bluuebunny/crossref_metadata_2025 huggingface dataset:
Mountain hares Lepus timidus and tourism: stress events and reactions
Authors: Rehnus Maik , Wehrle Martin , Palme Rupert
Published: October 2013

Winter tourism in the European Alps has developed rapidly over the past few decades, leading to the expansion of ski resorts, growing numbers of visitors and a massive increase in snow sport activities such as free‐ride skiing and snowboarding, backcountry skiing and snowshoeing. Wildlife is often disturbed by these largely unpredictable activities, and animals may have limited opportunities to adapt. Mountain hares Lepus timidus are affected by this increase in alpine tourism, but their physiological and behavioural reactions to tourist activity are still unknown.

We measured the levels of faecal glucocorticoid metabolites (GCM) in wild mountain hares living in areas that had no, medium or high levels of tourist activity during winter in 2011. Furthermore, we compared the changes in GCM excretion, behaviour and food intake of six captive mountain hares following predator challenge experiments from early to mid‐winter.

Our field results showed that GCM excretion is positively correlated with increased tourism intensity. In the predator challenge experiments, hares spent less time resting and grooming (including re‐ingesting faecal pellets) during and after the stress treatments. These stress events lead to higher energy demands due to flushing, increased GCM levels, and disrupted the energy intake that hares derive from faeces.

We conclude that mountain hares living in areas with frequent human winter recreational activities show changes in physiology and behaviour that demand additional energy in winter, when access to food resources is limited by snow.

Synthesis and applications. To bring down the frequency of stress threats for mountain hares, we recommend that managers keep forests inhabited by mountain hares free of tourism infrastructure and retain undisturbed forest patches within skiing areas. Other species such as black grouse Tetrao tetrix and/or capercaillie Tetrao urogallus are also likely to benefit from such management activities because they share similar habitat requirements with mountain hares.
Cerebral open flow microperfusion: A new in vivo technique for continuous measurement of substance transport across the intact blood–brain barrier
Authors: Birngruber Thomas , Ghosh Arijit , Perez‐Yarza Veronica , Kroath Thomas , Ratzer Maria , Pieber Thomas R , Sinner Frank
Published: October 2013

The blood–brain barrier (BBB) limits substance transport to the brain and is therefore the major hurdle to overcome when developing neuroactive drugs. Herein, we report on cerebral open flow microperfusion (cOFM) as a new membrane‐free technique for measuring substance transport across the intact BBB.

The cOFM technique is based on a probe that is inserted into the brain, rupturing the BBB. The BBB is re‐established within 15 days, which then allows sampling of interstitial brain fluid under physiological conditions. The aims of the present proof‐of‐concept study were to: (i) determine the time between cOFM probe insertion and BBB re‐establishment; and (ii) demonstrate the ability of cOFM to sample the interstitial cerebral fluid with an intact BBB.

The cOFM probe was inserted into the frontal lobe of Sprague–Dawley rats, resulting in BBB rupture. Re‐establishment of the BBB was determined using Evans blue (EB) dye, which is an established marker for BBB intactness because it does not cross the intact BBB. Evaluating EB levels in the brain tissue indicated that the BBB was healed 11 days after probe insertion.

To demonstrate transport across the healed BBB, we used sodium fluorescein (Naf), a sensitive, low molecular weight marker that can cross the intact BBB and can be used to monitor changes in BBB permeability. Significantly increased Naf levels were found in the interstitial fluid when hyperosmolar mannitol (known to open the BBB) was introduced via cOFM, which indicated partial opening of the BBB surrounding the cOFM probe.

In conclusion, we show herein that cOFM allows monitoring of BBB permeability, which should be useful for measuring pharmacokinetics across the BBB and pharmacodynamics in the brain.
Riluzole reduces arrhythmias and myocardial damage induced by coronary occlusion in anaesthetized pigs
Authors: Weiss Steven M , Dahlstrom Jane E , Saint David A
Published: October 2013

The cardiac persistent sodium current (INaP) presents a novel target for cardiac ischaemic protection. Herein we investigated the effects of the INaP blocker riluzole in a pig model of regional myocardial ischaemia.

Landrace or Large White pigs were subjected to 3 h ligation of the left anterior descending coronary artery (LAD). Pigs received either saline (500 mL/h, i.v.) throughout the experiment (control; n = 7) or riluzole (2 mg/kg in 2 mL propylene glycol in 100 mL saline, i.v.; RIL; n = 7) between 15 and 5 min prior to ligation. The arrhythmia score was calculated in 5 min epochs. Myocardial damage was assessed using epicardial image analysis and histological sectioning.

In the control group, all seven pigs developed premature ventricular contractions (PVC), seven developed non‐sustained arrhythmias and six of seven developed sustained arrhythmias. Of the sustained arrhythmias, 23 of 28 instances were initiated by R‐on‐T extrasytoles (extrasystoles within the vulnerable period that can trigger re‐entrant arrhythmias). In the RIL group, all seven pigs developed PVC, six of seven developed non‐sustained arrhythmias and only three developed sustained arrhythmias, of which two of five instances were R‐on‐T initiated. The riluzole‐treated pigs exhibited less myocardial damage than pigs in the control group (65% smaller surface area (P = 0.008) on gross epicardial inspection, 51% less oedema (P = 0.01), 53% less fibre waviness (P = 0.029) assessed by haematoxylin and eosin staining and 79% fewer fragmented nuclei (P = 0.009) assessed by terminal deoxyribonucleotidyl transferase‐mediated dUTP–digoxigenin nick end‐labelling).

In conclusion, riluzole significantly reduced Phase 2 (the period associated with irreversible damage) ischaemic R‐on‐T triggered and non‐R‐on‐T arrhythmias and myocardial damage occurring during the 3 h period of regional ischaemia.
Methodological limitations in the evaluation of policies to reduce nitrate leaching from New Zealand agriculture
Authors: Doole Graeme J. , Marsh Dan K.
Published: October 2013

The land‐use optimisation framework, NZFARM, has been promoted as a tool that can be used to assess the economic and environmental impacts of policy on regional land use. This paper outlines how methodological limitations presently restrict its capacity to provide meaningful insight into the relative value of alternative land‐use configurations. The model is calibrated using positive mathematical programming, which has been shown in the literature to result in models that yield arbitrary output outside of the calibrated baseline. There is a high likelihood that this is the case, as no validation appears to have been carried out. Significant model development will be required before NZFARM outputs can be used with any confidence to inform future policy development. We conclude with suggestions on how NZFARM and models of its kind can be further developed to improve their capacity for meaningful simulation.
Streptococcus thermophilus strains of plant origin as dairy starters: Isolation and characterisation
Authors: Umamaheswari Thiyagamoorthy , Anbukkarasi Kaliyaperumal , Singh Prashant , Tomar Sudhir K , Singh Rameshwar
Published: October 2013

Streptococcus thermophilus strains have been isolated mainly from dairy environments. To prospect for new strains of S. thermophilus, isolation was made from different plant sources. In this study, 74 plant isolates were characterised as S. thermophilus by a polyphasic approach and by 16S rRNA sequencing. The isolates were further evaluated for their physiological and biochemical properties. Plant isolates exhibited good acid production and varying proteolytic activity. All the isolates showed acetaldehyde and capsular exopolysaccharide (EPS) production and few revealed diacetyl production. In contrast to industrial strains, six isolates were able to ferment galactose and 25 were found to have no urease activity. Both the plant isolates and reference dairy cultures were found to possess similar physiological and biochemical properties and can be considered for developing new starters.
The Effect of SN‐6, a Novel Sodium‐Calcium Exchange Inhibitor, on Contractility and Calcium Handling in Isolated Failing Rat Ventricular Myocytes
Authors: Gandhi Ajay , Siedlecka Urszula , Shah Adarsh P. , Navaratnarajah Manoraj , Yacoub Magdi H. , Terracciano Cesare M.
Published: October 2013

Background and Purpose

Specific Na+/Ca2+ exchanger (NCX) inhibition is a potential strategy to correct reduced contractility and depleted sarcoplasmic reticulum (SR) Ca2+ content in heart failure (HF). SN‐6, a benzyloxyphenyl derivative and proposed selective NCX inhibitor, could be used for this purpose. This study aimed to evaluate the effects of SN‐6 on contractility and Ca2+ handling in normal and failing rat cardiomyocytes.

Experimental Approach

HF was induced in rats by coronary artery ligation. Left ventricular myocytes were isolated and superfused with increasing concentrations of SN‐6.

Key Results

Sarcomere shortening, induced by field‐stimulation, was reduced in amplitude with increasing concentrations of SN‐6 compared with control solution. This effect was greater in failing cells. Kinetics of contractility (time to 90% peak and time to 50% relaxation) were significantly faster. Despite this, intracellular Ca2+ transients demonstrated no change in the peak amplitude at low concentrations of SN‐6, suggesting that SN‐6 may affect myofilament sensitivity to Ca2+. Ten micro molar SN‐6 significantly reduced peak Ca2+ amplitude by 61.57% and 64.73% in normal and failing cells, respectively. Diastolic Ca2+ was significantly increased at 1 μM SN‐6. SR Ca2+ content, assessed by rapid application of caffeine, was reduced in failing cells with 1 μM SN‐6. Peak ICa, measured by whole‐cell patch clamping, was significantly reduced in normal and failing myocytes at 1 μM SN‐6.

Conclusions and Implications

Our data suggest that SN‐6 is not a selective inhibitor of NCX and impairs contractility and Ca2+ handling. Its use, together with similar putative NCX blockers, in correcting the contractile abnormalities of heart failure requires further studies.
Analyst Report Readability
Authors: De Franco Gus , Hope Ole‐Kristian , Vyas Dushyantkumar , Zhou Yibin
Published: October 2013

Using an extensive database of 356,463 sell‐side equity analysts' reports from 2002 to 2009, this study is one of the first to analyze the readability of analysts' reports. We first examine the determinants of variations in analyst report readability. Using several proxies for ability, we show that reports are more readable when issued by analysts with higher ability. Second, we test the relation between analysts' report readability and stock trading volume reactions. We find that trading volume reactions increase with the readability of analysts' text, consistent with theoretical models that predict that more precise information (and hence more informative signals) results in investors' initiating trades. These results support the view that the readability of analysts' reports is important to analysts and capital market participants.
Joint analysis of additive, dominant and first‐order epistatic effects of four genes (IGF2, MC4R, PRKAG3 and LEPR) with known effects on fat content and fat distribution in pigs
Authors: López‐Buesa P. , Burgos C. , Galve A. , Varona L.
Published: October 2013

LEPR, MC4R, IGF2 and PRKAG3 are genes with known effects on fat content and distribution in pig carcass and pork. In a study performed with Duroc × Landrace/Large White pigs, we have found that IGF2 has strong additive effects on several carcass conformational traits and on fatty acid composition in several anatomical locations. MC4R shows additive effects on saturated fatty acid content in several muscles. On the other side, almost no additive effect has been found for PRKAG3 and very few for LEPR. In this work, no dominant effect has been found for any of the four genes. Using a Bayesian Lasso approach, we have been able now to find first‐order epistatic (mainly dominant–additive) effects between LEPR and PRKAG3 for intramuscular fat content and for saturated fatty acid content in L. dorsii, B. femoralis, Ps. major and whole ham. The presence of interactions between genes in the shaping of traits of such importance as intramuscular fat content and composition highlights the complexity of heritable traits and the difficulty of gene‐assisted selection for such traits.
Input subsidy programs in sub‐Saharan Africa: a synthesis of recent evidence
Authors: Jayne T.S. , Rashid Shahidur
Published: October 2013

Input subsidy programs have once again become a major plank of agricultural development strategies in Africa. Ten African governments spend roughly US$1 billion annually on input subsidy programs (ISPs), amounting to 28.6% of their public expenditures on agriculture. This article reviews the microlevel evidence on ISPs undertaken since the mid 2000s. We examine the characteristics of subsidy beneficiaries, crop response rates to fertilizer application and their influence on the performance of subsidy programs, the impacts of subsidy programs on national fertilizer use and the development of commercial input distribution systems, and finally the impact of ISPs on food price levels and poverty rates. The weight of the evidence indicates that the costs of the programs generally outweigh their benefits. Findings from other developing areas with a higher proportion of crop area under irrigation and with lower fertilizer prices—factors that should provide higher returns to fertilizer subsidies than in Africa—indicate that at least a partial reallocation of expenditures from fertilizer subsidies to R&D and infrastructure would provide higher returns to agricultural growth and poverty reduction. However, because ISPs enable governments to demonstrate tangible support to constituents, they are likely to remain on the African landscape for the foreseeable future. Hence, the study identifies ways in which benefits can be enhanced through changes in implementation modalities and complementary investments within a holistic agricultural intensification strategy. Among the most important of these are efforts to reduce the crowding out of commercial fertilizer distribution systems and programs to improve soil fertility to enable farmers to use fertilizer more efficiently. The challenges associated with achieving these gains are likely to be formidable.
Interdependent self‐construal moderates coping with (but not the initial pain of) ostracism
Authors: Ren Dongning , Wesselmann Eric D. , Williams Kipling D.
Published: October 2013

Ostracism – being excluded and ignored – can cause psychological distress. There has been little research examining how a person's concept of self might influence the effects of ostracism. In the current study, we sought to examine the effect of self‐construal on the distress created by ostracism. Specifically, we assessed the potential moderating effects of self‐construal on both the initial distress of ostracism and the coping process. Participants, recruited in China, completed a self‐construal measure and were either included or ostracized in an online ball‐tossing game. They then reported need‐satisfaction both immediately following the game and after a filler task. Interdependent self‐construal facilitated participants' recovery from some of the negative effects of ostracism, but did not have an impact on the initial pain.
Influence of multi‐lumen extensions on fluid flow through intravenous cannulae
Authors: Levine D. M. , Garden A. L. , Truong H. T. , Bergemann J. , Eames P.
Published: October 2013

Multi‐lumen extensions used to infuse multiple fluids via a single intravenous cannula might increase resistance and so limit the flow that can be achieved. We constructed low‐pressure and high‐pressure models and compared the effect of two different multi‐lumen extensions on flow rate. Both multi‐lumen extensions reduced flows by up to 76% (p < 0.001). The effect was greatest with large cannulae and in the high‐pressure model, with the longer and narrower extension most impeding flow. Multi‐lumen extensions can therefore significantly impede fluid flow, and should be avoided or removed when rapid infusion is required. These effects are less important in paediatric anaesthesia where smaller cannulae are used. Manufacturers should include internal diameter or flow effects on the packaging of these extensions to assist clinicians in making such decisions.
Adalimumab maintains remission of Crohn's disease after up to 4 years of treatment: data from CHARM and ADHERE
Authors: Panaccione R. , Colombel J.‐F. , Sandborn W. J. , D'Haens G. , Zhou Q. , Pollack P. F. , Thakkar R. B. , Robinson A. M.
Published: October 2013

Background

Therapies that maintain remission for patients with Crohn's disease are essential. Stable remission rates have been demonstrated for up to 2 years in adalimumab‐treated patients with moderately to severely active Crohn's disease enrolled in the CHARM and ADHERE clinical trials.

Aim

To present the long‐term efficacy and safety of adalimumab therapy through 4 years of treatment.

Methods

Remission (CDAI <150), response (CR‐100) and corticosteroid‐free remission over 4 years, and maintenance of these endpoints beyond 1 year were assessed in CHARM early responders randomised to adalimumab. Corticosteroid‐free remission was also assessed in all adalimumab‐randomised patients using corticosteroids at baseline. Fistula healing was assessed in adalimumab‐randomised patients with fistula at baseline. As observed, last observation carried forward and a hybrid nonresponder imputation analysis for year 4 (hNRI) were used to report efficacy. Adverse events were reported for any patient receiving at least one dose of adalimumab.

Results

Of 329 early responders randomised to adalimumab induction therapy, at least 30% achieved remission (99/329) or CR‐100 (116/329) at year 4 of treatment (hNRI). The majority of patients (54%) with remission at year 1 maintained this endpoint at year 4 (hNRI). At year 4, 16% of patients taking corticosteroids at baseline were in corticosteroid‐free remission and 24% of patients with fistulae at baseline had healed fistulae. The incidence rates of adverse events remained stable over time.

Conclusions

Prolonged adalimumab therapy maintained clinical remission and response in patients with moderately to severely active Crohn's disease for up to 4 years. No increased risk of adverse events or new safety signals were identified with long‐term maintenance therapy. (clinicaltrials.gov number: NCT00077779).
Re‐‘homing’ the ex‐offender: constructing a ‘prisoner dyspora'
Authors: Turner Jennifer
Published: October 2013

Recent work within and beyond the geography discipline has come to understand that where might be imagined a sharp boundary between the ‘hidden’ inside and outside of prisons, there is in fact a myriad of materials that cleave and bind penal geographies that mark the prison wall as a site of transaction and exchange. Recidivism in the UK is of serious concern, rendering the ‘prisoner’ a participant of a very unique and dynamic type of border exchange. In light of this, this paper questions how this impacts prisoners' identities and attachments to ‘home’. Although ex‐offenders may idealise a return to the communities where they lived prior to incarceration, the ability to re‐integrate is often limited. This may be attributed to the transformations that individuals undergo while spending time in prison, such as the possession of a criminal record. In grounding this discussion in the case of a company that employs ‘ex‐offenders’, I examine the implications of belonging to such a group of ‘conventional employees’ and ‘those with criminal records’; revealing tensions that complicate matters of belonging. This paper therefore posits the prison as a kind of ‘homeland’ that continues to significantly shape one's identity following their out‐migration. Those leaving prison find themselves unable to display conventional attachments to the outside society, while performing a dystopian relationship with the prison homeland, allowing for a consideration of what I have termed the ‘prisoner dyspora’.
Cardiac complications and diabetes in thalassaemia major: a large historical multicentre study
Authors: Pepe Alessia , Meloni Antonella , Rossi Giuseppe , Caruso Vincenzo , Cuccia Liana , Spasiano Anna , Gerardi Calogera , Zuccarelli Angelo , D'Ascola Domenico G. , Grimaldi Salvatore , Santodirocco Michele , Campisi Saveria , Lai Maria E. , Piraino Basilia , Chiodi Elisabetta , Ascioti Claudio , Gulino Letizia , Positano Vincenzo , Lombardi Massimo , Gamberini Maria R.
Published: October 2013

The relationship between diabetes mellitus (DM) and cardiac complications has never been systematically studied in thalassaemia major (TM). We evaluated a large retrospective historical cohort of TM to determine whether DM is associated with a higher risk of heart complications. We compared 86 TM patients affected by DM with 709 TM patients without DM consecutively included in the Myocardial Iron Overload in Thalassaemia database where clinical/instrumental data are recorded from birth to the first cardiovascular magnetic resonance (CMR) exam. All of the cardiac events considered were developed after the DM diagnosis. In DM patients versus non‐DM patients we found a significantly higher frequency of cardiac complications (46·5% vs. 16·9%, P < 0·0001), heart failure (HF) (30·2% vs. 11·7%, P < 0·0001), hyperkinetic arrhythmias (18·6% vs. 5·5%, P < 0·0001) and myocardial fibrosis assessed by late gadolinium enhancement (29·9% vs. 18·4%, P = 0·008). TM patients with DM had a significantly higher risk of cardiac complications [odds ratio (OR) 2·84, P < 0·0001], HF (OR 2·32, P = 0·003), hyperkinetic arrhythmias (OR 2·21, P = 0·023) and myocardial fibrosis (OR 1·91, P = 0·021), also adjusting for the absence of myocardial iron overload assessed by T2* CMR and for the covariates (age and/or endocrine co‐morbidity). In conclusion, DM significantly increases the risk for cardiac complications, HF, hyperkinetic arrhythmias and myocardial fibrosis in TM patients.
Myeloma stem cell concepts, heterogeneity and plasticity of multiple myeloma
Authors: Hajek Roman , Okubote Samuel A. , Svachova Hana
Published: October 2013

Multiple myeloma (MM) is a haematological malignancy characterized by the accumulation of clonal plasma cells (PCs) in the bone marrow (BM). Although novel therapeutic strategies have prolonged survival of patients, the disease remains difficult to treat with a high risk of relapse. The failure of therapy is thought to be associated with a persistent population of the so‐calledMMstem cells or myeloma initiating cells (MIC) that exhibit tumour‐initiating potential, self‐renewal and resistance to chemotherapy. However, the population responsible for the origin and sustainability of tumour mass has not been clearly characterized so far. This review summarizes current myeloma stem cell concepts and suggests that high phenotypic and intra‐clonal heterogeneity, together with plasticity potential ofMMmight be other contributing factors explaining discrepancies among particular concepts and contributing to the treatment failure.
Assessing the extirpative quality of a radical prostatectomy technique: categorisation and mapping of technical errors
Authors: Barré Christian , Thoulouzan Matthieu , Aillet Geneviève , Nguyen Jean‐Michel
Published: October 2013

Objective

To examine the extirpative quality of an open radical prostatectomy (RP) technique by first categorising and mapping all intraprostatic incisions into benign tissue and then determining a cumulative technical error rate given by all intraprostatic incisions into benign and malignant tissue.

Patients and Methods

We performed a retrospective review of prospectively collected data relating to 1065 men with clinically localised prostate cancer who underwent open retropubic RP (70.6% nerve‐sparing surgery [NSS]) by a single surgeon (January 2005 to December 2011).

We recorded all intraprostatic incisions: (i) iatrogenic positive surgical margins (PSMs), (ii) deep or superficial benign capsular incisions (BCIs), (iii) incisions into benign prostate glands at the prostate apex or bladder neck (benign glandular tissue incisions [BGTIs]), and determined incision location, length and nature (solitary/multiple).

We evaluated: (i) associations between benign incisions, NSS and PSMs, (ii) significant predictors for PSM risk by multivariate analysis, (iii) postoperative biochemical recurrence (BCR)‐free survival (Kaplan–Meier method).

Results

Intraprostatic incision rates were 2.3% pT2 PSMs, 6.0% BCIs and 5.4% BGTIs. There were slight variations in rate over time and with NSS technique. Benign incisions were located as follows: 46.8% right posterolateral, 37.5% left posterolateral, and 15.7% bilateral for BCIs; 58.6% bladder neck and 41.4% apical for BGTIs.

The median (range) incision length, for solitary and multiple incisions respectively, was 4 (1–13) and 9 (2–25) mm for BCIs and 1 (1–5) and 2 (2–6) mm for BGTIs.

BCI rate, but not BGTI rate, was significantly associated with NSS (P = 0.004) and PSM (P = 0.005), and increased PSM risk 3.6‐fold.

A PSM increased BCR risk two‐fold (odds ratio 2.078, 95% confidence interval 1.383–3.122).

BCR‐free survival decreased significantly even for short PSMs (<1 mm; P < 0.001).

Conclusions

Although the pT2 PSM rate was low (2.3%), the cumulative technical error rate (patients with at least one pT2 PSM, BCI or BGTI) was five‐fold higher (12.5%).

Categorising and mapping intraprostatic incisions is a tool surgeons can use in self‐audits to identify areas of potential improvement, reduce errors, and improve surgical skills.
Parthanatos: mitochondrial‐linked mechanisms and therapeutic opportunities
Authors: Fatokun Amos A , Dawson Valina L , Dawson Ted M
Published: October 2013

Cells die by a variety of mechanisms. Terminally differentiated cells such as neurones die in a variety of disorders, in part, via parthanatos, a process dependent on the activity of poly (ADP‐ribose)‐polymerase (PARP). Parthanatos does not require the mediation of caspases for its execution, but is clearly mechanistically dependent on the nuclear translocation of the mitochondrial‐associated apoptosis‐inducing factor (AIF). The nuclear translocation of this otherwise beneficial mitochondrial protein, occasioned by poly (ADP‐ribose) (PAR) produced through PARP overactivation, causes large‐scale DNA fragmentation and chromatin condensation, leading to cell death. This review describes the multistep course of parthanatos and its dependence on PAR signalling and nuclear AIF translocation. The review also discusses potential targets in the parthanatos cascade as promising avenues for the development of novel, disease‐modifying, therapeutic agents.

Linked Articles

This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue‐8
P16INK4A as a surrogate biomarker for human papillomavirus‐associated oropharyngeal carcinoma: Consideration of some aspects
Authors: Wang Hongzhi , Sun Rui , Lin Hui , Hu Wei‐han
Published: October 2013

Human papillomavirus (HPV)‐associated oropharyngeal squamous cell carcinomas (OPSCCs) frequently show different clinical and pathological features, which tend to be younger age, better performance status, less tobacco and alcohol consumption, more poorly differentiated histopathology, but usually with better treatment response and prognosis compared with HPV‐negative OPSCCs. In tumor tissue, HPV infection is closely correlated with p16INK4A expression, which has been suggested to be a surrogate biomarker of HPV infection. However, there is diversity of sensitivity and specificity about p16INK4A in surrogate detection of HPV status. Herein, we summarize the current knowledge and note some aspects for consideration concerning p16INK4A as a surrogate biomarker for HPV‐associated OPSCC.
Insulin autoimmune syndrome (Hirata Disease) in European Caucasians taking α‐lipoic acid
Authors: Gullo Damiano , Evans Joseph L. , Sortino Grazia , Goldfine Ira D. , Vigneri Riccardo
Published: October 2013

Objective

Lipoic acid (LA) is a widely used nutritional supplement and is sometimes used as an adjuvant treatment for diabetic neuropathy and other conditions. Insulin autoimmune syndrome (IAS, Hirata disease) is a rare cause of spontaneous hypoglycaemia, extremely high serum insulin levels and high titres of autoantibodies against endogenous insulin despite no prior exposure to exogenous insulin. In Japanese individuals, IAS is associated with the human leucocyte antigen (HLA) HLA‐DRB1*04:06 allele and often occurs upon exposure to sulphhydryl‐containing compounds including LA. Only one case has been reported in Caucasians. We now report six Caucasian patients taking LA with IAS and describe a unique HLA subtype in these patients.

Research Design and Methods

Six Caucasian patients (M = 3; F = 3), median age 63 years, presented with spontaneous episodes of fasting and postabsorptive hypoglycaemia associated with mainly neuroglycopenic symptoms. No patient was treated with insulin or had an insulinoma. Hypoglycaemic symptoms appeared 30 and 120 days after taking lipoic acid (LA; 600 mg/day). Case histories and standard laboratory analyses were utilized.

Results

Discontinuation of LA resulted in a reduction in hypoglycaemic episodes. All patients were treated with oral or iv glucose and prednisone (12·5–25 mg/day). HLA analysis revealed the HLA‐DRB1*04:03 allele in five patients, while the HLA‐DRB1*04:06 allele was present in one patient.

Conclusions

This is the first report of LA‐related IAS in Caucasians who possess the HLA‐DRB1*04:03 allele, implicating this allele in the genetic susceptibility to IAS in Caucasians. The greater occurrence of the HLA‐DRB1*04:03 allele in Caucasian and other populations, combined with the growing use of LA in developed countries, may be a future predictor of additional cases of IAS.
Genetics of hypertrophic cardiomyopathy in Norway
Authors: Berge K.E. , Leren T.P.
Published: October 2013

Genetic testing for hypertrophic cardiomyopathy (HCM) became available in Norway in 2003. Here, we describe the results of this testing in probands with HCM referred until the end of 2012. The translated exons of MYBPC3, MYH7, TNNI3, TNNT2, MYL2 and MYL3 were analyzed in two groups of probands. In Group 1, comprising 696 probands above 1 year of age, a mutation was found in 203 patients (29.2%). Of those, 5.9% were carriers of two mutations. Mean age in double mutation carriers, single mutation carriers and mutation negative probands was 44 years (±19 years), 50 years (±15 years) and 55 years (±16 years), respectively. In Group 2, comprising 26 infants below the age of 1, a mutation was found in 15.4%. A total of 120 different mutations were found of which 51 (42.5%) were novel.
Impact of Genetically Engineered Varieties on the Cost Structure of Corn and Soybean Production in Canada
Authors: Saha Bishnu , Sarker Rakhal , Mitura Verna
Published: October 2013

This paper investigates the impact of genetically engineered (GE) varieties on the cost structure of corn and soybean production in Canada. Employing an adoption index for each farm and a time trend with farm‐level data on production costs of grain corn and soybeans from 2000 to 2007, a translog cost function and the associated input‐share equations are estimated. The use of the adoption index improves the estimates of technological change and multifactor productivity (MFP) growth. The results demonstrate that the adoption of GE corn and soybean reduced the variable costs of production by 0.62% per year. The MFP of corn and soybean grew by 2.0% per year during the study period, and 31% of this growth is attributable to GE varieties of these crops. The results also reveal that the adoption of GE varieties reduced the cost shares of fertilizer, herbicides and pesticides, and machinery in corn and soybean production. While the adoption of GE varieties increased the cost shares of seeds and custom works including labor, only the former was statistically significant.
Selection criteria for selective dorsal rhizotomy in children with spastic cerebral palsy: a systematic review of the literature
Authors: Grunt Sebastian , Fieggen A Graham , Vermeulen R Jeroen , Becher Jules G , Langerak Nelleke G
Published: October 2013

Aim

Information regarding the selection procedure for selective dorsal rhizotomy (SDR) in children with spastic cerebral palsy (CP) is scarce. Therefore, the aim of this study was to summarize the selection criteria for SDR in children with spastic CP.

Method

A systematic review was carried out using the following databases: MEDLINE, CINAHL, EMBASE, PEDro, and the Cochrane Library. Additional studies were identified in the reference lists. Search terms included ‘selective dorsal rhizotomy’, ‘functional posterior rhizotomy’, ‘selective posterior rhizotomy’, and ‘cerebral palsy’. Studies were selected if they studied mainly children (<18y of age) with spastic CP, if they had an intervention of SDR, if they had a detailed description of the selection criteria, and if they were in English. The levels of evidence, conduct of studies, and selection criteria for SDR were scored.

Results

Fifty‐two studies were included. Selection criteria were reported in 16 International Classification of Functioning, Disability and Health model domains including ‘body structure and function’ (details concerning spasticity [94%], other movement abnormalities [62%], and strength [54%]), ‘activity’ (gross motor function [27%]), and ‘personal and environmental factors’ (age [44%], diagnosis [50%], motivation [31%], previous surgery [21%], and follow‐up therapy [31%]). Most selection criteria were not based on standardized measurements.

Interpretation

Selection criteria for SDR vary considerably. Future studies should describe clearly the selection procedure. International meetings of experts should develop more uniform consensus guidelines, which could form the basis for selecting candidates for SDR.
Heart Failure Following Creation of an Arteriovenous Fistula for Hemodialysis
Authors: Fadel Bahaa M. , Alhashim Abdelmohsen , Al‐Admawi Mohamad , Bech‐Hanssen Odd , Di Salvo Giovanni
Published: October 2013

Careful analysis of the Doppler profile, performance of maneuvers during image acquisition, and comparison of data with prior studies are basic tools that allow us to provide useful clinical information and improved diagnostic accuracy. Here, we discuss a patient in whom a thorough evaluation of the Doppler pattern at rest and during maneuvers and the identification of temporal changes in cardiac hemodynamics helped establish a diagnosis.
Host selection, oviposition behaviour and leaf traits in a specialist willow sawfly on species of Salix (Salicaceae)
Authors: BRACCINI CELINA L. , VEGA ANDREA S. , CHLUDIL HUGO D. , LEICACH SILVIA R. , FERNANDEZ PATRICIA C.
Published: October 2013

Plant genotype influences plant–herbivore interactions by affecting insect attraction, acceptance and development. Here we linked oviposition behaviour of the specialist willow sawfly Nematus oligospilus Förster (Hymenoptera: Tenthredinidae) with leaf traits on different Salix L. (Salicaceae) genotypes. This was done as a first step to find oviposition cues that guide females to their host plants.

By means of choice and no‐choice bioassays we analysed host selection according to willow genotype and leaf surface. We also studied larval performance, adult fecundity and effect of experience on host selection. Nematus oligospilus prefers to oviposit on S. nigra. The least preferred genotype, S. viminalis, showed better larval performance and highest adult fecundity. Host preference was not modified by larval feeding experience.

By means of light and scanning electron microscopy we described ovipositor and leaf micromorphology. The egg is laid inside the epidermis or between the epidermis and adjacent chlorenchyma, showing a tight association with the leaf. Leaf toughness was lowest for S. nigra and higher for S. viminalis and S. babylonica. Total nitrogen and protein content were higher on S. viminalis and S. babylonica. Total phenolics and phenolic glycosides were the highest and more diverse on S. nigra. Salicin content levels correlate with oviposition preference, suggesting the role of salicylates as oviposition stimulants.

Results suggest that oviposition preference on S. nigra may be related to lower leaf toughness and ease of injection of female saw‐like ovipositor, and motivated by the presence of phenolic glycosides. Nitrogen levels may explain better larval performance and adult fecundity in S. viminalis. Thus, a balance among the different leaf traits determines the outcomes observed in this study.
Imaging the seizure during surgery with a hyperspectral camera
Authors: Noordmans Herke Jan , Ferrier Cyrille , de Roode Rowland , Leijten Frans , van Rijen Peter , Gosselaar Peter , Klaessens John , Verdaasdonk Ruud
Published: October 2013

An epilepsy patient with recurring sensorimotor seizures involving the left hand every 10 min, was imaged with a hyperspectral camera during surgery. By calculating the changes in oxygenated, deoxygenated blood, and total blood volume in the cortex, a focal increase in oxygenated and total blood volume could be observed in the sensory cortex, corresponding to the seizure‐onset zone defined by intracranial electroencephalography (EEG) findings. This probably reflects very local seizure activity. After multiple subpial transections in this motor area, clinical seizures abated.
Multiple congenital ocular anomalies and the silver dapple gene
Authors: Matthews A. G.
Published: October 2013

See also article by Premont et al.
Dimethylfumarate induces apoptosis in human mast cells
Authors: Förster Anja , Preussner Liane M. , Seeger Jens M. , Rabenhorst Anja , Kashkar Hamid , Mrowietz Ulrich , Hartmann Karin
Published: October 2013

Mast cells modulate autoimmune diseases such as psoriasis and multiple sclerosis. Fumaric acid esters (FAEs) are widely used for the treatment of psoriasis, and dimethylfumarate (DMF) has recently been approved for multiple sclerosis. In this study, we analysed the cytotoxic effect of FAEs on human mast cells. Specifically, cell death was analysed in the human mast cell line HMC‐1 and in primary cord blood‐derived mast cells (CBMCs) after incubation with fumaric acid (FA), monomethylfumarate (MMF), DMF and calcium bis(monomethylfumarate) (Ca‐MF). Our data show that only DMF potently induces apoptotic cell death in HMC‐1 cells and CBMCs. DMF‐mediated apoptosis was associated with increased expression of Bax and Bak and activation of caspase‐9 and caspase‐6. Interestingly, DMF also enhanced the sensitivity of CBMCs towards TRAIL‐ and dexamethasone‐induced apoptosis. These findings demonstrate for the first time that DMF induces apoptosis of human mast cells, primarily via the mitochondrial apoptotic pathway. Our study contributes to the understanding of the beneficial effects of FAEs in autoimmune diseases and provides a rationale for exploiting FAEs for other diseases associated with mast cells.
A novel adamantyl benzylbenzamide derivative, AP736, suppresses melanogenesis through the inhibition of cAMP‐PKA‐CREB‐activated microphthalmia‐associated transcription factor and tyrosinase expression
Authors: Lee Chang Seok , Jang Won‐Hee , Park Miyoung , Jung Kyoungmi , Baek Heung Soo , Joo Yung Hyup , Park Young‐Ho , Lim Kyung‐Min
Published: October 2013

Melanogenesis is essential for the protection of skin against UV, but excessive production of melanin causes unaesthetic hyperpigmentation. Much effort is being made to develop effective depigmenting agents. Here, we found that a tyrosinase inhibitor, AP736 (5‐adamantan‐1‐yl‐N‐(2,4‐dihydroxy‐benzyl)‐2,4‐dimethoxy‐benzamide) potently suppresses tyrosinase expression, and the mechanism underlying was elucidated. AP736 attenuated the melanin production induced by diverse melanogenic stimuli in murine and human melanocytes. It suppressed the expression of key melanogenic enzymes; tyrosinase, tyrosinase‐related protein‐1 and tyrosinase‐related protein‐2. The expression of microphthalmia‐associated transcription factor (MiTF), a major promoter of melanogenesis was also decreased. AP736 inhibited the activation of cAMP response element‐binding protein (CREB) and phosphokinase A (PKA), and cAMP elevation, reflecting that cAMP‐PKA‐CREB signalling axis was suppressed, resulting in the downregulation of MiTF and tyrosinase. Along with the previously reported tyrosinase inhibitory activity, the suppression of cAMP‐PKA‐CREB‐mediated MiTF and tyrosinase expression by AP736 may be efficient for the treatment for hyperpigmentation.
Is climate warming more consequential towards poles? The phenology of Lepidoptera in Finland
Authors: Valtonen Anu , Leinonen Reima , Pöyry Juha , Roininen Heikki , Tuomela Jukka , Ayres Matthew P.
Published: October 2013

The magnitude and direction of phenological shifts from climate warming could be predictably variable across the planet depending upon the nature of physiological controls on phenology, the thermal sensitivity of the developmental processes and global patterns in the climate warming. We tested this with respect to the flight phenology of adult nocturnal moths (3.33 million captures of 334 species) that were sampled at sites in southern and northern Finland during 1993–2012 (with years 2005–2012 treated as an independent model validation data set). We compared eight competing models of physiological controls on flight phenology to each species and found strong support for thermal controls of phenology in 66% of the species generations. Among species with strong thermal control of phenology in both the south and north, the average development rate was higher in northern vs. southern populations at 10 °C, but about the same at 15 and 20 °C. With a 3 °C increase in temperature (approximating A2 scenario of IPPC for 2090–2099 relative to 1980–1999) these species were predicted to advance their phenology on average by 17 (SE ± 0.3) days in the south vs. 13 (±0.4) days in the north. The higher development rates at low temperatures of poleward populations makes them less sensitive to climate warming, which opposes the tendency for stronger phenological advances in the north from greater increases in temperature.
Opting Out (Without Kids): Understanding Non‐Mothers' Workplace Exit in Popular Autobiographies
Authors: Wilhoit Elizabeth D.
Published: October 2013

Since the term appeared in 2003, popular media and academics have been interested in the phenomenon of ‘opting out’ — elite women choosing to leave their jobs to stay at home with their children. Although it is unclear whether the opt‐out revolution actually exists, this conversation has resulted in a wealth of scholarship on women leaving successful jobs to care for their children, particularly how maternity might be a graceful time to exit gendered organizations. However, there is not scholarship considering women without children who opt out of the dominant career model. In this study, I look at three popular autobiographies of women who left successful careers to pursue alternative work (farming, baking). I found that the women sought meaning in their work, control over their labour process, and a new definition of success. These narratives provide broader insight into the constraints of the dominant career model and gendered organizations as well as the particular difficulties for non‐mothers to opt out.
Comparison of ultrasound and magnetic resonance imaging for diagnosis and follow‐up of joint lesions in patients with haemophilia
Authors: Sierra Aisa C. , Lucía Cuesta J. F. , Rubio Martínez A. , Fernández Mosteirín N. , Iborra Muñoz A. , Abío Calvete M. , Guillén Gómez M. , Moretó Quintana A. , Rubio Félix D.
Published: October 2013

Haematomas and recurrent haemarthroses are a common problem in haemophilia patients from early age. Early diagnosis is critical in preventing haemophilic arthritis, and recent years have seen excellent advances in musculoskeletal ultrasound as a diagnostic tool in soft tissue lesions. In this study, we compared the results of ultrasound imaging for the diagnosis of musculoskeletal injuries in haemophilia patients with scores obtained using magnetic resonance (MRI) scans. A total of 61 haemophilia patients aged 4–82 years were included in this study. Both knees and ankles of each patient were assessed using the Gilbert (clinical assessment) and Pettersson scores (X‐ray assessment). Patients with severe haemophilia (n = 30) were examined using ultrasound and MRI (Denver scoring system). Results obtained with ultrasound and MRI in severe patients were correlated using the Pearson test. In patients with severe haemophilia, normal joints were similarly assessed with MRI and ultrasound (κ = 1.000). By component of joint assessment, haemarthrosis was similarly diagnosed with both techniques in all joints (κ = 1.000). A good positive correlation was found between these techniques in detecting and locating synovial hyperplasia (κ = 0.839–1.000, knees and ankles respectively), and erosion of margins (κ = 0.850–1.000). The presence of bone cysts or cartilage loss was better detected with MRI (κ = 0.643–0.552 for knees and ankles, and κ = 0.643–0.462 respectively). Ultrasound is useful in detecting joint bleeds, synovial hyperplasia and joint erosions, with results comparable to those of MRI. A quick and affordable technique, ultrasound imaging may be useful for monitoring joint bleeds and structure normalization and maintenance in routine practice.
Unanswered Questions in Headache: So What Is Photophobia, Anyway?
Authors: Ahn Andrew H. , Brennan K. C.
Published: October 2013

Photophobia refers to a sensory disturbance provoked by light. However, because it arises distinctly in a broad range of clinical conditions, its definition remains elusive. Many underscore the painful sensory aspects of photophobia, while others emphasize its unpleasant, affective qualities. To add further complexity, recent discoveries in photophobia research have raised disparate and potentially conflicting results. In this installment of an occasional series, we asked clinicians and scientists to give their interpretation of what these discoveries tell us about photophobia in the clinic, and vice versa.