bluuebunny/crossref_metadata_2025 huggingface dataset:
The anaphase-promoting complex/cyclosome (APC/C) is required for rereplication control in endoreplication cycles
Authors: Zielke Norman , Querings Silvia , Rottig Carmen , Lehner Christian , Sprenger Frank
Published: June 2008

Endoreplicating cells undergo multiple rounds of DNA replication leading to polyploidy or polyteny. Oscillation of Cyclin E (CycE)-dependent kinase activity is the main driving force in Drosophila endocycles. High levels of CycE–Cdk2 activity trigger S phase, while down-regulation of CycE-Cdk2 activity is crucial to allow licensing of replication origins. In mitotic cells relicensing in S phase is prevented by Geminin. Here we show that Geminin protein oscillates in endoreplicating salivary glands of Drosophila. Geminin levels are high in S phase, but drop once DNA replication has been completed. DNA licensing is coupled to mitosis through the action of the anaphase-promoting complex/cyclosome (APC/C). We demonstrate that, even though endoreplicating cells never enter mitosis, APC/C activity is required in endoreplicating cells to mediate Geminin oscillation. Down-regulation of APC/C activity results in stabilization of Geminin protein and blocks endocycle progression. Geminin is only abundant in cells with high CycE–Cdk2 activity, suggesting that APC/C–Fzr activity is periodically inhibited by CycE–Cdk2, to prevent relicensing in S-phase cells.
Sustaining implicit contracts when agents have career concerns: the role of information disclosure
Authors: Mukherjee Arijit
Published: June 2008

Firms often augment career concerns incentives with implicit incentive contracts. I formalize the interaction between these two incentives, and highlight its implications on a firm's decision to disclose its workers' productivity information. Disclosure enhances career concerns but inhibits implicit contracts. I show two main results. First, implicit contracts weaken (i.e., substitute) career concerns if the prior belief about the worker's ability is low, and vice versa. Second, when these incentives are substitutes, the optimal disclosure policy follows a cutoff rule: patient firms are opaque, and transparent firms never offer implicit contracts. These results need not hold if the incentives are complements.
Learning by bidding
Authors: Hossain Tanjim
Published: June 2008

We analyze a dynamic second‐price auction with an informed bidder and an uninformed bidder who, upon seeing a posted price, learns whether his valuation is above that price. In the essentially unique equilibrium, an informed bidder bids in the first period if her valuation is below some cutoff and bids only in the last period otherwise. An uninformed bidder bids in every period to optimally change the price unless the price is above his valuation or he is the high bidder. This model also provides a rationale behind the use of a secret reserve price in private‐value settings.
Durable goods and residential demand for energy and water: evidence from a field trial
Authors: Davis Lucas W.
Published: June 2008

This article describes a household production model in which energy‐efficient durable goods cost less to operate so households may use them more. The model is estimated using household‐level data from a field trial in which participants received high‐efficiency clothes washers free of charge. The estimation strategy exploits this quasi‐random replacement of washers to derive precise estimates of the household production technology and a demand function for clothes washing. During the field trial, households increased clothes washing on average by 5.6% after receiving a high‐efficiency washer, implying a price elasticity of −.06. The complete model is used to evaluate the cost‐effectiveness of recent changes in minimum efficiency standards for clothes washers.
Search with learning: understanding asymmetric price adjustments
Authors: Yang Huanxing , Ye Lixin
Published: June 2008

In many retail markets, prices rise faster than they fall. We develop a model of search with learning to explain this phenomenon of asymmetric price adjustments. By extending our static game analysis to the dynamic setting, we demonstrate that asymmetric price adjustments arise naturally. When a positive cost shock occurs, all the searchers immediately learn the true state; the search intensity, and hence the prices, fully adjust in the next period. When a negative cost shock occurs, it takes longer for nonsearchers to learn the true state, and the search intensity increases gradually, leading to slow falling of prices.
Laboratory evidence on the effectiveness of corporate leniency programs
Authors: Hinloopen Jeroen , Soetevent Adriaan R.
Published: June 2008

The number of cartels detected in the United States and in Europe has increased considerably since the introduction of corporate leniency programs in antitrust legislation. It cannot, however, be ruled out that this apparent success results in part from increased cartel activity. We explore the effects of corporate leniency programs on pricing and cartel activity by use of an experiment. We find that in the lab (i) fewer cartels are established when a leniency program is in place, and (ii) cartels that do exist are less successful in charging prices above the static Nash equilibrium price and have lower survival rates.
Primary hyperparathyroidism and the skeleton
Authors: Mosekilde Leif
Published: June 2008

Today, primary hyperparathyroidism (PHPT) in the developed countries is typically a disease with few or no obvious clinical symptoms. However, even in the asymptomatic cases the endogenous excess of PTH increases bone turnover leading to an insidious reversible loss of cortical and trabecular bone because of an expansion of the remodelling space and an irreversible loss of cortical bone due to increased endocortical resorption. In contrast trabecular bone structure and integrity to a large extent is maintained and there may be a slight periosteal expansion. Most studies have reported decreased bone mineral density (BMD) in PHPT mainly located at cortical sites, whereas sites rich in trabecular bone only show a modest reduction or even a slight increase in BMD. The frequent occurrence of vitamin D insufficiency and deficiency in PHPT and increased plasma FGF23 levels may also contribute to the decrease in BMD. The effect of smoking is unsolved. Epidemiological studies have shown that the relative risk of spine and nonspine fractures is increased in untreated PHPT starting up to 10 years before the diagnosis is made. Successful surgery for PHPT normalizes bone turnover, increases BMD and decreases fracture risk based on larger epidemiological studies. However, 10 years after surgery fracture risk appears to increase again due to an increase in forearm fractures.

There are no randomized controlled studies (RCTs) demonstrating a protective effect of medical treatment on fracture risk in PHPT. Less conclusive studies suggest that vitamin D supplementation may have a beneficial effect on plasma PTH and BMD in vitamin D deficient PHPT patients. Hormone replacement therapy (HRT) and maybe SERM appear to reduce bone turnover and increase BMD. However, their nonskeletal side‐effects preclude their use for this purpose. Bisphosphonates reduce bone turnover and increase BMD in PHPT as in osteoporosis and may be a therapeutical option in selected patients with low BMD. Obviously, there is a need for larger RCTs with fractures as end‐points that appraise this possibility. Calcimimetics reduce plasma calcium and PTH in PHPT but has no beneficial effect on bone turnover or BMD. In symptomatic hypercalcaemic PHPT with low BMD where curative surgery is impossible or contraindicated a combination of a calcimimetic and a bisphosphonate may be an undocumented therapeutical option that needs further evaluation.
Facial and pituitary morphology are related in Dutch patients with GH deficiency
Authors: De Graaff L. C. G. , Baan J. , Govaerts L. C. P. , Hokken‐Koelega A. C. S.
Published: June 2008

Objective  Classical GH deficiency (GHD) is associated with typical phenotypic features. We have analysed standardized photographs of 137 Caucasian patients with GHD, in order to examine the relations between auxological, biochemical, pituitary and facial morphometric features.

Patients and measurements  We analysed pictures of 137 patients: 73 (55 Males/18 Females) with Isolated GHD and 64 (48 M/16 F) with multiple pituitary hormone deficiency (MPHD). Of each patient, standardized frontal and lateral digital pictures were taken and analysed using Adobe Photoshop 5·0.

Results  Canthal index (CI), the relative distance between the eyes, was related to pituitary morphology. Patients with an ectopic posterior pituitary (EPP) had significantly higher CI values than patients without EPP. We found CI > 39 to be a good cut‐off value to select children with highest probability of having EPP. The combination of CI > 39 with the presence of hormonal deficiencies additional to GHD strongly predicted EPP: 93% of the patients with a CI > 39 and additional hormonal deficiencies had EPP, in contrast to 77% of the patients with additional hormonal deficiencies but a CI < 39, and 29% of the patients with none of these criteria (P = 0·0001).

Conclusion  CI, measured on digital pictures, is associated with ectopia of the posterior pituitary and this might be caused by an altered midline development, affecting both the pituitary and the facial structures of GHD patients.
Role for postoperative cortisol response to desmopressin in predicting the risk for recurrent Cushing's disease
Authors: Romanholi Daniella Jesus Patrick Carminatti , Machado Marcio Carlos , Pereira Camila Canteiro , Danilovic Debora Seguro , Pereira Maria Adelaide Albergaria , Cescato Valter Angelo S. , Neto Malebranche Berardo C. Cunha , Musolino Nina Rosa Castro , De Mendonça Berenice Bilharinho , Salgado Luiz Roberto
Published: June 2008

In the early postoperative period of Cushing's disease patients, desmopressin may stimulate ACTH secretion in the remnant corticotrophic tumour, but not in nontumour suppressed cells.

Objective  The aim of this study is to evaluate the serum cortisol responses to desmopressin after pituitary surgery, establishing an optimal cut‐off for absolute increment (Δ) of serum cortisol (F) suitable to predict recurrence risk.

Design  Retrospective case record study.

Patients  Fifty‐seven Cushing's disease patients submitted to pituitary surgery and desmopressin stimulation in the early postoperative with a long‐term follow‐up (20–161 months) were studied.

Methods and measurements  Serum cortisol levels after desmopressin test (10 µg IV) 15–30 days after adenomectomy were used to determine ΔF (absolute increment of F: F peak − F baseline). Sensitivity and specificity of ΔF were calculated and a ROC curve was performed to establish an optimal cut‐off for ΔF to predict recurrence risk.

Results  Fifteen patients had immediate postoperative failure (basal F > 165 nmol/l; 6 µg/dl) and one patient was lost during the follow‐up. Forty‐one patients achieved initial remission and were followed‐up. Five of 11 patients who recurred had ΔF > 193 nmol/l (7 µg/dl), but none of 30 patients who remained in prolonged remission showed ΔF > 193 nmol/l after postoperative desmopressin stimulation.

Conclusions  Persistence of cortisol response (ΔF > 193 nmol/l) to desmopressin in the early postoperative period can help to identify Cushing's disease patients with initial remission who present risk for later recurrence.
Transforming clinical practice amongst community nurses: mentoring for COPD patient self‐management
Authors: Robinson Andrew , Courtney‐Pratt Helen , Lea Emma , Cameron‐Tucker Helen , Turner Paul , Cummings Elizabeth , Wood‐Baker Richard , Walters Eugene Haydn
Published: June 2008

Aims and objectives.  To report on the process of transforming clinical practice amongst community nurses through a mentoring programme implemented to support self‐management amongst community‐based sufferers of chronic obstructive pulmonary disease.

Background.  The increasing incidence of and health burden from, chronic diseases has led to the emergence of more proactive, integrated chronic disease management approaches across the acute and primary care sectors. An important part of these approaches is the direct involvement of patients in their own care. Despite some difficulties with comparing the benefits of chronic disease self‐management programmes, many evaluations report some benefit and all highlight the importance of health professionals in supporting self‐management behaviours. In the primary care sector, community nurses are ideally situated to support these behaviours, but to do this effectively transformation of nursing practice must occur.

Design.  Qualitative, longitudinal study informed by action research methods and involving monthly group discussions with community nurse mentors.

Methods.  Community nurses from four community health centres in Tasmania were trained in motivational interviewing techniques to promote self‐management amongst chronic obstructive pulmonary disease patients. Nurses’ mentoring experiences were monitored during group discussions and subjected to thematic analysis.

Results.  The paper reports the findings of the first 12 months of the project. In this phase, nurses experienced a transformation in their constructions of chronic obstructive pulmonary disease and their clinical practice. This involved a shift from a fatalistic, prescriptive, biomedical approach to a primary healthcare approach characterised by empathy, consultation, facilitation and a holistic focus.

Conclusions.  Community nurses face challenges in supporting chronic disease self‐management. These challenges can be overcome and a transformation in clinical practice instilled.

Relevance to clinical practice.  This study highlights that it is possible to support community nurses to take a lead role in the ongoing management of chronic disease in the community.
Genetic evidence for male‐biased dispersal in the three‐spined stickleback (Gasterosteus aculeatus)
Authors: CANO J. M , MÄKINEN H. S , MERILÄ J
Published: June 2008

Sex‐biased dispersal is capable of generating population structure in nonisolated populations and may affect adaptation processes when selective conditions differ among populations. Intrasexual competition for local resources and/or mating opportunities predicts a male‐biased dispersal in polygynous species and a female bias in monogamous species. The patterns of sex‐biased dispersal in birds and mammals are well explained by their respective mating systems, but the picture emerging from fish studies is still mixed. Using neutral genetic markers, we investigated whether there is any evidence for sex‐biased dispersal among Baltic Sea populations of the three‐spined stickleback (Gasterosteus aculeatus). The null hypothesis of non sex‐biased dispersal was rejected in favour of male‐biased dispersal in this species. As the three‐spined stickleback has a polygynous mating system, the observed male bias in dispersal is consistent with the hypothesis that local mate competition might drive the observed pattern. Although more research both on the proximate and ultimate causes behind the observed pattern is needed, our results serve as a first step towards understanding patterns of sex‐biased dispersal in this species.
Crystal structure of Escherichia coli phage HK620 tailspike: podoviral tailspike endoglycosidase modules are evolutionarily related
Authors: Barbirz Stefanie , Müller Jürgen J. , Uetrecht Charlotte , Clark Alvin J. , Heinemann Udo , Seckler Robert
Published: June 2008

Bacteriophage HK620 infects Escherichia coli H and is closely related to Shigella phage Sf6 and Salmonella phage P22. All three Podoviridae recognize and cleave their respective host cell receptor polysaccharide by homotrimeric tailspike proteins. The three proteins exhibit high sequence identity in the 110 residues of their N‐terminal particle‐binding domains, but no apparent sequence similarity in their major, receptor‐binding parts. We have biochemically characterized the receptor‐binding part of HK620 tailspike and determined its crystal structure to 1.38 Å resolution. Its major domain is a right‐handed parallel β‐helix, as in Sf6 and P22 tailspikes. HK620 tailspike has endo‐N‐acetylglucosaminidase activity and produces hexasaccharides of an O18A1‐type O‐antigen. As indicated by the structure of a hexasaccharide complex determined at 1.6 Å resolution, the endoglycosidase‐active sites are located intramolecularly, as in P22, and not between subunits, as in Sf6 tailspike. In contrast, the extreme C‐terminal domain of HK620 tailspike forms a β‐sandwich, as in Sf6 and unlike P22 tailspike. Despite the different folds, structure‐based sequence alignments of the C‐termini reveal motifs conserved between the three proteins. We propose that the tailspike genes of P22, Sf6 and HK620 have a common precursor and are not mosaics of unrelated gene fragments.
Biological and Molecular Variability of Zucchini yellow mosaic virus in Iran*
Authors: Bananej Kaveh , Keshavarz Tayyebeh , Vahdat Aisan , Hosseini Salekdeh Ghasem , Glasa Miroslav
Published: June 2008

Zucchini yellow mosaic virus (ZYMV; family Potyviridae, genus Potyvirus) causes high yield losses to cucurbits in many parts of the world. The virus was detected for the first time in Iran in 1988, but the isolates have not been characterized. To study the genetic and biological diversity among Iranian ZYMV isolates, a set of twelve isolates, obtained during an extensive survey conducted from 2003 to 2006 in the major cucurbit‐growing areas, were characterized. An experimental host range study of these isolates (referred as Iran‐1 to Iran‐12) revealed some variation in their biological properties. The nucleotide sequences of the genomic portion spanning the C‐terminal part of NIb and N‐terminal part of coat protein (CP) coding region were determined and compared with other available sequences. The identity among Iranian ZYMV isolates at the amino acid level reached 95.6–100%. The Iranian ZYMV isolates did not form a compact cluster in the phylogenetic tree, and the phylogenetic analyses and the estimation of genetic distance indicate that the Iranian ZYMV group consists of several independent introductions that evolved separately.
Microstructurally controlled monazite chronology of ultrahigh‐temperature granulites from southern India: Implications for the timing of Gondwana assembly
Authors: Santosh M. , Tsunogae Toshiaki , Tsutsumi Yukiyasu , Iwamura Masayuki
Published: June 2008

Ultrahigh‐temperature (UHT) granulite facies rocks from the Achankovil Shear Zone area and the southern domain of the Madurai Granulite Block in South India contain monazite useful for in situ microprobe U–Pb dating. The UHT rocks examined consist of garnet + cordierite (retrograde) + quartz + mesoperthite + biotite + plagioclase + Fe‐Ti oxides ± orthopyroxene ± sillimanite and accessory zircon and monazite. Sillimanite occurs only as inclusions in garnet. Microstructural observations suggest garnet, orthopyroxene, spinel and mesoperthite are products of peak metamorphism. Post‐peak formation of cordierite ± orthopyroxene ± quartz and cordierite + spinel + Fe‐Ti oxides assemblages is also observed. Geothermobarometry on orthopyroxene and garnet‐orthopyroxene bearing assemblages suggest peak UHT conditions of T = 940–1040°C and P = 8.5–9.5 kbar. This was followed by a retrograde stage of 3.5–4.5 kbar and 720 ± 60°C, estimated from garnet‐cordierite assemblages. A small population of rounded, probably detrital, monazites in these rocks yield ages from Meso‐ to Neoproterozoic indicating a heterogeneous source. The youngest associated spot ages are 660–600 Ma suggesting protolith deposition up to ca 600 Ma. In contrast, the vast majority of monazites that crystallized during the latest metamorphic event show late Neoproterozoic to Cambrian ages. Probability‐density plots of monazite age data show a ‘peak’ between 533 and 565 Ma, but this peak need not reflect a particular thermal event. Collating ages from homogenous metamorphic monazites associated with minerals stable at peak P‐T conditions suggests peak metamorphism in these rocks occurred at 580–600 Ma. Together with a re‐evaluation of available data from adjacent granulite blocks in southern India, these data suggest the main metamorphic event coinciding with the suturing of India with the Gondwana amalgam probably occurred 580–600 Ma. The 500–550 Ma ages commonly reported in previous studies might represent post‐peak thermal events.
Glioneuronal tumor with neuropil‐like islands: A new entity
Authors: Agarwal Shipra , Suri Vaishali , Rishi Arvind , Shukla Bhaskar , Garg Ajay , Sharma Mehar Chand , Sinha Sumit , Sarkar Chitra
Published: June 2008

Glioneuronal tumor with neuropil‐like islands (GTNI) is a distinctive and rare tumor characterized by both glial and neuronal differentiation. However, unlike other mixed glioneuronal tumors, which are characterized by a favorable prognosis, this neoplasm has been found to be potentially aggressive. We report here a case arising in a 60‐year old male patient who presented with seizures, forgetfulness and right‐sided hemiparesis, due to a left frontal lobe tumor. Unlike most cases described in the literature, the present tumor was unique in its radiological appearance, which was cystic. On microscopic evaluation, the glial component was chiefly gemistocytic punctuated by neuropil‐like islands. Strong nuclear immunolabeling of p53 and absence of 1p/19q deletion by fluorescence in situ hybridization assay were consistent with those in previous reports.
Intraoperative ultrasonography in an era of minimally invasive urology
Authors: Ukimura Osamu , Okihara Koji , Kamoi Kazumi , Naya Yoshio , Ochiai Atsushi , Miki Tsuneharu
Published: June 2008

Abstract:  Recent evidence has suggested certain advantages of the intraoperative use of ultrasonography (US) for urology. Advances in US technology include availability of compact, specially‐formed US probes (i.e. endoluminal, laparoscopic, transrectal, and transvaginal) and new US functions (such as Doppler, harmonic, 3D, virtual sonography, 4D, contrast‐enhanced, elastography, the fusion system with computed tomography/magnetic resonance imaging, and augmented reality). These have the potential to enhance visualization of the surgical anatomy, even beyond the surgical view, and thus increase the precision of surgery. US has been demonstrated to be the most widely‐used intraoperative imaging, with the advantages of its real‐time nature, non‐invasiveness and easy‐handling. Importantly, it can be performed by urologists, who in contemporary practice are going to need increasing familiarity with intraoperative imaging. This review article focused on US intervention and intraoperative US, and current data were summarized regarding the advantages, limitations, and future potential of US technology in the modern era of minimally‐invasive urology.
PAEDIATRIC MOTORBIKE INJURIES: DO CHILDREN RIDING MOTORBIKES GET THE SAME INJURIES AS THOSE RIDING BICYCLES?
Authors: Robertson Jonathon , Garrett Peter
Published: June 2008

Background:  Health workers have the impression that injuries sustained by children on motorcycles are more severe and debilitating than those of children on bicycles. This was not reflected by data collected for a statewide trauma registry: the two groups looked very similar at first glance.

Methods:  A retrospective chart review audit was carried out to further collect clinical data that might be deemed to be consequential to patients, their families and the health system, to see if this initial finding was reproduced.

Results:  Registry outcomes such as length of stay and mortality were no different, but number of procedures required, number of injuries and functional injuries were very different.

Conclusions:  Showing that children are more severely injured when riding motorcycles rather than bicycles is needed to promote cultural and legislative change.
Endobronchial ultrasound convex‐probe transbronchial needle aspiration as the first diagnostic test in patients with pulmonary masses and associated hilar or mediastinal nodes
Authors: Fielding D. , Windsor M.
Published: June 2008

Background: In the diagnosis of patients with a lung mass and hilar or mediastinal lymph nodes (N1or N2) it may be that patients are unnecessarily having biopsies of the primary lung cancer when sampling of the nodes would give both a tissue diagnosis and staging. By comparing node station and size in patients having just one procedure (endobronchial ultrasound transbronchial needle aspiration [EBUS TBNA]) with those having extra procedures on the primary mass before EBUS TBNA, similarity of nodes in the two groups might suggest that the extra procedures were unnecessary.

Methods: A prospective case series of patients with coexistent lung mass and N1or N2 nodes compared results for EBUS TBNA in patients with no prior bronchoscopy (group A) with patients who had a bronchoscopy or transthoracic needle aspiration elsewhere directed at the primary mass (group B).

Results: Sixty‐eight EBUS TBNA procedures were carried out in 67 patients with 23 patients in group A, and 45 in group B. Nodes sampled included stations 2, 3, 4, 7, 10, 11 and 12. Node size was approximately the same in both groups, 16.5 ± 6 mm in group A and 16.9 ± 6 mm in group B. For malignancy sensitivity by EBUS TBNA was 94% in group A and 95% in group B, with surgical sampling showing three TBNA false negatives.

Conclusion: There was no difference between the two groups in node size or location. Diagnostic yield overall was high. With expanding use of EBUS TBNA, a new guideline for its initial application in such patients could reduce the overall number of procedures.
Perceptions and attitudes of rehabilitation medicine physicians on complementary and alternative medicine in Australia
Authors: Mak J. C. S. , Mak L. Y. H. , Shen Q. , Faux S.
Published: June 2008

Background:  The growing demand for complementary and alternative medicine (CAM) is undeniable. We report a first study about the attitudes and behaviour of Australian rehabilitation physicians to CAM.

Methods:  A prospective cross‐sectional survey was undertaken to document the prevalence of, knowledge about and referrals to CAM therapies and their perceived effectiveness, by a sample of Australian rehabilitation physicians.

Results:  Thirty‐six out of 94 actively practising rehabilitation physicians from the Australasian Faculty of Rehabilitation Medicine, the Royal Australasian College of Physicians, replied to the survey, a response rate of 38%, and 85% reported familiarity with CAM, the most familiar therapies being acupuncture (80%), yoga (74%) and Tai‐Chi (72%). CAM referral was reported in 84%, 38% personally used CAM, 94% of patients enquired about CAM therapies, 32% of respondents routinely enquired about CAM use. Age, sex and year of Fellowship were not associated with familiarity, personal use or frequency of patient enquiry about CAM. Those who reported to be very familiar with CAM were more likely to routinely enquire about CAM use (P = 0.028) and be more confident in prescribing certain CAM therapies (P < 0.05).

Conclusion:  Australian rehabilitation physicians report similar CAM referral rates to Canadian physiatrists and Australian general practitioners. The most commonly prescribed therapies were acupuncture, yoga and Tai‐Chi. Almost all patients use CAM therapies, but only a minority of rehabilitation physicians enquires about CAM use on a regular basis. The latter may avoid potentially harmful drug interactions, as well as improve the quality of the physician–patient relationship.
Treatment‐induced stable, moderate reduction in blood cell counts correlate to disease control in early rheumatoid arthritis
Authors: Lester S. E. , Proudman S. M. , Lee A. T. Y. , Hall C. A. , McWilliams L. , James M. J. , Cleland L. G.
Published: June 2008

Background: Treatment of rheumatoid arthritis (RA) has become more intensive, thereby raising concerns regarding toxicities, including leucopenia. The objective was to analyse cell counts obtained as routine surveillance for adverse effects to assess the effect of intensive treatment and treatment dosage and to examine correlations to disease activity scores.

Methods: Patients with early RA were treated with combinations of disease‐modifying anti‐inflammatory drugs according to pre‐defined rules, with dose adjustments contingent on residual disease activity and tolerance.

Results: Mean leucocyte, neutrophil and platelet counts fell with levels that correlated to disease activity scores. The strongest correlation was between platelets and disease activity scores. There was a modest, inverse correlation between methotrexate dose and monocyte and lymphocyte counts. No serious toxicity associated with the therapy was seen.

Conclusion: Moderate reductions in cell counts are well tolerated in RA and appear to contribute to disease control.
Spatiotemporal organization of α‐motoneuron activity in the human spinal cord during different gaits and gait transitions
Authors: Ivanenko Y. P. , Cappellini G. , Poppele R. E. , Lacquaniti F.
Published: June 2008

Here we studied the spatiotemporal organization of motoneuron (MN) activity during different human gaits. We recorded the electromyographic (EMG) activity patterns in 32 ipsilateral limb and trunk muscles from normal subjects while running and walking on a treadmill (3–12 km/h). In addition, we recorded backward walking and skipping, a distinct human gait that comprises the features of both walking and running. We mapped the recorded EMG activity patterns onto the spinal cord in approximate rostrocaudal locations of the MN pools. The activation of MNs tends to occur in bursts and be segregated by spinal segment in a gait‐specific manner. In particular, sacral and cervical activation timings were clearly gait‐dependent. Swing‐related activity constituted an appreciable fraction (> 30%) of the total MN activity of leg muscles. Locomoting at non‐preferred speeds (running and walking at 5 and 9 km/h, respectively) showed clear differences relative to preferred speeds. Running at low speeds was characterized by wider sacral activation. Walking at high non‐preferred speeds was accompanied by an ‘atypical’ locus of activation in the upper lumbar spinal cord during late stance and by a drastically increased activation of lumbosacral segments. The latter findings suggest that the optimal speed of gait transitions may be related to an optimal intensity of the total MN activity, in addition to other factors previously described. The results overall support the idea of flexibility and adaptability of spatiotemporal activity in the spinal circuitry with constraints on the temporal functional connectivity of hypothetical pulsatile burst generators.
Risk factor assessment for new onset diabetes: literature review
Authors: Bakris George , Stockert Jack , Molitch Mark , Zhou Qian , Champion Annette , Bacher Peter , Sowers James ,   on behalf of the STAR Investigators
Published: June 2008

Metabolic syndrome (MS), typified by hypertension, abdominal obesity, dyslipidaemia and impaired glucose metabolism, is a precursor of type 2 diabetes. Thiazide diuretics (TD) and beta‐blockers are associated with increased risk of diabetes in patients with hypertension; however, the role of these agents in development of diabetes in MS patients is unknown. We reviewed the literature regarding risk factors for diabetes development and compared this with data from the Study of Trandolapril/Verapamil SR And Insulin Resistance (STAR), which investigated the effects of two fixed‐dose combinations (FDCs) [trandolapril/verapamil SR and losartan/hydrochlorothiazide (L/H)] on glucose control and new diabetes in MS patients. In STAR, logistic regression modelling identified haemoglobin A1c [odds ratio (OR) 4.21 per 1% increment; p = 0.003), L/H treatment (OR 4.04; p = 0.002) and 2‐h oral glucose tolerance test glucose levels (OR 1.39 per 10 mg/dl increments; p < 0.001) as baseline predictors of diabetes. These data support prior analyses and suggest that choice of antihypertensive agent is important. Patients with MS may be at lower risk of diabetes when using a FDC calcium channel blocker + angiotensin‐converting enzyme inhibitor compared with an angiotensin receptor blocker + TD.
Hereditary phenotypes in nocturnal enuresis
Authors: Schaumburg Henriette L. , Kapilin Ulla , Blåsvær Christa , Eiberg Hans , Von Gontard Alexander , Djurhuus Jens Christian , Rittig Søren
Published: June 2008

OBJECTIVE

To identify phenotypic characteristics in three large families with autosomal dominant nocturnal enuresis (NE), and to elucidate whether such characteristics persist after cessation of symptoms.

SUBJECTS AND METHODS

From three unrelated NE kindreds (A–C) we included 98 living members of whom 34 either had active NE (>one wet night/month after the age of 5 years) or a history of NE. The family members were interviewed to identify NE type and severity. Subsequently, night‐time urine production was recorded for 2 weeks at home and 4 days of frequency‐volume charts were completed.

RESULTS

There was coexistence of both primary and secondary NE (family A), coexistence of monosymptomatic NE and incontinence (families A and C), pure monosymptomatic NE (family B) and pure day‐time incontinence (family C). However, the NE phenotype of family A was characterized by nocturnal polyuria and normal bladder capacity, whereas family C was characterized by normal nocturnal urine production and reduced bladder capacity. Interestingly, there were no differences between former affected and unaffected family members in any of the families for night‐time urine production, nocturia frequency, nocturia volumes, day‐to‐night ratios, or bladder capacity.

CONCLUSION

The clinical phenotype in three large families with hereditary severe NE was heterogeneous within and between families. However, the NE phenotype seemed to differ between two of the families for nocturnal urine production, bladder capacity, and response to desmopressin. These results indicate that the genes responsible for NE in these families are not related directly to the presence of primary vs secondary NE or coexisting day‐time problems. However, there might be genetically determined differences in bladder capacity and/or nocturnal urine production.
RESEARCH SECTION: Looking back on school – the views of adult graduates of a residential special school for children with emotional and behavioural difficulties
Authors: Hornby Garry , Witte Chrystal
Published: June 2008

The authors of this article, Garry Hornby and Chrystal Witte, conducted a follow‐up study with adult graduates of a residential special school for children with emotional and behavioural difficulties in New Zealand. Twenty‐one graduates were located and interviewed ten to 14 years after they had left the residential school. The interviews focused on various factors related to the graduates' quality of life (reported elsewhere) and on their views of their education, both at the residential school and at mainstream schools, which are reported in this paper. It was found that these adult graduates were overwhelmingly positive about the support they received while at the residential school. They talked, for example, about the help they received in addressing their learning and behavioural difficulties. However, they were consistently negative with regard to their experiences of mainstreaming. For example, respondents noted the lack of understanding that they experienced from mainstream teachers. In drawing out the implications of the findings from this study, Garry Hornby and Chrystal Witte suggest that one factor which could result in improving outcomes for these students is better special needs training for teachers in mainstream schools.
IS THERE A ‘SECESSION OF THE WEALTHY’? PRIVATE HEALTH INSURANCE UPTAKE AND NATIONAL HEALTH SYSTEM SUPPORT
Authors: Costa‐Font Joan , Jofre‐Bonet Mireia
Published: June 2008

The purchase of private health insurance (PHI) as a means to partially supplement the National Health System (NHS) coverage is often regarded as a potential signal for a declining support for the NHS. Exploiting the fact that PHI is typically purchased by the most affluent, in this paper we test the so called ‘secession of the wealthy’ hypothesis whereby the likelihood of expressing ‘lack of support for the NHS’ increases with having supplementary PHI. Using empirical data from Catalonia, we draw upon an empirical strategy that circumvents an obvious simultaneity problem by estimating both a recursive bivariate probit as well as an IV probit. After controlling for insurance premium, household income and other socio‐demographic determinants, we find that the purchase of PHI reduces the propensity of individuals to support the NHS. We also find evidence that PHI is a luxury good and sensitive to fiscal incentives.
Land use/cover, landforms and fragmentation patterns in a tropical dry forest in the southern Pacific region of Mexico
Authors: Galicia Leopoldo , Zarco‐Arista Alba Esmeralda , Mendoza‐Robles Karla Ivette , Palacio‐Prieto José Luis , García‐Romero Arturo
Published: June 2008

In spite of widely documented studies of deforestation rates and land use/cover changes in tropical dry forests in Mexico, relatively little is known about fragmentation patterns in such forests. This study defines the spatial distribution of landforms and land use/cover types the lower Papagayo River basin and examines their influence on fragmentation patterns and biological diversity in a tropical dry forest in that southern Pacific region. The land use/cover map was constructed from aerial photographs, Landsat TM imagery (2000) and fieldwork. Landform units were defined based on altitude, slope, lithology and morphology. Landscape fragmentation parameters were obtained using FRAGSTATS (version 3.3) considering the numbers of patches, mean, minimum and maximum patch size, edge density, total edge and connectivity. Results show tropical dry forest to be remnant vegetation (~11 per cent), characterized by isolation and low connectivity. Land use/cover types have different effects on fragmentation patterns. Agriculture and cattle raising produce similar numbers of patches, but with a different mean size; and human settlements have a scattered distribution pattern. The abandonment of rural agricultural livelihoods has favoured the expansion of secondary tropical dry forest characterized by continuity and high connectivity, which suggests a high regeneration potential from land abandonment. It can be concluded that tropical dry forest fragmentation and recovery at regional scales depend on such landscape attributes as lithology, slope, geomorphology and management.
Creating a Bigger Bath Using the Deferred Tax Valuation Allowance
Authors: Christensen Theodore E. , Paik Gyung H. , Stice Earl K.
Published: June 2008

Abstract:  The provisions of SFAS No. 109 allow US companies to make an earnings big bath even bigger through the establishment of a deferred tax valuation allowance. At the time a firm recognizes a non‐cash charge, it also recognizes a deferred tax asset to represent the future tax benefits of the charge. Recognition of the deferred tax asset partially mitigates the negative earnings impact of the special charge. However, if the firm does not expect to have sufficient future taxable income to utilize the future tax benefits of the charge, SFAS No. 109 requires the firm to establish a deferred tax valuation allowance, effectively eliminating the recognized deferred tax asset. Thus, the establishment of the valuation allowance amplifies the negative earnings impact of the non‐cash charge. We use a valuation allowance prediction model to identify firms that create a larger‐than‐expected valuation allowance; these firms may be creating a large valuation allowance as a reserve to be used to manage earnings in a subsequent period. We find that the vast majority of these larger‐than‐expected valuation allowances apparently reflect informed management pessimism about the future in that these firms actually do have poorer operating performance in subsequent periods. We do not find any evidence that subsequent reversals of valuation allowances are used to turn a loss into a profit. However, we do find a very small number of firms that appear to have used a valuation allowance reversal to meet or beat the mean analyst forecast.
Emotional processing in male adolescents with childhood‐onset conduct disorder
Authors: Herpertz Sabine C. , Huebner Thomas , Marx Ivo , Vloet Timo D. , Fink Gereon R. , Stoecker Tony , Jon Shah N. , Konrad Kerstin , Herpertz‐Dahlmann Beate
Published: June 2008

Background:  Boys with early onset of conduct disorder (CD), most of whom also meet diagnostic criteria of a comorbid attention deficit hyperactivity disorder (ADHD), tend to exhibit high levels of aggression throughout development. While a number of functional neuroimaging studies on emotional processing have been performed in antisocial adults, little is known about how CD children process emotional information.

Method:  Functional magnetic resonance imaging data were analyzed in 22 male adolescents aged 12 to 17 years with childhood‐onset CD (16 of them with comorbid ADHD) compared to 22 age‐matched male healthy controls. In order to consider the likely confounding of results through ADHD comorbidity, we performed a supplementary study including 13 adolescent subjects with pure ADHD who were compared with healthy controls. To challenge emotional processing of stimuli, a passive viewing task was applied, presenting pictures of negative, positive or neutral valence.

Results:  When comparing CD/combined disorder patients with healthy controls, we found enhanced left‐sided amygdala activation in response to negative pictures as compared to neutral pictures in the patient group. In addition, these boys exhibited no reduced activation in the orbitofrontal, anterior cingulate and insular cortices. By contrast, children with pure ADHD did not show any abnormalities in amygdala activation but showed decreased neural activity in the insula only in response to negative pictures.

Conclusions:  Increased rather than reduced amygdala activation found in our study may indicate an enhanced response to environmental cues in adolescents with early‐onset CD (most of whom also met the condition of ADHD), and is not consistent with the assumption of a reduced capacity to take note of affective information in the social environment. Further studies with an emphasis on developmental aspects of affect regulation are needed to clarify the relationship between CD and adult personality pathology associated with different modes of persistent antisocial behavior.
Identifying symptoms of ovarian cancer: a qualitative and quantitative study
Authors: Bankhead CR , Collins C , Stokes‐Lampard H , Rose P , Wilson S , Clements A , Mant D , Kehoe ST , Austoker J
Published: June 2008

Introduction  Symptoms of ovarian cancer are often vague and consequently a high proportion of women with ovarian cancer are not referred to the appropriate clinic.

Objective  To identify diagnostic factors for ovarian cancer.

Design  A qualitative and quantitative study.

Setting  Four UK hospitals.

Sample  One hundred and twenty‐four women referred to hospital with suspected ovarian malignancy.

Methods  Women were interviewed prior to diagnosis (n = 63), or soon after. A thematic analysis was conducted. Emergent symptoms were quantitatively analysed to identify distinguishing features of ovarian cancer.

Main outcomes  Symptoms in women with and without ovarian cancer.

Results  Diagnoses comprised 44 malignancies, 59 benign gynaecological pathologies and 21 normal findings. Of the malignancies, 25 women had stage III or more disease, with an average age of 59 years. The benign/normal cohort was significantly younger (48 years). Multivariate analysis revealed persistent abdominal distension (OR 5.2, 95% CI 1.3–20.5), postmenopausal bleeding (OR 9.2, 95% CI 1.1–76.1), appetite loss (OR 3.2, 95% CI 1.1–9.2), early satiety (OR 5.0, 95% CI 1.6–15.7) and progressive symptoms (OR 3.6, 95% CI 1.3–9.8) as independent, statistically significant variables associated with ovarian cancer. Fluctuating distension was not associated with ovarian cancer (OR 0.4, 95% CI 0–4.1). Women frequently used the term bloating, but this represented two distinct events: persistent abdominal distension and fluctuating distension/discomfort.

Conclusions  Ovarian cancer is not a silent killer. Clinicians should distinguish between persistent and fluctuating distension. Recognition of the significance of symptoms described by women could lead to earlier and more appropriate referral.
Should adnexal mass size influence surgical approach? A series of 186 laparoscopically managed large adnexal masses
Authors: Ghezzi F , Cromi A , Bergamini V , Uccella S , Siesto G , Franchi M , Bolis P
Published: June 2008

Objective  To evaluate the feasibility and safety of laparoscopic management of adnexal masses ≥10 cm in size.

Design  Prospective cohort study.

Setting  Two Gynecology Departments of University Hospitals.

Population  All women presenting with an adnexal mass ≥10 cm in diameter were candidates for laparoscopic management. Women were excluded from laparoscopic approach if there was evidence of ascites or gross metastatic disease. Neither the sonographic features of the cyst nor elevated serum CA125 level was used to exclude women from having a laparoscopic approach.

Methods  A single operative protocol was followed for all women. All removed specimens were sent for immediate pathological evaluation.

Main outcome measures  Rate of conversion to laparotomy, incidence of cancer encountered, and operative complications.

Results  One hundred and eighty‐six women underwent laparoscopic evaluation for an adnexal mass of 10 cm or larger in size. The average preoperative mass size was 12.1 ± 4.9 cm. A benign pathological condition was found in 86.6% (161/186) of the women, primary ovarian cancer in 16 (8.6%) women, a metastatic tumour of gastrointestinal origin in 1 (0.5%) woman, and a low malignant potential ovarian tumour in 8 (4.3%) women. Laparoscopic management was successful for 174 (93.5%) women. Reasons for conversion to laparotomy included anticipated technical difficulty (n = 7) and malignancy (n = 5). No intraoperative complications occurred in the entire study group.

Conclusions  The vast majority of large adnexal masses can be safely resected laparoscopically, provided that there is expertise in laparoscopic surgery, immediate access to frozen section diagnosis, and preparation of patient to receive an adequate cancer surgery where indicated.
Vaccination against HPV: indications for women and the impact on the cervical screening programme
Authors: Heideman DAM , Snijders PJF , Berkhof J , Verheijen RHM , Helmerhorst TJM , Meijer CJLM
Published: June 2008

A novel approach for primary prevention of cervical cancer has become available by the discovery of efficient prophylactic human papillomavirus (HPV) vaccines based on virus‐like particles. This review elaborates on the progress in the field of prophylactic HPV vaccination achieved in the past decade, provides indications for prophylactic HPV vaccination, and discusses the impact on public health and the current secondary prevention system. In summary, with current vaccines, effective prevention and control of cervical cancer within the next decades requires an integrated vaccination‐screening approach, including routine prophylactic vaccination to young women and adapted cervical screening for older women (≥30 years).