Optimization of whispering gallery resonator design for biosensing applications.

Whispering gallery modes (WGMs) within microsphere cavities enable highly sensitive label-free detection of changes in the surrounding refractive index. This detection modality is of particular interest for biosensing applications. However, the majority of biosensing work utilizing WGMs to date has been conducted with resonators made from either silica or polystyrene, while other materials remain largely uninvestigated. By considering characteristics such as the quality factor and sensitivity of the resonator, the optimal WGM sensor design can be identified for various applications. This work explores the choice of resonator refractive index and size to provide design guidelines for undertaking refractive index biosensing using WGMs.

Identification of translational dermatology research priorities in the U.K.: results of an electronic Delphi exercise.

BACKGROUND: Translational research is the direct application of basic and applied research to patient care. It is estimated that there are at least 2000 different skin diseases; thus, there are considerable challenges in seeking to undertake research on each of these disorders. OBJECTIVES: This electronic Delphi (e-Delphi) exercise was conducted in order to generate a list of translational dermatology research questions that are regarded as a priority for further investigations. METHODS: During the first phase of the e-Delphi exercise, 228 research questions were generated by an expert panel that included clinical academic dermatologists, clinical dermatologists, nonclinical scientists, dermatology trainees and representatives from patient support groups. RESULTS: Following completion of the second and third phases, 40 questions on inflammatory skin disease, 20 questions on structural skin disorders/genodermatoses, 37 questions on skin cancer and eight miscellaneous questions were designated as priority translational dermatology research questions (PRQs). In addition to PRQs on a variety of disease areas (including multiple PRQs on psoriasis, eczema, squamous cell carcinoma and melanoma), there were a number of cross-cutting themes that identified a need to investigate mechanisms/pathogenesis of disease and the necessity to improve treatments for patients with skin disease. CONCLUSIONS: It is predicted that this list of PRQs will help to provide a strategic direction for translational dermatology research in the U.K. and that addressing this list of questions will ultimately provide clinical benefit for substantial numbers of patients with skin disorders.

Clinical guidelines on hyperlipidaemia: recent developments, future challenges and the need for an Australian review.

Large reductions in cardiovascular disease (CVD) mortality have been achieved over the last 50 years in developed countries. The health policies that have contributed so much to this success have largely been coordinated by means of expert guidelines for the management of the classic modifiable risk factors such as blood pressure, diabetes and blood lipids. National and international guidelines for lipid management have demonstrated a high degree of consistency between numerous sets of recommendations. It has been argued that some important components of the consensus that has been established over the past decade have been challenged by the latest guidelines of the American Heart Association - American College of Cardiologists (AHA-ACC). Clinicians can be reassured that continued reliance on extensive scientific evidence has reaffirmed the importance of lipid metabolism as a modifiable risk factor for atherosclerotic cardiovascular disease. On the other hand, the recent AHA-ACC guidelines suggest changes in the strategies by which metabolic risk factors may be modified. This small number of important changes should not be sensationalised because these differences usefully reflect the need for guidelines to evolve to accommodate different contexts and changing perspectives as well as emerging issues and new information for which clinical trial evidence is incomplete. This article will consider the recent policies and responses of national and supranational organisations on topics including components of CVD risk assessment, sources of CVD risk information and re-appraisal of lipid-lowering interventions. Timely review of Australian lipid management guidelines will require consideration of these issues because they are creating a new context within which new guidelines must evolve.

Computed tomographic angiography measures of coronary plaque in clinical trials: opportunities and considerations to accelerate drug translation.

Atherosclerotic coronary artery disease (CAD) is the causal pathological process driving most major adverse cardiovascular events (MACE) worldwide. The complex development of atherosclerosis manifests as intimal plaque which occurs in the presence or absence of traditional risk factors. There are numerous effective medications for modifying CAD but new pharmacologic therapies require increasingly large and expensive cardiovascular outcome trials to assess their potential impact on MACE and to obtain regulatory approval. For many disease areas, nearly a half of drugs are approved by the U.S. Food & Drug Administration based on beneficial effects on surrogate endpoints. For cardiovascular disease, only low-density lipoprotein cholesterol and blood pressure are approved as surrogates for cardiovascular disease. Valid surrogates of CAD are urgently needed to facilitate robust evaluation of novel, beneficial treatments and inspire investment. Fortunately, advances in non-invasive imaging offer new opportunity for accelerating CAD drug development. Coronary computed tomography angiography (CCTA) is the most advanced candidate, with the ability to measure accurately and reproducibly characterize the underlying causal disease itself. Indeed, favourable changes in plaque burden have been shown to be associated with improved outcomes, and CCTA may have a unique role as an effective surrogate endpoint for therapies that are designed to improve CAD outcomes. CCTA also has the potential to de-risk clinical endpoint-based trials both financially and by enrichment of participants at higher likelihood of MACE. Furthermore, total non-calcified, and high-risk plaque volume, and their change over time, provide a causally linked measure of coronary artery disease which is inextricably linked to MACE, and represents a robust surrogate imaging biomarker with potential to be endorsed by regulatory authorities. Global consensus on specific imaging endpoints and protocols for optimal clinical trial design is essential as we work towards a rigorous, sustainable and staged pathway for new CAD therapies.

Public attitudes towards genomic risk profiling as a component of routine population screening.

Including low penetrance genomic variants in population-based screening might enable personalization of screening intensity and follow up. The application of genomics in this way requires formal evaluation. Even if clinically beneficial, uptake would still depend on the attitudes of target populations. We developed a deliberative workshop on two hypothetical applications (in colorectal cancer and newborn screening) in which we applied stepped, neutrally-framed, information sets. Data were collected using nonparticipant observation, free-text comments by individual participants, and a structured survey. Qualitative data were transcribed and analyzed using thematic content analysis. Eight workshops were conducted with 170 individuals (120 colorectal cancer screening and 50 newborn screening for type 1 diabetes). The use of information sets promoted informed deliberation. In both contexts, attitudes appeared to be heavily informed by assessments of the likely validity of the test results and its personal and health care utility. Perceived benefits included the potential for early intervention, prevention, and closer monitoring while concerns related to costs, education needs regarding the probabilistic nature of risk, the potential for worry, and control of access to personal genomic information. Differences between the colorectal cancer and newborn screening groups appeared to reflect different assessments of potential personal utility, particularly regarding prevention.

An analysis of specific batting demands in the women's The Hundred competition.

Background: No research has investigated the shortest format of the game of cricket, The Hundred competition. Furthermore, women's cricket research is particularly limited, with most focusing on injuries and little literature investigating specific batting demands. These demands are important if training programmes are to mimic the game's movement patterns. Objectives: The purpose of this study was to analyse specific batting demands and variables associated with the women's The Hundred competition. Methods: Thirty-one matches from the Women's 2021 The Hundred competition were analysed using Hudl Sportscode Elite. Variables analysed included: bowler type (seam or spin), free hits, no ball runs, reason for no ball (height/wide/front foot), run scored (0, 1, 2, 3, 4, 6), type of key event (fall of wicket, bowling referral, batting referral, umpire referral, bowling time out, rain delay, or injury) as well as time between deliveries and sets, overall and between the power play and non-power play. A total of 6073 deliveries were analysed. Results: A significant difference (p<0.05) was observed for time between deliveries for spin bowlers (26.90±22.16 s) compared to seam bowlers(31.70±20.37 s) as well as time between sets for the power play (58.00±13.28 s) and non-power play phases (63.70±42.00 s). Additionally, in the power play, most runs were made up of "1's" and "4's". In the non-power play phase, "1's" made up the biggest contribution of runs (as a percentage). Conclusion: The fact that singles make up a significant portion of a typical match means that strength and conditioning coaches should incorporate high-intensity sprint-type training into training programmes to mimic these demands.

The role of selected pre-match covariates on the outcome of One-day International (ODI) cricket matches.

Background: The identification of key factors that systematically influence a team's success is important and has led to the application of statistical models in sport. Predicting the outcome of a One Day International (ODI) cricket match, using only pre-match covariates, has been minimally investigated. Objectives: This research sought to investigate the impact that venue, toss outcome, toss decision, and match type have on the chances of winning an ODI match. Methods: A total of 1228 men's international ODI matches were analysed. A logistic regression model was used to identify the significance of these pre-match covariates on the result of the matches. Results: The results varied across all teams, suggesting that there are individualised factors driving these differences and that generalising the impact pre-match covariates have in every team is unrealistic. New Zealand and India displayed a significant home advantage effect, whereas Australia had a strong tendency towards a significant disadvantage when they won the toss. However, for most teams, toss outcome, toss decision, and match type did not significantly impact the outcome of an ODI match. Conclusion: New Zealand and Australia were the most predictable teams, whereas South Africa and Pakistan were regarded as unpredictable when pre-match covariates were used to forecast the outcome of their ODI matches.

Comparison of the effects of different statins and doses on lipid levels in patients with diabetes: results from VOYAGER.

BACKGROUND AND AIMS: Diabetes mellitus is a well-known risk factor for cardiovascular disease, and brings an increased risk of vascular events and a higher mortality rate. Treatment guidelines recommend statins in patients with diabetes, with low-density lipoprotein cholesterol (LDL-C) targets of 100 mg dl(-1) (∼2.5 mmol l(-1)), and 80 (∼2.0 mmol l(-1)) or 70 mg dl(-1) (∼1.8 mmol l(-1)) in especially high-risk patients. The current study used the VOYAGER (an indiVidual patient data-meta-analysis Of statin therapY in At risk Groups: Effects of Rosuvastatin, atorvastatin, and simvastatin) database to characterise effects of rosuvastatin, atorvastatin and simvastatin in different doses on lipid levels in diabetes patients. METHODS AND RESULTS: The VOYAGER database included individual patient data from 37 studies involving comparisons of rosuvastatin with either atorvastatin or simvastatin. Of the 32 258 patients included, 8859 (27.5%) had diabetes. Rosuvastatin appeared to be the most efficacious of the three statins, both for lowering LDL-C and for reaching a target level of <70 mg dl(-1) for LDL-C. It was also more effective than atorvastatin at raising high-density lipoprotein cholesterol in the diabetes population. These results are consistent with the overall VOYAGER results. CONCLUSIONS: This meta-analysis of 8859 patients with diabetes mellitus shows favourable effects on lipids with the three statins studied, in line with results for the overall VOYAGER population. The importance of using an effective statin at an effective dose to reach treatment goals for such high-risk patients is evident.

An activated protein kinase C alpha gives a differentiation signal for hematopoietic progenitor cells and mimicks macrophage colony-stimulating factor-stimulated signaling events.

Highly enriched, bipotent, hematopoietic granulocyte macrophage colony-forming cells (GM-CFC) require cytokines for their survival, proliferation, and development. GM-CFC will form neutrophils in the presence of the cytokines stem cell factor and granulocyte colony-stimulating factor, whereas macrophage colony-stimulating factor leads to macrophage formation. Previously, we have shown that the commitment to the macrophage lineage is associated with lipid hydrolysis and translocation of protein kinase C alpha (PKCalpha) to the nucleus. Here we have transfected freshly prepared GM-CFC with a constitutively activated form of PKCalpha, namely PKAC, in which the regulatory domain has been truncated. Greater than 95% of the transfected cells showed over a twofold increase in PKCalpha expression with the protein being located primarily within the nucleus. The expression of PKAC caused macrophage development even in the presence of stimuli that normally promote only neutrophilic development. Thus, M-CSF-stimulated translocation of PKCalpha to the nucleus is a signal associated with macrophage development in primary mammalian hematopoietic progenitor cells, and this signal can be mimicked by ectopic PKAC, which is also expressed in the nucleus.

Cytokine-mediated protein kinase C activation is a signal for lineage determination in bipotential granulocyte macrophage colony-forming cells.

Granulocyte macrophage colony-forming cells (GM-CFC) have the potential to develop into either macrophages and/or neutrophils. With a highly enriched population of these cells we have found that although GM-CFC are equally responsive to macrophage colony stimulating factor (M-CSF) and stem cell factor (SCF) in terms of DNA synthesis, M-CSF stimulated the development of colonies containing macrophages in soft gel assays, while SCF promoted neutrophilic colony formation. When SCF and M-CSF were combined, mainly macrophage development was stimulated both in soft agar colony-forming assays and liquid cultures. An analysis of some potential signaling mechanisms associated with cytokine-mediated developmental decisions in GM-CFC revealed that M-CSF, but not SCF, was able to chronically stimulate phosphatidylcholine breakdown and diacylglycerol production, indicating that protein kinase C (PKC) may be involved in the action of M-CSF. Furthermore, M-CSF, but not SCF, can increase the levels of PKC alpha (PKC alpha) expression and stimulate the translocation of PKC alpha to the nucleus. When the PKC inhibitor, calphostin C, was added to GM-CFC cultured in M-CSF then predominantly neutrophils were produced, conversely PKC activators added with SCF stimulated macrophage development. The data indicate a role for PKC in M-CSF-stimulated macrophage development from GM-CFC.

A survey of the quality and accuracy of information leaflets about skin cancer and sun-protective behaviour available from UK general practices and community pharmacies.

BACKGROUND: Better information promotes sun protection behaviour and is associated with earlier presentation and survival for malignant melanoma. Aim To assess the quality of patient information leaflets about skin cancer and sun-protective behaviour available from general practices and community pharmacies. DESIGN OF STUDY: A structured review of patient information leaflets. Setting All community pharmacies and general practices in one Primary Care Trust were invited to supply leaflets. METHODS: Readability was assessed using the SMOG scoring system. Presentation and content were reviewed using the Ensuring Quality Information for Patients (EQIP) guidelines. Three consultant dermatologists assessed each leaflet for accuracy. RESULTS: Thirty-one different patient information leaflets were returned. Thirteen (42%) were published in the previous 2 years, but 10 (32%) were over 5 years old. Nine (29%) leaflets were produced by the NHS or Health Education Authority, and 8 (27%) were linked to a commercial organization. One leaflet had readability in the primary education range (SMOG score = 6), and none with the recommended range for health education material (SMOG score < or = 5). Two leaflets (6%) were in the highest quartile of EQIP score for presentation and content. Five leaflets (17%) had a major inaccuracy such as over-reliance on sun screen products instead of shade and clothing. CONCLUSIONS: Leaflets were of variable quality in presentation and content. All required a reading age higher than recommended. All leaflets with major inaccuracies had links with commercial organizations. This study raises important issues about the potential conflict between marketing and health messages in the way sun creams are promoted.

Sources of nitrogen dioxide (NO2) in New Zealand homes: findings from a community randomized controlled trial of heater substitutions.

UNLABELLED: Houses in New Zealand have inadequate space heating and a third of households use unflued gas heaters. As part of a large community intervention trial to improve space heating, we replaced ineffective heaters with more effective, non-polluting heaters. This paper assesses the contribution of heating and household factors to indoor NO2 in almost 350 homes and reports on the reduction in NO2 levels due to heater replacement. Homes using unflued gas heaters had more than three times the level of NO2 in living rooms [geometric mean ratio (GMR) = 3.35, 95% CI: 2.83-3.96, P < 0.001] than homes without unflued gas heaters, whereas homes using gas stove-tops had significantly elevated living room NO2 levels (GMR = 1.42, 95% CI: 1.05-1.93, P = 0.02). Homes with heat pumps, flued gas heating, or enclosed wood burners had significantly lower levels of NO2 in living areas and bedrooms. In homes that used unflued gas heaters as their main form of heating at baseline, the intervention was associated with a two-third (67%) reduction in NO2 levels in living rooms, when compared with homes that continued to use unflued gas heaters. Reducing the use of unflued gas heating would substantially lower NO2 exposure in New Zealand homes. PRACTICAL IMPLICATIONS: Understanding the factors influencing indoor NO2 levels is critical for the assessment and control of indoor air pollution. This study found that homes that used unflued gas combustion appliances for heating and cooking had higher NO2 levels compared with homes where other fuels were used. These findings require institutional incentives to increase the use of more effective, less polluting fuels, particularly in the home environment.

Structural diversity of the major surface antigen of Plasmodium falciparum merozoites.

The structures of the major merozoite surface antigen of Plasmodium falciparum and the gene encoding it were indistinguishable for the Wellcome strain and the Thai clone T9/94 but different for clones T9/96, T9/98, and T9/101. The central portion of the gene is subject to the greatest variation in structure. The protein from all five lines was found to be posttranslationally modified by covalent addition of both carbohydrate and fatty acid.

Population exposure to hazardous air quality due to the 2015 fires in Equatorial Asia.

Vegetation and peatland fires cause poor air quality and thousands of premature deaths across densely populated regions in Equatorial Asia. Strong El-Niño and positive Indian Ocean Dipole conditions are associated with an increase in the frequency and intensity of wildfires in Indonesia and Borneo, enhancing population exposure to hazardous concentrations of smoke and air pollutants. Here we investigate the impact on air quality and population exposure of wildfires in Equatorial Asia during Fall 2015, which were the largest over the past two decades. We performed high-resolution simulations using the Weather Research and Forecasting model with Chemistry based on a new fire emission product. The model captures the spatio-temporal variability of extreme pollution episodes relative to space- and ground-based observations and allows for identification of pollution sources and transport over Equatorial Asia. We calculate that high particulate matter concentrations from fires during Fall 2015 were responsible for persistent exposure of 69 million people to unhealthy air quality conditions. Short-term exposure to this pollution may have caused 11,880 (6,153-17,270) excess mortalities. Results from this research provide decision-relevant information to policy makers regarding the impact of land use changes and human driven deforestation on fire frequency and population exposure to degraded air quality.

Therapeutic monitoring of continuous infusion etoposide in small-cell lung cancer.

PURPOSE: To investigate the feasibility of therapeutic monitoring of etoposide at different plasma concentrations of the drug, and the resulting pharmacodynamic effects of such an approach. PATIENTS AND METHODS: Forty-nine previously untreated small-cell lung cancer (SCLC) patients received single-agent etoposide every 3 weeks by continuous infusion over 5 days. Plasma etoposide concentrations were monitored 18 and 66 hours into the infusion to permit dose modification. The first cohort of 15 patients began treatment with etoposide 2 micrograms/mL, with dose escalation to 3 micrograms/mL for cycles 3 and 4 and 4 micrograms/mL for cycles 5 and 6, toxicity permitting. The second cohort of 34 patients commenced at 3 micrograms/mL, with dose escalation to 4 and 5 micrograms/mL on cycles 3 and 5, respectively. RESULTS: Mean plasma etoposide concentration during the first treatment cycle was 93.4% +/- 26.6% of the target level at 18 hours (57% of patients within +/- 20% of the target) and 98.9% +/- 14.5% of the target level at 66 hours (82% of patients within +/- 20%). Hematologic toxicity was more pronounced in those treated with 3 micrograms/mL versus 2 micrograms/mL (median nadir neutrophil count, 1.3 v 2.6 x 10(9)/L, P = .032). Tumor responses, typically documented by the third cycle, were similar in each cohort (71% in patients commenced at 2 micrograms/mL and 70% at 3 micrograms/mL). Treatment cohort was not independently predictive of survival. CONCLUSION: Therapeutic monitoring of infusional etoposide is feasible and dramatically reduces interpatient pharmacokinetic variability. Although this was a small nonrandomized trial, the observation of different hematologic toxicity at the two starting concentrations but similar antitumor activity further suggests that these effects may be associated with different plasma etoposide concentrations.

Combinations of colony-stimulating factors promote enhanced proliferative potential in enriched granulocyte-macrophage colony-forming cells.

The effects of combinations of colony-stimulating factors (CSFs) have been assessed using a highly enriched population of murine granulocyte-macrophage colony-forming cells (GM-CFC). Unlike the situation observed with more primitive myeloid progenitor cells, little or no effect on the numbers of colonies formed from GM-CFC in response to specific combinations of growth factors was observed; however, the size of the majority of colonies formed was greatly increased. The largest increase in the number of cells per colony was observed when interleukin-3 (IL-3) was present with either granulocyte-macrophage colony-stimulating factor (GM-CSF), GM-CSF plus granulocyte-colony-stimulating factor (G-CSF), or macrophage colony-stimulating factor (M-CSF); there was a > five-fold increase when compared to colony size in the presence of IL-3 alone. The combination of G-CSF with IL-3 was not able to promote an increase in mean colony size; however, G-CSF plus GM-CSF did give a significant increase. Where combinations of hematopoietic growth factors led to increased numbers of cells per colony, the delayed addition of one of the cytokines to soft gel assays for a period > 2 days led to a loss of the observed enhancement in the number of cells per colony. In cultures of progenitor cells enriched by centrifugal elutriation and that contained combinations of CSFs, there was an increase in the number of GM-CFC over a 2-day incubation period. The distinct effects observed with GM-CSF, IL-3, and G-CSF on GM-CFC suggest that they influence different molecular signaling mechanisms within common target progenitor cells.

Flt3 ligand can promote survival and macrophage development without proliferation in myeloid progenitor cells.

Flt3 ligand elicits a variety of effects on early hemopoietic progenitors by occupying its cognate receptor, Flt3, a member of the type III tyrosine kinase receptor family. The cytokines macrophage colony-stimulating factor (M-CSF) and stem cell factor (SCF) bind to related members of this tyrosine kinase receptors family, c-fms and c-kit, respectively. The relative effects of the cytokines M-CSF, SCF, and Flt3L on the proliferation and development of the late myeloid progenitors granulocyte-macrophage colony-forming cells (GM-CFC) were investigated. Distinct biologic responses were stimulated by ligand binding to these different tyrosine kinase receptors in enriched GM-CFC. M-CSF stimulated GM-CFC to proliferate and develop into macrophages. SCF, on the other hand, stimulated GM-CFC to develop into neutrophils. Flt3 ligand had a relatively small proliferative effect on enriched GM-CFC compared to SCF and M-CSF and had no ability to either stimulate colony formation or synergize with these two cytokines in promoting DNA synthesis, colony formation, or expansion in liquid culture. Flt3 ligand, however, was capable of maintaining the clonogenic potential of GM-CFC and acted as an anti-apoptotic agent as assessed using the Annexin-V apoptosis assay. GM-CFC cultured in Flt3 ligand eventually formed macrophages and neutrophils in liquid culture. Labeling with the membrane-associated cell tracker dye PKH26 indicated that the majority of the enriched GM-CFC responded to Flt3 ligand by undergoing limited proliferation and macrophage development, whereas other cells survived but did not proliferate and differentiate into macrophages. Thus, Flt3 ligand promoted survival and stimulated development without proliferation in primary-enriched myeloid progenitor cells.

Parents' evaluation of the IDEFICS intervention: an analysis focussing on socio-economic factors, child's weight status and intervention exposure.

INTRODUCTION: From April 2008 to August 2010 the Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS (IDEFICS) intervention aimed to encourage healthier diets, higher physical activity levels and lower stress levels among European children and their families. While the intervention was intended to improve children's health, we also wished to assess whether there were unwelcome aspects or negative side-effects. Therefore all parents of children who participated in the IDEFICS intervention were asked for their views on different aspects of the intervention. METHODS: A total of 10,016 parents of children who participated in the IDEFICS survey and who were involved in the intervention were invited to complete a questionnaire on positive and negative impacts of the intervention. Responses to each of the statements were coded on a four point Likert-type scale. Demographic data were collected as part of the baseline (T0 ) and first follow-up (T1 ) surveys; intervention exposure data was also collected in the T1 follow-up survey. Anthropometric data was collected in the same surveys, and child's weight status was assessed according to Cole and Lobstein. After initial review of the univariate statistics multilevel logistic regression was conducted to analyse the influence of socio-economic factors, child's weight status and intervention exposure on parental responses. RESULTS: In total 4,997 responses were received. Approval rates were high, and few parents reported negative effects. Parents who reported higher levels of exposure to the intervention were more likely to approve of it and were also no more likely to notice negative aspects. Less-educated and lower income parents were more likely to report that the intervention would make a lasting positive difference, but also more likely to report that the intervention had had negative effects. Parents of overweight and obese children were more likely to report negative effects - above all, that 'the intervention had made their child feel as if he/she was "fat" or "overweight." ' CONCLUSION: While the results represent a broad endorsement of the IDEFICS intervention, they also suggest the importance of vigilance concerning the psychological effects of obesity interventions on overweight and obese children.

Measurement of intracorneal cohesion in man using in vivo techniques.

Measurement of intracorneal cohesion in vivo should provide quantitative information concerning the process of esquamation. In this investigation three techniques have been employed to measure the internal binding forces within the stratum corneum in vivo. The first technique, cohesography, directly measures the force required to remove stratum corneum of partial thickness from a known area of skin. Sex and site differences were detected using this method. A second technique employs a surfometer to measure the surface contours of the internal face of skin surface biopsies. Quantitative assessment of surfometer tracings reflects both internal structure of stratum corneum and its cohesive property. Positive correlations were found using these two techniques on the forearms of 16 normal subjects. A scrub technique has also been used which can deliver a controllable and measurable stimulus to the skin surface to release corneocytes. Counting the number of corneocytes released provides a further measure of internal cohesion of the stratum corneum but the results did not correlate with the other two techniques. It is suggested that the use of all three techniques might provide a profile of the cohesive property of the stratum corneum.