bluuebunny/crossref_metadata_2025 huggingface dataset:
Autoregulation of Coronary Blood Flow in the Isolated Beating Pig Heart
Authors: Schampaert Stéphanie , van 't Veer Marcel , Rutten Marcel C.M. , van Tuijl Sjoerd , de Hart Jurgen , van de Vosse Frans N. , Pijls Nico H.J.
Published: March 2013

The isolated beating pig heart model is an accessible platform to investigate the coronary circulation in its truly morphological and physiological state, whereas its use is beneficial from a time, cost, and ethical perspective. However, whether the coronary autoregulation is still intact is not known. Here, we study the autoregulation of coronary blood flow in the working isolated pig heart in response to brief occlusions of the coronary artery, to step‐wise changes in left ventricular loading conditions and contractile states, and to pharmacologic vasodilating stimuli. Six slaughterhouse pig hearts (473 ± 40 g) were isolated, prepared, and connected to an external circulatory system. Through coronary reperfusion and controlled cardiac loading, physiological cardiac performance was achieved. After release of a coronary occlusion, coronary blood flow rose rapidly to an equal (maximum) level as the flow during control beats, independent of the duration of occlusion. Moreover, a linear relation was found between coronary blood flow and coronary driving pressure for a wide variation of preload, afterload, and contractility. In addition, intracoronary administration of papaverine did not yield a transient increase in blood flow indicating the presence of maximum coronary hyperemia. Together, this indicates that the coronary circulation in the isolated beating pig heart is in a permanent state of maximum hyperemia. This makes the model excellently suitable for testing and validating cardiovascular devices (i.e., heart valves, stent grafts, and ventricular assist devices) under well‐controlled circumstances, whereas it decreases the necessity of sacrificing large mammalians for performing classical animal experiments.
Arginase inhibition improves coronary microvascular function and reduces infarct size following ischaemia–reperfusion in a rat model
Authors: Grönros J. , Kiss A. , Palmér M. , Jung C. , Berkowitz D. , Pernow J.
Published: March 2013

Aim

Ischaemia–reperfusion injury is associated with reduced bioavailability of nitric oxide (NO) and microvascular dysfunction. One emerging mechanism behind reduced NO bioavailability is upregulation of arginase, which metabolizes the NO synthase substrate l‐arginine. This study investigated the effects of arginase inhibition on coronary flow velocity and infarct size during reperfusion.

Methods

Anaesthetized rats, subjected to 30‐min coronary artery ligation and reperfusion up to 8 days, were treated with vehicle or the arginase inhibitor Nω‐hydroxy‐nor‐l‐arginine (nor‐NOHA; 100 mg kg−1) intravenously 15 min before ischaemia. Coronary flow velocity was determined repeatedly during reperfusion.

Results

Arginase activity in the ischaemic‐reperfused myocardium was increased already at 20 min of reperfusion and maintained at 8 days. Infarct size was reduced by arginase inhibition at 2 h (39 ± 3% of the area at risk (AAR) vs. 51 ± 2% in the vehicle group, P < 0.01) and at 8 days of reperfusion (13 ± 2% of the left ventricle (LV) vs. 22 ± 2%, P < 0.05). Basal coronary flow velocity was higher during reperfusion in the group given nor‐NOHA, and it correlated inversely to infarct size (P < 0.01, r = −0.60). Hyperaemic coronary flow velocity was also increased in the nor‐NOHA‐treated group compared to vehicle at 24 h and at day 8 (P < 0.05).

Conclusion

It is concluded that arginase activity is increased already during early reperfusion. Arginase inhibition increases coronary flow velocity and reduces infarct size that is sustained 8 days after reperfusion. Inhibition of arginase may thus be a promising therapeutic target to prevent the development of microvascular dysfunction and myocardial injury following ischaemia–reperfusion.
Between a rock and a soft place: microtopography of the locomotor substrate and the morphology of the setal fields of Namibian day geckos (Gekkota: Gekkonidae: Rhoptropus)
Authors: Russell Anthony P. , Johnson Megan K.
Published: March 2013

Many species of gekkotans possess adhesive subdigital pads that allow them to adhere to, and move on, a wide variety of surfaces. The natural surfaces exploited by these lizards may be rough, undulant and unpredictable and therefore likely provide only limited, patchy areas for adhesive contact. Here, we examine the microtopography of rock surfaces used by seven species of Rhoptropus and compare this to several rough and smooth artificial surfaces employed in previous studies of gekkotan adhesion. These data are considered in relation to the form, configuration, compliance and functional morphology of the setal fields of these species. Our results demonstrate that natural rock surfaces are rough and unpredictable at the scale of the setal arrays, with equal amounts of variation existing within and between the various types of rock surfaces examined. Such surfaces differ from smooth and rough artificial surfaces in the proportion of surface area available for attachment and the relative predictability of surface undulance. Generally, setal field characteristics of individual species are not relatable to specific substrates, but instead are configured to allow for sufficient attachment to a wide variety of unpredictable surfaces. Our findings provide insight into the evolution and microanatomy of the adhesive system of gekkotan lizards and its adaptive relationship to topographically unpredictable surfaces.
Comparable Lumefantrine Oral Bioavailability when Co‐administered With Oil‐Fortified Maize Porridge or Milk in Healthy Volunteers
Authors: Mwebaza Norah , Jerling Markus , Gustafsson Lars L. , Obua Celestino , Waako Paul , Mahindi Margarita , Ntale Muhammad , Beck Olof , Hellgren Urban
Published: March 2013

Co‐administration of artemether–lumefantrine with milk is recommended to improve lumefantrine (L) absorption but milk may not be available in resource‐limited settings. This study explored the effects of cheap local food in Uganda on oral bioavailability of lumefantrine relative to milk. In an open‐label, four‐period crossover study, 13 healthy adult volunteers were randomized to receive a single oral dose of artemether–lumefantrine (80 mg artemether/480 mg lumefantrine) with water, milk, maize porridge or maize porridge with oil on separate occasions. Plasma lumefantrine was assayed using high‐performance liquid chromatography with ultraviolet detection. Pharmacokinetic exposure parameters were determined by non‐compartmental methods using WinNonlin. Peak concentrations (Cmax) and area under concentration–time curve restricted to 48 hr after single dosing (AUC(0–48)) were selected for relative bioavailability evaluations using confidence interval approach for average bioequivalence. Lumefantrine exposure was comparable in milk and maize porridge plus oil study groups. When artemether–lumefantrine was administered with maize porridge plus oil, average bioequivalence ranges (means ratios 90% CI, 0.84–1.88 and 0.85–1.69 for Cmax and AUC(0–48), respectively) were within and exceeded acceptance ranges relative to milk (90% CI, 0.80–1.25). Both fasted and maize porridge groups demonstrated similarly much lower ranges of lumefantrine exposures (bioinequivalence) relative to milk. If milk is not available, it is thus possible to recommend fortification of carbohydrate‐rich food with little fat (maize porridge plus vegetable oil) to achieve similarly optimal absorption of lumefantrine after artemether–lumefantrine administration.
Maternal “Junk Food” Diet During Pregnancy as a Predictor of High Birthweight: Findings from the Healthy Beginnings Trial
Authors: Wen Li Ming , Simpson Judy M. , Rissel Chris , Baur Louise A.
Published: March 2013

Background

A high infant birthweight is associated with future risk of a range of adverse health consequences. This study sought to determine whether maternal “junk food” diet (energy‐dense, nutrient‐poor) predicts high birthweight in first‐time mothers in southwest Sydney, Australia.

Methods

A community‐based longitudinal study was conducted with a total of 368 first‐time mothers and their newborns. Information about maternal “junk food” diet, including high consumption of soft drink, fast food, and/or processed meat and chips, and self‐reported prepregnant weight and height of first‐time mothers was collected by a face‐to‐face interview with mothers between 24 and 34 weeks of pregnancy. Birthweight was measured in hospital and reported by the mother, together with gestational age, when the baby was 6 months old. Logistic regression modeling was used to determine the factors predicting birthweight greater than 4.0 kg.

Results

Eleven percent of newborns weighed more than 4.0 kg (12% boys, 9% girls). Compared with mothers who had a “junk food” diet, mothers who had not consumed “junk food” during pregnancy were significantly less likely to have a newborn weighing more than 4.0 kg, with adjusted odds ratio (AOR) 0.36, 95 percent confidence interval (CI) 0.14–0.91, p = 0.03, after adjusting for maternal weight status and gestational age. Compared with healthy and underweight mothers, overweight or obese mothers were more likely to have a newborn weighing more than 4.0 kg (AOR overweight 3.03, 95% CI 1.35–6.80; obese 3.79, 95% CI 1.41–10.25) after allowing for “junk food” diet and gestational age.

Conclusions

Maternal “junk food” diet during pregnancy and prepregnant overweight and obesity were independent predictors of high infant birthweight. Early childhood obesity interventions should consider addressing these factors. (BIRTH 40:1 March 2013)
Zip‐related genital injury
Authors: Bagga Herman S. , Tasian Gregory E. , McGeady James , Blaschko Sarah D. , McCulloch Charles E. , McAninch Jack W. , Breyer Benjamin N.
Published: March 2013

Objective

To describe the epidemiology of genital injuries caused by trouser zips and to educate both consumers and the caregivers of patients who sustain such injuries.

Patients and Methods

The National Electronic Injury Surveillance System, a dataset validated to provide a probability sample of patients who present to emergency departments (EDs) in the USA with injuries, was analysed to characterize zip‐related genital injuries occurring between 2002 and 2010.

A total of 523 cases were analysed to obtain national estimates.

Results

Between 2002 and 2010, an estimated 17 616 patients presented to US EDs with trouser zip injuries to the genitals.

The penis was almost always the only genital organ involved.

Zip injuries represented nearly one‐fifth of all penile injuries.

Amongst adults, zips were the most frequent cause of penile injuries.

Annual zip‐related genital injury incidence remained stable over the study period.

Conclusions

Zip‐related genital injuries affect both paediatric and adult cohorts.

Practitioners should be familiar with various zip‐detachment strategies for these populations.
Seminal vesicle involvement at salvage radical prostatectomy
Authors: Meeks Joshua J. , Walker Marc , Bernstein Melanie , Eastham James A.
Published: March 2013

Objective

To describe the incidence and clinical outcomes of seminal vesicle invasion (SVI) at salvage radical prostatectomy (SRP) and to describe the accuracy of SV biopsy. As SRP is used after biochemical recurrence (BCR) of prostate cancer after radiotherapy (RT) to gain local oncological control. The SVs receive lower doses of radiation from external‐beam RT (EBRT) to avoid rectal exposure and are not targeted with brachytherapy (BT) with low‐risk prostate cancer.

Patients and Methods

SRP was performed on 206 men with BCR after RT at a tertiary care institution between 1998 and 2011. Post‐RT biopsy and SRP specimens were reviewed by a genitourinary pathologist.

Results

SVI was detected in 65 (32%) of 206 patients. No difference was found between EBRT alone (65% vs 63%) and BT (29% vs 31%) with or without EBRT in patients with SVI. Men with SVI had higher rates of cT3 disease (20% vs 8%) and Gleason score ≥ 8 at SRP (52% vs 21%).

BCR‐free survival at 5 years was 18% and 56% in patients with and without SVI (hazard ratio 2.85, 95% confidence interval 1.87–4.36, P < 0.001), yet the rate of local recurrence was low (11%).

Prostate cancer was identified in nine of 18 patients who underwent SV biopsy and was the only location of prostate cancer in two patients.

Conclusions

SVI is a prognostic indicator for BCR after SRP, but local recurrence in patients with SVI after SRP remains low.

We recommend SV biopsy to improve staging and cancer detection in men with BCR after radiotherapy.
Non‐invasive molecular imaging for preclinical cancer therapeutic development
Authors: O'Farrell AC , Shnyder SD , Marston G , Coletta PL , Gill JH
Published: March 2013

Molecular and non‐invasive imaging are rapidly emerging fields in preclinical cancer drug discovery. This is driven by the need to develop more efficacious and safer treatments, the advent of molecular‐targeted therapeutics, and the requirements to reduce and refine current preclinical in vivo models. Such bioimaging strategies include MRI, PET, single positron emission computed tomography, ultrasound, and optical approaches such as bioluminescence and fluorescence imaging. These molecular imaging modalities have several advantages over traditional screening methods, not least the ability to quantitatively monitor pharmacodynamic changes at the cellular and molecular level in living animals non‐invasively in real time. This review aims to provide an overview of non‐invasive molecular imaging techniques, highlighting the strengths, limitations and versatility of these approaches in preclinical cancer drug discovery and development.
Loss of constitutive activity is correlated with increased thermostability of the human adenosine A2A receptor
Authors: Bertheleme Nicolas , Singh Shweta , Dowell Simon J , Hubbard Julia , Byrne Bernadette
Published: March 2013

Background and Purpose

Thermostabilization by mutagenesis is one method which has facilitated the determination of high‐resolution structures of the adenosine A2A receptor (A2AR). Sets of mutations were identified, which both thermostabilized the receptor and resulted in preferential agonist (Rag23 mutant) or antagonist (Rant5 and Rant21) binding forms as assessed by radioligand binding analysis. While the ligand‐binding profiles of these mutants are known, the effects these mutations have on receptor activation and downstream signalling are less well characterized.

Experimental Approach

Here we have investigated the effects of the thermostabilizing mutations on receptor activation using a yeast cell growth assay. The assay employs an engineered Saccharomyces cerevisiae, MMY24, which couples receptor activation to cell growth.

Key Results

Analysis of the receptor activation profile revealed that the wild‐type (WT) A2AR had considerable constitutive activity. In contrast, the Rag23, Rant5 and Rant21 thermostabilized mutants all exhibited no constitutive activity. While the preferentially antagonist‐binding mutants Rant5 and Rant21 showed a complete lack of agonist‐induced activity, the Rag23 mutant showed high levels of agonist‐induced receptor activity. Further analysis using a mutant intermediate between Rag23 and WT indicated that the loss of constitutive activity observed in the agonist responsive mutants was not due to reduced G‐protein coupling.

Conclusions and Implications

The loss of constitutive activity may be an important feature of these thermostabilized GPCRs. In addition, the constitutively active and agonist‐induced active conformations of the A2AR are distinct.
Effects of vildagliptin versus sitagliptin, on cardiac function, heart rate variability and mitochondrial function in obese insulin‐resistant rats
Authors: Apaijai Nattayaporn , Pintana Hiranya , Chattipakorn Siriporn C , Chattipakorn Nipon
Published: March 2013

Background and Purpose

Long‐term high‐fat diet (HFD) consumption has been shown to cause insulin resistance, which is characterized by hyperinsulinaemia with metabolic inflexibility. Insulin resistance is associated with cardiac sympathovagal imbalance, cardiac dysfunction and cardiac mitochondrial dysfunction. Dipeptidyl peptidase‐4 (DPP‐4) inhibitors, vildagliptin and sitagliptin, are oral anti‐diabetic drugs often prescribed in patients with cardiovascular disease. Therefore, in this study, we sought to determine the effects of vildagliptin and sitagliptin in a murine model of insulin resistance.

Experimental Approach

Male Wistar rats weighing 180–200 g, were fed either a normal diet (20% energy from fat) or a HFD (59% energy from fat) for 12 weeks. These rats were then divided into three subgroups to receive vildagliptin (3 mg·kg−1·day−1), sitagliptin (30 mg·kg−1·day−1) or vehicle for another 21 days. Metabolic parameters, oxidative stress, heart rate variability (HRV), cardiac function and cardiac mitochondrial function were determined.

Key Results

Rats that received HFD developed insulin resistance characterized by increased body weight, plasma insulin, total cholesterol and oxidative stress levels along with a decreased high‐density lipoprotein (HDL) level. Moreover, cardiac dysfunction, depressed HRV, cardiac mitochondrial dysfunction and cardiac mitochondrial morphology changes were observed in HFD rats. Both vildagliptin and sitagliptin decreased plasma insulin, total cholesterol and oxidative stress as well as increased HDL level. Furthermore, vildagliptin and sitagliptin attenuated cardiac dysfunction, prevented cardiac mitochondrial dysfunction and completely restored HRV.

Conclusions and Implications

Both vildagliptin and sitagliptin share similar efficacy in cardioprotection in obese insulin‐resistant rats.
Being Mimicked Increases Prosocial Behavior in 18‐Month‐Old Infants
Authors: Carpenter Malinda , Uebel Johanna , Tomasello Michael
Published: March 2013

Most previous research on imitation in infancy has focused on infants' learning of instrumental actions on objects. This study focused instead on the more social side of imitation, testing whether being mimicked increases prosocial behavior in infants, as it does in adults (van Baaren, Holland, Kawakami, & van Knippenberg, 2004). Eighteen‐month‐old infants (N = 48) were either mimicked or not by an experimenter; then either that experimenter or a different adult needed help. Infants who had previously been mimicked were significantly more likely to help both adults than infants who had not been mimicked. Thus, even in infancy, mimicry has positive social consequences: It promotes a general prosocial orientation toward others.
Is the Secure Base Phenomenon Evident Here, There, and Anywhere? A Cross‐Cultural Study of Child Behavior and Experts’ Definitions
Authors: Posada German , Lu Ting , Trumbell Jill , Kaloustian Garene , Trudel Marcel , Plata Sandra J. , Peña Paola P. , Perez Jennifer , Tereno Susana , Dugravier Romain , Coppola Gabrielle , Constantini Alessandro , Cassibba Rosalinda , Kondo‐Ikemura Kiyomi , Nóblega Magaly , Haya Ines M. , Pedraglio Claudia , Verissimo Manuela , Santos Antonio J. , Monteiro Ligia , Lay Keng‐Ling
Published: March 2013

The evolutionary rationale offered by Bowlby implies that secure base relationships are common in child–caregiver dyads and thus, child secure behavior observable across diverse social contexts and cultures. This study offers a test of the universality hypothesis. Trained observers in nine countries used the Attachment Q‐set to describe the organization of children's behavior in naturalistic settings. Children (N = 547) were 10–72 months old. Child development experts (N = 81) from all countries provided definitions of optimal child secure base use. Findings indicate that children from all countries use their mother as a secure base. Children's organization of secure base behavior was modestly related to each other both within and across countries. Experts’ descriptions of the optimally attached child were highly similar across cultures.
The German national registry for primary immunodeficiencies (PID)
Authors: Gathmann B , Goldacker S , Klima M , Belohradsky B H , Notheis G , Ehl S , Ritterbusch H , Baumann U , Meyer-Bahlburg A , Witte T , Schmidt R , Borte M , Borte S , Linde R , Schubert R , Bienemann K , Laws H-J , Dueckers G , Roesler J , Rothoeft T , Krüger R , Scharbatke E C , Masjosthusmann K , Wasmuth J-C , Moser O , Kaiser P , Groß-Wieltsch U , Classen C F , Horneff G , Reiser V , Binder N , El-Helou S M , Klein C , Grimbacher B , Kindle G
Published: March 2013

In 2009, a federally funded clinical and research consortium (PID–NET, http://www.pid-net.org) established the first national registry for primary immunodeficiencies (PID) in Germany. The registry contains clinical and genetic information on PID patients and is set up within the framework of the existing European Database for Primary Immunodeficiencies, run by the European Society for Primary Immunodeficiencies. Following the example of other national registries, a central data entry clerk has been employed to support data entry at the participating centres. Regulations for ethics approvals have presented a major challenge for participation of individual centres and have led to a delay in data entry in some cases. Data on 630 patients, entered into the European registry between 2004 and 2009, were incorporated into the national registry. From April 2009 to March 2012, the number of contributing centres increased from seven to 21 and 738 additional patients were reported, leading to a total number of 1368 patients, of whom 1232 were alive. The age distribution of living patients differs significantly by gender, with twice as many males than females among children, but 15% more women than men in the age group 30 years and older. The diagnostic delay between onset of symptoms and diagnosis has decreased for some PID over the past 20 years, but remains particularly high at a median of 4 years in common variable immunodeficiency (CVID), the most prevalent PID.
A novel mutation in IGFALS, c.380T>C (p.L127P), associated with short stature, delayed puberty, osteopenia and hyperinsulinaemia in two siblings: insights into the roles of insulin growth factor‐1 (IGF1)
Authors: Hess Ora , Khayat Morad , Hwa Vivian , Heath Karen E. , Teitler Amnon , Hritan Yifat , Allon‐Shalev Stavit , Tenenbaum‐Rakover Yardena
Published: March 2013

Background

The acid‐labile subunit (ALS) protein is crucial for maintaining the circulating IGF/IGFBP system. Inactivating mutations of IGFALS result in IGF1 deficiency associated with growth retardation. Although the first IGFALS mutation in humans was described in 2004, only 16 mutations have been reported since. Moreover, the phenotype of affected patients as a consequence of ALS deficiency is still highly variable. We assessed whether children with idiopathic short stature (ISS) harbour mutations in IGFALS and characterized affected patients' phenotype.

Design

Sixty‐five children with ISS were enrolled in the study. Serum ALS levels were measured by ELISA, and IGFALS was sequenced.

Results

A novel homozygous mutation in IGFALS, c.380T>C (p.L127P), was identified in two siblings of a consanguineous family. The proband, a 17·75‐year‐old male, was −1·9 SDS in height and −4·5 SDS in weight. Exaggerated stimulated GH (38 ng/ml) and extremely low IGF1 and IGFBP3 (<25 and <500 ng/ml, respectively) indicated GH insensitivity. Both affected siblings had low or no ALS (43 and 0 mU/ml, respectively). They were also mildly small for gestational age, severely underweight and showed osteopenia, insulin insensitivity and delayed and slow puberty progression.

Conclusions

Acid‐labile subunit deficiency due to IGFALS mutations is a rare cause of growth retardation in children. The unique combination of features presented by the two affected siblings emphasizes the important role of IGF1 in bone formation, insulin regulation and the pubertal process, in addition to its crucial effect on growth. Long‐term follow‐up is indicated since the clinical outcome with respect to osteoporosis, diabetes mellitus and fertility has not been recognized.
Effects of a 3‐week dehydroepiandrosterone administration on sleep, sex steroids and multiple 24‐h hormonal profiles in postmenopausal women: a pilot study
Authors: Caufriez Anne , Leproult Rachel , L'Hermite‐Balériaux Mireille , Kerkhofs Myriam , Copinschi Georges
Published: March 2013

Objective

Dehydroepiandrosterone (DHEA) administration is widely evocated as a ‘fountain of youth’, but previous studies have provided inconsistent results. We aimed to investigate in healthy postmenopausal women the effects of a 3‐week oral DHEA administration on individual steroid levels, multiple 24‐h hormonal profiles and sleep architecture.

Design

Seven healthy nonobese postmenopausal women, off hormone replacement therapy for ≥2 months, were investigated in a randomized, crossover, double‐blind, placebo‐controlled study. For 3 weeks, subjects took daily at 2300 h a capsule of either 50 mg DHEA or placebo. Sleep was polygraphically recorded during the last two nights, and blood samples were drawn at 15‐min intervals during the last 24 h.

Results

Under DHEA, testosterone and estradiol levels were increased in all individuals. Individual increments were highly variable, not related to each other, and were not related to placebo values. However, the testosterone to estradiol ratio was markedly increased under DHEA. DHEA administration had little, if any, effect on thyroid function, GH secretion, prolactin, ACTH and cortisol profiles. DHEA effects on sleep appeared to be mediated by its conversion to androgens and oestrogens: sleep quality was enhanced by increments in testosterone and dampened by increments in estradiol levels.

Conclusion

As DHEA‐induced elevations in testosterone and estradiol levels varied widely between individuals and were largely unpredictable, DHEA administration might not be the most appropriate approach to compensate for the reduction observed in androgen and oestrogen production in postmenopausal women. DHEA supplementation may result either in sleep stimulation or in inhibition, depending on the ratio between DHEA‐induced increments in testosterone vs estradiol.
Polymicrogyria with dysmorphic basal ganglia? Think tubulin!
Authors: Amrom D. , Tanyalçin I. , Verhelst H. , Deconinck N. , Brouhard G.J. , Décarie J.‐C. , Vanderhasselt T. , Das S. , Hamdan F.F. , Lissens W. , Michaud J.L. , Jansen A.C.
Published: March 2013

Dominant mutations in TUBB2B have been reported in patients with polymicrogyria. We further explore the phenotype associated with mutations in TUBB2B. Twenty patients with polymicrogyria (five unilateral) were tested for mutations in TUBB2B by Sanger sequencing. We identified two novel de novo mutations, c.743C>T (p.Ala248Val) and c.1139G>T (p.Arg380Leu) in exon 4 of TUBB2B in three unrelated families. Brain magnetic resonance images showed polymicrogyria involving predominantly the perisylvian regions. In addition, there was a dysmorphic appearance of the basal ganglia, thin corpus callosum, enlargement of the ventricles, thinning of the white matter and hypoplasia of pons and cerebellar vermis. This combination of associated features was absent in all 17 patients with polymicrogyria in whom no mutation was identified. This report underlines that the association of polymicrogyria with thin or absent corpus callosum, dysmorphic basal ganglia, brainstem and vermis hypoplasia is highly likely to result from mutations in TUBB2B and provides further insight in how mutations in TUBB2B affect protein function.
Land Regularization in Brazil and the Global Land Grab
Authors: de L.T. Oliveira Gustavo
Published: March 2013

This article investigates the seemingly contradictory policies adopted by the Brazilian state to prevent land grabs in one region while encouraging agribusiness investments in another. The government recently initiated a programme intended to regularize titles of 300,000 homesteaders in unassigned public land in the Amazon region. This effort in state making over a largely illegible landscape is aimed at offsetting large‐scale illegal land grabs and ongoing (though significantly curtailed) deforestation. In contrast, legal large‐scale agribusiness investments are exacerbating deforestation and the concentration of land ownership in the Cerrado region through well‐established state mechanisms. While the imposition of legibility may regulate land concentration and degradation, legible landscapes also facilitate investments that drive both concentration and degradation. The author argues that the regularization programme undertaken in the Amazon structures land grabbing nationally — not because large amounts of public land are in fact being privatized through regularization, but because it actively undermines land redistribution programmes elsewhere in the country and consolidates transportation and production infrastructure in the Amazon–Cerrado transition zone. The state‐making framework developed here captures the heterogeneity of global land grab processes, indicating the ways in which these are obstructed but not discarded by different government agencies, stalled but not yet overturned by Brazilian civil society.
Identity, Territory and Land Conflict in Brazil
Authors: Sullivan LaShandra
Published: March 2013

In the last century, national and international movements in capital and ideas have contributed to the radical transformation of the Brazilian countryside. In Mato Grosso do Sul, Guarani have been displaced onto reservations (through often extra‐legal means) due to deforestation for cattle ranches and agricultural plantations. Guarani land activists link displacement to problems like starvation and high crime rates. Today, protest occupations of plantations result in sometimes violent counter‐mobilization by plantation owners. This article investigates the production of ethnic boundaries between self‐identified ‘Indians’ and ‘non‐Indians’, which become articulated as territorial. It interrogates how these boundaries are both produced by and contribute to the economic development policies driving the land grab in Brazil.
Governing Global Land Deals: The Role of the State in the Rush for Land
Authors: Wolford Wendy , Borras Saturnino M. , Hall Ruth , Scoones Ian , White Ben
Published: March 2013

Over the past decade, there has been a dramatic increase in large‐scale land deals, often from public lands to the hands of foreign or domestic investors. Popularly referred to as a ‘global land grab’, new land acquisitions are drawing upon, restructuring and challenging the nature of both governance and government. In the Introduction to this special issue, we argue for an analysis of land deals that draws upon the insights of political ecology, cultural politics and agrarian studies to illuminate the micro‐processes of transaction and expropriation as well as the broader structural forces at play. We argue that ‘the state’ is often invoked as a key player in land grabbing but states never operate with one voice; rather we need to unbundle the state, to see government and governance as processes, people and relationships. To develop this approach, we focus on territory, sovereignty, authority and subjects not as static objects but as relationships produced in and through place, property, power and production. Understanding the dynamic nature of these relationships is critical to understanding the highly variable form and content of large‐scale land deals in different settings around the world. The papers in this special issue help to develop this perspective and this Introduction highlights important areas of convergence among them.
The Political Construction of Wasteland: Governmentality, Land Acquisition and Social Inequality in South India
Authors: Baka Jennifer
Published: March 2013

Through a micro‐level study of a biofuel‐related land acquisition in rural Tamil Nadu, India, this article reveals how state–subject relations are shaping modern land deal politics. Through its political construction of the concept of ‘wasteland’ and its associated wasteland development programme, the Indian state has facilitated a series of questionable land acquisitions, reshaping agrarian livelihoods in the process. A class of land brokers has emerged to help carry out the state's project of converting ‘wastelands’ to more ‘productive’, state‐defined uses such as biofuel cultivation and industrial expansion. Those whose lands have been acquired as part of these programmes have undergone a transition to wage labour, increasing the prolitarianization of agrarian communities. By documenting the mechanics of this ‘wasteland governmentality’, this study contributes to a political sociology of the state by unpacking the linkages between the state and agrarian subjects in the context of the ‘global land grab’.
Second heart field and the development of the outflow tract in human embryonic heart
Authors: Yang Yan‐Ping , Li Hai‐Rong , Cao Xi‐Mei , Wang Qin‐Xue , Qiao Cong‐Jin , Ya Jing
Published: March 2013

The second heart field (SHF) is indicated to contribute to the embryonic heart development. However, less knowledge is available about SHF development of human embryo due to the difficulty of collecting embryos. In this study, serial sections of human embryos from Carnegie stage 10 (CS10) to CS16 were stained with antibodies against Islet‐1 (Isl‐1), Nkx2.5, GATA4, myosin heavy chain (MHC) and α‐smooth muscle actin (α‐SMA) to observe spatiotemporal distribution of SHF and its contribution to the development of the arterial pole of cardiac tube. Our findings suggest that during CS10 to CS12, SHF of the human embryo is composed of the bilateral pharyngeal mesenchyme, the central mesenchyme of the branchial arch and splanchnic mesoderm of the pericardial cavity dorsal wall. With development, SHF translocates and consists of ventral pharyngeal mesenchyme and dorsal wall of the pericardial cavity. Hence, the SHF of human embryo shows a dynamic spatiotemporal distribution pattern. The formation of the Isl‐1 positive condense cell prongs provides an explanation for the saddle structure formation at the distal pole of the outflow tract. In human embryo, the Isl‐1 positive cells of SHF may contribute to the formation of myocardial outflow tract (OFT) and the septum during different development stages.
Left Ventricular Stroke Volume Quantification by Contrast Echocardiography – Comparison of Linear and Flow‐Based Methods to Cardiac Magnetic Resonance
Authors: Dele‐Michael Abiola O. , Fujikura Kana , Devereux Richard B. , Islam Fahmida , Hriljac Ingrid , Wilson Sean R. , Lin Fay , Weinsaft Jonathan W.
Published: March 2013

Background

Echocardiography (echo)‐quantified LV stroke volume (SV) is widely used to assess systolic performance after acute myocardial infarction (AMI). This study compared 2 common echo approaches – predicated on flow (Doppler) and linear chamber dimensions (Teichholz) – to volumetric SV and global infarct parameters quantified by cardiac magnetic resonance (CMR).

Methods

Multimodality imaging was performed as part of a post‐AMI registry. For echo, SV was measured by Doppler and Teichholz methods. Cine‐CMR was used for volumetric SV and LVEF quantification, and delayed‐enhancement (DE) CMR for infarct size.

Results

Overall, 142 patients underwent same day echo and CMR. On echo, mean SV by Teichholz (78 ± 17 mL) was slightly higher than Doppler (75 ± 16 mL; Δ = 3 ± 13 mL; P = 0.02). Compared to SV on CMR (78 ± 18 mL), mean difference by Teichholz (Δ = −0.2 ± 14; P = 0.89) was slightly smaller than Doppler (Δ = −3 ± 14; P = 0.02), but limits of agreement were similar between CMR and echo methods (Teichholz: −28, 27 mL, Doppler: −31, 24 mL). For Teichholz, differences with CMR SV were greatest among patients with anteroseptal or lateral wall hypokinesis (P < 0.05). For Doppler, differences were associated with aortic valve abnormalities or root dilation (P = 0.01). SV by both echo methods decreased stepwise in relation to global LV injury as assessed by CMR‐quantified LVEF and infarct size (P < 0.01).

Conclusions

Teichholz and Doppler calculated SV yield similar magnitude of agreement with CMR. Teichholz differences with CMR increase with septal or lateral wall contractile dysfunction, whereas Doppler yields increased offsets in patients with aortic remodeling.
Acute Mitral Regurgitation during Transapical Aortic Valve Implantation: Usefulness of Intraprocedural Transesophageal Echocardiography
Authors: Huttin Olivier , Angioi Michael , Maureira Pablo , Selton‐Suty Christine
Published: March 2013

Mini‐Abstract

We report a case of acute mitral regurgitation due to a temporary distortion of the mitral valve apparatus during apical transcatheter aortic valve implantation (TAVI). A few minutes after penetrating the apex, the patient developed severe hypotension and cardiac arrest. A hemodynamic support with femoral–femoral extracorporeal circulation was immediately installed. Transesophageal echocardiography (TEE) revealed that the guidewire interfered with the subvalvular mitral apparatus generating severe acute mitral regurgitation. The patient's condition improved immediately after guidewire removal and there was no residual mitral regurgitation. This case clearly shows the importance and the usefulness of performing a thorough and complete TEE monitoring to prevent and identify complications.
Coincidence of Congenital Agenesis of Left Lung and Common Atrium: A Very Rare Case
Authors: Nabati Maryam , Bagheri Babak , Habibi Valiolla
Published: March 2013

Pulmonary agenesis is characterized by undeveloped pulmonary vessels, bronchi as well as lung parenchyma and is a rare congenital anomaly with unknown etiology. It is usually diagnosed during childhood. Nearly, one third of these patients have concomitant congenital heart diseases. While more than 50% of these patients die before the age of 5 years, some other patients may be asymptomatic throughout their life. On the other hand, common atrium, another rare congenital anomaly, is characterized by complete absence of the atrial septum and is usually accompanied by atrioventricular valve malformations. An 18‐year‐old male presented with concomitant pulmonary agenesis and common atrium and had not undergone surgery due to high risk for mortality.
Toxicity of baited spinosad formulations to Ceratitis capitata: from the laboratory to the application
Authors: Gazit Yoav , Gavriel Sagi , Akiva Ruti , Timar Doron
Published: March 2013

GF‐120, a fruit fly bait designed to attract and kill adult fruit flies, was tested in the laboratory and outdoors to determine effects of pre‐treatment diet and bait aging on mortality of Mediterranean fruit fly, Ceratitis capitata (Wiedemann) (Diptera: Tephritidae). Two spinosad‐based compounds, GF‐120 and Tracer® Ultra, had generated two distinctive dose–mortality responds, with LC80, LC90, and LC99 values of 2.4, 2.8, and 4.1 p.p.m., and 255, 479, and 1 143 p.p.m., respectively. The residues of GF‐120 drops, after feeding to the flies, generated 14.3% mortality. The droplet size of the baited spray plays an important role. The toxicity of large drops lasted more than that of small droplets. In the field, exposure to the sun further deteriorates the compound, which lost 50% of its toxicity within 6 days. Disappearance of the compound in the field, due to consumption by various insects, also played a role as 50% of the GF‐120 drops disappeared within 7 days. As mortality was directly related to the amount of insecticide eaten, the effect of GF‐120 depended on the feeding status of the flies: well‐fed flies were almost unaffected compared with starved ones.
Distress and negative experiences of the caregiving relationship in early psychosis: does social cognition play a role?
Authors: Tomlinson Eleanor , Onwumere Juliana , Kuipers Elizabeth
Published: March 2013

Aim

This study explored the relationship between individuals with early psychosis and first‐degree relatives who were carers, to see whether negative and distressing experiences of the patient–carer relationship were associated with social cognition difficulties in both groups.

Method

The study had a cross‐sectional correlational design. A total of 33 patients with early psychosis (within 3 years of first psychotic episode) and 24 first‐degree relative carers (all parents) completed measures of mood, expressed emotion and negative experiences of caregiving. Social cognition measures of theory of mind and emotion recognition were also collected.

Results

Patient perceptions of carer criticism were related to increased anxiety and depression. Carer negative experiences of caregiving were related to higher levels of expressed emotion, anxiety and depression. Both patients and carers showed impaired performance on social cognition tasks. However, patient social cognition was not related to perceptions of carer criticism or symptoms. Carer social cognition was not related to expressed emotion or carer burden.

Conclusion

Even in the early stages of psychosis, both patients and carers were reporting negative experiences of the caregiving relationship. These were related to higher levels of anxiety and depression. Social cognition difficulties were found in both early psychosis patients and first‐degree relatives, but did not relate to caregiving relationships. The findings underscore the importance of providing targeted family interventions to individuals with early psychosis and their carers that address appraisals of the relationship and low mood.
Natural history of hepatitis C in thalassemia major: a long‐term prospective study
Authors: Lai Maria E. , Origa Raffaella , Danjou Fabrice , Leoni Gian B. , Vacquer Stefania , Anni Franco , Corrias Claudia , Farci Patrizia , Congiu Giovanna , Galanello Renzo
Published: March 2013

Background

Transfusion‐acquired hepatitis C virus (HCV) remains an important problem among patients with thalassemia. In this study, we evaluated the natural history of post‐transfusional hepatitis C in thalassemia major, paying special attention to spontaneous viral clearance, to factors influencing the chronicity rate and fibrosis progression.

Design and Methods

A prospective study to evaluate the incidence and etiology of transfusion‐related hepatitis was started in 1980. In patients who developed hepatitis C, HCV RNA, ALT, and ferritin were measured over time. The correlation between interleukin‐28B gene polymorphisms and viral clearance was also analyzed.

Results

Seventy‐three of 135 patients (62.2%) acquired HCV. An extended follow‐up (22 to 30 yr) with HCV RNA assessment was available in 52 patients. Of them, 23 (44.2%) cleared the virus. The proportion of IL‐28B genotypes was different between the subjects who cleared the virus and the subjects who did not. Fibrosis progression was similar in HCV RNA–positive and HCV RNA–negative patients. Liver iron was the only factor associated with the fibrosis.

Conclusions

In thalassemia patients with HCV infection, liver iron does not play a major role in influencing the chronicity rate, whereas it is significantly associated with the fibrosis.
Frames of reference for eye–head gaze shifts evoked during frontal eye field stimulation
Authors: Monteon Jachin A. , Wang Hongying , Martinez‐Trujillo Julio , Crawford J. Douglas
Published: March 2013

The frontal eye field (FEF), in the prefrontal cortex, participates in the transformation of visual signals into saccade motor commands and in eye–head gaze control. The FEF is thought to show eye‐fixed visual codes in head‐restrained monkeys, but it is not known how it transforms these inputs into spatial codes for head‐unrestrained gaze commands. Here, we tested if the FEF influences desired gaze commands within a simple eye‐fixed frame, like the superior colliculus (SC), or in more complex egocentric frames like the supplementary eye fields (SEFs). We electrically stimulated 95 FEF sites in two head‐unrestrained monkeys to evoke 3D eye–head gaze shifts and then mathematically rotated these trajectories into various reference frames. In theory, each stimulation site should specify a specific spatial goal when the evoked gaze shifts are plotted in the appropriate frame. We found that these motor output frames varied site by site, mainly within the eye‐to‐head frame continuum. Thus, consistent with the intermediate placement of the FEF within the high‐level circuits for gaze control, its stimulation‐evoked output showed an intermediate trend between the multiple reference frame codes observed in SEF‐evoked gaze shifts and the simpler eye‐fixed reference frame observed in SC‐evoked movements. These results suggest that, although the SC, FEF and SEF carry eye‐fixed information at the level of their unit response fields, this information is transformed differently in their output projections to the eye and head controllers.
Prenatal ontogeny of the dopamine‐dependent neurobehavioral phenotype in Pitx3‐deficient mice
Authors: Kleven Gale A. , Joshi Priyanka , Voogd Marco , Ronca April E.
Published: March 2013

Mouse models with prenatal alterations in dopaminergic functioning can provide new opportunities to identify fetal behavioral abnormalities and the underlying neural substrates dependent on dopamine. In this study, we tested the hypothesis that prenatal loss of nigrostriatal function is associated with fetal akinesia, or difficulty initiating movement. Specific behaviors were analysed in fetal offspring derived from pregnant Pitx3ak/2J and C57BL/6J dams on the last 4 days before birth (E15‐18 of a 19‐day gestation). Using digital videography, we analysed: (i) behavioral state, by quantification of high‐ and low‐amplitude movements, (ii) interlimb movement synchrony, a measure of the temporal relationship between spontaneous movements of limb pairs, (iii) facial wiping, a characteristic response to perioral tactile stimulation similar to the defensive response in human infants, and (iv) oral grasp of a non‐nutritive nipple, a component of suckling in the human infant. Pitx3 mutants showed a selective decrease in interlimb movement synchrony rates at the shortest (0.1 s) temporal interval coupled with significantly increased latencies to exhibit facial wiping and oral grasp. Collectively, our findings provide evidence that the primary fetal neurobehavioral deficit of the Pitx3 mutation is akinesia related to nigrostriatal damage. Other findings of particular interest were the differences in neurobehavioral functioning between C57BL/6J and Pitx3 heterozygous subjects, suggesting the two groups are not equivalent controls. These results further suggest that fetal neurobehavioral assessments are sensitive indicators of emerging neural dysfunction, and may have utility for prenatal diagnosis.
Macroevolution of life‐history traits in passerine birds: adaptation and phylogenetic inertia
Authors: Pienaar Jason , Ilany Amiyaal , Geffen Eli , Yom‐Tov Yoram
Published: March 2013

We used a recent passerine phylogeny and comparative method to evaluate the macroevolution of body and egg mass, incubation and fledging periods, time to independence and time with parents of the main passerine lineages. We hypothesised that passerine reproductive traits are affected by adaptation to both past and present environmental factors and phenotypic attributes such as body mass. Our results suggest that the evolution of body and egg mass, time to independence, incubation and fledging times are affected by strong phylogenetic inertia and that these breeding traits are all affected by body mass. Time with parents, where major lineages exhibit their own fixed optima and body mass does not have an effect, and clutch size which is affected by body mass and additionally by climate regimes, do not exhibit any phylogenetic inertia.