bluuebunny/crossref_metadata_2025 huggingface dataset:
Socioeconomic characteristics, housing conditions and criminal offences among women with cervical neoplasia
Authors: Billström Emma , Sundström‐Poromaa Inger , Stålberg Karin , Asplund Anna , Hellberg Dan
Published: April 2013

Objective

To investigate the association between cervical neoplasia and socioeconomic factors, housing conditions and criminal offences.

Design

Longitudinal observational study.

Setting

Falun county hospital, Sweden.

Population

A total of 1331 women diagnosed with cervical intraepithelial neoplasia I‐III or cervical cancer between 1967 and 1978 were compared with 2604 age‐matched controls from the same geographical area in Sweden.

Methods

The Population and Housing Censuses were used for information about civil status, education, housing conditions, employment and socioeconomic status. The Swedish Register of Conviction Decisions was used to access information on criminal offences.

Main outcome measures

Socioeconomic status, housing conditions, criminal offences.

Results

Women with cervical neoplasia had a lower socioeconomic status and a lower educational level than their age‐matched controls. They were more often divorced and did not own their home as often as controls. A significant association with criminal offences was observed, and it persisted after adjustment for socioeconomic status. Differences in socioeconomic factors between women with cervical neoplasia and their controls had not diminished in the younger, compared with the older, part of the study population.

Conclusions

The results indicate that women with cervical neoplasia belong to a socioeconomically disadvantaged group. Furthermore, the study provides information about an association with criminal offences.
Accuracy of amplitude‐integrated electroencephalography in the prediction of neurodevelopmental outcome in asphyxiated infants receiving hypothermia treatment
Authors: Csekő AJ , Bangó M , Lakatos P , Kárdási J , Pusztai L , Szabó M
Published: April 2013

Aim

Both hypothermia and central nervous system (CNS) drugs may alter the predictive accuracy of amplitude‐integrated electroencephalography (aEEG) in hypoxic–ischaemic encephalopathy (HIE). The aim was to assess the predictive value of aEEG in hypothermia‐treated HIE infants. Furthermore, we intended to investigate the association of cumulative doses of CNS drugs with aEEG recovery.

Methods

Seventy term HIE infants treated with hypothermia for 72 h were continuously monitored by single‐channel aEEG. Doses of administered morphine, phenobarbitone and midazolam were recorded. Poor outcome was defined as death or severe neurodevelopmental delay at 18‐24 months (Bayley Scales of Infant Development II), good outcome as absence of these criteria.

Results

Poor outcome n = 26, good outcome n = 44. Positive predictive values (PPV) of an abnormal background pattern to predict poor outcome were 0.5 at 6 h; 0.65 at 24 h; 0.82 at 48 h and 0.92 at 60 h. All infants who developed sleep–wake cycling (SWC) had a favourable outcome; the nondevelopment of SWC resulted in a PPV of 0.73 for a poor outcome. Cumulative doses of the investigated drugs did not differ between infants having an onset of a recovered background pattern before or after 24 h.

Conclusion

Amplitude‐integrated electroencephalography provides reliable prediction of outcome from the 48th hour during hypothermia in HIE infants. Commonly used CNS drugs in HIE infants do not significantly delay aEEG recovery.
Indoles mitigate the development of experimental autoimmune encephalomyelitis by induction of reciprocal differentiation of regulatory T cells and Th17 cells
Authors: Rouse Michael , Singh Narendra P , Nagarkatti Prakash S , Nagarkatti Mitzi
Published: April 2013

Background and Purpose

Dietary indole derivatives, indole‐3‐carbinol (I3C) and diindolylmethane (DIM), possess anti‐cancer properties and exhibit the characteristics of aryl hydrocarbon receptor (AhR) ligands. Because AhR activation has recently been shown to regulate T cell differentiation, we tested the hypothesis that I3C and DIM may mediate anti‐inflammatory properties by promoting regulatory T cell (T‐regs) differentiation while inhibiting Th17 cells.

Experimental Approach

We investigated the therapeutic efficacy of I3C and DIM against experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). The efficacy was evaluated based on clinical scores of paralysis, histopathology, serum cytokines and infiltration of T cells in the CNS. We next studied the mechanism of induction of T cells against myelin oligodendrocyte glycoprotein (MOG35–55) peptide, both in vivo and in vitro, specifically investigating the differentiation of T‐regs and Th17 cells, and determined if indoles were acting through AhR.

Key Results

Pretreatment of EAE mice with I3C or DIM completely prevented the clinical symptoms and cellular infiltration into the CNS. Also, post‐treatment of EAE with I3C or DIM proved highly effective in curtailing the overall severity of the disease. In addition, I3C or DIM promoted the generation of T‐regs, while down‐regulating the induction of MOG‐specific Th17 cells. The regulation of FoxP3 induction and suppression of Th17 cells by indoles in vivo and in vitro were found to be AhR‐dependent.

Conclusions and Implications

Together, our studies demonstrate for the first time that I3C and DIM may serve as novel therapeutics to suppress neuroinflammation seen during MS through activation of AhR.
Nebulized thiocyanate improves lung infection outcomes in mice
Authors: Chandler J D , Min E , Huang J , Nichols D P , Day B J
Published: April 2013

Background and Purpose

Nebulized saline solutions are used in the treatment of multiple pulmonary diseases including cystic fibrosis (CF), asthma and chronic obstructive pulmonary disease (COPD). The benefits of these therapies include improved lung function, phlegm clearance and fewer lung infections. The thiocyanate anion (SCN) is a normal component of the airway epithelial lining fluid (ELF) secreted by pulmonary epithelia with antioxidant and host defence functions. We sought to test if SCN could be nebulized to combat lung infection by bolstering innate immune defence and antioxidant capacity.

Experimental Approach

We established an effective antioxidant concentration of SCN in vitro using a bronchiolar epithelial cell line. We then developed a nebulization method of SCN in mice that increased ELF SCN above this concentration up to 12 h and used this method in a prolonged Pseudomonas aeruginosa infection model to test if increasing SCN improved host defence and infection outcomes.

Key Results

SCN protected against cytotoxicity in vitro from acute and sustained exposure to inflammation‐associated oxidative stress. Nebulized SCN effectively reduced bacterial load, infection‐mediated morbidity and airway inflammation in mice infected with P. aeruginosa. SCN also sustained adaptive increases in reduced GSH in infected mice.

Conclusions and Implications

SCN is a dually protective molecule able to both enhance host defence and decrease tissue injury and inflammation as an antioxidant. Nebulized SCN could be developed to combat lung infections and inflammatory lung disease.
Structure‐activity relationships of pentamidine‐affected ion channel trafficking and dofetilide mediated rescue
Authors: Varkevisser R , Houtman M J C , Linder T , de Git K C G , Beekman H D M , Tidwell R R , IJzerman A P , Stary‐Weinzinger A , Vos M A , van der Heyden M A G
Published: April 2013

Background and Purpose

Drug interference with normal hERG protein trafficking substantially reduces the channel density in the plasma membrane and thereby poses an arrhythmic threat. The chemical substructures important for hERG trafficking inhibition were investigated using pentamidine as a model drug. Furthermore, the relationship between acute ion channel block and correction of trafficking by dofetilide was studied.

Experimental Approach

hERG and KIR2.1 trafficking in HEK293 cells was evaluated by Western blot and immunofluorescence microscopy after treatment with pentamidine and six pentamidine analogues, and correction with dofetilide and four dofetilide analogues that displayed different abilities to inhibit IKr. Molecular dynamics simulations were used to address mode, number and type of interactions between hERG and dofetilide analogues.

Key Results

Structural modifications of pentamidine differentially affected plasma membrane levels of hERG and KIR2.1. Modification of the phenyl ring or substituents directly attached to it had the largest effect, affirming the importance of these chemical residues in ion channel binding. PA‐4 had the mildest effects on both ion channels. Dofetilide corrected pentamidine‐induced hERG, but not KIR2.1 trafficking defects. Dofetilide analogues that displayed high channel affinity, mediated by pi‐pi stacks and hydrophobic interactions, also restored hERG protein levels, whereas analogues with low affinity were ineffective.

Conclusions and Implications

Drug‐induced trafficking defects can be minimized if certain chemical features are avoided or ‘synthesized out’; this could influence the design and development of future drugs. Further analysis of such features in hERG trafficking correctors may facilitate the design of a non‐blocking corrector for trafficking defective hERG proteins in both congenital and acquired LQTS.
Functional expression of KCNQ (Kv7) channels in guinea pig bladder smooth muscle and their contribution to spontaneous activity
Authors: Anderson U A , Carson C , Johnston L , Joshi S , Gurney A M , McCloskey K D
Published: April 2013

Background and Purpose

The aim of the study was to determine whether KCNQ channels are functionally expressed in bladder smooth muscle cells (SMC) and to investigate their physiological significance in bladder contractility.

Experimental Approach

KCNQ channels were examined at the genetic, protein, cellular and tissue level in guinea pig bladder smooth muscle using RT‐PCR, immunofluorescence, patch‐clamp electrophysiology, calcium imaging, detrusor strip myography, and a panel of KCNQ activators and inhibitors.

Key Results

KCNQ subtypes 1–5 are expressed in bladder detrusor smooth muscle. Detrusor strips typically displayed TTX‐insensitive myogenic spontaneous contractions that were increased in amplitude by the KCNQ channel inhibitors XE991, linopirdine or chromanol 293B. Contractility was inhibited by the KCNQ channel activators flupirtine or meclofenamic acid (MFA). The frequency of Ca2+‐oscillations in SMC contained within bladder tissue sheets was increased by XE991. Outward currents in dispersed bladder SMC, recorded under conditions where BK and KATP currents were minimal, were significantly reduced by XE991, linopirdine, or chromanol, and enhanced by flupirtine or MFA. XE991 depolarized the cell membrane and could evoke transient depolarizations in quiescent cells. Flupirtine (20 μM) hyperpolarized the cell membrane with a simultaneous cessation of any spontaneous electrical activity.

Conclusions and Implications

These novel findings reveal the role of KCNQ currents in the regulation of the resting membrane potential of detrusor SMC and their important physiological function in the control of spontaneous contractility in the guinea pig bladder.
Open Innovation and Firm Performance: The Mediating Role of Social Capital
Authors: Rass Matthias , Dumbach Martin , Danzinger Frank , Bullinger Angelika C. , Moeslein Kathrin M.
Published: April 2013

This article examines the role of social relations and networks in open innovation settings. Building on extant open innovation literature as well as on social capital theory, we develop a model that conceptualizes social capital as a mediator between the implementation of open innovation instruments and firm performance. In doing so, this paper adds to the understanding of the role of structure and content of social relations in open innovation contexts as well as of sustainable side‐effects of open innovation. In particular, we argue that apart from a direct effect of open innovation instruments on firm performance, there is also a mediated relationship between these variables. More precisely, we propose that the implementation of open innovation instruments strengthens an organization's social capital, which is, in turn, positively related to firm performance.
‘Information is information’: a public perspective on incidental findings in clinical and research genome‐based testing
Authors: Daack‐Hirsch S , Driessnack M , Hanish A , Johnson VA , Shah LL , Simon CM , Williams JK
Published: April 2013

The potential for genomic incidental findings is increasing with the use of genome‐based testing. At the same time approaches to clinical decision making are shifting to shared decision‐making models involving both the healthcare community and the public. The public's voice has been nearly absent in discussions on managing incidental findings. We conducted nine focus groups and nine interviews (n = 63) with a broad cross‐section of lay public groups to elucidate public viewpoints on incidental findings that could occur as a result of genome‐based testing in clinical and research situations. Data were analyzed using qualitative content analysis. Participants wanted incidental findings disclosed to them whether or not these were clinical or research findings. Participants used different terms to define and describe incidental findings; they wanted to know that incidental findings are possible and be given a choice to learn about them. Personal utility was an important reason for disclosure, and participants believed that managing information is a shared responsibility between professionals and themselves. Broad public input is needed in order to understand and incorporate the public's perspective on management of incidental findings as disclosure guidelines, and policies are developed in clinical and research settings.
Multiplex targeted high‐throughput sequencing for Mendelian cardiac disorders
Authors: Fokstuen S. , Makrythanasis P. , Nikolaev S. , Santoni F. , Robyr D. , Munoz A. , Bevillard J. , Farinelli L. , Iseli C. , Antonarakis S.E. , Blouin J.‐L.
Published: April 2013

Mendelian cardiomyopathies and arrhythmias are characterized by an important genetic heterogeneity, rendering Sanger sequencing very laborious and expensive. As a proof of concept, we explored multiplex targeted high‐throughput sequencing (HTS) as a fast and cost‐efficient diagnostic method for individuals suffering from Mendelian cardiac disorders. We designed a DNA capture assay including all exons from 130 genes involved in cardiovascular Mendelian disorders and analysed simultaneously four samples by multiplexing. Two patients had familial hypertrophic cardiomyopathy (HCM) and two patients suffered from long QT syndrome (LQTS). In patient 1 with HCM, we identified two known pathogenic missense variants in the two most frequently mutated sarcomeric genes MYH7 and MYBPC. In patient 2 with HCM, a known acceptor splice site variant in MYBPC3 was found. In patient 3 with LQTS, two missense variants in the genes SCN5A and KCNQ were identified. Finally, in patient 4 with LQTS a known missense variant was found in MYBPC3, which is usually mutated in patients with cardiomyopathy. Our results showed that multiplex targeted HTS works as an efficient and cost‐effective tool for molecular diagnosis of heterogeneous disorders in clinical practice and offers new insights in the pathogenesis of these complex diseases.
Congenital posterior pole cataract and adult onset dilating cardiomyopathy: expanding the phenotype of αB‐crystallinopathies
Authors: van der Smagt J.J. , Vink A. , Kirkels J.H. , Nelen M. , ter Heide H. , Molenschot M.M.C. , Weger R.A. , Schellekens P.A.W. , Hoogendijk J. , Dooijes D.
Published: April 2013

Mutations in the αB‐crystallin gene (CRYAB) have been reported in desmin‐related myopathies, with or without cardiac involvement. Mutations in this gene have also been documented in large multi‐generation families with autosomal dominant congenital posterior pole cataract (CPPC). In these congenital cataract families no cardiac or muscular phenotype was reported. This report describes a family with an unusual read‐through mutation in CRYAB, leading to the elongation of the normal αB‐crystallin protein with 19 amino acid residues. Affected family members combine a CPPC with an adult onset dilated cardiomyopathy (DCM), thereby expanding the αB‐crystallinopathy phenotype. Repolarisation abnormalities preceded the onset of cardiomyopathy and were already present in childhood. No skeletal myopathy was observed. This report illustrates that congenital cataract can be a prelude to more severe disease even outside the context of inborn errors of metabolism. The identification of a CRYAB mutation in this family supports the notion that mutations in this gene are a rare cause of genetically determined DCM. The combined congenital cataract/cardiomyopathy phenotype adds to our understanding of the complex phenotypic spectrum of αB‐crystallinopathies.
Predictors of Left Ventricular Function Deterioration in Patients With Left Bundle Branch Block and Ejection Fraction >50%
Authors: Angheloiu George O. , Saul Melissa , Edelman Kathy , Shah Hemal , Mezu Ure L. , Saba Samir
Published: April 2013

Resynchronization therapy has become standard of care in patients with left bundle branch block (LBBB), congestive heart failure (CHF), and low ejection fraction (EF). In order to characterize the left ventricular (LV) function evolution in patients with LBBB and baseline preserved LVEF, records of all patients who visited an academic echocardiography laboratory during a period of 4 years were retrospectively investigated. Patients were included if they had a baseline EF >50%, LBBB on surface electrocardiography, and at least one follow‐up echocardiogram no earlier than 3 months after the baseline study. The endpoint was the occurrence of EF deterioration to values ≤40%. Clinical variables associated with this outcome were identified. Forty‐nine patients satisfied the entry criteria. Over a mean 13±8.5 months of follow‐up (range 3 to 36), 8 patients (16%) experienced EF deterioration ≤40%. History of CHF prior to baseline echocardiogram and LV mass >300 g were associated with this phenomenon (P=.004 and P=.015, respectively), with a negative predictive value of 100% and 92%, respectively. Our data profiles a risk‐stratification methodology in patients with LBBB and baseline EF >50% and possibly a triage strategy toward resynchronization therapy in this population.
Hairdressers presenting to an occupational dermatology clinic in Melbourne, Australia
Authors: Lyons Georgina , Roberts Hugh , Palmer Amanda , Matheson Melanie , Nixon Rosemary
Published: April 2013

Background. Hairdressers constitute one of the largest occupational groups attending our occupational dermatology clinic in Melbourne, Australia.

Objectives. To perform a retrospective review of the clinical assessments of hairdressers and trainee hairdressers attending our clinic, including patch testing results.

Patients/materials/methods. We used our clinic database to identify trainee and qualified hairdressers who had attended our occupational dermatology clinic between January 1993 and December 2010.

Results. One hundred and sixty‐four hairdressers and hairdressing apprentices were identified. One hundred and fifty‐seven had a diagnosis of occupational contact dermatitis (OCD), with allergic contact dermatitis being the primary diagnosis in 71% and irritant contact dermatitis in 20%. Involvement of more than one body part was suggestive of allergic contact dermatitis (p = 0.05). Sixty‐five per cent of participants were found to have more than one factor contributing to their OCD. Allergic contact dermatitis was more common in apprentices than in qualified hairdressers. Ammonium persulfate, p‐phenylenediamine, toluene‐2,5‐diamine and glyceryl monothioglycolate were the most common occupational allergens. Nickel allergy was seen in 31% of hairdressers, but considered to be occupationally relevant in only 3%.

Conclusions. Multiple sensitizations and multiple factors contributing to OCD in hairdressers are common. More needs to be done to prevent the development of OCD in hairdressers in our geographical region.
A rightward shift of the distribution of fasting and post‐load glucose in northern Sweden between 1990 and 2009 and its predictors. Data from the Northern Sweden MONICA study
Authors: Lilja M. , Eliasson M. , Eriksson M. , Söderberg S.
Published: April 2013

Aims

Most Swedish studies show stable diabetes prevalence despite increasing obesity, but glucose levels may shift upwards below the diagnostic threshold for diabetes. Our aim was to explore trends in glucose distribution in northern Sweden; whether these trends were uniformly distributed throughout the spectrum of glucose concentrations; and to relate trends to traditional risk factors and the obesity‐related adipokine leptin.

Methods

The project consisted of four cross‐sectional surveys between 1990 and 2009, with 7069 participants aged 25–64 years. The overall participation rate was 74.4%. Trend analyses of glucose concentrations along the entire distribution and linear regression in relation to survey years and risk markers were used.

Results

Fasting and post‐load glucose increased in women (both P < 0.001) and post‐load glucose in men (P = 0.004). The increase was seen in most deciles of glucose concentrations. The prevalence of impaired glucose tolerance doubled in women to 14.5% and tripled in men to 10.1% (both P = 0.004). The prevalence of impaired fasting glucose rose in women from 4.5 to 7.7% (P < 0.001). The prevalence of diabetes was unchanged—6.4% in 2009. In men, leptin, together with traditional risk factors, explained 7.8 and 10.8% of the variance in fasting (P = 0.008) and post‐load (P < 0.001) glucose, respectively.

Conclusions

Increasing fasting and post‐load glucose concentrations were seen in most deciles of the glucose distribution, indicating a shift in the entire population. Leptin was significantly associated with fasting and post‐load glucose in men.
Enhanced carbohydrate craving in patients with poorly controlled Type 2 diabetes mellitus
Authors: Yu J. H. , Shin M. S. , Kim D. J. , Lee J. R. , Yoon S.‐Y. , Kim S. G. , Koh E. H. , Lee W. J. , Park J.‐Y. , Kim M.‐S.
Published: April 2013

Aims

Although hyperphagia is a common manifestation of diabetes mellitus, data on food craving in patients with diabetes are limited. This study compared food craving in patients with Type 2 diabetes mellitus and a control group without diabetes.

Methods

A total of 210 subjects (105 with Type 2 diabetes and 105 age‐, sex‐ and BMI‐matched control subjects) participated in two food craving surveys. The surveys were as follows: the General Food Cravings Questionnaire—Trait, which assesses the general trait of food craving; and the Food Cravings Questionnaire—State, which assesses the state of food craving or current desire for high‐carbohydrate or high‐fat foods in response to pictures of food. Follow‐up Food Cravings Questionnaire—State surveys were administered approximately 3 months later to the subjects with diabetes. Survey results were analysed to assess relationships between food craving and glycaemic control.

Results

The General Food Cravings Questionnaire—Trait scores in the group with Type 2 diabetes and the control group were not significantly different. The group with Type 2 diabetes had higher carbohydrate craving scores, but lower fat craving scores, than the control group. Carbohydrate craving scores in subjects with diabetes were positively correlated with HbA1c. In follow‐up surveys, carbohydrate craving scores declined in patients with improved glycaemic control.

Conclusions

The surveys showed that patients with Type 2 diabetes had higher carbohydrate cravings and lower fat cravings than the age‐, sex‐ and BMI‐matched control group. Carbohydrate craving in patients with diabetes was associated with poor glycaemic control.
Investigation of known estimated glomerular filtration rate loci in patients with Type 2 diabetes
Authors: Deshmukh H. A. , Palmer C. N. A. , Morris A. D. , Colhoun H. M.
Published: April 2013

Aims

To replicate the association of genetic variants with estimated glomerular filtration rate (GFR) and albuminuria, which has been found in recent genome‐wide studies in patients with Type 2 diabetes.

Methods

We evaluated 16 candidate single nucleotide polymorphisms for estimated GFR in 3028 patients with Type 2 diabetes sampled from clinics across Tayside, Scotland, UK, who were included in the Genetics of Diabetes Audit and Research Tayside (GoDARTs) study. These single nucleotide polymorphisms were tested for their association with estimated GFR at entry to the study, with albuminuria, and with time to stage 3B chronic kidney disease (estimated GFR<45 ml/min/1.73 m2). We also stratified the effects on estimated GFR in patients with (n = 2096) and without albuminuria (n = 613).

Results

rs1260326 in GCKR (β=1.30, P = 3.23E‐03), rs17319721 in SHROOM3 (β = −1.28, P‐value = 3.18E‐03) and rs12917707 in UMOD (β = 2.0, P‐value = 8.84E‐04) were significantly associated with baseline estimated GFR. Analysis of effects on estimated GFR, stratified by albuminuria status, showed that in those without albuminuria (normoalbuminura; n = 613), UMOD had a significantly stronger effect on estimated GFR (βnormo = 4.03 ± 1.23 vs βalbuminuria = 1.72 ± 0.76, P = 0.002) compared with those with albuminuria, while GCKR (βnormo = 0.45 ± 0.89 vs βalbuminuria = 1.12 ± 0.55, P = 0.08) and SHROOM3 (βnormo = −0.07 ± 0.89 vs βalbuminuria = −1.43 ± 0.53, P = 0.003) had a stronger effect on estimated GFR in those with albuminuria. UMOD was also associated with a lower rate of transition to stage 3B chronic kidney disease (hazard ratio = 0.83[0.70, 0.99], P = 0.03).

Conclusion

The genetic variants that regulate estimated GFR in the general population tend to have similar effects in patients with Type 2 diabetes and in this latter population, it is important to adjust for albuminuria status while investigating the genetic determinants of renal function.
Validation of the German Diabetes Risk Score within a population‐based representative cohort
Authors: Hartwig S. , Kuss O. , Tiller D. , Greiser K. H. , Schulze M. B. , Dierkes J. , Werdan K. , Haerting J. , Kluttig A.
Published: April 2013

Aim

To validate the German Diabetes Risk Score within the population‐based cohort of the Cardiovascular Disease – Living and Ageing in Halle (CARLA) study.

Methods

The sample included 582 women and 719 men, aged 45–83 years, who did not have diabetes at baseline. The individual risk of every participant was calculated using the German Diabetes Risk Score, which was modified for 4 years of follow‐up. Predicted probabilities and observed outcomes were compared using Hosmer–Lemeshow goodness‐of‐fit tests and receiver–operator characteristic analyses. Changes in prediction power were investigated by expanding the German Diabetes Risk Score to include metabolic variables and by subgroup analyses.

Results

We found 58 cases of incident diabetes. The median 4‐year probability of developing diabetes based on the German Diabetes Risk Score was 6.5%. The observed and predicted probabilities of developing diabetes were similar, although estimation was imprecise owing to the small number of cases, and the Hosmer–Lemeshow test returned a poor correlation (chi‐squared = 55.3; P = 5.8*10‐12). The area under the receiver–operator characteristic curve (AUC) was 0.70 (95% CI 0.64–0.77), and after excluding participants ≥66 years old, the AUC increased to 0.77 (95% CI 0.70–0.84). Consideration of glycaemic diagnostic variables, in addition to self‐reported diabetes, reduced the AUC to 0.65 (95% CI 0.58–0.71). A new model that included the German Diabetes Risk Score and blood glucose concentration (AUC 0.81; 95% CI 0.76–0.86) or HbA1c concentration (AUC 0.84; 95% CI 0.80–0.91) was found to peform better.

Conclusions

Application of the German Diabetes Risk Score in the CARLA cohort did not reproduce the findings in the European Prospective Investigation into Cancer and Nutrition (EPIC) Potsdam study, which may be explained by cohort differences and model overfit in the latter; however, a high score does provide an indication of increased risk of diabetes.
Examining Critical Junctures in Macroeconomic Policy in Nondemocratic States:Algeria andJordan in Comparative Perspective
Authors: Hogan John , Cavatorta Francesco
Published: April 2013

The article uses the critical junctures framework in examining changes in macroeconomic policy inAlgeria andJordan during the late 1980s to determine if these policy changes constituted critical junctures. Both cases are significantly different from those studied previously using the framework, as neither state was a liberal democracy. The absence of democracy, and as a consequence of accountability, is a factor with which the critical junctures framework has not previously had to contend. This study will also enable us determine if the framework is sufficiently robust to be applied to the examination of macroeconomic policy changes in nondemocratic states. The findings show that in both countries political liberalization did not follow upon economic liberalization, giving lie to the often expressed assumption that economic liberalization and democratization go hand in hand. Instead, as the ruling elites in both countries sought to revive their economies, while maintaining their own positions in society, economic policy reforms required a gesture toward democratization but little else.
Should We Refinance Unfunded Social Security?
Authors: Gahramanov Emin , Tang Xueli
Published: April 2013

Within a continuous‐time overlapping generations model, featuring endogenous intensive margin of the labour supply and retirement decision, we analyse the issue of passing the burden of payroll revenues onto consumption or capital. We find that large long‐run welfare gains occur when pension benefits are refinanced by consumption taxes. However, the transition to the new steady state is very painful for a large fraction of existing cohorts. On the other hand, the capital base is too small to sustain pension benefits but could be made larger if capital taxes are raised. Yet that would entail significant welfare losses.
Effect of hypolipidemic treatment on emerging risk factors in mixed dyslipidemia: a randomized pilot trial
Authors: Kei Anastazia , Liberopoulos Evangelos , Tellis Kostantinos , Rizzo Manfredi , Elisaf Moses , Tselepis Alexandros
Published: April 2013

Background

The effects of different hypolipidemic treatment strategies on emerging atherosclerosis risk factors remain unknown.

Materials and methods

This is a prespecified analysis of a prospective, randomized, open‐label, blinded end point (PROBE) study (ClinicalTrials.gov identifier: NCT01010516). Patients (n = 100) with mixed dyslipidaemia on a standard statin dose who had not achieved lipid targets were randomized to switch to the highest dose of rosuvastatin (40 mg/day) or to add‐on‐statin extended release nicotinic acid (ER‐NA)/laropiprant (LRPT) or to add‐on‐statin micronized fenofibrate for a total of 3 months.

Results

Following 3 months of treatment, low‐density lipoprotein (LDL) particle size increased equally in all groups. Similarly, all treatments were associated with comparable small dense LDL cholesterol reduction. Apolipoprotein B levels decreased by 15%, 7% and 4% in the rosuvastatin, add‐on ER‐NA/LRPT and add‐on fenofibrate group, respectively (P < 0·01 for all compared with baseline, P < 0·01 for all comparisons between groups). Only add‐on ER‐NA/LRPT was associated with lipoprotein (a) reduction (26%, P < 0·01 compared with baseline). Rosuvastatin monotherapy and add‐on ER‐NA/LRPT groups were associated with 56% and 24% reduction in high‐sensitivity C‐reactive protein levels (hsCRP), respectively (P < 0·01 compared with baseline), while add‐on fenofibrate was not associated with changes in hsCRP concentration. Lipoprotein‐associated phospholipase A2 (Lp‐PLA2) activity decreased similarly in both rosuvastatin and add‐on fenofibrate groups, while add‐on ER‐NA/LRPT was associated with a more pronounced Lp‐PLA2 activity reduction. ER‐NA/LRPT was associated with more side effects compared with rosuvastatin and add‐on fenofibrate.

Conclusions

Add‐on ER‐NA/LRPT followed by switch to the highest dose rosuvastatin were associated with more pronounced beneficial modifications in emerging cardiovascular risk factors compared with add‐on fenofibrate in patients with mixed dyslipidaemia.
Aberrant microRNA expression in multiple myeloma
Authors: Dimopoulos Konstantinos , Gimsing Peter , Grønbæk Kirsten
Published: April 2013

Multiple myeloma (MM) is a devastating disease with a complex biology, and in spite of improved survivability by novel treatment strategies over the last decade, MM is still incurable by current therapy. MicroRNAs (miRNAs) are small, non‐coding RNA molecules that regulate gene expression at a post‐transcriptional level. More than half of all protein coding genes are estimated to be controlled by miRNAs, and their expression is frequently deregulated in many diseases, including cancer. Recent studies have reported aberrant miRNA expression patterns in MM, and the function of individual miRNAs in MM has been investigated in detail in cell culture and animal models. Here, we review the current knowledge on the role of miRNAs in MM pathogenesis and discuss their potential as prognostic biomarkers and targets for treatment.
Attitudinal Analyses of Toleration and Respect and the Problem of Institutional Applicability
Authors: Lægaard Sune
Published: April 2013

Toleration and respect are types of relations between different agents. The standard analyses of toleration and respect are attitudinal; toleration and respect require subjects to have appropriate types of attitudes towards the objects of toleration or respect. The paper investigates whether states can sensibly be described as tolerant or respectful in ways theoretically relevantly similar to the standard analyses. This is a descriptive question about the applicability of concepts rather than a normative question about whether, when and why states should be tolerant or respectful. The problem of institutional application is that institutions in general and the state in particular arguably cannot have attitudes of the required kind. This problem is distinct from, and broader than, well‐known problems about whether political toleration is normatively legitimate. To make sense of political toleration or respect, the paper proposes that the analysis of institutional toleration and respect should not be solely agent‐centred (as in attitudinal analyses) or patient‐centred (as in explanations of the good of toleration or respect in terms of the effects of being tolerated or respected). The analysis should also include features about the relation itself. We can describe institutions as tolerant or respectful in a sense relevantly similar to the standard analyses if we focus on the public features of the relation between institutions and citizens or groups, without ascribing attitudes in the problematic sense.
EU Work–Family Policies—Challenging Parental Roles or Reinforcing Gendered Stereotypes?
Authors: Weldon‐Johns Michelle
Published: April 2013

Shared parenting is premised on both working parents having the right to care. However, the work–family conflict at the EU level has traditionally focused on working mothers. This was reinforced in Hofmann v Barmer Ersatzkasse [1986] 1 CMLR 242 and Commission v Italy [1984] 3 CMLR 169, and in the enactment and application of the Parental Leave Directive 96/34/EC. In both instances, fathers' role in childcare has been secondary, at best, to that of mothers. The question of shared parenting, and enabling all working parents to care, underpins proposals to amend the Pregnant Workers Directive 92/85/EEC and the revised Parental Leave Directive 2010/18/EU. This article examines the development of EU work–family policies with reference to Fineman's notion of family care, and the right to care for all working parents. It considers whether a more defined role for fathers is beginning to emerge or maternal care is further entrenched.
Brittle failure of inclined key‐hole notches in isostatic graphite under in‐plane mixed mode loading
Authors: Lazzarin P. , Berto F. , Ayatollahi M. R.
Published: April 2013

In the present contribution, the fracture behaviour of specimens made of isostatic graphite and weakened by inclined key‐hole notches is investigated. Different loading mixities are considered varying the inclination angle of the notch with respect to the direction of the applied load.

The new data permit to enlarge the scarce number of results available in the literature for the same material under prevalent in‐plane shear loading.

A criterion based on local energy is used for the fracture assessment to summarise all the data in a single scatter band independent of the notch geometry and mode mixity. The local energy‐based criterion allows to predict with sound accuracy the critical loads of the specimens independent of the mode mixity from pure mode I to prevalent mode II. A final synthesis is reported in the paper, summarising the new data together with previous results on the same material from U‐notched specimens subjected to mode I + II loading.
Mycoplasma genitalium in male urethritis: Diagnosis and treatment in Japan
Authors: Hamasuna Ryoichi
Published: April 2013

Male urethritis is a common disease for urologists, with the most common pathogens being, Chlamydia trachomatis and Neisseria gonorrhoeae. When the tests fail to detect these pathogens, the presented urethritis is called non‐chlamydial non‐gonococcal urethritis. Mycoplasma genitalium is one of the pathogens for non‐chlamydial non‐gonococcal urethritis. The test for detecting M. genitalium, which is commercially available in Japan, is not accepted by the Japanese insurance system now. The detection rate of M. genitalium from patients with non‐gonococcal urethritis is 10–20% in Japan. Antimicrobial susceptibility testing for M. genitalium showed that macrolide has the strongest activity and the minimum inhibitory concentrations of tetracyclines were not substantially lower. Some kinds of fluoroquinolones, such as sitafloxacin and moxifloxacin, have stronger activities against M. genitalium. For non‐gonococcal urethritis, macrolides and tetracycline are recommended in some guidelines. In clinical studies, tetracyclines are less effective against M. genitalium than azithromycin, and azithromycin regimens including 1 g stat or 2 g stat are now recommended for urethritis with M. genitalium. However, macrolide‐resistant M. genitalium strains have recently emerged and are spreading worldwide. This macrolide‐resistance is closely related to mutations on the 23S rRNA gene. Sitafloxacin and moxifloxacin have shown good efficacies for M. genitalium in some clinical studies. If the azithromycin regimens fail, we must consider the use of fluoroquinolones, such as sitafloxacin, in Japan. The most important issues include the acceptance of M. genitalium examinations by the national insurance system and the individual treatment of C. trachomatis and M. genitalium in the not‐too‐distant future.
Explaining Urban Migration from Mexico City to the USA: Social Networks and Territorial Attachments
Authors: Mendoza Cristóbal
Published: April 2013

Using a representative survey on a municipality in Mexico City, the article explores the relevance of both social networks and place attachments for US migration. By comparing households with and without migrants, the logistic regression models show that social networks make emigration more selective with respect “education”, but less selective regarding “sex” and “marital status”. These results shed new light on the mechanism through which social networks operate in urban settings. Even if a municipality that is very homogeneous in terms of poverty and employment opportunities, variations on the socio‐demographic profile of the would‐be emigrants to the USA are found depending on the household′s social networks. As for territorial variables, the general impression is one of placelessness, apart from attachment to the municipality, but here again social networks act as an intervening variable.
Whither and Whence Hong Kong Migration Studies?
Authors: Bailey Adrian J. , Alex Lau K. L.
Published: April 2013

On 1 July 2012, Hong Kong (HK) celebrated the 15th Anniversary of its change of sovereignty to the People's Republic of China (PRC). During this period, migration has diversified greatly. Various new visa categories have been created. People from Mainland China and the rest of the world come to HK for work and settlement and HK people have gone to Mainland and overseas to study and work. To appreciate and better plan the growing diversity of migration to, from, and through HK, this article benchmarks the current legal categorizations of migration and calls for the development of a coherent theoretical approach that can better harmonize research and policy. We believe a transdisciplinary view can help generate the range of evidence needed to plan for diversity, and that this is best coordinated through a new HK Migration Observatory.
Successful coil embolization for life‐threatening hemorrhage in childhood leukemia induction therapy
Authors: Hayakawa Jun , Ueda Takahiro , Fujiwara Yusuke , Ozaki Yusuke , Wakita Satoshi , Maeda Miho , Fukunaga Yoshitaka
Published: April 2013

An 11‐year‐old boy was experienced severe life‐threatening hemorrhage from a branch of the superior mesenteric artery (SMA) after acute lymphoblastic leukemia induction therapy. The patient had a history of attention deficit hyperactivity disorder (ADHD), diagnosed at 3 years of age. Subsequent to discontinuing his psychotropic medication, the patient’s mental status deteriorated and treatment with midazolam for 3 weeks was necessary to allow the completion of the leukemia induction regimen. On day 51, although there was no indication of thrombocytopenia or a coagulation disorder, the patient began to hemorrhage suddenly from anal with resulting hypovolemic shock, and large‐volume blood transfusion was initiated. Although upper and lower endoscopy failed to determine the location of the hemorrhage, angiography enabled us to determine that it was a branch of the SMA (the middle colic artery #6), and selective arterial embolization was used to arrest the bleeding. There could have been underlying causes, such as, a probable malformation or aneurysm in that area, although there was no indication before or after the event. This is a rare case of arterial hemorrhage from a branch of the SMA that occurred in a pediatric patient idiopathically during the induction therapy of leukemia.
Girl with xanthogranulomatous pyelonephritis and bronchiectasis: Case report
Authors: Nadeem Montasser , Oni Oluwole A , Ryan Martin , Puri Prem , Coghlan David , Greally Peter
Published: April 2013

Xanthogranulomatous pyelonephritis (XGP) is a rare chronic inflammatory disorder of the kidney. Infiltration to lung and liver can occur. We present a rare complication of locally invasive XGP extending beyond the diaphragm to the lung to cause bronchiectasis in an adolescent girl with chronic productive cough, weight loss and no urinary symptoms. The patient underwent open left radical nephrectomy, where it was noted that the left kidney lay very high with significant perinephric inflammation and was densely adherent to the diaphragm and partially adherent to the spleen. XGP was confirmed on histology.
Subcutaneous fat necrosis after selective head cooling in an infant
Authors: Kuboi Toru , Kusaka Takashi , Okazaki Kaoru , Kaku Uiko , Kakinuma Ryota , Kondo Masatoshi , Nishida Akira
Published: April 2013

Hypoxic‐ischemic encephalopathy in neonates causes irreversible damage to tissue and organs and results in multiple organ failure and poor outcome. Therapeutic hypothermia is the most effective therapy in neonates with hypoxic‐ischemic encephalopathy. We report here a case of subcutaneous fat necrosis (SCFN) after therapeutic hypothermia by selective head cooling. Selective head cooling was provided for 72 h after birth. SCFN developed on the patient's cheeks and back at the age of 21 days. Thus, SCFN may be caused by selective head cooling, similarly to whole‐body cooling.
Evaluating the potential of group singing to enhance the well‐being of older people
Authors: Davidson Jane W , McNamara Beverley , Rosenwax Lorna , Lange Andrea , Jenkins Sue , Lewin Gill
Published: April 2013

Aim

To evaluate the effect of a singing program developed specifically for older community‐dwelling people on measures of health and well‐being.

Method

An eight‐week singing program was developed and evaluated using standardised measures of health and well‐being, measures designed to examine specific singing program outcomes, and semi‐structured interviews. Participants aged 70 years and older were recruited through a home care service provider (n = 17) and an advertisement in a community newspaper (n = 19).

Results

Standard outcome measures indicated that the program had little effect on health and well‐being. However, study‐specific measures indicated that many participants had positive gains. Those in the home care group required more assistance to attend and continue in the program than those in the general community. Participants reported that the community‐based singing facilitator was essential to the program's success.

Conclusion

Well‐structured community‐based singing programs have the potential to impact positively upon the well‐being of older people, but program viability depends on support with recruitment, transport and funding.
Relation of symptom‐induced impairment with other illness parameters in clinic‐referred youth
Authors: Gadow Kenneth D. , Kaat Aaron J. , Lecavalier Luc
Published: April 2013

Objective

To examine the relation of caregiver ratings of psychiatric symptom‐induced impairment with number and severity of symptoms and informant agreement in consecutive child psychiatry outpatient referrals.

Methods

Parents and teachers completed a broadband DSM‐IV‐referenced rating scale with disorder‐specific impairment for 636 youth (6–18 years). Illness parameters included impairment, number and severity of symptoms, and their combination (symptom + impairment) as well as categorical (cut‐off) and dimensional scoring.

Results

Agreement between impairment and other illness parameters showed considerable variation as a function of type of parameter, disorder, and informant, but to lesser extent age and gender. Many youth who met impairment cut‐off for specific disorders did not meet symptom cut‐off. Conversely, most youth who met symptom cut‐off were impaired. Symptom cut‐off evidenced greater convergence with impairment cut‐off than combined symptom + impairment cut‐offs. Severity of impairment was moderately to highly correlated with number and severity of symptoms. Parents' and teachers' ratings indicated little disorder‐specific agreement about youth who met impairment cut‐off, symptom cut‐off, or combined symptom + impairment cut‐off. Therefore, sole reliance on one informant greatly underestimates the pervasiveness of impairment.

Conclusion

Findings are consistent with the notion that each illness parameter represents a unique conceptual construct, which has important clinical and research implications.