Feral Donkey Distribution and Ecological Impacts in a Hyper-Arid Region.

The feral donkey (Equus asinus L.) is an invasive species in Saudi Arabia and can cause severe damage to natural and cultural heritage. Over the last 30 years, feral donkeys have become a serious problem, as their abundance and geographic distribution has increased drastically. The impacts of feral donkeys are not well documented, and information about their abundance and distribution is lacking, certainly in Saudi Arabia, which hampers the implementation of effective management plans. Accordingly, we used the minimum population number approach (MPN) to determine the number of feral donkeys in this part of northwest Saudi Arabia. A total of 1135 feral donkeys were encountered in the region. The area around Khaybar harbors ~25% (n = 338) of the feral donkey population, whereas Tayma and AlGhrameel nature reserves were the least-inhabited sites (almost absent). The average population density of feral donkeys was estimated as 1.03 (0.19 SE) donkey/km2. We documented the negative ecological impact of feral donkeys on natural resources, which constituted overgrazing that resulted in habitat fragmentation and competition for resources with native species. We propose urgent actions to control the presence of feral donkeys in the region and suggest humane eradication as the most efficient and applicable to significantly reduce the negative impacts of feral donkeys.

Opportunities and challenges for 2D heterostructures in battery applications: a computational perspective.

With an increasing demand for large-scale energy storage systems, there is a need for novel electrode materials to store energy in batteries efficiently. 2D materials are promising as electrode materials for battery applications. Despite their excellent properties, none of the available single-phase 2D materials offers a combination of properties required for maximizing energy density, power density, and cycle life. This article discusses how stacking distinct 2D materials into a 2D heterostructure may open up new possibilities for battery electrodes, combining favourable characteristics and overcoming the drawbacks of constituent 2D layers. Computational studies are crucial to advancing this field rapidly with first-principles simulations of various 2D heterostructures forming the basis for such investigations that offer insights into processes that are hard to determine otherwise. We present a perspective on the current methodology, along with a review of the known 2D heterostructures as anodes and their potential for Li and Na-ion battery applications. 2D heterostructures showcase excellent tunability with different compositions. However, each of them has distinct properties, with its own set of challenges and opportunities for application in batteries. We highlight the current status and prospects to stimulate research into designing new 2D heterostructures for battery applications.

Pharmacology of novel small-molecule tubulin inhibitors in glioblastoma cells with enhanced EGFR signalling.

We recently reported that CMPD1, originally developed as an inhibitor of MK2 activation, primarily inhibits tubulin polymerisation and induces apoptosis in glioblastoma cells. In the present study we provide detailed pharmacological investigation of CMPD1 analogues with improved molecular properties. We determined their anti-cancer efficacy in glioblastoma cells with enhanced EGFR signalling, as deregulated EGFR often leads to chemoresistance. Eight analogues of CMPD1 with varying lipophilicity and basicity were synthesised and tested for efficacy in the cell viability assay using established glioblastoma cell lines and patient-derived primary glioblastoma cells. The mechanism of action for the most potent analogue 15 was determined using MK2 activation and tubulin polymerisation assays, together with the immunofluorescence analysis of the mitotic spindle formation. Apoptosis was analysed by Annexin V staining, immunoblotting analysis of bcl-2 proteins and PARP cleavage. The apoptotic activity of CMPD1 and analogue 15 was comparable across glioblastoma cell lines regardless of the EGFR status. Primary glioblastoma cells of the classical subtype that are characterized by enhanced EGFR activity were most sensitive to the treatment with CMPD1 and 15. In summary, we present mechanism of action for a novel small molecule tubulin inhibitor, compound 15 that inhibits tubulin polymerisation and mitotic spindle formation, induces degradation of anti-apoptotic bcl-2 proteins and leads to apoptosis of glioblastoma cells. We also demonstrate that the enhanced EGFR activity does not decrease the efficacy of tubulin inhibitors developed in this study.

Child maltreatment and adult psychopathology in an Irish context.

One-hundred-ninety-nine adult mental health service users were interviewed with a protocol that included the Childhood Trauma Questionnaire, the Structured Clinical Interviews for Axis I and II DSM-IV disorders, the Global Assessment of Functioning scale, the SCORE family assessment measure, the Camberwell Assessment of Need Short Appraisal Schedule, and the Readiness for Psychotherapy Index. Compared to a U.S. normative sample, Irish clinical cases had higher levels of maltreatment. Cases with comorbid axis I and II disorders reported more child maltreatment than those with axis I disorders only. There was no association between types of CM and types of psychopathology. Current family adjustment and service needs (but not global functioning and motivation for psychotherapy) were correlated with a CM history. It was concluded that child maltreatment may contribute to the development of adult psychopathology, and higher levels of trauma are associated with co-morbid personality disorder, greater service needs and poorer family adjustment. A history of child maltreatment should routinely be determined when assessing adult mental health service users, especially those with personality disorders and where appropriate evidence-based psychotherapy which addresses childhood trauma should be offered.

The association of cold weather and all-cause and cause-specific mortality in the island of Ireland between 1984 and 2007.

BACKGROUND: This study aimed to assess the relationship between cold temperature and daily mortality in the Republic of Ireland (ROI) and Northern Ireland (NI), and to explore any differences in the population responses between the two jurisdictions. METHODS: A time-stratified case-crossover approach was used to examine this relationship in two adult national populations, between 1984 and 2007. Daily mortality risk was examined in association with exposure to daily maximum temperatures on the same day and up to 6 weeks preceding death, during the winter (December-February) and an extended cold period (October-March), using distributed lag models. Model stratification by age and gender assessed for modification of the cold weather-mortality relationship. RESULTS: In the ROI, the impact of cold weather in winter persisted up to 35 days, with a cumulative mortality increase for all-causes of 6.4% (95% CI = 4.8%-7.9%) in relation to every 1°C drop in daily maximum temperature, similar increases for cardiovascular disease (CVD) and stroke, and twice as much for respiratory causes. In NI, these associations were less pronounced for CVD causes, and overall extended up to 28 days. Effects of cold weather on mortality increased with age in both jurisdictions, and some suggestive gender differences were observed. CONCLUSIONS: The study findings indicated strong cold weather-mortality associations in the island of Ireland; these effects were less persistent, and for CVD mortality, smaller in NI than in the ROI. Together with suggestive differences in associations by age and gender between the two Irish jurisdictions, the findings suggest potential contribution of underlying societal differences, and require further exploration. The evidence provided here will hope to contribute to the current efforts to modify fuel policy and reduce winter mortality in Ireland.

Prospective relationship of duration of untreated psychosis to psychopathology and functional outcome over 12 years.

BACKGROUND: The duration of untreated psychosis is well recognised as an independent predictor of symptomatic and functional outcome in the short term and has facilitated the development of worldwide early intervention programmes. However, the extent and mechanisms by which it might influence prognosis beyond a decade remain poorly understood. METHODS: The authors examined the relationship between duration of untreated psychosis and outcome 12years after a first episode of psychosis and assessed whether its relationship with function is affected by symptoms in a prospective, 12-year follow-up of an epidemiologically-based inception cohort. RESULTS: Longer duration of untreated psychosis predicted poorer remission status, more severe positive and negative symptoms, and greater impairment in general functioning, social functioning and quality of life at 12years on standardised measures, independent of other factors at baseline. It was not associated with gainful employment, for which education was the only predictor, or independent living, for which age was the only predictor. The relationship between duration of untreated psychosis and functional outcome was mediated by concurrent psychopathology, particularly negative symptoms. CONCLUSIONS: These results provide qualified support for the potential long-term benefit of reduction in the duration of untreated psychosis in terms of improvement in symptoms and functional outcome. Its failure to predict real-life outcomes such as independent living and gainful employment could reflect the importance of pre-existing socio-cultural factors such as individual opportunity. The relationship between duration of untreated psychosis and negative symptoms was largely responsible for its effect on function, suggesting a possible long-term protective mechanism against disability.

Nonadherence to medication four years after a first episode of psychosis and associated risk factors.

OBJECTIVES: This study examined concurrent associations and predictors at first indication of nonadherence to antipsychotic medication four years after a first episode of psychosis. METHODS: A prospective cohort of 171 patients in urban Ireland with a first episode of psychosis was followed up four years after inception (follow-up primary analysis, N=84; secondary analysis, N=104). RESULTS: At the four-year follow-up 76% were adherent and 24% were not. Nonadherence was concurrently associated with substance misuse (p<.01), increased symptomatology (p<.01), less insight (p=.01), lower global functioning (p<.01), and negative attitudes toward medication (p<.01). Compared with other patients, those who were nonadherent had more readmissions (p=.01). Predictors of future nonadherence were substance misuse (p=.02) and duration of untreated psychosis (p=.04). CONCLUSIONS: This prospective investigation confirms previous cross-sectional studies. The association between longer duration of untreated psychosis and nonadherence warrants further research because it could be interpreted as further evidence of the importance of early intervention.

Schizophrenia and the city: A review of literature and prospective study of psychosis and urbanicity in Ireland.

Urbanicity has been repeatedly associated with increased incidence of schizophrenia. This article (a) presents results of a prospective study of urbanicity and schizophrenia in Ireland and (b) reviews the literature relating to urbanicity and schizophrenia. We prospectively compared incidence of schizophrenia and other psychoses in urban and rural catchment areas (over 4years and 7years, respectively) using face-to-face, DSM-III-R diagnostic interviews. Incidence of schizophrenia in males was higher in urban compared to rural areas, with an age-adjusted incidence rate ratio (IRR) of 1.92 (1.52-2.44) for males and 1.34 (1.00-1.80) for females. Incidence of affective psychosis was lower in urban compared to rural areas for males (IRR 0.48; 0.34-0.67) and females (IRR 0.60; 0.43-0.83). These findings are consistent with the literature, which provides persuasive evidence that risk for schizophrenia increases with urban birth and/or upbringing, especially among males. Register-based studies support this conclusion more consistently than studies using face-to-face diagnostic interviews, the difference being related to power. The mechanism of association is unclear but may relate to biological or social/environmental factors or both, acting considerably before psychotic symptoms manifest. There is a diversity of potential candidates, including air pollution, cannabis and social exclusion. Urbanicity may have a synergistic effect with genetic vulnerability. Future research is likely to focus on the relationship between urbanicity and neural maldevelopment, the possibility of rural protective factors (e.g. social capital, low social fragmentation), urbanicity in developing countries, cultural variables and geographical location, and associations between urbanicity and other disorders (e.g. affective psychosis).

Prevalence and clinical correlates of depression in the acute phase of first episode schizophrenia.

BACKGROUND: Reported rates of depression in schizophrenia vary considerably. OBJECTIVE: To measure the prevalence of depression in a first episode sample of people with schizophrenia. METHODS: All referrals with a first episode of schizophrenia diagnosed using SCID interviews were assessed pre-discharge and again six months later. We used the Calgary Depression Scale for Schizophrenia (CDSS) and Positive and Negative Syndrome Scale (PANSS) to assess the severity of symptoms. RESULTS: Pre-discharge, 10.4% of the sample met CDSS criteria for depression. According to the PANSS depression (PANSS -D) subscale, 3% of patients were depressed, with a mean score of 7.48 (SD = 2.97). Only 3% of patients pre-discharge were found to be depressed on both the CDSS and the PANSS-D. Six months later 6.5% were depressed according to the CDSS. However none reached depression criteria according to the PANSS-D. The CDSS correlated with PANSS-D both pre-discharge and at follow-up. Feelings of depression and self-deprecation were the most common symptoms at baseline and follow-up. The CDSS was unrelated to negative symptoms at both stages. A lifetime history of alcohol abuse increased the risk for depression. CONCLUSION: Rates of depression in this sample were low. The CDSS appears to discriminate between depression and negative symptoms. Like the general population, alcohol misuse is a risk factor for depression in first episode schizophrenia.

Employment status amongst those with psychosis at first presentation.

INTRODUCTION: Employment is generally beneficial to health and quality of life. Despite many advances in the treatment of psychosis there are continuing reports of high levels of unemployment. In most studies of first episode psychosis (FEP) only rudimentary rates of employment are provided. We sought to establish the prevalence of employment amongst those with FEP from a geographically defined area, to compare employment categories for differences in demographical and clinical characteristics and finally, to examine factors associated with employment. METHODS: All cases of FEP were assessed from a defined suburban area with a structured clinical interview for DSM-III-R diagnosis and a standardised assessment protocol. Employment status was divided into employed, non-labour force work and unemployed. RESULTS: Of 162 cases of psychosis, those employed (46%) were indistinguishable from those in non-labour force work (21%). Those unemployed (33%) had significantly longer DUP, more negative symptoms and lower quality of life than those engaged in non-labour force work or those employed. Having a non-affective psychosis (chi(2) = 0.05, OR = 1.2; 95% CI 1.0, 1.4) was associated with being unemployed at presentation. Better (beta = -0.2, P = 0.00) academic premorbid adjustment was associated with being employed at presentation. CONCLUSIONS: Although 67% of those with FEP from a geographically defined area are engaged in purposeful work, the rate of unemployment is nine times the local rate. Longer DUP and negative symptoms are associated with unemployment at presentation. Standardised reporting of employment status would greatly assist research in this area.

Beyond the critical period: longitudinal study of 8-year outcome in first-episode non-affective psychosis.

BACKGROUND: The critical period hypothesis proposes that deterioration occurs aggressively during the early years of psychosis, with relative stability subsequently. Thus, interventions that shorten the duration of untreated psychosis (DUP) and arrest early deterioration may have long-term benefits. AIMS: To test the critical period hypothesis by determining whether outcome in non-affective psychosis stabilises beyond the critical period and whether DUP correlates with 8-year outcome; to determine whether duration of untreated illness (DUI) has any independent effect on outcome. METHOD: We recruited 118 people consecutively referred with first-episode psychosis to a prospective, naturalistic cohort study. RESULTS: Negative and disorganised symptoms improved between 4 and 8 years. Duration of untreated psychosis predicted remission, positive symptoms and social functioning at 8 years. Continuing functional recovery between 4 and 8 years was predicted by DUI. CONCLUSIONS: These results provide qualified support for the critical period hypothesis. The critical period could be extended to include the prodrome as well as early psychosis.

Phylogeography of Tibetan snowcock (Tetraogallus tibetanus) in Qinghai-Tibetan Plateau.

Data from eight microsatellite loci were used to infer the evolutionary and past demographic processes in 97 Tibetan snowcocks sampled from eight different geographical locations on the Qinghai-Tibetan Plateau. Analysis of the microsatellite DNA markers indicated that Tibetan snowcock on the plateau were geographically structured, and that phylogenetic analyses identified three phylogroups, namely those from Xunhua, the Qilian Mountains and all others. The use of Bayesian Clustering and Population Assignment analyses of the microsatellite genotypes revealed clear differentiation among the eight sampled groups of Tibetan snowcock, indicating strong isolation of these sub-populations. Therefore, we suggested that the distribution pattern of Tibetan snowcock observed today resulted from adaptation to the climatic conditions and glacial cycles on the Qinghai-Tibetan Plateau. In addition, BOTTLENECK analysis indicated that Tibetan snowcock had recently passed through evolutionary bottlenecks. These results suggested that effective conservation measures should be undertaken to protect Tibetan snowcock from an increased probability of extinction.

Lifetime history of substance misuse in first-episode psychosis: prevalence and its influence on psychopathology and onset of psychotic symptoms.

INTRODUCTION: Substance misuse (SM) (drug/alcohol dependence or abuse) in psychotic illness is an increasingly recognized problem. We aimed to estimate the prevalence and examine the influence of SM on age at onset of psychosis and psychopathology among patients with first-episode psychosis. METHOD: One hundred seventy-one consecutive patients with first-episode psychosis were assessed. SM, age of onset of psychosis and psychopathology were determined using valid instruments. RESULTS: Seventy-seven (46%) patients had a lifetime history of SM and were predominately males, had more positive symptoms, and in the majority of cases (84%), started misusing substances before the onset of psychosis (SM-BP). There was no difference in age of onset between patients with SM-BP and the rest of the sample. CONCLUSION: Lifetime history of SM is common and may influence psychopathology, but does not appear to influence or bring forward the age at onset of psychotic symptoms.

Is the duration of untreated psychosis temporally stable?

Although there is some evidence that duration of untreated psychosis (DUP) is geographically stable, few have examined whether the phenomenon is temporally stable. We examined DUP in two cohorts within two discrete time periods (1995-1999 and 2003-2005) spanning a decade in the same geographically defined community psychiatric service with no early intervention programme. Patients were diagnosed by Structured Clinical Interview for DSM (SCID) and we determined the DUP using the Beiser Scale. The DUP of the 240 participants did not differ significantly between study periods.

Ireland's long-stay charge refunds: mental capacity and dilemmas in a psychiatric institution.

OBJECTIVE: All patients who resided in state provided long-stay care in Ireland were required to pay the state for that care until 2006. In 2001 the Irish Ombudsman and Information Commissioner had highlighted the issue of the entitlement of people with medical cards to provision of free long-stay care. The Health Repayment scheme was subsequently set up in 2006 to facilitate the repayment of long-stay charges wrongly paid by patients. Issues of mental capacity arise particularly in the context of long-stay psychiatric patients applying for repayment of long-stay charges. Our aim was to devise a test suitable to assess the capacity of an individual to make an application for refund charges. METHOD: There was no specific test in existence to assess the capacity of an individual to make an application for refund of charges. A suitable test was devised based on the available literature which assessed whether the person understands the 'nature and effects' of making a refund application. Fifty-eight long-stay patients were deemed to be entitled to apply for a refund. RESULTS: Staff identified 47 (80%) patients as possibly lacking the capacity to make an application. Of these, 14 patients (29.8%) were found to have capacity to make an application (mean age 58.5 years) with 33 (70.2%) found to lack capacity (mean age 73 years). Of those with capacity 50% had a diagnosis of schizophrenia/schizoaffective disorder. None had cognitive impairment of degenerative origin. Of those who lacked capacity 45.5% had a diagnosis of dementia. All of the patients with dementia who were assessed were found to lack capacity whereas 59% of those with a diagnosis of schizophrenia/schizoaffective disorder lacked capacity. CONCLUSION: A substantial number of long-stay psychiatric patients may lack the capacity to make particular decisions. In this study the group who lacked capacity were an elderly group with dementia common. This process raised a dilemma about how a patient without capacity to make a refund application can then manage the money claimed on their behalf and whether guardianship safeguards are necessary.

Is violence at presentation by patients with first-episode psychosis associated with duration of untreated psychosis?

INTRODUCTION: Violence in first episode psychosis poses significant challenges for mental health staff and patients' families. Violence has been shown to be related to psychopathology. Duration of untreated psychosis (DUP) has been shown to influence psychopathology at presentation in first-episode psychosis, but little is known about the direct relationship between violence at presentation and DUP. We therefore sought to examine the relationship between these two variables. METHODS: Patients were all individuals aged between 16 and 65 years, with a DSM-III-R diagnosis of psychotic illness, taking part in a First Episode study. We used the Structured Clinical Interview (SCID-I), Positive and Negative Symptom Scale (PANSS), Beiser Scale and the Modified Overt Aggression Scale (MOAS) to evaluate diagnosis, psychopathology, DUP and violent behaviour respectively. Data for each case were retrospectively examined for violence, for the week prior to and week following first contact with psychiatric services, blind to diagnosis, DUP and psychopathology scores. RESULTS: We assessed 157 patients. About 46 patients (29%) were violent. Violence rates did not differ across diagnostic groups, while DUP varied significantly across diagnostic groups (P = 0.001). Violence was not associated with DUP across all psychoses (P = 0.41). In the schizophrenia subgroup (n = 94), thirty individuals (32%) were violent. In a logistic regression, logDUP was not associated with violence (P = 0.11). Violence was predicted by involuntary admission status (P = 0.04) and global positive symptoms (P = 0.03). DUP was associated weakly with negative symptoms (P = 0.01) but not associated with positive or general psychopathology. Neither pre nor post-contact violence was associated (P = 0.79 and P = 0.09 respectively) with DUP. DISCUSSION: Contrary to a recent study, we did not find an association between violence at presentation and DUP. The relationships between violence, DUP and psychopathology are complex and may be compounded by potential difficulties inherent in the PANSS. CONCLUSION: Programs to reduce DUP may not impact on rates of violence at presentation in First Episode Psychosis (FEP).

Determinants of duration of untreated psychosis in an Irish catchment area sample.

OBJECTIVE: To examine the variables that influence of duration of untreated psychosis (DUP) prior to presentation in persons with a first episode of psychosis. METHOD: Prospective examination of consecutive first presentations with DSM-IV psychosis attending a community based psychiatric service. RESULTS: One hundred and seventy-one patients had an average duration of untreated psychosis of 18 months and a median of five months. The mean duration of untreated mania was 1.5 months, median 0.75 months. DUP was predicted by social withdrawal and diagnosis in the total group and by prodrome in the schizophrenia/schizophreniform group. DUP was not associated with age at onset of psychosis, educational years or living status. CONCLUSIONS: There are significant differences in DUP between diagnostic groups. Increased social withdrawal is associated with a longer DUP.

Untreated illness and outcome of psychosis.

BACKGROUND: There has been controversy as to whether early intervention in psychosis can improve the outcome of the disorder. AIMS: To establish if there is an association between duration of untreated psychosis and the 4-year outcome of persons with a first episode of psychosis. METHOD: Prospective naturalistic follow-up study of the outcome of consecutive first presentations with DSM-IV psychosis attending a community-based psychiatric service. RESULTS: A longer duration of untreated psychosis was associated with a significantly poorer functional and symptomatic outcome 4 years later. For schizophrenia and schizophreniform disorder, each increment in duration of untreated psychosis was associated with a 7.8 point decrease in global functioning and an increase in positive symptoms scores by 1.9 points. CONCLUSIONS: This study extends the findings of short-term follow-up studies by confirming an association between duration of untreated psychosis and 'mid-term' outcome.

Suicidality in first episode psychosis.

Many studies have confirmed that the risk of suicide is high in the period after first presentation. There is relatively little information about the risk of suicide using illness onset as the starting point. We assessed suicidality in a cohort of 166 individuals from an urban catchment area during the period of untreated psychosis and at 4 year follow up. Nearly 10% of individuals attempted suicide prior to presentation. Four years later 18% had made a suicide attempt and 3% completed suicide. Suicide attempts prior to presentation were associated with a longer duration of untreated psychosis.

Diagnostic specificity and predictors of neurological soft signs in schizophrenia, bipolar disorder and other psychoses over the first 4 years of illness.

BACKGROUND: Neurological soft signs (NSS) are well described among patients with schizophrenia, the neurology of other psychoses is relatively unexplored and few comparative studies have prospectively examined these signs in first-episode patients. METHODS: We assessed neurological functioning in 242 patients presenting with a first episode of psychosis (in accordance with DSM-IV diagnosis) using the Condensed Neurological Examination (CNE). We sought to determine whether NSS were specific to patients with schizophrenia, bipolar affective disorder and other forms of psychosis. We also examined the factors associated with and predictive of neurodysfunction at first presentation and at 4 year follow-up. RESULTS: NSS were not specific to any diagnostic group. Neurological functioning was closely associated with psychopathology and mixed-handedness at first presentation. At follow-up there was a statistically significant improvement in neurological functioning. Persistent neurodysfunction at this stage was related to enduring negative symptoms and associated with poorer outcome. DISCUSSION: Schizophrenia and bipolar disorder are indistinguishable in terms of neurodysfunction at presentation. At presentation and 4 years NSS closely parallel psychopathology and mixed-handedness indicating that NSS may be a function of these factors or possibly an independent factor operates equally upon both symptoms and neurological function.