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Parental mentalization refers to a parents’ capacity and interest to consider the individual experience and mental state underlying the behaviors of the child. Higher mentalization is considered a key aspect for parental sensitivity in interaction, fostering child’s socioemotional and self-regulatory development. Yet, previous studies have not examined the dynamic pathways through which the maternal mentalization may develop, nor their effects on child development. Thus, in the current person-oriented study, first, we identify distinct profiles and longitudinal trajectories of maternal mentalization from pregnancy to child’s 2 years of age. Second, we test how the profiles and trajectories associate with children’s internalizing and externalizing problems, social–emotional competence and effortful control at the age of 2 years. Third, we examine how the profiles and trajectories associate with contextual demographic and child related. The substudy was part of the FinnBrain Birth Cohort and included families from general population (n = 2,687). Mothers reported their parental reflective functioning (PRF) at late pregnancy, 6 months and 2 years of child’s age. Both mothers (n = 1,437) and fathers (n = 715) reported the developmental child outcomes at the child’s age of 2 years. Latent Profile Analysis and Latent Transition Analysis were used to identify PRF profiles and trajectories. The results showed decreasing heterogeneity in PRF from pregnancy to child’s age of 6 months and 2 years (i.e., four, three and two latent classes, respectively). Most mothers progressed towards high PRF over time. Second, the profiles and trajectories depicting high PRF associated with child high social–emotional competence at the age of 2 years, yet no clear positive effects were found on child’s problems and effortful control. The group of mixed PRF trajectories showed strongest association with child’s internalizing and externalizing problems. Finally, there were theoretically meaningful associations between the PRF trajectories and both the contextual (e.g., parity) and child related (e.g., infant temperament) factors. This was the first study to explore the early unfolding of maternal mentalization. The results are discussed in relation with the potential mechanisms accounting for child development and with the nature and limitations of self-reported parental mentalization.

STUDY QUESTION Does adolescent attachment to parents and peers differ between singletons and twins born with ART or natural conception (NC)? SUMMARY ANSWER Adolescent attachment anxiety with the father was higher among NC singletons than among ART and NC twins, whereas attachment avoidance with the father was higher in ART singletons than in NC singletons and NC twins. No differences were found in attachment to the mother, best friend or romantic partner. WHAT IS KNOWN ALREADY Most studies have not found differences between ART and NC singletons in parent–adolescent relationships, but twin relationships may be more at risk. No previous study has examined all four groups in the same study, or specifically looked at attachment relationships. STUDY DESIGN, SIZE, DURATION This was an 18-year, prospective and controlled longitudinal study with families of 496 ART singletons, 101 ART twin pairs, 476 NC singletons and 22 NC twin pairs. Families were recruited during the second trimester of pregnancy; the ART group was recruited from five infertility clinics in Finland and the control group was recruited from a hospital outpatient clinic during a routine visit. PARTICIPANTS/MATERIALS, SETTING, METHODS Mothers and fathers gave background information for this study during pregnancy, and during the child’s first year and early school age (7–8 years). For the ART group, infertility characteristics and prenatal medical information was also obtained from the patient registry of the infertility clinics. Children (originally 50% girls) filled in electronic questionnaires related to their attachment to mother, father, best friend and romantic partner (Experiences in Close Relationships—Relationship Structures) at 17–19 years of age. MAIN RESULTS AND THE ROLE OF CHANCE Adolescent attachment anxiety to father was higher in NC singletons than in ART twins, P = 0.004 and marginally higher than in NC twins, P = 0.06. Adolescent attachment avoidance to father was higher in ART singletons than in NC singletons, P = 0.006 and marginally higher than in NC twins, P = 0.055. LIMITATIONS, REASONS FOR CAUTION The sample size was small especially in the NC twin group and there was drop-out over the 18-year time period, especially among boys and families with lower parental education level. The study only included native Finnish-speaking families. The results could differ in a more diverse population. ART singletons were younger and had fewer siblings than ART twins and NC children, and ART and NC twins had more newborn health risks than ART and NC singletons. WIDER IMPLICATIONS OF THE FINDINGS The study adds to a growing body of evidence that neither ART treatments nor being a twin places mother–child relationships or peer relationships at long-term risk. However, in our study, which was the first to examine both ART and twinhood simultaneously, we found that there may be more problems in father–adolescent relationships, but only in ART singletons and only related to attachment avoidance. Our findings suggest that men, as well as women, should receive enough support in pre- and peri-natal health care during and after infertility treatments. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by Academy of Finland (grant number 2501308988), the Juho Vainio Foundation and the Finnish Cultural Foundation. The authors report no conflict of interest. TRIAL REGISTRATION NUMBER N/A.

BackgroundInvolvement of the nervous system is a common but poorly understood manifestation of systemic lupus erythematosus (SLE), termed neuropsychiatric SLE (NPSLE). Although studies have reported varying prevalence estimates [1], NPSLE affects at least 20% of patients with SLE within the first years of the disease course [2]. The management of neuropsychiatric SLE (NPSLE) is poorly optimised and specific treatment is lacking.ObjectivesThe aim of this study was to investigate expression quantitative trait loci (eQTLs), the transcriptome, and autoimmunity-related cytokines and autoantibodies in patients with central nervous system (CNS) lupus to gain insights into underlying genetics and biologic mechanisms towards identification of novel drug targets.MethodsWe analysed differentially expressed genes (DEGs), pathways and their druggability via the Drug Gene Interaction database (DGIdb) [3] in active CNS lupus (n=26) versus healthy controls (HC; n=497), and eQTLs in active or past CNS lupus (n=53), based on validated (identified in two independent SLE populations) DEGs in SLE (n=350) versus HC (n=497), in whole blood collected within the frame of the European PRECISESADS consortium [4]. CNS lupus was defined according to SLE Disease Activity Index 2000 (SLEDAI-2K) [5] CNS items or by CNS manifestations such as chorea, acute confusional state, transverse myelitis, aseptic meningitis, and optic neuritis in the absence of predisposing conditions unrelated to SLE. Genome-wide RNA-sequencing and genotyping was previously performed by Illumina assays, and serum levels of 17 cytokines were analysed using a Luminex assay and ELISA [4].ResultsAmong 5631 significant and validated DEGs in active CNS patients compared with HC, 1922 unique DEGs were tagged to 21 and 176 significant KEGG [6] and Reactome [7] pathways, respectively. Pathways included “Interferon signalling”, “TNF signalling” and “Toll-like Receptor Cascades”. The pathways included 29 of 59 DEGs with a |fold change (FC)| > 1.5, 6 genes from 14 significant cis-eQTLs and 10 genes from 22 trans-eQTLs, and 2 genes from 8 cytokines that differed significantly between active CNS lupus and HC. These genes could be targeted by 496 different drugs, with the Bruton tyrosine kinase (BTK) inhibitor ibrutinib and the anti-CD20 B cell depleting monoclonal rituximab with ability to interfere with tumour protein P53 (TP53) activity, and a complement C3a Receptor (C3aR) antagonist being of particular interest.ConclusionIntegrated multilevel omics analysis revealed a set of enriched pathways of potential interest for future drug investigation in CNS lupus, including BTK and C3aR inhibition, and B cell depletion.References[1]Unterman A, Nolte JE, Boaz M, Abady M, Shoenfeld Y, Zandman-Goddard G. Neuropsychiatric syndromes in systemic lupus erythematosus: a meta-analysis. Semin Arthritis Rheum. 2011 Aug; 41(1):1-11[2]Hanly JG, Urowitz MB, Su L, Bae SC, Gordon C, Wallace DJ, et al. Prospective analysis of neuropsychiatric events in an international disease inception cohort of patients with systemic lupus erythematosus. Ann Rheum Dis. 2010 Mar; 69(3):529-535[3]Wagner AH, Coffman AC, Ainscough BJ, Spies NC, Skidmore ZL, Campbell KM, et al. DGIdb 2.0: mining clinically relevant drug-gene interactions. Nucleic Acids Res. 2016 Jan 4; 44(D1):D1036-1044[4]Barturen G, Babaei S, Català-Moll F, Martínez-Bueno M, Makowska Z, Martorell-Marugán J, et al. Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases. Arthritis Rheumatol. 2021 Jun; 73(6):1073-1085[5]Gladman DD, Ibanez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol. 2002 Feb; 29(2):288-291[6]Kanehisa M, Furumichi M, Tanabe M, Sato Y, Morishima K. KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4; 45(D1):D353-d361[7]Jassal B, Matthews L, Viteri G, Gong C, Lorente P, Fabregat A, et al. The reactome pathway knowledgebase. Nucleic Acids Res. 2020 Jan 8; 48(D1):D498-d503AcknowledgementsThe PRECISESADS clinical consortiumDisclosure of InterestsNone declared

BackgroundLupus nephritis (LN) is one of the most severe organ manifestations of systemic lupus erythematosus (SLE) and constitutes an important cause of morbidity and death among patients with SLE [1]. The associated renal injury, and ultimately damage, is the result of an immune-mediated process which involves leukocytes, immune complexes, complement and cytokines [2].ObjectivesLupus nephritis (LN) is one of the most severe organ manifestations of systemic lupus erythematosus (SLE) and constitutes an important cause of morbidity and death among patients with SLE [1]. The associated renal injury, and ultimately damage, is the result of an immune-mediated process which involves leukocytes, immune complexes, complement and cytokines [2].MethodsWe analysed differentially expressed genes (DEGs), pathways and their druggability via the Drug Gene Interaction database (DGIdb) [3] in active LN (n=41) versus healthy controls (HC; n=497), and eQTLs in active or past LN (n=87), based on validated (identified in two independent SLE populations) DEGs in SLE (n=350) vs HC (n=497), in whole blood collected within the frame of the European PRECISESADS consortium [4]. Genome-wide RNA-sequencing and genotyping was previously performed by Illumina assays, and serum levels of 17 cytokines and 18 autoantibodies were analysed using a Luminex assay, ELISA, IDS-iSYS and SPAPLUS analyser [4].ResultsA total of 6 869 significant and validated DEGs were identified in active LN patients compared with HC. Of these, 1010 validated DEGs were tagged to 34 KEGG pathways including 24 DEGs with a |fold change (FC)| > 1.5, genes of 18 cis-eQTLs and 3 trans-eQTLs, and 1 gene from cytokines that differed significantly between active LN and HC. Moreover, 2446 validated DEGs were tagged to 216 Reactome pathways included 85 DEGs with a |FC| > 1.5, genes of 21 cis-eQTLs and 5 trans-eQTLs, and 1 gene from cytokines that differed significantly between active LN and HC. These genes could be targeted by 203 different drugs, with the proteasome inhibitor bortezomib interfering with cathepsin B (CTSB) regulation and cyclophosphamide interfering with the regulation of tumour necrosis factor receptor superfamily member 1A (TNFRSF1A) being of particular interest.ConclusionIntegrated multilevel omics analysis in LN revealed a set of enriched pathways of potential interest for future drug investigation. A prospect for proteasome inhibition was implicated.References[1]Croca SC, Rodrigues T, Isenberg DA. Assessment of a lupus nephritis cohort over a 30-year period. Rheumatology (Oxford). 2011 Aug; 50(8):1424-1430.[2]Anders HJ, Saxena R, Zhao MH, Parodis I, Salmon JE, Mohan C. Lupus nephritis. Nat Rev Dis Primers. 2020 Jan 23; 6(1):7.[3]Wagner AH, Coffman AC, Ainscough BJ, Spies NC, Skidmore ZL, Campbell KM, et al. DGIdb 2.0: mining clinically relevant drug-gene interactions. Nucleic Acids Res. 2016 Jan 4; 44(D1):D1036-1044.[4]Barturen G, Babaei S, Català-Moll F, Martínez-Bueno M, Makowska Z, Martorell-Marugán J, et al. Integrative Analysis Reveals a Molecular Stratification of Systemic Autoimmune Diseases. Arthritis Rheumatol. 2021 Jun; 73(6):1073-1085.[5]Kanehisa M, Furumichi M, Tanabe M, Sato Y, Morishima K. KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4; 45(D1):D353-d361.[6]Jassal B, Matthews L, Viteri G, Gong C, Lorente P, Fabregat A, et al. The reactome pathway knowledgebase. Nucleic Acids Res. 2020 Jan 8; 48(D1):D498-d503.AcknowledgementsThe PRECISESADS Clinical ConsortiumDisclosure of InterestsNone declared

Background:Despite improvements in medical care that have contributed to prolonged life expectancy for people living with systemic lupus erythematosus (SLE) over the past decades, they still suffer from substantial diminutions of health-related quality of life (HRQoL) compared with the general population and with other chronic diseases.Some studies have demonstrated that conventional synthetic and biological disease-modifying agents contribute to improvements in SLE patients’ HRQoL, and responders to treatment have been shown to report greater improvements than non-responders. Although these observations are clinically relevant, improvement following a therapeutic intervention does not necessarily signify that the individual has achieved a satisfactory health state perception. In rheumatoid arthritis, significant pain and severe fatigue persist in a substantial proportion of patients who achieve a good clinical response to treatment or remission. This paradoxical observation has not been thoroughly explored in SLE.Objectives:To determine the prevalence of adverse HRQoL outcomes in patients with SLE who achieved an adequate clinical response after a 52-week long period on standard therapy plus belimumab or placebo, within the frame of two phase III clinical trials. We further aimed to compare frequencies of adverse HRQoL outcomes across different age categories and ethnic groups, and sought to identify contributing factors.Methods:We included patients who met the primary endpoint of the BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) trials (N=760/1684), i.e. attainment of the SLE Responder Index 4 at week 52. Accordingly, evaluation of adverse HRQoL outcomes was based on patient reports at week 52 from treatment initiation, using the Medical Outcomes Study Short Form 36 (SF-36) health survey and the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-Fatigue) scale. Adverse HRQoL outcomes were defined as (i) SF-36 scale scores ≤ the 5th percentile derived from age- and sex-matched US population-based norms from the SF-36 health survey user manual; and (ii) FACIT-Fatigue scores Pearson’s chi-square or Fisher’s exact tests were used to investigate associations between dichotomous variables. Comparisons of continuous data between SLE patients and age- and sex-matched norms were performed using the Wilcoxon signed-rank test. Multivariable logistic regression models were created in order to assess independence and priority of potential factors associated with adverse HRQoL outcomes.Results:We found clinically important diminutions of HRQoL in SLE patients compared with matched norms and high frequencies of adverse HRQoL outcomes, the highest in SF-36 general health (29.1%), followed by FACIT-Fatigue (25.8%) and SF-36 physical functioning (25.4%). Overall, frequencies were higher with increasing age. Black/African American and White/Caucasian patients reported higher frequencies than Asians and Indigenous Americans, while Hispanics experienced adverse HRQoL less frequently than non-Hispanics. Increasing organ damage was associated with adverse physical but not mental HRQoL outcomes; disease activity showed no impact. In multivariable logistic regression analysis, addition of belimumab to standard therapy was associated with lower frequencies of adverse SF-36 physical functioning (OR: 0.59; 95% CI: 0.39–0.91; P=0.016) and FACIT-F (OR: 0.53; 95% CI: 0.34–0.81; P=0.004).Conclusion:Substantial proportions of SLE patients reported adverse HRQoL outcomes despite adequate clinical response to treatment, especially in physical aspects. Particularly high proportions were seen within Black/African American and White/Caucasian patients. Add-on belimumab may be protective against adverse physical functioning and severe fatigue. Our results corroborate that HRQoL diminutions constitute a substantial burden in patients with SLE, and highlight the limitations of current therapeutic strategies.Acknowledgements:The authors would like to thank GlaxoSmithKline (Uxbridge, UK) for sharing the data from the BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) trials with the Clinical Study Data Request (CSDR) consortium, Dimitris Ladakis, Joaquin Matilla and Martin Pehr for contributing to the management of data, as well as all participating patients.Disclosure of Interests:Alvaro Gomez: None declared, Julius Lindblom: None declared, Victor Qiu: None declared, Arvid Cederlund: None declared, Alexander Borg: None declared, Sharzad Emamikia: None declared, Yvonne Enman: None declared, Jon Lampa: None declared, Ioannis Parodis Grant/research support from: Research funding and/or honoraria from Amgen, Elli Lilly and Company, Gilead Sciences, GlaxoSmithKline and Novartis.

Falling is a common accident among older people. Automatic fall detectors are one method of improving security. However, in most cases, fall detectors are designed and tested with data from experimental falls in younger people. This study is one of the first to provide fall-related acceleration data obtained from real-life falls. Wireless sensors were used to collect acceleration data during a six-month test period in older people. Data from five events representing forward falls, a sideways fall, a backwards fall, and a fall out of bed were collected and compared with experimental falls performed by middle-aged test subjects. The signals from real-life falls had similar features to those from intentional falls. Real-life forward, sideways and backward falls all showed a pre impact phase and an impact phase that were in keeping with the model that was based on experimental falls. In addition, the fall out of bed had a similar acceleration profile as the experimental falls of the same type. However, there were differences in the parameters that were used for the detection of the fall phases. The beginning of the fall was detected in all of the real-life falls starting from a standing posture, whereas the high pre impact velocity was not. In some real-life falls, multiple impacts suggested protective actions. In conclusion, this study demonstrated similarities between real-life falls of older people and experimental falls of middle-aged subjects. However, some fall characteristics detected from experimental falls were not detectable in acceleration signals from corresponding heterogeneous real-life falls.

Despite acting as a barrier for the organs they encase, epithelial cells turn over at some of the fastest rates in the body. However, epithelial cell division must be tightly linked to cell death to preserve barrier function and prevent tumour formation. How does the number of dying cells match those dividing to maintain constant numbers? When epithelial cells become too crowded, they activate the stretch-activated channel Piezo1 to trigger extrusion of cells that later die1. However, it is unclear how epithelial cell division is controlled to balance cell death at the steady state. Here we show that mammalian epithelial cell division occurs in regions of low cell density where cells are stretched. By experimentally stretching epithelia, we find that mechanical stretch itself rapidly stimulates cell division through activation of the Piezo1 channel. To stimulate cell division, stretch triggers cells that are paused in early G2 phase to activate calcium-dependent phosphorylation of ERK1/2, thereby activating the cyclin B transcription that is necessary to drive cells into mitosis. Although both epithelial cell division and cell extrusion require Piezo1 at the steady state, the type of mechanical force controls the outcome: stretch induces cell division, whereas crowding induces extrusion. How Piezo1-dependent calcium transients activate two opposing processes may depend on where and how Piezo1 is activated, as it accumulates in different subcellular sites with increasing cell density. In sparse epithelial regions in which cells divide, Piezo1 localizes to the plasma membrane and cytoplasm, whereas in dense regions in which cells extrude, it forms large cytoplasmic aggregates. Because Piezo1 senses both mechanical crowding and stretch, it may act as a homeostatic sensor to control epithelial cell numbers, triggering extrusion and apoptosis in crowded regions and cell division in sparse regions.

A speech coder tailored especially for the frame-erasure channel-the sinusoidal voice over packet coder (SVOPC)-is proposed. Based on a classified approach, avoiding interframe coding techniques, and synthesizing its output from slowly varying parameters, the coder is inherently robust to packet loss. SVOPC is based on quasi-harmonic modeling of the linear prediction (LP) residual. Both the sinusoidal amplitudes and phases are explicitly encoded using new methods based on Gaussian mixture models. A wide-band (16-kHz sampling frequency) implementation of the coder provides synthesized speech of good subjective quality at around 20 kbps. SVOPC is evaluated by means of subjective listening tests, and compared to a reference system based on G.722.2 (the AMR wide-band codec). Under frame erasure conditions (5%-30% frame erasures generated according to a Gilbert model), SVOPC clearly outperforms G.722.2.

Lately, Gaussian mixture (GM) models have found new applications in speech processing, and particularly in speech coding. This paper provides a review of GM based quantization and prediction. The main contribution is a discussion on GM model optimization. Two previously presented algorithms of EM-type are analyzed in some detail, and models are estimated and evaluated experimentally using theoretical measures as well as GM based speech spectrum coding and prediction. It has been argued that since many sources have a bounded support, this should be utilized in both the choice of model, and the optimization algorithm. By low-dimensional modeling examples, illustrating the behavior of the two algorithms graphically, and by full-scale evaluation of GM based systems, the advantages of a bounded support approach are quantified. For all evaluation techniques in the study, model accuracy is improved when the bounded support approach is adopted. The gains are typically largest for models with diagonal covariance matrices.

Creep data at 982 C and 950 C have been presented for the single crystal alloy CMSX-4. At these temperatures the creep rate is initially very low and 50% of the creep life is consumed in reaching {approximately}1% strain. Some steady-state creep occurred at 950 C. Low strains are important; plots of log, strain rate versus log, strain give more weight to low strains and also showed that tertiary creep is strain controlled. A linear strain softening approach described the increase in creep rate reasonably well. Creep curves, where time had been normalized with respect to the rupture life, could be superimposed at a given temperature, in spite of widely differing rupture lives. Normalized creep curves can only be superimposed if primary creep is negligible, but could be used as a means of estimating the rupture life of a long term test after a few millistrains have been reached.

Lateral diffusion in oriented bilayers of saturated cholesterol-containing phosphatidylcholines, dipalmitoylphosphatidylcholine and dimyrilstoylphosphatidylcholine upon their limiting hydration has been studied by NMR with impulse gradient of magnetic field. For both systems, similar dependences of the coefficient of lateral diffusion on temperature and cholesterol concentration were observed, which agree with the phase diagram showing the presence of regions of ordered and unordered liquid-crystalline phases and a two-phase region. Under similar conditions, the coefficient of lateral diffusion for dipalmytoylphosphatidylcholine has lower values, which is in qualitative agreement with its greater molecular mass. A comparison of data for dipalmytoylphosphatidylcholine with the results obtained earlier for dipalmytoylsphyngomyelin/cholesterol under the same conditions shows, despite a similarity in phase diagrams, greater (two- to threefold) differences in the values of the coefficient of lateral diffusion and a different mode of dependence of the coefficient on cholesterol concentration. A comparison of data for dimyrilstoylphosphatidylcholine with the results obtained previously shows that the values of the coefficient of lateral diffusion and the mode of its dependence on cholesterol concentration coincide in the region of higher concentrations (more than 15 mole %) and differ in the region of lower concentrations (below 15 mole %). The discrepancies may be explained by different contents of water in the systems during the measurements. At a limiting hydration (more than 35%) of water, the coefficient of lateral diffusion decreases with increasing cholesterol concentration. If the content of water is about 25% (as a result of equilibrium hydration from vapors), the coefficient of lateral diffusion of phosphatidylcholine is probably independent of cholesterol concentration. This results from a denser packing of molecules in the bilayer at a lower water concentration, an effect that competes with the ordering effect of cholesterol.

A framework for flexible and efficient coding of general stereo audio signals is proposed. Methods based on the framework can be used together with an arbitrary single channel (mono) coder to achieve seamless transition from pure parametric stereo coding to waveform approximating coding as the bitrate is increased. The idea, based on sum-difference encoding of time-aligned signal components, is presented as a general framework. An example implementation is demonstrated to have the desired convergence properties towards transparent quality.

We propose a low-delay packet loss concealment scheme for packetized voice communication. The scheme operates on the source-filter components of the speech signal and is to be implemented in receivers of a potential system. A sinusoidal model of successfully received speech is utilized to recover lost frames using both extrapolation and interpolation techniques. Informal subjective testing shows promising results; recovered packet losses are often inaudible to a listener.

In recent years a male group of anabolic-androgenic steroid misusers has been identified to share socio-demographic and personality related background factors with misusers of psychotropic substances, as well as being involved in habits of multiple drug use. The present study aimed to assess whether anabolic-androgenic steroids (AAS) would affect the density of the dopamine receptors in areas implicated in reward and behaviour in the male rat brain. The effects of 2 weeks of treatment with i.m. injections of nandrolone decanoate (15 mg/kg/day) on the expression of the D(1)-like and D(2)-like receptors were evaluated by autoradiography. Specific binding of D(1)-like receptors was significantly down regulated in the caudate putamen, the nucleus accumbens core and shell. D(2)-like receptor densities were down regulated in the nucleus accumbens shell, but up regulated in the caudate putamen, the nucleus accumbens core and the ventral tegmental area. These results are compatible with nandrolone induced neuroadaptive alterations in dopamine circuits associated with motor functions and behavioural paradigms known to be affected following AAS misuse.

To evaluate how and when mice run on a running wheel and how ad libitum access to the wheel affect behavior, feed intake, and weight gain.Seventeen 2-month-old C57BL/6J mice had access to the wheel, whereas 19 control mice did not. After 3 to 6.5 weeks, behavior was video-recorded over 24 h for each mouse.Experimental mice ran an average 2 km/24 h in 114 min. Highest running activity took place at the onset of darkness. Experimental mice spent 22 min more feeding on the cage floor than did control mice. These times were deducted from those for all other behaviors: 74 min from resting time, 39 min from climbing and feeding on the cage lid, 14 min from locomotion on the cage floor, and 10 min from grooming. In relative figures, deduction from sleeping time was only 9%, whereas climbing time was halved.Climbing on the cage lid has a similar circadian rhythm as does wheel running and high-energy expenditure. Because experimental mice climbed less, their weight gain and feed intake were similar to those of control mice. Thus, wheel running can substitute for other forms of energy-consuming behaviors and vice versa.

A great many studies in the literature describe the variety of ways to provide physical training to small laboratory animals. Forced running on a treadmill or swimming training require considerable effort from the researcher, but permit the investigator to control the amount of exercise. Another option is to provide animals with access to running wheels, which they can voluntarily operate. Wheels can be used to investigate the running behavior of the animals. Wheel motion usually has been detected with magnets and microswitches and has been recorded using strip chart recorders or electromechanical counters. Computers also have been used in recording, but the measured parameters usually have been able to define only the total distance run in a fixed period. We designed a system, using running wheels, that can be used for long periods, up to years, for training a large number of laboratory mice simultaneously (maximal n = 96). The running parameters estimated by our system include running distance, speed, and time. Cumulative estimates of the running parameters can be produced for any period, as short as 1 sec. It is also easy to perform statistical analyses on the data. Using the system, we investigated the running behavior of 21 young C57BL/6 male mice. After the fast growth period, until 8 weeks of age, the mice ran 4 to 5 km/day at an average speed of 23 m/min, and spent 3 h running each day. This took place during the hours of darkness.

Objective To evaluate the effectiveness of current medical and psychological interventions for individuals at risk of sexually abusing children, both in known abusers and those at risk of abusing. Design Systematic review of interventions designed to prevent reoffending among known abusers and prevention for individuals at risk of sexually abusing children. Randomised controlled trials and prospective observational studies were eligible. Primary outcomes were arrests, convictions, breaches of conditions, and self reported sexual abuse of children after one year or more. Results After review of 1447 abstracts, we retrieved 167 full text studies, and finally included eight studies with low to moderate risk of bias. We found weak evidence for interventions aimed at reducing reoffending in identified sexual abusers of children. For adults, evidence from five trials was insufficient regarding both benefits and risks with psychological treatment and pharmacotherapy. For adolescents, limited evidence from one trial suggested that multisystemic therapy prevented reoffence (relative risk 0.18, 95% confidence interval 0.04 to 0.73); lack of adequate research prevented conclusions about effects of other treatments. Evidence was also inadequate regarding effectiveness of treatment for children with sexual behavioural problems in the one trial identified. Finally, we found no eligible research on preventive methods for adults and adolescents who had not sexually abused children but were at higher risk of doing so (such as those with paedophilic sexual preference). Conclusion There are major weaknesses in the scientific evidence, particularly regarding adult men, the main category of sexual abusers of children. Better coordinated and funded high quality studies including several countries are urgently needed. Until conclusive evidence is available, realistic clinical strategies might involve reduction of specific risk factors for sex crimes, such as sexual preoccupation, in abusers at risk of reoffending.

Low cycle fatigue (LCF) tests have been performed at 565°C on welded joints and on microstructures to be found in or near welded joints in a low alloy ferritic steel, 0.5Cr, 0.5Mo, 0.25V. The microstructures studied were the parent metal, the coarse-grained structure of the heat affected zone (HAZ), fine-grained structure of HAZ and the weld metal. Tests have also been carried out with and without a 5 minute hold-time at maximum compressive strain on cross-weld samples which incorporated all of the above microstructures.

This paper describes changes to specimen grips and specimen design in order to creep test steels at temperatures a little below the spalling temperature and at low stresses (long times) where a large amount of oxidation occurs. High ductility and oxidation of a creep specimen often mean that the thermocouples lose contact with the specimen surface and the specimen itself cannot be removed from the grips after testing. The improvements involve the use of corrosion resistant alloys with reasonable high temperature strength for the loading bars and grips, a change in grip design and measuring the temperature inside the specimen.