Patent Ductus Arteriosus and Lung Magnetic Resonance Imaging Phenotype in Moderate and Severe Bronchopulmonary Dysplasia-Pulmonary Hypertension.

Rationale: Hemodynamically significant patent ductus arteriosus (hsPDA) in premature infants has been associated with bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH). However, these associations remain incompletely understood. Objectives: To assess the associations between hsPDA duration and clinical outcomes, PH, and phenotypic differences on lung magnetic resonance imaging (MRI). Methods: In this retrospective cohort study, we identified all infants with BPD at <32 weeks' gestation who also underwent research lung MRI at <48 weeks' postmenstrual age (PMA) from 2014 to 2022. Clinical echocardiograms were reviewed for hsPDA and categorized as no hsPDA, hsPDA 1-60 days, and hsPDA >60 days. Outcome variables included BPD severity, PH at 36 weeks' PMA, PH after 36 weeks' PMA in the absence of shunt (PH-pulmonary vascular disease [PVD]), tracheostomy or death, and lung phenotype by MRI via modified Ochiai score, indexed total lung volume, and whole-lung hyperdensity. Logistic regression and ANOVA were used. Measurements and Main Results: In total, 133 infants born at 26.2 ± 1.9 weeks, weighing 776 ± 276 g, were reviewed (47 with no hsPDA, 44 with hsPDA 1-60 days, and 42 with hsPDA >60 d). hsPDA duration > 60 days was associated with BPD severity (P < 0.01), PH at 36 weeks' PMA (adjusted odds ratio [aOR], 9.7 [95% confidence interval (CI), 3.3-28.4]), PH-PVD (aOR, 6.5 [95% CI, 2.3-18.3]), and tracheostomy or death (aOR, 3.0 [95% CI, 1.0-8.8]). Duration of hsPDA > 60 days was associated with higher Ochiai score (P = 0.03) and indexed total lung volume (P = 0.01) but not whole-lung hyperdensity (P = 0.91). Conclusions: In infants with moderate or severe BPD, prolonged exposure to hsPDA is associated with BPD severity, PH-PVD, and increased parenchymal lung disease by MRI.

Variation of Mid shaft Antero-posterior and Transverse Diameter of Femur in Bangladeshi People.

Femoral morphometric variation is a dynamic system for different region, which is influenced by geographical, physiological and environmental factors, due to the adaptation, functional and remodeling responses of bones. This descriptive cross-sectional study was conducted on 150 (64 right and 86 left) fully ossified dry human femur of Bangladeshi people to find out the variation of mid shaft antero-posterior and transverse diameter of femur. Sample was collected in the Department of Anatomy, Mymensingh Medical College (MMC), Bangladesh from January 2019 to December 2019. All samples were assessed to eliminate fractured, pathologically damaged and remodeled bones. The diameters were measured with the help of digital Vernier slide calipers. The mean±SD mid shaft antero-posterior diameter of right and left femur were 25.03±2.86 mm and 25.54±2.65mm respectively. The mean±SD transverse diameter of right and left femur was 24.24±2.43mm and 24.54±2.38mm respectively. The knowledge of variations in the parameters of dry femora will help the orthopedicians for the treatment and management of femoral shaft fracture. These data also provide information about mid shaft diameter of femur of Bangladeshi people and to compare these data to those from various other races. Thus it could contribute for the design of well-fitting prosthesis which suits the Bangladeshi population. This value may be considered while making a best-fit femoral prosthesis.

Favourable Tolerability and Drug Survival of Tioguanine Versus Methotrexate After Failure of Conventional Thiopurines in Crohn's Disease.

BACKGROUND AND AIMS: Both methotrexate and tioguanine can be considered as treatment options in patients with Crohn's disease after failure of conventional thiopurines. This study aimed to compare tolerability and drug survival of methotrexate and tioguanine therapy after failure of conventional thiopurines in patients with Crohn's disease. METHODS: We conducted a retrospective, multicentre study, including patients with Crohn's disease initiating monotherapy methotrexate or tioguanine after failure [all causes] of conventional thiopurines. Follow-up duration was 104 weeks or until treatment discontinuation. The primary outcome was cumulative therapy discontinuation incidence due to adverse events. Secondary outcomes included total number of [serious] adverse events, and ongoing monotherapy. RESULTS: In total, 219 patients starting either methotrexate [n = 105] or tioguanine [n = 114] were included. In all 65 [29.7%] patients (methotrexate 43.8% [46/105 people], tioguanine 16.7% [19/114 people], p <0.001) discontinued their treatment due to adverse events during follow-up. Median time until discontinuation due to adverse events was 16 weeks (interquartile range [IQR] 7-38, p = 0.812). Serious adverse events were not significantly different. Patients treated with methotrexate experienced adverse events more often [methotrexate 83%, tioguanine 46%, p <0.001]. Total monotherapy drug survival after 104 weeks was 22% for methotrexate and 46% for tioguanine [p <0.001]. CONCLUSIONS: We observed a higher cumulative discontinuation incidence due to adverse events for methotrexate [44%] compared with tioguanine [17%] in Crohn's disease patients after failure of conventional thiopurines. The total adverse events incidence during methotrexate use was higher, whereas serious adverse events incidence was similar. These favourable results for tioguanine treatment may guide the selection of immunosuppressive therapy after failure of conventional thiopurines.

Correlates of a caregiver-reported child sleep problem and variation by community disadvantage.

BACKGROUND: Previous studies of sleep patterns and perceived problems in early childhood indicate variation by family socioeconomic status. The purpose of this study was to examine variation in correlates of a caregiver-perceived child sleep problem across and within levels of community disadvantage in a large US sample. METHODS: Caregivers of 14,980 young children (ages 0-35.9 months) in the US completed the Brief Infant Sleep Questionnaire-Revised (BISQ-R) on the freely and publicly available Johnson's® Bedtime® Baby Sleep App. Zip code was used to identify a Distressed Communities Index (DCI) score, which represents community disadvantage based on neighborhood indicators. RESULTS: Across all levels of community disadvantage, caregivers who reported greater impact of child sleep on their own sleep, bedtime difficulty, more frequent and longer night wakings, and increased total nighttime sleep were more likely to endorse a child sleep problem. These associations varied by level of community disadvantage. For caregivers living in more disadvantaged communities, impact of child sleep on their own sleep and night wakings were the strongest correlates of endorsing a child sleep problem, whereas for those in more advantaged communities the impact of child sleep on their own sleep and night wakings as well as additional aspects of sleep health, such as short sleep duration, were associated with endorsement of a child sleep problem. CONCLUSIONS: Findings suggest that families living in more distressed communities are most likely to identify the impact of child sleep on their own sleep and night wakings in reporting a child sleep problem, whereas those from more prosperous communities consider these factors as well as other sleep parameters, including sleep duration. Clinicians should consider expanding screening questions for child sleep problems to include the perceived impact on caregiver sleep.

Socioeconomic disadvantage and sleep in early childhood: Real-world data from a mobile health application.

OBJECTIVES: To examine whether increased socioeconomic disadvantage, indexed using a measure of community distress, was associated with variation in caregiver-reported early childhood sleep patterns and problems in a large US sample using a mobile health application (app). DESIGN: Cross-sectional. SETTING: Data were collected using the free, publicly available Johnson's Bedtime© baby sleep app. PARTICIPANTS: A total of 14,980 caregivers (85.1% mothers) of children ages 6-35.9 months (M = 13.88 months; 52.6% boys) participated in this study. MEASURES: Caregivers reported on child sleep using the Brief Infant Sleep Questionnaire-Revised. Socioeconomic disadvantage was indexed by zip code using the Distressed Communities Index (DCI), which combines seven US census indicators of socioeconomic disadvantage. DCI scores range from prosperous (lowest quintile) to distressed (highest quintile). RESULTS: Socioeconomic disadvantage was significantly associated with later bedtimes, longer sleep onset latency, and shorter nighttime and 24-hour (total) sleep duration, with children living in distressed communities showing the poorest sleep. However, caregivers living in distressed communities reported a significantly lower prevalence of overall child sleep problems (43% vs 58% in prosperous communities), and more confidence in managing child sleep (42% vs 34% in prosperous communities). CONCLUSIONS: Children living in the most distressed communities have the poorest reported sleep patterns and bedtime behaviors; however, their caregivers are less likely to report problematic child sleep. These findings highlight the need for community-level sleep health promotion interventions, as well as further investigation of caregiver perceptions about child sleep and sleep health promotion among families living in socioeconomically disadvantaged contexts.

A petascale automated imaging pipeline for mapping neuronal circuits with high-throughput transmission electron microscopy.

Electron microscopy (EM) is widely used for studying cellular structure and network connectivity in the brain. We have built a parallel imaging pipeline using transmission electron microscopes that scales this technology, implements 24/7 continuous autonomous imaging, and enables the acquisition of petascale datasets. The suitability of this architecture for large-scale imaging was demonstrated by acquiring a volume of more than 1 mm3 of mouse neocortex, spanning four different visual areas at synaptic resolution, in less than 6 months. Over 26,500 ultrathin tissue sections from the same block were imaged, yielding a dataset of more than 2 petabytes. The combined burst acquisition rate of the pipeline is 3 Gpixel per sec and the net rate is 600 Mpixel per sec with six microscopes running in parallel. This work demonstrates the feasibility of acquiring EM datasets at the scale of cortical microcircuits in multiple brain regions and species.

Effectiveness of an mHealth Intervention for Infant Sleep Disturbances.

Bedtime problems and night wakings are highly prevalent in infants. This study assessed the real-world effectiveness of an mHealth behavioral sleep intervention (Customized Sleep Profile; CSP). Caregivers (83.9% mothers) of 404 infants (age 6 to 11.9 m, M = 8.32 m, 51.2% male) used the CSP (free and publicly available behavioral sleep intervention delivered via smartphone application, Johnson's® Bedtime® Baby Sleep App). Caregivers completed the Brief Infant Sleep Questionnaire-Revised (BISQ-R) at baseline and again 4 to 28 days later. Changes in sleep patterns were analyzed, based on sleep problem status (problem versus no problem sleepers; PS; NPS). Sleep onset latency improved in both groups. Earlier bedtimes, longer continuous stretches of sleep, as well as decreased number and duration of night wakings, were evident in the PS group only. The BISQ-R Total score, total nighttime sleep, and total 24-hour sleep time improved for both groups, with a greater change for the PS group. Further, caregivers of infants in the PS group decreased feeding (bedtime and overnight) and picking up overnight, and perceived better sleep. Bedtime routine regularity, bedtime difficulty, sleep onset difficulty, and caregiver confidence improved for both groups, with the PS group showing a greater magnitude of change. Thus, a real-world, publicly available, mHealth behavioral sleep intervention was associated with improved outcomes for older infants. Intervention recommendations resulted in changes in caregivers' behavior and improvements in caregiver-reported sleep outcomes in infants, in as few as 4 days.

Increased Discontinuation Rates of Anti-TNF Therapy in Elderly Inflammatory Bowel Disease Patients.

BACKGROUND AND AIMS: There is paucity of data on safety and efficacy of anti-tumour necrosis factor [TNF] in elderly inflammatory bowel disease [IBD] patients. We aimed to compare the long-term treatment failure rates and safety of a first anti-TNF agent in IBD patients between different age groups [<40 years/40-59 years/≥60 years]. METHODS: IBD patients who started a first anti-TNF agent were identified through IBDREAM, a multicentre prospective IBD registry. Competing risk regression was used to study treatment failure, defined as time to drug discontinuation due to adverse events [AEs] or lack of effectiveness, with discontinuation due to remission as a competing risk. RESULTS: A total of 895 IBD patients were included; 546 started anti-TNF at age <40 [61.0%], 268 at age 40-59 [29.9%], and 81 at age ≥60 [9.1%]. Treatment failure rate was higher in the two older groups (subhazard rate [SHR] age ≥60 1.46, SHR age 40-59 1.21; p = 0.03). The SHR in the elderly [>60] was 1.52 for discontinuation due to AEs and 1.11 for lack of effectiveness. Concomitant thiopurine use was associated with a lower treatment failure rate (SHR 0.78, 95% confidence interval [CI] 0.62-0.98, p = 0.031). Serious adverse event [SAE] rate, as well as serious infection rate, were significantly higher in elderly IBD patients [61.2 versus 16.0 and 12.4 per 1000 patient-years, respectively] whereas the malignancy rate was low in all age groups. CONCLUSIONS: Elderly IBD patients starting a first anti-TNF agent showed higher treatment failure rates, but concomitant thiopurine use at baseline was associated with lower failure rates. Elderly IBD patients demonstrated higher rates of SAEs and serious infections.

Norm-referenced scoring system for the Brief Infant Sleep Questionnaire - Revised (BISQ-R).

OBJECTIVES: To develop an age-based norm-referenced scoring system for the Brief Infant Sleep Questionnaire - Revised (BISQ-R). METHODS: In sum, 33,835 submissions (data sample 1) of the expanded and revised BISQ-R by caregivers of infants and toddlers (1-36 months) were analyzed in the US via a publicly-available smartphone application, Johnson's® Bedtime®. Three subscales were created: Infant Sleep (IS; 5 items), Parent Perception (PP; 3 items), and Parent Behavior (PB; 11 items). The scoring algorithm was based on an age-based normative system, and each subscale was scored using a weighted average of items. Primary application of the scoring model was performed on a follow up set of 16,531 submissions (data sample 2). Secondary application was tested on an original web-based ecology study (data sample 3). Tertiary application was tested using previously published datasets consisting of a longitudinal study (data sample 4) and randomized control trial behavioral intervention study (data sample 5). RESULTS: Overall application of the scoring algorithm was confirmed across multiple samples. Each subscale (IS, PP, PB) and total score (T) is age referenced (scores range from 0 to 100). Cross-comparison between subscales across studies reveal consistent and convergent relationships. CONCLUSIONS: The BISQ-R provides a comprehensive assessment of infant and toddler sleep patterns, as well as parent perception and parent behaviors that may contribute to sleep outcomes. The age-based norm-referenced scoring system is publicly available to be used by researchers and clinicians.

Measuring Amber Initiator tRNA Orthogonality in a Genomically Recoded Organism.

Using engineered initiator tRNA for precise control of protein translation within cells has great promise within future orthogonal translation systems to decouple housekeeping protein metabolism from that of engineered genetic systems. Previously, E. coli strain C321.ΔA. exp lacking all UAG stop codons was created, freeing this "amber" stop codon for other purposes. An engineered "amber initiator" tRNACUAfMet that activates translation at UAG codons is available, but little is known about this tRNA's orthogonality. Here, we combine for the first time the amber initiator tRNACUAfMet in C321.ΔA. exp and measure its cellular effects. We found that the tRNACUAfMet expression resulted in a nearly 200-fold increase in fluorescent reporter expression with a unimodal population distribution and no apparent cellular fitness defects. Proteomic analysis revealed upregulated ribosome-associated, tRNA degradation, and amino acid biosynthetic proteins, with no evidence for off-target translation initiation. In contrast to previous work, we show that UAG-initiated proteins carry N-terminal methionine, but have no evidence for glutamine. Together, our results identify beneficial features of using the amber initiator tRNACUAfMet to control gene expression while also revealing fundamental challenges to using engineered initiator tRNAs as the basis for orthogonal translation initiation systems.

Caregiver-perceived sleep outcomes in toddlers sleeping in cribs versus beds.

OBJECTIVE: Little is known about whether sleep space impacts toddler sleep outcomes. We examined the prevalence of crib-sleeping and its association with caregiver-reported sleep patterns and problems in a large sample of toddlers from Western countries. METHODS: Participants were caregivers of 1983 toddlers ages 18.0-35.9 months (51.7% male; mean age 25.3 months) from Australia, Canada, New Zealand, the United Kingdom, and the United States sleeping in a crib or bed in a separate room from caregivers. Caregiver-reported sleep patterns and problems were collected via a free, publicly available child sleep smartphone application. RESULTS: Across countries/regions, rates of crib-sleeping decreased linearly with age, with 63.4% of toddlers ages 18.0-23.9 months, 34.3% of toddlers ages 24.0-29.9 months, and 12.6% of toddlers ages 30.0-35.9 months sleeping in a crib. Across age groups and countries, crib sleeping was significantly associated with an earlier bedtime, shorter sleep onset latency, fewer night awakenings, longer stretches of time asleep, increased nighttime sleep duration, and decreased bedtime resistance and sleep problems. The duration of night awakenings did not significantly differ by sleep space. CONCLUSION: Sleeping in a crib instead of a bed is associated with enhanced caregiver-reported sleep quantity and quality for toddlers in Western countries. Consistent with practice recommendations, deferring the crib-to-bed transition until age 3 years may benefit toddlers' sleep in Western contexts. Additional research is needed to identify the impact of sleep space on child sleep in other countries/regions.

A Survey of Practicing Sleep Coaches.

BACKGROUND: Sleep coaches are individuals of various backgrounds who offer services to families struggling with behavioral childhood sleep problems. We conducted a survey of coaches to further elucidate scope of practice, practice patterns, geographic distribution, education, training, and beliefs regarding qualification requirements. METHODS: A Web-based survey was completed by 142 individuals who identified as a sleep coach. RESULTS: Coaches were distributed across 17 countries and 5 continents. Overall, 65% of coaches served clients in countries beyond their home country. Within the United States, coaches were generally located in more affluent and well-educated zip codes near large metropolitan centers, 91% served clients beyond their home state, and 56% served clients internationally. Educational background varied across coaches (12% high school degree, 51% bachelor's degree, 32% master's degree, 2% doctoral degree, 1.5% JD degree). Few coaches (20%) were or had been licensed health care providers or carried malpractice insurance (38%). Coaches usually provided services for children < 4 months of age to about 6 years of age, and were much less likely to provide services for children with comorbid neurodevelopmental (32%) or significant medical disorders (19%). Coaches reported an average of 3 new and 6 total clients per week and working 20 hr per week on average. Most coaches (76%) felt that a formal sleep coach training program was the most important qualification for practice. CONCLUSIONS: These results highlight a diversity of background, training, and geographical distribution of sleep coaches, and may help inform discussions regarding guidelines for training and credentialing of sleep coaches.

Sleep location and parent-perceived sleep outcomes in older infants.

OBJECTIVES: Initial studies indicate more independent and consolidated sleep in the first few months in infants who sleep separately. Little is known, however, about the relationship of sleep location (separate room, room-sharing, bed-sharing) with sleep outcomes in older infants (ages 6-12 months). It was expected that those who sleep in a separate room would have better parent-perceived sleep outcomes and more positive sleep health behaviors. METHODS: Parents of 6236 infants (6-12 months) in the United States (US) and 3798 in an international sample (Australia, Brazil, Canada, Great Britain, and New Zealand) completed a smartphone app-based expanded version of the validated Brief Infant Sleep Questionnaire. RESULTS: A total of 37.2% of the infants in the US and 48.4% in the international sample slept in a separate room. In both samples, infants who slept in a separate room as opposed to room-sharing or bed-sharing had parent-perceived sleep outcomes and sleep-related behaviors that reflected earlier bedtimes, shorter time to fall asleep, more nighttime and total sleep, and increased sleep consolidation. They were also more likely to have a consistent bedtime routine and to fall asleep independently, as well as less likely to feed to sleep at bedtime and during the night. In addition, parents of separate room sleepers perceived bedtime to be less difficult and sleep to be better overall. CONCLUSIONS: Overall, 6- to 12-month-old infants who slept in a separate room had better reported sleep outcomes and fewer parent-perceived disturbances at bedtime than infants who room-shared with their parents, as well compared to those who slept in their parents' bed.

Implementation of a nightly bedtime routine: How quickly do things improve?

BACKGROUND: Institution of a consistent bedtime routine has been demonstrated to improve sleep in young children within two weeks. However, no studies have investigated the rate of this change and when most change occurs. The purpose of this study was to examine the nightly change in infant sleep and maternal perceptions after implementing a bedtime routine. METHODS: Mothers (n=134) and their infant (8-18 months) were randomly assigned to implementation of a bedtime routine intervention for a two-week period. RESULTS: Two-level piecewise linear growth models showed that the intervention resulted in the most rapid change in the first three nights of the intervention across sleep outcomes, including sleep onset latency, the frequency and duration of nighttime awakenings, sleep consolidation, and maternal perceptions of bedtime ease, sleep quality, and infant mood. No significant additional improvement in sleep onset latency emerged after these first three nights, whereas small additional improvements occurred for all other outcomes throughout the remainder of the intervention period. CONCLUSIONS: These results indicate that sleep disturbances in infants and toddlers can be quickly ameliorated within just a few nights after implementation of a consistent bedtime routine, including a bath, massage, and quiet activities. Future research should consider the potential mechanisms behind these relatively fast improvements in sleep, such as reduced household chaos or physiological changes (e.g. core body temperature, cortisol).

Hard water softening effect of a baby cleanser.

BACKGROUND: Hard water is associated with atopic dermatitis (eczema). We wanted to determine if a baby cleanser and its individual components altered free ionized calcium (Ca2+) in a simulated hard water baby bath. For these studies, an in vitro determination of free Ca2+ in a simulated hard water baby bath, and an in vivo exploratory study of free Ca2+ absorption into skin from hard water were performed. METHODS: Free Ca2+ was measured with an ion-sensitive electrode in vitro in hard water (100-500 ppm, Ca2+) before and after addition of the cleanser and/or its components. In an exploratory study, absorption of Ca2+ into skin from hard water was determined in three female participants (aged 21-29 years). RESULTS: At an in-use dilution of 1%, the test cleanser reduced free Ca2+ from ~500 ppm to <200 ppm; a 10% in-use dilution bound virtually all free Ca2+. The anionic surfactant component contributed the most to this effect. In the exploratory in vivo study, we measured a reduction of ~15% in free Ca2+ from simulated hard water over 10 minutes. CONCLUSION: Baby cleansers can bind free Ca2+ and reduce the effective water hardness of bath water. Reducing the amount of free Ca2+ in the water will reduce the availability of the ion for binding to the skin. Altering or reducing free Ca2+ concentrations in bath water may be an important parameter in creating the ideal baby bath.

Development of infant and toddler sleep patterns: real-world data from a mobile application.

The aim of this study was to investigate the development of infant and toddler sleep patterns. Data were collected on 841 children (aged from birth to 36 months) via a free, publicly available, commercially sponsored iPhone app. Analyses were conducted on caregiver recordings of 156 989 sleep sessions across a 19-month period. Detailed visualizations of the development of sleep across the first 3 years of life are presented. In the first 3 months, sleep sessions primarily lasted less than 3.5 h throughout the day. Between 3 and 7 months old, sleep consolidated into two naps of about 1.5 h in length and a night-time sleep session of about 10.5 h. Across age groups, a negative relationship was observed between the start of bedtime and the length of the night-time sleep session (i.e. later bedtime is associated with a shorter night-time sleep period). The length of daytime sleep sessions (naps) varied with age, decreasing between 1 and 5 months old, and then increasing monotonically through 28 months. Morning wake time was observed to be invariant in children aged 5-36 months. Sleep patterns are ever-changing across the first few years with wide individual variability. Sleep patterns start to develop more clearly at 5-6 months, when longer night-time sleep duration begins and sleep consolidation occurs. Daytime sleep patterns appeared to become more consistent and consolidated later in age than night-time sleep. Finally, there is greater variability in bedtimes than wake times, with bedtimes having a greater influence on night-time sleep duration.

Developmental Changes in Skin Barrier and Structure during the First 5 Years of Life.

The structure of the stratum corneum (SC) and the corresponding skin barrier develops from before birth up to about 4 years of age. Large subject-to-subject variability within an age group requires a large population to observe trends in skin barrier properties over time. Barrier function, quantified by transepidermal water loss (TEWL) and SC thickness, was measured on the upper inner arm and dorsal forearm in subjects aged 3 months to 4 years (n = 171) and a subset of mothers (n = 44). The rate of skin surface area expansion as a function of age peaked before birth (∼90 cm2/week) and declined to a steady plateau (∼10 cm2/week) by 1 year of age. SC thickness increased and TEWL decreased, but did not reach adult values until 3-4 years of age. A better understanding of how skin hydration changes after birth suggests that barrier function may be related mechanistically to skin surface area expansion.

In vitro assessment of skin irritation potential of surfactant-based formulations by using a 3-D skin reconstructed tissue model and cytokine response.

The personal care industry is focused on developing safe, more efficacious, and increasingly milder products, that are routinely undergoing preclinical and clinical testing before becoming available for consumer use on skin. In vitro systems based on skin reconstructed equivalents are now established for the preclinical assessment of product irritation potential and as alternative testing methods to the classic Draize rabbit skin irritation test. We have used the 3-D EpiDerm™ model system to evaluate tissue viability and primary cytokine interleukin-1α release as a way to evaluate the potential dermal irritation of 224 non-ionic, amphoteric and/or anionic surfactant-containing formulations, or individual raw materials. As part of our testing programme, two representative benchmark materials with known clinical skin irritation potential were qualified through repeated testing, for use as references for the skin irritation evaluation of formulations containing new surfactant ingredients. We have established a correlation between the in vitro screening approach and clinical testing, and are continually expanding our database to enhance this correlation. This testing programme integrates the efforts of global manufacturers of personal care products that focus on the development of increasingly milder formulations to be applied to the skin, without the use of animal testing.