bluuebunny/crossref_metadata_2025 huggingface dataset:
Reporting of minimum clinically important differences in surgical trials
Authors: Kashani Irwin , Hall Jane L. , Hall John C.
Published: April 2009

Background:  The minimum clinically important difference (MCID) is the smallest difference in outcome between the groups that would be of clinical interest. It influences the estimates that are made to determine the required sample side. The aim of this study was to explore the reporting of the MCID in surgical trials.

Method:  Surgical trials that were published between January 1981 and December 2006 in five prestigious surgical journals were evaluated. Selected for study were trials that studied two groups and reported the main outcome event as a proportion.

Results:  Only 21% (100/486) of the admissible surgical trials mentioned a value for the MCID when estimating the sample size. There was a trend, however, for compliance with these factors to increase during the study period. The present post‐hoc calculations of the required sample size, which were based on the observed differences between the groups at the end of the study, suggested that one‐third of the trials should have accrued at least fivefold the number of patients. Although reporting an estimate of the sample size was associated with the study of more patients (median sample size 145 vs 100), it was not associated with the reporting of more positive results, that is, 61% (95/155) versus 65% (214/331).

Conclusion:  There has been an improvement in the proportion of surgical trials reporting formal estimates of sample size during the last three decades. But the construct of these estimates is often suspect because of a failure to provide realistic values for the MCID.
Novel approach to laparoscopic resection of tumours of the distal pancreas
Authors: Das De Soumen , Wei Cheah Kow Alfred , Hin Liau Kui , Hee Lim Khong , Kiat Ho Choon
Published: April 2009

Background:  Laparoscopic resection for small lesions of the pancreas has recently gained popularity. We report our initial experience with a new approach to laparoscopic spleen‐preserving distal pancreatectomy so that the maximum amount of normal pancreas can be preserved while ensuring adequate resection margins and preservation of the spleen and splenic vessels.

Methods:  Three patients underwent laparoscopic distal pancreatectomy with spleen and splenic vessel preservation over a 2‐month period. Surgical techniques and patient outcomes were examined.

Results:  All three patients were females, with ages ranging from 31 to 47 years. Two patients underwent resection using the conventional medial‐to‐lateral dissection as the lesion was close to the body or proximal tail of the pancreas. The third patient had a lesion in the distal tail of the pancreas and surgery was carried out in a lateral‐to‐medial manner. This new approach minimized excessive sacrifice of normal pancreatic tissue for such distally located lesions. The splenic artery and vein were preserved in all cases and there was no significant difference in clinical outcome, operative time or intraoperative blood loss.

Conclusion:  Laparoscopic distal pancreatectomy with preservation of the spleen and splenic vessels is a feasible surgical technique with acceptable outcome. We have shown that a tailored approach to dissection and pancreatic transection based on the location of the lesion allows the maximum amount of normal pancreatic tissue to be preserved without additional morbidity. Although the conventional ‘medial‐to‐lateral’ approach is recommended for more proximal tumours of the pancreas, distal lesions can be safely addressed using the ‘lateral‐to‐medial’ approach.
Alternating vigilance states: new insights regarding neuronal networks and mechanisms
Authors: Fort P. , Bassetti C. L. , Luppi P‐H.
Published: April 2009

Since the discovery of rapid eye movement (REM) sleep (also known as paradoxical sleep; PS), it is accepted that sleep is an active process. PS is characterized by EEG rhythmic activity resembling that of waking with a disappearance of muscle tone and the occurrence of REMs, in contrast to slow‐wave sleep (SWS, also known as non‐REM sleep) identified by the presence of delta waves. Here, we review the most recent data on the mechanisms responsible for the genesis of SWS and PS. Based on these data, we propose an updated integrated model of the mechanisms responsible for the sleep–wake cycle. This model introduces for the first time the notion that the entrance and exit of PS are induced by different mechanisms. We hypothesize that the entrance from SWS to PS is due to the intrinsic activation of PS‐active GABAergic neurons localized in the posterior hypothalamus (co‐containing melanin‐concentrating hormone), ventrolateral periaqueductal gray and the dorsal paragigantocellular reticular nucleus. In contrast, the exit from PS is induced by the inhibition of these neurons by a PS‐gating system composed of GABAergic neurons localized in the ventrolateral periaqueductal gray and just ventral to it, and waking systems such as the pontine and medullary noradrenergic neurons and the hypothalamic hypocretin neurons. Finally, we review human neurological disorders of the network responsible for sleep and propose hypotheses on the mechanisms responsible for REM behavior disorder and narcolepsy.
Identifying the lethal fish egg parasite Ichthyodinium chabelardi as a member of Marine Alveolate Group I
Authors: Skovgaard Alf , Meneses Isabel , Angélico Maria Manuel
Published: April 2009

Cells of the parasitic, unicellular eukaryote Ichthyodinium chabelardi were isolated from eggs of sardine (Sardina pilchardus) and from a previously unrecognized host, bogue (Boops boops), off the Atlantic coast of Portugal. Immediately after release from the infected fish egg or newly hatched larva, I. chabelardi cells were spherical and non‐motile. After few minutes, spherical cells became flagellated and motile. Following 2–3 days of incubation and several divisions, spherical flagellated cells developed a twisted elongate shape and moved vigorously. Sequences of the small‐subunit ribosomal RNA gene (SSU rDNA) were identical for I. chabelardi of both hosts and so were sequences of ITS1, ITS2 and the 5.8S rRNA gene. This genetic similarity suggests that eggs of sardine and bogue were infected by one single population of I. chabelardi. The SSU rRNA gene sequence of I. chabelardi was, in turn, 97% similar to those of two identical Asian isolates of Ichthyodinium sp. Phylogenetic analyses showed high support for the inclusion of Ichthyodinium in the so‐called Marine Alveolate Group I (MAGI). Two morphologically well‐described genera, namely Ichthyodinium and Dubosquella, have now been shown to belong to this group of seemingly exclusively parasitic alveolates.
Viability and potential for immigration of airborne bacteria from Africa that reach high mountain lakes in Europe
Authors: Hervàs Anna , Camarero Lluís , Reche Isabel , Casamayor Emilio O.
Published: April 2009

We have analysed the diversity of the bacteria, which grow after addition of concentrated airborne particles and desert dust in different microcosms combinations with water samples from oligotrophic alpine lakes. We used, on the one hand, airborne bacteria transported by an African dust plume and collected in a high mountain area in the central Pyrenees (Spain). On the other hand, we collected desert dust in Mauritania (c. 3000 km distance, and a few days estimated airborne journey), a known source region for dust storms in West Africa, which originates many of the dust plumes landing on Europe. In all the dust‐amended treatments we consistently observed bacterial growth of common phyla usually found in freshwater ecosystems, i.e. Alpha‐, Beta‐ and Gammaproteobacteria, Actinobacteria, and a few Bacteroidetes, but with different composition based on lake water pretreatment and dust type. Overall, we tentatively split the bacterial community in (i) typical freshwater non‐airborne bacteria, (ii) cosmopolitan long‐distance airborne bacteria, (iii) non‐freshwater low‐distance airborne bacteria, (iv) non‐freshwater long‐distance airborne soil bacteria and (v) freshwater non‐soil airborne bacteria. We identified viable long‐distance airborne bacteria as immigrants in alpine lakes (e.g. Sphingomonas‐like) but also viable putative airborne pathogens with the potential to grow in remote alpine areas (Acinetobacter‐like and Arthrobacter‐like). Generation of atmospheric aerosols and remote dust deposition is a global process, largely enhanced by perturbations linked to the global change, and high mountain lakes are very convenient worldwide model systems for monitoring global‐scale bacterial dispersion and pathogens entries in remote pristine environments.
Hereditary mixed polyposis syndrome due to a BMPR1A mutation
Authors: O’Riordan J. M. , O’Donoghue D. , Green A. , Keegan D. , Hawkes L. A. , Payne S. J. , Sheahan K. , Winter D. C.
Published: April 2009

The conditions Juvenile Polyposis Syndrome (JPS) and Hereditary Mixed Polyposis Syndrome (HMPS) are associated with an increased risk of colorectal carcinoma. The genetic mechanisms which explain these conditions have until recently been poorly understood. Recent interest has focused on the transforming growth factor (TGF)‐β signalling pathway and, in particular, on mutations in the SMAD4 gene. However, not all cases of JPS and HMPS have mutations in SMAD4 and focus has now shifted to other components of the TGF‐β pathway to clarify the genetic mechanisms involved in these conditions. In this report, we describe the significance of a bone morphogenetic protein receptor type 1A gene mutation in an Irish family.
Comparative study of contour transtar and STARR procedure for the treatment of obstructed defecation syndrome (ODS) – feasibility, morbidity and early functional results
Authors: Isbert C. , Reibetanz J. , Jayne D. G. , Kim M. , Germer C.‐T. , Boenicke L.
Published: April 2009

Aim  Stapled transanal rectal resection (STARR) is a promising new treatment for obstructed defecation syndrome (ODS). It may be performed using either a double‐stapling technique (PPH‐STARR) or with the new Contour Transtar (CT) device. The aim of this study was to evaluate the two techniques with respect to morbidity and functional outcomes.

Method  Patients presenting with ODS were evaluated using standardized clinical and radiological investigations and prospectively entered into a database. A total of 150 Patients were treated with either PPH‐STARR (n = 68) or CT (n = 82) and further evaluated at 12 month postoperatively.

Results  The mean size of the resected specimen was 27 cm2 (SD ±4.86 cm2) in the PPH‐STARR group and 46 cm2 (SD ±10.6 cm2) in the CT group [P < 0.001]. Morbidity was 7.3% (n = 5) in the PPH‐STARR group and 7.5% (n = 6) in the CT group. The most common complication was minor postoperative bleeding in both groups (PPH‐STARR: n = 2, 2.9%; CT: n = 2, 2.4%) Overall there were no septic complications and no surgical re‐interventions. There was a tendency for more postoperative pain following CT (n = 3, 3.6%) as compared with PPH‐STARR (n = 1, 1.4%). Constipation Scores (CCS) were 15.50 ± 5.71 in the PPH‐STARR group and 15.70 ± 5.84 in the CT group preoperatively and decreased significantly to 8.25 (SD ±1.45) and 8.01 (SD ±2.31) 12‐months after surgery. Values did not differ significantly between the two groups.

Conclusions  Contour Transtar is as safe and effective as PPH‐STARR and provides a true circumferential resection of rectal intussusception. This may benefit selected patients and result in improved long‐term durability of the technique.
Systematic review on ventral rectopexy for rectal prolapse and intussusception
Authors: Samaranayake C. B. , Luo C. , Plank A. W. , Merrie A. E. H. , Plank L. D. , Bissett I. P.
Published: April 2009

Objective  This systematic review assesses the effectiveness of ventral rectopexy (VR) surgery for treatment of rectal prolapse (RP) and rectal intussusception (RI) in adults.

Method  MEDLINE, EMBASE, Scopus and other relevant databases were searched to identify studies. Randomized controlled trials or nonrandomized studies with more than 10 patients receiving ventral mesh rectopexy surgery were considered for the review.

Results  Twelve nonrandomized case series studies with 728 patients in total are included in the review. Seven studies used the Orr‐Loygue procedure (VR with posterior rectal mobilization to the pelvic floor) and five studies used VR without posterior rectal mobilization. Overall weighted mean percentage decrease in faecal incontinence (FI) rate was 45%. The weighted mean percentage decrease in constipation rate was 24%. Weighted mean recurrence rate was 3.4%.

Conclusions  There are limitations in published literature on VR. The available data indicate that VR has low recurrence and improves FI in patients suffering from these conditions. There is a greater reduction in postoperative constipation if VR is used without posterior rectal mobilization.
Anastomotic leakage after curative anterior resection for rectal cancer: short and long‐term outcome
Authors: Bertelsen C. A. , Andreasen A. H. , Jørgensen T. , Harling H. ,   on behalf of the Danish Colorectal Cancer Group
Published: April 2009

Objective  The influence of symptomatic anastomotic leakage (AL) after anterior resection (AR) for rectal cancer on short and long‐term mortality and local and distant recurrence was analysed.

Method  All patients with a first diagnosis of rectal carcinoma were prospectively registered in a national database. This comprised 1494 Danish citizens who had had a curative AR between May 2001 and December 2004. Data on survival and recurrence were obtained from the National Patient Register. Multivariate analyses were performed.

Results  Anastomotic leakage increased the 30‐day mortality [odds ratio (OR) 4.01 (95% CI 2.24–7.17)]. Of other possible risk factors, only age had a significant interaction with leakage, as the risk of death within 30 days of AR decreased with increasing age. Long‐term survival decreased significantly after AL [hazard ratio (HR) of 1.63, CI 1.21–2.19]. A total of 97 (6.7%) and 258 (18.0%) patients had local and distant recurrence respectively in the follow‐up period. The risk of local and distant recurrence after AL was not different with HR of 1.50 (CI 0.84–2.69) and 1.13 (CI 0.76–1.69) respectively. No other factors influenced the risk of recurrence due to AL.

Conclusion  Anastomotic leakage after AR for rectal cancer increases the 30‐day and long‐term mortality, but AL did not increase the risk of local and distant recurrence.
The Role of Education in Economic Growth in East Asia: a survey
Authors: Permani Risti
Published: April 2009

This paper surveys the literature on the links between education and economic growth in East Asia. It finds that education is important for economic growth but it is not a sufficient condition. The complementarity between education and other factors in enhancing productivity and efficiency is commonly seen as the driving force of economic growth. However, the empirical evidence is ambiguous due to econometric problems. Statistical analysis suggests that education and economic growth in East Asia have two‐way causality. Nevertheless, valuing education has been a widely‐accepted part of Asian values. As a result, education consistently presents as a significant income determinant and consequentially a growth factor, regardless of whether education can increase productivity. East Asian education systems are also formed and extended in close relation to the stages of their economic development: the higher the level of economic development, the greater the demand for better and higher education systems.
Responding to High Commodity Prices
Authors: Sugden Craig
Published: April 2009

The recent commodity price boom resulted from rising demand in the face of a long period of low supply growth and market distortions. Structural factors are expected to return international commodity prices to relatively high levels as the global economy recovers. The Asian and Pacific economies and the region's poor will be among the most exposed to a rebound in prices. The recent response to high commodity prices can be improved upon. At the global level, the priority for Asian and Pacific governments is to seek a commitment to lessening distortions favouring bio‐fuels. At the regional level, there is a need to address the use of trade restrictions on food commodities in Asia, notably rice. At a national level, the long‐term neglect of the rural economy warrants correction; and efforts to expand and make social safety nets more ‘market friendly’ are called for.
Direct Risk Aversion
Authors: Simonsohn Uri
Published: April 2009

Why would people pay more for a $50 gift certificate than for the opportunity to receive a gift certificate worth either $50 or $100, with equal probability? This article examines three possible mechanisms for this recently documented uncertainty effect (UE): First, awareness of the better outcome may devalue the worse one. Second, the UE may have arisen in the original demonstration of this effect because participants misunderstood the instructions. Third, the UE may be due to direct risk aversion, that is, actual distaste for uncertainty. In Experiment 1 , the UE was observed even though participants in the certainty condition were also aware of the better outcome; this result eliminates the first explanation. Experiment 2 shows that most participants understand the instructions used in the original study and that the UE is not caused by the few who do not. Overall, the experiments demonstrate that the UE is robust, large (prospects are valued at 65% of the value of the worse outcome), and widespread (at least 62% of participants exhibit it).
Rent‐sharing and Collective Bargaining Coverage: Evidence from Linked Employer–Employee Data
Authors: Guertzgen Nicole
Published: April 2009

Using a linked employer–employee dataset, this paper analyses the relationship between firm profitability and wages. Particular emphasis is given to the question of whether the sensitivity of wages to firm‐specific rents varies with collective bargaining coverage. To address this issue, we distinguish sector‐ and firm‐specific wage agreements and wage determination without any bargaining coverage. Our findings indicate that individual wages are positively related to firm‐specific quasi‐rents in the non‐union sector and under firm‐specific contracts. Industry‐wide wage contracts, however, are associated with a significantly lower responsiveness of wages to firm‐level profitability.
The Sensorium at Work: The Sensory Phenomenology of the Working Body
Authors: Hockey John , Allen-Collinson Jacquelyn
Published: April 2009

The sociology of the body and the sociology of work and occupations have both neglected to some extent the study of the ‘working body’ in paid employment, particularly with regard to empirical research into the sensory aspects of working practices. This gap is perhaps surprising given how strongly the sensory dimension features in much of working life. This article is very much a first step in calling for a more phenomenological, embodied and ‘fleshy’ perspective on the body in employment, and examines some of the theoretical and conceptual resources available to researchers wishing to focus on the lived working-body experiences of the sensorium. We also consider some possible representational forms for a more evocative, phenomenologically-inspired portrayal of sensory, lived-working-body experiences, and offer suggestions for future avenues of research.
Feeling and Finding on the Register of Suggestion: Reflections on the ‘Event’ of Researching Community Mental Health Care
Authors: Stronge Paul
Published: April 2009

The paper posits an intervention in current debates around ‘method making’ in the social sciences, drawing on the experience of undertaking an ethnographic study of a community mental health team in East London. Theoretical recourse is made to the process philosophy of A.N. Whitehead and to the enduring provenance of the problem of ‘suggestion’ in the history of medicine and psychology. These offer rich and provocative theoretical resources with which to rethink the interpenetration of subject and object and ‘feeling’ and ‘finding’. Whitehead's work provides a general philosophical framework whereby the ongoing subjective experience of the researcher can no longer be sharply demarcated from the ‘data’ encountered. Meanwhile the adoption of a ‘register of suggestion’ opens up insights into the inevitably selective and singular character of any given methodological procedure. It maintains the importance of affective factors at the forefront of analysis, and brings into focus the parts played by indeterminacy and risk in the research event.
Temporary Migration and Bilateral Trade Flows
Authors: Jansen Marion , Piermartini Roberta
Published: April 2009

Empirical evidence on migration and trade has established that permanent migration promotes trade. This finding has been interpreted as proof for the role of migrants in reducing trade‐related transaction costs such as contract enforcement costs or information costs. This paper contributes to improving our understanding of trade‐related transaction costs by analysing empirically whether temporary migrants, like permanent migrants, have an impact on bilateral trade flows. Temporary migrants can be expected to be less integrated in the host country than permanent migrants. At the same time, their knowledge of the home country can, on average, be expected to be more up‐to‐date. Our findings therefore give insights as to the relative importance of knowledge on the host and the home country for trade‐related transaction costs. Using a gravity approach in our empirical analysis, we find that temporary migration has a positive and significant effect on trade and that temporary migration tends to have a stronger and more significant effect on both imports and exports than permanent migration. Interestingly, the role of temporary migrants in reducing trade costs does not appear to be associated with their skills.
Imports and Exports at the Level of the Firm: Evidence from Belgium
Authors: Muûls Mirabelle , Pisu Mauro
Published: April 2009

This paper explores a newly available panel dataset merging balance sheet and international trade transaction data for Belgium. Both imports and exports appear to be highly concentrated among few firms and seem to have become more so over time. Focusing on manufacturing, we find that facts previously reported in the literature as applying only to exports actually apply to imports too. We note that the number of trading firms diminishes as the number of export destinations or import origins increases. The same is true if we consider the number of products traded. Our results generally point to a process of self‐selection in both export and import markets. Also, the productivity advantage of exporters reported in the literature may be overstated because imports were not considered. We find that firms that both import and export are the most productive, followed, in descending order, by importers only, exporters only and non‐traders. Our results also show the existence of fixed costs of imports, which appear to be of similar magnitude as those of exports.
Industry Concentration and Welfare: On the Use of Stock Market Evidence from Horizontal Mergers
Authors: FRIDOLFSSON SVEN‐OLOF , STENNEK JOHAN
Published: April 2009

There is diverging empirical evidence on the competitive effects of horizontal mergers: consumer prices (and thus presumably competitors' profits) often rise while competitors' share prices fall. Our model of endogenous mergers provides a possible reconciliation. It is demonstrated that anti‐competitive mergers may reduce competitors' share prices, if the merger announcement informs the market that the competitors lost a race to buy the target. Also the use of ‘first rumour’ as an event may create similar problems of interpretation. We also indicate how the event‐study methodology may be adapted to identify competitive effects and thus the welfare consequences for consumers.
Effect of climate therapy at Gran Canaria on vitamin D production, blood glucose and lipids in patients with psoriasis
Authors: Osmancevic A , Nilsen LT , Landin‐Wilhelmsen K , Søyland E , Abusdal Torjesen P , Hagve TA , Nenseter MS , Krogstad AL
Published: April 2009

Background  Climate therapy (heliotherapy) of psoriasis is an effective and natural treatment. Ultraviolet radiation (UVB) from the sun improves psoriasis and induces vitamin D3 synthesis.

Objective  The aim of the study was to investigate the effect of climate therapy on vitamin D3 synthesis, blood glucose, lipids and vitamin B12 in psoriasis patients.

Methods  Twenty Caucasian patients (6 women and 14 men; mean age, 47.2 years; range, 24–65) with moderate to severe psoriasis [mean Psoriasis Area and Severity Index (PASI) score 9.8; range, 3.8–18.8] received climate therapy at the Gran Canarias for 3 weeks. Blood samples were drawn before and after 15 days of sun exposure. In addition, the patients’ individual skin UV doses based on UV measurements were estimated.

Results  Sun exposure for 15 days lead to a 72.8% (± 18.0 SD) reduction in the PASI score in psoriasis patients. Although no direct correlation was observed between PASI score improvement and UVB dose, the sun exposure improved the vitamin D, lipid and carbohydrate status of the patients. The serum concentrations of 25‐hydroxyvitamin D [25(OH)D] increased from 57.2 ± 14.9 nmol/L before therapy to 104.5 ± 15.8 nmol/L (P < 0.0001) after 15 days of sun exposure; the serum levels of 1,25‐dihydroxyvitamin D [1,25(OH)2D] increased from 146.5 ± 42.0 to 182.7 ± 59.1 pmol/L (P = 0.01); the ratio of low‐density lipoprotein cholesterol and high‐density lipoprotein cholesterol decreased from 2.4 to 1.9 (P < 0.001); and the haemoglobin A1c (HbA1c) levels decreased from 5.6 ± 1.7% to 5.1 ± 0.3% (P < 0.0001).

Conclusion  Climate therapy with sun exposure had a positive effect on psoriasis, vitamin D production, lipid and carbohydrate status.
First evaluation of polymerase chain reaction assays used for diagnosis of Mycoplasma genitalium in Russia
Authors: Shipitsyna E , Zolotoverkhaya E , Dohn B , Benkovich A , Savicheva A , Sokolovsky E , Jensen JS , Domeika M , Unemo M
Published: April 2009

Background  Diagnosis of Mycoplasma genitalium is entirely based on nucleic acid amplification tests (NAATs). In Russia, several M. genitalium polymerase chain reaction (PCR) assays have been developed; however, any evaluation of their performance has never been performed.

Objective  To assess the performance of five PCRs developed and currently used in Russia for diagnosis of M. genitalium.

Materials and methods  Vaginal swabs and first voided urine samples (FVUs) from 281 females and urethral swabs and FVUs from 125 males were analysed using three conventional PCRs and two real‐time PCRs developed by three Russian companies. As reference tests, a real‐time PCR targeting the MgPa adhesin gene was used; positive results were confirmed by two conventional PCRs targeting the 16S rRNA gene and MgPa gene, respectively. For evaluation of detection limits and analytical specificities, a blinded control panel consisting of dilutions of six strains of M. genitalium and 14 other Mycoplasma species was tested.

Results  The prevalence of M. genitalium was 2.5% among females and 9.6% among males. The highest sensitivity (71.4–100% in different specimens) was exhibited by one real‐time PCRs. Conventional PCRs from two manufacturers failed to detect M. genitalium in any of the seven positive female FVUs. All tests had a 100% clinical specificity; however, one cross‐reacted with Mycoplasma pneumoniae.

Conclusions  Only one of the five Russian PCRs displayed reasonable sensitivity for all specimen types, but the specificities of all assays were high. Accordingly, improvements regarding sensitivity of all the tests are needed. However, larger studies, including other populations, evaluating these assays are crucial.
Revisiting MSUD in Portuguese Gypsies: Evidence for a Founder Mutation and for a Mutational Hotspot within the BCKDHA Gene
Authors: Quental Sofia , Gusmão Alfredo , Rodríguez‐Pombo Pilar , Ugarte Magdalena , Vilarinho Laura , Amorim António , Prata Maria J.
Published: April 2009

Maple syrup urine disease (MSUD) is a rare autosomal recessive disorder of branched‐chain amino acid metabolism. In the context of the wide mutational spectrum known for this disease, a few common mutations have been described in populations where founder effects played a major role in modeling diversities. In Portugal, for instance, a high proportion of patients are of Gypsy origin and all share the same mutation (c.117delC‐α; p.R40GfsX23), causing the neonatal severe form of MSUD. In this study, we used four microsatellite markers closely flanking the BCKDHA gene (E1α protein) to demonstrate that c.117delC‐α is a founder mutation responsible for the high incidence of the disorder among Portuguese Gypsies. These results are of medical relevance since carrier tests and prenatal diagnosis can be offered to families at risk, particularly because the carrier frequency of c.117delC‐α was estimated at 1.4% among the healthy Portuguese Gypsies from the South of the country. Finally we present evidence that the genomic region of the BCKDHA gene where c.117delC‐α is located is likely a mutational hotspot, since recurrence of c.117delC‐α was observed in two distinct population groups.
Feeding the vertebrate retina from the Cambrian to the Tertiary
Authors: Yu C. Q. , Schwab I. R. , Dubielzig R. R.
Published: April 2009

The retina of the vertebrate eye is metabolically active and requires nutritive support. During the last 540 million years it has evolved into forms as complicated and nutritionally demanding as those found in avian or primate eyes. Diffusion from the choroid is generally able to supply the metabolic needs of thin retinae. However, when the thickness exceeds the limits of diffusion, structures are needed to supplement the vascular supply from the choroid. These supplemental nutritive devices include the choroidal gland, the falciform process and preretinal vascular plexus of fish, the conus papillaris of lizards, the pecten oculi of birds, the intraretinal vessels of mammals and a few novel systems that remain difficult to classify. These vascular systems are among the most variable features of the vertebrate eye. Here, we review classical and recent findings regarding such retinal nutrition systems, propose a three category classification for them based on histologic origins and speculate on the evolutionary forces which drove their development.
Leaves in the lowest and highest winds: temperature, force and shape
Authors: Vogel Steven
Published: April 2009

Climatic extremes can be as significant as averages in setting the conditions for successful organismal function and in determining the distribution of different forms. For lightweight, flexible structures such as leaves, even extremes lasting a few seconds can matter. The present review considers two extreme situations that may pose existential risks. Broad leaves heat rapidly when ambient air flows drop below c. 0.5 m s−1. Devices implicated in minimizing heating include: reduction in size, lobing, and adjustments of orientation to improve convective cooling; low near‐infrared absorptivity; and thickening for short‐term heat storage. Different features become relevant when storm gusts threaten to tear leaves and uproot trees with leaf‐level winds of 20 m s−1 or more. Both individual leaves and clusters may curl into low‐drag, stable cones and cylinders, facilitated by particular blade shapes, petioles that twist readily, and sufficient low‐speed instability to initiate reconfiguration. While such factors may have implications in many areas, remarkably little relevant experimental work has addressed them.

Contents

Summary
13

I.
Introduction
13

II.
Very low but steady wind
14

III.
Very low and fluctuating wind
17

IV.
Very high winds
20

V.
Leaf form as adaptation
23

Acknowledgements
24

References
24
Increases in cytoplasmic dopamine compromise the normal resistance of the nucleus accumbens to methamphetamine neurotoxicity
Authors: Thomas David M. , Francescutti‐Verbeem Dina M. , Kuhn Donald M.
Published: April 2009

Methamphetamine (METH) is a neurotoxic drug of abuse that damages the dopamine (DA) neuronal system in a highly delimited manner. The brain structure most affected by METH is the caudate–putamen (CPu) where long‐term DA depletion and microglial activation are most evident. Even damage within the CPu is remarkably heterogenous with lateral and ventral aspects showing the greatest deficits. The nucleus accumbens (NAc) is largely spared of the damage that accompanies binge METH intoxication. Increases in cytoplasmic DA produced by reserpine,l‐DOPA or clorgyline prior to METH uncover damage in the NAc as evidenced by microglial activation and depletion of DA, tyrosine hydroxylase (TH), and the DA transporter. These effects do not occur in the NAc after treatment with METH alone. In contrast to the CPu where DA, TH, and DA transporter levels remain depleted chronically, DA nerve ending alterations in the NAc show a partial recovery over time. None of the treatments that enhance METH toxicity in the NAc and CPu lead to losses of TH protein or DA cell bodies in the substantia nigra or the ventral tegmentum. These data show that increases in cytoplasmic DA dramatically broaden the neurotoxic profile of METH to include brain structures not normally targeted for damage by METH alone. The resistance of the NAc to METH‐induced neurotoxicity and its ability to recover reveal a fundamentally different neuroplasticity by comparison to the CPu. Recruitment of the NAc as a target of METH neurotoxicity by alterations in DA homeostasis is significant in light of the important roles played by this brain structure.
Sulfasalazine inhibits the growth of primary brain tumors independent of nuclear factor‐κB
Authors: Chung W. Joon , Sontheimer Harald
Published: April 2009

Nuclear factor‐κB (NF‐κB) is a pleiotropic transcription factor that generally enhances cellular resistance to apoptotic cell death. It has been shown to be constitutively active in some cancers and is being pursued as potential anticancer target. Sulfasalazine which is used clinically to treat Crohn’s disease has emerged as a potential inhibitor of NF‐κB and has shown promising results in two pre‐clinical studies to target primary brain tumors, gliomas. Once digested, sulfasalazine is cleaved into sulfapyridine and 5‐aminosalicylic acid (5‐ASA; mesalamine) by colonic bacteria, and the latter, too, is reported to suppress NF‐κB activity. We now show that glioma cells obtained from patient biopsies or glioma cell lines do not show significant constitutive NF‐κB activation, unless exposed to inflammatory cytokines. This does not change when gliomas are implanted into the cerebrum of severe combined immundeficient mice. Nevertheless, sulfasalazine but not its cleaved form 5‐ASA caused a dose‐dependent inhibition of glioma growth. This effect was entirely attributable to the inhibition of cystine uptake via the system xc− cystine–glutamate transporter. It could be mimicked by S‐4‐carboxy‐phenylglycine (S‐4‐CPG) a more specific system xc− inhibitor, and lentiviral expression of a constitutively active form of IκB kinase b was unable to overcome the growth retarding effects of sulfasalazine or S‐4‐CPG. Both drugs inhibited cystine uptake causing a chronic depletion of intracellular GSH and consequently compromised cellular redox defense which stymied tumor growth. This data suggests that system xc− is a promising therapeutic target in gliomas and possibly other cancers and that it can be pharmacologically inhibited by Sulfasalazine, an FDA‐approved drug.
Involvement of P2Y receptors in pyridoxal‐5′‐phosphate‐induced cardiac preconditioning
Authors: Millart Hervé , Alouane Loubna , Oszust Floriane , Chevallier Stephane , Robinet Arnaud
Published: April 2009

Using an isolated non‐working rat heart model, this study investigated the mechanisms of pharmacological pre‐conditioning (PC) induced by P2Y receptor stimulation with pyridoxal‐5′‐phosphate (PLP). After 6‐hydroxydopamine pretreatment and a 15‐min stabilization period, isolated rat hearts were perfused for 25 min then subjected to 40 min of global ischemia and 30 min of reperfusion (I/R); exposed for 15 min to 0.05 μm PLP bracketed for 25 min with broad‐spectrum P2 antagonists (suramin or PPADS) or with more specific P2Y antagonists (AMPαS or MRS2578), 1 μm each, followed by a 5‐min PLP‐free perfusion before I/R; treated during 25 min with either glybenclamide (GLY, 1 μm), 5‐hydroxydecanoic acid (5‐HD, 100 μm), U73122 (0.5 μm), H89 (1 μm), or KN93 (1 μm), with an infusion starting 5 min before PLP. The main endpoints were the rate–pressure product (RPP), creatine kinase (CK) release and area necrosis. Recovery of RPP, measured 5 min after reperfusion, was rapidly improved by PLP, blocked by the P2 antagonists, and decreased with the different inhibitors. Fifteen minutes after the end of ischemia, CK release reached maximal values in all groups. PLP provided significant protection, whereas the P2 antagonists, 5‐HD, a mitochondrial selective KATP antagonist and GLY a non‐selective KATP channel blocker, suppressed the protective effect on myocardial injury. The suppression of the cardioprotective effects of PLP by AMPαS, the PKA inhibitor (H89), and phospholipase C blocker (U73122) is in agreement with the P2Y11 receptor as a receptor for PLP‐induced PC. The suppression of the cardioprotective effects of PLP by MRS2578 and U73122 is in agreement with the P2Y6 receptor as a receptor for PLP‐induced PC. Pre‐ischemic exposure to nanomolar concentrations of PLP is protective against I/R. P2Y11 and P2Y6 represents the most likely candidate receptors for PLP‐induced cardiac PC.
Heart rate variability during sleep and sleep apnoea in a population based study of 387 women
Authors: Kesek Milos , Franklin Karl A. , Sahlin Carin , Lindberg Eva
Published: April 2009

Increased sympathetic activity during sleep has been suggested as a link between obstructive sleep apnoea syndrome and cardiovascular disease. Heart rate variability (HRV) is a measure of autonomic effect on the heart. Different parameters have been associated with sympathetic and parasympathetic activity. We have studied HRV in different sleep stages and related the HRV‐pattern to sleep apnoea in a population‐based sample of 387 women. We investigated the HRV‐parameters standard deviation of all R‐R intervals (SDNN), root of the averaged square of successive differences (RMSSD), low frequency component (LF), high frequency component (HF), ratio of low frequency component to high frequency component LF/HF and VSAI [variation in sympathetic activity between rapid eye movement (REM) and slow wave sleep, defined as LFREM−LFSWS]. The HRV‐parameters were compared with the results of a full‐night polysomnography. Hourly incidence of obstructive episodes was used for classifying the subjects into four apnoea‐hypopnoea index (AHI)‐groups (<5, ≥5 and <15, 15–30 and >30 events). Individual sleep stages were analysed by pooling all recordings. Women with high AHI had higher heart rate and LF/HF ratio. In subjects with AHI >30, LF/HF ratio however dropped to same level as with AHI <5. Subjects with high AHI had low VSAI. Levels of SDNN, LF and LF/HF ratio during REM and light sleep were similar to wakefulness. In slow wave sleep the parameters decreased. In conclusion, moderately increased prevalence of obstructive apnoeas was associated with signs of higher sympathetic activity. High AHI was however associated with a HRV‐pattern suggestive of depressed sympathetic drive and lowered ability to increase it during REM.
The residual humanism of hybridity: retaining a sense of the earth
Authors: Lulka David
Published: April 2009

The concept of hybridity has become an influential theoretical tool for examining and reconsidering relations between society and nature. Although benefits have accrued from this school of thought, this paper contends the deployment of hybridity within the geographic discipline falls short of its reconstitutional claims. These shortcomings are a consequence of the original sources used to develop the language and logic of hybridity. Although the concept of hybridity has a long history in the biological sciences, the utilisation of hybridity in the geographic discipline has predominantly relied upon evolving theories developed in science and technology studies. This paper indicates how Haraway’s cyborg and Latour’s Middle Kingdom limit the scope of hybridity by portraying humanity as central to hybridity. The pervasive centrality of humans within the literature on hybridity (1) limits the ability of geographers to embrace poststructuralism in its entirety and (2) diminishes the discipline’s claim to credibly represent the (natural) landscape. This paper argues for a thicker hybridity by borrowing from emergent theories in the biological sciences, wherein hybridity is conceived as a common occurrence that frequently takes place outside the direct purview of society. Rather than reifying nature, thick hybridity forces society to embrace environmental uncertainty more than it has heretofore.
Targeted disruption of Smad3 confers resistance to the development of dimethylnitrosamine‐induced hepatic fibrosis in mice
Authors: Latella Giovanni , Vetuschi Antonella , Sferra Roberta , Catitti Valentina , D'Angelo Angela , Zanninelli Giuliana , Flanders Kathleen C. , Gaudio Eugenio
Published: April 2009

Background: Hepatic fibrosis is characterized by a progressive accumulation of fibrillar extracellular matrix (ECM) proteins including collagen, which occurs in most types of chronic liver diseases. Transforming growth factor‐β (TGF‐β)/Smad3 signalling plays a central role in tissue fibrogenesis, acting as a potent stimulus of ECM accumulation.

Aim: To evaluate the potential protective role of Smad3 deficiency in the pathogenesis of liver fibrosis induced by dimethylnitrosamine (DMN) in Smad3 null mice.

Methods: Chronic hepatitis‐associated fibrosis was induced in 13 Smad3 null and 13 wild‐type (WT) mice by intraperitoneal DMN administration (10 μg/g body weight/day) for three consecutive days per week for 6 weeks. The liver was excised for macroscopic examination and histological, morphometric and immunohistochemical (IHC) analyses. For IHC, α‐smooth muscle actin (α‐SMA), collagen types I–III, TGF‐β1, connective tissue growth factor (CTGF), Smad3, Smad7 and CD3 antibodies were used.

Results: At macroscopic examination, the liver of DMN‐treated Smad3 WT appeared harder with a dark brown colouring and necrotic areas compared with that from null mice. Histological and morphometric evaluation revealed a significantly higher degree of hepatic fibrosis and accumulation of connective tissue in the Smad3 WT compared with null mice. IHC evaluation showed a marked increase in α‐SMA, CTGF, collagen I‐III, TGF‐β and Smad3 staining in the liver of Smad3 WT compared with that in null mice, whereas Smad7 was increased only in null mice.

Conclusions: The results indicate that Smad3 loss confers resistance to the development of DMN‐induced hepatic fibrosis. The reduced fibrotic response appears to be due to a reduction of fibrogenic myofibroblast activation and ECM production and accumulation. Smad3 could be a novel target for potential treatment of fibrosis complicating chronic hepatitis.
Diabetes pattern on the 75 g oral glucose tolerance test is a risk factor for hepatocellular carcinoma in patients with hepatitis C virus
Authors: Konishi Ichiro , Hiasa Yoichi , Shigematsu Syuichiro , Hirooka Masashi , Furukawa Shinya , Abe Masanori , Matsuura Bunzo , Michitaka Kojiro , Horiike Norio , Onji Morikazu
Published: April 2009

Background: Patients with hepatitis C virus (HCV) frequently show glucose intolerance. Diabetes mellitus (DM) has been proposed to be a risk factor for hepatocellular carcinoma (HCC).

Aims: The aim of this study is to clarify the influence of glucose intolerance as evaluated by the 75 g oral glucose tolerance test (OGTT) on hepatocarcinogenesis in patients with HCV.

Methods: This study was carried out in a cohort of 197 patients with HCV who had not been previously diagnosed as having DM. All patients underwent the 75 g OGTT at entry. They were also screened for HCC and, thereafter, the rate of hepatocarcinogenesis was compared between the patients with and without glucose intolerance.

Results: Based on the results of the 75 g OGTT, 125 (63%) had normal glucose tolerance (NGT), 49 (25%) had impaired glucose tolerance (IGT) and 23 (12%) had the DM pattern. HCC occurred more frequently in patients with the DM pattern than in patients with either NGT or IGT. Even in patients without advanced liver fibrosis, HCC was more frequently observed in patients with DM than in patients with NGT. A multiple logistic regression analysis showed advanced liver fibrosis, the DM pattern on the 75 g OGTT, an older age and γ‐glutamyltransferase to all be independent risk factors related to hepatocarcinogenesis.

Conclusions: A DM pattern on the 75 g OGTT was thus found to be associated with hepatocarcinogenesis and the 75 g OGTT is considered to be useful for identifying this risk factor for HCC in patients with HCV.
Return of Fire to a Free‐Flowing Desert River: Effects on Vegetation
Authors: Stromberg Juliet C. , Rychener Tyler J. , Dixon Mark D.
Published: April 2009

After a long period in which fuel loads were sparse, fire recently has occurred with high frequency in the ungrazed riparian zone of the Upper San Pedro River in southern Arizona’s Chihuahuan Desert. We studied four accidental fires that occurred during 1994–2003 (two in different years at the same site). Woody vegetation was contrasted between three burned sites and matched spatial controls, and before and after the most recent fire. Herbaceous vegetation was sampled in multiple years producing a chronosequence of time since fire (from 4 months to 8 years). Riparian fire was associated with reductions in woody plant species diversity and canopy cover. In contrast, fire caused a short‐term (2 year) pulse of herbaceous plant diversity, driven by annual species, and persistent increase in herbaceous cover. Path analysis indicated that the increase in herbaceous cover was mediated in part by the reduction in tree canopy cover. Ordination (nonmetric multidimensional scaling) and regression analysis also indicated that canopy cover and/or fire played a role in structuring the herbaceous community, although its effects were secondary to that of hydrologic factors (stream flow rate, seasonal flood size). By converting riparian forests to grasslands and savannahs, fire may be shifting structure of the Upper San Pedro floodplain vegetation closer toward conditions present during past centuries when fire was frequent in the upland desert grasslands and embedded riparian corridor.
Pain Remapping in Migraine: A Novel Characteristic Following Trigeminal Nerve Injury
Authors: Hussain Aamir , Stiles Marlind A. , Oshinsky Michael L.
Published: April 2009

(Headache 2010;50:669‐674)

The location of pain during the headache phase of migraine varies between individuals as well as between attacks in some individuals. We have observed a “remapping” or a change in the location of migraine pain following injury to the trigeminal system that is a novel characteristic to migraine and has not been described in other trigeminal pain syndromes of the head, neck, and face. Recognition of this clinical feature implies that the pathophysiology of migraine is impressionable and may be why diagnosis and treatment are often delayed.