Application of scaling to mouse spontaneous movement: Path curvature varies with speed and linear distance features isochrony.

To conserve sequential behavior in relation to the topographic challenges of space, it is proposed that humans and nonhuman animals can organize behavior using different scaling principles. To deal with increases in linear distance, isochrony suggest that there is a corresponding increase in speed, whereas to deal with changes in curvature, speed is adjusted according to a power function. The present study investigates whether these principles provide a framework for describing the organization of mouse behavior in a variety of standard experimental tasks. The structure of movement was examined in ambulation during open field exploration; manipulation in a string-pulling task, in which a string is advanced hand over hand to retrieve food; and rung-walking, in which the limbs successively step from rung to rung on a horizontal ladder. Both principles were found to be conserved in the organization of mouse behavior across scales of movement. These principles provide novel measures of the temporal and geometric features of movement in the mouse and insights into how the temporal and geometric features of movement are conserved within different species.

Age-related changes in the organization of spontaneously occurring behaviors.

Age-related changes in spatial and temporal processing have been documented across a range of species. Rodent studies typically investigate differences in performance between adult and senescent animals; however, progressive loss of neurons in the hippocampus and cortex has been observed to occur as early as after adolescence. Therefore, the current study evaluated the effects of age in three- and ten-month-old female rats on the organization of movement in open field and food protection behaviors, two tasks that have previously dissociated hippocampal and cortical pathology. Age-related differences were observed in general measures of locomotion, spatial orientation, and attentional processing. The results of the current study are consistent with age-related changes in the processing of spatial information and motivation that occur earlier in life than previously anticipated. These observations establish a foundation for future studies evaluating interventions that influence these age-related differences in performance.

Stickler syndrome - lessons from a national cohort.

In 2011 NHS England commissioned a new national specialist MDT service for patients and families affected by Stickler syndrome. The Stickler syndromes form part of the spectrum of inherited vitreoretinopathies and are the most common cause of retinal detachment in childhood and the most common cause of familial retinal detachment. Now in its 10th year, the Stickler Highly Specialised Service (HSS) has assessed 1673 patients from 785 families. Using a combination of accurate phenotyping and molecular genetic analysis it is possible to identify the underlying genetic mutation in over 95% of cases including those with deep intronic mutations likely to be missed by conventional exome panel analysis and which require whole gene sequencing and supplementary functional analysis to confirm pathogenicity. The vast majority that presents to ophthalmologists will be from one of three autosomal dominant sub-groups with a high associated risk of retinal detachment but the diagnosis is often overlooked, especially in adults. In contrast to many other blinding retinal conditions, blindness through giant retinal tear detachment particularly in children is largely preventable provided these high-risk groups are identified and appropriate evidence-based prophylaxis offered. This article summarises ten selected briefcase histories from the national dataset with key learning points from each.

Differential organization of open field behavior in mice following acute or chronic simulated GCR exposure.

Astronauts undertaking deep space travel will receive chronic exposure to the mixed spectrum of particles that comprise Galactic Cosmic Radiation (GCR). Exposure to the different charged particles of varied fluence and energy that characterize GCR may impact neural systems that support performance on mission critical tasks. Indeed, growing evidence derived from years of terrestrial-based simulations of the space radiation environment using rodents has indicated that a variety of exposure scenarios can result in significant and long-lasting decrements to CNS functionality. Many of the behavioral tasks used to quantify radiation effects on the CNS depend on neural systems that support maintaining spatial orientation and organization of rodent open field behavior. The current study examined the effects of acute or chronic exposure to simulated GCR on the organization of open field behavior under conditions with varied access to environmental cues in male and female C57BL/6 J mice. In general, groups exhibited similar organization of open field behavior under dark and light conditions. Two exceptions were noted: the acute exposure group exhibited significantly slower and more circuitous homeward progressions relative to the chronic group under light conditions. These results demonstrate the potential of open field behavior organization to discriminate between the effects of select GCR exposure paradigms.

Understanding the relationship between patient language and outcomes in internet-enabled cognitive behavioural therapy: A deep learning approach to automatic coding of session transcripts.

Objective: Understanding patient responses to psychotherapy is important in developing effective interventions. However, coding patient language is a resource-intensive exercise and difficult to perform at scale. Our aim was to develop a deep learning model to automatically identify patient utterances during text-based internet-enabled Cognitive Behavioural Therapy and to determine the association between utterances and clinical outcomes. Method: Using 340 manually annotated transcripts we trained a deep learning model to categorize patient utterances into one or more of five categories. The model was used to automatically code patient utterances from our entire data set of transcripts (∼34,000 patients), and logistic regression analyses used to determine the association between both reliable improvement and engagement, and patient responses. Results: Our model reached human-level agreement on three of the five patient categories. Regression analyses revealed that increased counter change-talk (movement away from change) was associated with lower odds of both reliable improvement and engagement, while increased change-talk (movement towards change or self-exploration) was associated with increased odds of improvement and engagement. Conclusions: Deep learning provides an effective means of automatically coding patient utterances at scale. This approach enables the development of a data-driven understanding of the relationship between therapist and patient during therapy.

Depressive symptoms among women in Raqqa Governorate, Syria: associations with intimate partner violence, food insecurity, and perceived needs.

BACKGROUND: Raqqa Governorate, Syria has recently been affected by overlapping conflicts related to the Syrian Civil war and occupation by ISIS, resulting in widespread displacement and disruption of economic livelihoods. However, little information is currently known about mental health needs and risk factors among women. Therefore, this study sought to examine potential risk factors for depressive symptoms among married women living in northern Syria. METHODS: Data were collected between March and April 2018 as part of an evaluation of an International Rescue Committee cash transfer program targeted toward vulnerable households. Using cross-sectional data from 214 married women participating in the program, linear regression models were generated to explore the associations between depressive symptoms [nine-item Patient Health Questionnaire (PHQ-9)] and its potential risk factors, including food insecurity, perceived deprivation of basic needs [the Humanitarian Emergency Settings Perceived Needs Scale (HESPER) scale], and past-3-month intimate partner violence (IPV). RESULTS: The average depressive symptom score was 10.5 (s.d.: 4.9; range: 2-27). In the final adjusted model, any form of recent IPV (ß = 2.25; 95% CI 0.92-3.57; p = 0.001), severe food insecurity (ß = 1.62; 95% CI 0.27-2.96; p = 0.02) and perceived needs (ß = 0.38; 95% CI 0.18-0.57; p = 0.0002) were associated with an increase in depressive symptoms. CONCLUSION: Study findings point to the need to address the mental health needs of women in conflict-affected areas of Syria. Programming to address risk factors for depression, including IPV and other factors associated with daily stressors such as food insecurity and deprivation of basic needs, may be effective in reducing depression in this population.

Progression and stop organization reveals conservation of movement organization during dark exploration across rats and mice.

Spatial orientation is a ubiquitous feature of animal behavior. Environmental and self-movement cues are sources of information used to maintain spatial orientation. The literature has typically focused on differences between mice and rats using environmental cues to guide movement. The current study uses the organization of exploratory behavior under dark conditions to investigate species differences in self-movement cue processing. Mouse and rat exploratory behavior was recorded under dark conditions on a circular table without walls. The resulting movements were segmented in progressions (movement ≥ 3 cm/s) and stops (movement < 3 cm/s). Mice exhibited longer travel distances, faster progression peak speeds, and weaker tendency to scale progression peak speeds to Euclidean distances relative to rats. In contrast, similar levels of performance were observed on measures (progression path circuity, change in heading, stability of stopping behavior) sensitive to vestibular pathology. These results are consistent with species differences in a variety of performance variables; however, self-movement cue based spatial orientation did not differentiate between mice and rats. This work establishes a translational foundation for future work investigating the neurobiology of self-movement cue processing using species-unique neuroscience techniques.

Identification and disruption of bacteria associated with sheep scab mites-novel means of control?

Psoroptes ovis mites, which cause psoroptic mange (sheep scab), were investigated to identify potential bacterial targets for endosymbiont control of sheep scab. In addition, transmission of bacteria to the sheep skin was investigated through the characterisation of bacteria present in P. ovis faecal trails and on the fleece environment by internal transcribed spacer (ITS) sequencing. A diverse range of bacteria was identified in addition to a potential endosymbiont candidate, Comamonas sp, which was detected in P. ovis by both ITS PCR and endosymbiont-specific PCR. Disruption of these bacteria within P. ovis, through the use of antibiotics, was explored; with significant reduction in mean mite survival when administered antibiotic diets compared with controls (LR4 = 23.12, P < 0.001). The antibiotic treatments also significantly affected the bacterial density (CFU/mite) within P. ovis, indicating that mite survival may be linked to the bacterial communities that they harbour. Although antibiotics are not suitable for practical application, these results suggest disrupting bacteria associated with P. ovis should be further investigated for novel control.

Cognitive impairment in depression: a systematic review and meta-analysis.

BACKGROUND: This review aimed to address the question of whether cognitive impairment should be considered a core feature of depression that may be a valuable target for treatment. METHOD: We conducted a systematic review and meta-analysis of cognitive function, assessed with a single neuropsychological test battery, the Cambridge Neuropsychological Test Automated Battery (CANTAB), in patients with depression during symptomatic and remitted states. Inclusion of studies comparing patients remitted from depression and controls enabled us to investigate whether cognitive impairment persists beyond episodes of low mood in depression. RESULTS: Our meta-analysis revealed significant moderate cognitive deficits in executive function, memory and attention in patients with depression relative to controls (Cohen's d effect sizes ranging from -0.34 to -0.65). Significant moderate deficits in executive function and attention (Cohen's d ranging from -0.52 to -0.61) and non-significant small/moderate deficits in memory (Cohen's d ranging from -0.22 to -0.54) were found to persist in patients whose depressive symptoms had remitted, indicating that cognitive impairment occurs separately from episodes of low mood in depression. CONCLUSIONS: Both low mood and cognitive impairment are associated with poor psychosocial functioning. Therefore, we argue that remediation of cognitive impairment and alleviation of depressive symptoms each play an important role in improving outcome for patients with depression. In conclusion, this systematic review and meta-analysis demonstrates that cognitive impairment represents a core feature of depression that cannot be considered an epiphenomenon that is entirely secondary to symptoms of low mood and that may be a valuable target for future interventions.

Identifying environmental drivers of insect phenology across space and time: Culicoides in Scotland as a case study.

Interpreting spatial patterns in the abundance of species over time is a fundamental cornerstone of ecological research. For many species, this type of analysis is hampered by datasets that contain a large proportion of zeros, and data that are overdispersed and spatially autocorrelated. This is particularly true for insects, for which abundance data can fluctuate from zero to many thousands in the space of weeks. Increasingly, an understanding of the ways in which environmental variation drives spatial and temporal patterns in the distribution, abundance and phenology of insects is required for management of pests and vector-borne diseases. In this study, we combine the use of smoothing techniques and generalised linear mixed models to relate environmental drivers to key phenological patterns of two species of biting midges, Culicoides pulicaris and C. impunctatus, of which C. pulicaris has been implicated in transmission of bluetongue in Europe. In so doing, we demonstrate analytical tools for linking the phenology of species with key environmental drivers, despite using a relatively small dataset containing overdispersed and zero-inflated data. We demonstrate the importance of landcover and climatic variables in determining the seasonal abundance of these two vector species, and highlight the need for more empirical data on the effects of temperature and precipitation on the life history traits of palearctic Culicoides spp. in Europe.

Impacts of climate, host and landscape factors on Culicoides species in Scotland.

Culicoides biting midges (Diptera: Ceratopogonidae) vector a wide variety of internationally important arboviral pathogens of livestock and represent a widespread biting nuisance. This study investigated the influence of landscape, host and remotely-sensed climate factors on local abundance of livestock-associated species in Scotland, within a hierarchical generalized linear model framework. The Culicoides obsoletus group and the Culicoides pulicaris group accounted for 56% and 41%, respectively, of adult females trapped. Culicoides impunctatus Goetghebuer and C. pulicaris s.s. Linnaeus were the most abundant and widespread species in the C. pulicaris group (accounting for 29% and 10%, respectively, of females trapped). Abundance models performed well for C. impunctatus, Culicoides deltus Edwards and Culicoides punctatus Meigen (adjusted R(2) : 0.59-0.70), but not for C. pulicaris s.s. (adjusted R(2) : 0.36) and the C. obsoletus group (adjusted R(2) : 0.08). Local-scale abundance patterns were best explained by models combining host, landscape and climate factors. The abundance of C. impunctatus was negatively associated with cattle density, but positively associated with pasture cover, consistent with this species' preference in the larval stage for lightly grazed, wet rush pasture. Predicted abundances of this species varied widely among farms even over short distances (less than a few km). Modelling approaches that may facilitate the more accurate prediction of local abundance patterns for a wider range of Culicoides species are discussed.

Rectal Chlamydia trachomatis infection in women. Is it overlooked?

Screening for rectal chlamydia was not routinely offered in our department until we had a local outbreak of lymphogranuloma venereum (LGV) in men who have sex with men (MSM) in 2004/2005. We later decided to extend the screening to high-risk women (women who had receptive anal sex, contacts of gonorrhoea, women, with anorectal symptoms, women who had been sexually assaulted). A retrospective study of 152 women from whom 160 rectal chlamydia swabs were taken was carried out. Twenty (12.5%) swabs were positive, 19 of which were also positive at the cervix. All were non-LGV serovars. The groups at greatest risk were high-risk women aged less than 20 years and women with proven gonococcal infection where the prevalence was 22.6% and 30%, respectively. We conclude that rectal chlamydial infection in women may be common and further studies are needed to elucidate its importance.

Impulsive aggression in adults with attention-deficit/hyperactivity disorder.

OBJECTIVE: DSM-IV criteria for attention-deficit/hyperactivity disorder (ADHD) include examples of 'impulsivity'. This term can refer to various dysfunctional behaviours, including some examples of aggressive behaviour. However, impulsive aggression is not included in the DSM-IV criteria for ADHD. The associations of impulsive aggression with ADHD were investigated. METHOD: Seventy-three male adults with DSM-IV ADHD, and their informants, completed questionnaires. Impulsive aggression was assessed by ratings of two criteria for borderline personality disorder (BPD), involving hot temper and/or self-harm. RESULTS: Logistic regression indicated that features of DSM-IV ADHD were predictors of comorbid impulsive aggression. However, compared with ADHD features, verbal IQ and comorbid psychopathology were more strongly associated with impulsive aggression. CONCLUSION: The findings support the inclusion of features of impulsive aggression, such as hot temper/short fuse, in the ADHD syndrome in adults. These overlap with features of BPD. The findings inform the selection of research samples.

Chlamydia trachomatis infection: the efficacy and safety of a fast-track referral and treatment system.

We introduced a Nurse/Health Advisor-led fast-track service for treating patients diagnosed with chlamydia outside a genitourinary medicine setting and contacts of chlamydia/non-specific urethritis/cervicitis wherever diagnosed. Asymptomatic patients were treated without initial testing and asked to return for full screening at four to six weeks. We assessed the efficacy and safety of the system and need for follow-up after treatment. Case-notes of 226 patients (121 men and 105 women) were analysed, of whom 140 attended follow-up. With the exception of one case of gonorrhoea, no other serious sexually transmitted infection was detected. Twenty-seven (19.2%) patients were re-treated for either chlamydia (six patients, 4.4%) or non-specific genital infection or because of having unprotected intercourse with untreated or partially treated partners. We conclude that in our relatively low-risk population, our fast-track service is safe and effective. Test of cure for chlamydia seems essential because of the high percentage of patients requiring re-treatment.

Reinforcement and reversal learning in first-episode psychosis.

BACKGROUND: Abnormalities in reinforcement learning and reversal learning have been reported in psychosis, possibly secondary to subcortical dopamine abnormalities. METHODS: We studied simple discrimination (SD) learning and reversal learning in a sample of 119 first-episode psychosis patients from the Cambridge early psychosis service (CAMEO) and 107 control participants. We used data on reinforcement learning and reversal learning extracted from the Cambridge Neuropsychological Test Automated Battery Intradimensional-Extradimensional shift task, which measures cognitive flexibility but also involves simple reinforcement learning (SD learning) and reversal learning stages. We also gathered diagnostic information to examine whether there were any differences between patients ultimately diagnosed with schizophrenia-spectrum disorders and those diagnosed with affective psychosis. RESULTS: Psychosis patients demonstrated deficits in simple reinforcement learning (SD learning) and in reversal learning, with no differences between affective psychosis and schizophrenia-spectrum psychosis. There was a significant modest correlation between reversal errors and negative symptoms (Spearman rho = 0.3, P = .02). CONCLUSIONS: There are reinforcement learning abnormalities in first-episode psychosis, which correlate with negative symptoms, suggesting a possible role for orbitofrontal cortex and ventral striatal pathology in the pathogenesis of motivational deficits in psychosis.

Outcome measures after TVT for mixed urinary incontinence.

This study assessed the outcome of tension-free vaginal tape (TVT) in the treatment of mixed incontinence using the Medical Epidemiologic and Social Aspects of Ageing (MESA) questionnaire and other outcome measures used by the British Society of Urogynaecology (BSUG) database. Forty women undergoing TVT completed a MESA questionnaire pre-operatively and at 6 months post-operatively. Information was also obtained about three outcome measures of the BSUG database-patients' global impression of outcome and stress and urge symptom analyses. Stress and urge incontinences were either cured or improved in 78 and 75 % of women, respectively, after TVT. The results of post-operative patients' global impression of outcome showed great or moderate improvement in 75% of cases and had 69% reduction in mean MESA scores (p value less than 0.001). Symptom improvement based on MESA scores relates well with the basic outcome measures for stress and urge incontinences used by the BSUG database.

Substantia nigra/ventral tegmental reward prediction error disruption in psychosis.

While dopamine systems have been implicated in the pathophysiology of schizophrenia and psychosis for many years, how dopamine dysfunction generates psychotic symptoms remains unknown. Recent theoretical interest has been directed at relating the known role of midbrain dopamine neurons in reinforcement learning, motivational salience and prediction error to explain the abnormal mental experience of psychosis. However, this theoretical model has yet to be explored empirically. To examine a link between psychotic experience, reward learning and dysfunction of the dopaminergic midbrain and associated target regions, we asked a group of first episode psychosis patients suffering from active positive symptoms and a group of healthy control participants to perform an instrumental reward conditioning experiment. We characterized neural responses using functional magnetic resonance imaging. We observed that patients with psychosis exhibit abnormal physiological responses associated with reward prediction error in the dopaminergic midbrain, striatum and limbic system, and we demonstrated subtle abnormalities in the ability of psychosis patients to discriminate between motivationally salient and neutral stimuli. This study provides the first evidence linking abnormal mesolimbic activity, reward learning and psychosis.

Profile of neurocognitive impairments associated with female in-patients with anorexia nervosa.

BACKGROUND: Although many studies have reported impairments of neurocognitive performance in patients with anorexia nervosa (AN), these have involved a wide range of assessment methods and some findings are inconsistent. METHOD: Twenty-five female in-patients with a DSM-IV diagnosis of AN, identified from three units specializing in the treatment of eating disorders, volunteered for the study. Twenty-five non-clinical control subjects were recruited, matched for age, gender and estimated IQ. Subjects were assessed with a range of computer-administered neurocognitive tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB), which has been validated in many studies of neuropsychiatric disorders. RESULTS: The patient group showed significant but moderate impairments (i.e. less than one standard deviation below the mean performance of the control group) on tests of spatial recognition memory, a planning task and rapid visual information processing, while a subgroup of patients (n = 14) showed greater degrees of impairments on at least one of these tests. The degrees of impairments did not correlate with body mass index (BMI). No impairments were observed on tests of spatial span, pattern recognition memory, spatial working memory, matching-to-sample, paired associates learning and set-shifting. CONCLUSIONS: The findings, in relation to a mean BMI of 15.3, are compatible with, in general, subtle impairments in neurocognition in AN. However, in those patients with relatively severe degrees of impairments, these may have adverse effects on complex tasks of social and occupational functioning. Further research is needed on the nature of relevant causal mechanisms, including the effects of potentially confounding variables.

The neuropsychology of obsessive compulsive disorder: the importance of failures in cognitive and behavioural inhibition as candidate endophenotypic markers.

Obsessive compulsive disorder (OCD) is a highly debilitating neuropsychiatric condition with estimated lifetime prevalence of 2-3%, more than twice that of schizophrenia. However, in contrast to other neuropsychiatric conditions of a comparable or lesser prevalence, relatively little is understood about the aetiology, neural substrates and cognitive profile of OCD. Despite strong evidence for OCD being familial, with risk to first-degree relatives much greater than for the background population, its genetic underpinnings have not yet been adequately delineated. Although cognitive dysfunction is evident in the everyday behaviour of OCD sufferers and is central to contemporary psychological models, theory-based studies of neurocognitive function have yet to reveal a reliable cognitive signature, and interpretation has often been confounded by failures to control for co-morbidities. The neuroimaging findings in OCD are amongst the most robust reported in the psychiatric literature, with structural and functional abnormalities frequently reported in orbitofrontal cortex, anterior cingulate cortex, and caudate nucleus. In spite of this, our relative lack of understanding of OCD neurochemical processes continues to impede progress in the development of novel pharmacological treatment approaches. Integrating the neurobiological, cognitive, and clinical findings, we propose that OCD might usefully be conceptualised in terms of lateral orbitofrontal loop dysfunction, and that failures in cognitive and behavioural inhibitory processes appear to underlie many of the symptoms and neurocognitive findings. We highlight existing limitations in the literature, and the potential utility of endophenotypes in overcoming these limitations. We propose that neurocognitive indices of inhibitory functions may represent a useful heuristic in the search for endophenotypes in OCD. This has direct implications not only for OCD but also for putative obsessive-compulsive spectrum conditions including attention deficit hyperactivity disorder, Tourette's syndrome, and trichotillomania (compulsive hair pulling).