bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Associated with the Use of and Compliance with the IIA Standards: A Study of Anglo‐culture CAEs
Authors: Abdolmohammadi Mohammad J.
Published: February 2009

Chief audit executives (CAEs) are required to use and comply with The International Standards for the Professional Practice of Internal Auditing (Standards). However, this study finds that 13.5 percent of CAEs in Anglo‐culture countries do not use the Standards. Furthermore, of those who use the Standards a significant number fail to comply with specific standards. Multivariate tests of data from CAEs in this study show that ‘Length of IIA membership’ and ‘Internal auditing certification’ are positively associated with use. Other significant variables are ‘Superseded by local/government regulations or standards,’‘Not perceived as value added by management/board’ and ‘Compliance not expected in the country’ that are inversely related to use. The length of training is also positively associated with compliance, while other significant variables are internal audit certification, ‘Standards are too costly,’‘Not perceived as value added by management/board’ and ‘Inadequate internal audit staff’ that are negatively associated with compliance. The paper ends with a discussion of the implications of these results for practice and research.
Internal Auditing and Consulting Practice: A Comparison between UK/Ireland and Italy
Authors: Selim Georges , Woodward Sally , Allegrini Marco
Published: February 2009

Changes to the definition of internal auditing have increased the scope of internal audit by explicitly including consulting activities. Yet, despite recognition and clarification of the consulting role for internal audit, little subsequent research has been undertaken. Hence, we aim in this article to provide a comparison of the nature, extent and consequences of the definitional change on internal audit consulting activities undertaken by a sample of IIA members in the UK/Ireland and Italy. A comparison of the results of the two self‐completion questionnaire surveys reveals a significant rise in the levels and scope of activities in consulting in both countries but this has been greater in the UK/Ireland. While there are similarities between the countries, more UK/Ireland members are involved in change management and project management, while a majority of Italian members are involved in model design and implementation. In both countries, internal auditors are experiencing both benefits and drawbacks.
Pharmacotherapy in sickle cell disease – state of the art and future prospects
Authors: Hankins Jane , Aygun Banu
Published: February 2009

In the last decade, the care of patients with sickle cell disease (SCD) has undergone important advances with better understanding of disease pathophysiology and improvement in standards of care, especially among paediatric patients. Although many new drugs are currently being investigated and are at different stages of development, the pace of drug discovery and utilization has been slow and suboptimal. Hydroxycarbamide (hydroxyurea) has been investigated and utilized for at least two decades. Hydroxycarbamide’s efficacy has been demonstrated, albeit with different levels of evidence, in paediatric and adult populations, and yet clinician and patient acceptance and use have been far from ideal. In this review we discuss the current usage of hydroxycarbamide and its possible future indications in SCD, as well as the use of new compounds that have very different mechanisms of action, which may prove safe and efficacious when used alone or in combination in patients with SCD.
Lack of association of soluble endothelial protein C receptor and PROCR 6936A/G polymorphism with the risk of venous thromboembolism in a prospective study
Authors: Yamagishi Kazumasa , Cushman Mary , Heckbert Susan R. , Tsai Michael Y. , Folsom Aaron R.
Published: February 2009

Prior case–control studies reported that levels of the soluble form of the endothelial protein C receptor (sEPCR) were strongly controlled by the PROCR 6963A/G polymorphism and higher levels were a risk factor for venous thromboembolism (VTE). We sought to prospectively examine the association of sEPCR and the 6963A/G polymorphism with the incidence of VTE. The Longitudinal Investigation of Thromboembolism Etiology (LITE) pooled data from the Cardiovascular Health Study (CHS) and the Atherosclerosis Risk in Communities (ARIC) Study on men and women aged ≥45 years. A nested case–control study of 458 incident VTE and 1038 controls was performed. sEPCR levels were distributed trimodally according to 6963A/G polymorphism. Adjusting for age, sex and race, there was no overall association between sEPCR level and VTE: odds ratio (OR) [95% confidence interval] for highest versus lowest quartile = 1·17[0·86–1·59]. However, higher sEPCR was associated with VTE in non‐whites (OR = 1·84[1·05–3·22]) and women (OR = 1·51[1·01–2·26]). The 6963A/G polymorphism was not associated with VTE risk (OR = 0·93[0·70–1·25]). In conclusion, sEPCR levels and the PROCR 6963A/G polymorphism were not associated overall with increased risk of VTE.
HHV‐6 DNA throughout the tissues of two stem cell transplant patients with chromosomally integrated HHV‐6 and fatal CMV pneumonitis
Authors: Hubacek Petr , Virgili Anna , Ward Katherine N. , Pohlreich David , Keslova Petra , Goldova Barbora , Markova Marketa , Zajac Miroslav , Cinek Ondrej , Nacheva Elisabeth P. , Sedlacek Petr , Cetkovsky Petr
Published: February 2009

Two patients with the characteristic high human herpesvirus 6 (HHV‐6) DNA loads in peripheral blood caused by chromosomally integrated (CI) virus received a haematopoietic stem cell transplant (HSCT) from a donor without CI HHV‐6. Both patients died in consequence of cytomegalovirus (CMV) pneumonitis. At autopsy, high amounts of CMV DNA were detected in lungs but at much lower levels in other organs. In contrast HHV‐6 DNA was detected at high levels throughout the organs with the exception of donor‐derived haematopoietic tissue. In individuals with chromosomal integration, HHV‐6 DNA is found in every tissue of recipient origin indicating inheritance through the germ line.
Three‐dimensional in vitro cell biology models of ovarian and endometrial cancer
Authors: Grun B.  , Benjamin E.  , Sinclair J.  , Timms J. F.  , Jacobs I. J.  , Gayther S. A.  , Dafou D. 
Published: February 2009

Objectives:  This study aims to establish three‐dimensional (3D) cell culture models of human ovarian and endometrial cancers and to compare biological and morphological characteristics of these models with those of two‐dimensional (2D) models of the same cell lines and the primary tumours.

Methods:  3D models of ovarian and endometrial cancer cell cultures were established using a Rotary Cell Culture System. Immunohistochemical profiling and differential proteomics were used to characterize biological characteristics of multicellular spheroids (MCS) formed from these cultures. These were compared to characteristics of the same cells established in 2D and of the primary tumours from which the cell lines were derived.

Results:  MCSs from 3D cell cultures appeared histologically similar to the primary tumours. Immunohistochemical profiling of multiple markers, including CA125, BCL2 and p53, showed that patterns of protein expression in MCSs resemble those of the primary tumours. Proteomic profiling identified several differentially expressed protein markers between 2D and 3D cultures. These included prohibitin, which was down‐regulated in 3D cultures suggesting cells proliferate less compared to 2D cultures; and VDAC1 and annexin 4, which were up‐regulated in 3D cultures suggesting greater levels of apoptosis in 3D compared to 2D models.

Conclusion:  Establishing 3D models of cancer cell lines is likely to be of value for studying the molecular and biological mechanisms of ovarian/endometrial tumour progression and for testing novel molecular targets for cancer therapy.
Phylogeography of a flooded forest specialist fish from central Amazonia based on intron DNA: the cardinal tetra Paracheirodon axelrodi
Authors: COOKE GEORGINA M. , CHAO NING L. , BEHEREGARAY LUCIANO B.
Published: February 2009

1. Historic and extant landscape structures and environmental conditions are known to influence phylogeographic patterns and population histories in organisms from Amazonia. Recent work suggests that events of the Tertiary Period have played a significant role in generating biodiversity in this exceptionally rich but understudied region. However, species distributions and population structures are also affected by recent environmental and physical changes, especially within highly dynamic ecosystems.

2. The cardinal tetra is a small luminous fish native to the dynamic flooded forest ecosystems of the Rio Negro and Orinoco basins of South America. This very popular aquarium fish represents the single most important species in the ornamental fishery of the Rio Negro, an activity of high socio‐economic value for local riverine communities. Here we use a fine‐scale sampling regime and sequence data from the second intron of the Ribosomal protein S7 (S7 2) to investigate population structure, colonisation history and genealogical relationships in cardinal tetras of the Rio Negro.

3. High levels of S7 2 polymorphisms revealed phylogeographic patterns across several temporal settings that appear associated with the complex dynamics of the region. Our results suggest a long history of isolation and persistence of cardinal tetra populations in the headwaters and upper regions of the Rio Negro and recent events of colonisation within the incipient Rio Negro floodplain. These colonisation events were followed by recent population expansions likely facilitated by the establishment of the extensive Rio Negro floodplain, an anabranching ecosystem of Holocene age.

4. Our reconstruction of the phylogeographic history of cardinal tetras based on S7 2 intron sequence data reflects the complex influence of both geomorphological and climatic events through time in the Rio Negro basin. Our findings also indicate that in order to maintain the cardinal tetra fishery as a sustainable activity for rural Amazonians, the fishery should be restricted to the middle Rio Negro, the region of the basin where population replenishment is more likely to occur.
Inter‐ and intra‐specific differences in the number of larval instars in British populations of 24 species of stoneflies (Plecoptera)
Authors: ELLIOTT J. M.
Published: February 2009

1. Ontogenetic changes during the life cycle of aquatic insects are important not only in life‐history studies but also in evaluating food‐web structure. They require information on the growth and number of larval instars but such information is lacking for many species, including Plecoptera. Therefore, the chief objectives of the present study were to determine inter‐ and intra‐specific differences in the number of larval instars in British populations of 24 species of stoneflies, to test Dyar’s hypothesis that growth followed a geometric progression, and to synthesise this information with previously published values for four British species.

2. Larvae were reared at constant temperatures in the laboratory from eggs from 63 populations (one to six populations per species). First instars from each population were divided into three batches and each batch was reared at one of three constant temperatures. For each species, the rearing temperature and source population had no significant effect on the mean size of each larval instar.

3. The relationship between the geometric mean length of each instar and instar number was well described by an exponential equation (P < 0.001, r2 > 0.9 for all species), thus supporting Dyar’s hypothesis. Only one species, Brachyptera risi, had the same number of instars for males and females (12–13). For the other 15 herbivorous species and the four smaller carnivorous ones, the number of instars was higher for females than males (range 11–16 for males, 12–17 for females). The larger size of the females was due to their additional instars, not a sex difference in growth rates. In contrast, there was a clear growth separation of the sexes after the 9th or 10th instar for the four largest carnivores. The number of larval instars was highest for these four species (range 16–19 for males, 18–23 for females), and females were much larger than males.

4. A multiple regression equation with data from the present and previous studies (n = 27) showed that variability in the mean length of the first instar and the maximum number of larval instars for each species accounted for 88% and 91% of the variability in the mean length of the final instar for males and females, respectively.

5. Values for Plecoptera in other countries were in general agreement with those in the present study, especially in the same families. Two old, but widely quoted, high values are doubtful. The present study and four previous ones provide a sound basis for ontogenetic studies on 28 species of Plecoptera and their role in aquatic ecosystems.
The effect of ocean acidification and temperature on the fertilization and embryonic development of the Sydney rock oyster Saccostrea glomerata (Gould 1850)
Authors: PARKER LAURA M. , ROSS PAULINE M. , O'CONNOR WAYNE A.
Published: February 2009

This study investigated the synergistic effects of ocean acidification (caused by elevations in the partial pressure of carbon dioxide pCO2) and temperature on the fertilization and embryonic development of the economically and ecologically important Sydney rock oyster, Saccostrea glomerata (Gould 1850). As pCO2 increased, fertilization significantly decreased. The temperature of 26 °C was the optimum temperature for fertilization, as temperature increased and decreased from this optimum, fertilization decreased. There was also an effect of pCO2 and temperature on embryonic development. Generally as pCO2 increased, the percentage and size of D‐veligers decreased and the percentage of D‐veligers that were abnormal increased. The optimum temperature was 26 °C and embryonic development decreased at temperatures that were above and below this temperature. Abnormality of D‐veligers was greatest at 1000 ppm and 18 and 30 °C (≥90%) and least at 375 ppm and 26 °C (≤4%). Finally prolonged exposure of elevated pCO2 and temperature across early developmental stages led to fewer D‐veligers, more abnormality and smaller sizes in elevated CO2 environments and may lead to lethal effects at suboptimal temperatures. Embryos that were exposed to the pCO2 and temperature treatments for fertilization and embryonic development had fewer D‐veligers, greater percentage of abnormality and reduced size than embryos that were exposed to the treatments for embryonic development only. Further at the elevated temperature of 30 °C and 750–1000 ppm, there was no embryonic development. The results of this study suggest that predicted changes in ocean acidification and temperature over the next century may have severe implications for the distribution and abundance of S. glomerata as well as possible implications for the reproduction and development of other marine invertebrates.
Water availability controls microbial temperature responses in frozen soil CO2 production
Authors: ÖQUIST MATS G. , SPARRMAN TOBIAS , KLEMEDTSSON LEIF , DROTZ STINA HARRYSSON , GRIP HARALD , SCHLEUCHER JÜRGEN , NILSSON MATS
Published: February 2009

Soil processes in high‐latitude regions during winter are important contributors to global carbon circulation, but our understanding of the mechanisms controlling these processes is poor and observed temperature response coefficients of CO2 production in frozen soils deviate markedly from thermodynamically predicted responses (sometimes by several orders of magnitude). We investigated the temperature response of CO2 production in 23 unfrozen and frozen surface soil samples from various types of boreal forests and peatland ecosystems and also measured changes in water content in them after freezing. We demonstrate that deviations in temperature responses at subzero temperatures primarily emanates from water deficiency caused by freezing of the soil water, and that the amount of unfrozen water is mainly determined by the quality of the soil organic matter, which is linked to the vegetation cover. Factoring out the contribution of water limitation to the CO2 temperature responses yields response coefficients that agree well with expectations based on thermodynamic theory concerning biochemical temperature responses. This partitioning between a pure temperature response and the effect of water availability on the response of soil CO2 production at low temperatures is crucial for a thorough understanding of low‐temperature soil processes and for accurate predictions of C‐balances in northern terrestrial ecosystems.
Replacement therapy for invasive procedures in patients with haemophilia: literature review, European survey and recommendations
Authors: HERMANS C. , ALTISENT C. , BATOROVA A. , CHAMBOST H. , DE MOERLOOSE P. , KARAFOULIDOU A. , KLAMROTH R. , RICHARDS M. , WHITE B. , DOLAN G. ,   on behalf of the European Haemophilia Therapy Standardisation Board
Published: February 2009

Summary.  Although most surgical and invasive procedures can be performed safely in patients with haemophilia, the optimal level and duration of replacement therapy required to prevent bleeding complications have not been established conclusively. For providing more insight into optimal therapy during invasive procedures, a literature review of surgical procedures in patients with haemophilia was conducted. Concomitantly, current practice was surveyed in 26 European Haemophilia Comprehensive Care Centres, representing 15 different countries. The review identified 110 original papers published between 1965 and 2007. Of these, only two studies were randomized controlled trials. Target levels and the duration of replacement therapy in the published studies were as follows. For major orthopaedic surgery: preoperative targets were 80–90%; postoperative targets showed a high degree of variation, with trough levels ranging from 20% to 80%, duration 10–14 days; for liver biopsy, 70–100%, 1–7 days; tonsillectomy: 90–100%, 5–11 days; indwelling venous access device insertion: 100%, 3–10 days; circumcision: 50–60%, 2–4 days; dental surgery: 30–50%, single treatment. With the exception of dental surgery, current practice in Europe, as assessed by the survey, was largely in agreement with published data. In conclusion, this study provides both a comprehensive review and a large survey of replacement therapy in patients with haemophilia undergoing invasive procedures; these data have informed the consensus practical treatment recommendations made in this paper. This study highlights the need for better‐designed studies in order to better define minimal haemostatic levels of replacement therapy and optimal treatment duration.
Bone morphogenetic protein‐6 induces the expression of inducible nitric oxide synthase in macrophages
Authors: Kwon Seok J. , Lee Geun T. , Lee Jae‐Ho , Kim Wun J. , Kim Isaac Y.
Published: February 2009

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor‐β (TGF‐β) superfamily. In the present study, we investigated the effect of BMPs on the production of inducible nitric oxide synthase (iNOS) in the murine macrophage cell line, RAW 264.7, and in mouse peritoneal macrophages. Among the BMPs, only BMP‐6 induced iNOS expression in a time‐dependent and dose‐dependent manner in both cell types. Induction of iNOS was inhibited by both cycloheximide and actinomycin D, indicating that the induction of iNOS expression by BMP‐6 requires new protein synthesis. Mechanistic studies revealed that the BMP‐6‐induced iNOS expression requires both Smads and nuclear factor‐kappa B (NF‐κB) signalling pathways. Furthermore, induction of interleukin‐1β (IL‐1β) was necessary for iNOS induction by BMP‐6. These observations suggest that BMP‐6 stimulates macrophages to produce iNOS through IL‐1β via Smad and NF‐κB signalling pathways and that BMP‐6 may be an important regulator of macrophages.
Osteopontin is not crucial to protective immunity during murine tuberculosis
Authors: Van Der Windt Gerritje J. W. , Wieland Catharina W. , Wiersinga Willem J. , Florquin Sandrine , Van Der Poll Tom
Published: February 2009

Upon infection with Mycobacterium (M.) tuberculosis, the development of a strong T helper 1 (Th1)‐mediated adaptive immune response is considered as being most important for containment of the infection. Osteopontin (OPN) is a phosphorylated glycoprotein that is chemotactic for inflammatory cells and has been implicated in the induction of Th1 responses and granulomatous disease. We tested the hypothesis that OPN facilitates protective immunity during M. tuberculosis infection using wild‐type (WT) and OPN knockout (KO) mice in a model of pulmonary tuberculosis. OPN expression was up‐regulated in alveolar macrophages and lymphoid cells during M. tuberculosis infection. There were no significant differences in bacterial outgrowth, inflammation or recruitment of lymphocytes, macrophages and polymorphonuclear cells in the lungs after 2 and 5 weeks of infection. However, the numbers of CD4+ and CD8+ T cells were reduced in the absence of OPN 5 weeks after infection. Similar concentrations of cytokine were observed in lungs from both WT mice and OPN KO mice; however, there was a trend towards decreased levels of interferon‐γ (IFN‐γ) in OPN KO mice 5 weeks after infection. Despite an unaltered immune response in the early phase of tuberculosis, OPN KO mice had a modest survival advantage. Of note, both pulmonary bacterial loads and lung inflammation were reduced in these mice 31 weeks after infection. These data suggest that OPN is not crucial for protective immunity upon M. tuberculosis infection and during the late phase of tuberculosis may even be detrimental for the host.
Local irradiation of murine melanoma affects the development of tumour‐specific immunity
Authors: Liao Yu‐Pei , Wang Chun‐Chieh , Schaue Dörthe , Iwamoto Keisuke S. , McBride William H.
Published: February 2009

Radiation therapy affects the immune system. In addition to killing radiosensitive immune cells, it can induce functional changes in those cells that survive. Our recent studies showed that the exposure of dendritic cells (DCs) to radiation in vitro influences their ability to present tumour antigen in vivo. Here we show that local radiation therapy of B16 melanoma tumours inhibits the development of systemic immunity to the melanoma antigen MART‐1. This inhibition could not be overcome by intratumoral injection of DCs expressing human MART‐1 after radiation therapy, suggesting that a form of immune suppression might have developed. On the other hand, injection of MART‐expressing DCs prior to tumour irradiation was able to prevent inhibition from developing. These results suggest that local radiation therapy may block the generation of immunity under some circumstances and that strategies may be required to prevent this and allow radiation‐induced cell death to translate fully into the development of systemic immunity.
Conceptualizing and measuring the virtuality of teams
Authors: Schweitzer Linda , Duxbury Linda
Published: February 2009

Virtual teams (VTs) are teams whose members do not share a common workspace all of the time, and must therefore collaborate using communication and collaboration tools such as email, videoconferencing, etc. Although the body of research on VTs is quickly expanding, to date, the field has yet to produce a comprehensive and coherent foundation upon which future research can be based, and empirical findings based on a substantive sample of real VTs remain limited at this time. This study fills a void in the VT literature with respect to defining and operationalizing the construct of degree of virtuality, and responds to calls for research that studies ongoing VTs, under real conditions. Data were collected from 30 VTs working in a Canadian technology‐based organization.

Degree of virtuality was defined to include three dimensions: the proportion of work time that the VT members spend working apart (team time worked virtually), the proportion of the team's members who work virtually (member virtuality) and the degree of separation of the team's members (distance virtuality). The VTs in this study were found to have varying degrees of virtuality, and although the three dimensions were not highly intercorrelated, all were found to be significantly correlated to variables that have been previously linked to VT effectiveness. The correlations were all in the expected direction (negative), indicating that higher degrees of virtuality are associated with perceived decreases in the quality of team interactions and performance. The results of this research would suggest that the more that teams move away from the proximate form, the more the traditional measures of team effectiveness are negatively impacted.
Strategies for caries risk assessment in children and adolescents at public dental clinics in a Swedish county
Authors: SARMADI ROXANA , GABRE PIA , GAHNBERG LARS
Published: February 2009

Background.  Since caries prevalence has decreased and become polarized, high‐risk preventive strategies have been widely adopted. The underlying factors leading to assessment and management of caries risk are poorly understood.

Aim.  The aim of this study was to identify the factors forming the basis for dentist's caries risk assessment in dental care for children and adolescents.

Design.  From all 3372 children in a Swedish county identified as at high risk for developing caries, a sample of dental records from 432 children, aged 3–19 years, were randomly selected to be analysed in the study. Information about medical and social history, dental status, dietary habits, oral hygiene, and salivary data was obtained from the records.

Results.  The results show that the only data registered in the majority of the dental records were dental status from the clinical examination and bitewing radiographs. In approximately half of the dental records, medical history and data concerning oral hygiene were registered. Dental history and dietary habits were noted in approximately 25% of the dental records, whereas other risk factors/indicators were occasionally registered.

Conclusions.  Dentists mainly base their caries risk assessments on past caries experience, a reliable risk indicator for assessing the risk of being affected by caries again. In children with no experience of caries, knowledge of other risk factors/indicators needs to be available to perform a caries risk assessment. In this study, documentation of such knowledge was strongly limited.
The lifestyle of patients with chronic fatigue syndrome and the effect on fatigue and functional impairments
Authors: Goedendorp M. M. , Knoop H. , Schippers G. M. , Bleijenberg G.
Published: February 2009

Background:  Little is known about the lifestyle of patients with chronic fatigue syndrome (CFS) and its influence on symptoms of CFS. The present study aimed to investigate the lifestyle of patients with CFS, and to assess whether lifestyle factors are related to fatigue and functional impairments.

Methods:  Two hundred and forty‐seven patients fulfilling the Center for Disease Control criteria for CFS were included. Validated questionnaires were used to collect data on lifestyle factors, smoking, intake of alcohol, fat, fibres, fruit and vegetables, body mass index (BMI), fatigue severity and functional impairments.

Results:  Of the CFS patients, 23% smoked, 32% had an unhealthy BMI, and none had an unhealthy alcohol intake. A majority had an unhealthy food intake: 70% had unhealthy fat, fruit and vegetable intake, and 95% had unhealthy fibre intake. Compared with the general Dutch population, significantly fewer CFS patients were overweight. Significantly more female CFS patients abstained from alcohol, and fewer male CFS patients smoked. Unhealthy lifestyle factors were not significantly associated with fatigue severity or functional impairments.

Conclusions:  CFS patients tend to lead a healthier lifestyle compared to the general Dutch population. However, no relationship was found between lifestyle factors and fatigue severity and functional impairments in CFS.
Changes in biochemical indices of bone metabolism in post‐menopausal women following a dietary intervention with fortified dairy products
Authors: Manios Y. , Moschonis G. , Panagiotakos D. B. , Farajian P. , Trovas G. , Lyritis G. P.
Published: February 2009

Background:  In southern Europe, calcium supplementation alone is a common practice for osteoporosis prevention. The present study aimed to examine whether calcium supplementation alone could be as effective in achieving favourable changes on bone metabolism indices of Greek post‐menopausal women as a holistic dietary approach combining consumption of dairy products fortified with calcium and vitamin D3 and nutrition counselling sessions for five winter months.

Methods:  A sample of 101 post‐menopausal women was randomised to a dairy intervention group (IG: n = 39), receiving approximately 1200 mg of calcium and 7.5 μg of vitamin D3 per day via fortified dairy products and attending biweekly nutrition counselling sessions; a calcium‐supplemented group (SG: n = 26) receiving a total of 1200 mg calcium per day; and a control group (CG: n = 36).

Results:  Regarding insulin‐like growth factor (IGF)‐I, a higher increase was observed for the IG compared to the changes in the CG and the SG (P = 0.049). Regarding serum parathyroid hormone (PTH) levels, the increase observed in the CG was higher than the changes observed in the other two groups but the differences were of marginal significance (P = 0.055). No significant differences were observed among groups regarding the changes in serum osteocalcin and type I collagen cross‐linked C‐telopeptide levels.

Conclusions:  The application of a holistic intervention approach combining nutrition counselling and consumption of fortified dairy products for five winter months induced some more favourable changes in IGF‐I and PTH levels compared to calcium supplementation alone. Intervention periods longer than 5 months might be required to achieve significant differences among groups for bone remodelling biomarkers as well.
Adults with intellectual disabilities: prevalence, incidence and remission of aggressive behaviour and related factors
Authors: Cooper S.‐A. , Smiley E. , Jackson A. , Finlayson J. , Allan L. , Mantry D. , Morrison J.
Published: February 2009

Introduction  Aggressive behaviours can be disabling for adults with intellectual disabilities (ID), with negative consequences for the adult, their family and paid carers. It is surprising how little research has been conducted into the epidemiology of these needs, given the impact they can have. This study investigates point prevalence, 2‐year incidence and 2‐year remission rates for aggressive behaviour (physically aggressive, destructive and verbally aggressive), and it investigates which factors are independently associated with aggressive behaviour.

Methods  All adults with ID – within a geographically defined area of Scotland, UK – were recruited to a longitudinal cohort. At baseline, assessments were undertaken of demography, lifestyle, supports, development, problem behaviours, disabilities and physical and mental health. These were repeated for a 2‐year period.

Results  At baseline, the participation rate was 1023 (65.5%). After 2 years, the cohort retention was 651 adults. The point prevalence of Diagnostic Criteria for Psychiatric Disorders for Use with Adults with Learning Disabilities/Mental Retardation (DC‐LD) aggressive behaviour was 9.8% (95% confidence interval = 8.0–11.8%), 2‐year incidence was 1.8%, and 2‐year remission rate from all types of aggressive behaviour meeting DC‐LD criteria was 27.7%. The factors independently associated with aggressive behaviours were lower ability, female gender, not living with a family carer, not having Down syndrome, having attention‐deficit hyperactivity disorder and having urinary incontinence. Incidence of aggressive behaviour meeting DC‐LD criteria in adult life is similar to that for each of psychotic, anxiety and organic disorders.

Conclusions  Aggressive behaviour is common among adults with ID, but contrary to previous suggestions, more than a quarter remit within the short to medium term. This is important knowledge for professionals as well as the person and her/his family and paid carers. There is much yet to learn about the mechanisms underpinning aetiology and maintenance of aggressive behaviour in this population, and exploratory epidemiological investigations such as this have a role to play in progressing research towards further hypothesis testing and trials to influence clinical practice, service development and policy.
Fecundity selection predicts Bergmann's rule in syngnathid fishes
Authors: WILSON ANTHONY B.
Published: February 2009

The study of latitudinal increases in organismal body size (Bergmann's rule) predates even Darwin's evolutionary theory. While research has long concentrated on identifying general evolutionary explanations for this phenomenon, recent work suggests that different factors operating on local evolutionary timescales may be the cause of this widespread trend. Bergmann's rule explains body size variation in a diversity of warm‐blooded organisms and there is increasing evidence that Bergmann's rule is also widespread in ectotherms. Bergmann's rule acts differentially in species of the Syngnathidae, a family of teleost fishes noted for extreme adaptations for male parental care. While variation in body size of polygamous Syngnathus pipefish is consistent with Bergmann's rule, body size is uncorrelated with latitude in monogamous Hippocampus seahorses. A study of populations of Syngnathus leptorhynchus along a natural latitudinal and thermal gradient indicates that increases in body size with latitude maintain the potential reproductive rate of males despite significant decreases in ambient temperatures. Polygyny is necessary in order to maximize male reproductive success in S. leptorhynchus, suggesting a possible a link between fecundity selection and Bergmann's rule in this species.
Multiple introductions of the Spiroplasma bacterial endosymbiont into Drosophila
Authors: HASELKORN TAMARA S. , MARKOW THERESE A. , MORAN NANCY A.
Published: February 2009

Bacterial endosymbionts are common in insects and can have dramatic effects on their host's evolution. So far, the only heritable symbionts found in Drosophila have been Wolbachia and Spiroplasma. While the incidence and effects of Wolbachia have been studied extensively, the prevalence and significance of Spiroplasma infections in Drosophila are less clear. These small, gram‐positive, helical bacteria infect a diverse array of plant and arthropod hosts, conferring a variety of fitness effects. Male‐killing Spiroplasma are known from certain Drosophila species; however, in others, Spiroplasma appear not to affect sex ratio. Previous studies have identified different Spiroplasma haplotypes in Drosophila populations, although no extensive surveys have yet been reported. We used a multilocus sequence analysis to reconstruct a robust Spiroplasma endosymbiont phylogeny, assess genetic diversity, and look for evidence of recombination. Six loci were sequenced from over 65 Spiroplasma‐infected individuals from nine different Drosophila species. Analysis of these sequences reveals at least five separate introductions of four phylogenetically distinct Spiroplasma haplotypes, indicating that more extensive sampling will likely reveal an even greater Spiroplasma endosymbiont diversity. Patterns of variation in Drosophila mitochondrial haplotypes in Spiroplasma‐infected and uninfected flies imply imperfect vertical transmission in host populations and possible horizontal transmission.
Community composition, host range and genetic structure of the fungal entomopathogen Beauveria in adjoining agricultural and seminatural habitats
Authors: MEYLING NICOLAI V. , LÜBECK METTE , BUCKLEY ELLEN P. , EILENBERG JØRGEN , REHNER STEPHEN A.
Published: February 2009

Although intensively investigated for biological control of insect pests, little is known about the ecology of the fungal entomopathogenic genus Beauveria in natural or agricultural habitats. In this study, we used molecular phylogenetic and genotypic information to infer species diversity, reproductive potential and genetic structure of Beauveria occurring within a single arable field and bordering hedgerow in Denmark. Isolates were sampled from cultivated field and hedgerow soils, from insects harbouring latent fungal infections, and from the phylloplanes of three plant species common in the hedgerow flora. A nuclear phylogeny of this local Beauveria assemblage resolved seven phylogenetic species, including (i) five phylogenetic species within Beauveria bassiana sensu stricto; (ii) Clade C, a taxonomically uncharacterized species that is morphologically indistinguishable but phylogenetically distant from B. bassiana s.s.; and (iii) Beauveria brongniartii. All seven species were present throughout the hedgerow habitat, including as infections in insects. Significantly, only B. bassiana s.s. phylogenetic species Eu_1 was isolated from tilled soils. Mating type polymerase chain reaction assays demonstrated that all five B. bassiana s.s. phylogenetic species possess bipolar outcrossing mating systems. Of these, only the Eu_1 population contained two mating types; however, a 31:2 skew in MAT1:MAT2 mating types suggests a low frequency of sexual reproduction in this population. The four remaining B. bassiana s.s. phylogenetic species were fixed for single mating types and these populations are evidently clonal. Multilocus microsatellite genotyping revealed polymorphism in all five phylogenetic species of B. bassiana s.s.; however, all show evidence of clonal genetic structure.
Major histocompatibility complex variability in the clonal Amazon molly, Poecilia formosa: is copy number less important than genotype?
Authors: LAMPERT K. P. , FISCHER P. , SCHARTL M.
Published: February 2009

The evolution of sex is still a major unsolved puzzle in biology. One of the most promising theoretical models to answer this question is the Red Queen hypothesis. The Red Queen hypothesis proposes a fast adaptation of pathogens to common genotypes and therefore a negative frequency‐dependent selection against common genotypes. Clonal organisms should be especially endangered when co‐occurring with closely related sexual species. In this context, major histocompatibility (MHC) genes have been discussed to be auspicious candidates that could provide the genetic basis on which selection for immune competence could act. In this study, we investigated MHC variability in a clonal teleost fish: the Amazon molly, Poecilia formosa. The Amazon molly is an ideal candidate to test the Red Queen hypothesis as it is a clonal species but co‐occurs with a closely related sexual species and should therefore be especially susceptible to pathogen infection. We found that allele numbers did in general not differ between sexual and clonal ‘species’ but that genotypic variability is reduced in the clonally reproducing fish, especially in the polyploids. We conclude that in clonal organisms, genotype frequency might be more important for immune competence than MHC allele number. Amazon mollies and their co‐occurring parental species clearly fulfil a prerequisite of the Red Queen hypothesis and should therefore provide an ideal system to experimentally test this basic principle probably underlying the evolution of sex.
Glycogen contributes to the environmental persistence and transmission of Vibrio cholerae
Authors: Bourassa Lori , Camilli Andrew
Published: February 2009

Pathogenic Vibrio cholerae cycle between the nutrient‐rich human intestinal tract and nutrient‐poor aquatic environments and currently few bacterial factors are known that aid in the transition between these disparate environments. We hypothesized that the ability to store carbon as glycogen would facilitate both bacterial fitness in the aquatic environment and transmission of V. cholerae to new hosts. To investigate the role of glycogen in V. cholerae transmission, we constructed mutants that cannot store or degrade glycogen. Here, we provide the first report of glycogen metabolism in V. cholerae and demonstrate that glycogen prolongs survival in nutrient‐poor environments that are known ecological niches of V. cholerae, including pond water and rice‐water stool. Additionally, glycogen contributes to the pathogenesis of V. cholerae in a transmission model of cholera. A role for glycogen in the transmission of V. cholerae is further supported by the presence of glycogen granules in rice‐water stool vibrios from cholera patients, indicating that glycogen is stored during human infection. Collectively, our findings indicate that glycogen metabolism is critical for V. cholerae to transition between host and aquatic environments.
A new direction for manganese homeostasis in bacteria: identification of a novel efflux system in Streptococcus pneumoniae
Authors: Jakubovics Nicholas S. , Valentine Ruth A.
Published: February 2009

The ability to control intracellular levels of transition metals such as Mn2+, Fe2+ and Zn2+ is critical for the virulence of many pathogenic bacteria. In this issue of Molecular Microbiology, Rosch et al. describe the first identification of a Mn2+ efflux system in bacteria, MntE of Streptococcus pneumoniae, and demonstrate that it is required for virulence in an animal model. Disruption of the mntE gene leads to widespread transcriptional changes that are distinct from responses to extracellular Mn2+. These findings reveal, for the first time, that a bacterial trace metal efflux system plays a role in disease. Thus, MntE represents a new lead for the development of antimicrobials specifically aimed at disrupting microbial metal ion homeostasis.
Role of the manganese efflux system mntE for signalling and pathogenesis in Streptococcus pneumoniae
Authors: Rosch Jason W. , Gao Geli , Ridout Granger , Wang Yong‐Dong , Tuomanen Elaine I.
Published: February 2009

The ability of bacteria to sense and respond to both environmental and intracellular metal concentrations plays an important role in pathogenesis. The acquisition of manganese is vital for the virulence of several bacterial species. Although manganese uptake systems have been well studied in bacteria, no manganese efflux system has yet been identified. In this study we have identified a cation diffusion facilitator (CDF) protein (Sp1552) of unknown substrate specificity that functions as a manganese export system in Streptococcus pneumoniae. We designated the gene for this manganese efflux system mntE and found that the mutant strain was highly sensitive to manganese stress. Although the mutant was more resistant to oxidative stress and produced more H2O2 and pili, it had reduced virulence in a murine model of infection, indicating that manganese export plays a role in host pathogenesis. There was a distinct differential transcriptional response to extracellular and intracellular manganese accumulation. Our study indicates that manganese efflux is required for invasive disease and may provide a useful antimicrobial target to devise future therapeutics.
A haplotype in the inducible T‐cell tyrosine kinase is a risk factor for seasonal allergic rhinitis
Authors: Benson M. , Mobini R. , Barrenäs F. , Halldén C. , Naluai Å. T. , Säll T. , Cardell L. O.
Published: February 2009

Background:  Identification of disease‐associated single nucleotide polymorphisms (SNPs) in seasonal allergic rhinitis (SAR) may be facilitated by focusing on genes in a disease‐associated pathway.

Objective:  To search for SNPs in genes that belong to the T‐cell receptor (TCR) pathway and that change in expression in allergen‐challenged CD4+ cells from patients with SAR.

Methods:  CD4+ cells from patients with SAR were analysed with gene expression microarrays. Allele, genotype and haplotype frequencies were compared in 251 patients and 386 healthy controls.

Results:  Gene expression microarray analysis of allergen‐challenged CD4+ cells from patients with SAR showed that 25 of 38 TCR pathway genes were differentially expressed. A total of 62 SNPs were analysed in eight of the 25 genes; ICOS, IL4, IL5, IL13, CSF2, CTLA4, the inducible T‐cell tyrosine kinase (ITK) and CD3D. Significant chi‐squared values were identified for several markers in the ITK kinase gene region. A total of five SNPs were nominally significant at the 5% level. Haplotype analysis of the five significant SNPs showed increased frequency of a haplotype that covered most of the coding part of ITK. The functional relevance of ITK was supported by analysis of an independent material, which showed increased expression of ITK in allergen‐challenged CD4+ cells from patients, but not from controls.

Conclusion:  Analysis of SNPs in TCR pathway genes revealed that a haplotype that covers a major part of the coding sequence of ITK is a risk factor for SAR.
Opposite gene by environment interactions in Karelia for CD14 and CC16 single nucleotide polymorphisms and allergy
Authors: Zhang G. , Khoo S.‐K. , Laatikainen T. , Pekkarinen P. , Vartiainen E. , Von Hertzen L. , Hayden C. M. , Goldblatt J. , Mäkelä M. , Haahtela T. , Le Souëf P. N.
Published: February 2009

Background:  Finnish Karelians have a higher prevalence of allergic disease than Russian Karelians. As both populations are generally from the same ethnic group, the Karelian population offers a unique opportunity to analyse genetic and allergic disease interactions between ‘Western’ and ‘Eastern’ environments.

Objectives:  We investigated associations between allergic diseases and CD14 and CC16 polymorphisms in Finnish vs Russian Karelian women.

Methods:  Adult female Karelians (330 Finnish and 274 Russian) were recruited, examined for a range of symptoms and conditions including rhinitis, itchy rash, asthma and atopy and genotyped for CD14 C‐159T and CC16 A38G.

Results:  For both CD14 C‐159T and CC16 A38G, the risk allele for atopic phenotypes in Finnish Karelia was the protective allele in Russian Karelia. For CD14 C‐159T, an interactive effect on ever itchy rash (Pinteraction = 0.004), itchy rash <12 mo (Pinteraction = 0.001) and dry cough at night in the past 12 months (<12 months) (Pinteraction = 0.011) was found; the risk allele was C in Russians and T in Finns. For CC16 A38G, an interaction was significant for ever rhinitis (Pinteraction = 0.006), rhinitis <12 mo (Pinteraction = 0.004), and marginally significant for ever hayfever (Pinteraction = 0.07), allergic eye symptoms <12 mo (Pinteraction = 0.09); their risk allele was G in Russians and A in Finns.

Conclusion:  An Eastern vs Western environment appears to exert an effect via opposite alleles on risk of allergic diseases in adult women.