Environmental heterogeneity promotes individual specialisation in habitat selection in a widely distributed seabird.

Individual specialisations in behaviour are predicted to arise where divergence benefits fitness. Such specialisations are more likely in heterogeneous environments where there is both greater ecological opportunity and competition-driven frequency dependent selection. Such an effect could explain observed differences in rates of individual specialisation in habitat selection, as it offers individuals an opportunity to select for habitat types that maximise resource gain while minimising competition; however, this mechanism has not been tested before. Here, we use habitat selection functions to quantify individual specialisations while foraging by black-legged kittiwakes Rissa tridactyla, a marine top predator, at 15 colonies around the United Kingdom and Ireland, along a gradient of environmental heterogeneity. We find support for the hypothesis that individual specialisations in habitat selection while foraging are more prevalent in heterogeneous environments. This trend was significant across multiple dynamic habitat variables that change over short time-scales and did not arise through site fidelity, which highlights the importance of environmental processes in facilitating behavioural adaptation by predators. Individual differences may drive evolutionary processes, and therefore these results suggest that there is broad scope for the degree of environmental heterogeneity to determine current and future population, species and community dynamics.

Environmental heterogeneity decreases reproductive success via effects on foraging behaviour.

Environmental heterogeneity shapes the uneven distribution of resources available to foragers, and is ubiquitous in nature. Optimal foraging theory predicts that an animal's ability to exploit resource patches is key to foraging success. However, the potential fitness costs and benefits of foraging in a heterogeneous environment are difficult to measure empirically. Heterogeneity may provide higher-quality foraging opportunities, or alternatively could increase the cost of resource acquisition because of reduced patch density or increased competition. Here, we study the influence of physical environmental heterogeneity on behaviour and reproductive success of black-legged kittiwakes, Rissa tridactyla. From GPS tracking data at 15 colonies throughout their British and Irish range, we found that environments that were physically more heterogeneous were associated with longer trip duration, more time spent foraging while away from the colony, increased overlap of foraging areas between individuals and lower breeding success. These results suggest that there is greater competition between individuals for finite resources in more heterogeneous environments, which comes at a cost to reproduction. Resource hotspots are often considered beneficial, as individuals can learn to exploit them if sufficiently predictable. However, we demonstrate here that such fitness gains can be countered by greater competition in more heterogeneous environments.

Metapopulation dynamics of roseate terns: Sources, sinks and implications for conservation management decisions.

Habitat management to restore or create breeding sites may allow metapopulations to increase in size and reduce the risk of demographic stochasticity or disasters causing metapopulation extinction. However, if newly restored or created sites are of low quality, they may act as sinks that draw individuals away from better quality sites to the detriment of metapopulation size. Following intensive conservation effort, the metapopulation of roseate tern (Sterna dougallii) in NW Europe is recovering from a large crash in numbers, but most former colonies remain unoccupied and hence are potential targets for restoration. To inform conservation efforts, we studied the dynamics of this metapopulation with a multistate integrated population model to assess each of the three main colonies for important demographic contributors to population growth rate, source/sink status and possible density dependence. All three study colonies are managed for roseate terns (and other tern species) in similar ways, but the demographic processes vary considerably between colonies. The largest colony is a source involved in almost all dispersal, and its growth is determined by survival rates and productivity. Productivity and juvenile apparent survival at the largest colony appear to be density-dependent. Although the mechanisms are unclear, this may provide an increasing impetus for emigration of recruits to other colonies in future. The smallest of the three colonies is a sink, relying on immigration for its growth. Simulation models suggest the metapopulation would be c. 10% larger in the absence of dispersal to the sink colony. This work indicates that, due to variable site quality, aims to enhance both distribution and size of metapopulations may be mutually exclusive. In this case, before future attempts to encourage recolonisation of former sites, assessments of site suitability should be undertaken, focusing on food availability and isolation from predators to maximise the likelihood of attaining levels of productivity and survival that avoid creation of a sink population to the detriment of the overall metapopulation size.

Breeding density, fine-scale tracking, and large-scale modeling reveal the regional distribution of four seabird species.

Population-level estimates of species' distributions can reveal fundamental ecological processes and facilitate conservation. However, these may be difficult to obtain for mobile species, especially colonial central-place foragers (CCPFs; e.g., bats, corvids, social insects), because it is often impractical to determine the provenance of individuals observed beyond breeding sites. Moreover, some CCPFs, especially in the marine realm (e.g., pinnipeds, turtles, and seabirds) are difficult to observe because they range tens to ten thousands of kilometers from their colonies. It is hypothesized that the distribution of CCPFs depends largely on habitat availability and intraspecific competition. Modeling these effects may therefore allow distributions to be estimated from samples of individual spatial usage. Such data can be obtained for an increasing number of species using tracking technology. However, techniques for estimating population-level distributions using the telemetry data are poorly developed. This is of concern because many marine CCPFs, such as seabirds, are threatened by anthropogenic activities. Here, we aim to estimate the distribution at sea of four seabird species, foraging from approximately 5,500 breeding sites in Britain and Ireland. To do so, we GPS-tracked a sample of 230 European Shags Phalacrocorax aristotelis, 464 Black-legged Kittiwakes Rissa tridactyla, 178 Common Murres Uria aalge, and 281 Razorbills Alca torda from 13, 20, 12, and 14 colonies, respectively. Using Poisson point process habitat use models, we show that distribution at sea is dependent on (1) density-dependent competition among sympatric conspecifics (all species) and parapatric conspecifics (Kittiwakes and Murres); (2) habitat accessibility and coastal geometry, such that birds travel further from colonies with limited access to the sea; and (3) regional habitat availability. Using these models, we predict space use by birds from unobserved colonies and thereby map the distribution at sea of each species at both the colony and regional level. Space use by all four species' British breeding populations is concentrated in the coastal waters of Scotland, highlighting the need for robust conservation measures in this area. The techniques we present are applicable to any CCPF.

Polycyclic aromatic hydrocarbons (PAHs) in seabird eggs in Ireland.

Seabird eggs are considered a favourable matrix for monitoring marine pollutants and are widely used as higher trophic level indicators. Concentrations of Polycyclic aromatic hydrocarbons (Σ15PAH) were determined in the eggs of four piscivorous seabirds in Ireland from multiple colonies for the first time, Common Guillemot Uria aalge, Northern Gannet Morus bassanus, Common Tern Sterna hirundo and Arctic Tern S. paradisaea. PAH concentrations were generally lower than levels detected in eggs from other seabird studies and considerably lower than concentrations associated with no adverse effect in the eggs of domestic avian species. This study indicates potential site and species differences in PAH concentrations. Baseline data of PAHs in a range of seabird species from this study may provide an important reference point should a major pollution event occur in European waters, such as an oil spill.

Persistent pollutants in fresh and abandoned eggs of Common Tern (Sterna hirundo) and Arctic Tern (Sterna paradisaea) in Ireland.

Higher levels of persistent pollutants (Σ16PCB, Σ6PBDE, ΣHCH, ΣDDT, ΣCHL) were detected in fresh eggs of Common Terns Sterna hirundo from Rockabill Island near Dublin (Ireland's industrialised capital city) compared to Common and Arctic Terns S. paradisaea from Ireland's west coast. Intra-clutch variation of pollutant levels in Common Terns was shown to be low, providing further evidence that random sampling of one egg may be an appropriate sampling strategy. Significant differences in pollutant concentrations were detected between fresh and abandoned eggs on Rockabill. However, abandoned eggs can still provide a useful approximation of pollutants in bird eggs if non-destructive sampling is preferred. Levels of p,p' -DDE in tern eggs have decreased over time according to this study, in concurrence with worldwide trends. Results in this study fall below toxicological thresholds for birds and OSPARs EcoQO thresholds set for Common Tern eggs, except for mercury and HCH in the west coast.

Legacy and emerging contaminants in common guillemot Uria aalge eggs in Ireland and Wales.

Guillemot eggs from multiple Irish colonies and one Welsh colony were analysed for legacy pollutants such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and other organochlorine compounds (OCs), as well as metals. Stable isotope ratios of carbon (δ13C) and nitrogen (δ15N) were measured in eggs to understand the influence of diet on contaminant levels detected. Wide-scope target and suspect screening techniques were used on a single guillemot egg, providing novel information on contaminants of emerging concern. Stable isotope ratio analysis showed that guillemots from Great Saltee Island and Lambay Island (Ireland's east coast) had a similar carbon source (δ13C) and fed at similar trophic levels (δ15N), pollutant levels were higher in eggs from Lambay Island near Dublin, Ireland's industrialised capital city. Guillemot eggs from Aughris Head (Atlantic west coast of Ireland), and Skomer Island (Wales) had differing isotopic niches to other colonies. Egg samples from Aughris Head had the lowest levels of pollutants in this study (with the exception of mercury) and amongst the lowest levels reported worldwide. In contrast, Skomer Island had the highest level of pollutants with higher concentrations of Σ16PCB, Σ6PBDE and HCB than Irish colonies, most likely a result of its proximity to historically industrial areas. Levels of PCBs, p,p' -DDE and mercury in guillemot eggs have decreased over time according to this study, in concurrence with worldwide trends. Levels of pollutants in guillemot eggs, in this study, fall below existing thresholds for adverse effects in other species, with the exception of mercury.

Persistent pollutants in Northern Gannet Morus bassanus eggs in Ireland: Levels and colony differences.

Seabird eggs are considered a favourable matrix for monitoring marine pollutants and are widely used as higher trophic level indicators. Persistent organic pollutants such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and other organochlorine compounds (OCs) as well as metals have been shown to have deleterious impacts on seabirds. The Northern Gannet Morus bassanus is an avian sentinel; the largest breeding seabird in Ireland and an obligate piscivore. Gannet eggs were collected from two island colonies off the east coast of Ireland in locations with divergent history of industrialisation. Contaminant levels were measured and differences in concentrations between colonies compared. Stable isotope ratios of carbon (δ13C) and nitrogen (δ15N) were measured in each egg to understand the influence of diet and trophic position on contaminant levels detected. Significantly higher levels of Σ14PCBs, Σ7PBDEs and total mercury were detected in Gannet eggs from Lambay Island near Dublin (Ireland's industrialised capital city) compared to Great Saltee Island. No differences were observed in levels of other OCs (HCB, ΣHCH, ΣCHL, ΣDDT) between the two colonies. Though Gannets travel significant distances when foraging for food, tracking studies have demonstrated that birds from proximal breeding colonies maintain exclusive feeding areas. Stable isotope ratio analysis in this study demonstrated that Gannets at both locations occupy similar dietary niches, indicating that dietary differences may not be the driver of differing contaminant levels between colonies. Levels of persistent pollutants in the Gannet eggs fall below most existing thresholds for adverse effects and are within internationally reported values. Recent population growth and range expansion of Gannets in Ireland suggest that persistent pollutants are not having an immediate impact on the Gannet population. This study will inform potential monitoring programmes that can help Ireland achieve good environmental status under the European Union's Marine Strategy Framework Directive.

miRNA mutations are not a common cause of deafness.

Mutations in miRNA genes have been implicated in hearing loss in human families and mice. It is also possible that mutations in miRNA binding sites of inner ear targets alter gene expression levels and lead to hearing loss. To investigate these possibilities we screened predicted target genes of the miR-183 miRNA cluster known to be expressed in the inner ear sensory epithelium. In one Iranian family segregating autosomal recessive non-syndromic hearing loss (ARNSHL), we identified a homozygous variant in a predicted miR-96/182 binding site in the 3'UTR of the RDX (DFNB24) gene. However, in vitro functional studies showed that this site is not a functional target for miR-96/182. We extended our study to include the miR-183 genes themselves and 24 additional predicted target genes of the miRNA-183 cluster. Screening these miRNAs and target sequences in numerous families segregating either autosomal dominant non-syndromic deafness (ADNSHL) or ARNSHL did not identify any potential deafness-causing mutations. These results suggest that mutations disrupting gene regulation by the miR-183 cluster are not a common cause of human hearing loss.

Novel Variants in Hearing Loss Genes and Associations With Audiometric Thresholds in a Multi-ethnic Cohort of US Patients With Cochlear Implants.

OBJECTIVES: To investigate novel variants in hearing loss genes and clinical factors affecting audiometric outcomes of cochlear implant (CI) patients. BACKGROUND: Approximately 50% of hearing loss has a genetic etiology, with certain genetic variants more prevalent in specific ethnic groups. Different variants and some clinical variables including inner ear malformations result in different prognoses or clinical outcomes after CI. METHODS: Medical and genetic testing records of pediatric CI patients were reviewed for clinical variables. Minor allele frequencies of variants were obtained from Genome Aggregation Database (gnomAD) and variants were classified for pathogenicity. Standard statistical testing was done using Fisher's exact, Wilcoxon, and Spearman correlation tests. RESULTS: Eighteen CI patients with genetic test results had pathogenic variants, including six patients with syndromic hearing loss and six patients with known GJB2 variants. Novel pathogenic variants were noted in CHD7, ADGRV1, and ARID1B, with variants in the latter two genes identified in Hispanic patients. Overall, carriage of genetic variants was associated with better pre-CI audiometric thresholds at 2000 Hz (p = 0.048). On the other hand, post-CI thresholds were significantly worse in patients with inner ear malformations, particularly in patients with atretic cochlear nerve canals. CONCLUSION: Four novel pathogenic variants were identified, which contributes to knowledge of allelic spectrum for hearing loss especially in Hispanic patients. In this cohort, carriage of pathogenic variants particularly of GJB2 variants was associated with better pre-CI audiometric thresholds, while patients with inner ear malformations had worse post-CI audiometric thresholds.

Advances in Molecular and Cellular Therapies for Hearing Loss.

Development of effective therapeutics for hearing loss has proven to be a slow and difficult process, evidenced by the lack of restorative medicines and technologies currently available to the otolaryngologist. In large part this is attributable to the limited regenerative potential in cochlear cells and the secondary degeneration of the cochlear architecture that commonly follows sensorineural hearing impairment. Therapeutic advances have been made using animal models, particularly in regeneration and remodeling of spiral ganglion neurons, which retract and die following hair cell loss. Natural regeneration in avian and reptilian systems provides hope that replacement of hair cells is achievable in humans. The most exciting recent advancements in this field have been made in the relatively new areas of cellular replacement and gene therapy. In this review we discuss recent developments in gene- and cell-based therapy for hearing loss, including detailed analysis of therapeutic mechanisms such as RNA interference and stem cell transplantation, as well as in utero delivery to the mammalian inner ear. We explore the advantages and limitations associated with the use of these strategies for inner ear restoration.

Advances in molecular and cellular therapies for hearing loss.

Development of effective therapeutics for hearing loss has proven to be a slow and difficult process, evidenced by the lack of restorative medicines and technologies currently available to the otolaryngologist. In large part this is attributable to the limited regenerative potential in cochlear cells and the secondary degeneration of the cochlear architecture that commonly follows sensorineural hearing impairment. Therapeutic advances have been made using animal models, particularly in regeneration and remodeling of spiral ganglion neurons, which retract and die following hair cell loss. Natural regeneration in avian and reptilian systems provides hope that replacement of hair cells is achievable in humans. The most exciting recent advancements in this field have been made in the relatively new areas of cellular replacement and gene therapy. In this review we discuss recent developments in gene- and cell-based therapy for hearing loss, including detailed analysis of therapeutic mechanisms such as RNA interference and stem cell transplantation, as well as in utero delivery to the mammalian inner ear. We explore the advantages and limitations associated with the use of these strategies for inner ear restoration.

A Review of Traditional Vaccine-Preventable Diseases and the Potential Impact on the Otolaryngologist.

Introduction A majority of otolaryngologists have not had direct experience with many vaccine-preventable diseases since the creation of national vaccination programs. Despite the elimination of endemic transmission of some of these diseases in the United States, outbreaks can occur anywhere and still pose a threat to public health around the world. Recent outbreaks and changing trends in exemption rates indicate that it is important for physicians to maintain a working knowledge of how these diseases present and of the recommended treatment guidelines. Objectives This review will evaluate the current state of vaccination rates, vaccine exemption rates and disease incidence in the United States and in the world. It will also examine the clinical presentation and treatment recommendations of these diseases. Data Synthesis United States estimated vaccination rates, vaccine exemption rates and vaccine-preventable disease incidences were obtained from data compiled by the Centers for Disease Control and Prevention. World vaccination rates and disease incidences were obtained from the World Health Organization databases, which compile official figures reported by member states. A PubMed literature review provided information on the current state of vaccination exemptions and outbreaks in the United States. Conclusion Vaccination and vaccine exemption rates continue to put the United States and many areas of the world at risk for outbreaks of vaccine-preventable diseases. Clinical guidelines should be reviewed in the event of a local outbreak.

Revision cochlear implant surgery in children: Surgical and audiological outcomes.

OBJECTIVES/HYPOTHESIS: To determine the incidence of cochlear implant failure and to examine surgical and audiological outcomes. STUDY DESIGN: Retrospective review, case series. METHODS: This study sought indications for revision surgery, surgical findings, and outcomes, and audiological outcomes in pediatric cochlear implant patients. Pre- and postcochlear reimplantation word recognition performance was analyzed using a modified version of the Pediatric Ranked Order Speech Perception (PROSPER) score. RESULTS: Over a 20-year period, a total of 868 cochlear implants were performed in 578 patients. The overall institutional reimplant rate was 5.9%. The indications for explantation were hard failure (30), soft failure (23), and medical/surgical indication (13). A significant portion of devices belonged to vendor recalled batches (15) or were damaged by head trauma (eight). Full electrode insertion was achieved in all 62 reimplantations. Post-reimplantation Boston Children's Hospital modified PROSER scores were either stable or improved compared to pre-reimplantation scores. CONCLUSIONS: The need for cochlear implant revision/reimplantation is infrequent, but the rate is not inconsequential. Hard and soft device failures account for the majority of reimplants. Surgical complications during reimplantation is low, and post-reimplantation audiological performance is excellent. LEVEL OF EVIDENCE: 4. Laryngoscope, 2619-2624, 2018.

Opportunistic sampling to quantify plastics in the diet of unfledged Black Legged Kittiwakes (Rissa tridactyla), Northern Fulmars (Fulmarus glacialis) and Great Cormorants (Phalacrocorax carbo).

Seabirds can interact with marine litter, mainly by entanglement or ingestion. The ingestion of plastics can lead to starvation or physical damage to the digestive tract. For chicks, it could additionally lead to reduced growth, affecting survival and fledging. This study quantified the ingestion of plastics by seabird chicks via an opportunistic sampling strategy. When ringing is carried out at colonies, birds may spontaneously regurgitate their stomach contents due to the stress or as a defence mechanism. Regurgitates were collected from nestlings of three different species: Black-legged Kittiwake (Rissa tridactyla, n=38), Northern Fulmar (Fulmarus glacialis, n=14) and Great Cormorant (Phalacrocorax carbo, n=28). Plastic was present in all species, with the highest frequency of occurrence (FO) in Northern Fulmar chicks (28.6%), followed by Black-legged Kittiwakes (7.9%) and Great Cormorants (7.1%). The observed load of plastics on chicks, which have not yet left the nest, highlights the pervasive nature of plastic pollution.

Presence of plastic litter in pellets from Great Cormorant (Phalacrocorax carbo) in Ireland.

Plastic pollution has been the subject of much research in the last decade. Seabirds can mistake plastic fragments for prey, which can perforate or block the digestive tract and cause ulcers. Most commonly, seabirds accumulate this indigestible matter in their stomachs, obtaining no nutrition and may die from starvation. Certain species of seabirds however, have the ability of regurgitating indigestible matter in the form of pellets. This study aimed to investigate the ingestion of plastics by live seabirds through the examination of regurgitated pellets (n=92) from a Great Cormorant (Phalacrocorax carbo) breeding colony and a winter roost in Ireland. Plastic prevalence was consistently 3.2% at both sites. The presence of plastic litter highlights the fact that all species of seabird are susceptible to interact with marine litter regardless of feeding habits, although at different rates. More research is needed to understand the driving factors involved in plastic ingestion among different species.

Parasympathetic control of the heart. I. An interventriculo-septal ganglion is the major source of the vagal intracardiac innervation of the ventricles.

The locations, projections, and functions of the intracardiac ganglia are incompletely understood. Immunocytochemical labeling with the general neuronal marker protein gene product 9.5 (PGP 9.5) was used to determine the distribution of intracardiac neurons throughout the cat atria and ventricles. Fluorescence microscopy was used to determine the number of neurons within these ganglia. There are eight regions of the cat heart that contain intracardiac ganglia. The numbers of neurons found within these intracardiac ganglia vary dramatically. The total number of neurons found in the heart (6,274 +/- 1,061) is almost evenly divided between the atria and the ventricles. The largest ganglion is found in the interventricular septum (IVS). Retrogradely labeled fluorescent tracer studies indicated that the vagal intracardiac innervation of the anterior surface of the right ventricle originates predominantly in the IVS ganglion. A cranioventricular (CV) ganglion was retrogradely labeled from the anterior surface of the left ventricle but not from the anterior surface of the right ventricle. These new neuroanatomic data support the prior physiological hypothesis that the CV ganglion in the cat exerts a negative inotropic effect on the left ventricle. A total of three separate intracardiac ganglia innervate the left ventricle, i.e., the CV, IVS, and a second left ventricular (LV2) ganglion. However, the IVS ganglion provides the major source of innervation to both the left and right ventricles. This dual innervation pattern may help to coordinate or segregate vagal effects on left and right ventricular performance.

Parasympathetic control of the heart. III. Neuropeptide Y-immunoreactive nerve terminals synapse on three populations of negative chronotropic vagal preganglionic neurons.

The vagal postganglionic control of cardiac rate is mediated by two intracardiac ganglia, i.e., the sinoatrial (SA) and posterior atrial (PA) ganglia. Nothing is known about the vagal preganglionic neurons (VPNs) that innervate the PA ganglion or about the neurochemical anatomy of central afferents that innervate these VPNs. These issues were examined using light microscopic retrograde labeling methods and dual-labeling electron microscopic histochemical and immunocytochemical methods. VPNs projecting to the PA ganglion are found in a narrow column exclusively in the ventrolateral nucleus ambiguus (NA-VL). These neurons are relatively large (37.6 +/- 2.7 microm by 21.3 +/- 3.4 microm) with abundant cytoplasm and intracellular organelles, rare somatic and dendritic spines, round uninvaginated nuclei, and myelinated axons. Previous physiological data indicated that microinjections of neuropeptide Y (NPY) into the NA-VL cause negative chronotropic effects. The present morphological data demonstrate that NPY-immunoreactive nerve terminals formed 18 +/- 4% of the axodendritic or axosomatic synapses and close appositions on VPNs projecting to the PA ganglion. Three approximately equal populations of VPNs in the NA-VL were retrogradely labeled from the SA and PA ganglia. One population each projects to the SA ganglion, the PA ganglion, or to both the SA and PA ganglia. Therefore, there are both shared and independent pathways involved in the vagal preganglionic controls of cardiac rate. These data are consistent with the hypothesis that the central and peripheral parasympathetic controls of cardiac rate are coordinated by multiple potentially redundant and/or interacting pathways and mechanisms.

Salt intake by normotensive and spontaneously hypertensive rats: two-bottle and lick rate analyses.

Spontaneously hypertensive rats (SHR) overconsume NaCl compared to the normotensive Wistar Kyoto rat (WKY) rat. In the present experiment, two-bottle preference for NaCl (0.01, 0.03, 0.1, 0.3, 0.5, 1.0, 3.0 M) and lick rate analyses were used to identify the possible mechanisms that underlie the intake of NaCl by male SHR. Two-bottle preference and absolute NaCl intake by SHR were greater than that of WKY rats. When NaCl intake was calculated on the basis of body weight, SHR consumed more NaCl per 100 g body weight than did WKY. Also, during the one-bottle test, SHR consumed more 0.1 and 0.3 M NaCl per 100 g body weight than did WKY. The increased intake of NaCl by SHR was most evident for 0.3 M NaCl. Intake is determined by the initial rate of licking and the decline in lick rate over time. Nonlinear regression analysis of lick rate showed that the initial lick rates (licks/min) were similar for male WKY and SHR. Lick rate declined more rapidly when WKY rats drank 0.3 M than when they drank 0.1 M NaCl, a result consistent with the role of negative feedback in controlling the decay in lick rate. This concentration-dependent change in lick rate was not seen in SHR. Also, SHR lick rate for 0.1 and 0.3 M NaCl decelerated more slowly than that of WKY rats. The increased intake of hypertonic NaCl by SHR was due to a decrease in the decline in lick rate, suggesting that SHR are less responsive to ingestion-contingent negative feedback.

Chemical penetration enhancers.

Chemical penetration enhancers are utilized in topical preparations as a method for enhancing permeation of drugs across the skin. In particular, they are utilized for transdermal delivery of medications in an attempt to produce a systemic response, to avoid first-pass metabolism, and to decrease the gastrointestinal transit time observed with oral medications. A review of the selection of chemical penetration enhancers, their mechanism of action, the most common chemical penetration enhancers in each class, and alternatives will be discussed in detail.