bluuebunny/crossref_metadata_2025 huggingface dataset:
Structured Spousal Violence Risk Assessment: Combining Risk Factors and Victim Vulnerability Factors
Authors: Belfrage Henrik , Strand Susanne
Published: May 2010

Police officers in two police counties in Sweden were trained in using an extended version of the Brief Spousal Assault Form for the Evaluation of Risk (B-SAFER) in consecutive real life cases of reported spousal assault during the period May 2005 – December 2006 (N = 698). Besides the original 10 perpetrator risk factors included in the B-SAFER, an additional 5 victim vulnerability factors were coded. All B-SAFER factors were then analyzed versus the degree of risk the police officers concluded. The aim was to investigate whether victim vulnerability factors to any extent contribute to the police officers’ risk assessments in the context of spousal assault and to study how common such factors are, and also if these factors can be coded in an acceptable way. The results showed a strong correlation between number of B-SAFER factors and the degree of risk that the police officers assessed. Generally, the more B-SAFER factors that were coded as present, the higher the risk for recidivism was coded by the police. Victim vulnerability factors were less common than perpetrator risk factors, but had an equally strong correlation to the overall risk assessed by the police. We conclude that victim vulnerability factors seem to have an important role when assessing spousal violence risk and thus should preferably be included in structured spousal assault risk assessment tools.
Violence against Caregivers by Relatives with Schizophrenia
Authors: Chan BillyWing-Yum
Published: May 2010

Sixty-one caregivers (37 women and 24 men) in the Greater Toronto Area in Ontario, Canada, who lived with and provided care to 51 relatives with schizophrenia, participated in a survey to identify dynamic risks factors that may have precipitated violence in these families. Twenty-six percent and 31% of caregivers experienced at least one incident of severe and one incident of minor physical assault respectively, in the past 12 months. Forty-four percent and 64% of caregivers experienced at least one incident of severe and one incident of minor psychological aggression respectively during the same period. Stepwise multiple regression analyses evidenced the intensity of Threat/Control-Override (TCO) symptoms in relatives with schizophrenia as the only significant predictor of physical assault against caregivers. Caregivers’ Critical Comments against relatives with schizophrenia and the intensity of TCO symptoms in ill relatives were significant predictors of psychological aggression against caregivers.
Personality and Reconviction in Crime: A Three-year Follow-up Study of Male Criminal Recidivists
Authors: Rydén-Lodi Birgitta , Burk WilliamJ. , Stattin Håkan , af Klinteberg Britt
Published: May 2010

The objective of the present study was to identify personality characteristics associated with reconviction and reimprisonment in severely criminal male subjects. A further objective was to assess whether personality traits are useful for identifying those offenders who cease versus continue a criminal career. Using KSP, EPQ-I and SSS inventories, self-reported personality traits were investigated in 100 incarcerated male recidivists (age range 30–38 years) and non-criminal male comparisons. Follow-up data were obtained three years after release from prison. The subjects were grouped according to reconviction level, yielding four groups: Ss totally free of convictions (FC), Ss convicted but not imprisoned (CNP), Ss with one to three prison convictions (TCP), and Ss with four or more prison convictions (FCP). Results indicated that the study group differed markedly from the non-criminals with regard to most personality traits, while there were few significant differences between the conviction groups. However, the FC Ss had lower scores than the FCP Ss on the EPQ Psychoticism and SSS Disinhibition scales when previous time spent in prison and age at the first examination session were controlled for. They also had higher scores on KSP Guilt. Furthermore, logistic regression analysis indicated that the higher the extraversion and psychic anxiety, the less likely it was for the individual to have been reimprisoned at follow-up. In contrast, the higher the irritability and monotony avoidance the more likely it was for the person to have been reimprisoned.
Conciliation or Condemnation? Prison Employees' and Young Peoples' Attitudes Towards Sexual Offenders
Authors: Kjelsberg Ellen , Loos Liv Heian
Published: May 2010

Prison employees’ attitudes towards sexual offenders were monitored by the Attitudes toward Sexual Offenders scale (ATS) before (N = 105) and again one year after (N = 90) an educational program on sexual offenders. In addition, 412 college students completed the ATS. All answered a number of questions exploring the respondents’ general beliefs about sexual offenders and their punishment. The prison employees held significantly more positive attitudes towards sexual offenders than college students did. Among prison employees, prison officers held the least positive attitudes. While increasing age correlated positively with more positive attitudes, no gender differences were observed. The educational program did not seem to have any effect on the prison employees’ attitudes one year later, as measured by the ATS.
Adjudicative Competence Evaluations of Juvenile and Adult Defendants: Judges' Views Regarding Essential Components of Competence Reports
Authors: Viljoen JodiL. , Wingrove Twila , Ryba NancyL.
Published: May 2010

Adjudicative competence evaluations are commonly requested for adult criminal defendants, and are becoming increasingly common among juvenile defendants as well. However, we do not have an understanding of what information judges seek in these evaluations. In this study, juvenile and criminal court judges from seven states (N = 166) were surveyed. Results indicated that judges: (1) consider clinicians' ultimate opinion to be an essential component of reports, and more important than descriptive information and rationales for opinions; (2) view forensic and psychological testing as valuable; (3) look for similar but not identical characteristics in juvenile and adult competence evaluations; and (4) consider opinions about maturity to be an important component of competence evaluations in juvenile court.
Identification of Critical Items on the Massachusetts Youth Screening Instrument – 2 (MAYSI-2) in Incarcerated Youth
Authors: Cruise KeithR. , Dandreaux DanielleM. , Marsee MonicaA. , DePrato DebraK.
Published: May 2010

Previous research has indicated that the Massachusetts Youth Screening Instrument – Second Version (MAYSI-2) has clinical utility in screening and identifying justice-involved youth with mental health problems. In an effort to expand research on the validity of the MAYSI-2, the current study investigated patterns of endorsement on MAYSI-2 items to identify “critical items” that may serve as important indicators of serious mental health problems. Results identified a subset of MAYSI-2 items for male (13 items) and female youth (14 items) that hold promise in identifying youth with serious mental health problems. Gender-specific critical items scales were formed with optimized categorical cut-scores identified which were comparable to the standard MAYSI-2 scale scoring procedures. The critical items scales produced excellent internal consistency and promising predictive validity. Potential clinical applications and steps for further validation of this adjunctive scoring approach are offered.
The Violent Offender Treatment Program (VOTP): Development of a Treatment Program for Violent Patients in a High Security Psychiatric Hospital
Authors: Braham Louise , Jones David , Hollin CliveR.
Published: May 2010

There are growing numbers of offenders with a mental illness convicted of violent behaviors in both the penal and mental health systems. To date however, there have been limited effective treatments reported for this population. This article describes the development, delivery and outcome of a pilot treatment program developed to meet this need (VOTP) within high secure psychiatric services. The program is based on current literature and clinical experience combined to provide a comprehensive theoretical model. The program thus account for theoretical and therapeutic content as well as responsivity and other delivery issues. The program is structured and manualized, multi modal, and delivered in approximately 280 hours of group therapy plus a range of weekly individual work and support. Staff training is an essential component of the work. So far, promising results are forthcoming. They include reductions in behavioral manifestations of violence, a decrease in perceived level of risk and an increase in coping and interpersonal skills.
Risk Assessment in Forensic Patients with Schizophrenia: The Predictive Validity of Actuarial Scales and Symptom Severity for Offending and Violence over 8 – 10 Years
Authors: Thomson Lindsay , Davidson Michelle , Brett Caroline , Steele Jonathan , Darjee Rajan
Published: May 2010

Assessment of risk of violence is essential in the management of patients with schizophrenia admitted to secure hospitals. The present study was conducted to test the validity of actuarial measures and psychotic symptoms in the prediction of further violence and offending in this group. The H-10 scale of the HCR-20, Violence Risk Appraisal Guide and Psychopathy Checklist-Revised were scored retrospectively. Symptom severity was rated at interview and persistence from notes. Outcome was measured using criminal records and recorded incidents of aggression over an 8-10 year period. Seventy-six percent of patients were involved in more than 1800 incidents defined as physical contact with a victim or damage to property, and 28% in a serious incident defined as injury to a victim requiring hospital treatment, a contact sexual incident or fire setting. Fifteen percent of patients were convicted of any offense and 5% of a violent offense. The risk scales had moderate to high predictive accuracy for offenses and violent offenses but failed to predict incidents or serious incidents. Symptom severity and persistence predicted incidents but not offenses. Violence within this population is common. Actuarial measures of risk assessment are valid predictors of offending and violent offending but psychotic symptoms are more relevant to the prediction of violent incidents. Assessments of likely inpatient aggression must emphasize symptoms.
One naive T cell, multiple fates in CD8+ T cell differentiation
Authors: Gerlach Carmen , van Heijst Jeroen W.J. , Swart Erwin , Sie Daoud , Armstrong Nicola , Kerkhoven Ron M. , Zehn Dietmar , Bevan Michael J. , Schepers Koen , Schumacher Ton N.M.
Published: May 2010

The mechanism by which the immune system produces effector and memory T cells is largely unclear. To allow a large-scale assessment of the development of single naive T cells into different subsets, we have developed a technology that introduces unique genetic tags (barcodes) into naive T cells. By comparing the barcodes present in antigen-specific effector and memory T cell populations in systemic and local infection models, at different anatomical sites, and for TCR–pMHC interactions of different avidities, we demonstrate that under all conditions tested, individual naive T cells yield both effector and memory CD8+ T cell progeny. This indicates that effector and memory fate decisions are not determined by the nature of the priming antigen-presenting cell or the time of T cell priming. Instead, for both low and high avidity T cells, individual naive T cells have multiple fates and can differentiate into effector and memory T cell subsets.
The XC chemokine receptor 1 is a conserved selective marker of mammalian cells homologous to mouse CD8α+ dendritic cells
Authors: Crozat Karine , Guiton Rachel , Contreras Vanessa , Feuillet Vincent , Dutertre Charles-Antoine , Ventre Erwan , Vu Manh Thien-Phong , Baranek Thomas , Storset Anne K. , Marvel Jacqueline , Boudinot Pierre , Hosmalin Anne , Schwartz-Cornil Isabelle , Dalod Marc
Published: May 2010

Human BDCA3+ dendritic cells (DCs) were suggested to be homologous to mouse CD8α+ DCs. We demonstrate that human BDCA3+ DCs are more efficient than their BDCA1+ counterparts or plasmacytoid DCs (pDCs) in cross-presenting antigen and activating CD8+ T cells, which is similar to mouse CD8α+ DCs as compared with CD11b+ DCs or pDCs, although with more moderate differences between human DC subsets. Yet, no specific marker was known to be shared between homologous DC subsets across species. We found that XC chemokine receptor 1 (XCR1) is specifically expressed and active in mouse CD8α+, human BDCA3+, and sheep CD26+ DCs and is conserved across species. The mRNA encoding the XCR1 ligand chemokine (C motif) ligand 1 (XCL1) is selectively expressed in natural killer (NK) and CD8+ T lymphocytes at steady-state and is enhanced upon activation. Moreover, the Xcl1 mRNA is selectively expressed at high levels in central memory compared with naive CD8+ T lymphocytes. Finally, XCR1−/− mice have decreased early CD8+ T cell responses to Listeria monocytogenes infection, which is associated with higher bacterial loads early in infection. Therefore, XCR1 constitutes the first conserved specific marker for cell subsets homologous to mouse CD8α+ DCs in higher vertebrates and promotes their ability to activate early CD8+ T cell defenses against an intracellular pathogenic bacteria.
A malignant hyperthermia–inducing mutation in RYR1 (R163C): alterations in Ca2+ entry, release, and retrograde signaling to the DHPR
Authors: Estève Eric , Eltit José M. , Bannister Roger A. , Liu Kai , Pessah Isaac N. , Beam Kurt G. , Allen Paul D. , López José R.
Published: May 2010

Bidirectional signaling between the sarcolemmal L-type Ca2+ channel (1,4-dihydropyridine receptor [DHPR]) and the sarcoplasmic reticulum (SR) Ca2+ release channel (type 1 ryanodine receptor [RYR1]) of skeletal muscle is essential for excitation–contraction coupling (ECC) and is a well-understood prototype of conformational coupling. Mutations in either channel alter coupling fidelity and with an added pharmacologic stimulus or stress can trigger malignant hyperthermia (MH). In this study, we measured the response of wild-type (WT), heterozygous (Het), or homozygous (Hom) RYR1-R163C knock-in mouse myotubes to maintained K+ depolarization. The new findings are: (a) For all three genotypes, Ca2+ transients decay during prolonged depolarization, and this decay is not a consequence of SR depletion or RYR1 inactivation. (b) The R163C mutation retards the decay rate with a rank order WT > Het > Hom. (c) The removal of external Ca2+ or the addition of Ca2+ entry blockers (nifedipine, SKF96365, and Ni2+) enhanced the rate of decay in all genotypes. (d) When Ca2+ entry is blocked, the decay rates are slower for Hom and Het than WT, indicating that the rate of inactivation of ECC is affected by the R163C mutation and is genotype dependent (WT > Het > Hom). (e) Reduced ECC inactivation in Het and Hom myotubes was shown directly using two identical K+ depolarizations separated by varying time intervals. These data suggest that conformational changes induced by the R163C MH mutation alter the retrograde signal that is sent from RYR1 to the DHPR, delaying the inactivation of the DHPR voltage sensor.
A malignant hyperthermia–inducing mutation in RYR1 (R163C): consequent alterations in the functional properties of DHPR channels
Authors: Bannister Roger A. , Estève Eric , Eltit José M. , Pessah Isaac N. , Allen Paul D. , López José R. , Beam Kurt G.
Published: May 2010

Bidirectional communication between the 1,4-dihydropyridine receptor (DHPR) in the plasma membrane and the type 1 ryanodine receptor (RYR1) in the sarcoplasmic reticulum (SR) is responsible for both skeletal-type excitation–contraction coupling (voltage-gated Ca2+ release from the SR) and increased amplitude of L-type Ca2+ current via the DHPR. Because the DHPR and RYR1 are functionally coupled, mutations in RYR1 that are linked to malignant hyperthermia (MH) may affect DHPR activity. For this reason, we investigated whether cultured myotubes originating from mice carrying an MH-linked mutation in RYR1 (R163C) had altered voltage-gated Ca2+ release from the SR, membrane-bound charge movement, and/or L-type Ca2+ current. In myotubes homozygous (Hom) for the R163C mutation, voltage-gated Ca2+ release from the SR was substantially reduced and shifted (∼10 mV) to more hyperpolarizing potentials compared with wild-type (WT) myotubes. Intramembrane charge movements of both Hom and heterozygous (Het) myotubes displayed hyperpolarizing shifts similar to that observed in voltage-gated SR Ca2+ release. The current–voltage relationships for L-type currents in both Hom and Het myotubes were also shifted to more hyperpolarizing potentials (∼7 and 5 mV, respectively). Compared with WT myotubes, Het and Hom myotubes both displayed a greater sensitivity to the L-type channel agonist ±Bay K 8644 (10 µM). In general, L-type currents in WT, Het, and Hom myotubes inactivated modestly after 30-s prepulses to −50, −10, 0, 10, 20, and 30 mV. However, L-type currents in Hom myotubes displayed a hyperpolarizing shift in inactivation relative to L-type currents in either WT or Het myotubes. Our present results indicate that mutations in RYR1 can alter DHPR activity and raise the possibility that this altered DHPR function may contribute to MH episodes.
Neuron–astrocyte interactions in the medial nucleus of the trapezoid body
Authors: Reyes-Haro Daniel , Müller Jochen , Boresch Margarethe , Pivneva Tatjyana , Benedetti Bruno , Scheller Anja , Nolte Christiane , Kettenmann Helmut
Published: May 2010

The calyx of Held (CoH) synapse serves as a model system to analyze basic mechanisms of synaptic transmission. Astrocyte processes are part of the synaptic structure and contact both pre- and postsynaptic membranes. In the medial nucleus of the trapezoid body (MNTB), midline stimulation evoked a current response that was not mediated by glutamate receptors or glutamate uptake, despite the fact that astrocytes express functional receptors and transporters. However, astrocytes showed spontaneous Ca2+ responses and neuronal slow inward currents (nSICs) were recorded in the postsynaptic principal neurons (PPNs) of the MNTB. These currents were correlated with astrocytic Ca2+ activity because dialysis of astrocytes with BAPTA abolished nSICs. Moreover, the frequency of these currents was increased when Ca2+ responses in astrocytes were elicited. NMDA antagonists selectively blocked nSICs while D-serine degradation significantly reduced NMDA-mediated currents. In contrast to previous studies in the hippocampus, these NMDA-mediated currents were rarely synchronized.
Identification of a protein–protein interaction between KCNE1 and the activation gate machinery of KCNQ1
Authors: Lvov Anatoli , Gage Steven D. , Berrios Virla M. , Kobertz William R.
Published: May 2010

KCNQ1 channels assemble with KCNE1 transmembrane (TM) peptides to form voltage-gated K+ channel complexes with slow activation gate opening. The cytoplasmic C-terminal domain that abuts the KCNE1 TM segment has been implicated in regulating KCNQ1 gating, yet its interaction with KCNQ1 has not been described. Here, we identified a protein–protein interaction between the KCNE1 C-terminal domain and the KCNQ1 S6 activation gate and S4–S5 linker. Using cysteine cross-linking, we biochemically screened over 300 cysteine pairs in the KCNQ1–KCNE1 complex and identified three residues in KCNQ1 (H363C, P369C, and I257C) that formed disulfide bonds with cysteine residues in the KCNE1 C-terminal domain. Statistical analysis of cross-link efficiency showed that H363C preferentially reacted with KCNE1 residues H73C, S74C, and D76C, whereas P369C showed preference for only D76C. Electrophysiological investigation of the mutant K+ channel complexes revealed that the KCNQ1 residue, H363C, formed cross-links not only with KCNE1 subunits, but also with neighboring KCNQ1 subunits in the complex. Cross-link formation involving the H363C residue was state dependent, primarily occurring when the KCNQ1–KCNE1 complex was closed. Based on these biochemical and electrophysiological data, we generated a closed-state model of the KCNQ1–KCNE1 cytoplasmic region where these protein–protein interactions are poised to slow activation gate opening.
State-dependent electrostatic interactions of S4 arginines with E1 in S2 during Kv7.1 activation
Authors: Wu Dick , Delaloye Kelli , Zaydman Mark A. , Nekouzadeh Ali , Rudy Yoram , Cui Jianmin
Published: May 2010

The voltage-sensing domain of voltage-gated channels is comprised of four transmembrane helices (S1–S4), with conserved positively charged residues in S4 moving across the membrane in response to changes in transmembrane voltage. Although it has been shown that positive charges in S4 interact with negative countercharges in S2 and S3 to facilitate protein maturation, how these electrostatic interactions participate in channel gating remains unclear. We studied a mutation in Kv7.1 (also known as KCNQ1 or KvLQT1) channels associated with long QT syndrome (E1K in S2) and found that reversal of the charge at E1 eliminates macroscopic current without inhibiting protein trafficking to the membrane. Pairing E1R with individual charge reversal mutations of arginines in S4 (R1–R4) can restore current, demonstrating that R1–R4 interact with E1. After mutating E1 to cysteine, we probed E1C with charged methanethiosulfonate (MTS) reagents. MTS reagents could not modify E1C in the absence of KCNE1. With KCNE1, (2-sulfonatoethyl) MTS (MTSES)− could modify E1C, but [2-(trimethylammonium)ethyl] MTS (MTSET)+ could not, confirming the presence of a positively charged environment around E1C that allows approach by MTSES− but repels MTSET+. We could change the local electrostatic environment of E1C by making charge reversal and/or neutralization mutations of R1 and R4, such that MTSET+ modified these constructs depending on activation states of the voltage sensor. Our results confirm the interaction between E1 and the fourth arginine in S4 (R4) predicted from open-state crystal structures of Kv channels and reveal an E1–R1 interaction in the resting state. Thus, E1 engages in electrostatic interactions with arginines in S4 sequentially during the gating movement of S4. These electrostatic interactions contribute energetically to voltage-dependent gating and are important in setting the limits for S4 movement.
Behavioural thermoregulation in two freshwater fish species
Authors: Ward A. J. W. , Hensor E. M. A. , Webster M. M. , Hart P. J. B.
Published: May 2010

In the presence of a vertical thermal gradient, juvenile three‐spined sticklebacksGasterosteus aculeatusand minnowsPhoxinus phoxinuspositioned themselves higher in the water column compared with adult conspecifics. This result was consistent regardless of whether age cohorts were tested separately or together. Furthermore, juveniles but not adult fishes positioned themselves higher in water column in the presence of a thermal gradient compared with those in the absence of a thermal gradient. JuvenileG. aculeatusand adult fish of both species did opt to position themselves higher in the water column in the hours immediately following a feeding event relative to their positions in the same gradient when they had not fed.
Altitudinal variation in fish assemblage diversity in streams of the central Andes of Colombia
Authors: Jaramillo‐Villa U. , Maldonado‐Ocampo J. A. , Escobar F.
Published: May 2010

This study documents differences in fish assemblages for 32 freshwater streams located between 258 and 2242 m a.s.l. on the eastern slopes of the central range of the Colombian Andes. A total of 2049 fishes belonging to 62 species, 34 genera and 16 families were collected. Species richness declined rapidly with altitude; nearly 90% of the species were recorded between 250 and 1250 m a.s.l. Three of the four physico‐chemical variables, of the water, temperature, dissolved oxygen and pH, explained 53·5% of the variation in species richness along the altitudinal gradient, with temperature the most important (37·6%). An analysis of species composition showed that the distinctiveness of the fish fauna increased with elevation, with the greatest turnover observed between 1000 and 1750 m a.s.l. On this altitudinal gradient, turnover was dominated by the loss of species rather than gain, and dominance by just a few species was greater at higher elevations. Turnover was also observed along the altitudinal gradient in the structure of the three functional groups (torrential, pool and pelagic species). The study focused on understanding the pattern of diversity of fish communities inhabiting the Andes in Colombia. Anthropogenic effects on the altitudinal distribution of fish species in the region, however, are largely unknown and would require further investigations.
Immunoglobulin G fragment C receptor polymorphisms and KRAS mutations: Are they useful biomarkers of clinical outcome in advanced colorectal cancer treated with anti‐EGFR‐based therapy?
Authors: Paez David , Paré Laia , Espinosa Iñigo , Salazar Juliana , Del Rio Elisabeth , Barnadas Agustí , Marcuello Eugenio , Baiget Montserrat
Published: May 2010

KRAS mutations have been identified as a strong predictor of resistance to anti‐epidermal growth factor receptor (EGFR) therapies. Besides inhibiting the EGFR pathway, anti‐EGFR monoclonal antibodies may exert antitumor effects through antibody‐dependent cell‐mediated cytotoxicity (ADCC). Through this mechanism, the antibody fragment C portion (Fcγ) interacts with Fc receptors (FcγRs) expressed by immune effectors cells. We investigated the association of FcγR polymorphisms and KRAS mutation with the clinical outcome of 104 refractory metastatic colorectal cancer (mCRC) patients treated with anti‐EGFR antibodies. FcγRIIa‐H131R and FcγRIIIa‐V158F polymorphisms were analyzed in genomic DNA using a 48.48 dynamic array on the BioMark system (Fluidigm, South Sanfrancisco, CA, USA). Tumor tissues from 96 cases were screened for KRAS mutations. KRAS mutation was associated with a lower response rate (RR) (P = 0.035) and a shorter progression‐free survival (PFS) (3 vs 7 months; P = 0.36). FcγRIIa‐H131R and FcγRIIIa‐V158F polymorphisms did not show statistically significant associations with response, PFS, or KRAS status. In the logistic regression analysis, KRAS status (P = 0.04) and skin toxicity (P = 0.03) were associated with RR. By multivariate analysis, the clinical risk classification (P = 0.006) and skin toxicity (P < 0.0001) were found to be independent risk factors for PFS. In conclusion, the FcγRIIa and FcγRIIIa polymorphisms are not useful as molecular markers for clinical outcome in mCRC patients. To date, the EORTC (European Organization for Research and Treatment of Cancer Classification), skin toxicity, and KRAS status are the only reliable biomarkers to identify patients that would benefit from anti‐EGFR therapy. (Cancer Sci 2010)
Systematic review: the use of nitrous oxide gas for lower gastrointestinal endoscopy
Authors: Welchman S. , Cochrane S. , Minto G. , Lewis S.
Published: May 2010

Aliment Pharmacol Ther 2010; 32: 324–333

Background  Nitrous oxide gas (N2O) has been proposed as an alternative to intravenous (i.v.) analgesia in patients undergoing lower gastrointestinal endoscopy.

Aim  To perform a systematic review of randomized studies where N2O was compared against control in patients undergoing either flexible sigmoidoscopy or colonoscopy.

Methods  Electronic databases were searched; reference lists were checked and letters were sent to authors requesting data. Methodological quality was assessed. Data were tabulated on the duration and difficulty of the procedure, quality of sedation and speed of patient recovery.

Results  A total of 11 studies were identified containing 623 patients. No differences were seen between groups for duration, difficulty of procedure or complications. Patient‐reported pain was similar for N2O when undergoing flexible sigmoidoscopy vs. no sedation and when undergoing colonoscopy vs. i.v. sedation. Differences in delivery of N2O were identified. In all studies, N2O was associated with a more rapid recovery than i.v. sedation.

Conclusion  For patients undergoing colonoscopy, N2O provides comparable analgesia to i.v. sedation. The rapid psychomotor recovery with N2O enables quicker patient discharge and removes the need for a patient to be chaperoned. Benefit was not seen from N2O in patients undergoing flexible sigmoidoscopy possibly because it was delivered on demand rather than continuously.
Clinical trial: evaluation of gastric acid suppression with three doses of immediate‐release esomeprazole in the fixed‐dose combination of PN 400 (naproxen/esomeprazole magnesium) compared with naproxen 500 mg and enteric‐coated esomeprazole 20 mg: a randomized, open‐label, Phase I study in healthy volunteers
Authors: Miner P. , Plachetka J. , Orlemans E. , Fort J. G. , Sostek M.
Published: May 2010

Aliment Pharmacol Ther 2010; 32: 414–424

Background  PN 400 is a fixed‐dose combination formulated to provide sequential delivery of immediate‐release (IR) esomeprazole and enteric‐coated (EC) naproxen.

Aim  To evaluate gastric acid suppression with three doses of esomeprazole in PN 400 compared with EC esomeprazole 20 mg.

Methods  In this Phase I, randomized, open‐label study, 28 healthy adults received PN 400 b.d. (naproxen 500 mg plus esomeprazole 10, 20 and 30 mg) and non‐EC naproxen 500 mg b.d. plus EC esomeprazole 20 mg o.d., each for 9 days in a crossover fashion. The primary endpoint was percentage of time on day 9 that intragastric pH was >4.0; secondary endpoints included pharmacokinetics and safety.

Results  Day 9 percentage of time where intragastric pH was >4.0 was 76.5%, 71.4%, 40.9% and 59.9% for PN 400 containing 30, 20 and 10 mg esomeprazole, and naproxen plus esomeprazole 20 mg respectively. This was significantly greater for PN 400 containing 30 and 20 mg esomeprazole vs. naproxen plus esomeprazole 20 mg (95% CI: 13.0–26.0 and 7.8–20.7 respectively). The pharmacokinetics of PN 400 were consistent with its formulation. No serious adverse events occurred.

Conclusion  PN 400 containing 20 mg esomeprazole was the lowest dose to achieve gastric acid suppression comparable to EC esomeprazole 20 mg and was selected for further evaluation.
Natural history of acute colonic diverticular bleeding: a prospective study in 133 consecutive patients
Authors: Poncet G. , Heluwaert F. , Voirin D. , Bonaz B. , Faucheron J.‐L.
Published: May 2010

Aliment Pharmacol Ther 2010; 32: 466–471

Background  Bleeding recurrence rate after spontaneous haemostasis of colonic diverticular haemorrhage varies in the literature, and a small minority of patients will require endoscopic, radiological or surgical intervention.

Aim  To study the natural history of colonic diverticular bleeding in consecutive patients.

Methods  We studied prospectively consecutive patients admitted for colonic diverticular bleeding from 1997 to 2005. Data on age, gender, 30‐day mortality, therapeutic modality for bleeding management and subsequent rebleeding were collected.

Results  One hundred and thirty‐three patients (mean age 75.7 years) were recruited. Bleeding stopped spontaneously in 123 patients (92.4%). A more interventional approach was necessary in 10 patients. Thirty‐day mortality rate for first bleeding was 2.25%. Out of the 123 patients managed conservatively and submitted to an average follow‐up of 47.5 months, 17 (13.8%) presented at least one recurrent diverticular bleeding. Spontaneous haemostasis was obtained in all recurrent cases except one, who died. The estimated bleeding recurrence rate was 3.8% at 1 year, 6.9% at 5 years and 9.8% at 10 years.

Conclusions  The low estimated rebleeding rate and the fact that rebleeding can be treated conservatively in most cases suggest that an aggressive approach with intervention is not justified.
Clinical trial: prolonged beneficial effect of Helicobacter pylori eradication on dyspepsia consultations – the Bristol Helicobacter Project
Authors: Harvey R. F. , Lane J. A. , Nair P. , Egger M. , Harvey I. , Donovan J. , Murray L.
Published: May 2010

Aliment Pharmacol Ther 2010; 32: 394–400

Background  Chronic infection of the stomach with Helicobacter pylori is widespread throughout the world and is the major cause of peptic ulcer disease and gastric cancer. Short‐term benefit results from community programmes to eradicate the infection, but there is little information on cumulative long‐term benefit.

Aim  To determine whether a community programme of screening for and eradication of H. pylori infection produces further benefit after an initial 2‐year period, as judged by a reduction in GP consultations for dyspepsia.

Methods  A total of 1517 people aged 20–59 years, who were registered with seven general practices in Frenchay Health District, Bristol, had a positive 13C‐urea breath test for H. pylori infection and were entered into a randomized double‐blind trial of H. pylori eradication therapy. After 2 years, we found a 35% reduction in GP consultations for dyspepsia (previously reported). In this extension to the study, we analysed dyspepsia consultations between two and 7 years after treatment.

Results  Between two and 7 years after treatment, 81/764 (10.6%) of participants randomized to receive active treatment consulted for dyspepsia, compared with 106/753 (14.1%) of those who received placebo, a 25% reduction, odds ratio 0.84 (0.71, 1.00), P = 0.042.

Conclusions  Eradication of H. pylori infection in the community gives cumulative long‐term benefit, with a continued reduction in the development of dyspepsia severe enough to require a consultation with a general practitioner up to at least 7 years. The cost savings resulting from this aspect of a community H. pylori eradication programme, in addition to the other theoretical benefits, make such programmes worthy of serious consideration, particularly in populations with a high prevalence of H. pylori infection.
Microsatellite analysis revealed genetic diversity and population structure among Chinese cashmere goats
Authors: Di R. , Farhad Vahidi S. M. , Ma Y. H. , He X. H. , Zhao Q. J. , Han J. L. , Guan W. J. , Chu M. X. , Sun W. , Pu Y. P.
Published: May 2010

Most cashmere goats are found in northern China and Mongolia. They are regarded as precious resources for their production of high quality natural fibre for the textile industry. It was the first time that the genetic diversity and population structure of nine Chinese cashmere populations has been assessed using 14 ISAG/FAO microsatellite markers. In addition, two Iranian populations and one West African goat population were genotyped for comparison. Results indicated that the genetic diversity of Chinese cashmere goats was rich, but less than those of the Iranian goat populations. All pairwise FST values between the Chinese cashmere goat populations reached a highly significant level (P < 0.001), suggesting that they should all be considered as separate breeds. Finally, clustering analysis divided Chinese cashmere goats into at least two clusters, with the Tibetan Hegu goats alone in one cluster. An extensive admixture was detected among the Chinese goat breeds (except the Hegu), which have important implications for breeding management.
Concomitant use of ibuprofen and paracetamol and the risk of major clinical safety outcomes
Authors: De Vries Frank , Setakis Efrosini , Van Staa Tjeerd‐Pieter
Published: May 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

Non‐steroidal anti‐inflammatory drugs (NSAIDs) and paracetamol are widely used analgesics in the prescription and non‐prescription settings. Although both classes of drug are generally well tolerated, they can lead to well‐characterized adverse effects. Both drugs are widely co‐prescribed and it is of interest to understand better safety outcomes when the two drugs are taken concomitantly.

WHAT THIS STUDY ADDS?

Relative rates and hazard ratio patterns of safety outcomes were broadly similar for patients prescribed ibuprofen alone, paracetamol alone and concomitant ibuprofen and paracetamol. The risks of the various safety outcomes examined do not appear to be modified by concomitant use of ibuprofen and paracetamol compared with paracetamol or ibuprofen alone.

AIMS

To evaluate and compare the risk of specific safety outcomes in patients prescribed ibuprofen and paracetamol concomitantly with those in patients prescribed ibuprofen or paracetamol alone. The outcomes were evaluated according to dose, duration and exposure.

METHODS

The study used a retrospective longitudinal cohort design with data from the UK General Practice Research Database (GPRD). The study population included patients aged 18 years or over who were prescribed ibuprofen alone, paracetamol alone or concomitant ibuprofen and paracetamol (tablets or capsules only). The safety outcomes evaluated were upper gastrointestinal events, myocardial infarction, stroke, renal failure (excluding chronic), congestive heart failure, intentional or accidental overdose, suicidal behaviour and mortality. Time‐dependent Cox regression was used to estimate relative rates for the safety outcomes, by treatment group. A further analysis evaluated whether the hazard rates (i.e. absolute risks) varied over time with changes in drug exposure.

RESULTS

The study population included 1.2 million patients. There was considerable heterogeneity in both patient and exposure characteristics. When comparing with past users, for most safety outcomes, current users of concomitant paracetamol and ibuprofen had relative rates between those for current users of ibuprofen alone and paracetamol alone. The hazard rates were generally proportional over time, from current to past exposure, following a prescription for concomitant paracetamol and ibuprofen compared with ibuprofen alone or paracetamol alone.

CONCLUSIONS

The known risk of the safety outcomes examined does not appear to be modified by concomitant use of ibuprofen and paracetamol compared with paracetamol or ibuprofen alone.
How tumour necrosis factor blockers interfere with tuberculosis immunity
Authors: Harris J , Keane J
Published: May 2010

Tumour necrosis factor (TNF) is a potent inflammatory cytokine that plays an important role in immunity to numerous bacterial infections, including Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB) in humans. Infliximab, adalimumab, certolizumab pegol and etanercept are anti-TNF agents used to treat a range of inflammatory/autoimmune diseases, such as rheumatoid arthritis. The use of some of these drugs has been linked to reactivation TB. In addition to blocking TNF-mediated immune responses, some anti-TNF drugs have been found to interfere with innate immune responses, such as phagolysosomal maturation and monocyte apoptosis, as well as cell-mediated responses, including interferon-γ secretion by memory T cells, complement-mediated lysis of Mtb-reactive CD8+ T cells and increased regulatory T cell activity. This review summarizes some of the reported effects of TNF blockers on immune cell responses in the context of the observed clinical data on TB reactivation in patients on anti-TNF therapy.
The Type 1 Diabetes PhysioLab® Platform: a validated physiologically based mathematical model of pathogenesis in the non-obese diabetic mouse
Authors: Shoda L , Kreuwel H , Gadkar K , Zheng Y , Whiting C , Atkinson M , Bluestone J , Mathis D , Young D , Ramanujan S
Published: May 2010

Type 1 diabetes is an autoimmune disease whose clinical onset signifies a lifelong requirement for insulin therapy and increased risk of medical complications. To increase the efficiency and confidence with which drug candidates advance to human type 1 diabetes clinical trials, we have generated and validated a mathematical model of type 1 diabetes pathophysiology in a well-characterized animal model of spontaneous type 1 diabetes, the non-obese diabetic (NOD) mouse. The model is based on an extensive survey of the public literature and input from an independent scientific advisory board. It reproduces key disease features including activation and expansion of autoreactive lymphocytes in the pancreatic lymph nodes (PLNs), islet infiltration and β cell loss leading to hyperglycaemia. The model uses ordinary differential and algebraic equations to represent the pancreas and PLN as well as dynamic interactions of multiple cell types (e.g. dendritic cells, macrophages, CD4+ T lymphocytes, CD8+ T lymphocytes, regulatory T cells, β cells). The simulated features of untreated pathogenesis and disease outcomes for multiple interventions compare favourably with published experimental data. Thus, a mathematical model reproducing type 1 diabetes pathophysiology in the NOD mouse, validated based on accurate reproduction of results from multiple published interventions, is available for in silico hypothesis testing. Predictive biosimulation research evaluating therapeutic strategies and underlying biological mechanisms is intended to deprioritize hypotheses that impact disease outcome weakly and focus experimental research on hypotheses likely to provide insight into the disease and its treatment.
Vaginal vault cytology tests: analysis of a decade of data from a UK tertiary centre
Authors: Stokes‐Lampard H. , Wilson S. , Waddell C. , Bentley L.
Published: May 2010

H. Stokes‐Lampard, S. Wilson, C. Waddell and L. Bentley

Vaginal vault cytology tests: analysis of a decade of data from a UK tertiary centre

Objectives:  To examine temporal trends in the use of vault cytology tests in primary and secondary care and the demographics of those women tested.

Methods:  Retrospective analysis of routinely collected data concerning women who had a vault cytology test processed during a 10‐year period (1 April 1995 to 31 March 2005) at Birmingham Women’s NHS Foundation Trust.

Results:  A total of 8457 vault cytology tests from 3164 women (range 1–17 tests, median = 2) were processed, representing approximately 2% of the cervical cytology workload of the Department of Cytopathology at Birmingham Women's Hospital. There was a significant reduction in annual numbers processed (Pearson correlation −0.958, P < 0.001). Significant abnormalities (mild dyskaryosis or worse) were detected in 4.5%, with malignancy being detected in <0.1%. The unsatisfactory cytology test rate was 10.7% overall. There was a reduction in the numbers of vault cytology tests coming from the community, hospital outpatient clinics and operating theatres over time (χ2 for linear trend = 139.53, 9 d.f., P < 0.0001). Tests originating from community settings had the lowest disease detection rates: no malignancies and only two severe abnormalities were detected from almost 4000 primary care samples; abnormal results represented 2.8% (n = 113), of which the majority (n = 73) were borderline results. All cancers (n = 8) were detected in samples taken in gynaecology and colposcopy clinics.

Conclusions:  Vault cytology test usage appears to be reducing, particularly from outpatient clinics and primary care. Community detection rates are very low. Further research is required to establish the true costs and benefits of vaginal vault cytology.
Accuracy and perceptions of virtual microscopy compared with glass slide microscopy in cervical cytology
Authors: Evered A. , Dudding N.
Published: May 2010

A. Evered and N. Dudding

Accuracy and perceptions of virtual microscopy compared with glass slide microscopy in cervical cytology

Objective:  To evaluate virtual microscopy in terms of diagnostic performance and acceptability among practising cytologists.

Methods:  Twenty‐four experienced cytologists were recruited to examine 20 SurePath® cervical cytology slides by virtual microscopy. Diagnostic accuracy was compared with glass slide microscopy using an unbiased crossover experimental design. Responses were allocated a score of one for a correct identification of normal or abnormal (borderline/atypical changes in squamous or glandular cells or worse) and a score of zero for an incorrect response (a normal slide reported as abnormal or vice versa). Perceptions of virtual microscopy were assessed by questionnaire analysis.

Results:  Participants yielded a total of 285 responses for the virtual slide set and 300 for the glass slide set. The approximate time to screen a virtual slide was 18 minutes, compared with 8 minutes or less for a glass slide. Overall there was no significant difference between virtual microscopy and glass slide microscopy in terms of diagnostic accuracy (P = 0.22). Virtual microscopy under‐performed when images were captured over a narrow focal range (P = 0.01). Diagnostic accuracy of virtual microscopy equalled that of glass slide microscopy when participants were able to focus through the full thickness of the slide images (P = 0.07). The most common difficulties experienced by participants with virtual microscopy were freezing of the computer screen during image download, slow response of the computer during slide movement and, in some instances, ‘fuzzy’ images. Cytologists have a strong preference for glass slides over virtual microscopy despite the overall equal diagnostic performance of the two viewing modalities.

Conclusions:  Diagnostic accuracy of virtual microscopy can equal that of glass slide microscopy. However, without good computer network connections, wide focal range and software that permits effortless navigation across virtual slides, cytologists are unlikely to be convinced of the utility of this technology for cytology screening and diagnosis.
A multi‐trait approach reveals the structure and the relative importance of intra‐ vs. interspecific variability in plant traits
Authors: Albert Cécile Hélène , Thuiller Wilfried , Yoccoz Nigel Gilles , Douzet Rolland , Aubert Serge , Lavorel Sandra
Published: May 2010

1. Functional traits have been extensively used to describe, group and rank species according to their functions. There is now growing evidence that intraspecific functional variability, as well as interspecific variability, can have significant effects on community dynamics and ecosystem functioning. A core hypothesis for the use of functional traits expressed as species means, that their intraspecific variability is negligible compared with their interspecific variability, has however been too rarely tested empirically. We then addressed four questions: Is intraspecific functional variability across species ranges negligible compared with interspecific variability? Are the major resource economics trade‐off and functional strategies robust to individual trait variability? Are species rankings or ordination robust across species ranges once considering intraspecific variability? Can species be discriminated by their leaf traits?

2. Using an environmentally stratified sampling design within an alpine catchment, we collected five functional traits for 13 common plant species with contrasting life histories and traits. Several populations from a range of environmental conditions were then sampled for each species across their ranges.

3. With an original combination of single‐trait and multi‐trait analyses, we highlighted a non‐negligible contribution of intraspecific variability to overall functional trait variability (∼30%). Although not affecting general and well‐known functional trade‐offs and strategies, intraspecific functional variability had the potential to alter species ordination and produced a functional continuum rather than a clear‐cut species classification.

4. Deciding whether intraspecific functional variability can be considered as negligible – species being represented by mean trait values –, or not – species being represented by multivariate trait distributions –, is an essential question for multiple ecological issues. However, this decision cannot be generic, but will depend on the studied system and selected traits and species, as well as on study objectives.