bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase II study results of a replacement therapy for hereditary angioedema with subcutaneous C1‐inhibitor concentrate
Authors: Zuraw B. L. , Cicardi M. , Longhurst H. J. , Bernstein J. A. , Li H. H. , Magerl M. , Martinez‐Saguer I. , Rehman S. M. M. , Staubach P. , Feuersenger H. , Parasrampuria R. , Sidhu J. , Edelman J. , Craig T.
Published: May 2015

Background

Hereditary angioedema (HAE) due to C1 inhibitor deficiency manifests as recurrent swelling attacks that can be disabling and sometimes fatal. Long‐term prophylaxis with twice‐weekly intravenous injections of plasma‐derived C1‐inhibitor (pdC1‐INH) has been established as an effective treatment. Subcutaneous (SC) administration of pdC1‐INH has not been studied in patients with HAE.

Methods

This open‐label, dose‐ranging, crossover study (COMPACT Phase II) was conducted in 18 patients with type I or II HAE who received two of twice‐weekly 1500, 3000, or 6000 IU SC doses of highly concentrated volume‐reduced CSL830 for 4 weeks each. The mean trough plasma levels of C1‐INH functional activity, C1‐INH and C4 antigen levels during Week 4, and overall safety and tolerability were evaluated. The primary outcome was model‐derived steady‐state trough C1‐INH functional activity.

Results

After SC CSL830 administration, a dose‐dependent increase in trough functional C1‐INH activity was observed. C1‐INH and C4 levels both increased. The two highest dose groups (3000 and 6000 IU) achieved constant C1‐INH activity levels above 40% values, a threshold that was assumed to provide clinical protection against angioedema attacks. Compared with intravenous injection, pdC1‐INH SC injection with CSL830 showed a lower peak‐to‐trough ratio and more consistent exposures. All doses were well tolerated. Mild‐to‐moderate local site reactions were noted with pain and swelling being the most common adverse event.

Conclusions

Subcutaneous volume‐reduced CSL830 was well tolerated and led to a dose‐dependent increase in physiologically relevant functional C1‐INH plasma levels. A clinical outcome study of SC CSL830 in patients with HAE warrants further investigation.
Intraocular and systemic inflammation‐related cytokines during one year of ranibizumab treatment for neovascular age‐related macular degeneration
Authors: Fauser Sascha , Viebahn Ulrike , Muether Philipp S.
Published: May 2015

Purpose

To determine inflammation‐related intraocular and systemic cytokine concentrations in neovascular age‐related macular degeneration (nAMD) compared with controls and to assess the influence of long‐term intravitreal ranibizumab treatment over 1 year.

Methods

Aqueous humour and blood plasma of 21 controls and 17 treatment‐naive nAMD patients were collected prior to cataract surgery or ranibizumab treatment. Follow‐up specimens in nAMD patients were acquired immediately prior to subsequent ranibizumab injections as needed. Multiplex bead assays were conducted for ten inflammation‐related cytokines and vascular endothelial growth factor (VEGF). p‐values were Holm–Bonferroni‐corrected for multiple comparisons.

Results

Prior to ranibizumab treatment, initiation aqueous humour levels of monocyte chemo‐attractant protein (MCP)‐1/CCL2 (p = 0.005) and vascular cell adhesin molecule (VCAM) (p = 0.002) were elevated in nAMD compared with controls. Other intraocular cytokines did not differ, including VEGF. In plasma, no differences between nAMD patients and controls were found at baseline. Pro re nata ranibizumab treatment over 12 months with 8 ± 2 injections reduced aqueous VEGF (p < 0.0001) with a trend to reduced VEGF plasma concentrations (p = 0.046), with all specimens taken at least 28 days after the previous injection. All other local and systemic cytokines remained unchanged.

Conclusion

Neovascular age‐related macular degeneration is associated with local ocular MCP‐1/CCL2 and VCAM elevations, suggesting a local inflammatory involvement in the pathophysiology of nAMD. We did not detect systemic differences. Ranibizumab treatment does not result in local or systemic changes of these cytokines, in contrast to VEGF suppression. MCP‐1/CCL2 and VCAM may be potential additional treatment targets for nAMD.
Role of peroxisome proliferator‐activated receptor alpha in the expression of hepatic fatty acid oxidation‐related genes in chickens
Authors: Honda Kazuhisa , Saneyasu Takaoki , Sugimoto Haruka , Kurachi Kiyotaka , Takagi Shoko , Kamisoyama Hiroshi
Published: May 2015

Liver is the most important target organ for investigation of lipid metabolism in domestic fowls. However, little is known about the regulatory mechanism of fatty acid oxidation in chicken liver. In mammals, proliferator‐activated receptor alpha (PPARα), a transcription factor, plays an essential role in the regulation of hepatic fatty acid oxidation. The aim of the present study was to investigate the regulatory mechanisms of PPARα‐induced gene expression involved in hepatic fatty acid oxidation in chickens in vivo and in vitro. WY14643, a PPARα agonist, significantly increased the messenger RNA (mRNA) levels of carnitine palmitoyltransferase 1a (CPT1a) and acyl‐coenzyme A oxidase (ACO), but not long‐, middle‐ and short‐chain acyl‐coenzyme A dehydrogenase (LCAD, MCAD and SCAD, respectively), hydroxyacyl‐coenzyme A dehydrogenase (HAD), and PPARα itself in chicken hepatoma cells. In contrast, WY14643 significantly increased the mRNA levels of CPT1a, ACO, MCAD, SCAD, HAD and PPARα in human hepatoma cells. The mRNA levels of CPT1a and ACO in the liver were significantly increased by 6 h of fasting in chickens, whereas the mRNA levels of LCAD, MCAD, SCAD and HAD were unchanged. These results suggest that, unlike in mammals, CPT1a and ACO might play an important role in PPARα‐induced fatty acid oxidation in the liver of chickens.
Effect of time at pasture and herbage intake on profile of volatile organic compounds of dairy cow milk
Authors: Ueda Yasuko , Asakuma Sadaki , Miyaji Makoto , Akiyama Fumiaki
Published: May 2015

Volatile organic compounds (VOCs) in milk were investigated as quantitative markers of herbage intake (HI) at pasture. Eight Holstein cows were fed indoors with concentrate and conserved forages (grass silage, corn silage and hay) (NG), then were divided into three treatments according to the duration of access to pasture: 4 h (G4), 8 h (G8), and 20 h (G20) per day. The HIs were 4.3, 8.6, and 13.0 kg dry matter/day for the G4, G8 and G20 treatments, respectively. Milk from cows was sampled and analyzed VOCs by the steam distillation‐extraction method and gas chromatography‐mass spectrometry (GC‐MS). From the intensity of the GC peak area, the levels of 1‐phytene (3,7,11,15‐tetramethyl‐1‐hexadecene) and 2‐phytene (3,7,11,15‐tetramethyl‐2‐hexadecene) were lowest in NG treatment and markedly increased with grazing time at pasture. With simple regression analysis on the HI to each diterpenoid, a strong correlation was found between the intensity of 1‐phytene in the milk and the HI (r = 0.807, P < 0.001). 1‐phytene content in milk could be useful as a quantitative marker of the HI of grazing cows.
The use of recorded lectures in education and the impact on lecture attendance and exam performance
Authors: Bos Nynke , Groeneveld Caspar , van Bruggen Jan , Brand‐Gruwel Saskia
Published: May 2015

Universities increasingly record lectures and make them available online for students. Though the technology to record these lectures is now solidly implemented and embedded in many institutions, the impact of the usage of recorded lectures on exam performance is not clear. The purpose of the current study is to address the use of recorded lectures in an authentic setting by focusing on the actual time spent on the usage of recorded lectures and the impact on lecture attendance and exam performance. The participants were 396 first‐year university psychology students attending a mandatory course on biological psychology. During the course, student attendance to face‐to‐face lectures was registered and the viewing of the recordings monitored. Results revealed that a large amount of students used the recorded lectures as a substitute for lecture attendance. The group who uses recorded lectures as a supplement when developing a knowledge base score significantly higher on the assessment. When assessing higher order thinking skills, no significant differences were found between using recording lectures and attending lectures. This can be partly explained by relatively low predictive value either form of lectures have on exam performance.
How we prevent and manage infection in sickle cell disease
Authors: Sobota Amy , Sabharwal Vishakha , Fonebi Gwendoline , Steinberg Martin
Published: May 2015

Sickle cell disease (SCD) affects approximately 100 000 people in the US, 12 500 in the UK, and millions worldwide. SCD is typified by painful vaso‐occlusive episodes, haemolytic anaemia and organ damage. A secondary complication is infection, which can be bacterial, fungal or viral. Universal newborn screening, routine use of penicillin prophylaxis, availability of conjugated vaccines against S. pneumoniae and comprehensive care programmes instituted during the past few decades in industrialized countries have dramatically reduced childhood mortality and improved life expectancy. Yet patients with SCD remain at increased risk of infection. Unfortunately, the treatment of most bacterial infections that are common in SCD is not based on the results of randomized controlled clinical trials. In their absence, treatment decisions are based on consensus guidelines, clinical experience or adapting treatment applied in other diseases. This leads to wide variation in treatment among institutions and even between treating physicians in a single institution. Prevention of infection, when possible, is most important and we focus on prevention through targeted prophylaxis and vaccination. We will share our management strategies for managing the more common infections in SCD and provide the rationale for our recommendations.
Child's verbal ability and gender are associated with age at diagnosis in a sample of young children with ASD in Europe
Authors: Salomone E. , Charman T. , McConachie H. , Warreyn P.
Published: May 2015

Background

Autism spectrum disorder can in some cases be reliably diagnosed by age 2 years, but in community settings, the mean age at diagnosis is often considerably higher. Later diagnosis has been found to be associated with lower symptom severity, lower parental socioeconomic status and fewer parental concerns. Gender differences in age at diagnosis have been examined, with mixed evidence.

Methods

We examined the association of child's verbal ability and gender, and parental education, with age at diagnosis in a large sample of young children with autism spectrum disorder in 18 European countries (n = 1410).

Results

There was considerable variation in age at diagnosis across countries. Children with better communication skills were diagnosed significantly later than non‐verbal and minimally verbal children. There was also a significant interaction of gender with verbal ability on age at diagnosis, in that female children with complex phrase speech were diagnosed later than male children with the same level of verbal ability.

Conclusions

Our findings highlight the need to implement public awareness initiatives and training for professionals to promote early detection and, consequently, early intervention for autism spectrum disorder in Europe.
Short‐term effect of diode laser cyclophotocoagulation on intraocular pressure: a prospective study
Authors: Uppal Samreen , Stead Richard E , Patil Bheemanagouda B , Henry Emer , Moodie Jonathan , Vernon Stephen A , King Anthony J
Published: May 2015

Background

This aims to determine the immediate and short‐term risk of intraocular pressure spikes following diode laser cyclophotocoagulation.

Design

This study is a prospective, consecutive cohort study in a UK teaching hospital.

Participants

Fifty‐three consecutive patients undergoing cyclophotocoagulation were invited to participate in this study.

Methods

Intraocular pressure (IOP) measurements were taken immediately prior to cyclodiode laser, hourly for the first 3 h after laser, on the first and seventh postoperative days, and at three months following laser.

Main Outcome Measures

Eyes experiencing intraocular pressure elevation defined at two levels (≥3 mm Hg and ≥10 mm Hg from the pretreatment level) were identified.

Results

Seventeen eyes (34%) had an elevation in intraocular pressure (≥3 mmHg) during the first 3 h postoperatively with a mean increase of 10.3 mmHg. No preoperative or perioperative associations were found for a postcyclodiode spike within the first 3 postoperative hours.No association was found between pressure spikes and visual acuity, reduction of glaucoma medication or final postoperative intraocular pressure at 3 months. Eyes that did not have an IOP spike during the first 3 h postoperatively had a greater reduction in IOP at 3 months (15.2 mmHg vs. 10.2 mmHg; P = 0.184).

Conclusion

IOP spikes are common in the immediate period after cyclophotocoagulation. An elevation in IOP is noted after the first hour in the vast majority who experience a spike in the first 3 h post‐procedure.
Sino‐Nasal Outcome Test‐22: translation, cultural adaptation and validation in Portugal
Authors: de Vilhena D. , Duarte D. , Lopes G.
Published: May 2015

Objectives

Sino‐Nasal Outcome Test‐22 is a questionnaire that evaluates the specific quality of life in chronic rhinosinusitis and was widely used in scientific literature. The aim of our study was to translate and culturally adapt Sino‐Nasal Outcome Test‐22 for the Portuguese reality and validate the version obtained for use in Portugal.

Design

We translate Sino‐Nasal Outcome Test‐22 into European Portuguese according to the methodology recommended by the scientific literature. After translation, we proceeded with the evaluation of the questionnaire regarding its feasibility, reliability (internal consistency and test–retest reproducibility) and discriminant validity. Statistical analysis was performed using spss 22.0.

Setting

Patients treated at a single institute.

Participants

We applied Sino‐Nasal Outcome Test‐22 questionnaire to 15 volunteers with no nasal or sinus disease and to 50 patients with chronic rhinosinusitis.

Main outcome measures

Feasibility, reliability (internal consistency and test–retest reproducibility) and discriminant validity.

Results

We observed good internal consistency, with general Cronbach's α coefficient of 0.935, good test–retest reproducibility (32.5 versus 32, P < 0.001), with Pearson coefficient of 0.99 (P < 0.001) and Cohen Kappa coefficient of 0.898. The discriminant validity of the Portuguese version of Sino‐Nasal Outcome Test‐22 was confirmed by applying the Mann–Whitney U‐test (P < 0.001).

Conclusions

Until now, there were no validated questionnaires to evaluate quality of life in patients with chronic rhinosinusitis in Portugal. Translation and validation of Sino‐Nasal Outcome Test‐22 in Portugal will allow a more consistent assessment of the specific quality of life of these patients and the comparison with international data. Thus, we recommend this version for use with the Portuguese population with chronic rhinosinusitis.
HAVE RENEWABLE PORTFOLIO STANDARDS RAISED ELECTRICITY RATES? EVIDENCE FROM U.S. ELECTRIC UTILITIES
Authors: Tra Constant I.
Published: May 2015

Using a panel dataset of U.S. electric utilities, we investigate the effect of a Renewable Portfolio Standards (RPS) on the rates of electric utilities affected by the mandate. Our findings are twofold. First, we find that, on average, electric utilities affected by an RPS mandate charged a higher electricity rate. This would suggest that an RPS mandate is a costly constraint on the utilities that have to comply with the requirement. The second finding of our analysis is that marginal increases in a utility's RPS requirement do not necessarily translate into higher electricity rates. This would imply that the costs imposed on utilities affected by the RPS mandate tend to be fixed costs rather than variable costs. We also find that controlling for time‐varying unobserved factors at the state level is key to identifying the RPS effect on electricity retail rates. (JEL Q42, Q48, L98)
Dynamic cerebral autoregulation to induced blood pressure changes in human experimental and clinical sepsis
Authors: Berg Ronan M. G. , Plovsing Ronni R. , Bailey Damian M. , Holstein‐Rathlou Niels‐Henrik , Møller Kirsten
Published: May 2015

Previous studies have demonstrated that dynamic cerebral autoregulation to spontaneous fluctuations in blood pressure is enhanced following lipopolysaccharide (LPS) infusion, a human experimental model of early sepsis, whereas by contrast it is impaired in patients with severe sepsis or septic shock. In this study, we hypothesized that this pattern of response would be identical during induced changes in blood pressure. Dynamic cerebral autoregulation was assessed in nine healthy volunteers and six septic patients. The healthy volunteers underwent a 4‐h intravenous infusion of LPS (total dose: 2 ng kg−1). Mean arterial blood pressure (MAP, arterial transducer) and middle cerebral artery blood flow velocity (MCAv, transcranial Doppler ultrasound) were recorded continuously during thigh‐cuff deflation‐induced changes in MAP for the determination of a modified rate of regulation (RoR). This was performed before and after LPS infusion in healthy volunteers, and within 72 h following clinical diagnosis of sepsis in patients. In healthy volunteers, thigh‐cuff deflation caused a MAP reduction of 16 (13–20) % at baseline and 18 (16–20) % after LPS, while the MAP reduction was 12 (11–13) % in patients (P<0·05 versus volunteers at baseline; P<0·01 versus volunteers after LPS). The corresponding RoR values increased from 0·46 (0·31–0·49) s−1 at baseline to 0·58 (0·36–0·74) s−1 after LPS (P<0·05) in healthy volunteers, whereas they were similar to values observed in patients [0·43 (0·36–0·52) s−1; P = 0·91 versus baseline; P = 0·14 versus LPS]. While our findings support the concept that dynamic cerebral autoregulation is enhanced during the very early stages of sepsis, they remain inconclusive with regard to more advanced stages of disease, because thigh‐cuff deflation failed to induce sufficient MAP reductions in patients.
Comparative analysis of cytokeratin 15, TDAG51, cytokeratin 20 and androgen receptor in sclerosing adnexal neoplasms and variants of basal cell carcinoma
Authors: Evangelista Mara Therese P. , North Jeffrey P.
Published: May 2015

Background

Desmoplastic trichoepithelioma (DTE), morpheaform basal cell carcinoma (BCC) and microcystic adnexal carcinoma (MAC) are sclerosing adnexal neoplasms with overlapping histopathologic features. We compared cytokeratin 15, (CK15), T‐cell death‐associated gene 51 (TDAG51), cytokeratin 20 (CK20) and androgen receptor (AR) in differentiating these tumors and assessed their expression in BCC subtypes.

Methods

Fifteen DTE, 15 infundibulocystic BCC, 18 micronodular BCC, 18 morpheaform BCC and 6 MAC were assessed for CK15, TDAG51, CK20 and AR expression.

Results

Quantitative CK15 staining was higher in DTE compared with BCC (p < 0.0001) and MAC (p = 0.02). Quantitative TDAG51 staining was higher in DTE than BCC (p < 0.0001). The CK20+AR− immunophenotype was 100% sensitive and specific in diagnosing DTE. The CK20−AR+ immunophenotype was 95.24% specific and 83.33% sensitive for BCC. The CK20−AR− immunophenotype was 83.33% sensitive and 90.91% specific for MAC. CK15, CK20 and AR were positive in 87, 53 and 67% of infundibulocystic BCC cases, respectively.

Conclusion

Combination of CK20 and AR best differentiated these sclerosing adnexal neoplasms. Greater positivity for CK15 and TDAG51 generally favors benign lesions. Infundibulocystic BCC has higher CK20 and lower AR immunopositivity than other BCC variants and a high degree of CK15 and TDAG51 positivity.
Pediatric dermatohistopathology – histopathology of skin diseases in newborns and infants
Authors: Wobser Marion , Ernestus Karen , Hamm Henning
Published: May 2015

While neonatal skin physiology has been thoroughly examined using non‐invasive techniques in recent years, only few systematic studies and review articles addressing the histopathology of neonatal skin have been published thus far. In most cases, histopathological findings of dermatoses in neonatal skin do not significantly differ from those seen in adult skin. Nevertheless, a comprehensive knowledge of embryonic and fetal skin development as well as the microanatomical structure of neonatal skin can contribute to a better understanding of various dermatoses of infancy. In the first part of this review article, we present the histopathological features of such skin diseases, which, though generally rare, almost exclusively appear during the first weeks of life due to distinctive structural and functional features of neonatal skin. The second part is dedicated to classic dermatoses of infancy and their histopathological features.
Customer Use of Virtual Channels in Multichannel Services: Does Type of Activity Matter?
Authors: Sousa Rui , Amorim Marlene , Rabinovich Elliot , Sodero Anníbal C.
Published: May 2015

Many firms have recently adopted virtual channels, based most notably on the Internet and the phone, to complement the delivery of services to their customers by their existing physical facilities. The success of such multichannel (MC) strategies relies on the alignment of service design decisions—namely those concerning the allocation of service activities to virtual channels—with customers’ MC behavior. Although prior studies have looked at the intensity with which customers use virtual channels, they have not addressed virtual channel use for different types of service activities.

In our study, we investigate whether customers’ use of virtual channels for MC services varies with the type of service activities they engage in, and if so, in what way. In doing so, we address two objectives. First, we investigate the impact of accessibility to the physical channel on the degree of use of virtual channels (Internet and phone, aggregated) for different types of activities. Second, we look at channel preferences (Internet vs. phone) for different types of activities when customers do resort to virtual channels to conduct activities.

To address our objectives, we develop and test hypotheses regarding customers’ use of virtual channels based on the match between activity attributes (complexity and volume) and channel attributes (access efficiency, interface efficiency, interface richness). Using data from a MC bank, we find that the impact of accessibility to physical channels (specifically, customer distance) on customers’ use of virtual channels, as well as the relative use of Internet versus phone, depend on the type of activities.
Predicting the effects of whale population recovery on Northeast Pacific food webs and fisheries: an ecosystem modelling approach
Authors: Surma Szymon , Pitcher Tony J.
Published: May 2015

The recovery of whale populations from historical depletion may have the potential to noticeably affect Northeast Pacific ecosystems and fisheries. Surplus production models based on whaling catch records were used to reconstruct the historical abundances of five large whale species in the waters surrounding Haida Gwaii, British Columbia. The results suggest that the local abundances of all five species were vastly higher before the onset of modern whaling. A comparison of ecosystem models representing the states of the local marine food web before and after full whale recovery indicates that abundant whales could consume large proportions of the annual production of their principal prey, ranging up to 87% for Pacific herring (Clupea pallasii) and 72% for piscivorous rockfish (Sebastes spp.). Dynamic modelling of the food web effects of whale recovery, including simulations of simultaneous top‐down and bottom‐up forcing and a Monte Carlo sensitivity analysis, revealed noticeable (∼6–12%) top‐down effects on Pacific herring biomass owing to increased predation by humpback and fin whales. However, these effects cannot explain the magnitude of recent declines in local herring biomass. The dynamic modelling results also suggest that top‐down effects of whale recovery could result in reduced biomasses of large rockfish as a result of predation by sperm whales, as well as potential cascading effects on many demersal fish groups. These findings have numerous practical implications for ecosystem‐based fisheries management and whale conservation strategies in Northeast Pacific waters.
Advanced glycation end‐products accelerate the cardiac aging process through the receptor for advanced glycation end‐products/transforming growth factor‐β‐Smad signaling pathway in cardiac fibroblasts
Authors: Fang Min , Wang Junhong , Li Shiling , Guo Yan
Published: May 2015

Aims

The current study was carried out to evaluate the effect of advanced glycation end‐products (AGE) on cardiac aging and to explore its underlying mechanisms.

Methods

Neonatal rat cardiac fibroblasts were cultured and divided into four groups: control; AGE; AGE + receptor for AGE antibody and AGE + SB431542 (transforming growth factor‐β [TGF‐β]/Smad signaling pathway inhibitor, 10 μmol/L) group. After being cultured for 48 h, the cells were harvested and the senescence‐associated beta‐galactosidase expression was analyzed. Then the level of p16, TGF‐β, Smad/p‐smad and matrix metalloproteinases‐2 was evaluated by western blot.

Results

Significantly increased senescence‐associated beta‐galactosidase activity as well as p16 level was observed in the AGE group. Furthermore, AGE also significantly increased the TGF‐β1, p‐smad2/3 and metalloproteinases‐2 expression in cardiac fibroblasts (all P < 0.01). Meanwhile, either pretreatment with receptor for AGE‐Ab or SB431542 significantly inhibited the upregulated cardiac senescence (beta‐galactosidase activity and P16) and fibrosis‐associated (TGF‐β1, p‐smad2/3 and metalloproteinases‐2) markers induced by AGE.

Conclusions

Taken together, all these results suggested that AGE are an important factor for cardiac aging and fibrosis, whereas the receptor for AGE and TGF‐β/Smad signaling pathway might be involved in the AGE‐induced cardiac aging process. Geriatr Gerontol Int 2016; 16: 522‐527.
Impact of hospitalization on modification of drug regimens: Results of the criteria to assess appropriate medication use among elderly complex patients study
Authors: Sganga Federica , Landi Francesco , Vetrano Davide L , Corsonello Andrea , Lattanzio Fabrizia , Bernabei Roberto , Onder Graziano
Published: May 2015

Aim

To assess the impact of hospitalization on modification of drug burden among elderly patients.

Methods

The present prospective cohort study was carried out in acute care hospitals in Italy. The difference in the number of drugs used before hospital admission and those prescribed at discharge was calculated. The prevalence of (i) any increase (1 or more drugs); and (ii) an increase >50% in the number of drugs from admission to discharge was calculated, and the factors associated with these conditions were identified.

Results

The mean age of 1082 participants was 81.2 ± 7.3 years and 606 were women (56.0%), an increase in the number of drugs (1 or more drugs) between admission and discharge was observed in 672 participants (62.1% of study sample) and an “increase >50%” was observed in 372 participants (34.3%). “Any increase” was inversely associated with age and the number of drugs used before hospitalization, and it was positively associated with length of stay and diagnoses, including chronic obstructive pulmonary disease, ischemic heart disease and diabetes. “Increase >50%” was inversely associated with female sex, the number of drugs before hospitalization, involuntary loss of weight and intact cognitive status, and was positively associated with length of stay, chronic obstructive pulmonary disease, heart failure and diabetes.

Conclusions

Not only disease, but also demographic factors (age and gender) and geriatric syndromes (weight loss and cognitive status) might influence pharmacological burden. These data might be useful in order to target interventions aimed at improving drug use and reducing iatrogenic illness. Geriatr Gerontol Int 2016; 16: 593–599.
Association between employee benefits and frailty in community‐dwelling older adults
Authors: Avila‐Funes José Alberto , Paniagua‐Santos Diana Leticia , Escobar‐Rivera Vicente , Navarrete‐Reyes Ana Patricia , Aguilar‐Navarro Sara , Amieva Hélène
Published: May 2015

Aim

The phenotype of frailty has been associated with an increased vulnerability for the development of adverse health‐related outcomes. The origin of frailty is multifactorial and financial issues could be implicated, as they have been associated with health status, well‐being and mortality. However, the association between economic benefits and frailty has been poorly explored. Therefore, the objective was to determine the association between employee benefits and frailty.

Methods

A cross‐sectional study of 927 community‐dwelling older adults aged 70 years and older participating in the Mexican Study of Nutritional and Psychosocial Markers of Frailty was carried out. Employee benefits were established according to eight characteristics: bonus, profit sharing, pension, health insurance, food stamps, housing credit, life insurance, and Christmas bonus. Frailty was defined according to a slightly modified version of the phenotype proposed by Fried et al. Multinomial logistic regression models were run to determine the association between employee benefits and frailty adjusting by sociodemographic and health covariates.

Results

The prevalence of frailty was 14.1%, and 4.4% of participants rated their health status as “poor.” Multinomial logistic regression analyses showed that employee benefits were statistically and independently associated with the frail subgroup (OR 0.85; 95% CI 0.74–0.98; P = 0.027) even after adjusting for potential confounders.

Conclusions

Fewer employee benefits are associated with frailty. Supporting spreading employee benefits for older people could have a positive impact on the development of frailty and its consequences. Geriatr Gerontol Int 2016; 16: 606–611.
MET in gastric cancer – discarding a 10% cutoff rule
Authors: Metzger Marie‐Luise , Behrens Hans‐Michael , Böger Christine , Haag Jochen , Krüger Sandra , Röcken Christoph
Published: May 2015

Aims

We aimed to develop a putative predictive biomarker score for future hepatocyte growth factor receptor (MET)‐targeted therapy of gastric cancer (GC).

Methods and results

MET expression and MET amplification were analysed by immunohistochemistry (IHC) and chromogenic in‐situ hybridization (CISH) in 470 GC patients. Immunostaining was documented with the HistoScore. The percentage area of MET‐amplified tumour cell clones was assessed by virtual microscopy. The expression of MET was heterogeneous in primary and metastatic GC. Immunostaining intensity (MET‐IHC 2+/3+) correlated with MET amplification and a positive MET status was defined by a combination of MET‐IHC 2+ or 3+ with MET amplification, or MET‐IHC 3+ without MET amplification. The prognostic significance of the MET status was independent from the percentage area of positive tumour cells (e.g. <10 versus ≥10%). MET‐positive GCs were microsatellite stable and of KRAS/PIK3CA wild‐type. MET‐positive GCs had a very poor prognosis, with a median survival of 5.4 months and a hazard ratio of 2.126.

Conclusions

A combination of immunohistochemistry and CISH is suitable to assess MET status. If MET status is used as a predictive biomarker, prospective studies should pay specific attention to adequate tissue sampling, should ignore cutoff values for tumour areas, may consider the KRAS and PIK3CA genotype as negative predictive markers and should carry out the analysis expeditiously.
Laboratory measurements of ‘porosity‐free’ intrinsic Vp and Vs in an olivine gabbro of the Oman ophiolite: Implication for interpretation of the seismic structure of lower oceanic crust
Authors: Saito Satoshi , Ishikawa Masahiro , Arima Makoto , Tatsumi Yoshiyuki
Published: May 2015

In order to determine ‘porosity‐free’ intrinsic ultrasonic compressional (Vp) and shear wave (Vs) velocities and Vp/Vs of an olivine gabbro from the Oman ophiolite, we developed a new experimental system using a piston‐cylinder type high‐pressure apparatus. The new system allowed us to measure velocities at pressures ranging from 0.20 to 1.00 GPa and at temperatures up to 300°C for Vp and 400°C for Vs. At room temperature, the Vp and Vp/Vs increase rapidly with pressure up to 0.40 GPa, while between 0.45 and 1.00 GPa the increase is more gradual. The change in increasing rate is attributed to closure of porosity at pressures above 0.45 GPa. Based on the linear regression of data obtained at higher pressures (0.45–1.00 GPa) and extrapolation to the lower pressures, combined with temperature derivatives of velocities of the sample measured at 1.00 GPa, we determined the intrinsic Vp and Vs of the sample as a function of pressure (P, in GPa) and temperature (T, in °C). The intrinsic velocities can be expressed as Vp (km/s) = 7.004 + 0.096 × P − 0.00015 × T, and Vs (km/s) = 3.827 + 0.007 × P − 0.00008 × T. We evaluated the intrinsic Vp and Vs of the olivine gabbro at oceanic crustal conditions and compared them with a velocity depth‐profile of the borehole seismic observatory WP‐2 area in the northwestern Pacific Basin. Although the intrinsic Vp (∼7.0 km/s) and Vs (∼3.8 km/s) for the olivine gabbro studied are comparable to those of seismic layer 3 in the WP‐2 area, the estimated vertical gradients of intrinsic velocities are significantly smaller than those reported from layer 3. These results suggest that velocity profiles of layer 3 in the WP‐2 area may reflect the presence of a minor porosity in lower oceanic crust, which closes with increasing depth and/or continuous changes in mineralogy of layer 3 rocks.
A novel technique for simultaneous whole‐body and multi‐organ decellularization: umbilical artery catheterization as a perfusion‐based method in a sheep foetus model
Authors: Kajbafzadeh Abdol‐Mohammad , Khorramirouz Reza , Akbarzadeh Aram , Sabetkish Shabnam , Sabetkish Nastaran , Saadat Paria , Tehrani Mona
Published: May 2015

The aim of this study was to develop a method to generate multi‐organ acellular matrices. Using a foetal sheep model have developed a method of systemic pulsatile perfusion via the umbilical artery which allows for simultaneous multi‐organ decellularization. Twenty sheep foetuses were systemically perfused with Triton X‐100 and sodium dodecyl sulphate. Following completion of the whole‐body decellularization, multiple biopsy samples were taken from different parts of 21 organs to ascertain complete cell component removal in the preserved extracellular matrices. Both the natural and decellularized organs were subjected to several examinations. The samples were obtained from the skin, eye, ear, nose, throat, cardiovascular, respiratory, gastrointestinal, urinary, musculoskeletal, central nervous and peripheral nervous systems. The histological results depicted well‐preserved extracellular matrix (ECM) integrity and intact vascular structures, without any evidence of residual cellular materials, in all decellularized bioscaffolds. Scanning electron microscope (SEM) and biochemical properties remained intact, similar to their age‐matched native counterparts. Preservation of the collagen structure was evaluated by a hydroxyproline assay. Dense organs such as bone and muscle were also completely decellularized, with a preserved ECM structure. Thus, as shown in this study, several organs and different tissues were decellularized using a perfusion‐based method, which has not been previously accomplished. Given the technical challenges that exist for the efficient generation of biological scaffolds, the current results may pave the way for obtaining a variety of decellularized scaffolds from a single donor. In this study, there have been unique responses to the single acellularization protocol in foetuses, which may reflect the homogeneity of tissues and organs in the developing foetal body.
Addressing Information Needs to Reduce the Audit Expectation Gap: Evidence from Dutch Bankers, Audited Companies and Auditors
Authors: Litjens Robin , van Buuren Joost , Vergoossen Ruud
Published: May 2015

This study examines what the impact is of frequently proposed information needs on reducing the audit expectations gap (AEG), including information about the audited company, information about the audit process and changes to the auditors' report. We base our findings on a survey of 302 participants from the Netherlands, consisting of 61 bankers, 118 preparers and 123 auditors. We consider the AEG in essence to be a classic agency problem. We find that stakeholders fall back in basic strategies to maximize their own value: bankers require additional information, management is reluctant to let the auditor provide sensitive information and auditors try to minimize their risks. Further, we observe that only information about the audit process with respect to continuity and the reporting of errors in the financial statements may reduce the bankers' AEG. Finally, we observe that format changes to the auditors' report do not reduce the bankers' AEG.
Up in smoke: demarketing and consumer smoking cessation
Authors: White Christopher J. , Thomas Harrison
Published: May 2015

The concept of demarketing refers to the use of marketing techniques to reduce or eliminate demand for a product or service. A review of the demarketing literature relating to health and specifically antismoking initiatives indicated that, while research on this topic exists, much of it is not grounded in an acceptable attitudinal or behavioural theory. After determining the importance placed by a sample of 18–24‐year olds on nine demarketing initiatives, two dimensions were identified that best explained this construct. Items within these dimensions were summed and averaged to form single variables, which were then used to form the attitudinal component of the Model of Goal Directed Behaviour. The findings showed that two of these variables – one that captured product packaging aspects and another that consisted of place and price items – significantly influenced the desire to quit and indirectly influenced the intention to quit. Anticipated positive emotions, frequency of quitting attempts and perceived control over quitting also positively influenced the desire and/or intention to quit. The article concludes with a discussion that interprets these findings from a theoretical and practical perspective and suggests directions for future research.
Long‐term follow‐up and epidemiological trends in patients with pretibial myxedema: an 11‐year study from a tertiary care center in northern India
Authors: Sendhil Kumaran Muthu , Dutta Pinaki , Sakia Uma , Dogra Sunil
Published: May 2015

Introduction

Pretibial myxedema (PTM) is a rare manifestation of Graves' disease. There is paucity of data regarding long‐term follow‐up and response to treatment in PTM.

Materials and methods

Retrospective study wherein 30 patients of PTM presenting during 2001–2011 attending dermatology and endocrinology outpatient departments were analyzed.

Results

Among 30 patients with PTM, 12 were males and 18 females with a ratio of 1 : 1.5 males/females. Four morphological forms were identified: plaques (18 patients), diffuse non‐pitting edema of both lower legs (five), nodules (five), and elephantiasis lesions (two). Eighty percent were diagnosed with hyperthyroidism before the development of dermopathy. Twenty‐six patients presented with ophthalmopathy. Fourteen patients with plaque had an excellent response to topical clobetasol propionate ointment and attained complete resolution by 3.6 years. Out of 16 patients treated with combination therapy, which included nine treated with topical corticosteroids/intralesional triamcinolone and seven treated with oral, intralesional, and topical corticosteroids, nine attained complete resolution in the lesions by 3.4 years, and none relapsed anytime during four years of post‐treatment follow‐up. However, the remaining patients (elephantiasis and diffuse forms) failed to achieve complete resolution.

Conclusions

Plaques and nodules are common variants with a favorable clinical response to topical and intralesional corticosteroid; elephantine and diffuse forms responded poorly to therapy. Studies analyzing larger cohorts of patients with PTM and their long‐term follow‐up are limited, hence more such studies are required.
Regulation on Migrant Workers’ Employment in the Israeli Construction Sector
Authors: Ida Yoram , Talit Gal
Published: May 2015

This article deals with a reform in the regulation on employment of migrant workers which was implemented in the Israeli construction industry from 2005. This corporations‐based arrangement replaced a restrictive employment arrangement which tied the employee to a specific employer. The new regulation of work conditions and wages, coupled with a significant reduction in the number of work permits issued to construction, has improved work conditions and wages paid to migrant workers, and made their employment less attractive to employers. The reform also included elements designed to reduce the illegal employment phenomenon and to encourage migrant workers to leave the country at the end of their contracts. However, the new arrangement still restricted the mobility of migrant workers to some extent and had negative consequences such as a significant rise in the broker fees demanded of workers.
A Conversation with Jack Kalbfleisch and Jerry Lawless
Authors: Wild Chris J.
Published: May 2015

Half a century ago, two 18‐year‐olds arrive at university, are randomly paired as chemistry lab partners and become fast friends. Their careers and even family lives entwine, and both go on to join the pantheon of Canada's great statisticians. This all begins at a time when North American university education, and access to it, is growing explosively. It begins at a small start‐up university, an upstart start‐up that eschews conventional wisdom, finds a way to mine a seam of the brightest high school students and innovates—catching important waves and becoming a mathematical sciences powerhouse. In this interview, we explore these stories and some lessons that might be learned from them. Unfortunately lurking variables confound the easily implemented ‘put them in chemistry class in random pairs’ as a prescription for producing top‐flight statisticians.
Rapid Preparation of SiC Fibers Using a Curing Route of Electron Irradiation in a Low Oxygen Concentration Atmosphere
Authors: Su Zhiming , Zhang Litong , Li Yongcai , Li Siwei , Chen Lifu
Published: May 2015

Polycarbosilane (PCS) fiber was irradiated by electron beam at low dose in a flowing N2/O2 mixture with O2 concentration of 1%. After the pyrolysis of the irradiated precursor fibers, SiC fibers with high strength of 2.4 GPa were obtained. Microstructural evolutions of the resultant fibers were explored. It was found that during the irradiation, free radicals were formed in the PCS and were oxidized by oxygen as Si–OH groups. The Si–OH groups then transformed into Si–O–Si linkage and resulted in further cross‐linking of the PCS during pyrolysis. A remarkable structure gradient along the fiber diameter was formed under the coupled effects of irradiation and oxidation. The content of oxygen decreased from the fiber surface to the core, whereas the crystallinity of β‐SiC increased in the same direction. The electrical resistivity of the as‐prepared ceramic fiber was 80.7 Ω cm, showing good potential for being as electromagnetic wave absorber.
The current status of theory evaluation in nursing
Authors: Im Eun‐Ok
Published: May 2015

Aims

To identify the current status of theory evaluation in nursing and provide directions for theory evaluation for future development of theoretical bases of nursing discipline.

Background

Theory evaluation is an essential component in development of nursing knowledge, which is a critical element in development of nursing discipline. Despite earlier significant efforts for theory evaluation in nursing, a recent decline in the number of theory evaluation articles was noted and there have been few updates on theory evaluation in nursing.

Design

Discussion paper.

Data sources

A total of 58 articles published from 2003–2014 were retrieved through searches using the PUBMED, PsyInfo and CINAHL. The articles were sorted by the area of evaluation and analysed to identify themes reflecting the theory evaluation process.

Implications for nursing

Diverse ways of theory evaluation need to be continuously used in future theory evaluation efforts.

Conclusion

Six themes reflecting the theory evaluation process were identified: (a) rarely using existing theory evaluation criteria; (b) evaluating specifics; (c) using various statistical analysis methods; (d) developing instruments; (e) adopting in practice and education; and (f) evaluating mainly middle‐range theories and situation‐specific theories.
Operationalisation of quality of life for adults with severe disabilities
Authors: Gómez L. E. , Arias B. , Verdugo M. Á. , Tassé M. J. , Brown I.
Published: May 2015

Background

The operationalisation of quality of life for people with more severe disabilities has been acknowledged in the published research for more than two decades. This study aims to contribute to our knowledge and understanding of the quality of life of adults with severe disabilities by developing a set of quality of life indicators appropriate to this population using a Delphi method and the eight‐domain conceptual model proposed by Schalock & Verdugo ().

Method

The participating panel in the Delphi method included 12 experts who evaluated each proposed item according to four criteria: suitability, importance, observability and sensitivity. Descriptive analyses were used to select the best items in each of the four rounds of this Delphi study, as well as examining the coefficients of concordance that were calculated for the final pool of items.

Results

The four rounds of the Delphi study resulted in a final pool of 118 items (91 that were considered valid in the first round plus 27 items proposed, reformulated or discussed in the following rounds). Importance and sensitivity were the criteria that received the highest and lowest ratings, respectively, but also the ones that had the highest and lowest mean coefficients of concordance. Experts showed the strongest agreement for items related to material well‐being, while the weakest was found for items related to personal development.

Conclusions

This study further contributes to our understanding of how to operationalise and measure quality of life in adults with severe disabilities. The item pool generated may prove helpful in the development of instruments for the measurement of quality of life‐related outcomes in this population.
Competing for Order Flow in OTC Markets
Authors: LESTER BENJAMIN , ROCHETEAU GUILLAUME , WEILL PIERRE‐OLIVIER
Published: May 2015

We develop a model of a two‐sided asset market in which trades are intermediated by dealers and are bilateral. Dealers compete to attract order flow by posting the terms at which they execute trades—which can include prices, quantities, and execution speed—and investors direct their orders toward dealers who offer the most attractive terms. We characterize the equilibrium in a general setting, and we illustrate theoretically and numerically how the model can account for several important trading patterns in over‐the‐counter markets, which do not emerge from existing models.