Exploring metapopulation-scale suppression alternatives for a global invader in a river network experiencing climate change.

Invasive species can dramatically alter ecosystems, but eradication is difficult, and suppression is expensive once they are established. Uncertainties in the potential for expansion and impacts by an invader can lead to delayed and inadequate suppression, allowing for establishment. Metapopulation viability models can aid in planning strategies to improve responses to invaders and lessen invasive species' impacts, which may be particularly important under climate change. We used a spatially explicit metapopulation viability model to explore suppression strategies for ecologically damaging invasive brown trout (Salmo trutta), established in the Colorado River and a tributary in Grand Canyon National Park. Our goals were to estimate the effectiveness of strategies targeting different life stages and subpopulations within a metapopulation; quantify the effectiveness of a rapid response to a new invasion relative to delaying action until establishment; and estimate whether future hydrology and temperature regimes related to climate change and reservoir management affect metapopulation viability and alter the optimal management response. Our models included scenarios targeting different life stages with spatially varying intensities of electrofishing, redd destruction, incentivized angler harvest, piscicides, and a weir. Quasi-extinction (QE) was obtainable only with metapopulation-wide suppression targeting multiple life stages. Brown trout population growth rates were most sensitive to changes in age 0 and large adult mortality. The duration of suppression needed to reach QE for a large established subpopulation was 12 years compared with 4 with a rapid response to a new invasion. Isolated subpopulations were vulnerable to suppression; however, connected tributary subpopulations enhanced metapopulation persistence by serving as climate refuges. Water shortages driving changes in reservoir storage and subsequent warming would cause brown trout declines, but metapopulation QE was achieved only through refocusing and increasing suppression. Our modeling approach improves understanding of invasive brown trout metapopulation dynamics, which could lead to more focused and effective invasive species suppression strategies and, ultimately, maintenance of populations of endemic fishes.

Las especies invasoras pueden alterar dramáticamente un ecosistema, pero erradicarlas es complicado y suprimirlas es costoso una vez que están establecidas. Las incertidumbres en el potencial de expansión y el impacto de un invasor pueden derivar en una supresión retardada e inadecuada que permite el establecimiento. Los modelos de viabilidad meta poblacional pueden auxiliar en la planeación de estrategias para mejorar las respuestas ante especies invasoras y disminuir su impacto, lo cual puede ser particularmente importante ante el cambio climático. Usamos un modelo meta poblacional espacialmente explícito para explorar las estrategias de supresión usadas con la trucha café (Salmo trutta), una especie invasora y dañina establecida en el Río Colorado en el Parque Nacional del Gran Cañón. Nuestros objetivos fueron estimar la efectividad de las estrategias enfocadas en diferentes etapas de vida y subpoblaciones dentro de una meta población; cuantificar la efectividad de una respuesta rápida ante una nueva invasión en relación a retardar la acción hasta que ocurra el establecimiento; y estimar si los sistemas térmicos e hidrológicos relacionados con el cambio climático y la gestión de cuencas afectarán la viabilidad meta poblacional y alterarán la respuesta óptima de gestión en el futuro. Nuestros modelos incluyeron escenarios enfocados en diferentes etapas de vida con intensidades espacialmente variables de pesca eléctrica, destrucción de redes, cultivo incentivado de pescadores, piscicidas y un dique. La cuasi extinción (CE) sólo se obtuvo con una supresión a nivel meta poblacional enfocada en múltiples etapas de vida. Las tasas de crecimiento poblacional de la trucha fueron más sensibles a los cambios en edad cero y una gran mortalidad adulta. La duración de la supresión requerida para llegar a la CE para una subpoblación grande establecida fue de doce años en comparación con los cuatro de una respuesta rápida a una nueva invasión. Las subpoblaciones aisladas fueron vulnerables a la supresión; sin embargo, las subpoblaciones conectadas por medio de tributarios incrementaron la persistencia meta poblacional al fungir como refugios climáticos. La escasez de agua, cambios impulsores en el almacenamiento de la cuenca y el calentamiento subsecuente causarían declinaciones de la trucha, pero la CE meta poblacional sólo se logró con el reenfoque e incremento de la supresión. Nuestra estrategia de modelado mejora el entendimiento de las dinámicas meta poblacionales de la trucha café invasora, lo cual podría llevar a estrategias de supresión más enfocadas y efectivas y, finalmente, al mantenimiento de las poblaciones de peces endémicos. Exploración de alternativas a la supresión a escala meta poblacional de un invasor mundial en una red de ríos que experimenta el cambio climático.

Resilience of terrestrial and aquatic fauna to historical and future wildfire regimes in western North America.

Wildfires in many western North American forests are becoming more frequent, larger, and severe, with changed seasonal patterns. In response, coniferous forest ecosystems will transition toward dominance by fire-adapted hardwoods, shrubs, meadows, and grasslands, which may benefit some faunal communities, but not others. We describe factors that limit and promote faunal resilience to shifting wildfire regimes for terrestrial and aquatic ecosystems. We highlight the potential value of interspersed nonforest patches to terrestrial wildlife. Similarly, we review watershed thresholds and factors that control the resilience of aquatic ecosystems to wildfire, mediated by thermal changes and chemical, debris, and sediment loadings. We present a 2-dimensional life history framework to describe temporal and spatial life history traits that species use to resist wildfire effects or to recover after wildfire disturbance at a metapopulation scale. The role of fire refuge is explored for metapopulations of species. In aquatic systems, recovery of assemblages postfire may be faster for smaller fires where unburned tributary basins or instream structures provide refuge from debris and sediment flows. We envision that more-frequent, lower-severity fires will favor opportunistic species and that less-frequent high-severity fires will favor better competitors. Along the spatial dimension, we hypothesize that fire regimes that are predictable and generate burned patches in close proximity to refuge will favor species that move to refuges and later recolonize, whereas fire regimes that tend to generate less-severely burned patches may favor species that shelter in place. Looking beyond the trees to forest fauna, we consider mitigation options to enhance resilience and buy time for species facing a no-analog future.

Victimization, violence and facial affect recognition in a community sample of first-episode psychosis patients.

AIMS: This exploratory study is the first to examine previously identified variables of increased vulnerability to victimization, the prevalence of aggression in a cohort of patients with first-episode psychosis and the potential impact of impairments in facial affect recognition (FAR) on victimization. METHODS: Sixty-nine male participants completed assessments of IQ, substance use, psychopathy, childhood trauma, aggressive behaviour and psychopathology. Participants were asked about violent victimization in the past year and charges for violent offences. FAR was assessed using the Animated Full Facial Comprehension Test. RESULTS: The victimized group (n = 25) had significantly higher psychopathy traits (P = .042) and lower recognition of sadness (P < .01) compared to the non-victimized group (n = 44). Participants who reported charges for violent offences (n = 15) had significantly higher scores on measures of physical abuse in childhood (P < .01), substance use (P < .05 for cannabis, P < .001 for cocaine and amphetamine use), psychopathy traits (P < .01), psychopathology (P = .031) and lifetime aggressive behaviour (P < .01). The logistic regression models using FAR sadness and Psychopathic Personality Inventory-Revised (PPI-R) total score as predictors for victimization (χ 2 [2] = 13.81, P = .001; Nagelkerke R 2 = .30) and using physical abuse in childhood, PPI-R total score, and psychopathology as predictors for violent offences (χ 2 [3] = 14.89, P = .002; Nagelkerke R 2 = .36) were significant. CONCLUSIONS: These findings highlight the value of considering victimization in psychotic illness from a social information processing perspective in addition to known clinical and lifestyle factors. Based on these results, future studies could explore the use of affect recognition training early in the course of the illness as a possible intervention to reduce victimization.

Formula supplementation remains a risk for cow's milk allergy in breast-fed infants.

BACKGROUND: Many breastfed babies in Ireland receive formula supplementation within 24 hours of birth. We explored (a) impact of formula supplementation on the likelihood of developing cow's milk protein allergy (CMPA) and (b) current practice of formula supplementation (<24 hours) among mothers intending to breastfeed. METHOD: Fifty-five CMPA-diagnosed children, fed at <24 hours of age (breast only, formula only or breast with formula supplementation), were recruited, and 55 milk-tolerant age- and sex-matched controls were identified retrospectively in Cork University Maternity Hospital. Two logistic regressions (LoR) examined neonatal feed types on likelihood of developing CMPA while controlling for parental atopy and infant sex. Formula supplementation was then prospectively measured among a separate group of 179 breastfeeding mothers. Linear regression (LiR) analysis was used to examine the subjective and objective reasons for formula supplementation, in addition to examining pre-existing factors. RESULTS: Two LoR examined the infant groups: exclusively breastfed, exclusively formula-fed or breastfed with formula supplementation. The first LoR model which showed only formula supplementation was significant in prediction of development of CMPA (χ2 (3) = 25.74, P < .05), with 74% diagnostic accuracy when parental atopy and infant sex were controlled for. Breastfed infants given formula supplements were 7.03 (95% CI, 1.82-27.25) times more likely to exhibit CMPA than those who were exclusively breastfed. Formula supplementation was significant (OR 16.62, 95% CI 3.89-71.11), indicating that breastfed infants who were given formula supplements were 16 times more likely to exhibit CMPA than those who were exclusively bottle-fed. Exclusively formula-fed infants (odds ratio 0.42, 95% CI, 0.16-1.07) were not significantly more likely to exhibit CMPA than those who were exclusively breastfed in either model (P > .05). About 45.8% of breastfed infants (<24 hours) received supplemental formula. LiR investigated importance of the subjective and objective reasons, in predicting formula supplementation. This model was significant F(8,170) = 66.95, P < .05) explaining 75% of total variance. The subjective factors 'no latch' and 'mum unwell' were the strongest predictors (ß > .45). Objective factors and pre-existing factors had lower ß values with only mode of delivery and infant hypoglycaemia being significant. CONCLUSION: Breastfed babies are still being put at significantly increased risk of CMPA by receiving supplemental formula in the first 24 hours of life, despite the major predictors of supplementation being subjective and remediable in other ways. Mothers and healthcare providers should be better educated on the benefits of exclusive breastfeeding and resourced adequately to avoid unnecessary formula supplementation to reduce risk of development of CMPA.

The viability of probiotics in water, breast milk, and infant formula.

The aim of this study was to determine bacteriological stability of a probiotic mixture dispersed in various diluents. The commercially available probiotic (Infloran®), containing Bifidobacterium bifidum (109 CFU/250 mg tablet) and Lactobacillus acidophilus (109 CFU/250 mg tablet), was dispersed within expressed breast milk, sterile water, and infant formula and examined at temperatures of 4 and 21 °C. When stored at 4 °C, significant decreases (P < 0.05) in the level of L. acidophilus and B. bifidum were observed in expressed breast milk and sterile water after a 6-h period. However, when stored in infant formula, both strains remained stable over a 12-h period. When stored at 21 °C, a significant decrease (P < 0.05) was observed in the level of L. acidophilus in sterile water, expressed breast milk and infant formula throughout a 12-h period. However, no significant decrease was observed overtime in B. bifidum in all three diluents at this temperature. CONCLUSION: Our findings suggest that, when stored at 4 °C, this probiotic product can remain at a stable condition for 6 h in sterile water and infant formula; however, the viability of the probiotic decreases significantly after this period of time. Administration of this probiotic in sterile water can be an acceptable alternative to dispersion and administration in expressed breast milk. What is Known: • Administration of probiotics containing lactobacilli and bifidobacteria has become more widespread in neonatology, mainly as prophylaxis for the prevention of necrotising entercolitis in preterm infants. • Probiotic reconstitution, from its powder base, is not standardized and various diluents, including sterile water, breast milk, and infant formula, have been used. What is New: • When stored at 4 °C, a probiotic containing lactobacilli and bifidobacteria remains at a stable microbological condition for up to 6 h in sterile water. • Administration of this probiotic dispersed in sterile water, followed by an EBM feed, can be an acceptable alternative to dispersion and administration in EBM.

Standardized Parenteral Nutrition for the Transition Phase in Preterm Infants: A Bag That Fits.

The optimal composition of standardized parenteral nutrition (SPN) is not yet known, contributing to nutrient deficit accrual and growth failure, with the period of parenteral nutrition weaning, i.e., transition (TN) phase, being identified as particularly vulnerable. We created a comprehensive nutrition database, representative of the nutritional course of a diverse range of preterm infants (n = 59, birth weight ≤ 1500 g, gestation < 34 weeks) by collecting hourly macronutrient intake data as part of a prospective, observational study over 19 months. Using a nutrient modeling technique for the TN phase, various amino acid (AA) concentrations of SPN were tested within the database, whilst acknowledging the nutritional contribution from enteral feeds until target AA intakes were consistently achieved. From the modeling, the AA composition of SPN was determined at 3.5 g/100 mL, which was the maximum to avoid exceeding target intakes at any point in the TN phase. However, in order to consistently achieve target AA intakes, additional nutritional strategies were required, which included increasing the exclusion of enteral feeds in fluid and nutrient calculations from <20 mL/kg/day to <40 mL/kg/day, and earlier fortification of breastmilk at 80 mL/kg/day. This data-driven nutrient modeling process supported the development of an improved SPN regimen for our preterm population in the TN phase.

Transition Phase Nutrition Recommendations: A Missing Link in the Nutrition Management of Preterm Infants.

BACKGROUND: Despite the availability of international nutrition recommendations, preterm infants remain vulnerable to suboptimal nutrition. The standard approach of assessing nutrient intakes chronologically may make it difficult to identify the origin of nutrient deficits and/or excesses. OBJECTIVE: To develop a "nutrition phase" approach to evaluating nutrition support, enabling analysis of nutrient intakes during the period of weaning from parenteral nutrition (PN) to enteral nutrition (EN), called the transition (TN) phase, and compare the data with those analyzed using the standard "chronological age" approach to assess whether the identification of nutrient deficits and/or excesses can be improved. METHODS: Analysis of a comprehensive nutrition database developed using actual nutrient intake data collected on an hourly basis in 59 preterm infants (birth weight ≤1500 g, gestation <34 weeks) over the period of PN delivery (range, 2-21 days). RESULTS: The nutrition phase analysis approach revealed substantial macronutrient and energy deficits during the TN phase. In particular, deficits were identified as maximal during the EN-dominant TN phase (enteral feeds ≥80 mL/kg/d) of the infant's nutrition course. In contrast, the chronological age analysis approach did not reveal a corresponding pattern of deficit occurrence but rather intakes that approximated or exceeded recommendations. CONCLUSION: Actual intakes of nutrients, analyzed using a nutrition phase approach to evaluating nutrition support, enabled a more infant-driven rather than age-driven application of nutrition recommendations. This approach unmasked nutrient deficits occurring during the transition phase. Overcoming nutrient deficits in this nutrition phase should be prioritized to improve the nutrition management of preterm infants.

Quetiapine v. lithium in the maintenance phase following a first episode of mania: randomised controlled trial.

BackgroundLithium and quetiapine are considered standard maintenance agents for bipolar disorder yet it is unclear how their efficacy compares with each other.AimsTo investigate the differential effect of lithium and quetiapine on symptoms of depression, mania, general functioning, global illness severity and quality of life in patients with recently stabilised first-episode mania.MethodMaintenance trial of patients with first-episode mania stabilised on a combination of lithium and quetiapine, subsequently randomised to lithium or quetiapine monotherapy (up to 800 mg/day) and followed up for 1 year. (Trial registration: Australian and New Zealand Clinical Trials Registry - ACTRN12607000639426.)ResultsIn total, 61 individuals were randomised. Within mixed-model repeated measures analyses, significant omnibus treatment × visit interactions were observed for measures of overall psychopathology, psychotic symptoms and functioning. Planned and post hoc comparisons further demonstrated the superiority of lithium treatment over quetiapine.ConclusionsIn people with first-episode mania treated with a combination of lithium and quetiapine, continuation treatment with lithium rather than quetiapine is superior in terms of mean levels of symptoms during a 1-year evolution.

Adjunctive Taurine in First-Episode Psychosis: A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study.

OBJECTIVE: Taurine is an inhibitory neuromodulatory amino acid in the central nervous system that activates the GABA- and glycine-insensitive chloride channel and inhibits the N-methyl-D-aspartate receptor. It also functions as a neuroprotective agent and has a role in neural development and neurogenesis. The aim of this study was to determine the efficacy of adjunctive taurine in improving symptomatology and cognition among patients with a DSM-IV first-episode psychotic disorder. METHODS: 121 patients with first-episode psychosis, aged 18-25 years, attending early intervention services consented to participate in this randomized, double-blind, placebo-controlled trial conducted from January 2007 to May 2009. Patients taking low-dose antipsychotic medication were randomly assigned to receive once-daily taurine 4 g or placebo for 12 weeks. The coprimary outcomes were change in symptomatology (measured by the Brief Psychiatric Rating Scale [BPRS] total score) and change in cognition (measured by the Measurement and Treatment Research to Improve Cognition in Schizophrenia [MATRICS] Consensus Cognitive Battery composite score) at 12 weeks. Secondary outcomes included tolerability and safety and additional clinical and functioning measures. RESULTS: 86 participants (n = 47 taurine; n = 39 placebo) were included in the final analysis. Taurine significantly improved symptomatology measured by the BPRS total score (95% CI, 1.8-8.5; P = .004) and psychotic subscale (95% CI, 0.1-1.5; P = .026) compared to placebo. Additionally, improvements were observed in the Calgary Depression Scale for Schizophrenia (95% CI, 0.1-3.0; P = .047) and Global Assessment of Functioning (95% CI, 0.3-8.8; P = .04) scores. There was no group difference in composite cognitive score (95% CI, -1.7 to 1.0; P = .582). A significant group difference was found on one safety and tolerability item (psychic item 2, asthenia/lassitude/increased fatigability) of the Udvalg for Kliniske Undersogelser, with the taurine group showing a more favorable outcome (P = .006). CONCLUSIONS: Adjunctive taurine did not improve cognition, but it appears to improve psychopathology in patients with first-episode psychosis. The use of taurine warrants further investigation in larger randomized studies, particularly early in the course of psychosis. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00420823.

Seizure burden and neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy.

AIM: To examine the relationship between electrographic seizures and long-term outcome in neonates with hypoxic-ischemic encephalopathy (HIE). METHOD: Full-term neonates with HIE born in Cork University Maternity Hospital from 2003 to 2006 (pre-hypothermia era) and 2009 to 2012 (hypothermia era) were included in this observational study. All had early continuous electroencephalography monitoring. All electrographic seizures were annotated. The total seizure burden and hourly seizure burden were calculated. Outcome (normal/abnormal) was assessed at 24 to 48 months in surviving neonates using either the Bayley Scales of Infant and Toddler Development, Third Edition or the Griffiths Mental Development Scales; a diagnosis of cerebral palsy or epilepsy was also considered an abnormal outcome. RESULTS: Continuous electroencephalography was recorded for a median of 57.1 hours (interquartile range 33.5-80.5h) in 47 neonates (31 males, 16 females); 29 out of 47 (62%) had electrographic seizures and 25 out of 47 (53%) had an abnormal outcome. The presence of seizures per se was not associated with abnormal outcome (p=0.126); however, the odds of an abnormal outcome increased over ninefold (odds ratio [OR] 9.56; 95% confidence interval [95% CI] 2.43-37.67) if a neonate had a total seizure burden of more than 40 minutes (p=0.001), and eightfold (OR: 8.00; 95% CI: 2.06-31.07) if a neonate had a maximum hourly seizure burden of more than 13 minutes per hour (p=0.003). Controlling for electrographic HIE grade or treatment with hypothermia did not change the direction of the relationship between seizure burden and outcome. INTERPRETATION: In HIE, a high electrographic seizure burden is significantly associated with abnormal outcome, independent of HIE severity or treatment with hypothermia.

Chemical weathering as a mechanism for the climatic control of bedrock river incision.

Feedbacks between climate, erosion and tectonics influence the rates of chemical weathering reactions, which can consume atmospheric CO2 and modulate global climate. However, quantitative predictions for the coupling of these feedbacks are limited because the specific mechanisms by which climate controls erosion are poorly understood. Here we show that climate-dependent chemical weathering controls the erodibility of bedrock-floored rivers across a rainfall gradient on the Big Island of Hawai'i. Field data demonstrate that the physical strength of bedrock in streambeds varies with the degree of chemical weathering, which increases systematically with local rainfall rate. We find that incorporating the quantified relationships between local rainfall and erodibility into a commonly used river incision model is necessary to predict the rates and patterns of downcutting of these rivers. In contrast to using only precipitation-dependent river discharge to explain the climatic control of bedrock river incision, the mechanism of chemical weathering can explain strong coupling between local climate and river incision.

Optimising preterm nutrition: present and future.

The goal of preterm nutrition in achieving growth and body composition approximating that of the fetus of the same postmenstrual age is difficult to achieve. Current nutrition recommendations depend largely on expert opinion, due to lack of evidence, and are primarily birth weight based, with no consideration given to gestational age and/or need for catch-up growth. Assessment of growth is based predominately on anthropometry, which gives insufficient attention to the quality of growth. The present paper provides a review of the current literature on the nutritional management and assessment of growth in preterm infants. It explores several approaches that may be required to optimise nutrient intakes in preterm infants, such as personalising nutritional support, collection of nutrient intake data in real-time, and measurement of body composition. In clinical practice, the response to inappropriate nutrient intakes is delayed as the effects of under- or overnutrition are not immediate, and there is limited nutritional feedback at the cot-side. The accurate and non-invasive measurement of infant body composition, assessed by means of air displacement plethysmography, has been shown to be useful in assessing quality of growth. The development and implementation of personalised, responsive nutritional management of preterm infants, utilising real-time nutrient intake data collection, with ongoing nutritional assessments that include measurement of body composition is required to help meet the individual needs of preterm infants.

The temporal characteristics of seizures in neonatal hypoxic ischemic encephalopathy treated with hypothermia.

PURPOSE: The characteristics of electrographic seizures in newborns with hypoxic-ischaemic encephalopathy (HIE) treated with therapeutic hypothermia (TH) are poorly described. This retrospective, observational study provides reference data on the characteristics of seizures and their evolution over time in newborns with HIE receiving whole-body TH. METHOD: The cohort under analysis included 23 infants with HIE and seizures defined by multi-channel EEG recordings. Clinical presentation, details of TH and antiepileptic drugs used were recorded. Time from first to last-recorded electrographic seizure (seizure period) was calculated. Temporal characteristics of seizures - total burden, duration, number, burden in minutes per hour, distribution of burden over time (temporal evolution), time from seizure onset to maximum seizure burden (Tmsb), T1, and time from Tmsb to seizure offset, T2 - were analysed. RESULTS: The median age at electrographic seizure onset was 13.1h (IQR: 11.4 to 22.0). Tmsb was reached at a median age of 19.4 hours (IQR: 12.2 to 29.7). Median seizure period was 16.5h (IQR: 7.0 to 49.7), median number of seizures per hour was 1.9 (IQR: 1.0 to 3.3). The seizure burden was 4.0 min/h (IQR: 2.0 to 7.0). There was no consistent pattern in the temporal evolution of seizures in neonates treated with TH. The skewness was neither positive nor negative (p-value=0.15), there was no difference between the duration of T1 and T2 (p-value=0.09) and no difference in the seizure burden between T1 and T2 (p=0.09). There was an association between Tmsb and Phenobarbital (PB) administration (r=0.76, p-value<0.001). CONCLUSION: There is no consistent temporal evolution of seizure burden in neonates treated with TH. Seizures are diffuse, and their characteristics are variable.

Intensive case management for high-risk patients with first-episode psychosis: service model and outcomes.

BACKGROUND: The first episode of psychosis is a crucial period when early intervention can alter the trajectory of the young person's ongoing mental health and general functioning. After an investigation into completed suicides in the Early Psychosis Prevention and Intervention Centre (EPPIC) programme, the intensive case management subprogramme was developed in 2003 to provide assertive outreach to young people having a first episode of psychosis who are at high risk owing to risk to self or others, disengagement, or suboptimal recovery. We report intensive case management model development, characterise the target cohort, and report on outcomes compared with EPPIC treatment as usual. METHODS: Inclusion criteria, staff support, referral pathways, clinical review processes, models of engagement and care, and risk management protocols are described. We compared 120 consecutive referrals with 50 EPPIC treatment as usual patients (age 15-24 years) in a naturalistic stratified quasi-experimental real-world design. Key performance indicators of service use plus engagement and suicide attempts were compared between EPPIC treatment as usual and intensive case management, and psychosocial and clinical measures were compared between intensive case management referral and discharge. FINDINGS: Referrals were predominately unemployed males with low levels of functioning and educational attainment. They were characterised by a family history of mental illness, migration and early separation, with substantial trauma, history of violence, and forensic attention. Intensive case management improved psychopathology and psychosocial outcomes in high-risk patients and reduced risk ratings, admissions, bed days, and crisis contacts. INTERPRETATION: Characterisation of intensive case management patients validated the clinical research focus and identified a first episode of psychosis high-risk subgroup. In a real-world study, implementation of an intensive case management stream within a well-established first episode of psychosis service showed significant improvement in key service outcomes. Further analysis is needed to determine cost savings and effects on psychosocial outcomes. Targeting intensive case management services to high-risk patients with unmet needs should reduce the distress associated with pathways to care for patients, their families, and the community. FUNDING: National Health & Medical Research Council and the Colonial Foundation.

Mode of neonatal death in an Irish maternity centre.

UNLABELLED: Modes of neonatal dying vary among maternity centres, both within and between countries. There have been few reports concerning mode of dying from countries with low rates of termination of pregnancy, such as Ireland. We conducted a retrospective chart review of all neonatal deaths, between January 2010 and January 2013, within a single Irish maternity centre. The mode of dying was classified as one of (1) withholding life-sustaining treatment (LST), (2) withdrawal of LST in moribund infants, (3) withdrawal of LST for quality of life reasons or (4) death despite maximal intensive care treatment. There were a total of 64 deaths during the study period. Congenital abnormalities accounted for 47 % of deaths and prematurity for 41 % of deaths. Withholding LST was the most frequent mode of dying, occurring in 38 % of all deaths. A total of 12 % of neonatal deaths occurred despite maximal intensive care treatment. CONCLUSIONS: Congenital abnormalities were the most common cause of neonatal deaths. A high proportion followed LST being withheld, most likely a reflection of the low rates of medical termination in Ireland. Modes of dying in the neonatal period vary between maternity centres with culturally different backgrounds.

Vascular endothelial growth factor and brain-derived neurotrophic factor in quetiapine treated first-episode psychosis.

Objective. It has been suggested that atypical antipsychotics confer their effects via brain-derived neurotrophic factor (BDNF). We investigated the effect of quetiapine on serum levels of BDNF and vascular endothelial growth factor (VEGF) in drug-naive first-episode psychosis subjects. Methods. Fifteen patients drawn from a larger study received quetiapine treatment for twelve weeks. Baseline levels of serum BDNF and VEGF were compared to age- and sex-matched healthy controls and to levels following treatment. Linear regression analyses were performed to determine the relationship of BDNF and VEGF levels with outcome measures at baseline and week 12. Results. The mean serum BDNF level was significantly higher at week 12 compared to baseline and correlated with reductions in Brief Psychiatric Rating Scale (BPRS) and general psychopathology scores. Changes in serum VEGF levels also correlated significantly with a reduction in BPRS scores, a significant improvement in PANNS positive symptoms scores, and displayed a positive relationship with changes in BDNF levels. Conclusions. Our findings suggest that BDNF and VEGF are potential biomarkers for gauging improvement of psychotic symptoms. This suggests a novel neurotrophic-based mechanism of the drug effects of quetiapine on psychosis. This is the first report of VEGF perturbation in psychosis.

The individual-specific and diverse nature of the preterm infant microbiota.

OBJECTIVE: To examine the composition of the evolving microbiota of preterm infants at weeks 2 and 4 of life. SETTINGS: The paediatric intensive care unit of the Cork University Maternity Hospital. METHODS: The microbial diversity of faecal samples from 10 preterm infants was determined using 16S rRNA amplicon pyrosequencing technology. RESULTS: In total, 452 863 sequences were obtained from 20 faecal samples collected from 10 preterm infants, allowing a level of analysis not previously reported. The preterm infant microbiota samples were dominated by Proteobacteria (46%), followed by Firmicutes (45%), while the phyla Actinobacteria (2%) and Bacteroidetes (7%) were detected at much lower levels at week 2 of life. This colonisation pattern was similar at week 4 of life. At the family level, Enterobacteriaceae were detected at 50% and 58% at weeks 2 and 4, respectively. The preterm infants were characterised by a lack of detectable Bifidobacterium and Lactobacillus genera commonly associated with the infant gut. In addition to the dominance of the Proteobacteria, a high level of interindividual variation was observed, indeed the relative proportions of different phyla, families and genera in different infants ranged from <1% to >90%. CONCLUSIONS: The results indicate that in addition to an uncharacteristic microbiota relative to that reported for healthy term infants, there was a large interindividual variation in the faecal microbiota diversity of preterm infants suggesting that the preterm microbiota is individual-specific and does not display a uniformity among infants.

Microbiota diversity and stability of the preterm neonatal ileum and colon of two infants.

The composition of the microbiota associated with the human ileum and colon in the early weeks of life of two preterm infants was examined, with particular emphasis on the Lactobacillus and Bifidobacterium members. Culturing work showed that bifidobacteria and lactobacilli in the ileostomy changed over time, compared with the colostomy effluent where there was far less variation. The colostomy infant was dominated by two phyla, Actinobacteria and Firmicutes, while in the ileostomy samples, Proteobacteria emerged at the expense of Actinobacteria. Bacteroidetes were only detected following the reversal of the ileostomy in the final fecal sample and were not detected in any colonic fluid samples. Clostridia levels were unstable in the colostomy fluid, suggesting that the ileostomy/colostomy itself influenced the gut microbiota, in particular the strict anaerobes. Pyrosequencing analysis of microbiota composition indicated that bifidobacteria and lactobacilli are among the dominant genera in both the ileal and colonic fluids. Bifidobacteria and lactobacilli levels were unstable in the ileostomy fluid, with large reductions in numbers and relative proportions of both observed. These decreases were characterized by an increase in proportions of Streptococcus and Enterobacteriaceae. Clostridium was detected only in the colonic effluent, with large changes in the relative proportions over time.

The temporal evolution of electrographic seizure burden in neonatal hypoxic ischemic encephalopathy.

PURPOSE: Hypoxic ischemic encephalopathy (HIE) accounts for 60% of all neonatal seizures. There is emerging evidence that seizures cause additional injury to the developing brain that has sustained hypoxic ischemic injury. Temporal evolution of clinical seizure burden in HIE has been characterized, with maximum clinical seizure burden (the period of maximum seizure activity) being observed between 12 and 24 h of age. The purpose of our study was to investigate the distribution of electrographic seizure burden (the accumulated duration of seizures over a defined time period), following the initial hypoxic ischemic insult. METHODS: Fifteen full-term newborns with HIE and seizures, and a minimum of 48 h of continuous video-electroencephalography (EEG), were included in this retrospective study. Medical records of the infants were reviewed and details of clinical seizures and antiepileptic drugs were recorded. The time of maximum seizure burden was defined as the midpoint of an hour-long window, shifted in time by 1 s across the full EEG recording, which contained the maximum duration of seizures. The degree of temporal evolution of seizure burden within this period was tested. Temporal evolution was further analyzed by segmenting the time series into two periods; the time between the first recorded seizure and the maximum seizure burden (T(1)), and the time between the maximum seizure burden and the last recorded seizure (T(2)). Seizure burden, duration, and number of seizures per hour were analyzed within each time period. KEY FINDINGS: EEG was commenced at a median of 14 h of age. Maximum electrographic seizure burden was reached at a median age of 22.7 h. Time from first recorded seizure to maximum seizure burden (T(1)) was significantly shorter than time from maximum seizure burden to last recorded seizure (T(2)) (p-value = 0.01). Median seizure burden during T(1) was significantly higher than during T(2) (p-value = 0.007). There is temporal evolution of electrographic seizure burden in full-term newborns with HIE. There is a short period of high seizure burden (T(1)) followed by a longer period of lower seizure burden (T(2)). SIGNIFICANCE: Understanding the temporal evolution of seizure burden in HIE contributes further to our understanding of neonatal seizures, helps identify an optimal therapeutic window for seizure treatment, and provides a benchmark against which to measure the efficacy of new and innovative forms of neuroprotection and antiepileptic medication.