to Minas Basin and population estimates indicated the total at-sea number utilizing the Basin increased from c. 10 700 in 2010 to c. 37 500 in 2015. Abundance in the Basin was greatest along the north shore in spring and along the south shore in summer, suggesting clockwise movement following the residual current structure. Marked individuals were recaptured in other bays of the inner Bay of Fundy, north to Gaspé, Quebec, and south to New Jersey, U.S.A., with 26 recoveries from the Saint John River, NB, spawning run. Fish marked at other Canadian and U.S. sites were also recovered in Minas Basin. Since all A. oxyrinchus migrate into and out of the Basin annually they will be at risk of mortality if planned tidal power turbines are installed in Minas Passage., (© 2016 The Fisheries Society of the British Isles.)

Atlantic bluefin tuna (Thunnus thynnus) are distributed throughout the North Atlantic and are both economically valuable and heavily exploited. The fishery is currently managed as two spawning populations, with the GOM population being severely depleted for over 20 years. In April-August of 2010, the Deepwater Horizon oil spill released approximately 4 million barrels of oil into the GOM, with severe ecosystem and economic impacts. Acute oil exposure results in mortality of bluefin eggs and larvae, while chronic effects on spawning adults are less well understood. Here we used 16 years of electronic tagging data for 66 bluefin tuna to identify spawning events, to quantify habitat preferences, and to predict habitat use and oil exposure within Gulf of Mexico spawning grounds. More than 54,000 km 2 (5%) of predicted spawning habitat within the US EEZ was oiled during the week of peak oil dispersal, with potentially lethal effects on eggs and larvae. Although the oil spill overlapped with a relatively small portion of predicted spawning habitat, the cumulative impact from oil, ocean warming and bycatch mortality on GOM spawning grounds may result in significant effects for a population that shows little evidence of rebuilding., Competing Interests: The authors declare no competing financial interests.

Including equal numbers of positively and negatively keyed items is common in Five-Factor Model (FFM) personality measures. Much literature has demonstrated the presence of positive and negative keying factors in low-stakes testing situations, but there is a dearth of research investigating these factors in high-stakes testing. To address this gap, we investigated whether an FFM measure used in high-stakes testing was influenced by positive and negative keying factors. We also examined the overlap of the positive and negative keying factors with social desirability, rule-consciousness, acquiescence, and cognitive ability. Confirmatory factor analysis supported the inclusion of distinct factors associated with positively and negatively keyed items and suggested that the keying factors accounted for a substantial portion of variation in responses to FFM items. Social desirability and rule-consciousness were found to have significant relations with both keying factors, whereas acquiescence was only related to the negative keying factor. Implications for the construct validity of FFM measures used in high-stakes testing and directions for future research are discussed.

Background: Methods are required to identify abdominal aortic aneurysms (AAAs) at increased risk of rupture. Inflammatory characteristics of AAA can be visualised using advanced imaging techniques and have been proposed as potential predictors of aneurysm progression. The objective of this review was to determine which inflammatory imaging biomarkers are associated with AAA growth and rupture., Methods: A systematic review was carried out in accordance with the PRISMA guidelines. The electronic databases of Medline (PubMed), Embase, and the Cochrane Library were searched up to January 1, 2016 for studies to determine the potential association between inflammatory imaging biomarkers and AAA growth or rupture., Results: Seven studies were included, comprising 202 AAA patients. (18)F-fluoro-deoxy-glucose positron emission tomography ((18)F-FDG PET-CT) was evaluated in six studies. Magnetic resonance imaging with ultrasmall superparamagnetic particles of iron oxide (USPIO-MRI) was evaluated in one study. Two of six (18)F-FDG PET-CT studies reported a significant negative correlation (r=.383, p = .015) or a significant negative association (p = .04). Four of six (18)F-FDG PET-CT studies reported no significant association between (18)F-FDG uptake and AAA growth. The single study investigating USPIO-MRI demonstrated that AAA growth was three times higher in patients with focal USPIO uptake in the AAA wall compared to patients with diffuse or no USPIO uptake in the wall (0.66 vs. 0.24 vs. 0.22 cm/y, p = .020). In the single study relating (18)F-FDG uptake results to AAA rupture, the association was not significant., Conclusions: Current evidence shows contradictory associations between (18)F-FDG uptake and AAA growth. Data on the association with rupture are insufficient. Based on the currently available evidence, neither (18)F-FDG PET-CT nor USPIO-MRI can be implemented as growth or rupture prediction tools in daily practice. The heterogeneous results reflect the complex and partially unclear relationship between inflammatory processes and AAA progression., (Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)