bluuebunny/crossref_metadata_2025 huggingface dataset:
An adverse intrauterine environment: implications for injury and altered development of the brain
Authors: Rees Sandra , Harding Richard , Walker David
Published: October 2007

Abnormal development of the brain during fetal life is now thought to contribute to the aetiology of many functional and behavioural disorders that manifest throughout life. Many factors are likely to underlie such abnormal development including genetic makeup and an adverse intrauterine environment. This review will focus on prenatal hypoxic–ischemic injury and inflammatory/infective insults. A range of experimental models have been used to characterise lesions formed in response to these insults and to determine mechanisms of damage resulting from such events. Relatively brief periods of fetal hypoxia result in neuronal death (cerebellum, hippocampus, and cerebral cortex), white matter damage and reduced growth of neural processes. These effects are more profound at mid than late gestation. Chronic mild placental insufficiency can result in fetal growth restriction and deficits in neural connectivity and myelination. Exposure of the preterm fetus to inflammatory agents causes brain damage particularly in the white matter and this is exacerbated by hypoxia. These studies show that the timing, severity and nature of specific insults are critical in determining the pattern of injury and thus the extent to which neurological function will be affected postnatally. Defining the causes, patterns and mechanisms of brain injury is crucial if we are to develop rational neuroprotective strategies to reduce the burden of altered brain growth and poor functional and behavioural outcomes.
Modulation of parkin gene expression in noradrenergic neuronal cells
Authors: Park Euteum , Kim Seung , Kim Sung‐Jun , Park Yeol , Lee Jung‐Sup , Yoo Jin‐Cheol , Kim Chun‐Sung , Kim Do Kyung , Lee Sook‐Young , Chun Hong Sung
Published: October 2007

Typical autosomal recessive juvenile Parkinsonism (AR‐JP) is resulted from the loss of function mutation in the parkin gene. In an effort to learn more about the cell type‐specific functional role of parkin, we used in vitro model such as locus coeruleus (LC) noradrenergic (NA) neuronal progenitor cell line, LC3541. Employing this in vitro model, we revealed that parkin plays a crucial role in phenotypic differentiation of NA neurons. Our results showed that parkin mRNA was expressed during the differentiation of NA neuronal progenitor cell line and that the level of the parkin mRNA was down‐regulated by oxidative stress in the NA neuronal cells. Parkin protein overexpression in LC3541 cells induced expression of NA markers (TH, phox2a and DBH). Small interfering RNA (SiRNA) for parkin supressed NA differentiation and DBH expression. Preventing protein kinase A (PKA) activation with PKI attenuated expression of DBH in parkin overexpressed LC3541 cells. These findings suggest that the relative abundance of parkin enhances differentiation of NA phenotypes via a PKA‐dependent pathway.
Surgical Treatment of the Boxer’s Fracture: Transverse Pinning Versus Intramedullary Pinning
Authors: WINTER M. , BALAGUER T. , BESSIÈRE C. , CARLES M. , LEBRETON E.
Published: October 2007

The purpose of this study was to compare the surgical treatment of fractures of the little finger metacarpal neck, or “Boxer’s” fractures, by transverse pinning and intramedullary pinning. Thirty-six patients with fracture of the neck of the fifth metacarpal were included in a prospective comparative randomised study. A palmar splint was applied for 1 week after both procedures. Patients began physiotherapy three times per week for 30 days. The patients were evaluated clinically six times after surgery, up to the 90th day, with X-ray assessment on days 8, 45 and 90. The study showed that intramedullary pinning gave better functional outcomes than transverse pinning, although the former was more technically demanding.
Increased calcium intake does not completely counteract the effects of increased phosphorus intake on bone: an acute dose–response study in healthy females
Authors: Kemi Virpi E. , Kärkkäinen Merja U. M. , Karp Heini J. , Laitinen Kalevi A. E. , Lamberg-Allardt Christel J. E.
Published: October 2007

A high dietary P intake is suggested to have negative effects on bone through increased parathyroid hormone secretion, as high serum parathyroid hormone (S-PTH) concentration increases bone resorption. In many countries the P intake is 2- to 3-fold above dietary guidelines, whereas Ca intake is too low. This combination may not be optimal for bone health. In a previous controlled study, we found that dietary P dose-dependently increased S-PTH and bone resorption and decreased bone formation. The aim of the present study was to investigate the dose–response effects of Ca intake on Ca and bone metabolism with a dietary P intake higher than recommended. Each of the twelve healthy female subjects aged 21–40 years attended three 24-h study sessions, which were randomized with regard to a Ca dose of 0 (control day), 600 or 1200 mg, and each subject served as her own control. The meals on each study day provided 1850 mg P and 480 mg Ca. S-PTH concentration decreased (P < 0·001) and serum ionized Ca concentration increased (P < 0·001) with increasing Ca doses. The bone formation marker, serum bone-specific alkaline phosphatase, did not differ significantly (P = 0·4). By contrast, the bone resorption marker, urinary N-terminal telopeptide of collagen type I, decreased significantly with both Ca doses (P = 0·008). When P intake was above current recommendations, increased Ca intake was beneficial for bone, as indicated by decreased S-PTH concentration and bone resorption. However, not even a high Ca intake could affect bone formation when P intake was excessive.
Dietary validation of a new Australian food-frequency questionnaire that estimates long-chainn-3 polyunsaturated fatty acids
Authors: Sullivan Bethany L. , Brown Janelle , Williams Peter G. , Meyer Barbara J.
Published: October 2007

Currently, there is no FFQ designed to capture the intakes of the long-chain (LC)n-3 PUFA. The objectives of this study were to validate a new LCn-3 PUFA FFQ by comparison with 3 d weighed food records (FR) and to determine its reproducibility assessed 4 to 6 weeks apart. Healthy male and female subjects (n53) were recruited from Wollongong and the Australian Capital Territory, Australia. The FFQ and FR were analysed for LCn-3 PUFA intakes using a nutrient analysis software package and these intakes were compared using Wilcoxon signed rank tests and Spearman correlation coefficients. Bland–Altman analysis and quintile assignment assessed the agreement between the two methods and the FFQ's ability to rank individuals according to intakes, respectively. Comparison of intakes from FFQ and FR correlated significantly for total LCn-3 PUFA, EPA, docosapentaenoic acid (DPA) and DHA, 0·75, 0·64, 0·62 and 0·72, respectively (P < 0·05); hence, there is reasonable agreement between the FFQ and the FR in assessing LCn-3 PUFA intakes. Quintile assignments correctly assigned 49 % of subjects into the same quintiles and 87 % of subjects were correctly assigned either to the same or adjacent quintiles. The FFQ was reproducible for intakes of LCn-3 PUFA, EPA, DPA and DHA with Spearman correlation coefficients of 0·88, 0·88, 0·90 and 0·87, respectively. In conclusion, the new FFQ is a valid and reproducible method that can be used to estimate the LCn-3 PUFA intake of healthy adults.
Is there a difference in quality of life, comparing summer and winter, in patients who have undergone total laryngectomy?
Authors: Van Wyk F C , Vaz F , Harries M , Weighill J
Published: October 2007

Introduction:

Several studies have implied that patients' quality of life stabilises six months after undergoing total laryngectomy. However, these studies may well have overlooked persistent short term variations in patients' quality of life. The aim of this study was to assess the impact of seasonal change (i.e. summervswinter) on the quality of life of patients following total laryngectomy.

Methods:

A prospective, cross-sectional study of recurrence-free laryngectomy patients was performed, using the European Organization for Research and Treatment of Cancer (version three) QLQ-C30 questionnaires (EORTC QLQ-C30), during January 2004 (i.e. winter), August 2004 (summer) and January 2005 (winter).

Results:

Thirty-six patients were entered into the study. The response rate was 70.3 per cent. Patient's time elapsed since surgery varied from six months to 12 years. In all questionnaire domains, responses seemed remarkably consistent over time.

Conclusion:

No statistically significant differences were found between summer and winter scores in all the domains analysed by the EORTC QLQ-C30.
Improving correspondence to general practitioners regarding patients attending the ENT emergency clinic: a regional general practitioner survey and audit
Authors: Wasson J , Pearce L , Alun-Jones T
Published: October 2007

Introduction:

The ENT emergency clinic provides an important out-patient service; however, often, no correspondence is sent to the general practitioner.

Aim:

To conduct a general practitioner questionnaire audit in order to assess whether a standardised, computerised clinic letter template could improve communication between the ENT emergency clinic and patients' general practitioners.

Standard:

All ENT emergency clinic patients should have a summary letter sent to their general practitioner.

Methods:

One hundred general practitioner questionnaires were enclosed with the first 100 ENT emergency clinic template letters sent to patients' general practitioners.

Results:

Seventy-two general practitioners responded (72 per cent). Of these respondents, only 7 per cent had previously received regular correspondence from the ENT emergency clinic before the introduction of the computerised letter template. Following its implementation, such a letter was sent to 100 per cent of the clinic patients' general practitioners. Ninety-seven per cent of the general practitioners valued the template letter, with a mean satisfaction score of 8.4 on a 10-point scale. Eighty-six per cent of the general practitioners stated that they would not prefer a dictated letter.

Conclusion:

The introduction of a simple, computerised clinic letter template improves communication with ENT emergency clinic patients' general practitioners.
Twelve-month mental disorders in South Africa: prevalence, service use and demographic correlates in the population-based South African Stress and Health Study
Authors: Williams D. R. , Herman A. , Stein D. J. , Heeringa S. G. , Jackson P. B. , Moomal H. , Kessler R. C.
Published: October 2007

Background

South Africa's history and current social conditions suggest that mental disorders are likely to be a major contributor to disease burden, but there has been no national study using standardized assessment tools.

Method

The South African Stress and Health Study was a nationally representative in-person psychiatric epidemiological survey of 4351 adults (aged ⩾18 years) that was conducted as part of the WHO World Mental Health (WMH) Survey Initiative between January 2002 and June 2004. Twelve-month prevalence and severity of DSM-IV disorders, treatment, and sociodemographic correlates were assessed with Version 3.0 of the WHO Composite International Diagnostic Interview (CIDI 3.0).

Results

The 12-month prevalence of any DSM-IV/CIDI disorder was 16.5%, with 26.2% of respondents with disorder classified as severe cases and an additional 31.1% as moderately severe cases. The most common disorders were agoraphobia (4.8%), major depressive disorder (4.9%) and alcohol abuse or dependence (4.5%). Twenty-eight percent of adults with a severe or moderately severe disorder received treatment compared to 24.4% of mild cases. Some 13.8% of persons with no disorder received treatment. Treatment was mostly provided by the general medical sector with few people receiving treatment from mental health providers.

Conclusions

Psychiatric disorders are much higher in South Africa than in Nigeria and there is a high level of unmet need among persons with severe and moderately severe disorders.
The similiarity of facial expressions in response to emotion-inducing films in reared-apart twins
Authors: Kendler K. S. , Halberstadt L. J. , Butera F. , Myers J. , Bouchard T. , Ekman P.
Published: October 2007

Background

While the role of genetic factors in self-report measures of emotion has been frequently studied, we know little about the degree to which genetic factors influence emotional facial expressions.

Method

Twenty-eight pairs of monozygotic (MZ) and dizygotic (DZ) twins from the Minnesota Study of Twins Reared Apart were shown three emotion-inducing films and their facial responses recorded. These recordings were blindly scored by trained raters. Ranked correlations between twins were calculated controlling for age and sex.

Results

Twin pairs were significantly correlated for facial expressions of general positive emotions, happiness, surprise and anger, but not for general negative emotions, sadness, or disgust or average emotional intensity. MZ pairs (n=18) were more correlated than DZ pairs (n=10) for most but not all emotional expressions.

Conclusions

Since these twin pairs had minimal contact with each other prior to testing, these results support significant genetic effects on the facial display of at least some human emotions in response to standardized stimuli. The small sample size resulted in estimated twin correlations with very wide confidence intervals.
Rural environments reduce the genetic influence on adolescent substance use and rule-breaking behavior
Authors: Legrand L. N. , Keyes M. , McGue M. , Iacono W. G. , Krueger R. F.
Published: October 2007

Background

There is increasing evidence that certain environmental factors can modify genetic effects. This is an important area of investigation as such work will help to guide the development of new intervention programs. In this paper, we address whether rural environments moderate the genetic influence on adolescent substance use and rule-breaking behavior (i.e. externalizing psychopathology).

Method

Over 1200 Minnesotan 17-year-old twins were classified as either urban or rural. Externalizing behavior was operationalized as the use and abuse of alcohol and drugs along with symptoms of conduct, oppositional defiant, and antisocial personality disorders. Biometric factor modeling estimated whether the relative contribution of genetic and shared environmental factors varied from urban to rural settings.

Results

Residency effects reached statistical significance in the male sample only. In urban environments, externalizing behavior was substantially influenced by genetic factors, but in rural environments, shared environmental factors became more influential. This was apparent at both the individual-variable and factor levels.

Conclusions

These findings suggest a gene–environment interaction in the development of male adolescents' problem behaviors, including substance use. The results fit within an expanding literature demonstrating both the contextual nature of the heritability statistic and how certain environments may constrain the expression of genetic tendencies.
A meta-analysis of randomized trials of behavioural treatment of depression
Authors: Ekers D. , Richards D. , Gilbody S.
Published: October 2007

Background

Depression is a common, disabling condition for which psychological treatments, in particular cognitive behavioural therapies are recommended. Promising results in recent randomized trials have renewed interest in behavioural therapy. This systematic review sought to identify all randomized trials of behavioural therapy for depression, determine the effect of such interventions and examine any moderators of such effect.

Method

Randomized trials of behavioural treatments of depression versus controls or other psychotherapies were identified using electronic database searches, previous reviews and reference lists. Data on symptom-level, recovery/dropout rate and study-level moderators (study quality, number of sessions, severity and level of training) were extracted and analysed using meta-analysis and meta-regression respectively.

Results

Seventeen randomized controlled trials including 1109 subjects were included in this meta-analysis. A random-effects meta-analysis of symptom-level post-treatment showed behavioural therapies were superior to controls [standardized mean difference (SMD) −0.70, 95% CI −1.00 to −0.39, k=12, n=459], brief psychotherapy (SMD −0.56, 95% CI −1.0 to −0.12, k=3, n=166), supportive therapy (SMD −0.75, 95% CI −1.37 to −0.14, k=2, n=45) and equal to cognitive behavioural therapy (SMD 0.08, 95% CI −0.14 to 0.30, k=12, n=476).

Conclusions

The results in this study indicate behavioural therapy is an effective treatment for depression with outcomes equal to that of the current recommended psychological intervention. Future research needs to address issues of parsimony of such interventions.
Introduction: Infectious diseases
Authors: LEVIN SIMON A.
Published: October 2007

In any discussion of the great challenges facing humanity in addressing global environmental problems, a small number of topics automatically rise to the top: climate change, the loss of biodiversity, and the sustainability of the services ecosystems provide us. But no threats to human welfare are more urgent than those posed by infectious diseases; we suffer already the devastating consequences of the emergence of new diseases such as HIV, the reemergence of old ones such as tuberculosis, and simply the increasing toll of endemic diseases such as malaria. Non-human animals play fundamental roles in the spread of many of these diseases – as reservoirs, as vectors, and as cauldrons for the creation of new types. Land-use practices and environmental management both affect the persistence and spread of endemic diseases, such as malaria. Furthermore, as animal populations increase their ranges, due to climate change and human-facilitated alien introductions, the potential for disease spread also increases. These factors, together with the increasing mobility of the human population, conspire to make these environmental problems of great and immediate concern.
REVISITING THE OPTIMAL STATIONARY PUBLIC INVESTMENT POLICY IN ENDOGENOUS GROWTH ECONOMIES
Authors: MARRERO GUSTAVO A.
Published: October 2007

One part of the literature on endogenous growth concerns models where public infrastructure affects the private production process. An unsolved puzzle in this literature concerns observed public investment-to-output ratios for developed economies, which tend to fall short of theoretical model-based optimal ratios. We reexamine the optimal choice of public investment in a more general framework. This setting allows for long-lasting capital stocks, a lower depreciation rate for public capital than for private capital, an elasticity of intertemporal substitution that differs from unity, and the need to finance a nontrivial share of public services in output. Given other fundamentals in the economy, we show that the optimal public investment-to-output ratio is smaller for low-growth economies, for economies populated by consumers with low preferences for substituting consumption intertemporally, and when public capital is durable. For a calibrated economy, we show that a combination of these factors solves the public investment puzzle.
The molecular pathogenesis of Paget disease of bone
Authors: Layfield Robert
Published: October 2007

Paget disease of bone (PDB) is a condition characterised by increased bone remodelling at discrete lesions throughout the skeleton. The primary cellular abnormality in PDB involves a net increase in the activity of bone-resorbing osteoclasts, with a secondary increase in bone-forming osteoblast activity. Genetic factors are known to play an important role, with mutations affecting different components of the RANK–NF-κB signalling pathway having been identified in patients with PDB and related disorders. Whilst the disease mechanism in these cases is likely to involve aberrant RANK-mediated osteoclast NF-κB signalling, the precise relationship between other potential contributors, such as viruses and environmental factors, and the molecular pathogenesis of PDB is less clear. This review considers the roles of these different factors in PDB, and concludes that a fuller understanding of their contributions to disease aetiology is likely to be central to future advances in the clinical management of this debilitating skeletal disorder.
Erfahrungen von Patienten und Angehörigen während des Aufenthaltes auf einer Nursing Unit
Authors: Boinay Franziska , Spichiger Elisabeth
Published: October 2007

Das Universitätsspital des Kantons Bern (Inselspital) führte 2004 einen Pilotversuch mit einer Nursing Unit (NU) durch. Auf dieser Station wurden Patienten betreut, die keine engmaschige ärztliche Behandlung mehr brauchten, sondern primär eine komplexe, professionelle pflegerische Betreuung benötigten, welche nicht von anderen Spitälern, von Pflegeheimen, der Spitex oder Angehörigen übernommen werden konnte. Mit dieser qualitativen Studie wurden Erfahrungen von Patienten und Angehörigen mit dem Betreuungskonzept der NU untersucht. Mittels eines thematisch fokussierten Interviews wurden neun Patienten und fünf Angehörige befragt. Zur Datenauswertung wurde die qualitative Inhaltsanalyse eingesetzt. Die Ergebnisse zeigen, dass Patienten und Angehörige das neue Betreuungskonzept weitgehend akzeptierten. Vorteilhaft erlebten sie das ruhige und erholsame Klima, die patientenzentrierte und kontinuierliche Betreuung durch kompetente Pflegende, die Schulung sowie die Austrittsplanung. Einige Studienteilnehmer berichteten von mangelhafter Information beim Übertritt auf die NU, ungenügenden Situationseinschätzungen oder ungeeigneten Schulungsunterlagen. Die Studie gibt Hinweise auf positive Auswirkungen eines patientenzentrierten Betreuungsprozesses.
The Vienna Risk-Taking Test - Traffic
Authors: Hergovich Andreas , Arendasy Martin E. , Sommer Markus , Bognar Bettina
Published: October 2007

Abstract. The study reports results regarding the dimensionality and construct validity of a newly developed, objective, video-based personality test that assesses the willingness to take risks in traffic situations. On the basis of the theory of risk homeostasis developed by Wilde, different traffic situations with varying degrees of objective danger were filmed. During the test the respondents are asked to indicate at which point the action that is contingent on the described situation will become too dangerous to carry out. Latencies at the item level were recorded as a measure for the subjectively accepted degree of a person's willingness to take risks in the sense of the risk homeostasis theory by Wilde. In a study on 274 people with different educational levels and gender, the unidimensionality of the test as corresponding to the latency model by Scheiblechner was investigated. The results indicate that the Vienna Risk-Taking Test - Traffic assesses a unidimensional, latent personality trait that can be interpreted as subjectively accepted degree of risk (target risk value).
Holland's Secondary Constructs of Vocational Interests and Career Choice Readiness of Secondary Students
Authors: Hirschi Andreas , Läge Damian
Published: October 2007

Abstract. This study examined the relationship between the secondary constructs of Holland's (1997) theory of vocational interests and career choice readiness (career maturity) attitudes with 358 Swiss secondary students. The hypothesis was tested that the secondary constructs consistency, coherence, differentiation, and congruence are measures for the degree of vocational interest development. Thus, they should belong to the content domain in career choice readiness and should show meaningful relations to career-choice readiness attitudes. The hypothesis was confirmed for congruence, coherence, and differentiation. Interest-profile consistency showed no relation to career-choice readiness attitudes. Vocational identity emerged as a direct measure for career-choice readiness attitudes. Realism of career aspirations was related to career-choice readiness attitudes and coherence of career aspirations. Profile elevation was positively connected to more career planning and career exploration. Differences between gender, ethnicity, and school-types are presented. Implications for career counseling and assessment practice are discussed.
Assessing Individual Differences in Working Models of Caregiving
Authors: Reizer Abira , Mikulincer Mario
Published: October 2007

Abstract. In the current series of studies, we developed a self-report measure of mental representations of caregiving (MRC). Study 1 (N = 841) describes the development and factor structure of the MRC scale. Studies 2-4 provided convergent, discriminant, and construct validity of the MRC scale, by examining its associations with attachment dimensions, empathy, emotional control, relational interdependent self-construal, communal orientation, and value priorities. Study 5 revealed significant associations between caregiving representations and parenting attitudes (desire to have a child, feelings toward parenthood, and expectations of self-efficacy as a parent). Overall, the results provide highly consistent evidence for the reliability and validity of the new MRC scale. The implications of individual differences in mental representation of caregiving for prosocial behavior and helping are discussed.
Importance of the sea surface curvature to interpret the normalized radar cross section
Authors: Mouche A. A. , Chapron B. , Reul N. , Hauser D. , Quilfen Y.
Published: October 2007

Asymptotic models (small perturbation and small slope approximation at first‐order, Kirchhoff approximation or two‐scale model) used to predict the normalized radar cross section of the sea surface generally fail to reproduce in detail backscatter radar measurements. In particular, the predicted polarization ratio versus incidence and azimuth angles is not in agreement with experimental data. This denotes the inability of these standard models to fully take into account the roughness properties with respect to the sensor's configuration of measurement (frequency, incidence, and polarization). On the basis of particular assumptions, to decompose the scattered electromagnetic field between zones covered with freely propagating waves and others where roughness and slopes are enhanced, recent works were able to match observations. In this paper, we do not assume such a decomposition but study the latest improvements obtained in the field of approximate scattering theories of random rough surfaces using the local and resonant curvature approximations. These models are based on an extension of the Kirchhoff Approximation up to first order to relate explicitly the curvature properties of the sea surface to the polarization strength of the scattered electromagnetic field. Consistency with previous approaches is discussed. As shown, dynamically taking into account the sea surface curvature properties of the surface is crucial to better interpret normalized radar cross‐section and polarization ratio sensitivities to both sensor characteristics and geophysical environment conditions. The proposed developments, termed the Resonant Curvature Approximation (RCA), are found to reproduce experimental data versus incidence angle and azimuth direction. The polarization sensitivity to the wind direction and incidence angle is largely improved. Finally, Gaussian statistical assumption adopted to derive the analytical expression of the normalized radar cross section is also discussed. In particular, the third‐order cumulant function is shown to better reproduce the second‐order up‐/down‐wind azimuth modulation. The proposed developments appear very promising for improvement of our understanding and analysis of both sea surface radar backscatter and Doppler signals.
Direct shortwave radiative forcing of sulfate aerosol over Europe from 1900 to 2000
Authors: Marmer E. , Langmann B. , Fagerli H. , Vestreng V.
Published: October 2007

On the basis of historical simulations of the atmospheric distribution of sulfate aerosol over Europe, we have estimated the evolution of the direct shortwave radiative forcing due to sulfate aerosol from 1900 to the present day. Following the trend of atmospheric sulfate burden, the radiative forcing reaches its peak in the 1980s. Since then, environmental policies regulating SOx emissions successfully reduced the atmospheric load. On average, the forcing of the year 2000, representing present day, equals that of the 1950s. Spatially, the forcing maxima experienced a shift from the northwest to the southeast during the century. The ship emissions of sulfur keep increasing since the 1980s, hence their relative contribution to the sulfate load and radiative forcing constantly increased, from 3% in the 1980s to over 10% in the year 2000. Forcing is strongest during summertime, with a seasonal mean of −2.7 W m−2 in the 1980s and −1.2 W m−2 in summer 2000. The mean forcing efficiency is slightly reduced from −246 W (g sulfate)−1 in the 1900s to −230 W (g sulfate)−1 in the year 2000, and it declines with changed geographical distribution of sulfur emissions.
Atmospheric conditions on early Mars and the missing layered carbonates
Authors: Bullock Mark A. , Moore Jeffrey M.
Published: October 2007

Widespread, massive layered sediments, studied by surface rovers and Mars‐orbiting spectrometers, are found to be rich in sulfates. No similarly massive carbonates have been detected. We present the results of coupled atmospheric and geochemical calculations of the formation of the sulfate‐rich Meridiani sediments, and offer an explanation for why extensive layered carbonates are not found there or elsewhere on Mars. Large scale volcanism from the build‐up of Tharsis during the late Noachian would have injected large amounts of SO2 into the atmosphere. Efficient photochemical conversion of SO2 to H2SO4 would have caused widespread sulfuric acid/water clouds, similar to those seen on Venus today. Precipitation from these clouds and acidification of surface water would have sustained a thick, warm CO2 atmosphere via carbonate inhibition. Such an atmosphere could have been subjected to loss to space via impact erosion and sputtering. Once atmospheric SO2 gas production dropped and waters become more alkaline, the remaining CO2 in the atmosphere collapsed to form poorly consolidated carbonate patinas on rock surfaces and in open fractures.
Pharmacokinetics, efficacy, and safety of LMWHs in venous thrombosis and stroke in neonates, infants and children
Authors: Nowak‐Göttl U , Bidlingmaier C , Krümpel A , Göttl L , Kenet G
Published: October 2007

Since the early nineties it has been shown that low molecular weight heparin (LMWH) has significant advantages over unfractionated heparin and oral anticoagulants for both the treatment and the prevention of thrombosis, not only in adults, but also in children. The present review was based on an ‘EMBASE’, ‘Medline’ and ‘PubMed’ search including literature published in any language since 1980 on LMWH in neonates, infants and children. It included paediatric pharmacokinetic studies, the use of LMWH in children with venous thrombosis, LMWH administration in paediatric patients with ischaemic stroke, and its use in order to prevent symptomatic thromboembolism in children at risk. An increasing rate of off‐label use of LMWH in children has been reported, showing that LMWHs offer important benefits to children with symptomatic thromboembolic events and poor venous access. Two well‐conducted pharmacokinetic studies in this age group showed that neonates and younger infants require higher LMWH doses than older children to achieve the targeted anti‐Xa levels, due to an increased extra vascular clearance. Recurrent symptomatic thromboses under LMWH occur in approximately 4% of children treated for venous thrombosis, and in 7% of children treated for stroke; major bleed was documented in 3% of children with therapeutic target LMWH anti‐Xa levels, whereas minor bleeding was reported in approximately 23% of children receiving either therapeutic or prophylactic doses, respectively. Further randomized controlled trials are recommended to evaluate the optimum duration and application for different LMWH indications in children.

British Journal of Pharmacology (2008) 153, 1120–1127; doi:10.1038/sj.bjp.0707447; published online 1 October 2007
Thiazolidinediones: effects on insulin resistance and the cardiovascular system
Authors: Quinn C E , Hamilton P K , Lockhart C J , McVeigh G E
Published: October 2007

Thiazolidinediones (TZDs) have been used for the treatment of hyperglycaemia in type 2 diabetes for the past 10 years. They may delay the development of type 2 diabetes in individuals at high risk of developing the condition, and have been shown to have potentially beneficial effects on cardiovascular risk factors. TZDs act as agonists of peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) primarily in adipose tissue. PPAR‐γ receptor activation by TZDs improves insulin sensitivity by promoting fatty acid uptake into adipose tissue, increasing production of adiponectin and reducing levels of inflammatory mediators such as tumour necrosis factor‐alpha (TNF‐α), plasminogen activator inhibitor‐1(PAI‐1) and interleukin‐6 (IL‐6). Clinically, TZDs have been shown to reduce measures of atherosclerosis such as carotid intima‐media thickness (CIMT). However, in spite of beneficial effects on markers of cardiovascular risk, TZDs have not been definitively shown to reduce cardiovascular events in patients, and the safety of rosiglitazone in this respect has recently been called into question. Dual PPAR‐α/γ agonists may offer superior treatment of insulin resistance and cardioprotection, but their safety has not yet been assured.

British Journal of Pharmacology (2008) 153, 636–645; doi:10.1038/sj.bjp.0707452; published online 1 October 2007
The multidrug transporter ABCG2 (BCRP) is inhibited by plant‐derived cannabinoids
Authors: Holland M L , Lau D T T , Allen J D , Arnold J C
Published: October 2007

Background and purpose:

Cannabinoids are used therapeutically for the palliation of the adverse side effects associated with cancer chemotherapy. However, cannabinoids also inhibit both the activity and expression of the multidrug transporter, P‐glycoprotein in vitro. Here we address the interaction of cannabinol (CBN), cannabidiol (CBD) and Δ9‐tetrahydrocannabinol (THC) with the related multidrug transporter, ABCG2.

Experimental approach:

Cannabinoid inhibition of Abcg2/ABCG2 was assessed using flow cytometric analysis of substrate accumulation and ATPase activity assays. The cytotoxicity and chemosensitization by cannabinoids was determined with cell viability assays. Expression of cannabinoid and vanilloid receptors was assessed using reverse transcriptase polymerase chain reaction, and cannabinoid modulation of ABCG2 expression was examined using immunoblotting.

Key results:

CBN, CBD and THC increased the intracellular accumulation of the Abcg2/ABCG2 substrate, mitoxantrone, in an over‐expressing cell line. The THC metabolite, (−)‐11‐nor‐9‐carboxy‐Δ9‐THC was much less potent. The plant cannabinoids inhibited both basal and substrate stimulated ATPase activity of human ABCG2. Cannabinoid cytotoxicity occurred in the absence of known cannabinoid cell surface receptors, and only at concentrations higher than those required for Abcg2/ABCG2 inhibition. Sub‐toxic concentrations of the cannabinoids resensitized the overexpressing cell line to the cytotoxic effect of Abcg2/ABCG2 substrates, mitoxantrone and topotecan. This occurred in the absence of any effect on ABCG2 expression.

Conclusions and implications:

Cannabinoids are novel Abcg2/ABCG2 inhibitors, reversing the Abcg2‐mediated multidrug‐resistant phenotype in vitro. This finding may have implications for the co‐administration of cannabinoids with pharmaceuticals that are ABCG2 substrates.

British Journal of Pharmacology (2007) 152, 815–824; doi:10.1038/sj.bjp.0707467; published online 1 October 2007
Effects of α‐lipoic acid on endothelial function in aged diabetic and high‐fat fed rats
Authors: Sena C M , Nunes E , Louro T , Proença T , Fernandes R , Boarder M R , Seiça R M
Published: October 2007

Background and purpose:

This study was conducted to investigate the effects of α‐lipoic acid (α‐LA) on endothelial function in diabetic and high‐fat fed animal models and elucidate the potential mechanism underlying the benefits of α‐LA.

Experimental approach:

Plasma metabolites reflecting glucose and lipid metabolism, endothelial function, urinary albumin excretion (UAE), plasma and aortic malondialdehyde (MDA) and urinary 8‐hydroxydeoxyguanosine (8‐OHdG) were assessed in non‐diabetic controls (Wistar rats), untreated Goto‐Kakizaki (GK) diabetic and high‐fat fed GK rats (fed with atherogenic diet only, treated with α‐LA and treated with vehicle, for 3 months). Vascular eNOS, nitrotyrosine, carbonyl groups and superoxide anion were also assessed in the different groups.

Key results:

α‐LA and soybean oil significantly reduced both total and non‐HDL serum cholesterol and triglycerides induced by atherogenic diet. MDA, carbonyl groups, vascular superoxide and 8‐OHdG levels were higher in GK and high‐fat fed GK groups and fully reversed with α‐LA treatment. High‐fat fed GK diabetic rats showed significantly reduced endothelial function and increased UAE, effects ameliorated with α‐LA. This endothelial dysfunction was associated with decreased NO production, decreased expression of eNOS and increased vascular superoxide production and nitrotyrosine expression.

Conclusions and implications:

α‐LA restores endothelial function and significantly improves systemic and local oxidative stress in high‐fat fed GK diabetic rats. Improved endothelial function due to α‐LA was at least partially attributed to recoupling of eNOS and increased NO bioavailability and represents a pharmacological approach to prevent major complications associated with type 2 diabetes.

British Journal of Pharmacology (2008) 153, 894–906; doi:10.1038/sj.bjp.0707474; published online 1 October 2007
Novel cannabinoid receptors
Authors: Brown A J
Published: October 2007

Cannabinoids have numerous physiological effects. In the years since the molecular identification of the G protein‐coupled receptors CB1 and CB2, the ion channel TRPV1, and their corresponding endogenous ligand systems, many cannabinoid‐evoked actions have been shown conclusively to be mediated by one of these specific receptor targets. However, there remain several examples where these classical cannabinoid receptors do not explain observed pharmacology. Studies using mice genetically deleted for the known receptors have confirmed the existence of additional targets, which have come to be known collectively as non‐CB1/CB2 receptors. Despite intense research efforts, the molecular identity of these non‐CB1/CB2 receptors remains for the most part unclear. Two orphan G protein‐coupled receptors have recently been implicated as novel cannabinoid receptors; these are GPR119, which has been proposed as a receptor for oleoylethanolamide, and GPR55 which has been proposed as a receptor activated by multiple different cannabinoid ligands. In this review I will present an introduction to non‐CB1/CB2 pharmacology, summarize information on GPR55 and GPR119 currently available, and consider their phylogenetic origin and what aspects of non‐CB1/CB2 pharmacology, if any, they help explain.

British Journal of Pharmacology (2007) 152, 567–575; doi:10.1038/sj.bjp.0707481; published online 1 October 2007
Cannabinoid CB2 receptors in the gastrointestinal tract: a regulatory system in states of inflammation
Authors: Wright K L , Duncan M , Sharkey K A
Published: October 2007

The emerging potential for the cannabinoid (CB) system in modulating gastrointestinal inflammation has gained momentum over the last few years. Traditional and anecdotal use of marijuana for gastrointestinal disorders, such as diarrhoea and abdominal cramps is recognized, but the therapeutic benefit of cannabinoids in the 21st century is overshadowed by the psychoactive problems associated with CB1 receptor activation. However, the presence and function of the CB2 receptor in the GI tract, whilst not yet well characterized, holds great promise due to its immunomodulatory roles in inflammatory systems and its lack of psychotropic effects. This review of our current knowledge of CB2 receptors in the gastrointestinal tract highlights its role in regulating abnormal motility, modulating intestinal inflammation and limiting visceral sensitivity and pain. CB2 receptors represent a braking system and a pathophysiological mechanism for the resolution of inflammation and many of its symptoms. CB2 receptor activation therefore represents a very promising therapeutic target in gastrointestinal inflammatory states where there is immune activation and motility dysfunction.

British Journal of Pharmacology (2008) 153, 263–270; doi:10.1038/sj.bjp.0707486; published online 1 October 2007
Familial combined hyperlipidaemia: how can genetic disorders be common, complex and comprehensible?
Authors: Sniderman Allan , Bailey Swneke D. , Engert C. Jamie
Published: October 2007

FCHL (familial combined hyperlipidaemia) is characterized by multiple phenotypes that are shaped by genes, the environment and time. A longitudinal study by Brouwers and co-workers, which appears in this issue of Clinical Science, points to the central role of the liver in defining the FCHL phenotypes and demonstrates how they vary over time in relation to energy excess. On the basis of their work and that of others, we propose that FCHL is a multiple gene/multiple pathway/multiple phenotype disease. The key feature of this model of common complex disease is that it posits testable faults in definable metabolic pathways, which supply the genetic underpinning of the disorder.
Interventional Nephrology and Dialysis: Chronic Peritoneal Dialysis Catheters: Overview of Design, Placement, and Removal Procedures
Authors: Ash Stephen R.
Published: October 2007

The success of chronic peritoneal dialysis (PD) depends to a large extent on the success of the chronic PD access device. For the nephrologist placing and removing PD catheters, or for the nephrologist advising surgeons in this role, this article provides a review of designs of PD catheters and differences in function and complications, methods of insertion of PD catheters and relation to catheter outcomes, techniques for “burying” the external portion of the PD catheter and benefits of this technique, and techniques for removing PD catheters. As nephrologists become more closely involved in the creation, monitoring, and maintenance of access devices for end‐stage renal disease (ESRD) patients, the successful function of these devices will increase. Nephrologists should make the critical decisions regarding the choice of access devices and methods for placement as they do for the choice to remove such access devices.
Interventional Nephrology and Dialysis: Bone Biopsy: Indications, Techniques, and Complications
Authors: Trueba David , Sawaya B. Peter , Mawad Hanna , Malluche Hartmut H.
Published: October 2007

Abstract Bone biopsy is the gold standard for diagnosing the type and severity of renal osteodystrophy (ROD) in end‐stage renal disease (ESRD) patients. In this article we review the indications, techniques, and complications of this minimally invasive procedure. The importance of careful preparation is emphasized.
Interventional Nephrology and Dialysis: Management of Complications of Endovascular Dialysis Access Procedures
Authors: Beathard Gerald A.
Published: October 2007

Endovascular procedures are becoming the standard of care for the management of hemodialysis (HD) vascular access dysfunction. As with any type of medical procedure, these techniques result in procedure‐related complications. The expected frequencies are low. The most frequent procedure‐related complication seen in association with angioplasty that dictates the need for intervention is tearing of the vein or vein rupture. The clinical significance of this complication is variable, ranging from none to disaster for the access. The difference lies in the severity of the tear. Management depends on the clinical presentation, ranging from symptomatic measures alone to the need to occlude the graft. Since endovascular thrombectomy is a combined procedure including angioplasty, all of the complications of that procedure can occur with this procedure as well. The major unique procedure‐related complication requiring interventional therapy is the occurrence of a symptomatic peripheral artery embolus. This complication can generally be managed successfully by mechanical endovascular means. It is essential that the interventionalist be prepared to manage these complications appropriately when they are encountered.
Enhanced upswing in immersed collisions of tethered spheres
Authors: Hsu Hui-Chi , Capart Hervé
Published: October 2007

Experiments and simplified computations are performed to study the influence of liquid motions on the dynamics of immersed pendulums. The pendulums consist of tethered spheres, swinging alone or colliding with one another in liquid initially at rest. Surprisingly, oscillations initiated in identical fashion are found to be damped less rapidly when spheres collide. Using refractive-index-matched materials and laser-illuminated tracers to visualize the flow between and around the spheres, we link this effect to the response of wake vortices. Set in motion by impact, a sphere emerges nearly wake-free from the collision, leading to reduced drag and enhanced upswing.
Measurement of pseudoturbulence intensity in monodispersed bubbly liquids for 10<Re<500
Authors: Martínez-Mercado Julián , Palacios-Morales Carlos A. , Zenit Roberto
Published: October 2007

Experiments were performed to measure the velocities of both phases in a monodispersed bubbly flow in a vertical column. Using water and water-glycerin mixtures, measurements were obtained for a range of Reynolds numbers from 10 to 500. For all cases, the Weber number was below 2. To generate a uniform stream of bubbles, an array of identical capillaries was used. To avoid coalescence, a small amount of salt was added to the interstitial fluid, which did not affect the fluid properties significantly. Measurements of the bubble phase velocity were obtained using a dual impedance probe and through high-speed digital video processing. A measurement of the vertical component of the fluctuating liquid velocity was obtained using a flying hotwire technique, which resolved the deficiency of this technique for flows with zero-mean velocity. To the best of our knowledge, this technique has not been used to study bubbly liquids in the past. It was found that for all cases, the bubble velocity decreases as the mean gas volume fraction increases. For vanishing gas volume fraction, the mean bubble velocity was found to be smaller than that calculated for an isolated bubble. The flow agitation, characterized by the velocity variance both in the liquid and the bubble phases, increases with bubble concentration. The bubble velocity variance was found to rapidly increase with gas volume fraction but to reach a nearly constant value for concentrations higher than 1.5% for all cases. The liquid velocity variance was found to increase linearly with gas concentration for large Re; for low Re the increase was at a smaller rate. The variance, normalized with the mean bubble velocity squared, increased as the Reynolds number decreased. Direct comparisons are performed with recent theoretical and computational studies for the same range of conditions.