Anesthetic considerations in interventional pulmonology.

PURPOSE OF REVIEW: In this review, we highlight the important anesthetic consideration that relate to interventional bronchoscopic procedures for the management of central airway obstruction due to anterior mediastinal masses, endoluminal endobronchial obstruction, peripheral bronchoscopy for diagnosis and treatment of lung nodules, bronchoscopic lung volume reduction and medical pleuroscopy for diagnosis and management of pleural diseases. RECENT FINDINGS: The advent of the field of Interventional Pulmonology has allowed for minimally invasive options for patients with a wide range of lung diseases which at times have replaced more invasive surgical procedures. Ongoing research has shed light on advancement in anesthetic techniques and management strategies that have increased the safety during peri-operative management during these complex procedures. Current evidence focusing on the anesthetic techniques is presented here. SUMMARY: The field of Interventional Pulmonology requires a tailored anesthetic approach. Recent advancements and ongoing research have focused on expanding the partnership between the anesthesiologist and interventional pulmonologists which has led to improved outcomes for patients undergoing these procedures.

Clearance of interstitial fluid (ISF) and CSF (CLIC) group-part of Vascular Professional Interest Area (PIA), updates in 2022-2023. Cerebrovascular disease and the failure of elimination of Amyloid-ß from the brain and retina with age and Alzheimer's disease: Opportunities for therapy.

This editorial summarizes advances from the Clearance of Interstitial Fluid and Cerebrospinal Fluid (CLIC) group, within the Vascular Professional Interest Area (PIA) of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART). The overarching objectives of the CLIC group are to: (1) understand the age-related physiology changes that underlie impaired clearance of interstitial fluid (ISF) and cerebrospinal fluid (CSF) (CLIC); (2) understand the cellular and molecular mechanisms underlying intramural periarterial drainage (IPAD) in the brain; (3) establish novel diagnostic tests for Alzheimer's disease (AD), cerebral amyloid angiopathy (CAA), retinal amyloid vasculopathy, amyloid-related imaging abnormalities (ARIA) of spontaneous and iatrogenic CAA-related inflammation (CAA-ri), and vasomotion; and (4) establish novel therapies that facilitate IPAD to eliminate amyloid ß (Aß) from the aging brain and retina, to prevent or reduce AD and CAA pathology and ARIA side events associated with AD immunotherapy.

Subunit-specific expression and function of AMPA receptors in the mouse locus coeruleus.

The locus coeruleus (LC) provides the principal supply of noradrenaline (NA) to the brain, thereby modulating an array of brain functions. The release of NA, and therefore its impact on the brain, is governed by LC neuronal excitability. Glutamatergic axons, from various brain regions, topographically innervate different LC sub-domains and directly alter LC excitability. However, it is currently unclear whether glutamate receptor sub-classes, such as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, are divergently expressed throughout the LC. Immunohistochemistry and confocal microscopy were used to identify and localise individual GluA subunits in the mouse LC. Whole-cell patch clamp electrophysiology and subunit-preferring ligands were used to assess their impact on LC spontaneous firing rate (FR). GluA1 immunoreactive clusters were associated with puncta immunoreactive for VGLUT2 on somata, and VGLUT1 on distal dendrites. GluA4 was associated with these synaptic markers only in the distal dendrites. No specific signal was detected for the GluA2-3 subunits. The GluA1/2 receptor agonist (S)-CPW 399 increased LC FR, whilst the GluA1/3 receptor antagonist philanthotoxin-74 decreased it. 4-[2-(phenylsulfonylamino)ethylthio]-2,6-difluoro-phenoxyacetamide (PEPA), a positive allosteric modulator of GluA3/4 receptors, had no significant effect on spontaneous FR. The data suggest distinct AMPA receptor subunits are targeted to different LC afferent inputs and have contrasting effects on spontaneous neuronal excitability. This precise expression profile could be a mechanism for LC neurons to integrate diverse information contained in various glutamate afferents.

Hypertensive disorders of pregnancy and long-term risk of maternal stroke-a systematic review and meta-analysis.

OBJECTIVE: Hypertensive disorders of pregnancy are associated with a long-term risk for cardiovascular disease among parous patients later in life. However, relatively little is known about whether hypertensive disorders of pregnancy are associated with an increased risk for ischemic stroke or hemorrhagic stroke in later life. This systematic review aimed to synthesize the available literature on the association between hypertensive disorders of pregnancy and the long-term risk for maternal stroke. DATA SOURCES: PubMed, Web of Science, and CINAHL were searched from inception to December 19, 2022. STUDY ELIGIBILITY CRITERIA: Studies were only included if the following criteria were met: case-control or cohort studies that were conducted with human participants, were available in English, and that measured the exposure of a history of hypertensive disorders of pregnancy (preeclampsia, gestational hypertension, chronic hypertension, or superimposed preeclampsia) and the outcome of maternal ischemic stroke or hemorrhagic stroke. METHODS: Three reviewers extracted the data and appraised the study quality following the Meta-analyses of Observational Studies in Epidemiology guidelines and using the Newcastle-Ottawa scale for risk of bias assessment. RESULTS: The primary outcome was any stroke (undifferentiated) and secondary outcomes included ischemic stroke and hemorrhagic stroke. The protocol for this systematic review was registered in the International Prospective Register of Systematic Reviews under identifier CRD42021254660. Of 24 studies included (10,632,808 study participants), 8 studies examined more than 1 outcome of interest. Hypertensive disorders of pregnancy were significantly associated with any stroke (adjusted risk ratio, 1.74; 95% confidence interval, 1.45-2.10). Preeclampsia was significantly associated with any stroke (adjusted risk ratio, 1.75; 95% confidence interval, 1.56-1.97), ischemic stroke (adjusted risk ratio, 1.74; 95% confidence interval, 1.46-2.06), and hemorrhagic stroke (adjusted risk ratio, 2.77; 95% confidence interval, 2.04-3.75). Gestational hypertension was significantly associated with any stroke (adjusted risk ratio, 1.23; 95% confidence interval, 1.20-1.26), ischemic stroke (adjusted risk ratio, 1.35; 95% confidence interval, 1.19-1.53), and hemorrhagic stroke (adjusted risk ratio, 2.66; 95% confidence interval, 1.02-6.98). Chronic hypertension was associated with ischemic stroke (adjusted risk ratio, 1.49; 95% confidence interval, 1.01-2.19). CONCLUSION: In this meta-analysis, exposure to hypertensive disorders of pregnancy, including preeclampsia and gestational hypertension, seems to be associated with an increased risk for any stroke and ischemic stroke among parous patients in later life. Preventive interventions may be warranted for patients who experience hypertensive disorders of pregnancy to reduce their long-term risk for stroke.

Relationship between adiponectin and blood pressure in obese Latino adolescent boys with a family history of type 2 diabetes.

INTRODUCTION: Adipokines are associated with several pathological states including, metabolic syndrome, obesity, insulin resistance and type 2 diabetes. One of these adipokines, adiponectin is of particular interest as it has been shown to have numerous anti-inflammatory effects, However, the association between adiponectin and blood pressure remains inconclusive especially in the Latino adolescent with obesity. PURPOSE: To investigate the relationship between plasma adiponectin and blood pressure in Latino adolescents' boys with obesity and a with a family history of Type 2 diabetes. METHODS: Thirty two Latino adolescent males with obesity aged 14-17 years with a family history of type 2 diabetes underwent a frequently sampled glucose tolerance test (FSIVGTT) to measure insulin sensitivity. Body composition was assessed using dual energy x-ray absorptiometry. Obesity was defined as having a BMI percentile ≥95. Blood pressure was assessed using the Dinamap automated blood pressure monitor, and the average of three readings was used in the analysis. Fasting plasma adiponectin was determined using radioimmunoassay. RESULTS: There were moderate positive significant correlations for adiponectin and Systolic blood pressure(SBP) (rho = 0.436, p < 0.027) and Diastolic blood pressure(DBP) (rho = 0.41,p < 0.028). A multivariate liner regression showed that plasma adiponectin could significantly detect 19% of the variance in SBP (p = 0.017, and 33% for DBP (p = 0.017). In a simple linear regression adiponectin was not related to any of our variables (p < 0.05). CONCLUSION: In conclusion, adiponectin was positively and significantly correlated to blood pressure in Latino adolescent with obesity. Future studies should investigate this relationship in a large sample of Latino adolescent youth.

Candida meningitis/ventriculitis over a decade. Increased morbidity and length of stay a concern.

AIM: The primary aim of this study was to review the diagnosis, management and outcome of Candida meningitis/ventriculitis in our hospital over a ten-year period. MATERIALS AND METHODS: We retrospectively reviewed all culture and 18s rRNA nucleic acid positive CSF specimens processed between 1st January 2010 and 31st December 2020. Patient records were subsequently reviewed to assess the significance of the isolate. RESULTS: Of 851 culture-positive cerebrospinal fluid (CSF) specimens, Candida spp. were isolated from 29 (3.4%), representing infection in 12 patients. One culture-negative specimen was positive for Candida on 18s rRNA testing. Of the 13 patients, eight were male; 61.5% and the median age was 47 years; range: 20-70. The median interval from admission to onset of infection and culture positivity was 24 days (range: 1-63 days). All patients had a central nervous system (CNS) device in situ (external ventricular drain: 11; ventriculoperitoneal shunt: 1; lumbar drain: 1). Four were colonised with Candida spp. before meningitis/ventriculitis diagnosis, from wounds (n = 3), respiratory (n = 3), and urine (n = 1) specimens. On culture, the most common species was Candida albicans (n = 8), followed by C. parapsilosis (n = 2), C. tropicalis (n = 1), and C. dubliniensis (n = 1). The median number of follow-up CSFs per patient was nine (range; 3-22), with a median of 6 days to CSF sterility (range 3-10 days). Treatment included; liposomal amphotericin B (n = 5), fluconazole (n = 2), liposomal amphotericin B, and flucytosine (n = 2), liposomal amphotericin B, fluconazole and flucytosine (n = 3), and intra-ventricular amphotericin B (n = 1). Median treatment duration was 25 days (range 11-76) and CNS device removal occurred in 12 patients. The median length-of-stay (LOS) was 58 days (range 24-406). On discharge, moderate to severe disability (Modified Rankin Scale [mRS] 3-5) was evident in eight patients. Two patients died and one was lost to follow-up. CONCLUSION: Meningitis/ventriculitis due to Candida spp. is an uncommon but challenging infection, usually associated with a device, increased morbidity, LOS, and necessitating prolonged treatment. Neurosurgeons need to be aware of these issues in managing and in communicating with such complex patients.

The association between hypertensive disorders of pregnancy and childhood asthma.

BACKGROUND: Asthma is a chronic long-term inflammatory disease of the airways and is a major global health challenge. The primary aim of this study was to investigate the association between hypertensive disorders of pregnancy (HDP) and the risk of asthma at or before the age of seven years using the UK Millennium Cohort Study (MCS). METHODS: Overall, 18,552 families were recruited for wave one of the MCS when the child was 9 months old, and subsequently participated in waves two, three and four when they were three, five and seven years respectively. HDP were self-reported by mothers in wave one. The primary outcome was a parent-reported diagnosis of "ever asthma" at seven years, based on responses to a validated questionnaire. RESULTS: Following adjustment for a range of potential confounding factors, HDP was found to be associated with asthma in the offspring (adjusted odds ratio (AOR 1.35; 95% CI: 1.15-1.59)). A larger effect estimate was observed amongst children exposed to HDP and born preterm (AOR 1.81; 95% CI: 1.25-2.61) or small for gestational age (SGA) (AOR = 1.58; (95% CI: 1.15-2.18)). CONCLUSIONS: In conclusion, children exposed to HDP may be at increased odds of asthma diagnosis by age seven, particularly if they were born preterm or SGA. IMPACT: There is a paucity of data investigating the relationship between hypertensive disorders of pregnancy and childhood asthma, with recent studies showing conflicting results. Our study investigated this relationship using a large cohort with ample information on a wide range of confounding factors. Our study showed that individuals exposed to HDP may be at increased odds of asthma diagnosis by age seven years, particularly if they were also born SGA or preterm.

Determining the need for a breast cancer awareness educational intervention for women with mild/moderate levels of intellectual disability: A qualitative descriptive study.

OBJECTIVE: Following a review of the existing body of literature, this study aimed to explore the need for a breast cancer awareness intervention specifically targeted at women with mild/moderate levels of intellectual disability (ID) and provide perspectives on the preferred processes and content underpinning an intervention. METHODS: A qualitative, descriptive design using semi-structured, individual (n = 5) and focus group (n = 5) interviews were used to engage with a non-probability, purposive sample of key stakeholders (n = 25) including women with mild/moderate levels of ID, caregivers and healthcare professionals. Data were analysed using qualitative content analysis. RESULTS: Findings highlighted that an educational intervention should focus on breast awareness as opposed to breast cancer awareness. Additionally, findings identified that a combined breast awareness and healthy living intervention could be effective. However, the intervention needs to have a multimodal, hands-on, person-centred approach to learning which is underpinned by theory. Furthermore, integrating the caregivers and healthcare professionals into the intervention is recommended. CONCLUSION: Findings from this study provide a foundation for developing and implementing a theoretically underpinned, multimodal, breast awareness and healthy living educational intervention for women with mild/moderate levels of ID.

Are micro enemas administered with a squeeze tube and a 5 cm-long nozzle as good or better than micro enemas administered with a 10 cm-long catheter attached to a syringe in people with a recent spinal cord injury? A non-inferiority, crossover randomised controlled trial.

STUDY DESIGN: Double blind, non-inferiority crossover randomised controlled trial. OBJECTIVES: To determine if micro enemas administered with a squeeze-tube and a 5 cm-long nozzle (squeeze-tube method) are as good or better than micro enemas administered with a 10 cm-long catheter attached to a syringe (catheter method) in people with a recent spinal cord injury. SETTING: Two inpatient spinal cord injury units located in Sydney, Australia. METHODS: Twenty people admitted to hospital with recent spinal cord injury were randomly assigned to two treatment sequences; 4 weeks of micro enemas delivered by the squeeze-tube method followed by 4 weeks of micro enemas delivered by the catheter method, or vice versa. Each treatment sequence was 8 weeks with a crossover at the end of week 4. The primary outcome was time to complete bowel care. Secondary outcomes reflected faecal incontinence, quality of life, perception of treatment effectiveness and participant reported time to complete bowel care. The primary and secondary outcomes were measured by blinded assessors in week 4 and week 8. A non-inferiority margin of 10 min for time to complete bowel care was set a priori. RESULTS: The mean between group difference (95% confidence interval) for the time to complete bowel care was -0.5 min (-2.8 to 1.8), where a negative value favours the catheter method. Results were similar for all secondary outcomes. CONCLUSIONS: Micro enemas delivered by the squeeze-tube method are as good or better than micro enemas delivered by the catheter method in people with a recent spinal cord injury.

Identification of intraneuronal amyloid beta oligomers in locus coeruleus neurons of Alzheimer's patients and their potential impact on inhibitory neurotransmitter receptors and neuronal excitability.

AIMS: Amyloid ß-oligomers (AßO) are potent modulators of Alzheimer's pathology, yet their impact on one of the earliest brain regions to exhibit signs of the condition, the locus coeruleus (LC), remains to be determined. Of particular importance is whether AßO impact the spontaneous excitability of LC neurons. This parameter determines brain-wide noradrenaline (NA) release, and thus NA-mediated brain functions, including cognition, emotion and immune function, which are all compromised in Alzheimer's patients. Therefore, the aim of the study was to determine the expression profile of AßO in the LC of Alzheimer's patients and to probe their potential impact on the molecular and functional correlates of LC excitability, using a mouse model of increased Aß production (APP-PSEN1). METHODS AND RESULTS: Immunohistochemistry and confocal microscopy, using AßO-specific antibodies, confirmed LC AßO expression both intraneuronally and extracellularly in both Alzheimer's and APP-PSEN1 samples. Patch clamp electrophysiology recordings revealed that APP-PSEN1 LC neuronal hyperexcitability accompanied this AßO expression profile, arising from a diminished inhibitory effect of GABA due to impaired expression and function of the GABA-A receptor (GABAA R) α3 subunit. This altered LC α3-GABAA R expression profile overlapped with AßO expression in samples from both APP-PSEN1 mice and Alzheimer's patients. Finally, strychnine-sensitive glycine receptors (GlyRs) remained resilient to Aß-induced changes and their activation reversed LC hyperexcitability. CONCLUSIONS: The data suggest a close association between AßO and α3-GABAA Rs in the LC of Alzheimer's patients, and their potential to dysregulate LC activity, thereby contributing to the spectrum of pathology of the LC-NA system in this condition.

The LOCalizer Radiofrequency Identification System: An Effective New Technology for Localizing Non-Palpable Breast Lesions for Surgery.

Background. Breast screening has decreased morbidity and mortality due to detection of early, non-palpable breast cancers. One of the challenges of performing breast-conserving surgery on non-palpable breast tumours is accurate localization of the cancer. We aimed to perform a feasibility study to examine the outcomes associated with the introduction of a novel radiofrequency identification system (RFID) called LOCalizer as an alternative to traditional wire-guided localization. Methods. Data were prospectively collected on all patients undergoing breast-conserving surgery using the LOCalizer RFID system in a regional cancer centre between July 2019 and March 2020. Patients had a RFID tag placed preoperatively and underwent surgical removal of the tag with the index lesion guided by a handheld LOCalizer probe. The primary aim was successful placement and retrieval of the RFID tag. Re-excision rates, specimen size, specimen weight, cancer subtype and complication rate were all recorded. Results. Sixty-nine patients aged between 50 and 69 years had a LOCalizer tag inserted between July 2019 and March 2020. Of these, 6 (8.7%) were diagnostic and 63 (91.3%) were therapeutic. There was no migration of RFID tags, and all tags were retrieved with the index lesion. The overall re-excision of margin rate was 17.4% (12/69). All re-excision of margins was due to positive radial margins. The overall complication rate was 1.4% with one grade 1 Clavien-Dindo morbidity. Conclusion. The LOCalizer RFID is an effective and safe wire-free localization method for non-palpable breast lesions.

Defining breast cancer awareness and identifying barriers to breast cancer awareness for women with an intellectual disability: A review of the literature.

INTRODUCTION: Incidence rates for developing breast cancer are similar for women regardless of intellectual ability. However, women with an intellectual disability present with advanced breast cancers, which often have a poor prognosis. METHOD: A structured narrative review of the literature was performed to explore the concepts of breast awareness and breast cancer awareness and subsequently, identify barriers to breast cancer awareness encountered by women with an intellectual disability. RESULTS: A total of 22 studies involving people with varying levels of intellectual disability informed this review. The barriers to breast cancer awareness encountered by women with an intellectual disability include: lack of their understanding, the role of the carer and literacy issues. CONCLUSION: Identifying the barriers to breast cancer awareness for women with an intellectual disability will help to facilitate breast cancer awareness which has the potential to result in better long-term outcomes through an early diagnosis of breast cancer.

Genetic and immunopathological analysis of CHCHD10 in Australian amyotrophic lateral sclerosis and frontotemporal dementia and transgenic TDP-43 mice.

OBJECTIVE: Since the first report of CHCHD10 gene mutations in amyotrophiclateral sclerosis (ALS)/frontotemporaldementia (FTD) patients, genetic variation in CHCHD10 has been inconsistently linked to disease. A pathological assessment of the CHCHD10 protein in patient neuronal tissue also remains to be reported. We sought to characterise the genetic and pathological contribution of CHCHD10 to ALS/FTD in Australia. METHODS: Whole-exome and whole-genome sequencing data from 81 familial and 635 sporadic ALS, and 108 sporadic FTD cases, were assessed for genetic variation in CHCHD10. CHCHD10 protein expression was characterised by immunohistochemistry, immunofluorescence and western blotting in control, ALS and/or FTD postmortem tissues and further in a transgenic mouse model of TAR DNA-binding protein 43 (TDP-43) pathology. RESULTS: No causal, novel or disease-associated variants in CHCHD10 were identified in Australian ALS and/or FTD patients. In human brain and spinal cord tissues, CHCHD10 was specifically expressed in neurons. A significant decrease in CHCHD10 protein level was observed in ALS patient spinal cord and FTD patient frontal cortex. In a TDP-43 mouse model with a regulatable nuclear localisation signal (rNLS TDP-43 mouse), CHCHD10 protein levels were unaltered at disease onset and early in disease, but were significantly decreased in cortex in mid-stage disease. CONCLUSIONS: Genetic variation in CHCHD10 is not a common cause of ALS/FTD in Australia. However, we showed that in humans, CHCHD10 may play a neuron-specific role and a loss of CHCHD10 function may be linked to ALS and/or FTD. Our data from the rNLS TDP-43 transgenic mice suggest that a decrease in CHCHD10 levels is a late event in aberrant TDP-43-induced ALS/FTD pathogenesis.

The Efficacy of Prophylactic Negative Pressure Wound Therapy for Closed Incisions in Breast Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Negative pressure wound therapy (NPWT) is a promising advance in the management of closed surgical incisions. NPWT application induces several effects locally within the wound including reduced lateral tension and improving lymphatic drainage. As a result, NPWT may improve wound healing and reduce surgical site complications. We aim to evaluate the efficacy of prophylactic application of NPWT in preventing surgical site complications for closed incisions in breast surgery. METHODS: This systematic review was reported according to PRISMA guidelines. The protocol was published in PROSPERO (CRD42018114625). Medline, Embase, CINAHL and Cochrane Library databases were searched for studies which compare the efficacy of NPWT versus non-NPWT dressings for closed incisions in breast surgery. Specific outcomes of interest were total wound complications, surgical site infection (SSI), seroma, haematoma, wound dehiscence and necrosis. RESULTS: Seven studies (1500 breast incisions in 904 patients) met the inclusion criteria. NPWT was associated with a significantly lower rate of total wound complications [odds ratio (OR) 0.36; 95% CI 0.19-069; P = 0.002], SSI (OR 0.45; 95% CI 0.24-0.86; P = 0.015), seroma (OR 0.28; 95% CI 0.13-0.59; P = 0.001), wound dehiscence (OR 0.49; 95% CI 0.32-0.72; P < 0.001) and wound necrosis (OR 0.38; 95% CI 0.19-0.78; P = 0.008). There was no significant difference in haematoma rate (OR 0.8; 95% CI 0.19-3.2; P = 0.75). Statistically significant heterogeneity existed for total wound complications, but no other outcomes. CONCLUSION: Compared with conventional non-NPWT dressings, prophylactic application of NPWT is associated with significantly fewer surgical site complications including SSI, seroma, wound dehiscence and wound necrosis for closed breast incisions.

Measuring the effectiveness of an automated text messaging active surveillance system for COVID-19 in the south of Ireland, March to April 2020.

We report the effectiveness of automated text messaging for active surveillance of asymptomatic close contacts of coronavirus disease (COVID-19) cases in the Cork/Kerry region of Ireland. In the first 7 weeks of the COVID-19 outbreak, 1,336 close contacts received 12,421 automated texts. Overall, 120 contacts (9.0%) reported symptoms which required referral for testing and 35 (2.6%) tested positive for COVID-19. Non-response was high (n = 2,121; 17.1%) and this required substantial clinical and administrative resources for follow-up.

The Pattern of AQP4 Expression in the Ageing Human Brain and in Cerebral Amyloid Angiopathy.

In the absence of lymphatics, fluid and solutes such as amyloid-ß (Aß) are eliminated from the brain along basement membranes in the walls of cerebral capillaries and arteries-the Intramural Peri-Arterial Drainage (IPAD) pathway. IPAD fails with age and insoluble Aß is deposited as plaques in the brain and in IPAD pathways as cerebral amyloid angiopathy (CAA); fluid accumulates in the white matter as reflected by hyperintensities (WMH) on MRI. Within the brain, fluid uptake by astrocytes is regulated by aquaporin 4 (AQP4). We test the hypothesis that expression of astrocytic AQP4 increases in grey matter and decreases in white matter with onset of CAA. AQP4 expression was quantitated by immunocytochemistry and confocal microscopy in post-mortem occipital grey and white matter from young and old non-demented human brains, in CAA and in WMH. Results: AQP4 expression tended to increase with normal ageing but AQP4 expression in severe CAA was significantly reduced when compared to moderate CAA (p = 0.018). AQP4 expression tended to decline in the white matter with CAA and WMH, both of which are associated with impaired IPAD. Adjusting the level of AQP4 activity may be a valid therapeutic target for restoring homoeostasis in the brain as IPAD fails with age and CAA.

Historical environmental change in Africa drives divergence and admixture of Aedes aegypti mosquitoes: a precursor to successful worldwide colonization?

Increasing globalization has promoted the spread of exotic species, including disease vectors. Understanding the evolutionary processes involved in such colonizations is both of intrinsic biological interest and important to predict and mitigate future disease risks. The Aedes aegypti mosquito is a major vector of dengue, chikungunya and Zika, the worldwide spread of which has been facilitated by Ae. aegypti's adaption to human-modified environments. Understanding the evolutionary processes involved in this invasion requires characterization of the genetic make-up of the source population(s). The application of approximate Bayesian computation (ABC) to sequence data from four nuclear and one mitochondrial marker revealed that African populations of Ae. aegypti best fit a demographic model of lineage diversification, historical admixture and recent population structuring. As ancestral Ae. aegypti were dependent on forests, this population history is consistent with the effects of forest fragmentation and expansion driven by Pleistocene climatic change. Alternatively, or additionally, historical human movement across the continent may have facilitated their recent spread and mixing. ABC analysis and haplotype networks support earlier inferences of a single out-of-Africa colonization event, while a cline of decreasing genetic diversity indicates that Ae. aegypti moved first from Africa to the Americas and then to Asia. ABC analysis was unable to verify this colonization route, possibly because the genetic signal of admixture obscures the true colonization pathway. By increasing genetic diversity and forming novel allelic combinations, divergence and historical admixture within Africa could have provided the adaptive potential needed for the successful worldwide spread of Ae. aegypti.

A Farm Transmission Model for Salmonella in Pigs, Applicable to E.U. Member States.

The burden of Salmonella entering pig slaughterhouses across the European Union is considered a primary food safety concern. To assist E.U. member states with the development of national control plans, we have developed a farm transmission model applicable to all member states. It is an individual-based stochastic susceptible-infected model that takes into account four different sources of infection of pigs (sows, feed, external contaminants such as rodents, and new stock) and various management practices linked to Salmonella transmission/protection (housing, flooring, feed, all-in-all-out production). A novel development within the model is the assessment of dynamic shedding rates. The results of the model, parameterized for two case study member states (one high and one low prevalence) suggest that breeding herd prevalence is a strong indicator of slaughter pig prevalence. Until a member state's' breeding herd prevalence is brought below 10%, the sow will be the dominant source of infection to pigs raised for meat production; below this level of breeding herd prevalence, feed becomes the dominant force of infection.

Assessing the Effectiveness of On-Farm and Abattoir Interventions in Reducing Pig Meat-Borne Salmonellosis within E.U. Member States.

As part of the evidence base for the development of national control plans for Salmonella spp. in pigs for E.U. Member States, a quantitative microbiological risk assessment was funded to support the scientific opinion required by the EC from the European Food Safety Authority. The main aim of the risk assessment was to assess the effectiveness of interventions implemented on-farm and at the abattoir in reducing human cases of pig meat-borne salmonellosis, and how the effects of these interventions may vary across E.U. Member States. Two case study Member States have been chosen to assess the effect of the interventions investigated. Reducing both breeding herd and slaughter pig prevalence were effective in achieving reductions in the number of expected human illnesses in both case study Member States. However, there is scarce evidence to suggest which specific on-farm interventions could achieve consistent reductions in either breeding herd or slaughter pig prevalence. Hypothetical reductions in feed contamination rates were important in reducing slaughter pig prevalence for the case study Member State where prevalence of infection was already low, but not for the high-prevalence case study. The most significant reductions were achieved by a 1- or 2-log decrease of Salmonella contamination of the carcass post-evisceration; a 1-log decrease in average contamination produced a 90% reduction in human illness. The intervention analyses suggest that abattoir intervention may be the most effective way to reduce human exposure to Salmonella spp. However, a combined farm/abattoir approach would likely have cumulative benefits. On-farm intervention is probably most effective at the breeding-herd level for high-prevalence Member States; once infection in the breeding herd has been reduced to a low enough level, then feed and biosecurity measures would become increasingly more effective.