bluuebunny/crossref_metadata_2025 huggingface dataset:
‘It's something you have to put up with’—service users’ experiences of in utero transfer: a qualitative study
Authors: Porcellato L , Masson G , O'Mahony F , Jenkinson S , Vanner T , Cheshire K , Perkins E
Published: January 2015

Objective

The purpose of this study was to gain in‐depth insight and enhance understanding of service users’ experiences of the in utero transfer (IUT) process, in order to inform policy and improve the current service provision of maternal care.

Design

Qualitative descriptive study using semi‐structured interviews.

Setting

Participant's home or hospital in the Midlands, UK.

Population

Fifteen women transferred in utero to a tertiary level maternity hospital; five male partners and two grandmothers.

Methods

Audio‐recorded individual or paired semi‐structured interviews transcribed verbatum and analysed thematically using nvivo 9.

Main outcome measures

Facilitators and barriers of the IUT experience.

Results

Findings suggest that IUT is an emotional experience that financially disadvantages patients and their families. Male partners were perceived to be most negatively affected by the experience. The quality of the IUT experience was influenced by a range of factors, including the lack of proximity to home and the lack of information. Patients had little knowledge or awareness of IUT, and most felt unprepared for displacement. Despite this, there was resigned acceptance that IUT was a necessary rather than adverse experience.

Conclusions

The experience of IUT for service users could be enhanced by ensuring that they are better informed about the process and the circumstances that necessitate displacement, that they are better informed about the hospital to which they are being transferred, and that they are transferred as close to home as possible. Efforts to minimise the emotional and socio‐economic impact of IUT on women and their families also need to be considered.
Diagnostic value of protein chips constructed by lung‐cancer‐associated markers selected by the T7 phage display library
Authors: Li Hong‐Mei , Guo Kang , Yu Zhuang , Feng Rui , Xu Ping
Published: January 2015

Background

Traditional diagnostic technology with tumor biomarkers is inefficient, expensive and requires a large number of serum samples. The purpose of this study was to construct human lung cancer protein chips with new lung cancer biomarkers screened by the T7‐phage display library, and improve the early diagnosis rate of lung cancer.

Methods

A T7‐phage cDNA display library was constructed of fresh samples from 30 lung cancer patients. With biopanning and high‐throughput screening, we gained the immunogenic phage clones from the cDNA library. The insert of selected phage was blasted at GeneBank for alignment to find the exact or the most similar known genes. Protein chips were then constructed and used to assay their expression level in lung cancer serum from 217 cases of lung cancer groups:80 cases of benign lung disease and 220 healthy controls.

Results

After four rounds of Biopanning and two rounds of enzyme‐linked immunosorbent assay, 12 phage monoclonal samples were selected from 2880 phage monoclonal samples. After blasting at GeneBank, six similar genes were used to construct diagnostic protein chips. The protein chips were then used to assay expression level in lung cancer serum. The expression level of six genes in lung cancer groups was significantly higher than those in the other two groups (P < 0.05).

Conclusions

In this study, we successfully constructed diagnostic protein chips with biomarkers selected from the lung cancer T7‐phage cDNA library, which can be used for the early screening of lung cancer patients.
Recruitment in a social carnivore before and after harvest
Authors: Ausband D. E. , Stansbury C. R. , Stenglein J. L. , Struthers J. L. , Waits L. P.
Published: January 2015

Knowledge about recruitment in a population can be critical when making conservation decisions, particularly for harvested species. Harvest can affect population demography in complex ways and this may be particularly true for cooperatively breeding species whose successful reproduction is often linked with complex social dynamics. We currently have a poor understanding of how harvest affects recruitment in cooperatively breeding species. We used non‐invasive genetic sampling and a natural experiment to estimate recruitment in a population of gray wolves Canis lupus before and after harvest in the northern Rocky Mountains, US (2008–2013). We hypothesized that recruitment would decline after hunting and trapping began and that the decline in recruitment would be attributable to the harvest of pups and not to the subtler mechanisms associated with group dynamics and reduced reproductive success. We collected fecal samples from wolves in 10 packs for 6 consecutive years, extracted DNA and genotyped 154 individual pups across 18 microsatellite loci. Population harvest rates averaged 23.8% (sd = 9.2). Our hypothesis that recruitment would decline was supported; survival from 3 to 15 months of age decreased from 0.60 [95% confidence interval (CI): 0.48–0.72] without harvest to 0.38 (95% CI: 0.28–0.48) with harvest and recruitment declined from 3.2 (95% CI: 2.1–4.3) to 1.6 (95% CI: 1.1–2.1) pups per pack after harvest was initiated. We cannot unequivocally dismiss other factors that could have reduced recruitment, however, an increase in recruitment when harvest temporarily ceased lends support to our conclusion that harvest reduced recruitment. We attributed just 18–38% of pup mortality directly to harvest and suggest that there are indirect effects of harvest on recruitment that may be associated with changes in group size and structure. Models that do not include both direct and indirect effects of harvest on recruitment may underestimate the potential impact of harvest on population growth in social species.
Pharmacokinetic interactions among imatinib, bosentan and sildenafil, and their clinical implications in severe pulmonary arterial hypertension
Authors: Renard Didier , Bouillon Thomas , Zhou Ping , Flesch Gerard , Quinn Debbie
Published: January 2015

Aims

This study characterized the population pharmacokinetics (PK) of imatinib in patients with severe pulmonary arterial hypertension (PAH), investigated drug–drug interactions (DDI) among imatinib, sildenafil and bosentan, and evaluated their clinical implications.

Methods

Plasma concentrations of imatinib, bosentan and sildenafil were collected in a phase III study and were used to characterize the PK of imatinib in this population. DDIs among the three drugs were quantified using a linear mixed model and log‐transformed drug concentrations.

Results

The population mean estimates of apparent clearance (CL/F) and volume (V/F) were 10.8 l h–1 (95% CI 9.2, 12.4 l h–1) and 267 l (95% CI 208, 326 l), respectively. It was estimated that sildenafil concentrations increased, on average, by 64% (95% CI 32%, 103%) and bosentan concentrations by 51% (95% CI 12%, 104%), in the presence of imatinib. Despite increased concentrations of co‐medications, treatment differences between imatinib and placebo for change in 6 min walk distance and pulmonary vascular resistance were relatively constant across the entire concentration range for sildenafil and bosentan. Overall, higher concentrations of imatinib and bosentan were not associated with increasing liver enzymes (serum glutamic oxaloacetic transaminases [SGOT]/serum glutamic‐pyruvic transaminase [SGPT]).

Conclusions

Population PKs of imatinib in patients with severe PAH were found comparable with those of patients with chronic myeloid leukemia. Imatinib was found effective regardless of the co‐medications and showed intrinsic efficacy beyond merely elevating the concentrations of the co‐medications due to DDIs. There was no evidence of increased risk of liver toxicity upon co‐administration with bosentan.
Peroxisystem: Harnessing systems cell biology to study peroxisomes
Authors: Schuldiner Maya , Zalckvar Einat
Published: January 2015

In recent years, high‐throughput experimentation with quantitative analysis and modelling of cells, recently dubbed systems cell biology, has been harnessed to study the organisation and dynamics of simple biological systems. Here, we suggest that the peroxisome, a fascinating dynamic organelle, can be used as a good candidate for studying a complete biological system. We discuss several aspects of peroxisomes that can be studied using high‐throughput systematic approaches and be integrated into a predictive model. Such approaches can be used in the future to study and understand how a more complex biological system, like a cell and maybe even ultimately a whole organism, works.
Cryptotanshinone, an orally bioactive herbal compound from Danshen, attenuates atherosclerosis in apolipoprotein E‐deficient mice: role of lectin‐like oxidized LDL receptor‐1 (LOX‐1)
Authors: Liu Zhiping , Xu Suowen , Huang Xiaoyang , Wang Jiaojiao , Gao Si , Li Hong , Zhou Changhua , Ye Jiantao , Chen Shaorui , Jin Zheng‐Gen , Liu Peiqing
Published: January 2015

Background and Purpose

Cryptotanshinone (CTS) is a major bioactive diterpenoid isolated from Danshen, an eminent medicinal herb that is used to treat cardiovascular disorders in Asian medicine. However, it is not known whether CTS can prevent experimental atherosclerosis. The present study was designed to investigate the protective effects of CTS on atherosclerosis and its molecular mechanisms of action.

Experimental Approach

Apolipoprotein E‐deficient (ApoE−/−) mice, fed an atherogenic diet, were dosed daily with CTS (15, 45 mg kg−1 day−1) by oral gavage. In vitro studies were carried out in oxidized LDL (oxLDL)‐stimulated HUVECs treated with or without CTS.

Key Results

CTS significantly attenuated atherosclerotic plaque formation and enhanced plaque stability in ApoE−/− mice by inhibiting the expression of lectin‐like oxLDL receptor‐1 (LOX‐1) and MMP‐9, as well as inhibiting reactive oxygen species (ROS) generation and NF‐κB activation. CTS treatment significantly decreased the levels of serum pro‐inflammatory mediators without altering the serum lipid profile. In vitro, CTS decreased oxLDL‐induced LOX‐1 mRNA and protein expression and, thereby, inhibited LOX‐1‐mediated adhesion of monocytes to HUVECs, by reducing the expression of adhesion molecules (intracellular adhesion molecule 1 and vascular cellular adhesion molecule 1). Furthermore, CTS inhibited NADPH oxidase subunit 4 (NOX4)‐mediated ROS generation and consequent activation of NF‐κB in HUVECs.

Conclusions and Implications

CTS was shown to have anti‐atherosclerotic activity, which was mediated through inhibition of the LOX‐1‐mediated signalling pathway. This suggests that CTS is a vasculoprotective drug that has potential therapeutic value for the clinical treatment of atherosclerotic cardiovascular diseases.

Linked Articles

This article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-23
AM841, a covalent cannabinoid ligand, powerfully slows gastrointestinal motility in normal and stressed mice in a peripherally restricted manner
Authors: Keenan C M , Storr M A , Thakur G A , Wood J T , Wager‐Miller J , Straiker A , Eno M R , Nikas S P , Bashashati M , Hu H , Mackie K , Makriyannis A , Sharkey K A
Published: January 2015

Background and Purpose

Cannabinoid (CB) ligands have been demonstrated to have utility as novel therapeutic agents for the treatment of pain, metabolic conditions and gastrointestinal (GI) disorders. However, many of these ligands are centrally active, which limits their usefulness. Here, we examine a unique novel covalent CB receptor ligand, AM841, to assess its potential for use in physiological and pathophysiological in vivo studies.

Experimental Approach

The covalent nature of AM841 was determined in vitro using electrophysiological and receptor internalization studies on isolated cultured hippocampal neurons. Mouse models were used for behavioural analysis of analgesia, hypothermia and hypolocomotion. The motility of the small and large intestine was assessed in vivo under normal conditions and after acute stress. The brain penetration of AM841 was also determined.

Key Results

AM841 behaved as an irreversible CB1 receptor agonist in vitro. AM841 potently reduced GI motility through an action on CB1 receptors in the small and large intestine under physiological conditions. AM841 was even more potent under conditions of acute stress and was shown to normalize accelerated GI motility under these conditions. This compound behaved as a peripherally restricted ligand, showing very little brain penetration and no characteristic centrally mediated CB1 receptor‐mediated effects (analgesia, hypothermia or hypolocomotion).

Conclusions and Implications

AM841, a novel peripherally restricted covalent CB1 receptor ligand that was shown to be remarkably potent, represents a new class of potential therapeutic agents for the treatment of functional GI disorders.
Boronophenylalanine, a boron delivery agent for boron neutron capture therapy, is transported by ATB0,+, LAT1 and LAT2
Authors: Wongthai Printip , Hagiwara Kohei , Miyoshi Yurika , Wiriyasermkul Pattama , Wei Ling , Ohgaki Ryuichi , Kato Itsuro , Hamase Kenji , Nagamori Shushi , Kanai Yoshikatsu
Published: January 2015

The efficacy of boron neutron capture therapy relies on the selective delivery of boron carriers to malignant cells. p‐Boronophenylalanine (BPA), a boron delivery agent, has been proposed to be localized to cells through transporter‐mediated mechanisms. In this study, we screened aromatic amino acid transporters to identify BPA transporters. Human aromatic amino acid transporters were functionally expressed in Xenopus oocytes and examined for BPA uptake and kinetic parameters. The roles of the transporters in BPA uptake were characterized in cancer cell lines. For the quantitative assessment of BPA uptake, HPLC was used throughout the study. Among aromatic amino acid transporters, ATB0,+, LAT1 and LAT2 were found to transport BPA with Km values of 137.4 ± 11.7, 20.3 ± 0.8 and 88.3 ± 5.6 μM, respectively. Uptake experiments in cancer cell lines revealed that the LAT1 protein amount was the major determinant of BPA uptake at 100 μM, whereas the contribution of ATB0,+ became significant at 1000 μM, accounting for 20–25% of the total BPA uptake in MCF‐7 breast cancer cells. ATB0,+, LAT1 and LAT2 transport BPA at affinities comparable with their endogenous substrates, suggesting that they could mediate effective BPA uptake in vivo. The high and low affinities of LAT1 and ATB0,+, respectively, differentiate their roles in BPA uptake. ATB0,+, as well as LAT1, could contribute significantly to the tumor accumulation of BPA at clinical dose.
N‐(2,4)‐dinitrophenyl‐L‐arginine Interacts with EphB4 and Functions as an EphB4 Kinase Modulator
Authors: Kamstra Rhiannon L. , Freywald Andrew , Floriano Wely B.
Published: January 2015

The erythropoietin‐producing hepatocellular carcinoma receptor B4 is a receptor tyrosine kinase whose expression is preserved in various malignancies, including colon, gastric, and breast carcinoma. Hepatocellular carcinoma receptor B4 presence in tumor cells and involvement in cancer suppression makes it a potential therapeutic target for activating compounds. Moreover, modulators of its activity also have a strong potential to be used in diagnosis and therapy monitoring. We used virtual ligand screening to identify novel hepatocellular carcinoma receptor B4 kinase modulators for experimental testing. Three independent assay platforms confirmed that dinitrophenyl‐L‐arginine is likely to affect the kinase activity of hepatocellular carcinoma receptor B4. An enzyme‐coupled spectrophotometric assay has been used to examine this possibility and may prove to be useful for assessing other novel kinase modulator candidates. Overall, our observations suggest that dinitrophenyl‐L‐arginine has an activating effect on hepatocellular carcinoma receptor B4 and, therefore, more efficient derivatives may have therapeutic effects in tumors where hepatocellular carcinoma receptor B4 exhibits antimalignant properties. The hepatocellular carcinoma receptor B4‐activating effect is discussed with respect to previously described mechanisms, using predicted and experimental structures for docked ligands. As a novel kinase activity modulator, dinitrophenyl‐L‐arginine may provide new insights into molecular mechanisms by which kinases are activated or regulated, and may serve as a lead compound for the generation of novel hepatocellular carcinoma receptor B4‐activating therapeutic compounds.
Balade Blanche: Putting New Museum Theory into Practice
Authors: Beaujot Ariel
Published: January 2015

Over the past decade, museum administrators, curators, and staff have begun to recognize a subset of visitors that is starting to view their roles in museums differently. No longer is this new museum audience willing to accept curators’ authoritative narratives passively. Instead, this group of visitors seeks to share authority with curators. In response, some curators have employed strategies to encourage visitors to participate more fully in museums by asking them to contribute to exhibits more actively and by creating exhibits that allow visitors to immerse themselves into the stories that are being communicated. This article explores how Balade Blanche, a historical ghost tour that took place in France in 2010, took on some of the new demands of this “participatory visitor” and put them into practice by sharing curatorial authority and creating an immersive experience.
Creating Discursive Space for Intercultural Encounters: La Casa Encendida, Madrid
Authors: Moore Michelle
Published: January 2015

As increasingly heterogeneous museum audiences seek to participate actively in museum discourses, a new question arises: who is included in the conversation? This article extends that question to cultural‐spatial production, and seeks to illuminate key players’ roles in creating spaces that welcome marginalized groups in order to facilitate intercultural encounters. It argues that inclusive, discursive environments are as much a product of “scripting as design.” La Casa Encendida (The Incandescent House), a cultural center in Madrid, Spain, is used as a case study. It is examined in two stages: first, the ambitions and strategies of its makers and managers are explored; second, project outcomes are tested following the staging of Mundo Extreme (Extreme World), an exhibition that aimed to mediate between the hidden cultural worlds of artists with intellectual disabilities and wider arts scenes. This analysis highlights the contribution of cultural‐spatial production and occupation strategies to facilitating, revealing, and drawing into dialogue marginalized groups.
Effect of subcutaneous insulin detemir on glucose flux and lipolysis during hyperglycaemia in people with type 1 diabetes
Authors: Herring R. A. , Shojaee‐Moradie F. , Umpleby A. M. , Jones R. , Jackson N. , Russell‐Jones D. L.
Published: January 2015

Aims

To investigate, using a novel non‐steady‐state protocol, the differential effects of subcutaneous (s.c.) detemir and NPH insulin on glucose flux and lipid metabolism after insulin withdrawal.

Methods

After a period of insulin withdrawal resulting in whole‐blood glucose concentration of 7 mmol/l, 11 participants (five men, mean age 41.0 years, mean body mass index 25 kg/m2) with type 1 diabetes (mean glycated haemoglobin concentration 57 mmol/mol, mean diabetes duration 14 years) received 0.5 units per kg body weight s.c. insulin detemir or NPH insulin in random order. Stable isotopes of glucose and glycerol were infused intravenously throughout the study protocol.

Results

Glucose concentration decreased after insulin treatment as a result of suppression of endogenous glucose production, which occurred to a similar extent with both detemir and NPH insulin. The rate of glucose disappearance (Rd) was not increased significantly with either type of insulin. When the effect of detemir and NPH insulin on glucose flux at glucose concentrations between 9 and 6 mmol/l was examined, glucose rate of appearance (Ra) was similar with the two insulins; however, glucose Rd was greater with NPH insulin than with detemir at glucose concentrations of 8.0, 8.5, 7.0 and 6.0 mmol/l (p < 0.05) The percentage change in glycerol Ra, a measure of lipolysis, was greater in the NPH group than in the detemir group (p = 0.04).

Conclusions

The results of the study are consistent with the hypothesis that detemir has a lesser effect on the periphery, as evidenced by a lesser effect on peripheral glucose uptake at specific glucose concentrations.
Identification of a direct GABAergic pallidocortical pathway in rodents
Authors: Chen Michael C. , Ferrari Loris , Sacchet Matthew D. , Foland‐Ross Lara C. , Qiu Mei‐Hong , Gotlib Ian H. , Fuller Patrick M. , Arrigoni Elda , Lu Jun
Published: January 2015

Interaction between the basal ganglia and the cortex plays a critical role in a range of behaviors. Output from the basal ganglia to the cortex is thought to be relayed through the thalamus, but an intriguing alternative is that the basal ganglia may directly project to and communicate with the cortex. We explored an efferent projection from the globus pallidus externa (GPe), a key hub in the basal ganglia system, to the cortex of rats and mice. Anterograde and retrograde tracing revealed projections to the frontal premotor cortex, especially the deep projecting layers, originating from GPe neurons that receive axonal inputs from the dorsal striatum. Cre‐dependent anterograde tracing in Vgat‐ires‐cre mice confirmed that the pallidocortical projection is GABAergic, and in vitro optogenetic stimulation in the cortex of these projections produced a fast inhibitory postsynaptic current in targeted cells that was abolished by bicuculline. The pallidocortical projections targeted GABAergic interneurons and, to a lesser extent, pyramidal neurons. This GABAergic pallidocortical pathway directly links the basal ganglia and cortex, and may play a key role in behavior and cognition in normal and disease states.
No abnormalities of intrinsic brain connectivity in the interictal phase of migraine with aura
Authors: Hougaard A. , Amin F. M. , Magon S. , Sprenger T. , Rostrup E. , Ashina M.
Published: January 2015

Background and purpose

Functional neuroimaging studies have shown hyperresponsiveness of cortical areas to visual stimuli in migraine patients with aura outside of attacks. This may be a key feature in the initiation of aura episodes and possibly also migraine headache attacks. It is unknown if cortical dysfunction is present at rest, i.e. in the absence of any external stimuli. Functional magnetic resonance imaging is a powerful technique for evaluating resting state functional connectivity, i.e. coherence of brain activity across cerebral areas. The objective of this study was to investigate resting‐state functional brain connectivity in migraineurs with aura outside of attacks using functional magnetic resonance imaging.

Methods

Forty patients suffering from migraine with visual aura and 40 individually age and gender matched healthy controls with no history or family history of migraine were investigated. Following advanced denoising, the data were analyzed both in a hypothesis‐driven fashion, testing for abnormalities involving 27 different brain areas of potential relevance to migraine with aura including the cortical visual areas, the amygdala and peri‐aqueductal grey matter, and in a data‐driven exploratory fashion (dual regression) in order to reveal any possible between‐group differences of resting state networks. Age, gender, attack frequency and disease duration were included as nuisance variables.

Results

No differences of functional connectivity were found between patients and controls.

Conclusions

The previously reported increased cortical hyperresponsivity in the interictal phase of migraine with aura is unlikely to be caused by abnormalities of intrinsic brain connectivity. The interictal migraine aura brain may be abnormally functioning only during exposure to external stimuli.
Hospital crossover increases utilization for people with epilepsy: A retrospective cohort study
Authors: Grinspan Zachary M. , Shapiro Jason S. , Abramson Erika L. , Jung Hye‐Young , Kaushal Rainu , Kern Lisa M.
Published: January 2015

Objectives

“Hospital crossover” occurs when people visit multiple hospitals for care, which may cause gaps in electronic health records. Although crossover is common among people with epilepsy, the effect on subsequent use of health services is unknown. Understanding this effect will help prioritize health care delivery innovations targeted for this population.

Methods

We collected de‐identified information from a health information exchange network describing 7,836 people with epilepsy who visited any of seven hospitals in New York, NY from 2009–2012. Data included demographics, comorbidities, and 2 years of visit information from ambulatory, inpatient, emergency department (ED), and radiology settings. We performed two complementary retrospective cohort analyses, in order to (1) illustrate the effect on a carefully selected subgroup, and (2) confirm the effect across the study population. First, we performed a matched cohort analysis on 410 pairs of individuals with and without hospital crossover in the baseline year. Second, we performed a propensity score odds weighted ordinal logistic regression analysis to estimate the effect across all 7,836 individuals. The outcomes were the use of six health services in the follow‐up year.

Results

In the matched pair analysis, baseline hospital crossover increased the odds of more visits in the ED (odds ratio 1.42, 95% confidence interval [CI] 1.05–1.95) and radiology settings (1.7, 1.22–2.38). The regression analysis confirmed the ED and radiology findings, and also suggested that crossover led to more inpatient admissions (1.35, 1.11–1.63), head CTs (1.44, 1.04–2), and brain MRIs (2.32, 1.59–3.37).

Significance

Baseline hospital crossover is an independent marker for subsequent increased health service use in multiple settings among people with epilepsy. Health care delivery innovations targeted for people with epilepsy who engage in hospital crossover should prioritize (1) sharing radiology images and reports (to reduce unnecessary radiology use, particularly head CTs), and (2) improving coordination of care (to reduce unnecessary ED and inpatient use).
Assessment of aminoglycoside dosing and estimated glomerular filtration rate in determining gentamicin and tobramycin area under the curve and clearance
Authors: Lim A. K. H. , Mathanasenarajah G. , Larmour I.
Published: January 2015

Background

Aminoglycoside clearance depends on kidney function, but the Australian Therapeutic Guidelines for antibiotics (version 14, 2010) recommend initial dosing based on weight without consideration of kidney function. Other guidelines that modify dosing based on kidney function estimates often use the Cockroft–Gault equation, but the role of the estimated glomerular filtration rate equations for this purpose is unclear.

Aim

To determine the performance of current guideline dosing in achieving target area‐under‐the‐curve and examine the relative precision of the estimated glomerular filtration rate equations compared with traditional Cockroft–Gault creatinine clearance in predicting aminoglycoside clearance.

Methods

We analysed 496 aminoglycoside treatment episodes involving 1377 infusions in adult patients. Conformity with antibiotic guideline dosing was achieved if the discrepancy between prescribed and recommended dose was less than 15%. Aminoglycoside clearance was determined from linear regression using a one compartment model with the Aminoglycoside Levels and Daily Dose Indicator programme. We assessed the precision of the Cockroft–Gault, Modification of Diet in renal Disease Study and Chronic Kidney Disease–Epidemiology Collaboration (CKD–EPI) equations in predicting aminoglycoside clearance by correlation and linear regression.

Results

Conformity with guideline dosing was not associated with achieving target area‐under‐the‐curve. The CKD‐EPI estimated glomerular filtration rate adjusted for body surface area showed the highest correlation (gentamicin, r = 0.66; tobramycin, r = 0.82) and best predictive model for aminoglycoside clearance.

Conclusion

Current guideline dosing may be suboptimal for achieving target area‐under‐the‐curve. The CKD‐EPI equation adjusted for patient body surface area best predicts aminoglycoside clearance, and could be evaluated as a covariate in determining initial aminoglycoside dosing.
Reversible lacrimal gland‐protective regulatory T‐cell dysfunction underlies male‐specific autoimmune dacryoadenitis in the non‐obese diabetic mouse model of Sjögren syndrome
Authors: Lieberman Scott M. , Kreiger Portia A. , Koretzky Gary A.
Published: January 2015

CD4+ CD25+ Foxp3+ regulatory T (Treg) cells are required to maintain immunological tolerance; however, defects in specific organ‐protective Treg cell functions have not been demonstrated in organ‐specific autoimmunity. Non‐obese diabetic (NOD) mice spontaneously develop lacrimal and salivary gland autoimmunity and are a well‐characterized model of Sjögren syndrome. Lacrimal gland disease in NOD mice is male‐specific, but the role of Treg cells in this sex‐specificity is not known. This study aimed to determine if male‐specific autoimmune dacryoadenitis in the NOD mouse model of Sjögren syndrome is the result of lacrimal gland‐protective Treg cell dysfunction. An adoptive transfer model of Sjögren syndrome was developed by transferring cells from the lacrimal gland‐draining cervical lymph nodes of NOD mice to lymphocyte‐deficient NOD‐SCID mice. Transfer of bulk cervical lymph node cells modelled the male‐specific dacryoadenitis that spontaneously develops in NOD mice. Female to female transfers resulted in dacryoadenitis if the CD4+ CD25+ Treg‐enriched population was depleted before transfer; however, male to male transfers resulted in comparable dacryoadenitis regardless of the presence or absence of Treg cells within the donor cell population. Hormone manipulation studies suggested that this Treg cell dysfunction was mediated at least in part by androgens. Surprisingly, male Treg cells were capable of preventing the transfer of dacryoadenitis to female recipients. These data suggest that male‐specific factors promote reversible dysfunction of lacrimal gland‐protective Treg cells and, to our knowledge, form the first evidence for reversible organ‐protective Treg cell dysfunction in organ‐specific autoimmunity.
Improvement of overlapping nuclear track densitometry
Authors: GHERGHEREHCHI M. , KIM S. Y. , AFARIDEH H. , KIM Y. S. , CHAI J. S.
Published: January 2015

Detection of tracks produced by α particles, protons or nuclear fission fragments in plastic detectors, viz., solid‐state nuclear track detectors, constitutes a very important tool in various areas. It is not easy for humans to count CR‐39 nuclear tracks manually, especially when the track density is very high. An automated computer program called KTTMS2, written in C++ and running with a user friendly interface, has been developed for recognition and parametric measurements of etched tracks in images captured from the surface of solid‐state nuclear track detectors. Well‐known edge detection methods were applied to estimate the precision and accuracy of nuclear track densitometry using the CR‐39 detector. Among the various routine edge detection methods, the Canny method was chosen because it was the most accurate technique. Because accuracy becomes more important as the track density increases, this allows more overlapping tracks to be detected. KTTMS2 (the proposed system) has an efficiency of 95% and can identify the noise as a background track (5%). Experimental results showed that the error percentage was reduced from 7.63% to 3.23% for high‐density tracks when the count was adjusted by the estimated overlapping tracks.
Erectile Dysfunction after Sickle Cell Disease–Associated Recurrent Ischemic Priapism: Profile and Risk Factors
Authors: Anele Uzoma A. , Burnett Arthur L.
Published: January 2015

Introduction

Risk factors associated with erectile dysfunction (ED) that results from recurrent ischemic priapism (RIP) in sickle cell disease (SCD) are incompletely defined.

Aim

This study aims to determine and compare ED risk factors associated with SCD and non-SCD-related “minor” RIP, defined as having ≥2 episodes of ischemic priapism within the past 6 months, with the majority (>75%) of episodes lasting <5 hours.

Methods

We performed a retrospective study of RIP in SCD and non-SCD patients presenting from June 2004 to March 2014 using the International Index of Erectile Function (IIEF), IIEF-5, and priapism-specific questionnaires.

Main Outcome Measures

Prevalence rates and risk factor correlations for ED associated with RIP.

Results

The study was comprised of 59 patients (40 SCD [mean age 28.2 ± 8.9 years] and 19 non-SCD [15 idiopathic and four drug-related etiologies] [mean age 32.6 ± 11.7 years]). Nineteen of 40 (47.5%) SCD patients vs. four of 19 (21.1%) non-SCD patients (39% overall) had ED (IIEF <26 or IIEF-5 <22) (P = 0.052). SCD patients had a longer mean time-length with RIP than non-SCD patients (P = 0.004). Thirty of 40 (75%) SCD patients vs. 10 of 19 (52.6%) non-SCD patients (P = 0.14) had “very minor” RIP (episodes regularly lasting ≤2 hours). Twenty-eight of 40 (70%) SCD patients vs. 14 of 19 (73.7%) non-SCD patients had weekly or more frequent episodes (P = 1). Of all patients with very minor RIP, ED was found among 14 of 30 (46.7%) SCD patients vs. none of 10 (0%) non-SCD patients (P = 0.008). Using logistic regression analysis, the odds ratio for developing ED was 4.7 for SCD patients, when controlling for RIP variables (95% confidence interval: 1.1–21.0).

Conclusions

ED is associated with RIP, occurring in nearly 40% of affected individuals overall. SCD patients are more likely to experience ED in the setting of “very minor” RIP episodes and are five times more likely to develop ED compared with non-SCD patients.
Invasion history affects genetic structure in island rat populations
Authors: Theuerkauf J. , Kuehn R. , Gula R. , Sztencel‐Jabłonka A. , Jourdan H. , Taugamoa A. , Labrousse D. , Bogdanowicz W.
Published: January 2015

Invasive species usually go through a period of reduced genetic variability due to a bottleneck. The genetic constitution of an invading population should therefore reflect the time since invasion and the number of introduction events. We studied genetic population structure of three rat species occurring sympatrically on the island of Futuna (46 km2), where they were introduced recently (Rattus rattus), 80–170 years ago (R. norvegicus) and about 3000 years ago (R. exulans). From 2007 to 2012, we trapped 3900 rats during a rodent regulation programme over 20 000 trap nights and took 565 rat tissue samples for genetic analyses. By examining genetic variation and spatial distribution of genetic resemblance, we evaluated the consequences of the time after introduction for genetic population structure. Observed heterozygosity, expected heterozygosity, number of alleles and allelic richness generally increased with increasing length of time a species was introduced to the island. The species with longer invasion history had also higher spatial admixture. However, in R. norvegicus, the observed heterozygosity was lower and inbreeding higher than expected by the invasion history. We relate this with the assumption that this species was introduced once or a few times and in low numbers, while R. exulans was intentionally introduced many times by Polynesian navigators and R. rattus had a high chance of being introduced on multiple occasions in recent times.
Maternal environment affects the genetic basis of seed dormancy in Arabidopsis thaliana
Authors: Postma Froukje M. , Ågren Jon
Published: January 2015

The genetic basis of seed dormancy, a key life history trait important for adaptive evolution in plant populations, has yet been studied only using seeds produced under controlled conditions in greenhouse environments. However, dormancy is strongly affected by maternal environmental conditions, and interactions between seed genotype and maternal environment have been reported. Consequently, the genetic basis of dormancy of seeds produced under natural field conditions remains unclear. We examined the effect of maternal environment on the genetic architecture of seed dormancy using a recombinant inbred line (RIL) population derived from a cross between two locally adapted populations of Arabidopsis thaliana from Italy and Sweden. We mapped quantitative trait loci (QTL) for dormancy of seeds produced in the greenhouse and at the native field sites of the parental genotypes. The Italian genotype produced seeds with stronger dormancy at fruit maturation than did the Swedish genotype in all three environments, and the maternal field environments induced higher dormancy levels compared to the greenhouse environment in both genotypes. Across the three maternal environments, a total of nine dormancy QTL were detected, three of which were only detected among seeds matured in the field, and six of which showed significant QTL × maternal environment interactions. One QTL had a large effect on dormancy across all three environments and colocalized with the candidate gene DOG1. Our results demonstrate the importance of studying the genetic basis of putatively adaptive traits under relevant conditions.
Deep sequencing of the olfactory epithelium reveals specific chemosensory receptors are expressed at sexual maturity in the European eel Anguilla anguilla
Authors: Churcher Allison M. , Hubbard Peter C. , Marques João Pedro , Canário Adelino V. M. , Huertas Mar
Published: January 2015

Vertebrate genomes encode a diversity of G protein‐coupled receptor (GPCR) that belong to large gene families and are used by olfactory systems to detect chemical cues found in the environment. It is not clear however, if individual receptors from these large gene families have evolved roles that are specific to certain life stages. Here, we used deep sequencing to identify differentially expressed receptor transcripts in the olfactory epithelia (OE) of freshwater, seawater and sexually mature male eels (Anguilla anguilla). This species is particularly intriguing because of its complex life cycle, extreme long‐distance migrations and early‐branching position within the teleost phylogeny. In the A. anguillaOE, we identified full‐length transcripts for 13, 112, 6 and 38 trace amine‐associated receptors, odorant receptors (OR) and type I and type II vomeronasal receptors (V1R and V2R). Most of these receptors were expressed at similar levels at different life stages and a subset of OR and V2R‐like transcripts was more abundant in sexually mature males suggesting that ORs and V2R‐like genes are important for reproduction. We also identified a set of GPCR signal transduction genes that were differentially expressed indicating that eels make use of different GPCR signal transduction genes at different life stages. The finding that a diversity of chemosensory receptors is expressed in the olfactory epithelium and that a subset is differentially expressed suggests that most receptors belonging to large chemosensory gene families have functions that are important at multiple life stages, while a subset has evolved specific functions at different life stages.
The influence of tissue herniation on diplopia and ocular motility in orbital blowout fractures
Authors: Alhamdani F. , Durham J. , Greenwood M. , Corbett I.
Published: January 2015

Aim

The aim of the study is to determine the effect of orbital tissue herniation, as determined by computed tomography (CT) scan, on diplopia and ocular motility scores in blowout fracture patients.

Materials and methods

Patients who sustained pure orbital blowout fractures in the period 2000–2010, and for whom CT scan reports were available, were included in the study. Three levels of tissue herniation were reported: none, fat only, and fat and muscle. Orthoptic assessment included binocular single vision (BSV) and uniocular fields of fixation (UFOF) scores.

Results

One hundred and twenty‐three patients were included in the study. Although mean BSV and UFOF scores decreased with increasing amounts of tissue prolapse, there was no significant difference between the BSV, UFOF scores of injuries with no tissue prolapse and those with only fat herniation (P > 0.05). A significant difference was noted between the BSV and UFOF scores of no/fat herniation and injuries with fat and muscle prolapse groups. Patients with muscle herniation had a tendency for an unfavourable outcome following surgical intervention.

Conclusion

We suggest that orbital fat herniation alone may not be an adequate indication for surgical intervention for correction of diplopia in orbital blowout fractures. Cases with orbital muscle herniation are more likely to have an unfavourable outcome in relation to diplopia.
Response styles, bipolar risk, and mood in students: The Behaviours Checklist
Authors: Fisk Claire , Dodd Alyson L. , Collins Alan
Published: January 2015

Objectives

An Integrative Cognitive Model of mood swings and bipolar disorder proposes that extreme positive and negative appraisals about internal states trigger ascent and descent behaviours, contributing to the onset and maintenance of mood swings. This study investigated the reliability and validity of a new inventory, the Behaviours Checklist (BC), by measuring associations with appraisals, response styles to positive and negative affect, bipolar risk, mania, and depression.

Design

Correlational analogue study.

Methods

Students (N = 134) completed the BC alongside measures of appraisals, response styles to positive and negative mood, mania, depression, and hypomanic personality (bipolar risk).

Results

The BC was of adequate reliability and showed good validity. Ascent behaviours and appraisals predicted bipolar risk, whereas descent behaviours and appraisals were associated with depression.

Conclusions

Appraisals, ascent, and descent behaviours may play an important role in the development and maintenance of mood swings. Limitations and research recommendations are outlined.

Practitioner points

Extreme positive and negative appraisals of internal states, and subsequent behavioural responses (ascent and descent behaviours), are associated with bipolar risk and bipolar mood symptoms in a student sample.

These processes are involved with mood dysregulation in clinical populations as well as bipolar risk in students, with implications for mood management.
Light Treatment Improves Sleep Quality and Negative Affectiveness in High Arctic Residents During Winter
Authors: Paul Michel A. , Love Ryan J. , Hawton Andrea , Brett Kaighley , McCreary Donald R. , Arendt Josephine
Published: January 2015

The seasonal extremes of photoperiod in the high Arctic place particular strain on the human circadian system, which leads to trouble sleeping and increased feelings of negative affect in the winter months. To qualify for our study, potential participants had to have been at Canadian Forces Station (CFS) Alert (82° 30′ 00″ N) for at least 2 weeks. Subjects filled out questionnaires regarding sleep difficulty, psychological well‐being and mood and wore Actigraphs to obtain objective sleep data. Saliva was collected at regular intervals on two occasions, 2 weeks apart, to measure melatonin and assess melatonin onset. Individuals with a melatonin rhythm that was in disaccord with their sleep schedule were given individualized daily light treatment interventions based on their pretreatment salivary melatonin profile. The light treatment prescribed to seven of the twelve subjects was effective in improving sleep quality both subjectively, based on questionnaire results, and objectively, based on the actigraphic data. The treatment also caused a significant reduction in negative affect among the participants. Since the treatment is noninvasive and has minimal associated side effects, our results support the use of the light visors at CFS Alert and other northern outposts during the winter for individuals who are experiencing sleep difficulty or low mood.
Hepatic adrenal rest tumor: Diagnostic pitfall and proposed algorithms to prevent misdiagnosis as lipid‐rich hepatocellular carcinoma
Authors: Sugiyama Tomoko , Tajiri Takuma , Hiraiwa Shinichiro , Inomoto Chie , Kajiwara Hiroshi , Kojima Seiichiro , Tobita Kouske , Nakamura Naoya
Published: January 2015

We present a case of adrenal rest tumor of the liver in which differential diagnosis from lipid rich‐hepatocellular carcinoma (HCC) was challenging. The patient was a 50‐year‐old woman in whom a 3‐cm tumorous mass was discovered in segment 7 of the liver during computed tomography evaluation of a uterine leiomyoma. The preoperative diagnosis was HCC, and subsegmental liver resection was performed. The tumor appeared as a well‐demarcated golden yellow nodule consisting of clear or partially eosinophilic cells arranged in a trabecular pattern. The initial impression of this lesion was that of clear cell type or lipid‐rich type HCC because it stained positive for Hep Par1, but negative for arginase‐1 and positive for CD56 which is one of the neuroendocrine markers. The lesion also stained positive for SF‐1 and 3β‐HSD, both of which are markers of adrenocortical tissue. The final diagnosis was hepatic adrenal rest tumor. Hepatic adrenal rest tumor should be considered in the differential diagnosis of segment 7 tumor. A diagnostic algorithm that includes immunohistochemical staining for CD56 and arginase‐1 is to rule out the possibility of lipid‐rich HCC.
Pharmaceutical industry, academia and patient advocacy organizations: What is the recipe for synergic (win–win–win) collaborations?
Authors: Rose Daniel M. , Marshall Richard , Surber Mark W.
Published: January 2015

Biological complexity and the need for highly differentiated medicines means that drug discovery and development have become increasingly challenging and expensive. Thus, new paradigms for research and drug development need to be created that bring together a wide array of expertise. One potential solution is collaboration between bio‐pharma and academic research centres. Two examples are discussed, one with a large pharma company (GlaxoSmithKline) and the other a small biotech (Genoa Pharmaceuticals). Patient advocacy organization can also have role in assisting in the creation of these partnerships by informing patients of ongoing research and clinical trials, and supporting the development of networks that can provide major benefit for both basic research and drug development. A major ‘hurdle’ for the creation of these relationships is the issue of intellectual property. Examples are provided of how this issue can be resolved.
ICP 2005 Construction Prices: Are They Underestimated in Developing Countries?
Authors: Breton Theodore R. , García John J.
Published: January 2015

Construction prices are lower in developing countries in ICP 2005, which has raised these countries' capital/output ratio in Penn World Tables 7 and 8 and affected growth analyses. We estimate the Colombia/U.S. price ratio for office and apartment buildings in 2005 as a test of the validity of the ICP 2005 methodology for estimating these prices. Our estimate of the Colombia/U.S. price ratio is almost twice the ICP 2005 estimate. We confirm the validity of our results by estimating the cost of constructing office and apartment buildings using 2005 prices for construction materials, equipment, and labor in both countries.