ClinCirc identifies alterations of the circadian peripheral oscillator in critical care patients.

BackgroundAssessing circadian rhythmicity from infrequently sampled data is challenging; however, these types of data are often encountered when measuring circadian transcripts in hospitalized patients.MethodsWe present ClinCirc. This method combines 2 existing mathematical methods (Lomb-Scargle periodogram and cosinor) sequentially and is designed to measure circadian oscillations from infrequently sampled clinical data. The accuracy of this method was compared against 9 other methods using simulated and frequently sampled biological data. ClinCirc was then evaluated in 13 intensive care unit (ICU) patients as well as in a separate cohort of 29 kidney-transplant recipients. Finally, the consequences of circadian alterations were investigated in a retrospective cohort of 726 kidney-transplant recipients.ResultsClinCirc had comparable performance to existing methods for analyzing simulated data or clock transcript expression of healthy volunteers. It had improved accuracy compared with the cosinor method in evaluating circadian parameters in PER2:luc cell lines. In ICU patients, it was the only method investigated to suggest that loss of circadian oscillations in the peripheral oscillator was associated with inflammation, a feature widely reported in animal models. Additionally, ClinCirc was able to detect other circadian alterations, including a phase shift following kidney transplantation that was associated with the administration of glucocorticoids. This phase shift could explain why a significant complication of kidney transplantation (delayed graft dysfunction) oscillates according to the time of day kidney transplantation is performed.ConclusionClinCirc analysis of the peripheral oscillator reveals important clinical associations in hospitalized patients.FundingUK Research and Innovation (UKRI), National Institute of Health Research (NIHR), Engineering and Physical Sciences Research Council (EPSRC), National Institute on Academic Anaesthesia (NIAA), Asthma+Lung UK, Kidneys for Life.

Infravec2 guidelines for the design and operation of containment level 2 and 3 insectaries in Europe.

With the current expansion of vector-based research and an increasing number of facilities rearing arthropod vectors and infecting them with pathogens, common measures for containment of arthropods as well as manipulation of pathogens are becoming essential for the design and running of such research facilities to ensure safe work and reproducibility, without compromising experimental feasibility. These guidelines and comments were written by experts of the Infravec2 consortium, a Horizon 2020-funded consortium integrating the most sophisticated European infrastructures for research on arthropod vectors of human and animal diseases. They reflect current good practice across European laboratories with experience of safely handling different mosquito species and the pathogens they transmit. As such, they provide experience-based advice to assess and manage the risks to work safely with mosquitoes and the pathogens they transmit. This document can also form the basis for research with other arthropods, for example, midges, ticks or sandflies, with some modification to reflect specific requirements.

Administration in fed state but not controlled release in the colon increases oral bioavailability of DF030263, a promising drug candidate for chronic lymphocytic leukemia.

For treatment of chronic cancers, the oral administration route is preferred as it provides numerous advantages over other delivery routes. However, these benefits of oral chemotherapy can be limited due to unfavorable pharmacokinetics. Accordingly, pharmacokinetic development of chemotherapeutic agents is crucial to the improvement of cancer treatment. In this study, assessment and optimization of biopharmaceutical properties of a promising drug candidate for cyclin-dependent kinase 9 (CDK9) inhibitor (DF030263) was performed to promote oral delivery. Oral bioavailability of DF030263 in fasted rats was 23.8%, and a distinct double-peak phenomenon was observed. A two-site absorption windows mechanism was proposed as a possible explanation to the phenomenon. The two-site absorption window hypothesis was supported by in vitro solubility assays in biorelevant fluids with different pH levels, as well as by in silico simulation by GastroPlus™. Controlled release to the colon was conducted in rats in order to exploit the colonic absorption window but did not improve the oral bioavailability. On the other hand, oral administration at postprandial conditions in rats (performed based on the high in vitro solubility in fed state simulated fluid and reduced pH-dependency) resulted in an almost 3-fold increase in bioavailability to 63.6%. In conclusion, this study demonstrates an efficient in vitro-in vivo-in silico drug development approach for improving the oral bioavailability of DF030263, a promising candidate for the treatment of chronic lymphocytic leukemia.

Quantifying and Modeling the Acquisition and Retention of Lumpy Skin Disease Virus by Hematophagus Insects Reveals Clinically but Not Subclinically Affected Cattle Are Promoters of Viral Transmission and Key Targets for Control of Disease Outbreaks.

Lumpy skin disease virus (LSDV) is a vector-transmitted poxvirus that causes disease in cattle. Vector species involved in LSDV transmission and their ability to acquire and transmit the virus are poorly characterized. Using a highly representative bovine experimental model of lumpy skin disease, we fed four model vector species (Aedes aegypti, Culex quinquefasciatus, Stomoxys calcitrans, and Culicoides nubeculosus) on LSDV-inoculated cattle in order to examine their acquisition and retention of LSDV. Subclinical disease was a more common outcome than clinical disease in the inoculated cattle. Importantly, the probability of vectors acquiring LSDV from a subclinical animal (0.006) was very low compared with that from a clinical animal (0.23), meaning an insect feeding on a subclinical animal was 97% less likely to acquire LSDV than one feeding on a clinical animal. All four potential vector species studied acquired LSDV from the host at a similar rate, but Aedes aegypti and Stomoxys calcitrans retained the virus for a longer time, up to 8 days. There was no evidence of virus replication in the vector, consistent with mechanical rather than biological transmission. The parameters obtained in this study were combined with data from studies of LSDV transmission and vector life history parameters to determine the basic reproduction number of LSDV in cattle mediated by each of the model species. This reproduction number was highest for Stomoxys calcitrans (19.1), followed by C. nubeculosus (7.1) and Ae. aegypti (2.4), indicating that these three species are potentially efficient transmitters of LSDV; this information can be used to inform LSD control programs.IMPORTANCE Lumpy skin disease virus (LSDV) causes a severe systemic disease characterized by cutaneous nodules in cattle. LSDV is a rapidly emerging pathogen, having spread since 2012 into Europe and Russia and across Asia. The vector-borne nature of LSDV transmission is believed to have promoted this rapid geographic spread of the virus; however, a lack of quantitative evidence about LSDV transmission has hampered effective control of the disease during the current epidemic. Our research shows subclinical cattle play little part in virus transmission relative to clinical cattle and reveals a low probability of virus acquisition by insects at the preclinical stage. We have also calculated the reproductive number of different insect species, therefore identifying efficient transmitters of LSDV. This information is of utmost importance, as it will help to define epidemiological control measures during LSDV epidemics and of particular consequence in resource-poor regions where LSD vaccination may be less than adequate.

Characteristics and Outcomes of Critically Ill Trauma Patients in Australia and New Zealand (2005-2017).

OBJECTIVES: To compare the characteristics of adults admitted to the ICU in Australia and New Zealand after trauma with nonelective, nontrauma admissions. To describe trends in hospital mortality and rates of discharge home among these two groups. DESIGN: Retrospective review (2005-2017) of the Australia and New Zealand Intensive Care Society's Center for Outcome and Resource Evaluation Adult Patient Database. SETTING: Adult ICUs in Australia and New Zealand. PATIENTS: Adult (≥17 yr), nonelective, ICU admissions. INTERVENTION: Observational study. MEASUREMENTS AND MAIN RESULTS: We compared 77,002 trauma with 741,829 nonelective, nontrauma patients. Trauma patients were younger (49.0 ± 21.6 vs 60.6 ± 18.7 yr; p < 0.0001), predominantly male (73.1% vs 53.9%; p < 0.0001), and more frequently treated in tertiary hospitals (74.7% vs 45.8%; p < 0.0001). The mean age of trauma patients increased over time but was virtually static for nonelective, nontrauma patients (0.72 ± 0.02 yr/yr vs 0.03 ± 0.01 yr/yr; p < 0.0001). Illness severity increased for trauma but fell for nonelective, nontrauma patients (mean Australia and New Zealand risk of death: 0.10% ± 0.02%/yr vs -0.21% ± 0.01%/yr; p < 0.0001). Trauma patients had a lower hospital mortality than nonelective, nontrauma patients (10.0% vs 15.8%; p < 0.0001). Both groups showed an annual decline in the illness severity adjusted odds ratio (odds ratio) of hospital mortality, but this was slower among trauma patients (trauma: odds ratio 0.976/yr [0.968-0.984/yr; p < 0.0001]; nonelective, nontrauma: odds ratio 0.957/yr [0.955-0.959/yr; p < 0.0001]; interaction p < 0.0001). Trauma patients had lower rates of discharge home than nonelective, nontrauma patients (56.7% vs 64.6%; p < 0.0001). There was an annual decline in illness severity adjusted odds ratio of discharge home among trauma patients, whereas nonelective, nontrauma patients displayed an annual increase (trauma: odds ratio 0.986/yr [0.981-0.990/yr; p < 0.0001]; nonelective, nontrauma: odds ratio 1.014/yr [1.012-1.016/yr; p < 0.0001]; interaction: p < 0.0001). CONCLUSIONS: The age and illness severity of adult ICU trauma patients in Australia and New Zealand has increased over time. Hospital mortality is lower for trauma than other nonelective ICU patients but has fallen more slowly. Trauma patients have become less likely to be discharged home than other nonelective ICU patients.

Discovery of a crystalline sulforaphane analog with good solid-state stability and engagement of the Nrf2 pathway in vitro and in vivo.

The antioxidant natural product sulforaphane (SFN) is an oil with poor aqueous and thermal stability. Recent work with SFN has sought to optimize methods of formulation for oral and topical administration. Herein we report the design of new analogs of SFN with the goal of improving stability and drug-like properties. Lead compounds were selected based on potency in a cellular screen and physicochemical properties. Among these, 12 had good aqueous solubility, permeability and long-term solid-state stability at 23 °C. Compound 12 also displayed comparable or better efficacy in cellular assays relative to SFN and had in vivo activity in a mouse cigarette smoke challenge model of acute oxidative stress.

Perioral Rejuvenation: A Prospective, Quantitative Dynamic Three-Dimensional Analysis of a Dual Modality Treatment.

BACKGROUND: The perioral region is the most dynamic anatomic area of the face and subject to complex and dramatic changes during aging. Successful treatment for perioral rejuvenation has yet to be identified, and prior studies have reported only subjective outcomes. OBJECTIVES: The purpose of this study was to utilize our validated dynamic 3-dimensional imaging technology to determine whether conservative neuromodulation combined with hyaluronic acid filler volumization can decrease perioral strain and increase volume with significant patient satisfaction. METHODS: An IRB-approved prospective study of a dual modality treatment for perioral rhytids was performed on females with perioral aging who had not had prior facial treatment within the past year. Eighteen (18) units of Dysport were injected into the upper and lower orbicularis oris and 1 cc of Restylane Silk was injected in volume-depleted perioral regions in each patient. Each patient underwent imaging with digital image correlation (DIC) and completed the FACE-Q survey prior to injection and at 14 days and 90 days postinjection. RESULTS: Thirty-two female patients were recruited. A significant reduction in perioral strain was observed at both day 14 and day 90. This was concomitant with a significant increase in perioral volume at day 14 that at 90 days was significantly retained in the marionette lines. Further, there was a significant improvement in patient satisfaction with overall facial appearance at day 14 that was maintained at 90 days. CONCLUSIONS: Conservative neuromodulation and hyaluronic acid filler volumization of the perioral region produces a significant reduction in strain correlating with high patient satisfaction, even at 90 days. This dual modality treatment is effective in rejuvenating the perioral region, and its future optimization will provide greater therapeutic options for this anatomically complex area.

Quantifying Pediatric Facial Palsy: : Using Digital Image Correlation to Objectively Characterize Pediatric Facial Symmetry.

OBJECTIVE: This study introduces digital image correlation (DIC) as a novel technology to objectively quantify pediatric facial symmetry. DESIGN: Descriptive cohort study of patients' facial symmetry as measured by DIC. SETTING: Academic tertiary care hospital. PATIENTS: 9 of 12 identified facial palsy and 13 of 26 identified control subjects participated. INTERVENTIONS: DIC was used to quantify facial strain and symmetry as patients made the 5 standard Sunnybrook facial expressions. Each subject was evaluated according to the Sunnybrook scale by 4 evaluators, 3 plastic surgeons, and 1 occupational therapist. MAIN OUTCOME MEASURE: The percentage asymmetry values were calculated and compared between the facial palsy and control groups using both DIC and Sunnybrook. RESULTS: Using DIC, facial palsy subjects had 32.99% asymmetry compared with 14.84% in controls (P < .01). Using Sunnybrook, facial palsy subjects had 24.11% asymmetry compared to 3.87% in controls (P < .01). The 2 metrics were positively correlated (P < .01). There was significant variability among the Sunnybrook evaluators (P = .02). CONCLUSIONS: DIC is a novel technique of objectively quantifying facial motion of the animated face. As surgical and medical approaches toward facial palsy expand, it is essential to have a means to compare results and improve patient outcomes.

How often do mosquitoes bite humans in southern England? A standardised summer trial at four sites reveals spatial, temporal and site-related variation in biting rates.

BACKGROUND: This field-based study examined the abundance and species complement of mosquitoes (Diptera: Culicidae) attracted to humans at four sites in the United Kingdom (UK). The study used a systematic approach to directly measure feeding by mosquitoes on humans at multiple sites and using multiple volunteers. Quantifying how frequently humans are bitten in the field by mosquitoes is a fundamental parameter in assessing arthropod-borne virus transmission. METHODS: Human landing catches were conducted using a standardised protocol by multiple volunteers at four rural sites between July and August 2013. Collections commenced two hours prior to sunset and lasted for a total of four hours. To reduce bias occurring due to collection point or to the individual attractiveness of the volunteer to mosquitoes, each collection was divided into eight collection periods, with volunteers rotated by randomised Latin square design between four sampling points per site. While the aim was to collect mosquitoes prior to feeding, the source of blood meals from any engorged specimens was also identified by DNA barcoding. RESULTS: Three of the four sites yielded human-biting mosquito populations for a total of 915 mosquitoes of fifteen species/species groups. Mosquito species composition and biting rates differed significantly between sites, with individual volunteers collecting between 0 and 89 mosquitoes (over 200 per hour) of up to six species per collection period. Coquillettidia richiardii (Ficalbi, 1889) was responsible for the highest recorded biting rates at any one site, reaching 161 bites per hour, whilst maximum biting rates of 55 bites per hour were recorded for Culex modestus (Ficalbi, 1889). Human-biting by Culex pipiens (L., 1758) form pipiens was also observed at two sites, but at much lower rates when compared to other species. CONCLUSIONS: Several mosquito species are responsible for human nuisance biting pressure in southern England, although human exposure to biting may be largely limited to evening outdoor activities. This study indicates Cx. modestus can be a major human-biting species in the UK whilst Cx. pipiens f. pipiens may show greater opportunistic human-biting than indicated by earlier studies.

The evolution of transmission mode.

This article reviews research on the evolutionary mechanisms leading to different transmission modes. Such modes are often under genetic control of the host or the pathogen, and often in conflict with each other via trade-offs. Transmission modes may vary among pathogen strains and among host populations. Evolutionary changes in transmission mode have been inferred through experimental and phylogenetic studies, including changes in transmission associated with host shifts and with evolution of the unusually complex life cycles of many parasites. Understanding the forces that determine the evolution of particular transmission modes presents a fascinating medley of problems for which there is a lack of good data and often a lack of conceptual understanding or appropriate methodologies. Our best information comes from studies that have been focused on the vertical versus horizontal transmission dichotomy. With other kinds of transitions, theoretical approaches combining epidemiology and population genetics are providing guidelines for determining when and how rapidly new transmission modes may evolve, but these are still in need of empirical investigation and application to particular cases. Obtaining such knowledge is a matter of urgency in relation to extant disease threats.This article is part of the themed issue 'Opening the black box: re-examining the ecology and evolution of parasite transmission'.

Breaking beta: deconstructing the parasite transmission function.

Transmission is a fundamental step in the life cycle of every parasite but it is also one of the most challenging processes to model and quantify. In most host-parasite models, the transmission process is encapsulated by a single parameter ß Many different biological processes and interactions, acting on both hosts and infectious organisms, are subsumed in this single term. There are, however, at least two undesirable consequences of this high level of abstraction. First, nonlinearities and heterogeneities that can be critical to the dynamic behaviour of infections are poorly represented; second, estimating the transmission coefficient ß from field data is often very difficult. In this paper, we present a conceptual model, which breaks the transmission process into its component parts. This deconstruction enables us to identify circumstances that generate nonlinearities in transmission, with potential implications for emergent transmission behaviour at individual and population scales. Such behaviour cannot be explained by the traditional linear transmission frameworks. The deconstruction also provides a clearer link to the empirical estimation of key components of transmission and enables the construction of flexible models that produce a unified understanding of the spread of both micro- and macro-parasite infectious disease agents.This article is part of the themed issue 'Opening the black box: re-examining the ecology and evolution of parasite transmission'.

Global change, parasite transmission and disease control: lessons from ecology.

Parasitic infections are ubiquitous in wildlife, livestock and human populations, and healthy ecosystems are often parasite rich. Yet, their negative impacts can be extreme. Understanding how both anticipated and cryptic changes in a system might affect parasite transmission at an individual, local and global level is critical for sustainable control in humans and livestock. Here we highlight and synthesize evidence regarding potential effects of 'system changes' (both climatic and anthropogenic) on parasite transmission from wild host-parasite systems. Such information could inform more efficient and sustainable parasite control programmes in domestic animals or humans. Many examples from diverse terrestrial and aquatic natural systems show how abiotic and biotic factors affected by system changes can interact additively, multiplicatively or antagonistically to influence parasite transmission, including through altered habitat structure, biodiversity, host demographics and evolution. Despite this, few studies of managed systems explicitly consider these higher-order interactions, or the subsequent effects of parasite evolution, which can conceal or exaggerate measured impacts of control actions. We call for a more integrated approach to investigating transmission dynamics, which recognizes these complexities and makes use of new technologies for data capture and monitoring, and to support robust predictions of altered parasite dynamics in a rapidly changing world.This article is part of the themed issue 'Opening the black box: re-examining the ecology and evolution of parasite transmission'.

Platelet Rich Plasma Augments Adipose-Derived Stem Cell Growth and Differentiation.

BACKGROUND: Adipose-derived stem cells (ASCs) are a powerful tool for cosmetic surgery and regenerative medicine. The use of autologous platelet rich plasma (PRP), particularly in combination with ASC-based therapy, has significantly expanded in recent years. Unfortunately, the mechanisms and optimal dosing responsible for the beneficial effects of PRP remain poorly understood. Here we investigate the effect of PRP on ASC growth and differentiation. OBJECTIVES: To assess the impact of different PRP feeding and cryopreservation protocols on ASC isolation, expansion, and differentiation. METHODS: Human PRP was isolated using the Magellan System (Arteriocyte). Fresh PRP (fPRP), flash frozen PRP (ffPRP), and cryopreserved PRP (cPRP) were added to human ASCs isolated from healthy patients. A panel of PRP supplementation protocols was analyzed for ASC adherence, proliferation, and osteogenesis. RESULTS: The fresh and cryopreserved PRP groups demonstrated reduced cell adherence compared to control (non-PRP) groups (P < 0.001), while the flash frozen PRP groups showed cell adherence equivalent to or better than controls. After 7 days of growth, ASC populations for fPRP and ffPRP Single Administration protocols were significantly higher than other feeding protocols and controls. This benefit was lost in cPRP groups. Optimized ffPRP protocols showed potential for spontaneous osteogenesis. CONCLUSIONS: Addition of ffPRP improves initial ASC adherence while a single administration of either fresh or flash frozen PRP without additional cell manipulation significantly augments subsequent ASC proliferation. The potential for spontaneous osteogenic differentiation upon PRP exposure invokes the need for additional molecular studies of PRP activity prior to further expansion to clinical applications.

Influence of Standardized Orientation on Patient Perception of Perioperative Care Following Alveolar Cleft Repair: A Survey Based Study of Patients Treated in a Large Academic Medical Center.

OBJECTIVE: This study aims to better understand patient-reported outcomes for iliac bone grafting surgery for alveolar cleft repair and to determine how standardizing perioperative patient instruction affects patient-reported outcomes. DESIGN: Retrospective survey-based assessment of patients undergoing iliac bone grafting with and without hospital-based systems standardization. SETTING: Academic tertiary care hospital. PATIENTS: Of the 195 identified patients, 127 participated. INTERVENTIONS: Survey on pain and satisfaction regarding iliac bone grafting surgery. MAIN OUTCOME MEASURES: Survey answers measured patient opinions about the surgery. Answers of the pre- and poststandardization patients were compared to determine the effect of standardizing patient instructions. RESULTS: Patients rated their satisfaction with the surgery and recovery a 4.5 and 4.4 out of 5, respectively. They rated their overall pain in the hospital a 5.5 out of 10 (4.9 in the mouth, 5.7 in the hip). Patients were discharged an average of 1.2 days after surgery and could return to normal daily activity in 6.1 days. Poststandardization patients were more likely to adhere to instructions regarding use of an antibacterial mouthrinse and a protective oral splint. CONCLUSIONS: Patients were highly satisfied with the iliac bone grafting procedure and the recovery and reported only moderate levels of postoperative pain. Implementing standardized patient instructions may not affect patient satisfaction or pain severity, but it significantly increased patient adherence to physician instructions.

Technical Considerations for Filler and Neuromodulator Refinements.

Background: The toolbox for cosmetic practitioners is growing at an unprecedented rate. There are novel products every year and expanding off-label indications for neurotoxin and soft-tissue filler applications. Consequently, aesthetic physicians are increasingly challenged by the task of selecting the most appropriate products and techniques to achieve optimal patient outcomes. Methods: We employed a PubMed literature search of facial injectables from the past 10 years (2005-2015), with emphasis on those articles embracing evidence-based medicine. We evaluated the scientific background of every product and the physicochemical properties that make each one ideal for specific indications. The 2 senior authors provide commentary regarding their clinical experience with specific technical refinements of neuromodulators and soft-tissue fillers. Results: Neurotoxins and fillers are characterized by unique physical characteristics that distinguish each product. This results in subtle but important differences in their clinical applications. Specific indications and recommendations for the use of the various neurotoxins and soft-tissue fillers are reviewed. The discussion highlights refinements in combination treatments and product physical modifications, according to specific treatment zones. Conclusions: The field of facial aesthetics has evolved dramatically, mostly secondary to our increased understanding of 3-dimensional structural volume restoration. Our work reviews Food and Drug Administration-approved injectables. In addition, we describe how to modify products to fulfill specific indications such as treatment of the mid face, décolletage, hands, and periorbital regions. Although we cannot directly evaluate the duration or exact physical properties of blended products, we argue that "product customization" is safe and provides natural results with excellent patient outcomes.

Advancing vector biology research: a community survey for future directions, research applications and infrastructure requirements.

Vector-borne pathogens impact public health, animal production, and animal welfare. Research on arthropod vectors such as mosquitoes, ticks, sandflies, and midges which transmit pathogens to humans and economically important animals is crucial for development of new control measures that target transmission by the vector. While insecticides are an important part of this arsenal, appearance of resistance mechanisms is increasingly common. Novel tools for genetic manipulation of vectors, use of Wolbachia endosymbiotic bacteria, and other biological control mechanisms to prevent pathogen transmission have led to promising new intervention strategies, adding to strong interest in vector biology and genetics as well as vector-pathogen interactions. Vector research is therefore at a crucial juncture, and strategic decisions on future research directions and research infrastructure investment should be informed by the research community. A survey initiated by the European Horizon 2020 INFRAVEC-2 consortium set out to canvass priorities in the vector biology research community and to determine key activities that are needed for researchers to efficiently study vectors, vector-pathogen interactions, as well as access the structures and services that allow such activities to be carried out. We summarize the most important findings of the survey which in particular reflect the priorities of researchers in European countries, and which will be of use to stakeholders that include researchers, government, and research organizations.

Challenges and priorities for modelling livestock health and pathogens in the context of climate change.

Climate change has the potential to impair livestock health, with consequences for animal welfare, productivity, greenhouse gas emissions, and human livelihoods and health. Modelling has an important role in assessing the impacts of climate change on livestock systems and the efficacy of potential adaptation strategies, to support decision making for more efficient, resilient and sustainable production. However, a coherent set of challenges and research priorities for modelling livestock health and pathogens under climate change has not previously been available. To identify such challenges and priorities, researchers from across Europe were engaged in a horizon-scanning study, involving workshop and questionnaire based exercises and focussed literature reviews. Eighteen key challenges were identified and grouped into six categories based on subject-specific and capacity building requirements. Across a number of challenges, the need for inventories relating model types to different applications (e.g. the pathogen species, region, scale of focus and purpose to which they can be applied) was identified, in order to identify gaps in capability in relation to the impacts of climate change on animal health. The need for collaboration and learning across disciplines was highlighted in several challenges, e.g. to better understand and model complex ecological interactions between pathogens, vectors, wildlife hosts and livestock in the context of climate change. Collaboration between socio-economic and biophysical disciplines was seen as important for better engagement with stakeholders and for improved modelling of the costs and benefits of poor livestock health. The need for more comprehensive validation of empirical relationships, for harmonising terminology and measurements, and for building capacity for under-researched nations, systems and health problems indicated the importance of joined up approaches across nations. The challenges and priorities identified can help focus the development of modelling capacity and future research structures in this vital field. Well-funded networks capable of managing the long-term development of shared resources are required in order to create a cohesive modelling community equipped to tackle the complex challenges of climate change.

A Quantitative Analysis of OnabotulinumtoxinA, AbobotulinumtoxinA, and IncobotulinumtoxinA: A Randomized, Double-Blind, Prospective Clinical Trial of Comparative Dynamic Strain Reduction.

BACKGROUND: U.S. Food and Drug Administration-approved formulations of botulinum toxin include onabotulinumtoxinA (Botox; Allergan, Inc., Irvine, Calif.), abobotulinumtoxinA (Dysport; Galderma Pharma S.A., Lausanne, Switzerland), and incobotulinumtoxinA (Xeomin; Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany). This study uses digital image correlation to compare dynamic strain reduction between available neurotoxins. METHODS: Seventy-three treatment-naive female patients aged were randomized to injection with onabotulinumtoxinA (20 units), abobotulinumtoxinA (60 units), or incobotulinumtoxinA (20 units) in the glabella. Imaging was conducted at 4, 14, and 90 days after injection. Change in average dynamic strain of the glabella was compared using ANOVA. RESULTS: At day 4, there was a 42.1 percent strain reduction in the onabotulinumtoxinA group, a 39.4 percent strain reduction in the abobotulinumtoxinA group, and a 19.8 percent strain reduction in the incobotulinumtoxinA group (onabotulinumtoxinA versus abobotulinumtoxinA, p = 0.77; onabotulinumtoxinA versus incobotulinumtoxinA, p = 0.02; and abobotulinumtoxinA versus incobotulinumtoxinA, p = 0.04). At day 14, there was a 66.1 percent strain reduction in the onabotulinumtoxinA group, a 51.4 percent strain reduction in the abobotulinumtoxinA group, and a 42.8 percent strain reduction in the incobotulinumtoxinA group (onabotulinumtoxinA versus abobotulinumtoxinA, p = 0.14; onabotulinumtoxinA versus incobotulinumtoxinA, p = 0.02; and abobotulinumtoxinA versus incobotulinumtoxinA, p = 0.36). At day 90, there was a 43.5 percent strain reduction in the onabotulinumtoxinA group, a 38.4 percent strain reduction in the abobotulinumtoxinA group, and a 25.3 percent strain reduction in the incobotulinumtoxinA group (onabotulinumtoxinA versus abobotulinumtoxinA, p = 0.66; onabotulinumtoxinA versus incobotulinumtoxinA, p = 0.12; and abobotulinumtoxinA versus incobotulinumtoxinA, p = 0.24). CONCLUSIONS: Using digital image correlation, the tested neuromodulators do not have equivalent strain reduction in the glabella at the doses used. These results confirm assertions of noninterchangeability. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Current Applications of Facial Volumization with Fillers.

LEARNING OBJECTIVES: After reading this article and watching the accompanying videos, the participant should be able to: 1. Assess patients seeking facial volumization and correlate volume deficiencies anatomically. 2. Identify appropriate fillers based on rheologic properties and anatomical needs. 3. Recognize poor candidates for facial volumization. 4. Recognize and treat filler-related side effects and complications. SUMMARY: Facial volumization is widely applied for minimally invasive facial rejuvenation both as a solitary means and in conjunction with surgical correction. Appropriate facial volumization is dependent on patient characteristics, consistent longitudinal anatomical changes, and qualities of fillers available. In this article, anatomical changes seen with aging are illustrated, appropriate techniques for facial volumization are described in the setting of correct filler selection, and potential complications are addressed.