Cross-Sectional Analysis of Spatial Working Memory Development in Children with Histories of Heavy Prenatal Alcohol Exposure.

BACKGROUND: In children with prenatal alcohol exposure, spatial working memory is affected and brain regions important for spatial working memory performance exhibit atypical neurodevelopment. We therefore hypothesized that children with prenatal alcohol exposure may also have atypical development of spatial working memory ability. METHODS: We examined the relation between spatial working memory and age using a cross-sectional developmental trajectory approach in youth with and without histories of heavy prenatal alcohol exposure. The Cambridge Neuropsychological Test Automated Battery Spatial Working Memory subtest was administered to children 5.0 to 16.9 years old. RESULTS: While the controls and children with prenatal alcohol exposure showed similar performance at younger ages, larger group differences were observed in older children. This effect was replicated in a separate sample. CONCLUSIONS: The atypical brain development that has previously been reported in children with heavy prenatal alcohol exposure may have clinically relevant implications for cognitive development; however, longitudinal cognitive analyses are needed.

Graded Cerebellar Lobular Volume Deficits in Adolescents and Young Adults with Fetal Alcohol Spectrum Disorders (FASD).

The extensive prenatal developmental growth period of the cerebellum renders it vulnerable to unhealthy environmental agents, especially alcohol. Fetal alcohol spectrum disorders (FASD) is marked by neurodysmorphology including cerebral and cerebellar volume deficits, but the cerebellar lobular deficit profile has not been delineated. Legacy MRI data of 115 affected and 59 unaffected adolescents and young adults were analyzed for lobular gray matter volume and revealed graded deficits supporting a spectrum of severity. Graded deficits were salient in intracranial volume (ICV), where the fetal alcohol syndrome (FAS) group was smaller than the fetal alcohol effects (FAE) group, which was smaller than the controls. Adjusting for ICV, volume deficits were present in VIIB and VIIIA of the FAE group and were more widespread in FAS and included lobules I, II, IV, V, VI, Crus II, VIIB, and VIIIA. Graded deficits (FAS < FAE) were consistently present in lobules VI; neither group showed volume deficits in Crus I or IX. Neuroradiological readings blind to diagnosis identified 20 anomalies, 8 involving the cerebellum, 5 of which were in the FAS group. We speculate that the regional cerebellar FASD-related volume deficits may contribute to diagnostically characteristic functional impairment involving emotional control, visuomotor coordination, and postural stability.

Analysis of Financial Risk Protection Indicators in Myanmar for Paediatric Surgery.

PURPOSE: To estimate proportion of Myanmar paediatric population at risk of impoverishment and catastrophic expenditure due to emergency surgical intervention. METHODS: Prospective data were collected at two tertiary surgical centres including income, household expenses, expenses related to surgery. Data analysis was performed to estimate out-of-pocket (OOP) direct medical costs and OOP total costs. Catastrophic expenditure: expense exceeded 10% of household income. Risk of impoverishment: net income drops were below an impoverishment threshold (PPP-purchasing power parity): I$ 2.00 PPP/day, I$ 1.25/day PPP, national poverty line. Distribution of income was estimated using a gamma distribution. Comparison to an adult cohort was performed using Chi-square test with a p value of <0.05 being significant. RESULTS: A total of 145 surveys were collected, and 119 (82.1%) contained sufficient data: Paediatric Centre (n = 99) and Adult Centre (n = 20). Overall average per patient direct medical and non-medical OOP costs was I$493: Centre 1: I$540 PPP (range I$41-6,588 PPP) and Centre 2: I$437 PPP (range I$ 36-1,405 PPP). 64% experienced catastrophic expense. There is no significant difference between the centres in the risks of impoverishment or catastrophic expenditure (p = 0.05). Up to 44% are at risk of catastrophic expenditure should surgery be required. Most of the risk (90%) is derived from direct non-medical costs. A high proportion were at the national poverty line threshold (36.1%). Seeking surgical treatment would imperil up to 37% at the national poverty line threshold, and up to 5.7% at the I$2 PPP per day limit. CONCLUSIONS: A large proportion of the Myanmar population are at risk of impoverishment or catastrophic expenditure should they require surgery. Financial risk protection mechanisms are needed.

The Economic Value of the Delivery of Primary Cleft Surgery in Timor Leste 2000-2017.

BACKGROUND: Plastic and reconstructive surgical teams visiting from Australia, a high-income country, have delivered cleft surgical services to Timor Leste since 2000 on a volunteer basis. This paper aims to estimate the economic benefit of correcting cleft deformities in this new nation as it evolved its healthcare delivery service from independence in 1999. METHODS: We have utilised a prospective database of all cleft surgical interventions performed during 44 plastic surgical missions over the last 18 years. The disability-adjusted life year (DALY) framework was used to calculate the total DALYs averted by primary cleft lip and palate repair. The 2004 global burden of disease disability weights were used. Economic benefits were calculated using the gross national income (GNI) and the value of a statistical life (VSL) methods for Timor Leste. Estimates were adjusted for treatment effectiveness, counterfactual cases, and complications. Cost estimates included the local hospitalisation costs, the foregone salaries of the visiting surgeons and nurses, other costs associated with providing surgical care, and an estimate for foregone wages of the patients or their carers. Sensitivity analysis was performed with income elasticity set to 0.55, 1.0, and 1.5. RESULTS: During 44 visiting plastic surgical missions to Timor Leste, 1500 procedures were performed, including 843 primary cleft lip and palate operations. The cleft procedures resulted in the aversion of 842 DALYs and an economic return to Timor Leste of USD 2.2 million (GNI-based) or USD 197,917 (VSL-based). Our programme cost USD 705 per DALY averted. The economic return on investment was 0.3:1 (VSL-based) or 3.8:1 (GNI-based). CONCLUSION: A sustained and consistent visiting team approach providing repair of cleft lip and palate defects has resulted in considerable economic gain for Timor Leste over an 18-year period. The training of a local surgeon and multidisciplinary team with ongoing support to the in-country cleft service is expected to reduce the cost per DALY averted once the surgeon and team are able to manage clefts independently.

Executive Functioning Correlates With Communication Ability in Youth With Histories of Heavy Prenatal Alcohol Exposure.

OBJECTIVES: Caregivers of youth with heavy prenatal alcohol exposure report impaired communication, which can significantly impact quality of life. Using data collected as part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD), we examined whether cognitive variables predict communication ability of youth with histories of heavy prenatal alcohol exposure. METHODS: Subjects (ages 10-16 years) comprised two groups: adolescents with heavy prenatal alcohol exposure (AE) and non-exposed controls (CON). Selected measures of executive function (NEPSY, Delis-Kaplan Executive Function System), working memory (CANTAB), and language were tested in the child, while parents completed communication ratings (Vineland Adaptive Behavior Scales - Second Edition). Separate multiple regression analyses determined which cognitive domains predicted communication ability. A final, global model of communication comprised the three cognitive models. RESULTS: Spatial Working Memory and Inhibition significantly contributed to communication ability across groups. Twenty Questions performance related to communication ability in the CON group only while Word Generation performance related to communication ability in the AE group only. Effects remained significant in the global model, with the exception of Spatial Working Memory. CONCLUSIONS: Both groups displayed a relation between communication and Spatial Working Memory and Inhibition. Stronger communication ability related to stronger verbal fluency in the AE group and Twenty Questions performance in the CON group. These findings suggest that alcohol-exposed adolescents may rely more heavily on learned verbal storage or fluency for daily communication while non-exposed adolescents may rely more heavily on abstract thinking and verbal efficiency. Interventions aimed at aspects of executive function may be most effective at improving communication ability of these individuals. (JINS, 2018, 24, 1026-1037).

Activation of extrasynaptic δ-GABAA receptors globally or within the posterior-VTA has estrous-dependent effects on consumption of alcohol and estrous-independent effects on locomotion.

Recent reports support higher than expected rates of binge alcohol consumption among women and girls. Unfortunately, few studies have assessed the mechanisms underlying this pattern of intake in females. Studies in males suggest that alcohol concentrations relevant to the beginning stages of binge intoxication may selectively target tonic GABAergic inhibition mediated by GABAA receptor subtypes expressing the δ-subunit protein (δ-GABAARs). Indeed, administration of agonists that interact with these δ-GABAARs prior to alcohol access can abolish binge drinking behavior in male mice. These δ-GABAARs have also been shown to exhibit estrous-dependent plasticity in regions relevant to drug taking behavior, like the hippocampus and periaqueductal gray. The present experiments were designed to determine whether the estrous cycle would alter binge drinking, or our ability to modulate this pattern of alcohol use with THIP, an agonist with high selectivity and efficacy at δ-GABAARs. Using the Drinking-in-the-Dark (DID) binge-drinking model, regularly cycling female mice were given 2h of daily access to alcohol (20%v/v). Vaginal cytology or vaginal impedance was assessed after drinking sessions to track estrous status. There was no fluctuation in binge drinking associated with the estrous cycle. Both Intra-posterior-VTA administration of THIP and systemic administration of the drug was also associated with an estrous cycle dependent reduction in drinking behavior. Pre-treatment with finasteride to inhibit synthesis of 5α-reduced neurosteroids did not disrupt THIP's effects. Analysis of δ-subunit mRNA from posterior-VTA enriched tissue samples revealed that expression of this GABAA receptor subunit is elevated during diestrus in this region. Taken together, these studies demonstrate that δGABAARs in the VTA are an important target for binge drinking in females and confirm that the estrous cycle is an important moderator of the pharmacology of this GABAA receptor subtype.

Academic Difficulties in Children with Prenatal Alcohol Exposure: Presence, Profile, and Neural Correlates.

BACKGROUND: Academic achievement was evaluated in children with heavy prenatal alcohol exposure to determine potential strengths and weaknesses, evaluate the utility of different definitions for identifying low academic performance, and explore the neural correlates that may underlie academic performance. METHODS: Children (8 to 16 years) were assessed using the WIAT-II. Patterns of performance were examined in 2 subject groups: children with heavy prenatal alcohol exposure (n = 67) and controls (n = 61). A repeated-measures MANCOVA examining group differences on academic domain (reading, spelling, math) scores was conducted. Post hoc comparisons examined within-group profiles. Numbers and percentage of children with low achievement were calculated using several criteria. In a subsample (n = 42), neural correlates were analyzed using FreeSurfer v5.3 to examine relations between cortical structure (thickness and surface area) and performance. RESULTS: The alcohol-exposed group performed worse than controls on all domains and had a unique academic profile, supported by a significant group × academic domain interaction (p < 0.001). For the alcohol-exposed group, math reasoning was significantly lower than numerical operations, which was significantly lower than spelling and word reading. Over half of the alcohol-exposed group (58.2%) demonstrated low achievement on 1 or more academic domains. The number and percentage of children meeting criteria for low achievement varied based on the domain and definition used. The imaging analysis identified several surface area clusters that were differentially related to math (L superior parietal and R lateral/middle occipital) and spelling (bilateral inferior and medial temporal) performance by group, with no relations for the other academic domains. Generally, scores improved as surface area decreased in controls, whereas no relation or a positive relation was observed in the alcohol-exposed group. CONCLUSIONS: Alcohol-exposed children demonstrated deficits in academic performance across domains and definitions, with a relative weakness in math functioning. Atypical brain development may contribute to these impairments in academic achievement. Understanding academic difficulties can assist in advocating effectively for alcohol-exposed children.

Current considerations for fetal alcohol spectrum disorders: identification to intervention.

PURPOSE OF REVIEW: This review highlights recent findings regarding the prevalence, public health impact, clinical presentation, intervention access and conceptualization of fetal alcohol spectrum disorders (FASDs). Despite ongoing work in prevention and identification of this population, the rates of drinking during pregnancy have increased and significant gaps remain in diagnosis and intervention. RECENT FINDINGS: Prenatal alcohol exposure is the most common preventable cause of developmental disability in the world. Research has focused on improving diagnostic clarity, utilizing technology and neuroimaging to facilitate identification, engaging broader stakeholders (including self-advocates) to inform understanding and needs, and increasing access to effective interventions. There is an emerging focus on developmental trajectories and experiences in young and middle adulthood. Public policy advocacy has also made great strides in recent years. SUMMARY: Increases in public awareness, greater concordance of diagnostic schema, leveraged use of novel technology, and the development of targeted interventions within a holistic, strengths-based conceptualization are important considerations for this population.

Brain Volume in Fetal Alcohol Spectrum Disorders Over a 20-Year Span.

Importance: Anomalous brain development and mental health problems are prevalent in fetal alcohol spectrum disorders (FASD), but there is a paucity of longitudinal brain imaging research into adulthood. This study presents long-term follow-up of brain volumetrics in a cohort of participants with FASD. Objective: To test whether brain tissue declines faster with aging in individuals with FASD compared with control participants. Design, Setting, and Participants: This cohort study used magnetic resonance imaging (MRI) data collected from individuals with FASD and control individuals (age 13-37 years at first magnetic resonance imaging [MRI1] acquired 1997-2000) compared with data collected 20 years later (MRI2; 2018-2021). Participants were recruited for MRI1 through the University of Washington Fetal Alcohol Syndrome (FAS) Follow-Up Study. For MRI2, former participants were recruited by the University of Washington Fetal Alcohol and Drug Unit. Data were analyzed from October 2022 to August 2023. Main Outcomes and Measures: Intracranial volume (ICV) and regional cortical and cerebellar gray matter, white matter, and cerebrospinal fluid volumes were quantified automatically and analyzed, with group and sex as between-participant factors and age as a within-participant variable. Results: Of 174 individuals with MRI1 data, 48 refused participation, 36 were unavailable, and 24 could not be located. The remaining 66 individuals (37.9%) were rescanned for MRI2, including 26 controls, 18 individuals with nondysmorphic heavily exposed fetal alcohol effects (FAE; diagnosed prior to MRI1), and 22 individuals with FAS. Mean (SD) age was 22.9 (5.6) years at MRI1 and 44.7 (6.5) years at MRI2, and 35 participants (53%) were male. The FAE and FAS groups exhibited enduring stepped volume deficits at MRI1 and MRI2; volumes among control participants were greater than among participants with FAE, which were greater than volumes among participants with FAS (eg, mean [SD] ICV: control, 1462.3 [119.3] cc at MRI1 and 1465.4 [129.4] cc at MRI2; FAE, 1375.6 [134.1] cc at MRI1 and 1371.7 [120.3] cc at MRI2; FAS, 1297.3 [163.0] cc at MRI1 and 1292.7 [172.1] cc at MRI2), without diagnosis-by-age interactions. Despite these persistent volume deficits, the FAE participants and FAS participants showed patterns of neurodevelopment within reference ranges: increase in white matter and decrease in gray matter of the cortex and decrease in white matter and increase in gray matter of the cerebellum. Conclusions and Relevance: The findings of this cohort study support a nonaccelerating enduring, brain structural dysmorphic spectrum following prenatal alcohol exposure and a diagnostic distinction based on the degree of dysmorphia. FASD was not a progressive brain structural disorder by middle age, but whether accelerated decline occurs in later years remains to be determined.

Tertiary Survey in the Days of Modern Imaging: Assessing the Detection Rate of Clinically Significant Injuries on Tertiary Survey in a Level 2 Trauma Centre.

AIM: To determine the utility of tertiary survey (TS) in patients subjected to whole-body CT (WBCT) or selective CT (SCT) following trauma. METHODS: A retrospective analysis was performed on trauma patients admitted to a level 2 trauma centre following the introduction of a standardised TS form in 2017. The initial imaging protocol (WBCT versus selective CT versus x-ray), subsequently requested imaging, standardised injury data, and length of stay (LOS) were recorded. Clinically significant injuries were defined as those with an Injury Severity Score (ISS) of 1 on the Abbreviated Injury Scale (AIS). RESULTS: Five hundred and seven patients were included. The rate of additional significant injuries at the time of TS was 1.18% (n=6), each requiring conservative management only. There was no significant difference in injury detection based on the initial imaging protocol; however, there were three near-misses identified. Of these patients, two underwent selective CT and one was subjected to a plain film series, with clinically significant injuries identified early upon completion of trauma imaging. Overall, 2.9% (n=15) of patients had completed trauma imaging during the same admission. WBCT was associated with higher ISS and length of stay (p<0.05). After controlling for ISS, there was no difference in length of stay between imaging modalities except in those patients with an ISS of 0 (no clinically significant injuries), who appeared to have longer admissions if subject to WBCT (p<0.001). CONCLUSION: The rate of missed injuries identified at TS is low. The imaging modality did not alter this. This may allow for the omission of the tertiary survey and earlier discharge in many trauma patients.

Tolerance to ethanol's ataxic effects and alterations in ethanol-induced locomotion following repeated binge-like ethanol intake using the DID model.

BACKGROUND: Tolerance to the behavioral and subjective effects of alcohol (ethanol) is thought to be a major predictive factor for the development of alcoholism. Evidence from rodent models has supported this view with those animals most likely to develop tolerance generally drinking and preferring ethanol more so than those resistant to it. Despite this evidence, very little is known about the behavioral relationships between ethanol-induced tolerance and consumption. The goal of this study was to evaluate the development of tolerance to the ataxic effects of ethanol using a mouse model of binge-like intake dubbed "Drinking in the Dark" (DID; Physiol Behav 2005, 84:53-63). We hypothesized that mice would become tolerant to the ataxic effects of ethanol as this behavior is known to be altered at the blood ethanol concentrations reached using this model (≥80 mg/dl). METHODS: To evaluate this, we gave daily DID ethanol or water access sessions to male C57BL/6J (B6) mice and monitored ataxia (and in some cases locomotion) at various time points. RESULTS: In general, mice given 14 consecutive days of ethanol access displayed tolerance to the ataxic effects of ethanol compared to water-drinking controls. These effects were coupled with alterations in locomotor behavior and in some cases differences in ethanol pharmacokinetics. CONCLUSIONS: Thus, we can conclude that tolerance to the behavioral effects of binge-like ethanol intake might play a key role in the daily maintenance of this behavior and that these effects may be evidence of important neuroadaptations involved in the development of alcoholism.

Ontogenetic differences in adolescent and adult C57BL/6J and DBA/2J mice: anxiety-like, locomotor, and consummatory behaviors.

Adolescence is a highly conserved period during which mammals undergo a number of hormonal, biological, and behavioral changes [Spear [2000] Neurosci. Biobehav. Rev. 24: 417-463]. Ethical constraints limit the research that can be done in human adolescents. Rodents provide a useful model of at least some of the features of adolescence, including increases in body growth, differences in sleep/wake, and eating patterns, as well as differences in risk-taking, novelty seeking, and exploratory behaviors. Much of the available developmental research has utilized rats; however, the use of inbred mouse strains provides a unique means to assess the genetic factors involved in behavioral differences during adolescence. We assessed differences between adults and adolescents in anxiety-like, locomotor, and consummatory behaviors using two commonly used inbred strains of mice, the DBA/2J and C57BL/6J strains. Age and genotype-dependent differences were found in all three behaviors measured, suggesting both factors are important determinants of behavior in mice.

Neurodevelopmental Trajectories Following Prenatal Alcohol Exposure.

Prenatal alcohol exposure (PAE) interferes with neurodevelopment. The brain is particularly susceptible to the adverse consequences of prenatal alcohol exposure, and numerous studies have documented changes to brain anatomy and function, as well as consequences for cognition, behavior, and mental health. Studies in typically developing individuals have shown that the brain undergoes dynamic developmental processes over an individual's lifespan. Furthermore, magnetic resonance imaging (MRI) studies in other neurodevelopmental and psychiatric disorders have shown that their developmental trajectories differ from the typical pattern. Therefore, to understand long-term clinical outcomes of fetal alcohol spectrum disorders (FASD), it is necessary to investigate changes in neurodevelopmental trajectories in this population. Here we review studies that have used MRI to evaluate changes in brain structure and function over time via cross-sectional or longitudinal methods in individuals with PAE. Research demonstrates that individuals with PAE have atypical cortical and white matter microstructural developmental trajectories through childhood and adolescence. More research is needed to understand how factors such as sex and postnatal experiences may further mediate these trajectories. Furthermore, nothing is known about the trajectories beyond young adulthood.

Mortality of patients with COVID-19 who undergo an elective or emergency surgical procedure: a systematic review and meta-analysis.

BACKGROUND: There have been several reports that co-infection with the novel coronavirus severe acute respiratory syndrome coronavirus 2 at the time of surgery increases mortality. The aim of this study was to estimate the effect size of coronavirus disease 2019 (COVID-19) on post-operative mortality by performing a systematic review and meta-analysis of the literature. METHODS: A systematic review and meta-analysis of the literature was performed. A search was undertaken using electronic bibliographic databases MEDLINE, EMBASE, PubMed and Cochrane Library to identify eligible studies published from 1 November 2019 until 21 August 2020. Eligible papers for meta-analysis were those that provided mortality rates following elective and emergency surgery in both COVID-19 positive and negative patients. Forest plots and estimates of odds of death related to having COVID-19 were formed using MedCalc version 9.6 software. Funnel plots to assess for publication bias and heterogeneity were formed in Meta-Essentials. RESULTS: There were 140 records screened for inclusion. Full texts of 39 articles were reviewed, and 36 articles were included in the qualitative synthesis. There were eight studies eligible for meta-analysis. There was a total of 193 operations performed on patients with a concurrent COVID-19 infection and 910 performed on patients who were COVID-19 negative. The odds ratio for mortality in patients who underwent a surgical procedure while COVID-19 positive was 7.9 (95% confidence interval: 3.2-19.4). CONCLUSION: This meta-analysis confirms that concurrent COVID-19 infection increases the risk of surgical mortality. The magnitude of this risk mandates that strategies are developed to mitigate the risk at both an individual and system level.

Adolescent C57BL/6J (but not DBA/2J) mice consume greater amounts of limited-access ethanol compared to adults and display continued elevated ethanol intake into adulthood.

BACKGROUND: Alcohol use is common during the adolescent period, a time at which a number of crucial neurobiological, hormonal, and behavioral changes occur (Spear, 2000). In order to more fully understand the complex interaction between alcohol use and these age-typical neurobiological changes, animal models must be utilized. Rodents experience a developmental period similar to that of adolescence. Although rat models have shown striking adolescent-specific differences in sensitivity to ethanol, little work has been done in mice despite the fact that the C57BL/6J (B6) and DBA2/J (D2) mice have been shown to markedly differ in ethanol preference drinking and exhibit widely different sensitivities to ethanol. METHODS: The current study examined ethanol intake in adolescent and adult B6 and D2 mice using a limited access alcohol exposure paradigm called Drinking in the Dark (DID). Additionally, the effect of adolescent (or adult) ethanol exposure on subsequent adult ethanol intake was examined by re-exposing the mice to the same paradigm once the adolescents reached adulthood. We hypothesized that adolescent (P25-45) mice would exhibit greater binge-like alcohol intake compared to adults (P60-80), and that B6 mice would exhibit greater binge-like alcohol intake compared to D2 mice. Moreover, we predicted that relative difference in binge-like alcohol intake between adolescents and adults would be greater in D2 mice. RESULTS: Adolescent B6 mice consumed more ethanol than adults in the DID model. There was no difference between adolescent and adult D2 mice. CONCLUSIONS: This work adds to the literature suggesting that adolescents will consume more ethanol than adults and that this exposure can result in altered adult intake. However, this effect seems largely dependent upon genotype. Future work will continue to examine age-related differences in ethanol intake, preference, and sensitivity in inbred mouse strains.

Neurodevelopment in adolescents and adults with fetal alcohol spectrum disorders (FASD): A magnetic resonance region of interest analysis.

The neurodevelopmental trajectory in individuals with fetal alcohol spectrum disorders (FASD) has not been well characterized. We examined age-related differences in the volume of the corpus callosum, basal ganglia, and cerebellum across adolescence and young adulthood, due to the sensitivity of these regions to prenatal alcohol exposure. T1-weighted anatomical magnetic resonance images (MRI) were acquired from a cross-sectional sample of subjects 13-30 years old who had received an alcohol-related diagnosis (FASD, n = 107) and typically developing controls (CON, n = 56). FreeSurfer v5.3 was used to obtain volumetric data for the corpus callosum, caudate, putamen, pallidum, and cerebellum. Analysis of variance (ANOVA) was used to examine the effects of group (FASD, CON), sex, and age on region volume. Data were analyzed with and without correction for intracranial volume (ICV). All subregions were significantly smaller in the FASD group compared to controls, and these findings persisted even after ICV correction. Furthermore, the FASD and control groups differed in their relationship between age and total volume of the corpus callosum, caudate, and cerebellum. Specifically, older FASD individuals had smaller total volume in these regions; this relationship was not seen in the control group. Control males demonstrated larger volumes than control females in all regions prior to ICV correction; however, sex differences were attenuated in the FASD group in both the pallidum and cerebellum. Sex differences remained after ICV correction in the pallidum and cerebellum. These cross-sectional findings suggest that at least some brain regions may become smaller at an earlier than expected age in individuals with FASD, and that sex is an important factor to consider when examining neural structures in FASD. Further evaluation is necessary using longitudinal methods and including older ages.

Universal access to safe, affordable, timely surgical and anaesthetic care in Papua New Guinea: the six global health indicators.

BACKGROUND: The unmet global burden of surgical disease is substantial. The Lancet Commission on Global Surgery (LCoGS) estimated that 5 billion people do not have access to safe, affordable and timely surgical care, with 80% of those without access living in low- and middle-income countries. The Milne Bay Province (pop 331 000) of Papua New Guinea, with an archipelago of islands up to 750 km from its capital, Alotau, has only one hospital capable of performing Caesarean Section, Emergency Laparotomy and managing an open fracture, the three Bellwether procedures. This paper aims to report the six Lancet Commission on Global Surgery metrics for Milne Bay Province. METHODS: The study was conducted between January and August 2019. Bellwether access was investigated by a prospective study on 115 patients presenting to hospital. The surgical, anaesthesia and obstetric (SAO) workforce, surgical volume and perioperative mortality rate, were calculated for 2012-2018 from hospital records and operation registers. Financial risk metrics were calculated by surveying 50 patients at discharge from hospital. RESULTS: Bellwether access: Only 27.8% (n = 32) of the study population (n = 115) experienced less than 2-hours second delay (journey time to hospital). The average SAO provider density was 1.8 per 100 000 population. There were 606 procedures performed per 100 000 with a mean annual perioperative mortality rate of 0.3%. Catastrophic expenditure is a risk for 29% of the population. CONCLUSION: Milne Bay Province can perform surgery safely, but there is limited access to timely surgical care when needed with a significant proportion put at financial risk by requiring it.

How will increasing surgical volume affect mortality in the Pacific, Papua New Guinea and Timor Leste?

BACKGROUND: Nine South Pacific nations, Papua New Guinea and Timor Leste, have collaborated to report and publish their surgical metrics as recommended by the Lancet Commission on Global Surgery (LCoGS). Currently, these countries experience about 750 postoperative deaths per year, representing 1% of crude mortality in the region. Given that more than 400 000 annual procedures are needed in the nine nations to reach the LCoGS target of 5000/100 000, we aimed to calculate the potential contribution of perioperative mortality to national mortality where these procedures are performed. METHODS: We utilized reported surgical metrics with current rates for surgical volume (SV) and perioperative mortality (POMR), as well as World Bank/WHO mortality statistics, to predict the likely impact of surgical scale-up to recommended targets by 2030. We tested correlations between SV and POMR in countries from our region using Pearson's r statistic. Funnel plots were used to evaluate the dataset for outliers. RESULTS: Surgical scale up would result in perioperative mortality contributing on average to 3.3% of all national crude mortality. This prediction assumes POMR stays the same, which is challenging to predict. In our region countries that achieved the LCoGS target (n = 5) had a lower POMR than countries that did not (n = 8). CONCLUSIONS: Surgical volumes in the South Pacific region must increase to meet the LCoGS target. Postoperative mortality as a proportion of all mortality may increase with the surgical scale up, however, the overall number of premature deaths is expected to reduce with better access to timely and safe surgical care.

Site-specific microinjection of baclofen into the anterior ventral tegmental area reduces binge-like ethanol intake in male C57BL/6J mice.

The GABAB agonist baclofen has been shown to alter ethanol intake in human and animal studies (E. M. Moore et al., 2007). GABA-subB receptors are located within the ventral tegmental area (VTA; A. Imperato & G. DiChiara, 1986) and therefore may be involved in modulating voluntary ethanol intake. The present study assessed the effects of baclofen in a variation on a new mouse model of binge-like ethanol intake that takes advantage of the nocturnal nature of this species (J. S. Rhodes, K. Best, J. K. Belknap, D. A. Finn, & J. C. Crabbe, 2005; J. S. Rhodes et al., 2007). Baclofen or saline was microinjected into the anterior or posterior VTA of male C57BL/6J mice. Immediately afterward, mice were presented with ethanol, water, or sugar water using the Drinking in the Dark model, a procedure of fluid administration for 2 hr, 3 hr into the dark cycle). Fluid intake was recorded at 30, 60, 90, and 120 min; retro-orbital sinus bloods were sampled upon termination of the 120-min ethanol access period. Baclofen reduced binge-like ethanol intake when microinjected into the anterior VTA, whereas posterior VTA microinjections did not alter ethanol intake. Baclofen had no effect on water or sugar water intake when administered to anterior or posterior VTA. These results add to the growing literature suggesting that GABA-subB receptor systems are important in the modulation of binge-like ethanol intake and suggest that the GABA-subB receptor system may have different roles in anterior versus posterior VTA.