bluuebunny/crossref_metadata_2025 huggingface dataset:
Childhood death auditing to improve paediatric care
Authors: Krug Angelika , Patrick Mark , Pattinson Robert C. , Stephen Cindy
Published: June 2006

Aim: Field‐testing a paediatric mortality audit system at eight sites in South Africa to assess its feasibility, to collect local data on common causes of death in children under 5 y, and to determine health system failure, missed opportunities of intervention and substandard care (modifiable factors). Methods: The study tested the Under‐5 Healthcare Problem Identification Programme (U5PIP). The sites represent different levels of paediatric healthcare. Study period: 1 September 2003–31 August 2004. Study population: Under‐5 patients admitted to study hospitals. Cases: Under‐5 patients who died in study hospitals. Results: In total, 1532 under‐5 deaths occurred, representing a case‐fatality rate of 7.8%. Main causes of death were lower respiratory tract infections (33%), gastroenteritis (15%) and septicaemia (12%). Sixty per cent of the deaths were HIV/AIDS related. Sixty‐nine per cent of children who died were underweight. Administrative modifiable factors were present in 31% of deaths. Clinical personnel‐related modifiable factors were detected in 26% at the clinic level and in 33–37% at the hospital level.

Conclusion: The U5PIP is feasible for ongoing mortality reviews by paediatric teams as part of routine work. Information on common causes of death and modifiable factors in this study focus on the impact of HIV/AIDS, malnutrition and resource allocation, and can be used for interventions to improve paediatric healthcare.
Determinants of compliance with methylphenidate therapy in children
Authors: HUGTENBURG JACQUELINE G. , WITTE IVO , HEERDINK EIBERT R.
Published: June 2006

Aim: To get more insight into factors that influence compliance with the use of methylphenidate. Methods: 22 pharmacies detected children who used methylphenidate. Their parents were sent a questionnaire on the use of methylphenidate. In a case‐control study, the influence of patient‐ and drug‐related factors on compliance, as reported by parents, was determined. Results: Parents returned 117 (75%) of 157 questionnaires sent out. Of these, 47.8% of the children missed a dose two times a month or more. Forgetting to take the medication (87.9%) was the most important reason. The case‐control study showed that children of 16–18 y were more likely to miss doses. Other patient‐ and drug‐related factors did not influence the missing of doses.

Conclusion: A number of known determinants for compliance do not influence the missing of doses of methylphenidate. With about 80% of the parents reporting that their child missed doses of methylphenidate less than 5 times per month, compliance was quite good for the majority of the children.
Analysis of Kawasaki disease showing elevated antibody titres of Yersinia pseudotuberculosis
Authors: TAHARA MASAHIRO , BABA KIYOSHI , WAKI KENJI , ARAKAKI YOSHIO
Published: June 2006

Aim: To elucidate a clinical difference between patients with Kawasaki disease documented with Yersinia pseudotuberculosis infection and patients with Kawasaki disease without Yersinia pseudotuberculosis infection. Patients and methods: From January 1985 to July 2004, 452 patients were diagnosed with Kawasaki disease. Forty‐two patients had elevated antibody titres of Yersinia pseudotuberculosis and/or positive stool culture (Yersinia‐positive group). Three hundred and thirty patients had no elevated antibody titres (Yersinia‐negative group). We compared the clinical characteristics retrospectively. Results: The age of onset in the Yersinia‐positive group (3.05±2.20 y) was significantly higher than that in the Yersinia‐negative group (2.31±2.05 y) (p=0.03). The age‐adjusted statistical analysis demonstrated that the incidence of coronary artery lesions (dilatations plus aneurysms) in the Yersinia‐positive group (22/42, 52.4%) was significantly higher than in the Yersinia‐negative group (105/330, 31.8%) (p=0.001), and the incidence of additional administration of immunoglobulin in the Yersinia‐positive group (13/36, 36.1%) was significantly higher than in the Yersinia‐negative group (41/256, 16.0%) (p=0.004).

Conclusion: Our data suggest that Yersinia pseudotuberculosis infection might play a role in the developing mechanism of poor response to therapy and the tendency to develop coronary artery lesions in Kawasaki disease patients.
Successful management of primary hypomagnesaemia with high‐dose oral magnesium citrate: A case report
Authors: BIRCAN IFFET , TURKKAHRAMAN DOGA , DURSUN OGUZ , KARAGUZEL GULAY
Published: June 2006

We report a 40‐d‐old female infant who presented to our clinic with afebrile generalized convulsive episodes due to severe hypomagnesaemia with secondary hypocalcaemia. Laboratory investigations revealed mild hypoparathyroidism, which was to return normal following magnesium (Mg) treatment, and normal fractional renal excretion of Mg (0.8%). After the diagnosis of primary hypomagnesaemia was established, the patient was discharged with oral Mg subcarbonate and intramuscular Mg sulphate. On regular follow‐up until the age of 4 y, the child was asymptomatic. Mean serum calcium levels remained normal, while mean serum Mg levels remained subnormal. During this 4‐y period, oral Mg dose was gradually increased while the doses and frequency of administration of parenteral Mg were decreased. Additionally, oral Mg subcarbonate was switched to Mg citrate because of its side effects. Finally, parenteral Mg was discontinued as the dosage of oral Mg supplementation reached a level of 90 mg/kg/d elemental Mg citrate, without any gastrointestinal side effects. Some screening tests were performed to evaluate the complications of chronic hypomagnesaemia. Bone age, bone densitometry, ECG and renal sonography were all normal. Our patient is now 5 y old and symptom free.

Conclusion: Treatment with high doses of oral Mg was successful in keeping our patient symptom free and normocalcaemic, but cannot fully normalize serum Mg concentrations. Thus, during the regular follow‐up of patients with primary hypomagnesaemia, the main target must be to increase oral Mg supplementation to a dosage which can maintain normocalcaemia rather than normomagnesaemia.
Medical follow‐up visits in adults 5–25 years after treatment for childhood acute leukaemia, lymphoma or Wilms’ tumour
Authors: Arvidson Johan , Söderhäll Stefan , Eksborg Staffan , Björk Olle , Kreuger Anders
Published: June 2006

Aim: One aspect of organizing medical follow‐up for adult survivors of childhood cancer is to determine to what extent the former patient experiences a need for health services. In the present paper, we studied how the healthcare needs, both subjectively and objectively, were fulfilled for our former patients. Methods: 335 survivors over 18 y of age, with a follow‐up time of more than 5 y after completion of therapy, were sent a questionnaire probing their present use of health services. Results: The response rate was 73%. A majority (60%) of the survivors had no regular follow‐up visits, and 42% of these reported that they missed not having one. More than one third were thus far dissatisfied with the follow‐up programme. Only 3% of those who had regular follow‐ups found them “unnecessary”. Complaints subjectively related to their diseases or treatments were reported by 47%. Out of all responders, 34% did not miss having regular follow‐up visits. Neither perceived disease‐related complaints nor radiation therapy was a predictor for having a scheduled follow‐up visit.

Conclusion: In the absence of a long‐term follow‐up programme, many survivors were not receiving proper medical healthcare, whether from their perspective or from a professional one.
Quality of life in neurologically healthy children with urinary incontinence
Authors: GLADH GUNILLA , ELDH MONICA , MATTSSON SVEN
Published: June 2006

Aim: To bring forward the arguments for active treatment of urine incontinence in otherwise healthy children, a quality‐of‐life (QoL) study was performed. Subjects and methods: A self‐rating QoL questionnaire, child‐adjusted and validated, was completed by 120 neurologically healthy children, aged 6–16 y, with urinary incontinence. Another 239 age‐matched children made up a control group. The two groups were compared both totally and in age‐related subgroups (6–8, 9–12, >12 y) concerning the index for all questions, for universal parts (without questions dealing with incontinence) as well as for specific key domains. Results: The patient group had a significantly lower index than the control group both with and without items related to incontinence (p <0.0001). Social situation, self‐esteem and self‐confidence were most influenced, particularly in the youngest children. Thirty‐one children (13%) of the control group reported incontinence and did not score their QoL as good as their continent peers but better than the study patients.

Conclusion: From the quality‐of‐life aspects, the study supports active treatment of urinary incontinence in children already at younger ages.
Effect of aerosolized rhDNase (Pulmozyme®) on pulmonary colonization in patients with cystic fibrosis
Authors: Frederiksen Birgitte , Pressler Tacjana , Hansen Annelise , Koch Christian , Høiby Niels
Published: June 2006

Background: Aerosolized recombinant human deoxyribonuclease (rhDNase I (Pulmozyme®)) has previously been shown to increase pulmonary function and reduce exacerbations of respiratory symptoms in cystic fibrosis (CF) patients with moderate to severe reduction in pulmonary function. Aim: To analyse whether aerosolized Pulmozyme® could reduce the number of bacterial infections in the lower respiratory airways of CF patients without chronic pulmonary infection. Methods: Patients were randomized either to aerosolized Pulmozyme® 2½ mg once daily or to no rhDNase treatment. The study period was 1 y, and the study was blinded for the Department of Clinical Microbiology. Results: Overall, the number of positive cultures was significantly higher in the untreated group (82%) compared with the treated group (72%) (p<0.05). The most striking difference was found for Staphylococcus aureus, with a prevalence of 30% in the untreated group compared with 16% in the treated group (χ2 test, p<0.0001). Pulmonary function (FEV1) in the treated group showed a significant increase of 7.3% compared to 0.9% in the untreated group (p<0.05).

Conclusion: Long‐term DNase treatment was beneficial to CF patients without chronic lower respiratory tract infection, leading to reduced demand for antibiotics and to improved lung function.
The availability and accessibility of basic paediatric resuscitation equipment in primary healthcare centres: Cause for concern?
Authors: GNANALINGHAM MUHUNTHA G. , HARRIS GAYLE , DIDCOCK ELIZABETH
Published: June 2006

Background: Paediatric emergencies in primary healthcare centres are serious events that occur more commonly than envisaged. However, at present, these centres appear to lack the training and equipment to manage common paediatric emergencies. Aim: To determine the availability and accessibility of basic resuscitation equipment in primary healthcare centres. Methods: A questionnaire survey of 27 primary healthcare centres within the Nottingham City region determined the availability and accessibility of basic paediatric resuscitation equipment and algorithms. Results: No practice had all 21 basic resuscitation items, with 59% of practices having ≤10 of these items. Only 11% of practices had all seven basic airway and breathing resuscitation items, with 52% of practices having ≤4 items. No practice had all eight basic items for circulation management, with 82% of practices having ≤4 of these items. Only two practices had all six basic drug items, with 85% of practices having ≤3 of these items. Only 26% of practices had algorithms for paediatric basic life support and common emergencies, and only 30% of practices kept their resuscitation equipment together. In the last 5 y, less than a fifth of general practitioners were trained in paediatric resuscitation.

Conclusion: Primary healthcare centres appear to lack the training and equipment to manage common paediatric emergencies. We recommend standardization of equipment and algorithms, training and assessment of key personnel, and critical incident reporting within primary healthcare centres.
Familial idiopathic atrial fibrillation with fetal bradyarrhythmia
Authors: ABURAWI ELHADI , THOMSON JOHN , BLACKBURN MICHAEL
Published: June 2006

A woman presented at 28 wk gestation with fetal bradycardia 50 bpm, which persisted until 42 wk when an asymptomatic male baby was delivered. Electrocardiograph at 3 wk of age documented an incessant atrial fibrillation with slow ventricular response. He continued to be asymptomatic, but on follow‐up at 16 y of age, 24‐h Holter monitor showed a heart rate of 23 bpm and pauses of up to 6 s when a VVIR programme endocardial pacing system was employed. ECG carried out on his asymptomatic father showed intermittent atrial fibrillation, again with a slow ventricular response.

Conclusion: Atrial fibrillation is extremely rare in children with normal cardiac structure. Most instances of fetal bradycardia are caused by congenital complete heart block. Other rare causes such as atrial fibrillation with fetal bradycardia need to be considered. This case might be a familial disorder and looks to have a good prognosis.
Toll‐like receptor signaling and IRF transcription factors
Authors: Honda Kenya , Taniguchi Tadatsugu
Published: June 2006

Interferon regulatory factors (IRFs) were originally discovered in the context of type I interferon (IFN‐α/β) gene induction, and subsequent studies on these transcription factors have revealed their remarkable functional diversity in regulating immune systems. Indeed, the critical involvement of IRF members in innate and adaptive immune responses has recently gained much attention, particularly with the recent discovery of Toll‐like receptors (TLRs) and analyses of their critical functions in linking the innate and adaptive immune responses.
iubmb Life, 58: 290‐295, 2006
Stochastic proton pumping ATPases: From single molecules to diverse physiological roles
Authors: Nakanishi‐Matsui Mayumi , Futai Masamitsu
Published: June 2006

We discuss the most recent reports on two proton pumps, F‐ATPase (ATP synthase) and V‐ATPase (endomembrane proton pump). They are formed from similar extrinsic (F1 or V1) and intrinsic (Fo or Vo) membrane sectors, and couple chemistry and proton transport through subunit rotation for apparently different physiological roles. Emphasis is placed on the stochastic rotational catalysis of F‐ATPase and isoforms of V‐ATPase.
iubmb Life, 58: 318‐322, 2006
Cytosolic phospholipase A2: Biochemical properties and physiological roles
Authors: Shimizu Takao , Ohto Takayo , Kita Yoshihiro
Published: June 2006

Phosphatidylcholine (PC) is a major constituent of biological membranes and a component of serum lipoproteins and pulmonary surfactants. The PC and other glycerophospholipid compositions of membranes change dynamically through stimulus‐dependent and independent pathways, principally by the action of two different types of enzymes; phospholipase A2 [EC 3.1.1.4] and acyl‐CoA:lysophospholipid acyltransferase [EC 2.3.1.23]. Phospholipase A2 is a key enzyme that catalyzes deacylation of the sn‐2 position of glycerophospholipids. This enzyme is critical in the remodeling of membrane lipids and formation of two subclasses of lipid mediators, fatty acid derivatives and lysophospholipids. Among many different subtypes of phospholipase A2 enzymes, we found that cytosolic phospholipase A2α (cPLA2α) is important in various pathological and physiological responses. Here, we summarize the phenotypes resulting from genetic ablation of cPLA2α, and the properties of newly discovered enzymes in the cPLA2 family. Comprehensive analysis of lipid mediators using liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) is useful for understanding the roles of individual mediators in physiological and pathological processes.
iubmb Life, 58: 328‐333, 2006
Complement‐mediated phagocytosis ‐ the role of Syk
Authors: Tohyama Yumi , Yamamura Hirohei
Published: June 2006

Phagocytosis is a central event in the innate immune responses that are triggered by the association between ligands on the surface of pathogens and receptors on the membrane of phagocytes. Particularly, complement‐mediated phagocytosis is accomplished by specific recognition of bound complement components by the corresponding complement receptors on the phagocytes. The protein‐tyrosine kinase, Syk, plays a central role in Fcγ receptor‐mediated phagocytosis in the adaptive immune system. From recent studies using a macrophage‐like differentiated cell line and serum‐treated zymosan, it was found that Syk also plays an essential role in complement‐mediated phagocytosis in innate immunity. Serum‐treated zymosan particles promptly attached to the cells and were subsequently engulfed via complement receptor3. During this process, Syk became tyrosine‐phosphorylated and accumulated around the nascent phagosomes. The transfer of Syk‐siRNA or dominant‐negative Syk (DN‐Syk) into macrophages resulted in impaired engulfment of pathogen. Collectively, Syk is required for the engulfment of pathogen in complement‐mediated phagocytosis.
iubmb Life, 58: 304‐308, 2006
Regulatory mechanisms and functions of MAP kinase signaling pathways
Authors: Imajo Masamichi , Tsuchiya Yoshiki , Nishida Eisuke
Published: June 2006

Mitogen‐activated protein kinase (MAPK) pathways play central roles in controlling diverse cellular functions. They are finely regulated by several mechanisms, including scaffolding of their components, and phosphorylation/dephosphorylation and compartmentalization of MAPKs. A number of molecules have been identified as regulators involved in these mechanisms. They modulate the magnitude and the specificity of MAPK signaling, and thereby regulate the wide variety of signaling outputs. Recent studies have identified novel functions of the MAPK signaling pathways. It is becoming clear that strict regulation of the MAPK pathways underlies their manifold functions in numerous biological processes.
iubmb Life, 58: 312‐317, 2006
Apoptosis and autoimmune diseases
Authors: Nagata Shigekazu
Published: June 2006

Apoptosis is a process by which harmful or useless cells are eliminated. This process can be divided into two steps, death and engulfment. Molecules involved in apoptosis have been identified, and mouse lines deficient in these genes have been established. Among these deficiencies, those in the death receptor system or the engulfment of apoptotic cells cause systemic lupus erythematosus, whereas inefficient DNA degradation causes anemia by activating innate immunity, leading to death during embryogenesis. The apoptotic process and the diseases caused by defects in it are briefly reviewed.
iubmb Life, 58: 358‐362, 2006
Protein turnover
Authors: Ohsumi Yoshinori
Published: June 2006

The mechanisms and physiological meanings of protein turnover are crucial subjects in the understanding of life. However, for a long time, protein degradation was neglected by most biologists, and was thought of as a rather passive cellular process.
iubmb Life, 58: 363‐369, 2006
Small GTPase Rab21 regulates cell adhesion and controls endosomal traffic of β1-integrins
Authors: Pellinen Teijo , Arjonen Antti , Vuoriluoto Karoliina , Kallio Katja , Fransen Jack A.M. , Ivaska Johanna
Published: June 2006

Dynamic turnover of integrin cell adhesion molecules to and from the cell surface is central to cell migration. We report for the first time an association between integrins and Rab proteins, which are small GTPases involved in the traffic of endocytotic vesicles. Rab21 (and Rab5) associate with the cytoplasmic domains of α-integrin chains, and their expression influences the endo/exocytic traffic of integrins. This function of Rab21 is dependent on its GTP/GDP cycle and proper membrane targeting. Knock down of Rab21 impairs integrin-mediated cell adhesion and motility, whereas its overexpression stimulates cell migration and cancer cell adhesion to collagen and human bone. Finally, overexpression of Rab21 fails to induce cell adhesion via an integrin point mutant deficient in Rab21 association. These data provide mechanistic insight into how integrins are targeted to intracellular compartments and how their traffic regulates cell adhesion.
Cytosolic inositol 1,4,5-trisphosphate dynamics during intracellular calcium oscillations in living cells
Authors: Matsu-ura Toru , Michikawa Takayuki , Inoue Takafumi , Miyawaki Atsushi , Yoshida Manabu , Mikoshiba Katsuhiko
Published: June 2006

We developed genetically encoded fluorescent inositol 1,4,5-trisphosphate (IP3) sensors that do not severely interfere with intracellular Ca2+ dynamics and used them to monitor the spatiotemporal dynamics of both cytosolic IP3 and Ca2+ in single HeLa cells after stimulation of exogenously expressed metabotropic glutamate receptor 5a or endogenous histamine receptors. IP3 started to increase at a relatively constant rate before the pacemaker Ca2+ rise, and the subsequent abrupt Ca2+ rise was not accompanied by any acceleration in the rate of increase in IP3. Cytosolic [IP3] did not return to its basal level during the intervals between Ca2+ spikes, and IP3 gradually accumulated in the cytosol with a little or no fluctuations during cytosolic Ca2+ oscillations. These results indicate that the Ca2+-induced regenerative IP3 production is not a driving force of the upstroke of Ca2+ spikes and that the apparent IP3 sensitivity for Ca2+ spike generation progressively decreases during Ca2+ oscillations.
Myosin motor Myo1c and its receptor NEMO/IKK-γ promote TNF-α–induced serine307 phosphorylation of IRS-1
Authors: Nakamori Yoshitaka , Emoto Masahiro , Fukuda Naofumi , Taguchi Akihiko , Okuya Shigeru , Tajiri Michiko , Miyagishi Makoto , Taira Kazunari , Wada Yoshinao , Tanizawa Yukio
Published: June 2006

Tumor necrosis factor-α (TNF-α) signaling through the IκB kinase (IKK) complex attenuates insulin action via the phosphorylation of insulin receptor substrate 1 (IRS-1) at Ser307. However, the precise molecular mechanism by which the IKK complex phosphorylates IRS-1 is unknown. In this study, we report nuclear factor κB essential modulator (NEMO)/IKK-γ subunit accumulation in membrane ruffles followed by an interaction with IRS-1. This intracellular trafficking of NEMO requires insulin, an intact actin cytoskeletal network, and the motor protein Myo1c. Increased Myo1c expression enhanced the NEMO–IRS-1 interaction, which is essential for TNF-α– induced phosphorylation of Ser307–IRS-1. In contrast, dominant inhibitory Myo1c cargo domain expression diminished this interaction and inhibited IRS-1 phosphorylation. NEMO expression also enhanced TNF-α–induced Ser307–IRS-1 phosphorylation and inhibited glucose uptake. In contrast, a deletion mutant of NEMO lacking the IKK-β–binding domain or silencing NEMO blocked the TNF-α signal. Thus, motor protein Myo1c and its receptor protein NEMO act cooperatively to form the IKK–IRS-1 complex and function in TNF-α–induced insulin resistance.
Excess Mcm2–7 license dormant origins of replication that can be used under conditions of replicative stress
Authors: Woodward Anna M. , Göhler Thomas , Luciani M. Gloria , Oehlmann Maren , Ge Xinquan , Gartner Anton , Jackson Dean A. , Blow J. Julian
Published: June 2006

In late mitosis and early G1, replication origins are licensed for subsequent use by loading complexes of the minichromosome maintenance proteins 2–7 (Mcm2–7). The number of Mcm2–7 complexes loaded onto DNA greatly exceeds the number of replication origins used during S phase, but the function of the excess Mcm2–7 is unknown. Using Xenopus laevis egg extracts, we show that these excess Mcm2–7 complexes license additional dormant origins that do not fire during unperturbed S phases because of suppression by a caffeine-sensitive checkpoint pathway. Use of these additional origins can allow complete genome replication in the presence of replication inhibitors. These results suggest that metazoan replication origins are actually comprised of several candidate origins, most of which normally remain dormant unless cells experience replicative stress. Consistent with this model, using Caenorhabditis elegans, we show that partial RNAi-based knockdown of MCMs that has no observable effect under normal conditions causes lethality upon treatment with low, otherwise nontoxic, levels of the replication inhibitor hydroxyurea.
Ups1p, a conserved intermembrane space protein, regulates mitochondrial shape and alternative topogenesis of Mgm1p
Authors: Sesaki Hiromi , Dunn Cory D. , Iijima Miho , Shepard Kelly A. , Yaffe Michael P. , Machamer Carolyn E. , Jensen Robert E.
Published: June 2006

Mgm1p is a conserved dynamin-related GTPase required for fusion, morphology, inheritance, and the genome maintenance of mitochondria in Saccharomyces cerevisiae. Mgm1p undergoes unconventional processing to produce two functional isoforms by alternative topogenesis. Alternative topogenesis involves bifurcate sorting in the inner membrane and intramembrane proteolysis by the rhomboid protease Pcp1p. Here, we identify Ups1p, a novel mitochondrial protein required for the unique processing of Mgm1p and for normal mitochondrial shape. Our results demonstrate that Ups1p regulates the sorting of Mgm1p in the inner membrane. Consistent with its function, Ups1p is peripherally associated with the inner membrane in the intermembrane space. Moreover, the human homologue of Ups1p, PRELI, can fully replace Ups1p in yeast cells. Together, our findings provide a conserved mechanism for the alternative topogenesis of Mgm1p and control of mitochondrial morphology.
Introduction to the Special Issue “Causal Complexity and Qualitative Methods”
Authors: Goertz Gary
Published: June 2006

This special issue of Political Analysis engages in a dialogue between qualitative and quantitative methods. It proposes that each has something to say to the other and more generally has a contribution to make to empirical social science.
5. Improved Regression Estimation of a Multivariate Relationship with Population Data on the Bivariate Relationship
Authors: Handcock Mark S. , Rendall Michael S. , Cheadle Jacob E.
Published: June 2006

Regression coefficients specify the partial effect of a regressor on the dependent variable. Sometimes the bivariate or limited multivariate relationship of that regressor variable with the dependent variable is known from population-level data. We show here that such population-level data can be used to reduce variance and bias about estimates of those regression coefficients from sample survey data. The method of constrained MLE is used to achieve these improvements. Its statistical properties are first described. The method constrains the weighted sum of all the covariate-specific associations (partial effects) of the regressors on the dependent variable to equal the overall association of one or more regressors, where the latter is known exactly from the population data. We refer to those regressors whose bivariate or limited multivariate relationships with the dependent variable are constrained by population data as being “directly constrained.” Our study investigates the improvements in the estimation of directly constrained variables as well as the improvements in the estimation of other regressor variables that may be correlated with the directly constrained variables, and thus “indirectly constrained” by the population data. The example application is to the marital fertility of black versus white women. The difference between white and black women's rates of marital fertility, available from population-level data, gives the overall association of race with fertility. We show that the constrained MLE technique both provides a far more powerful statistical test of the partial effect of being black and purges the test of a bias that would otherwise distort the estimated magnitude of this effect. We find only trivial reductions, however, in the standard errors of the parameters for indirectly constrained regressors.
Advanced colorectal polyps with the molecular and morphological features of serrated polyps and adenomas: concept of a ‘fusion’ pathway to colorectal cancer
Authors: Jass J R , Baker K , Zlobec I , Higuchi T , Barker M , Buchanan D , Young J
Published: June 2006

Aim : To establish and explain the pattern of molecular signatures across colorectal polyps.

Methods and results : Thirty‐two sessile serrated adenomas (SSA), 10 mixed polyps (MP), 15 traditional serrated adenomas (SA), 49 hyperplastic polyps (HP) and 84 adenomas were assessed for mutation of KRAS and BRAF and aberrant expression of p53. The findings were correlated with loss of expression of O‐6‐methylguanine DNA methyltransferase (MGMT). KRAS mutation occurred more frequently (26.5%) than BRAF mutation (4.8%) in adenomas (P < 0.001) and particularly in adenomas with villous architecture (50%). Loss of expression of MGMT correlated with KRAS mutation in small tubular adenomas (P < 0.04). BRAF mutation was frequent in HPs (67%) and SSAs (81%), while KRAS mutation was infrequent (4% and 3%, respectively). Of MPs and SAs, 72% had either BRAF or KRAS mutation. Aberrant expression of p53 was uncommon overall, but occurred more frequently in MPs and SAs (12%) than adenomas (1%) (P < 0.04) and there was concordant loss of expression of MGMT.

Conclusions : Molecular alterations that are characteristic of the serrated pathway and adenoma–carcinoma sequence can co‐occur in a minority of advanced colorectal polyps that then show morphological features of both pathways. These lesions account for only 2% of colorectal polyps, but may be relatively aggressive.
Thin‐wall ceramic CAD/CAM crown copings: strength and fracture pattern
Authors: BINDL A. , LÜTHY H. , MÖRMANN W. H.
Published: June 2006

summary  The strength and fracture pattern of posterior CAD/CAM‐generated crown copings with 0·4 mm wall thickness were evaluated in vitro hypothesizing that fracture resistance of YTZP‐zirconia copings might be independent of mode of cementation whether resin‐bonded or cemented because of the high strength of YTZP‐zirconia. Two sets of copings (n = 15) each were fabricated using CEREC inLab CAD/CAM from (i) lithiumdisilicate glass–ceramic, (ii) infiltration ceramic as controls and (iii) YTZP‐zirconia. Copings (n = 15) of ceramics (i), (ii) and (iii) each were (a) zinc–phosphate cemented, (b) adhesively seated on resin‐based composite dies and loaded until fracture. Load (N) data was analysed using anova and Scheffé tests. Crack pattern was evaluated on additional three sample cross‐sections for each group at fracture‐start. Radial cracks originated early at the cementation interfaces and cone cracks were observed finally at the loading sites. Mean load (N) values (±s.d.) of A‐copings at fracture‐start/‐end (i) 804 ± 195/862 ± 162, (ii) 923 ± 180/975 ± 147, (iii) 697 ± 110/1607 ± 145, were all significantly (P < 0·01) lower when compared with their B‐crown coping analogs (i) 1183 ± 318/1919 ± 326, (ii) 1621 ± 165/1820 ± 211, (iii) 731 ± 115/1973 ± 287 except for A3 and B3 at fracture‐start. This confirmed our hypothesis at fracture‐start (P > 0·05) but rejected it at fracture‐end (P < 0·01). The A3 fracture‐end data, even if significantly (P < 0·01) lower, came close to the B3 values by 18%. A3 was significantly (P < 0·001) stronger by 86/74% than A1/A2 at fracture‐end. The data indicates that YTZP‐zirconia copings have the potential to provide support for all‐ceramic core crowns, which may be adequate for non‐adhesive cementation.
In vivo evaluation of the biocompatibility of three current bonding agents
Authors: TEIXEIRA H. M. , DO NASCIMENTO A. B. L. , HEBLING J. , DE SOUZA COSTA C. A.
Published: June 2006

summary  The aim of this in vivo study was to evaluate the biocompatibility of three current bonding agents and calcium hydroxide cement. Sixty polyethylene tubes filled with the following materials: Group 1: Prime & Bond NT (PB – Dentsply, US; Group 2: Bond 1 (BO – Jeneric/Pentron, US); Group 3: Optibond Solo (OP – Kerr, US); and Group 4 (control): calcium hydroxide cement – Dycal (CH – Dentsply, US) were implanted into the connective tissue of 30 rats. After 15, 30 and 60 days, the implants were excised and the animals sacrificed. The biopsies were immersed in Karnovsky (pH, 7.2) fixative solution for 48 hours, and processed using routine histological technique. Six‐micron‐thick sections were cut and stained with hematoxilin and eosin and Masson's trichome technique. Microscopic evaluation was used to compare the connective tissue reactions caused by the experimental and control materials adjacent to the tube opening. At 15 days, the experimental and control materials triggered a moderate to intense inflammatory response which gave rise to a thick capsule adjacent to the tube opening. With time, the inflammatory reaction decreased. At 60 days, the connective tissue adjacent to the bonding agents exhibited a persistent inflammatory response mediated by macrophages and giant cells which were engulfing displaced resin components. On the other hand, for the control group (calcium hydroxide) no inflammatory response associated with a thin capsule adjacent to the material was observed even at the 30‐day period. The hard‐setting calcium hydroxide cement allowed complete healing and was considered more biocompatible than the bonding agents.
Preoperative plasma osteopontin level as a biomarker complementary to carbohydrate antigen 125 in predicting ovarian cancer
Authors: Nakae Mitsuhiro , Iwamoto Ichiro , Fujino Toshinori , Maehata Yoshiyasu , Togami Shin‐ichi , Yoshinaga Mitsuhiro , Douchi Tsutomu
Published: June 2006

Aim:  New biomarkers other than carbohydrate antigen (CA) 125 are needed for the detection of ovarian cancer. Osteopontin (OPN) is one of the candidates identified by high‐throughput complementary DNA microarray techniques. We evaluated the preoperative plasma OPN level as a diagnostic biomarker for ovarian cancer in comparison with CA125.

Methods:  Preoperative plasma OPN and CA125 levels were measured and compared in 32 patients with ovarian cancer, 34 patients with benign ovarian tumor, 30 patients with other gynecologic cancers and 31 healthy women. Preoperative plasma OPN levels were also assessed according to tumor stage, the volume of ascites and histological types. The sensitivity and specificity for predicting ovarian cancer was compared between OPN and CA125.

Results:  Preoperative plasma OPN levels were significantly higher in patients with ovarian cancer than in those with benign ovarian tumor, in other gynecologic patients or in healthy women. Stage IV ovarian cancer patients and ovarian cancer patients with ascites had higher plasma OPN levels than those without ascites and in a lower stage. There was no relation between OPN and the histological type. The sensitivity of preoperative plasma OPN in detecting ovarian cancer was 81.3% and almost reached that of CA125. The specificity was moderate. Sensitivity increased to 93.8% with the combination of CA125, compared to 84.4% with CA125 alone.

Conclusion:  Preoperative OPN is a useful biomarker for predicting ovarian cancer. It is especially useful when used complementary to CA125. Larger studies of patients with ovarian cancer showing a low CA125 level or in early stages of ovarian cancer are needed.
Paclitaxel/carboplatin versus cyclophosphamide/adriamycin/cisplatin as postoperative adjuvant chemotherapy for advanced endometrial adenocarcinoma
Authors: Hidaka Takao , Nakamura Takafumi , Shima Tomoko , Yuki Hiroyuki , Saito Shigeru
Published: June 2006

Aim:  There is no standard chemotherapy regimen for patients with advanced endometrial adenocarcinoma. In our hospital, a cyclophosphamide/adriamycin/cisplatin (CAP) regimen was commonly used as adjuvant chemotherapy. However, since October 1999 a paclitaxel/carboplatin regimen has been substituted for CAP. To evaluate the antitumor activity and toxic effects of those regimens, we retrospectively reviewed cases that were treated in our hospital.

Methods:  Twenty‐eight patients who underwent surgery and had histologically confirmed advanced endometrial adenocarcinoma, International Federation of Gynecology and Obstetrics stage III/IV, received combination chemotherapy. Treatment consisted of cisplatin, adriamycin and cyclophosphamide (CAP group, n = 16), or paclitaxel and carboplatin (paclitaxel/carboplatin group, n = 12). The response rate (RR), progression‐free survival (PFS), overall survival (OS), and toxicities were evaluated.

Results:  In the CAP group, complete response (CR) was observed in six patients and partial response (PR) in three, for an RR of 64.3%. In the paclitaxel/carboplatin group, CR was observed in five and PR in two, for an RR of 77.8%. The 3‐year PFS and OS rates were 50.0% and 75.0% in the paclitaxel/carboplatin group, and 37.5% and 50.0% in the CAP group, respectively, and there was no significant difference between the two groups. National Cancer Institute Common Toxicity Criteria grade 3–4 thrombocytopenia and gastrointestinal toxicities occurred significantly less frequently in the paclitaxel/carboplatin group (0% and 16.7%) than in the CAP group (31.3% and 68.8%) (P = 0.0389 and P = 0.0062).

Conclusions:  We conclude that paclitaxel/carboplatin is a promising regimen which could be substituted for CAP, with major activity and a highly acceptable toxicity profile for the treatment of advanced endometrial adenocarcinomas.
Evisceration of pregnant uterus through the incisional hernia site
Authors: Sahu Latika , Bupathy Arounassalame
Published: June 2006

The herniation of a gravid uterus through an incisional hernia site is a rare occurrence, but the evisceration of the gravid uterus through the incisional hernia is even rarer. The following is a case report of an evisceration of gravid uterus through an incisional hernia of a midline incision.
Puerperal uterine inversion: A report of four cases
Authors: Achanna Siva , Mohamed Zarina , Krishnan Mukudan
Published: June 2006

Acute puerperal uterine inversion is a life‐threatening and unpredictable obstetric emergency. If overlooked, it could lead to a maternal death. Although the precise cause is unknown, it is postulated to be caused by the mismanagement of the third stage of labor with premature traction of the umbilical cord and fundal pressure before placental separation. At the Ipoh General Hospital in Malaysia there were 31 394 deliveries and four acute uterine inversions occurring from 1 January 2002 to 30 June 2005. The four patients were between 25 and 36 years of age and their parities were between two and three. When manual repositioning of the uterus failed, successful correction was accomplished by the O’Sullivan’s hydrostatic method. One case had to undergo subtotal hysterectomy after repositioning because of massive hemorrhage secondary to placenta accreta. Early diagnosis, immediate treatment of shock, and replacement are essential.
Hemoglobin E‐Saskatoon and pregnancy: Report of two cases
Authors: Theodoridou Stamatia , Vyzantiadis Timoleon‐Achilleas , Theodoridis Theodoros , Tantanasis Theoharis , Karababa Photini , Loutradi Afroditi , Manitsa Anna
Published: June 2006

Hemoglobin E‐Saskatoon (β22‐Glu‐Lys) is found worldwide but is extremely rarely. Two cases of pregnant women who carried the abnormal hemoglobin and the various problems that arise from it are reported. A discussion of the combinations with other abnormal hemoglobin is also presented.
Post‐traumatic stress disorder in patients with gynecologic cancers
Authors: Sukegawa Akiko , Miyagi Etsuko , Suzuki Rie , Ogasawara Tomoka , Asai‐Sato Mikiko , Yoshida Hiroshi , Sugiura Ken , Nakazawa Tsuneo , Onose Ryo , Onishi Hideki , Hirahara Fumiki
Published: June 2006

We present three cases of post‐traumatic stress disorder (PTSD) that occurred in patients with gynecologic cancers. Case 1 and 2 had ovarian cancer and case 3 had endometrial cancer. The patients developed anxiety, difficulty in sleeping, and complaints of various discomforts after their diagnosis. On consulting with psychiatrists, PTSD was diagnosed based upon the DSM‐IV classification. In cases 1 and 2, the symptoms worsened during the patients’ primary treatment and interfered with their ability to continue the treatment. Psychiatric interventions were provided making it possible to complete their treatment. In case 3, the patient needed psychiatric intervention because of her psychological distress during her treatment. She was finally diagnosed as having PTSD. There are few reports regarding PTSD occurring in gynecologic cancer patients. However, attention should be given to the symptoms of these disorders so that patients may complete their standard therapies.
Endoscopic mucosal resection (EMR) in the management of large colo‐rectal polyps
Authors: Jameel J. K. A. , Pillinger S. H. , Moncur P. , Tsai H. H. , Duthie G. S.
Published: June 2006

Background  Colonoscopic polypectomy plays a major role in preventing colo‐rectal cancer. However, resection of sessile, broad‐based pedunculated and flat lesions carries a high risk of perforation. Endoscopic Mucosal Resection (EMR) may significantly reduce this risk. We aim to assess the safety and efficacy of EMR in our unit.

Patients and methods  A review of a prospective database over a 3‐year period identified 87 patients who underwent endoscopic polypectomy for polyps in sizes from 10 to 50 mm, performed by two experienced endoscopists. A total of 33 EMRs were performed on 30 lesions in 24 of these patients.

Results  Median size of lesions was 20 mm. Most were located in the rectum and sigmoid. 22 lesions were resected en‐bloc while 8 were resected piecemeal. Histologically these lesions were predominantly adenomatous polyps. An incidental focus of adenocarcinoma was found in 7 lesions. Histologically complete excision was achieved in 10 lesions. Although histological completeness of excision was not confirmed in 19 lesions, repeat colonoscopy confirmed successful excision. Only one lesion was incompletely excised requiring surgical resection. Bleeding occurred during 2 EMRs, both times successfully controlled by further injection of adrenaline locally. There was no case of bowel perforation. Further surveillance colonoscopy was performed according to established guidelines. Median follow‐up period was 21 months. None of the patients diagnosed with adenocarcinoma showed any evidence of recurrence.

Conclusion  Within our unit endoscopic mucosal resection appeared to be safe and effective procedure for resecting large colorectal polyps not suitable for conventional polypectomy. This data would support prompt referral of lesions fulfilling these criteria to specialist units offering this service to avoid unnecessary surgery.
The influence of instructional methods on the quality of online discussion
Authors: Kanuka Heather , Rourke Liam , Laflamme Elaine
Published: June 2006

In this case study, we examined the influence of five groups of communication activities on the quality of students’ contributions to online discussion. The activities were the nominal group technique, debate, invited expert, WebQuest and reflective deliberation. Quality of discussion was operationalised as cognitive presence, a construct developed to investigate the role of critical discourse in higher, distance education contexts. Using the quantitative content analysis technique, the postings of 19 students in an undergraduate university course were assigned to one of the four categories of cognitive presence. Across the five activities, the proportion and number of contributions categorised in the highest phases of cognitive presence was low (20.21%), but was highest during the Webquest and debate activities. There are three advantageous qualities of these two activities, we argue:

They were well structured.

They provided clearly defined roles and responsibilities for the students.

They provoked the students to explicitly confront others’ opinions.
Designing online courses that effectively engage learners from diverse cultural backgrounds
Authors: Wang Minjuan
Published: June 2006

This study examines the effect of an important cultural dimension—power distance index (PDI)—on learners’ perceptions of their online learning experiences. PDI refers to the degree to which a learner’s response to another individual in a learning setting is inhibited or otherwise negatively altered when the other individual holds a position that is superior or inferior to the learner’s own position. This study aims to generate guidelines for better design and facilitation of online courses that can effectively engage all students in the learning process. Research findings are particularly relevant to researchers and practitioners who are interested in the cultural aspects of online learning. This study contributes to the current knowledge base about designing effective online courses and about practicing culturally responsive teaching in an online setting.
The effectiveness of information and communication technology on the learning of written English for 5‐ to 16‐year‐olds
Authors: Andrews Richard , Freeman Allison , Hou Dan , McGuinn Nick , Robinson Alison , Zhu Judy
Published: June 2006

The last few years have seen an increase in research studies on the impact and effectiveness of information and communication technologies (ICTs) in the teaching and learning of English as a school subject. It is against that research background and against recent developments in policy and practice in the UK that the present systematic review of the effectiveness of different ICTs in the teaching and learning of English has been undertaken. The aim of this review was to shed light on whether ICTs are effective in the teaching and learning of English for 5‐ to 16‐year‐olds. A total of 2103 papers were found in the initial search of studies published between 1998 and 2003 on the topic of the review. An in‐depth review on the effectiveness of ICT in the teaching and learning of written composition in English concentrated on nine studies. As eight of the nine studies were judged to be of medium weight of evidence and were also different from each other in nature, it was not possible to arrive at a clear answer to our in‐depth research question. Rather, we wish to report that the field is in a preparadigmatic state where definitions of English, literacy and ICT are still relatively unclear, and where the causal and/or reciprocal relationships between them have yet to be fully theorised.
Post‐16 e‐learning content production: a synthesis of the literature
Authors: De Freitas Sara
Published: June 2006

This paper provides a metareview of how e‐learning content is currently being produced and embedded in the learning practice in further education, work‐based learning and community learning contexts. Based upon this metareview, the paper has identified four categories of content production used: (1) learner‐authored content, (2) practitioner‐authored content, (3) commercial‐ and public sector‐commissioned content and (4) combinations of these categories. The metareview also identifies several well‐used, practitioner‐based and institutional models for embedding e‐learning content into practice, exploring some of the implications of this upon practitioners.
Why are Older People More Likely to Vote? The Impact of Ageing on Electoral Turnout in Europe
Authors: Goerres Achim
Published: June 2006

This article analyses the reasons for higher voting participation among older people in Europe. Over their lifetimes, citizens tend to habituate voting and comply with a growing subjective norm of voting. Furthermore, the average voting participation of older people is influenced by their longer duration of residence, the lack of a mobilising partner, worse physical health and less education, although life experience replaces the function of formal education over a lifetime. Most of these factors are founded on the very nature of human behaviour and the social context of our life course. Thus, they arguably stand outside of the political process and will remain stable into the future.