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To test the functional implications of impaired white matter (WM) connectivity among patients with schizophrenia and their relatives, we examined the heritability of fractional anisotropy (FA) measured on diffusion tensor imaging data acquired in Pittsburgh and Philadelphia, and its association with cognitive performance in a unique sample of 175 multigenerational non-psychotic relatives of 23 multiplex schizophrenia families and 240 unrelated controls (total = 438).
We examined polygenic inheritance (h2r) of FA in 24 WM tracts bilaterally, and also pleiotropy to test whether heritability of FA in multiple WM tracts is secondary to genetic correlation among tracts using the Sequential Oligogenic Linkage Analysis Routines. Partial correlation tests examined the correlation of FA with performance on eight cognitive domains on the Penn Computerized Neurocognitive Battery, controlling for age, sex, site and mother's education, followed by multiple comparison corrections.
Significant total additive genetic heritability of FA was observed in all three-categories of WM tracts (association, commissural and projection fibers), in total 33/48 tracts. There were significant genetic correlations in 40% of tracts. Diagnostic group main effects were observed only in tracts with significantly heritable FA. Correlation of FA with neurocognitive impairments was observed mainly in heritable tracts.
Our data show significant heritability of all three-types of tracts among relatives of schizophrenia. Significant heritability of FA of multiple tracts was not entirely due to genetic correlations among the tracts. Diagnostic group main effect and correlation with neurocognitive performance were mainly restricted to tracts with heritable FA suggesting shared genetic effects on these traits.
Seabirds are one of the most threatened avian taxa and are hence a high conservation priority. Managing seabirds is challenging, requiring conservation actions at sea (e.g. Marine Protected Areas - MPAs) and on land (e.g. protection of breeding sites). Important Bird and Biodiversity Areas (IBAs) have been successfully used to identify sites of global importance for the conservation of bird populations, including breeding seabirds. The challenge of identifying suitable IBAs for tropical seabirds is exacerbated by high levels of dispersal, aseasonal and asynchronous breeding. The western Indian Ocean supports ~19 million breeding seabirds of 30 species, making it one of the most significant tropical seabird assemblages in the world. Within this is the British Indian Ocean Territory (BIOT), encompassing 55 islands of the Chagos Archipelago, which supports 18 species of breeding seabird and one of the world’s largest no-take MPAs. Between January and March in 1975 and 1996, eight and 45 islands respectively were surveyed for seabirds and the data used to designate 10 islands as IBAs. A further two were proposed following an expedition to 26 islands in February/March 2006. Due to the historic and restricted temporal and spatial nature of these surveys, the current IBA recommendations may not accurately represent the archipelago’s present seabird status and distribution. To update estimates of the BIOT breeding seabird assemblage and reassess the current IBA recommendations, we used seabird census data collected in every month except September from every island, gathered during 2008–2018. The maximum number of breeding seabirds for a nominal year was 281,596 pairs of 18 species, with three species making up 96%: Sooty Tern Onychoprion fuscatus - 70%, Lesser Noddy Anous tenuirostris - 18% and Red-footed Booby Sula sula - 8%. Phenology was a complex species-specific mix of synchronous and asynchronous breeding, as well as seasonal and aseasonal breeding. Nine of the 10 designated IBAs and the two proposed IBAs qualified for IBA status based on breeding seabirds. However, not every IBA qualified each year because Sooty Terns periodically abandoned breeding islands and Tropical Shearwater Puffinus bailloni breeding numbers dropped below IBA qualifying criteria in some years. Further, one survey per year does not always capture the periodic breeding of some tropical seabirds. We propose therefore, that IBAs in BIOT are better designated at the island cluster level rather than by specific island and require two surveys six months apart per year. This work highlights the merits of long-term, systematic, versus incidental surveys for breeding tropical seabirds and the subsequent associated designation of IBAs.
This rejoinder notes that several key points were discussed in response to the authors' review of brief psychosocial interventions for personality disorders. In particular, the commentary suggested that understanding key mechanisms of change and moderators of treatment outcome were especially important to make forward progress in streamlining treatments for personality disorders. Here the authors highlight several shared candidate mechanisms of change across brief treatments for personality disorders, including a focus on education regarding emotion regulation, interpersonal processes, and instilling hope and expectancies for change. They also discuss the possibility that moderators of treatment outcome should be examined across types of outcomes. Moreover, some outcomes may be more amenable to brief treatments than others. Recommendations for future research in this area are discussed.
In their chapter, Bach and Presnall-Shvorin (this volume) introduce guidelines for incorporating empirically-driven trait models of personality pathology, codified in the DSM-5 and ICD-11, into therapeutic practice. Though the authors of this commentary are supportive of the effort to bridge research with clinical practice, they suggest that a mechanistic model which accounts for personality processes underlying descriptive traits could offer greater precision than traits alone. Furthermore, they argue that clinical dysfunction can only be meaningfully defined and treated with an understanding of dynamic, contextualized aspects of personality. To illustrate how a mechanistic model could complement and extend Bach and Presnall’s recommendations, the authors present a case conceptualization using cybernetic theory. Finally, they review how idiographic data gleaned from ambulatory assessment methods provide insight into pathological processes ideal for therapeutic intervention. To achieve a generalizable approach flexible enough to adapt to the individual, they encourage the development of treatment models that go beyond traits to mechanistically link stable and dynamic personality features into a unified framework.
The last several decades have witnessed the emergence of several efficacious treatments for personality disorders, yet many of these treatments are lengthy and resource-intensive. There is a pressing public health need to identify briefer treatment options for the treatment of personality disorders. The present contribution is a comprehensive review of brief (i.e., less than one-year) psychosocial interventions for personality disorders. The authors' search criteria yielded 66 articles, which they summarize in this chapter. Of note, only a minority of these studies were randomized controlled trials, and nearly half focused on borderline personality disorders. A few brief treatments appear to be efficacious for personality disorders, namely short-term dynamic psychotherapy for Cluster C personality disorders, as well as manual-assisted cognitive therapy, six-month dialectical behavior therapy, and emotion regulation group therapy for borderline personality disorder and/or self-injury. Recommendations for future research in this area are discussed.
Neuroticism is associated with the onset and maintenance of a number of mental health conditions, as well as a number of deleterious outcomes (e.g. physical health problems, higher divorce rates, lost productivity, and increased treatment seeking); thus, the consideration of whether this trait can be addressed in treatment is warranted. To date, outcome research has yielded mixed results regarding neuroticism's responsiveness to treatment, perhaps due to the fact that study interventions are typically designed to target disorder symptoms rather than neuroticism itself. The purpose of the current study was to explore whether a course of treatment with the unified protocol (UP), a transdiagnostic intervention that was explicitly developed to target neuroticism, results in greater reductions in neuroticism compared to gold-standard, symptom focused cognitive behavioral therapy (CBT) protocols and a waitlist (WL) control condition.
Patients with principal anxiety disorders (N = 223) were included in this study. They completed a validated self-report measure of neuroticism, as well as clinician-rated measures of psychological symptoms.
At week 16, participants in the UP condition exhibited significantly lower levels of neuroticism than participants in the symptom-focused CBT (t(218) = −2.17, p = 0.03, d = −0.32) and WL conditions(t(207) = −2.33, p = 0.02, d = −0.43), and these group differences remained after controlling for simultaneous fluctuations in depression and anxiety symptoms.
Treatment effects on neuroticism may be most robust when this trait is explicitly targeted.
To examine genetic influences the anatomy of the Corpus Callosum (CC) in Bipolar Disorder (BD) by examining first-degree relatives in addition to BD patients.
We compared CCl size and shape in 180 individuals: 70 with BD, 45 of their unaffected first-degree relatives, and 75 healthy controls. The CC was extracted from a mid-sagittal slice from T1-weighted magnetic resonance images; its total area, length and curvature were compared across groups. A non-parametric permutation method was used to examine for alterations in width of the callosum along 39 points.
Validating our previous findings, a significant global reduction in CC thickness was seen in BD patients, with a disproportionate thinning in the anterior body. First-degree relatives did not differ in CC size or shape from controls. Duration of illness was associated with thinning in the anterior body, whereas Lithium treatment associated with thicker anterior CC midbody.
Global and regional CC thinning is a disease related feature of BD and may not represent a marker of familial disposition.
The Living Life to the Full college and free online courses are based on the Cognitive Behaviour Therapy (CBT) approach and is offered at Further Education Colleges and free of charge online (www.livinglifetothefull.com). The classes teaches key skills such as identifying and challenging unhelpful thoughts, problem solving etc.
In the college course, total mean scores at baseline for knowledge questions was 8.20 increasing to 11.07 gain 2.87 p=.042). Self assessed skills were 24.00 at baseline, increasing to 34.20 at session 8 (mean difference = 10.20 p=.001). The Training Acceptability Rating scale showed content scores at session 1 of 77% rising to 91% at session 8. Process scores were 73% at session 1 rising to 89%, showing training acceptability throughout the course. The online course has over 15,000 registered users. 70% are clinical cases of anxiety (HAD scale), and 55% depression. 24% of users are clinical cases and are not receiving any support from a practitioner. The site has had over 4 million hits in 10 months and an average of 1000 hits/hour.
Delivering CBT in this way seems to lead to gains in mental health literacy. Such courses may provide another useful option for helping people access CBT for mild to moderate problems of distress. A RCT of the core course materials has just been completed.
Schizophrenia patients have increased risk of cardiovascular disease (CVD) and mortality. Guidelines emphasise need for monitoring risk factors including ECG and blood pressure (BP). There is little naturalistic data on number and severity of categorical abnormalities detected.
A global health clinic was set up in 2004 to undertake systematic physical health monitoring in all schizophrenia outpatients within Larkfield CMHT. Patients received 2 hour assessments from trained nurses. BMI, laboratory (non-fasting) parameters, ECG and BP performed.
Since 2004 from 140 Schizophrenia outpatients 95 have been invited to attend screening of which 53 accepted (56%). An abnormal parameter was measured in 92% (n=49), 72% 2 abnormal findings (n=38) and 47% 3 or more. ECG abnormalities in 50% (n=26) of which 18 were significant findings (prior myocardial infarction and/or ischaemia, conduction blocks, right ventricular hypertrophy). Normal blood pressure using guidelines from British Hypertension Society (BHS) 2004 (<130/85) was determined in 36% (n=20), high-normal 11% (n=6) and varying grades of hypertension 53% (n=27). Grade 3 (severe) hypertension 8% (n=4). No patient had abnormal QTc >500 mscs. One male patient had QTc 458msecs.In 18 patients (34%) the ECG analysis was determined by the analyser to be difficult to analyse due to significant baseline patient movement.
Significant BP and ECG abnormalities are common and require evaluation for treatment. QTc abnormalities are detected significantly less often than other important abnormalities. Using the most conservative definition of hypertension 53% of this cohort would be defined as needing antihypertensive treatments and lifestyle interventions in 64%.
Ventricular enlargement is one of the most consistent brain changes associated with schizophrenia. However, there are only few cross-sectional studies in genetic at risk individuals, and no studies in individuals meeting ultra high risk (UHR) criteria of developing frank psychosis. This study investigates the timing of ventricular volume changes across the different stages of emerging psychotic disorders.
We measured ventricular volumes in 473 subjects comparing 135 UHR subjects (of whom 39 subsequently developed a psychotic illness), 162 first-episode psychosis (FEP) subjects, 89 chronic schizophrenia (CS) subjects with 87 normal controls (NC). 29 UHR, 25 FEP, 13 CS, and 24 HV had longitudinal follow up scans.
We found significant ventricular enlargement in FEP and CS, but not in UHR and NC. Longitudinal analysis confirmed ventricular enlargement in non-affective psychosis only. UHR patients had normal ventricular volumes regardless of whether they made transition to frank psychosis or not.
Our results are suggestive that ventricular enlargement is a consequence of transition and/or progression of illness rather than a risk marker in that it is apparent only after the onset of frank psychosis, with prominence in patients with schizophrenia-like psychoses. The results parallel our previous study in that hippocampal volumes were reduced in CS and normal in patients having non-schizophrenic psychoses as well in UHR individuals.
Numerous studies have applied novel multivariate statistical approaches to the analysis of brain alterations in patients with schizophrenia. However the diagnostic accuracy of the reported predictive models differs largely, making it difficult to evaluate the overall potential of these studies to inform clinical diagnosis.
We conducted a comprehensive literature search to identify all studies reporting performance of neuroimaging-based multivariate predictive models for the differentiation of patients with schizophrenia from healthy control subjects. The robustness of the results as well as the effect of potentially confounding continous variables (e.g. age, gender ratio, year of publication) was investigated.
The final sample consisted of n=37 studies studies including n=1491 patients with schizophrenia and n=1488 healthy controls. Metaanalysis of the complete sample showed a sensitivity of 80.7% (95%-CI: 77.0 to 83.9%) and a specificity of 80.2% (95%-CI: 83.3 to 76.7%). Separate analysis for the different imaging modalities showed similar diagnostic accuracy for the structural MRI studies (sensitivity 77.3%, specificity 78.7%), the fMRI studies (sensitivity 81.4%, specificity 82.4%) and resting-state fMRI studies (sensitivity 86.9%, specificity 80.3%). Moderator analysis showed significant effects of age of patients on sensitivity (p=0.021) and of positive-tonegative symptom ratio on specificity (p=0.028) indicating better diagnostic accuracy in older patients and patients with positive symptoms.
Our analysis indicate an overall sensitivity and overall specificity of around 80 % of neuroimaging-based predictive models for differentiating schizophrenic patients from healthy controls. The results underline the potential applicability of neuroimaging-based predictive models for the diagnosis of schizophrenia.
Impedance spectroscopy was conducted on colloidal ITO thin films that had been subjected to alternating oxygen and argon plasma treatments, followed by air annealing from 150 to 750 °C. An equivalent circuit consisting of an RC element nested within another RC element, featuring a negative resistance and a negative capacitance, fitted the data well. These results are interpreted as being due to surface plasmons that are a function of the presence of nanoporous ITO-rich regions surrounded by isolated ITO nanoparticles coated with an amorphous polymer that intertwines with the ITO-rich regions as a function of annealing treatment.
In the context of untimely access to community formal services, unmet needs of persons with dementia (PwD) and their carers may compromise their quality of life.
The Actifcare EU-JPND project (www.actifcare.eu) focuses on access to and (non) utilization of dementia formal care in eight countries (The Netherlands, Germany, United Kingdom, Sweden, Norway, Ireland, Italy, Portugal), as related to unmet needs and quality of life. Evaluations included systematic reviews, qualitative explorations, and a European cohort study (PwD in early/intermediate phases and their primary carers; n = 453 days; 1 year follow-up). Preliminary Portuguese results are presented here (FCT-JPND-HC/0001/2012).
(1) extensive systematic searches on access to/utilization of services; (2) focus groups of PwD, carers and health/social professionals; (3) prospective study (n = 66 days from e.g., primary care, hospital outpatient services, Alzheimer Portugal).
In Portugal, nationally representative data is scarce regarding health/social services utilization in dementia. There are important barriers to access to community services, according to users, carers and professionals, whose views not always coincide. The Portuguese cohort participants were 66 PwD (62.1% female, 77.3 ± 6.2 years, 55.5% Alzheimer's/mixed subtypes, MMSE 17.8 ± 4.8, CDR1 89.4%) and 66 carers (66.7% female, 64.9 ± 15.0 years, 56.1% spouses), with considerable unmet needs in some domains.
All Actifcare milestones are being reached. The consortium is now analyzing international differences in (un) timely access to services and its impact on quality of life and needs for care (e.g., formal community support is weaker in Portugal than in many European countries). National best-practice recommendations in dementia are also in preparation.
Abstract submitted on behalf of the Actifcare Eu-JPND consortium.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
We present an experimental investigation of steady particle-driven gravity currents with Reynolds numbers in the range 500–1600, and with the ratio of the initial current speed to the fall speed of the particles,
, in the range
. We identify three regimes: (i) For
, the particles settle close to the source at a velocity corresponding to their fall speed, consistent with the observation of sedimenting fronts in classical settling column experiments. (ii) In the range
, a steady gravity current develops within the tank. The experiments show that the depth of the gravity current gradually decreases away from the source and dye added to the source liquid appears above the gravity current along its entire length, suggesting that there is a sedimentation front, so that the volume and momentum fluxes of the current gradually decrease with distance from the source. We find that as
increases, the descent speed of the sedimentation front decreases relative to the fall speed of the particles, and the run-out length of the gravity current increases. We note that the density of the interstitial fluid corresponds to the density of the ambient fluid, so that any reduction in buoyancy of the gravity current is attributed to the sedimentation of particles on the floor of the tank and we do not observe lofting of the interstitial fluid. (iii) For
, the gravity currents reach the end of our experimental tank and we no longer observe a sedimentation front. For these experiments, it appears that the entrainment at the top of the current begins to match the sedimentation and so the current depth does not change significantly over the scale of the tank, but a larger scale experimental system would be needed to explore the full run-out behaviour for these larger values of
. For the intermediate case,
, we develop a model for the conservation of volume, momentum and buoyancy fluxes in the current, accounting for the sedimentation front and the release of fluid at the top surface of the gravity current, and we compare this with our new experimental data.
Q fever (caused by Coxiella burnetii) is thought to have an almost world-wide distribution, but few countries have conducted national serosurveys. We measured Q fever seroprevalence using residual sera from diagnostic laboratories across Australia. Individuals aged 1–79 years in 2012–2013 were sampled to be proportional to the population distribution by region, distance from metropolitan areas and gender. A 1/50 serum dilution was tested for the Phase II IgG antibody against C. burnetii by indirect immunofluorescence. We calculated crude seroprevalence estimates by age group and gender, as well as age standardised national and metropolitan/non-metropolitan seroprevalence estimates. Of 2785 sera, 99 tested positive. Age standardised seroprevalence was 5.6% (95% confidence interval (CI 4.5%–6.8%), and similar in metropolitan (5.5%; 95% CI 4.1%–6.9%) and non-metropolitan regions (6.0%; 95%CI 4.0%–8.0%). More males were seropositive (6.9%; 95% CI 5.2%–8.6%) than females (4.2%; 95% CI 2.9%–5.5%) with peak seroprevalence at 50–59 years (9.2%; 95% CI 5.2%–13.3%). Q fever seroprevalence for Australia was higher than expected (especially in metropolitan regions) and higher than estimates from the Netherlands (2.4%; pre-outbreak) and US (3.1%), but lower than for Northern Ireland (12.8%). Robust country-specific seroprevalence estimates, with detailed exposure data, are required to better understand who is at risk and the need for preventive measures.
Evidence suggests that early trauma may have a negative effect on cognitive functioning in individuals with psychosis, yet the relationship between childhood trauma and cognition among those at clinical high risk (CHR) for psychosis remains unexplored. Our sample consisted of 626 CHR children and 279 healthy controls who were recruited as part of the North American Prodrome Longitudinal Study 2. Childhood trauma up to the age of 16 (psychological, physical, and sexual abuse, emotional neglect, and bullying) was assessed by using the Childhood Trauma and Abuse Scale. Multiple domains of cognition were measured at baseline and at the time of psychosis conversion, using standardized assessments. In the CHR group, there was a trend for better performance in individuals who reported a history of multiple types of childhood trauma compared with those with no/one type of trauma (Cohen d = 0.16). A history of multiple trauma types was not associated with greater cognitive change in CHR converters over time. Our findings tentatively suggest there may be different mechanisms that lead to CHR states. Individuals who are at clinical high risk who have experienced multiple types of childhood trauma may have more typically developing premorbid cognitive functioning than those who reported minimal trauma do. Further research is needed to unravel the complexity of factors underlying the development of at-risk states.
A systematic review and network meta-analysis were conducted to assess the relative efficacy of internal or external teat sealants given at dry-off in dairy cattle. Controlled trials were eligible if they assessed the use of internal or external teat sealants, with or without concurrent antimicrobial therapy, compared to no treatment or an alternative treatment, and measured one or more of the following outcomes: incidence of intramammary infection (IMI) at calving, IMI during the first 30 days in milk (DIM), or clinical mastitis during the first 30 DIM. Risk of bias was based on the Cochrane Risk of Bias 2.0 tool with modified signaling questions. From 2280 initially identified records, 32 trials had data extracted for one or more outcomes. Network meta-analysis was conducted for IMI at calving. Use of an internal teat sealant (bismuth subnitrate) significantly reduced the risk of new IMI at calving compared to non-treated controls (RR = 0.36, 95% CI 0.25–0.72). For comparisons between antimicrobial and teat sealant groups, concerns regarding precision were seen. Synthesis of the primary research identified important challenges related to the comparability of outcomes, replication and connection of interventions, and quality of reporting of study conduct.
A systematic review and meta-analysis were conducted to determine the efficacy of selective dry-cow antimicrobial therapy compared to blanket therapy (all quarters/all cows). Controlled trials were eligible if any of the following were assessed: incidence of clinical mastitis during the first 30 DIM, frequency of intramammary infection (IMI) at calving, or frequency of IMI during the first 30 DIM. From 3480 identified records, nine trials were data extracted for IMI at calving. There was an insufficient number of trials to conduct meta-analysis for the other outcomes. Risk of IMI at calving in selectively treated cows was higher than blanket therapy (RR = 1.34, 95% CI = 1.13, 1.16), but substantial heterogeneity was present (I2 = 58%). Subgroup analysis showed that, for trials using internal teat sealants, there was no difference in IMI risk at calving between groups, and no heterogeneity was present. For trials not using internal teat sealants, there was an increased risk in cows assigned to a selective dry-cow therapy protocol, compared to blanket treatment, with substantial heterogeneity in this subgroup. However, the small number of trials and heterogeneity in the subgroup without internal teat sealants suggests that the relative risk between treatments may differ from the determined point estimates based on other unmeasured factors.