bluuebunny/crossref_metadata_2025 huggingface dataset:
Neighbourhood Spatial Order, the Local Economy and Firm Mobility in Urban Areas of the Netherlands
Authors: Beckers Pascal , Sleutjes Bart
Published: October 2014

Urban residential neighbourhoods in the Netherlands increasingly function as incubation zones for small‐scale businesses. Despite this development, little is known about whether and how the local production environment in these neighbourhoods shapes firm mobility behaviour. This article studies how two aspects of the local production environment — the built neighbourhood environment and zoning regulations — affect firm mobility of small‐scale businesses in urban residential neighbourhoods. To achieve this aim, we contrast two sets of urban neighbourhoods, pre‐ and post‐second world war neighbourhoods with a comparable low socio‐economic profile, but with distinct built environments and zoning regulations. We combine quantitative and qualitative methods to analyse available trade register data from the Dutch regional Chambers of Commerce, study neighbourhood zoning regulations, and conduct focus‐group and individual interviews with neighbourhood experts and entrepreneurs. The local built environment and its regulations appear to have a small but significant effect on the firm mobility behaviour of entrepreneurs in the neighbourhoods studied. Relocation intentions are higher among entrepreneurs in post‐war than in pre‐war neighbourhoods, which may (in part) be attributed to less favourable local institutional settings for businesses, but actual firm mobility does not differ between these neighbourhoods.
The prevention and treatment of postpartum haemorrhage: what do we know, and where do we go to next?
Authors: Weeks A
Published: October 2014

Postpartum haemorrhage (PPH) remains a major cause of maternal deaths worldwide, and is estimated to cause the death of a woman every 10 minutes. This review presents the latest clinical advice, including new evidence on controlled cord traction, misoprostol, and oxytocin. The controversy around the diagnosis of PPH, the limitations of universal prophylaxis, and novel ways to provide obstetric first aid are also presented. It ends with a call to develop high‐quality front‐line obstetric services that can deal rapidly with unexpected haemorrhages as well as minimising blood loss at critical times: major abruption, placenta praevia, and caesarean for prolonged labour.
Modeling Hospital‐Acquired Pressure Ulcer Prevalence on Medical‐Surgical Units: Nurse Workload, Expertise, and Clinical Processes of Care
Authors: Aydin Carolyn , Donaldson Nancy , Stotts Nancy A. , Fridman Moshe , Brown Diane Storer
Published: October 2014

Objective

This study modeled the predictive power of unit/patient characteristics, nurse workload, nurse expertise, and hospital‐acquired pressure ulcer (HAPU) preventive clinical processes of care on unit‐level prevalence of HAPUs.

Data Sources

Seven hundred and eighty‐nine medical‐surgical units (215 hospitals) in 2009.

Study Design

Using unit‐level data, HAPUs were modeled with Poisson regression with zero‐inflation (due to low prevalence of HAPUs) with significant covariates as predictors.

Data Collection/Extraction Methods

Hospitals submitted data on NQF endorsed ongoing performance measures to CALNOC registry.

Principal Findings

Fewer HAPUs were predicted by a combination of unit/patient characteristics (shorter length of stay, fewer patients at‐risk, fewer male patients), RN workload (more hours of care, greater patient [bed] turnover), RN expertise (more years of experience, fewer contract staff hours), and processes of care (more risk assessment completed).

Conclusions

Unit/patient characteristics were potent HAPU predictors yet generally are not modifiable. RN workload, nurse expertise, and processes of care (risk assessment/interventions) are significant predictors that can be addressed to reduce HAPU. Support strategies may be needed for units where experienced full‐time nurses are not available for HAPU prevention. Further research is warranted to test these finding in the context of higher HAPU prevalence.
Survey of American (USA) Gasolines (2008)
Authors: Hetzel Susan S.
Published: October 2014

The regulations for gasoline's content vary depending on the time of year and physical location within the United States while the refinery and distribution system mixes product batches; this results in variability of content.ASTME1618 requires both the aromatic and alkaneEIPpatterns of gasoline to compare with references. A survey was conducted by collecting gasoline from Florida to Oregon, from 85 to 93 octane. Samples were analyzed in accordance withASTME1618 in various states of evaporation. The range of differences found in the 90% evaporated alkaneEIPs is presented and showed a continuum of response when the n‐alkane response was compared with the branched alkane response. Similarly, the ratio of the alkaneEIPto the aromaticEIPalso showed a continuum of response at the 90% evaporated state. Gasoline samples with unusual characteristics are also discussed.
Comparison of effective I‐131 half‐life between thyroid hormone withdrawal and recombinant human thyroid‐stimulating hormone for thyroid cancer: A retrospective study
Authors: Grenfell Solveig , Roos Daniel , Rijken James , Higgs Braden , Kirkwood Ian
Published: October 2014

Introduction

Preparation for postoperative radioiodine ablation for differentiated thyroid carcinoma is performed by either thyroid hormone withdrawal or recombinant human thyroid‐stimulating hormone (rhTSH) administration. There is little information on the impact of the method of preparation with respect to whole‐body effective I‐131 half‐life and its potential clinical implications in the Australian setting.

Methods

A retrospective study was performed on patients admitted for adjuvant radioiodine ablation for non‐metastatic differentiated thyroid carcinoma at the Royal Adelaide Hospital over a 4½‐year period from 2009. Dose rate measurements were analysed for 19 rhTSH and 31 thyroid hormone withdrawal patients.

Results

The mean effective I‐131 half‐lives were 11.51 and 13.29 h for the rhTSH and thyroid hormone withdrawal groups, respectively, with no statistically significant difference between the two groups (P = 0.761). This result differs from previously published data where withdrawal periods were typically longer, resulting in slower renal clearance and longer half‐lives for withdrawal patients.

Conclusions

Our study did not demonstrate a significant difference in whole‐body effective half‐life of I‐131 between the two methods of preparation for radioiodine ablation. This suggests that putative advantages of rhTSH over withdrawal in terms of whole‐body radiation dose, duration of hospital admission and quality of life may be sensitive to duration of withdrawal.
Hypofractionated radiation treatment following mastectomy in early breast cancer: The Christchurch experience
Authors: Ko Dong‐Hwan I , Norriss Andrew , Harrington Christopher R , Robinson Bridget A , James Melissa L
Published: October 2014

Introduction

Although hypofractionated radiotherapy (HFRT) has become an accepted option for whole‐breast irradiation after breast‐conserving surgery, there is limited evidence to support HFRT to the chest wall following mastectomy. We retrospectively analysed post‐mastectomy patients treated with HFRT in Christchurch to determine whether HFRT yields acceptable efficacy and toxicity.

Methods

The Christchurch oncology database was used to identify breast cancer patients treated with adjuvant HFRT to the chest wall following a mastectomy between 2003 and 2008. Eligible post‐mastectomy patients were treated with 40 Gy in 16 daily fractions. Treatment outcomes assessed included local recurrence‐free survival, breast cancer survival, overall survival and acute toxicities.

Results

One hundred thirty‐three patients were identified. The median follow‐up period was 5.03 years. Three patients had a local recurrence as a first event, resulting in 5‐year local recurrence‐free survival of 97.6%. Five‐year overall survival and 5‐year breast cancer survival were 74.7% and 77.7%, respectively. The prospectively assessed acute toxicities were mostly grade 1. In particular, the incidence of grade 2 skin toxicity was 10.7%, and no patients experienced grade 3 skin toxicity.

Conclusion

The high local control rate with HFRT, combined with acceptable toxicity and the practical benefits of a shorter treatment time, supports its ongoing use in the eligible patient group. A randomised controlled trial would be necessary to more completely assess the acute and long‐term toxicity of HFRT compared with standard fractionation.
Vitamin D status in rheumatoid arthritis patients: relation to clinical manifestations, disease activity, quality of life and fibromyalgia syndrome
Authors: Gheita Tamer A. , Sayed Safaa , Gheita Heba A. , Kenawy Sanaa A.
Published: October 2014

Aim

To assess vitamin D levels in rheumatoid arthritis (RA) patients and to find their relation to clinical parameters, fibromyalgia syndrome (FMS), quality of life (QoL) and disease activity.

Methods

The study included 63 RA patients and 62 controls. Clinical examination and laboratory investigations were performed. For patients, the Disease Activity Score (DAS‐28), QoL index, Health Assessment Questionnaire II (HAQ II) and Modified Larsen score were calculated. 25‐OH‐vitamin D was measured in patients and controls.

Results

The patients’ mean age was 41.59 ± 9.69 years and disease duration 5.89 ± 3.67 years. The level of vitamin D in RA patients was significantly lower (23.11 ± 12.71 ng/mL) than that in the controls (32.59 ± 13.06 ng/mL) (P = 0.005) being deficient in 50.8%, insufficient in 23.8% and normal in 25.4%. The RA patients with FMS (n = 33) had significantly lower levels of vitamin D (19.08 ± 10.59 ng/mL) than those without (27.55 ± 13.51 ng/mL) (P = 0.008). The difference was significant on comparing those receiving hydroxychloroquine (17.39 ± 7.84 ng/mL) to those not (31.85 ± 13.85 ng/mL) (P < 0.001). Vitamin D significantly correlated with QoL index (r = 0.58, P < 0.001) and negatively with HAQ II (r = −0.36, P = 0.004) and BMI (r = −0.39, P = 0.001).

Conclusion

Special attention is required regarding vitamin D levels in RA patients with FMS and decreased QoL. Vitamin D should be corrected and supplementation considered among the RA management armamentarium.
Mining featured micro ribonucleic acids associated with lung cancer based on bioinformatics
Authors: Su Lin , Li Na , Huo Xueyun
Published: October 2014

Background

Few genetic markers useful for the screening of lung cancer risk exist. Although related research has shown that certain expression profiles of micro ribonucleic acids (miRNAs) are different in lung cancer versus the normal lung, such as miR‐29a and miR‐29s, the precise molecular mechanism of lung cancer remains obscure. In order to get a better understanding of the pathogenetic mechanism of lung cancer, we analyzed the differentially expressed genes (DEGs) and identified featured miRNAs in lung cancer tissues.

Methods

We used the gene expression profile GSE10072, including 49 gene chips of non‐tumor tissues and 58 gene chips of lung tumor specimens. The DEGs between these two groups were identified by Limma package in R language. The TarBase database was used to construct the networks of miRNA regulating DEGs related to lung cancer. After ordering miRNAs regulating DEGs, we further screened featured miRNAs combined with the miR2Disease database.

Results

A total of 5572 DEGs were obtained between lung cancer and control specimens. After constructing a miRNA regulatory network, a total of 398 regulations between 57 miRNAs and 321 target genes existed. By intergrating the miR2Disease database and using a sorting algorithm, a total of six featured miRNAs related to lung cancer were identified, including miR‐520h, miR‐133a, miR‐34, miR‐103, miR‐370, and miR‐148. They might be involved in lung cancer progression by regulating ABCG2, PKM2, VAMP2, GPD1, MAP3K8, and DNMT3B, respectively.

Conclusion

The top 10 significant miRNAs, such as miR‐520h, miR‐133a, miR‐34, and miR‐103 may be potential therapeutic targets for lung cancer.
Chronic Intermittent Ethanol Exposure and Withdrawal Alters (3α,5α)‐3‐Hydroxy‐Pregnan‐20‐One Immunostaining in Cortical and Limbic Brain Regions of C57BL/6J Mice
Authors: Maldonado‐Devincci Antoniette M. , Cook Jason B. , O'Buckley Todd K. , Morrow Danielle H. , McKinley Raechel E. , Lopez Marcelo F. , Becker Howard C. , Morrow A. Leslie
Published: October 2014

Background

The GABAergic neuroactive steroid (3α,5α)‐3‐hydroxy‐pregnan‐20‐one (3α,5α‐THP; allopregnanolone) has been studied during withdrawal from ethanol (EtOH) in humans, rats, and mice. Serum 3α,5α‐THP levels decreased, and brain levels were not altered following acute EtOH administration (2 g/kg) in male C57BL/6J mice; however, the effects of chronic intermittent ethanol (CIE) exposure on 3α,5α‐THP levels have not been examined. Given that CIE exposure changes subsequent voluntary EtOH drinking in a time‐dependent fashion following repeated cycles of EtOH exposure, we conducted a time‐course analysis of CIE effects on 3α,5α‐THP levels in specific brain regions known to influence drinking behavior.

Methods

Adult male C57BL/6J mice were exposed to 4 cycles of CIE to induce EtOH dependence. All mice were sacrificed and perfused at 1 of 2 time points, 8 or 72 hours following the final exposure cycle. Free‐floating brain sections (40 μm; 3 to 5 sections/region/animal) were immunostained and analyzed to determine relative levels of cellular 3α,5α‐THP.

Results

Withdrawal from CIE exposure produced time‐dependent and region‐specific effects on immunohistochemical detection of 3α,5α‐THP levels across cortical and limbic brain regions. A transient reduction in 3α,5α‐THP immunoreactivity was observed in the central nucleus of the amygdala 8 hours after withdrawal from CIE (−31.4 ± 9.3%). Decreases in 3α,5α‐THP immunoreactivity were observed 72 hours following withdrawal in the medial prefrontal cortex (−25.0 ± 9.3%), nucleus accumbens core (−29.9 ± 6.6%), and dorsolateral striatum (−18.5 ± 6.0%), while an increase was observed in the CA3 pyramidal cell layer of the hippocampus (+42.8 ± 19.5%). Sustained reductions in 3α,5α‐THP immunoreactivity were observed at both time points in the lateral amygdala (8 hours −28.3 ± 12.8%; 72 hours −27.5 ± 12.4%) and in the ventral tegmental area (8 hours −26.5 ± 9.9%; 72 hours −31.6 ± 13.8%).

Conclusions

These data suggest that specific neuroadaptations in 3α,5α‐THP levels may be present in regions of brain that mediate anxiety, stress, and reinforcement relevant to EtOH dependence. The changes that occur at different time points likely modulate neurocircuitry involved in EtOH withdrawal as well as the elevated drinking observed after CIE exposure.
Excess non‐psychiatric hospitalizations among employees with mental disorders: a 10‐year prospective study of the GAZEL cohort
Authors: Azevedo Da Silva M. , Lemogne C. , Melchior M. , Zins M. , Van Der Waerden J. , Consoli S. M. , Goldberg M. , Elbaz A. , Singh‐Manoux A. , Nabi H.
Published: October 2014

Objective

To examine whether non‐psychiatric hospitalizations rates were higher in those with mental disorders.

Method

In a cohort of 15 811 employees, aged 35–50 years in 1989, mental disorder status was defined from 1989 to 2000. Hospitalizations for all‐causes, myocardial infarction (MI), stroke, and cancer, were recorded yearly from 2001 to 2011. Negative binomial regression models were used to estimate hospitalization rates over the follow‐up.

Results

After controlling for baseline sociodemographic factors, health‐related behaviors, self‐rated health, and self‐reported medical conditions, participants with a mental disorder had significantly higher rates of all‐cause hospitalization [incidence rate ratio, IRR = 1.20 (95%, 1.14–1.26)], as well as hospitalization due to MI [IRR = 1.44 (95%, 1.12–1.85)]. For stroke, the IRR did not reach statistical significance [IRR = 1.37 (95%, 0.95–1.99)] and there was no association with cancer [IRR = 1.01 (95%, 0.86–1.19)]. A similar trend was observed when mental disorders groups were considered (no mental disorder, depressive disorder, mental disorders due to psychoactive substance use, other mental disorders, mixed mental disorders, and severe mental disorder).

Conclusion

In this prospective cohort of employees with stable employment as well as universal access to healthcare, we found participants with mental disorders to have higher rates of non‐psychiatric hospitalizations.
What has research over the past two decades revealed about the adverse health effects of recreational cannabis use?
Authors: Hall Wayne
Published: October 2014

Aims

To examine changes in the evidence on the adverse health effects of cannabis since 1993.

Methods

A comparison of the evidence in 1993 with the evidence and interpretation of the same health outcomes in 2013.

Results

Research in the past 20 years has shown that driving while cannabis‐impaired approximately doubles car crash risk and that around one in 10 regular cannabis users develop dependence. Regular cannabis use in adolescence approximately doubles the risks of early school‐leaving and of cognitive impairment and psychoses in adulthood. Regular cannabis use in adolescence is also associated strongly with the use of other illicit drugs. These associations persist after controlling for plausible confounding variables in longitudinal studies. This suggests that cannabis use is a contributory cause of these outcomes but some researchers still argue that these relationships are explained by shared causes or risk factors. Cannabis smoking probably increases cardiovascular disease risk in middle‐aged adults but its effects on respiratory function and respiratory cancer remain unclear, because most cannabis smokers have smoked or still smoke tobacco.

Conclusions

The epidemiological literature in the past 20 years shows that cannabis use increases the risk of accidents and can produce dependence, and that there are consistent associations between regular cannabis use and poor psychosocial outcomes and mental health in adulthood.
Cost‐effective development of highly polymorphic microsatellite in Japanese quail facilitated by next‐generation sequencing
Authors: Tadano R. , Nunome M. , Mizutani M. , Kawahara‐Miki R. , Fujiwara A. , Takahashi S. , Kawashima T. , Nirasawa K. , Ono T. , Kono T. , Matsuda Y.
Published: October 2014

Next‐generation sequencing technologies permit rapid and cost‐effective identification of numerous putative microsatellite loci. Here, from the genome sequences of Japanese quail, we developed microsatellite markers containing dinucleotide repeats and employed these for characterisation of genetic diversity and population structure. A total of 385 individuals from 12 experimental and one wild‐derived Japanese quail lines were genotyped with newly developed autosomal markers. The maximum number of alleles, expected heterozygosity and polymorphic information content (PIC) per locus were 10, 0.80 and 0.77 respectively. Approximately half of the markers were highly informative (PIC ≥ 0.50). The mean number of alleles per locus and observed heterozygosity within a line were in the range of 1.3–4.1 and 0.11–0.53 respectively. Compared with the wild‐derived line, genetic diversity levels were low in the experimental lines. Genetic differentiation (FST) between all pairs of the lines ranged from 0.13 to 0.83. Genetic clustering analyses based on multilocus genotypes of individuals showed that most individuals formed clearly defined clusters corresponding to the origins of the lines. These results suggest that Japanese quail experimental lines are highly structured. Microsatellite markers developed in this study may be effective for future genetic studies of Japanese quail.
Preparing surgeons for rural Australia: the RACS Rural Surgical Training Program
Authors: Chong Aaron , Kiroff George
Published: October 2014

Background

The Royal Australasian College of Surgeons' Rural Surgical Training Program (RSTP) ran from 1996 to 2007. As a formal review of the RSTP had never occurred, it remained unknown whether the RSTP had achieved its objectives of training surgeons for and retaining them in practice in rural Australia.

Methods

Sixty‐six RSTP fellows and 67 general surgery fellows were asked to complete a survey evaluating factors influencing the decision to pursue a rural surgical career, the influence of the RSTP on subsequent career pathways and the adequacy of the RSTP in preparing its trainees for rural work.

Results

Fifty‐one out of 66 RSTP fellows were noted to be in practice in metropolitan Australia, with only 15 in rural Australia. Responses obtained revealed rural surgical rotations during training as a major influence in the decision to perform rural work. Thirty out of 35 RSTP participants stated that the RSTP did not influence their subsequent careers. Six out of 15 RSTP respondents responded positively when asked about the adequacy of the RSTP in preparing its trainees for rural work.

Conclusion

The RSTP largely succeeded in preparing its trainees for rural work, but did not succeed in retaining the majority of its trainees in practice in rural Australia. It appears that targeting doctors at the point of admission to surgical training, in the hope that this would translate into more rural surgeons, did not result in improved retention in rural areas.
Combined use of endometrial sample and magnetic resonance imaging in the preoperative risk‐stratification of endometrial carcinomas
Authors: Luomaranta Anna , Bützow Ralf , Pauna Arja‐Riitta , Leminen Arto , Loukovaara Mikko
Published: October 2014

Objective

To compare two treatment strategies in women undergoing surgery for endometrial carcinoma.

Design

Retrospective cohort study.

Setting

Tertiary care center.

Population

1166 patients. Uterine biopsy/curettage was obtained in 1140 women, of whom 229 also had pelvic magnetic resonance imaging (MRI).

Methods

We compared two strategies: (i) routine pelvic lymphadenectomy and (ii) selective pelvic lymphadenectomy for women with high‐risk carcinomas as determined from preoperative histology and MRI. High‐risk carcinomas included grade 1–2 endometrioid carcinomas with ≥50% myometrial invasion, grade 3 endometrioid carcinomas, and nonendometrioid carcinomas. Others were considered low‐risk carcinomas.

Main outcome measures

Diagnostic indices, treatment algorithms.

Results

Of the women who underwent lymphadenectomy, positive pelvic nodes were found in 2.3% of low‐risk carcinomas and 18.3% of high‐risk carcinomas. The combination of preoperative histology and MRI detected high‐risk carcinomas with a sensitivity of 85.7%, a specificity of 75.0%, a positive predictive value of 74.4%, and a negative predictive value of 86.1%. Area under curve was 0.804. In the routine lymphadenectomy algorithm, 54.1% of lymphadenectomies were performed for low‐risk carcinomas. In the selective lymphadenectomy algorithm, 14.3% of women with high‐risk carcinomas did not receive lymphadenectomy. Missed positive pelvic nodes were estimated to occur in 2.1% of patients in the selective strategy. Similarly, the estimated risk for isolated para‐aortic metastasis was 2.1%, regardless of treatment strategy.

Conclusions

The combination of preoperative histology and MRI is moderately sensitive and specific in detecting high‐risk endometrial carcinomas. The clinical utility of the method is hampered by the relatively high proportion of high‐risk cases that remain unrecognized preoperatively.
Anti‐Müllerian hormone reduction after ovarian cyst surgery is dependent on the histological cyst type and preoperative anti‐Müllerian hormone levels
Authors: Lind Tekla , Hammarström Margareta , Lampic Claudia , Rodriguez‐Wallberg Kenny
Published: October 2014

Objective

To investigate changes in serum anti‐Müllerian hormone (AMH) concentrations following ovarian cyst surgery, and predictors of these changes.

Design

Prospective cohort study with follow up at 3 and 6 months.

Setting

University hospital.

Population

Women of reproductive age scheduled for ovarian cyst surgery.

Methods

Women were recruited between March 2011 and March 2012 (n = 75). Serum AMH concentrations were measured preoperatively and at 3 and 6 months postoperatively.

Main outcome measures

Changes in AMH after surgery and predictors for these changes.

Results

After surgery, median AMH levels decreased significantly from 2.7 μg/L (0.2–16.9) to 1.6 μg/L (0.2–9.9) at 3 months and were still low, 1.6 μg/L (0.2–8.3) at 6 months (both p < 0.001). In patients with unilateral cysts, a significant and more rapid AMH decrease was seen after enucleation of endometriomas (n = 19) vs. dermoid cysts (n = 22) (p = 0.010). The reduction was long‐lasting at 6 months. In a multivariate regression analysis, a higher baseline AMH concentration was predictive of AMH reduction at 3 [odds ratio (OR) 1.9, 95% CI 1.1–3.1] and 6 months postoperatively (OR 2.5, 95% CI 1.2–5.2). Women with normal or elevated baseline AMH presented with a significant reduction of −23% and −43% at 3 and 6 months, respectively, whereas women with low or very low AMH had minimal or no changes over time. Patient's age, cyst size, duration of surgery or intraoperative bleeding were not predictive of a postoperative AMH decrease.

Conclusions

Reduction of AMH was of greater magnitude and longer duration after enucleation of endometriomas and in women with normal and high preoperative AMH levels.
Adenosine receptors and renal ischaemia reperfusion injury
Authors: Rabadi M. M. , Lee H. T.
Published: October 2014

One of the frequent clinical complications that results in billions of dollars in healthcare costs annually in the United States is acute kidney injury (AKI). Ischaemia reperfusion (IR) injury is a major cause AKI. Unfortunately, no effective treatment or preventive measure for AKI exists. With increased surgical complexity coupled with increasing number of elderly, the incidence of AKI is becoming more frequent. Adenosine is a metabolic breakdown product of adenosine triphosphate (ATP) and contributes to the regulation of multiple physiological events. Extracellular adenosine activates four subtypes of adenosine receptors (AR) including A1AR, A2AAR, A2BAR and A3AR. In the kidney, adenosine regulates glomerular filtration rate, vascular tone, renin release and is an integrative part of tubular glomerular feedback signal to the afferent arterioles. In addition, each AR subtype powerfully modulates renal IR injury. The A1AR activation protects against ischaemic insult by reducing apoptosis, necrosis and inflammation. Activation of A2AAR protects against renal injury by modulating leucocyte‐mediated inflammation as well as directly reducing renal tubular inflammation. Activation of A2BAR acts via direct activation of renal parenchymal as well as renovascular receptors and is important in kidney preconditioning. Finally, activation of A3AR exacerbates renal damage following renal IR injury while A3AR antagonism attenuates renal damage following ischaemic insult. Latest body of research suggests that kidney AR modulation may be a promising approach to treat ischaemic AKI. This brief review focuses on the signalling pathways of adenosine in the kidney followed by the role for various AR modulations in protecting against ischaemic AKI.
Effects of dietary water‐soaked barley on amino acid digestibility, growth performance, pork quality and Longissimus dorsi muscle fatty acid profiles in pigs
Authors: Wang Jian Ping , Kim In Ho
Published: October 2014

Two experiments were conducted to assess the feeding value of water‐soaked barley (WB) as a replacement for dehulled barley (DB) in pigs. In experiment (Exp.) 1, eight barrows (body weight = 30.56 ± 0.78 kg) were fitted with a T‐cannula and allotted to a duplicated 4 × 4 Latin square design: WB10, 100g/kg WB; WB20, 200 g/kg WB; DB10, 100 g/kg DB; and DB20, 200 g/kg DB. In Exp. 2, 80 barrows (body weight = 70.56 ± 1.29 kg) were used in a 56‐day experiment: (i) WB15, 150 g/kg WB; (ii) WBD10, 100 g/kg WB and 50 g/kg DB; (iii) WBD5, 50 g/kg WB and 100 g/kg DB; and (iv) DB15, 150 g/kg DB. In Exp. 1, the apparent ileal digestibilities of total essential amino acids were higher (P < 0.05) in WB10 treatment than DB20. For Exp.2, the WB15 and WBD10 had higher pH and lower cooking loss (P < 0.05) than other two treatments. The WB15 treatment decreased (P < 0.05) the contents of palmitic acid (C16:0) in Longissimus dorsi muscle than WBD5 and DB15 treatments. In conclusion, it is suggested that water‐soaked barley improved some amino acid digestibility and the cooking loss and moderate fatty acid profiles in Longissimus dorsi muscle.
Hypothyroidism associated with acromegaly and insulin‐resistant diabetes mellitus in aSamoyed
Authors: Johnstone T , Terzo E , Mooney CT
Published: October 2014

Background

The aetiology of insulin resistance (IR) in naturally occurring canine hypothyroidism is poorly understood and likely multifactorial. Excess secretion of growth hormone (GH) by transdifferentiated pituitary cells may contribute toIRin some hypothyroid dogs, but although this has been demonstrated in experimental studies, it has not yet been documented in clinical cases.

Case report

A 4‐year‐old male entireSamoyed presented with an 8‐month history of pedal hyperkeratosis and shifting lameness, which had been unresponsive to zinc supplementation, antibiotics and glucocorticoid therapy. The dog also exhibited exercise intolerance and polydipsia of 12 and 2 months duration, respectively. On physical examination, obesity, poor coat condition, widened interdental spaces and mild respiratory stridor were noted. Initial laboratory test results revealed concurrent hypothyroidism and diabetes mellitus (DM). Further investigations showedIR,GHexcess and a paradoxical increase ofGHfollowing stimulation with thyrotropin‐releasing hormone.

Conclusions

To the authors' knowledge, this is the first reported case that suggests thatGHalterations may have clinical significance in naturally occurring hypothyroidism. Among other factors, hypothyroidism‐inducedGHexcess should be considered as a possible cause ofIRin patients suffering from hypothyroidism and concurrentDM. In such cases,DMmay reverse with treatment of hypothyroidism, as was documented in this case.
Survival advantage of cyromazine‐resistant sheep blowfly larvae on dicyclanil‐ and cyromazine‐treated Merinos
Authors: Levot GW , Langfield BJ , Aiken DJ
Published: October 2014

Objective

To determine whether a cyromazine‐resistant strain of Lucilia cuprina was able to establish strikes sooner than a susceptible strain on cyromazine‐ or dicyclanil‐treated sheep.

Methods

Groups of 7 sheep were treated with cyromazine or dicyclanil in accordance with label directions. Beginning 5 weeks after treatment, 5 sheep from each group were challenged by implantation of neonate larvae belonging to the cyromazine‐resistant strain ‘Nimmitabel‐selected’ and the susceptible blowfly strain ‘Field 2011’ according to standard larval implant technique. The implant sites were alternated between the shoulder, mid‐back and rump within the treatment zone. Similarly, implants of the resistant and susceptible strain larvae were alternated at each challenge such that the strain implanted on the left side of the sheep at one challenge was implanted on the right side at the next. Challenges were conducted at 3‐weekly intervals until the susceptible larvae formed strikes on at least 2 of the 5 sheep in a treatment group or until 29 weeks after treatment.

Results

Sheep treated with cyromazine or dicyclanil were protected from flystrike by the cyromazine‐susceptible strain for periods consistent with, or longer than, the registered product label claims. The cyromazine‐resistant strain created strikes several weeks sooner after treatment than did the susceptible strain. Accordingly, the protection periods provided by cyromazine and dicyclanil against the resistant strain were reduced from 14 and 18–24 weeks to <8 weeks and <11 weeks, respectively.

Conclusion

Resistance, even in the pure‐breeding resistant strain, was not so severe as to cause treatment failure with cyromazine or dicyclanil, but was sufficient to reduce the protection period provided. It is recommended that producers adopt management practices that minimise the development of resistance to these and other compounds.
Biomechanical evaluation of double Krackow sutures versus the three‐loop pulley suture in a canine gastrocnemius tendon avulsion model
Authors: Wilson L , Banks TA , Luckman P , Smith B
Published: October 2014

Objective

To compare two Krackow sutures with a three‐loop pulley suture for the reattachment of canine gastrocnemius tendons, using a tendon avulsion model.

Study design

In vitro biomechanical study.

Methods

Ten paired gastrocnemius tendons were severed at their insertions on the calcaneal tuberosity and repaired with either two modified Krackow sutures or a modified three‐loop pulley suture. Sutures were placed in the tendon ends and through diverging bone tunnels in the medial and lateral processes of the calcaneal tuberosity. Tensile loads required to (a) create a 3‐mm gap and (b) induce construct failure were measured.

Results

The mean load to achieve a 3‐mm gap was 77.22 ± 9.72 and 55.85 ± 9.91 N, and to result in construct failure was 106.88 ± 12.74 and 80.86 ± 12.23 N for the Krackow and three‐loop pulley suture patterns, respectively. These differences were statistically significant (P < 0.001 and P = 0.001, respectively).

Conclusion and clinical relevance

Two Krackow sutures were superior to the three‐loop pulley pattern in both resistance to 3‐mm gap formation and load to failure in a canine gastrocnemius avulsion model. The prevention of gap formation is critical for the success of tenorrhaphy. These results indicate that a suture pattern using two Krackow sutures may be clinically superior to the three‐loop pulley suture pattern in the repair of canine gastrocnemius avulsion. Further work is required to determine if this superiority is mirrored in the repair of other tendon avulsion or laceration scenarios.
Influence of gestational diabetes on the stereoselective pharmacokinetics and placental distribution of metoprolol and its metabolites in parturients
Authors: Antunes Natalícia de Jesus , Cavalli Ricardo Carvalho , Marques Maria Paula , Moisés Elaine Christine Dantas , Lanchote Vera Lucia
Published: October 2014

Aim

To investigate the influence of gestational diabetes mellitus (GDM) on the kinetic disposition and transplacental and amniotic fluid distribution of metoprolol and its metabolites O‐desmethylmetoproloic acid and α‐hydroxymetoprolol stereoisomers in hypertensive parturients receiving a single dose of the racemic drug.

Methods

The study was conducted on hypertensive parturients with well‐controlled GDM (n = 11) and non‐diabetic hypertensive parturients (n = 24), all receiving a single 100 mg oral dose of racemic metoprolol tartrate before delivery. Serial maternal blood samples (0–24 h) and umbilical blood and amniotic fluid samples were collected for the quantitation of metoprolol and its metabolite stereoisomers using LC‐MS/MS or fluorescence detection.

Results

The kinetic disposition of metoprolol and its metabolites was stereoselective in the diabetic and control groups. Well‐controlled GDM prolonged tmax for both enantiomers of metoprolol (1.5 vs. 2.5 h R‐(+)‐MET; 1.5 vs. 2.75 h S‐(−)‐MET) and O‐desmethylmetoproloic acid (2.0 vs. 3.5 h R‐(+)‐AOMD; 2.0 vs. 3.0 h S‐(−)‐OAMD), and for the four stereoisomers of α‐hydroxymetoprolol (2.0 vs. 3.0 h for 1′S,2R‐, 1′R,2R‐ and 1′R,2S‐OHM; 2.0 vs. 3.5 h for 1′S,2S‐OHM) and reduced the transplacental distribution of 1′S,2S‐, 1′R,2R‐, and 1′R,2S‐OHM by approximately 20%.

Conclusions

The kinetic disposition of metoprolol was enantioselective, with plasma accumulation of the S‐(−)‐MET eutomer. Well‐controlled GDM prolonged the tmax of metoprolol and O‐desmethylmetoproloic acid enantiomers and the α‐hydroxymetoprolol stereoisomers and reduced by about 20% the transplacental distribution of 1′S,2S‐, 1′R,2R‐, and 1′R,2S‐OHM. Thus, well‐controlled GDM did not change the activity of CYP2D6 and CYP3A involved in metoprolol metabolism.
Pharmacokinetics and safety of oseltamivir in patients with end‐stage renal disease treated with automated peritoneal dialysis
Authors: Patel Kashyap , Rayner Craig R. , Giraudon Mylène , Kamal Mohamed A. , Morcos Peter N. , Robson Richard , Kirkpatrick Carl M.
Published: October 2014

Aims

Patients with end‐stage renal disease (ESRD) are at increased risk of developing complications associated with influenza infection. Oseltamivir is indicated for influenza treatment in ESRD patients, but the disposition is poorly understood in this patient population. This study aimed to characterize the pharmacokinetics and tolerability of oseltamivir in automated peritoneal dialysis (APD) and construct a pharmacokinetic model to assist with optimized dosing.

Methods

Ten adults with ESRD were prescribed an aggressive APD regimen consisting of three continuous cycler‐assisted peritoneal dialysis (CCPD) sessions during the day and two continuous ambulatory (CAPD) sessions overnight. Oseltamivir was administered as a single 75 mg dose, immediately before APD treatment.

Results

Oseltamivir was rapidly eliminated via first‐pass metabolism, with most of the dose (Fraction metabolized = 0.964) reaching the circulation as the active metabolite, oseltamivir carboxylate. This metabolite was cleared slowly and was quantifiable throughout the sampling interval. The disposition of oseltamivir and oseltamivir carboxylate was described by a two‐ and a one‐compartment model, respectively. Metabolite clearance by CCPD [0.32 l h−1 (70 kg)−1] was 1.9‐fold faster than via CAPD [0.17 l h−1 (70 kg)−1], with renal elimination being dominant in patients with residual urine production. Model simulations showed that a single 75 mg dose attained target exposures in patients with negligible or low urine clearance. However, higher doses are recommended for further investigation in patients with high residual renal function. In all patients, oseltamivir was well tolerated.

Conclusions

In APD patients with anuria or low residual renal elimination, a single 75 mg dose of oseltamivir produced exposures at the upper end of the safety margin.
Implementation of External Cephalic Version in the Netherlands: A Retrospective Cohort Study
Authors: Vlemmix Floortje , Rosman Ageeth N. , te Hoven Susan , van de Berg Suzanne , Fleuren Margot A.H. , Rijnders Marlies E. , Beuckens Antje , Opmeer Brent C. , Mol Ben Willem J. , Kok Marjolein
Published: October 2014

Background

External cephalic version (ECV) reduces the rate of elective cesarean sections as a result of breech presentation. Several studies have shown that not all eligible women undergo an ECV attempt. The aim of this study was to evaluate the implementation of ECV in the Netherlands and to explain variation in implementation rates with hospital characteristics and individual factors.

Methods

We invited 40 hospitals to participate in this retrospective cohort study. We reviewed hospital charts for all singleton breech deliveries from 36 weeks' gestation and onwards between January 2008 and December 2009. We documented whether an ECV attempt was performed, reasons for not performing an attempt, mode of delivery, and hospital characteristics.

Results

We included 4,770 women from 36 hospitals. ECV was performed in 2,443 women (62.2% of eligible women, range 8.2–83.6% in different hospitals). Implementation rates were higher in teaching hospitals, hospitals with special office hours for ECV, larger obstetric units, and hospitals located in larger cities. Suboptimal implementation was mainly caused by health care providers who did not offer ECV.

Conclusion

ECV implementation rates vary widely among hospitals. Suboptimal implementation is mostly caused by the care provider not offering the treatment and secondly due to women not opting for the offered attempt. A prerequisite for designing a proper implementation strategy is a detailed understanding of the exact reasons for not offering and not opting for ECV.
Development of Peptidyl Lysine Dendrons: 1,3‐Dipolar Cycloaddition for Peptide Coupling and Antibody Recognition
Authors: Hüttl Christine , Hettrich Cornelia , Riedel Melanie , Henklein Petra , Rawel Harshadrai , Bier Frank F.
Published: October 2014

A straightforward synthesis strategy to multimerize a peptide mimotopes for antibody B13‐DE1 recognition is described based on lysine dendrons as multivalent scaffolds. Lysine dendrons that possess N‐terminal alkyne residues at the periphery were quantitative functionalized with azido peptides using click chemistry. The solid‐phase peptide synthesis (SPPS) allows preparing the peptide dendron in high purity and establishing the possibility of automation. The presented peptide dendron is a promising candidate as multivalent ligand and was used for antibody B13‐DE1 recognition. The binding affinity increases with higher dendron generation without loss of specificity. The analysis of biospecific interaction between the synthesized peptide dendron and the antibody was done via surface plasmon resonance (SPR) technique. The presented results show a promising tool for investigations of antigen–antibody reactions.
Journeys of adjustment: the experiences of adolescents living with juvenile idiopathic arthritis
Authors: Cartwright T. , Fraser E. , Edmunds S. , Wilkinson N. , Jacobs K.
Published: October 2014

Background

Juvenile idiopathic arthritis (JIA) is one of the most common diseases of childhood causing pain, swelling of joints and reduced mobility. Previous research has focused on the challenges and psychosocial impact of JIA, but there has been limited attention given to how young people adjust and adapt to living with a long‐term condition such as JIA. The aim of this qualitative study was therefore to explore adolescents' experiences of living with JIA, with particular focus on the process of adjustment.

Methods

Ten adolescents (7 female, 3 male) aged 13–17 years with good treatment adherence were recruited from an adolescent arthritis clinic. In‐depth interviews were conducted, and data were analysed by two researchers independently using interpretative phenomenological analysis.

Results

These adolescents described the physical and psychosocial ‘burden of living with JIA’ and the challenges faced by an underlying preoccupation ‘to be a normal teenager’. However, their accounts also revealed ways in which they regained agency and developed ‘resilience through taking control’ over their lives. This resilience helped the adolescents re‐establish a sense of well‐being through an ongoing process of ‘acceptance and self‐growth’.

Conclusions

Although much research has adopted a deficit model that focuses on adjustment problems, the current study highlights the resourcefulness of young people in managing the challenges of living with a long‐term condition. These experiences of successful adjustment can be used as the basis of positive, strength‐based intervention approaches for adolescents with arthritis to enhance resilience and well‐being.
False‐Belief Understanding and Social Preference Over the First 2 Years of School: A Longitudinal Study
Authors: Fink Elian , Begeer Sander , Hunt Caroline , de Rosnay Marc
Published: October 2014

The role of false belief in establishing children's social relationships during the transition to school was examined and compared to other social cognitive constructs. One hundred and fourteen 5‐year‐olds were recruited during their 1st year of school (Time 1); 106 children were retained 1 year later. False belief, emotion expression recognition, empathy, verbal ability, and peer‐rated social preference were measured at both times. False belief at Time 1 had a direct influence on concurrent social preference, over and above the influence of emotion expression recognition and empathy. False belief made no independent contribution to later social preference accounting for stability in social preference. The role of social cognitive development is discussed with respect to how children establish and maintain their position in a peer group.
Musical Training, Bilingualism, and Executive Function: A Closer Look at Task Switching and Dual‐Task Performance
Authors: Moradzadeh Linda , Blumenthal Galit , Wiseheart Melody
Published: October 2014

This study investigated whether musical training and bilingualism are associated with enhancements in specific components of executive function, namely, task switching and dual‐task performance. Participants (n = 153) belonging to one of four groups (monolingual musician, bilingual musician, bilingual non‐musician, or monolingual non‐musician) were matched on age and socioeconomic status and administered task switching and dual‐task paradigms. Results demonstrated reduced global and local switch costs in musicians compared with non‐musicians, suggesting that musical training can contribute to increased efficiency in the ability to shift flexibly between mental sets. On dual‐task performance, musicians also outperformed non‐musicians. There was neither a cognitive advantage for bilinguals relative to monolinguals, nor an interaction between music and language to suggest additive effects of both types of experience. These findings demonstrate that long‐term musical training is associated with improvements in task switching and dual‐task performance.
Cerebellar and cortical abnormalities in paediatric opsoclonus‐myoclonus syndrome
Authors: Anand Geetha , Bridge Holly , Rackstraw Peter , Chekroud Adam M , Yong Jean , Stagg Charlotte J , Pike Michael
Published: October 2014

Aim

Paediatric opsoclonus‐myoclonus syndrome (OMS) is a poorly understood condition with long‐term cognitive, behavioural, and motor sequelae. Neuroimaging has indicated cerebellar atrophy in the chronic phase, but this alone may not explain the cognitive sequelae seen in many children with OMS. This study aimed to determine the extent of structural change throughout the brain that may underpin the range of clinical outcomes.

Method

Nine participants with OMS (one male, eight females; mean age [SD] 14y, [6y 5mo], range 12–30y) and 10 comparison individuals (three males, seven females; mean age 12y 6mo, [4y 9mo], range 10–23y) underwent magnetic resonance imaging to acquire T1‐weighted structural images, diffusion‐weighted images, and magnetic resonance spectroscopy scans. Neuroblastoma had been present in four participants with OMS. Voxel‐based morphometry was used to determine changes in grey matter volume, tract‐based spatial statistics to analyze white matter integrity, and Freesurfer to analyze cortical thickness across visual and motor cortices.

Results

Whole‐brain analysis indicated that cerebellar grey matter was significantly reduced in the patients with OMS, particularly in the vermis and flocculonodular lobe. A region‐of‐interest analysis indicated significantly lower cerebellar grey matter volume, particularly in patients with the greatest OMS scores. Diffusion‐weighted images did not show effects at a whole brain level, but all major cerebellar tracts showed increased mean diffusivity when analysis was restricted to the cerebellum. Cortical thickness was reduced across the motor and visual areas in the OMS group, indicating involvement beyond the cerebellum.

Interpretation

Across individuals with OMS, there is considerable cerebellar atrophy, particularly in the vermis and flocculonodular lobes with atrophy severity associated with persistent symptomatology. Differences in cerebral cortical thickness indicate disease effects beyond the cerebellum.
Neuroimaging in pediatric opsoclonus‐myoclonus syndrome: beyond the search for neuroblastomas
Authors: Prabhu Sanjay P
Published: October 2014

This commentary is on the original article by Anand et al. on pages 265–272 of this issue.