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We describe the design procedure, optimization, and fabrication cycle of an index-pattern FP laser on an InP platform. The design parameters of the ridge and reflector (based on slots) are extracted through simulations. In addition, the performance of reflectors with varying slot widths is analyzed. Subsequently, the extracted parameters are used in a rate equation model to predict the performance of the laser in terms of its L $ - $ I characteristics and the sidemode suppression ratio (SMSR). Moreover, the simulated results are compared with the experimental characterization of lasers fabricated with estimated design parameters revealing that the index-pattern laser with 0.3 $\mu $m slot width delivers the best performance by demonstrating a threshold current of ∼30 mA and $\text{SMSR} > \text{30 dB}$.

ABSTRACT: This study used a stochastic simulation model to estimate the potential economic benefit of using timed artificial insemination (TAI) in combination with conventional unsorted (TCONV) and sexed (TSEX) semen in heifers only (TCONV-H, TSEX-H) and in both heifers and lactating cows (TCONV-HC, TSEX-HC) in a high-producing, pasture-based production system. The scenarios were compared with a conventional reproductive policy (CONV) in which heifers and cows were inseminated with conventional unsorted semen after estrus detection. Sensitivity analysis was also used to estimate the effect of hormone costs from TAI use on the profitability of each program relative to CONV. The mean annual (± standard deviation) profit advantage (ΔPROF) over CONV for TCONV-H, TCONV-HC, TSEX-H, and TSEX-HC scenarios were €3.90/cow ± 4.65, €34.11/cow ± 25.69, €13.96/cow ± 6.83, and €41.52/cow ± 42.86, respectively. Combined application of both technologies was shown to return a greater annual ΔPROF on average compared with that achievable from TAI alone. However, the risk of not returning a positive annual ΔPROF varied across the scenarios with higher risk in TCONV-H and TSEX-HC. Specifically, TCONV-H and TSEX-HC had a 24 and 18% chance, respectively, of not returning a positive annual ΔPROF. Sensitivity analysis showed that when hormone costs increased by €10/cow TCONV-H and TSEX-HC had a 38 and 23% chance, respectively, of not returning a positive annual ΔPROF. The range in ΔPROF for TCONV policies was most sensitive to the TAI pregnancy rate and TSEX policies were most sensitive to the relative fertility achieved with sexed compared with unsorted semen. This study has shown TAI and sexed semen are complementary technologies that can increase genetic gain and profitability in a pasture-based, dairy production system.

Introduction To fully comprehend and appreciate the impact of psychosurgery on treatment-resistant depression it is pertinent to review its initial development and subsequent history. By reviewing previous studies of psychosurgery, we can build a narrative of what was, what currently is and what might be. Assessing the complex philosophical dilemma of the mind and the impact this has on individuals’ concept of psychosurgery has helped to bridge the gap between Neurosurgery and Psychiatry. Objectives We aimed to examine this question, starting at the very beginnings of our concept of mind, working through to modern-day thinking, how we approach both neurosurgery and psychiatry and help to bridge the two. Methods A narrative review of the current literature concerning neurosurgery for mental disorders and said applications to modern psychiatry was conducted. Emphasis on philosophical thought processing in conjunction with the neurosurgical intervention was noted. Results Psychosurgery has its roots in the early philosophy of mind, concerned with distinguishing whether the mind is a physical entity or immaterial. Psychosurgery is reliant on a physical concept of the mind, or at the very least that the mind supervenes the physical brain. History has shown us examples of this, with the archetype of this being the story of Phineas Gage. Since its onset psychosurgery has moved in and out of vogue. After being met with early scepticism it later went on to be performed thousands of times to help cure schizophrenia. In the 1800s, Gottlieb Burkhardt pioneered initial surgical interventions on the brain with intended psychiatric outcomes, moving on to work from Egas Moniz and the development of leucotomies and famously lobotomies, to modern medical techniques of Deep Brain Stimulation. Conclusions Psychosurgery has faced much opposition throughout history due to the uniquely invasive nature of not just affecting us physically but also mentally and the implications that this has for us as humans and our understanding of ourselves. As both medical and cultural views of mental health have changed over time, so has our understanding of psychosurgery and its potential applications. It is possible that early attempts to implement psychosurgery, before the advent of modern medicine, did more harm to psychosurgery’s reputation than good. However, without those early forays, we may never have progressed to the modern techniques we now utilise. Disclosure of Interest None Declared

Background: Vitamin D deficiency is fast emerging as a global pandemic. In South Africa few studies have been conducted to determine the vitamin D status of the healthy population. Methods: This prospective study with an analytical component investigated vitamin D status of healthy undergraduate students at two time points (winter and summer) at Stellenbosch University. Serum 25(OH)D was determined, anthropometric measurements taken and dietary vitamin D intake estimated (food-frequency questionnaire). Skin tone was determined (Fitzpatrick skin type classification), and a skin reflectometry device used to measure dermal melanin content. Results: Results of 242 students indicated a mean serum 25(OH)D of 63.80 ± 41.35 ng/ml and a high prevalence of vitamin D sufficiency (88%). Significantly more females experienced suboptimal vitamin D levels than males (18 vs. 5%; p 0.01). Participants with lighter skin tones had higher levels of 25(OH)D than those with darker skin tones (chi-square = 24.02; p = 0.02). The majority (60.74%) had a normal BMI, although there was no significant relationship between BMI and serum 25 (OH)D (Spearman’s r=–0.11; p = 0.09). Total mean dietary vitamin D intake was 7.99 ± 13.81 mcg, with 87.2% having inadequate intake ( 15 mcg). The relationship between total vitamin D intake and serum 25(OH)D was found to be significant in winter (p 0.001) and summer (p = 0.01). Serum vitamin D levels were significantly higher in the winter phase (p 0.001). Conclusions: A low prevalence of vitamin D deficiency was found amongst healthy young adults, despite low dietary vitamin D intakes. Significant relationships were found between serum 25(OH)D and gender, skin tone and vitamin D intake. Further studies need to be conducted, especially in high-risk groups, before results are applied to the greater South African public.

The herd dynamic milk (HDM) model is a dynamic model capable of simulating the performance of individual dairy animals (from birth to death), with a daily time step. Within this study, the HDM model is described and evaluated in relation to milk production, body condition score (BCS) and BCS change throughout lactation by comparing model simulations against data from published experimental studies. The model’s response to variation in genetic potential, herbage allowance and concentrate supplementation was tested in a sensitivity analysis. Data from experiments in Ireland and France over a 3-year period (2009–11) were used to complete the evaluation. The aim of the Irish experiment was to determine the impact of different stocking rates (SRs) (SR1: 3.28 cow/ha, SR2: 2.51 cow/ha) on key physical, biological and economic performance. The aim of the French experiment was to evaluate over a prolonged time period, the ability of two breeds of dairy cows (Holstein and Normande) to produce and to reproduce under two feeding strategies (high level and low level) in the context of compact calving. The model evaluation was conducted at the herd level with separate evaluations for the primiparous and multiparous cows. The evaluation included the two extreme SRs for the Irish experiment, and an evaluation at the overall herd and individual animal level for the different breeds and feeding levels for the French data. The comparison of simulation and experimental data for all scenarios resulted in a relative prediction error, which was consistently

Life cycle assessment (LCA) and the Intergovernmental Panel on Climate Change (IPCC) guideline methodology, which are the principal greenhouse gas (GHG) quantification methods, were evaluated in this study using a dairy farm GHG model. The model was applied to estimate GHG emissions from two contrasting dairy systems: a seasonal calving pasture-based dairy farm and a total confinement dairy system. Data used to quantify emissions from these systems originated from a research study carried out over a 1-year period in Ireland. The genetic merit of cows modelled was similar for both systems. Total mixed ration was fed in the Confinement system, whereas grazed grass was mainly fed in the grass-based system. GHG emissions from these systems were quantified per unit of product and area. The results of both methods showed that the dairy system that emitted the lowest GHG emissions per unit area did not necessarily emit the lowest GHG emissions possible for a given level of product. Consequently, a recommendation from this study is that GHG emissions be evaluated per unit of product given the growing affluent human population and increasing demand for dairy products. The IPCC and LCA methods ranked dairy systems’ GHG emissions differently. For instance, the IPCC method quantified that the Confinement system reduced GHG emissions per unit of product by 8% compared with the grass-based system, but the LCA approach calculated that the Confinement system increased emissions by 16% when off-farm emissions associated with primary dairy production were included. Thus, GHG emissions should be quantified using approaches that quantify the total GHG emissions associated with the production system, so as to determine whether the dairy system was causing emissions displacement. The IPCC and LCA methods were also used in this study to simulate, through a dairy farm GHG model, what effect management changes within both production systems have on GHG emissions. The findings suggest that single changes have a small mitigating effect on GHG emissions (

No abstract available.

Tree nuts are rich in nutrients, and global production and consumption have doubled during the last decade. However, nuts have a range of quality defects that must be detected and removed during post-harvest processing. Tree nuts can develop hidden internal discoloration, and current sorting methods are prone to subjectivity and human error. Therefore, non-destructive, real-time methods to evaluate internal nut quality are needed. This study explored the potential for VNIR (400–1000 nm) hyperspectral imaging to classify brown center disorder in macadamias. This study compared the accuracy of classifiers developed using images of kernels imaged in face-up and face-down orientations. Classification accuracy was excellent using face-up (>97.9%) and face-down (>94%) images using ensemble and linear discriminate models before and after wavelength selection. Combining images to form a pooled dataset also provided high accuracy (>90%) using artificial neural network and support vector machine models. Overall, HSI has great potential for commercial application in nut processing to detect internal brown centers using images of the outside kernel surface in the VNIR range. This technology will allow rapid and non-destructive evaluation of intact nut products that can then be marketed as a high-quality, defect-free product, compared with traditional methods that rely heavily on representative sub-sampling.

Abstract Effectively preventing and controlling zoonotic diseases requires a One Health approach that involves collaboration across sectors responsible for human health, animal health (both domestic and wildlife), and the environment, as well as other partners. Here we describe the Generalizable One Health Framework (GOHF), a five-step framework that provides structure for using a One Health approach in zoonotic disease programs being implemented at the local, sub-national, national, regional, or international level. Part of the framework is a toolkit that compiles existing resources and presents them following a stepwise schematic, allowing users to identify relevant resources as they are required. Coupled with recommendations for implementing a One Health approach for zoonotic disease prevention and control in technical domains including laboratory, surveillance, preparedness and response, this framework can mobilize One Health and thereby enhance and guide capacity building to combat zoonotic disease threats at the human–animal–environment interface.

Dog vaccination is an effective rabies prevention measure, but widespread vaccination campaigns are challenging in settings like India with large free-roaming dog populations. Here, the authors describe a One Health campaign in Goa state which led to a large reduction of cases in dogs and elimination in humans.

Rabies is one of the most lethal infectious diseases, with those living in Asia and Africa having the highest risk of dying from rabies. We conducted a knowledge, attitudes and practices survey in urban and peri-urban areas of Bangladesh to describe canine bite rates, rabies knowledge, and healthcare seeking behaviors and barriers to human and dog vaccination. A bite risk assessment score (BRAS) and healthcare-seeking behavior score (HSBS) was calculated for each bite victim. Respondents were given two hypothetical situations to assess potential behaviors after a bite and willingness to pay for rabies vaccine and immunoglobulin. In total, 2,447 households participated in the survey and 85 bite victims were identified. The BRAS identified that 31% of bites posed no risk of rabies transmission. Multivariate analyses showed that living in Chittagong (β = 1.4; 95% CI: 0.1, 2.7) was associated with a higher HSBS. Findings presented here provide useful information regarding bite occurrences, healthcare-seeking behaviors, and a need for strategies to increase rabies awareness.

Levels of family functioning are an important consideration in determining appropriate clinical and educational intervention approaches for families and older adults. Theoretical and applied approaches are reviewed with the emphasis on specific interventions that support different levels of family functioning and caregiving. Additionally, different dynamics within the family and their relations with aging family members are examined. This paper updates and expands discussions on levels of family functioning considerations by Sterns et al. using Blocher’s theory of level of human effectiveness. Further levels of family functioning include the theories developed by Bowen’s family systems theory. A present-day consideration is important for counseling, case management, caregiving, and treatment planning to assist families and their aging family member.

Abstract Automotive radar and light detection and ranging (LiDAR) sensors have complementary strengths and weaknesses for 3D surface mapping. We present a method using Markov chain Monte Carlo sampling to recover surface returns from full‐wave longitudinal signals that takes advantage of the high spatial resolution of the LiDAR in range, azimuth and elevation together with the ability of the radar to penetrate obscuring media. The approach is demonstrated using both simulated and real data from an automotive system.

Using questionnaires and serologic testing, we evaluated bat and lyssavirus exposure among persons in an area of Nigeria that celebrates a bat festival. Bats from festival caves underwent serologic testing for phylogroup II lyssaviruses (Lagos bat virus, Shimoni bat virus, Mokola virus). The enrolled households consisted of 2,112 persons, among whom 213 (10%) were reported to have ever had bat contact (having touched a bat, having been bitten by a bat, or having been scratched by a bat) and 52 (2%) to have ever been bitten by a bat. Of 203 participants with bat contact, 3 (1%) had received rabies vaccination. No participant had neutralizing antibodies to phylogroup II lyssaviruses, but >50% of bats had neutralizing antibodies to these lyssaviruses. Even though we found no evidence of phylogroup II lyssavirus exposure among humans, persons interacting with bats in the area could benefit from practicing bat-related health precautions.

Background Acute post-mastectomy pain is frequently challenging to adequately treat with local anesthetic-based regional anesthesia techniques due to its relatively long duration measured in multiple weeks. Case We report three cases in which preoperative ultrasound-guided percutaneous intercostal nerve cryoneurolysis was performed to treat pain following mastectomy. Across all postoperative days and all three patients, the mean pain score on the numeric rating scale was 0 for each day. Similarly, no patient required any supplemental opioid analgesics during the entire postoperative period; and, no patient reported insomnia or awakenings due to pain at any time point. This was a significant improvement over historic cohorts. Conclusions Ultrasound-guided percutaneous cryoanalgesia is a potential novel analgesic modality for acute pain management which has a duration that better-matches mastectomy than other currently-described techniques. Appropriately powered randomized, controlled clinical trials are required to demonstrate and quantify both potential benefits and risks.

Pollen-parent effects on fruit size and quality have been found previously among competing self-pollinated and cross-pollinated fruit on the same Redlands Joy strawberry plant. These effects occur independently of the percentage of fertilized seeds on the fruit, but the expression of these effects on fruit size and some aspects of quality are greatest when calcium is in shortest supply. Here, we aimed to clarify at what developmental stages the self-pollinated and cross-pollinated fruit diverge in size and quality and whether differences between self-pollinated and cross-pollinated fruit are due to early differences in nutrient accumulation. Fruit were harvested at 1, 2 and 3 weeks after hand-pollination and at full ripeness, approximately 4 weeks after hand-pollination. We measured fruit mass, length, diameter, colour, and the concentrations of aluminium, boron, calcium, copper, iron, nitrogen, magnesium, manganese, sodium, phospho-rous, potassium and zinc. Temporary increases in fruit mass, length or diameter due to cross-pollination were evident at 1 or 2 weeks after pollination. Consistent increases in size and skin darkness from cross-pollination emerged in the final week of fruit development. We found little evidence that self-pollinated and cross-pollinated fruit differed in mineral nutrient accumulation at any stage of fruit development. The results demonstrate that cross-pollination effects on strawberry fruit size are evident briefly during early fruit growth but emerge mainly during the final week of fruit development. The effects of cross-pollination on fruit size are not the result of early differences in mineral nutrient accumulation between self-pollinated and cross-pollinated fruit.

Bone abnormalities affect all individuals with Down syndrome (DS) and are linked to abnormal expression of DYRK1A, a gene found in three copies in people with DS and Ts65Dn DS model mice. Previous work in Ts65Dn male mice demonstrated that both genetic normalization of Dyrk1a and treatment with ~9 mg/kg/day Epigallocatechin-3-gallate (EGCG), the main polyphenol found in green tea and putative DYRK1A inhibitor, improved some skeletal deficits. Because EGCG treatment improved mostly trabecular skeletal deficits, we hypothesized that increasing EGCG treatment dosage and length of administration would positively affect both trabecular and cortical bone in Ts65Dn mice. Treatment of individuals with DS with green tea extract (GTE) containing EGCG also showed some weight loss in individuals with DS, and we hypothesized that weights would be affected in Ts65Dn mice after EGCG treatment. Treatment with ~20 mg/kg/day EGCG for seven weeks showed no improvements in male Ts65Dn trabecular bone and only limited improvements in cortical measures. Comparing skeletal analyses after ~20mg/kg/day EGCG treatment with previously published treatments with ~9, 50, and 200 mg/kg/day EGCG showed that increased dosage and treatment time increased cortical structural deficits leading to weaker appendicular bones in male mice. Weight was not affected by treatment in mice, except for those given a high dose of EGCG by oral gavage. These data indicate that high doses of EGCG, similar to those reported in some treatment studies of DS and other disorders, may impair long bone structure and strength. Skeletal phenotypes should be monitored when high doses of EGCG are administered therapeutically.

BackgroundIdentifying Obstructive Sleep Apnea (OSA) phenotypes among middle-aged and older Hispanics/Latinos can facilitate personalized care, better inform treatment decisions, and could lead to improved clinical outcomes.MethodsWe focused on middle-aged and older adults (ages ≥45-74 years at baseline) with an apnea-hypopnea index (AHI) ≥5 from the HCHS/SOL (2008-2011) (unweighted n = 3,545). We used latent class analyses (LCA) to identify empirical and clinically meaningful OSA phenotypes. Sleep variables included AHI, percent sleep time SpO2ResultsAverage AHI, ESS, WHIIRS, and sleep duration were 18.1±19.5, 6.3±6.1, 7.4±6.6, and 7.8±1.7 hours, respectively, and 2.9% had zero percent time SpO2 ConclusionsOSA subtypes in diverse U.S. Hispanic/Latino adults have different cardiovascular complications. More targeted research, that takes these variations into account, could help ameliorate Hispanic/Latino sleep and cardiovascular health disparities.

Abstract Background Despite a number of different transgenes that can mediate DNA deletion in the developing lens, each has unique features that can make a given transgenic line more or less appropriate for particular studies. The purpose of this work encompasses both a review of transgenes that lead to the expression of Cre recombinase in the lens and a comparative analysis of currently available transgenic lines with a particular emphasis on the Le-Cre and P0-3.9GFPCre lines that can mediate DNA deletion in the lens placode. Although both of these transgenes are driven by elements of the Pax6 P0 promoter, the Le-Cre transgene consistently leads to ocular abnormalities in homozygous state and can lead to ocular defects on some genetic backgrounds when hemizygous. Result Although both P0-3.9GFPCre and Le-Cre hemizygous transgenic mice undergo normal eye development on an FVB/N genetic background, Le-Cre homozygotes uniquely exhibit microphthalmia. Examination of the expression patterns of these two transgenes revealed similar expression in the developing eye and pancreas. However, lineage tracing revealed widespread non-ocular CRE reporter gene expression in the P0-3.9GFPCre transgenic mice that results from stochastic CRE expression in the P0-3.9GFPCre embryos prior to lens placode formation. Postnatal hemizygous Le-Cre transgenic lenses express higher levels of CRE transcript and protein than the hemizygous lenses of P0-3.9GFPCre mice. Transcriptome analysis revealed that Le-Cre hemizygous lenses deregulated the expression of 15 murine genes, several of which are associated with apoptosis. In contrast, P0-3.9GFPCre hemizygous lenses only deregulated two murine genes. No known PAX6-responsive genes or genes directly associated with lens differentiation were deregulated in the hemizygous Le-Cre lenses. Conclusions Although P0-3.9GFPCre transgenic mice appear free from ocular abnormalities, extensive non-ocular CRE expression represents a potential problem for conditional gene deletion studies using this transgene. The higher level of CRE expression in Le-Cre lenses versus P0-3.9GFPCre lenses may explain abnormal lens development in homozygous Le-Cre mice. Given the lack of deregulation of PAX6-responsive transcripts, we suggest that abnormal eye development in Le-Cre transgenic mice stems from CRE toxicity. Our studies reinforce the requirement for appropriate CRE-only expressing controls when using CRE as a driver of conditional gene targeting strategies.

Zoonotic diseases represent a heavy global burden, causing important economic losses, impacting animal health and production, and costing millions of human lives. The vaccination of animals and humans to prevent inter-species zoonotic disease transmission is an important intervention. However, efforts to develop and implement vaccine interventions to reduce zoonotic disease impacts are often limited to the veterinary and agricultural sectors and do not reflect the shared burden of disease. Multisectoral collaboration, including co-development opportunities for human and animal vaccines, expanding vaccine use to include animal reservoirs such as wildlife, and strategically using vaccines to interrupt complex transmission cycles is needed. Addressing zoonoses requires a multi-faceted One Health approach, wherein vaccinating people and animals plays a critical role.

Background Women with a history of preeclampsia are at increased risk of cardiovascular morbidity and mortality. However, the underlying mechanisms of disease association, and the ideal method of monitoring this high‐risk group, remains unclear. This review aims to determine whether women with a history of preeclampsia show clinical or subclinical cardiac changes when evaluated with an echocardiogram. Methods and Results A systematic search of MEDLINE, EMBASE, and CINAHL databases was performed to identify studies that examined cardiac function in women with a history of preeclampsia, in comparison with those with normotensive pregnancies. In the 27 included studies, we found no significant differences between preeclampsia and nonpreeclampsia women with regard to left ventricular ejection fraction, isovolumetric relaxation time, or deceleration time. Women with a history of preeclampsia demonstrated a higher left ventricular mass index and relative wall thickness with a mean difference of 4.25 g/m2 (95% CI, 2.08, 6.42) and 0.03 (95% CI, 0.01, 0.05), respectively. In comparison with the nonpreeclampsia population, they also demonstrated a lower E/A and a higher E/e′ ratio with a mean difference of −0.08 (95% CI, −0.15, −0.01) and 0.84 (95% CI, 0.41, 1.27), respectively. Conclusions In comparison with women who had a normotensive pregnancy, women with a history of preeclampsia demonstrated a trend toward altered cardiac structure and function. Further studies with larger sample sizes and consistent echocardiogram reporting with the use of sensitive preclinical markers are required to assess the role of echocardiography in monitoring this high‐risk population group.

Rabies surveillance and control measures vary significantly between Caribbean islands. The Centers for Disease Control and Prevention currently recommends certain groups of U.S. travelers to any Caribbean island receive pre-exposure rabies immunization. However, most islands self-declare as “rabies free”, and have never publicly released data to support rabies-free claims. We used the Analytic Hierarchy Process to create pairwise comparison values among five risk factors determined by subject matter experts. Risk factor weights were calculated and used in a geospatial analysis to calculate a risk value for each island nation (higher values indicate higher risk). Risk values ranged from 8.73 (Trinidad) to 1.57 (The Bahamas, Turks and Caicos Islands). All four countries that have documented occurrences of laboratory confirmed rabid bats were ranked highest (Trinidad and Tobago, Grenada, Cuba, Dominican Republic), as well as Haiti. The top five highest risk countries that currently have no reports of bat rabies include St. Vincent and the Grenadines, Jamaica, Puerto Rico, the Cayman Islands, and Dominica. This study reviews the inter-island movement potential of bats, designates areas of high risk for bat-associated rabies within the Caribbean islands, and demonstrates a need for further surveillance efforts in bat populations within islands that self-declare as rabies free.

Canine rabies elimination can be achieved through mass vaccination of the dog population, as advocated by the WHO, OIE and FAO under the ‘United Against Rabies’ initiative. Many countries in which canine rabies is endemic are exploring methods to access dogs for vaccination, campaign structures and approaches to resource mobilization. Reviewing aspects that fostered success in rabies elimination campaigns elsewhere, as well as examples of largescale resource mobilization, such as that seen in the global initiative to eliminate poliomyelitis, may help to guide the planning of sustainable, scalable methods for mass dog vaccination. Elimination of rabies from the majority of Latin America took over 30 years, with years of operational trial and error before a particular approach gained the broad support of decision makers, governments and funders to enable widespread implementation. The endeavour to eliminate polio now enters its final stages; however, there are many transferrable lessons to adopt from the past 32 years of global scale-up. Additionally, there is a need to support operational research, which explores the practicalities of mass dog vaccination roll-out and what are likely to be feasible solutions at scale. This article reviews the processes that supported the scale-up of these interventions, discusses pragmatic considerations of campaign duration and work-force size and finally provides an examples hypothetical resource requirements for implementing mass dog vaccination at scale in Indian cities, with a view to supporting the planning of pilot campaigns from which expanded efforts can grow.

Bacterial pathogens must sense, respond and adapt to a myriad of dynamic microenvironmental stressors to survive. Adaptation is key for colonization and long-term ability to endure fluctuations in nutrient availability and inflammatory processes. We hypothesize that strains adapted to survive nutrient deprivation are more adept for colonization and establishment of chronic infection. In this study, we detected microevolution in response to transient nutrient limitation through mutation of icc. The mutation results in decreased 3',5'-cyclic adenosine monophosphate phosphodiesterase activity in nontypeable Haemophilus influenzae (NTHI). In a preclinical model of NTHI-induced otitis media (OM), we observed a significant decrease in the recovery of effusion from ears infected with the icc mutant strain. Clinically, resolution of OM coincides with the clearance of middle ear fluid. In contrast to this clinical paradigm, we observed that the icc mutant strain formed significantly more intracellular bacterial communities (IBCs) than the parental strain early during experimental OM. Although the number of IBCs formed by the parental strain was low at early stages of OM, we observed a significant increase at later stages that coincided with absence of recoverable effusion, suggesting the presence of a mucosal reservoir following resolution of clinical disease. These data provide the first insight into NTHI microevolution during nutritional limitation and provide the first demonstration of IBCs in a preclinical model of chronic OM.

Haiti has experienced numerous barriers to rabies control over the past decades and is one of the remaining Western Hemisphere countries to report dog-mediated human rabies deaths. We describe the circumstances surrounding a reported human rabies death in 2016 as well as barriers to treatment and surveillance reporting.

Liver cirrhosis is the 6th leading cause of death in adults aged 15–59 years in high-income countries. For many who progress to cirrhosis, the only prospect for survival is liver transplantation. While there is some indication that mesenchymal stem cells may be useful in reversing established liver fibrosis, there are limitations to their widespread use – namely their rarity, the need for extensive serial passaging and the associated potential for genomic instability and cellular senescence. To this end, we propose the use of allogeneic amnion epithelial cells. This clinical trial will assess the safety of intravenously delivered allogeneic human amnion epithelial cells (hAECs) in patients with compensated liver cirrhosis. This will also provide clinical data that will inform phases 2 and 3 clinical trials with the ultimate goal of developing hAECs as a therapeutic option for patients with cirrhosis who are at significant risk of disease progression. We will recruit 12 patients with compensated cirrhosis, based on their hepatic venous pressure gradient, for a dose escalation study. Patients will be closely monitored in the first 24 h post-infusion, then via daily telephone interviews until clinical assessment on day 5. Long term follow up will include standard liver tests, transient elastography and hepatic ultrasound. Ethics approval was obtained from Monash Health for this trial 16052A, “A Pilot Study Evaluating the Safety of Intravenously Administered Human Amnion Epithelial Cells for the Treatment of Liver Fibrosis, A First in Adult Human Study.” The trial will be conducted in accordance to Monash Health Human Ethics guidelines. Outcomes from this study will be disseminated in the form of conference presentations and submission to a peer reviewed journal. This trial has been registered on the Australian and New Zealand Clinical Trials Registry ACTRN12616000437460.