Correction: Time to revisit the endpoint dilution assay and to replace the TCID50 as a measure of a virus sample's infection concentration.

[This corrects the article DOI: 10.1371/journal.pcbi.1009480.].

Time to revisit the endpoint dilution assay and to replace the TCID50 as a measure of a virus sample's infection concentration.

The endpoint dilution assay's output, the 50% infectious dose (ID50), is calculated using the Reed-Muench or Spearman-Kärber mathematical approximations, which are biased and often miscalculated. We introduce a replacement for the ID50 that we call Specific INfection (SIN) along with a free and open-source web-application, midSIN (https://midsin.physics.ryerson.ca) to calculate it. midSIN computes a virus sample's SIN concentration using Bayesian inference based on the results of a standard endpoint dilution assay, and requires no changes to current experimental protocols. We analyzed influenza and respiratory syncytial virus samples using midSIN and demonstrated that the SIN/mL reliably corresponds to the number of infections a sample will cause per mL. It can therefore be used directly to achieve a desired multiplicity of infection, similarly to how plaque or focus forming units (PFU, FFU) are used. midSIN's estimates are shown to be more accurate and robust than the Reed-Muench and Spearman-Kärber approximations. The impact of endpoint dilution plate design choices (dilution factor, replicates per dilution) on measurement accuracy is also explored. The simplicity of SIN as a measure and the greater accuracy provided by midSIN make them an easy and superior replacement for the TCID50 and other in vitro culture ID50 measures. We hope to see their universal adoption to measure the infectivity of virus samples.

Intrageneric differences in the effects of acute temperature exposure on competitive behaviour of damselfishes.

Projected increases in global temperatures brought on by climate change threaten to disrupt many biological and ecological processes. Tropical ectotherms, like many fishes, can be particularly susceptible to temperature change as they occupy environments with narrow thermal fluctuations. While climate change models predict temperatures to increase over decades, thermal fluctuations are already experienced on a seasonal scale, which may affect the ability to capture and defend resources across a thermal gradient. For coral reef fish, losers of competitive interactions are often more vulnerable to predation, and this pressure is strongest just after settlement. Competitive interactions may determine future success for coral reef fishes, and understanding how temperature experienced during settlement can influence such interactions will give insight to community dynamics in a future warmer world. We tested the effect of increased temperatures on intraspecific competitive interactions of two sympatric species of reef damselfish, the blue damselfish Pomacentrus nagasakiensis, and the whitetail damselfish Pomacentrus chrysurus. Juvenile fishes were exposed to one of four temperature treatments, ranging from 26-32 °C, for seven days then placed into competitive arenas where aggressive interactions were recorded between sized matched individuals within each species. While there was no apparent effect of temperature treatment on aggressive behaviour for P. chrysurus, we observed up to a four-fold increase in aggression scores for P. nagasakiensis with increasing temperature. Results suggest that temperature experienced as juveniles can impact aggressive behaviour; however, species-specific thermal tolerances led to behavioural affects that differ among closely related species. Differential thermal tolerance among species may cause restructuring of the interaction network that underlies the structure of reef assemblages.

The photospheric origin of the Yonetoku relation in gamma-ray bursts.

Long duration gamma-ray bursts (GRBs), the brightest events since the Big Bang itself, are believed to originate in an ultra-relativistic jet breaking out from a massive stellar envelope. Despite decades of study, there is still no consensus on their emission mechanism. One unresolved question is the origin of the tight correlation between the spectral peak energy and peak luminosity discovered in observations. This Yonetoku relation is the tightest correlation found in the properties of the prompt phase of GRB emission, providing the best diagnostic for the radiation mechanism. Here we present three-dimensional hydrodynamical simulations, and post-process radiation transfer calculations, of photospheric emission from a relativistic jet. Our simulations reproduce the Yonetoku relation as a natural consequence of viewing angle. Although jet dynamics depend sensitively on luminosity, the correlation holds regardless. This result strongly suggests that photospheric emission is the dominant component in the prompt phase of GRBs.

Efficacy and patient opinion of wet-wrap dressings using 0.1% triamcinolone acetonide ointment vs cream in the treatment of pediatric atopic dermatitis: A randomized split-body control study.

BACKGROUND: Wet wraps can be an effective means of improving atopic dermatitis (AD). Little research has been done regarding the comparative efficacy of topical steroid vehicles and patient preference. OBJECTIVE: This study aimed to compare the efficacy of 0.1% triamcinolone acetonide ointment vs cream used with wet wraps in pediatric patients with AD and to explore patient preference/opinion. METHODS: We performed a small, randomized, investigator-blind prospective study of 39 pediatric patients experiencing symmetric, bilateral AD flares. Patients were instructed to apply a topical steroid cream to one extremity and apply the same topical steroid in an ointment vehicle to the other extremity using the wet-wrap technique once or twice daily for 3 to 5 consecutive days. Patients were evaluated at a follow-up visit. RESULTS: Comparison of the change in Investigator's Global Assessment scores disclosed no significant difference between efficacy ratings of cream (mean difference = 0.72) and ointment (mean difference = 0.59) when used with wet wraps (P = 0.22). Although patients found the ointment more difficult to apply, they were more likely to prefer ointments for future prescriptions (P < 0.01). CONCLUSION: Patient preference of corticosteroid vehicle is what should ultimately drive treatment. In this small study, we found no difference in efficacy between triamcinolone acetonide wet wraps with cream vs ointment. Dermatologists should select the vehicle of the patient's choice as it may increase satisfaction with treatment.

Guideline Values for Minimum Nasal Cross-Sectional Area in Children.

OBJECTIVE: The purpose was to determine age-specific values of the minimum cross-sectional area of the nasal airway in children without cleft lip or palate and to assess whether gender differences occur with growth in order to develop guidelines for assessment in children with clefts. PARTICIPANTS: All schoolchildren aged 8 to 17 years who met the research criteria were studied during rest breathing using the pressure-flow technique. The children came from a rural area of 3800 inhabitants. Consecutive age cohorts were used for comparisons. RESULTS: Nasal cross-sectional area increased in females from 0.38 cm2 in 8-year-olds to 0.58 cm2 in 17-year-olds. There was a decrease in size at ages 10 to 11 and 14 to 15 years. In males, the area increased from 0.40 to 0.68 cm2 and decreased slightly from 9 to 10 and 14 to 15 years. The annual changes were statistically significant in females between 8 and 9 and 11 to 13 years of age, and in males from 11 to 12, 13 to 14, and 15 to 17 years of age. Across gender, the only significant difference occurred at age 16. CONCLUSIONS: Our results indicate that the increase in nasal airway size is not consistent during growth. Nasal airway size showed almost equal values for both genders in young children but was systematically larger in boys from 14 years of age on. The results refer that by 17 years of age nasal airway may not have reached adult size in males.

Extended exposure to elevated temperature affects escape response behaviour in coral reef fishes.

The threat of predation, and the prey's response, are important drivers of community dynamics. Yet environmental temperature can have a significant effect on predation avoidance techniques such as fast-start performance observed in marine fishes. While it is known that temperature increases can influence performance and behaviour in the short-term, little is known about how species respond to extended exposure during development. We produced a startle response in two species of damselfish, the lemon damsel Pomacentrus moluccensis, and the Ambon damselfish Pomacentrus amboinensis, by the repeated use of a drop stimulus. We show that the length of thermal exposure of juveniles to elevated temperature significantly affects this escape responses. Short-term (4d) exposure to warmer temperature affected directionality and responsiveness for both species. After long-term (90d) exposure, only P. moluccensis showed beneficial plasticity, with directionality returning to control levels. Responsiveness also decreased in both species, possibly to compensate for higher temperatures. There was no effect of temperature or length of exposure on latency to react, maximum swimming speed, or escape distance suggesting that the physical ability to escape was maintained. Evidence suggests that elevated temperature may impact some fish species through its effect on the behavioural responses while under threat rather than having a direct influence on their physical ability to perform an effective escape response.

Diffuse Hepatic Hemangiomas Successfully Treated Using Sirolimus and High-Dose Propranolol.

Diffuse hepatic hemangiomas are a challenging disease that can be life threatening. We present the case of an infant with diffuse hepatic hemangiomas who failed first-line therapies but later responded to sirolimus and high-dose propranolol.

Leukocytoclastic vasculitis drug reaction to certolizumab pegol.

Tumor necrosis factor (TNF)-alpha antagonists are a common treatment modality for autoimmune disorders, but their use can be associated with many side effects, including various dermatologic conditions. Certolizumab pegol, a newer TNF antagonist that lacks the Fc portion of the IgG antibody, has recently been approved to treat psoriatic arthritis, rheumatoid arthritis, and Crohn's disease. Though other TNF antagonists have been associated with leukocytoclastic vasculitis, this finding has not yet been reported with certolizumab pegol. We present a case report of leukocytoclastic vasculitis caused by certolizumab pegol.

Unilateral striae distensae of the knee after a steroid injection for the treatment of Osgood-Schlatter disease.

We report a 12-year-old girl with new diagnosisof right knee Osgood-Schlatter who developedhorizontal purple striae below the right tibial tubercletwo months after a right knee intra-articular steroidinjection. She is the second reported case of unilaterallocalized striae after an intra-articular steroid injectionand the first with triamcinalone as the corticosteroid.

Perception and Respiratory Responses of the Upper Airway Mechanism to Added Resistance With Aging.

Objectives: To assess breathing behaviors and perception of added respiratory loads in young compared to old individuals, and to determine whether aging affects the perception and response to changes in nasal airway resistance. Study design: In a clinical study, 40 young (11-20 years) and 40 older (59-82 years) subjects were evaluated during rest breathing and during the application of added airway resistance loads. Methods: The pressure-flow technique was used to measure airflow rate (mL/s) and oral-nasal pressures (cmH2O) to calculate nasal resistance (cmH2O/L/s). To create calibrated resistance loads for the test conditions, we used a device modified from a precision iris diaphragm. Results: During rest breathing airflow rate was significantly lower for the younger group compared to older group. Using the loading device, 11-20-year-olds detected increased resistance at the level of 2.26 cmH2O/L/s compared to 4.55 cmH2O/L/s in 59-82-year-olds. In contrast to the younger group, mean airflow rate was higher during expiration than during inspiration among 59-82-year-olds except at rest breathing. Conclusions: The data revealed that the perception and respiratory response to increased airway resistance changed with aging. Younger subjects were more sensitive to changes within the airway. In both groups, subjects responded to increased airway resistance by decreasing airflow rate. However, expiratory phase became more active than inspiratory phase only in the older group. Level of Evidence: N/A.

Duration of Exposure to Elevated Temperature Affects Competitive Interactions in Juvenile Reef Fishes.

Climate change will affect key ecological processes that structure natural communities, but the outcome of interactions between individuals and species will depend on their thermal plasticity. We tested how short- and long-term exposure to projected future temperatures affects intraspecific and interspecific competitive interactions in two species of coral reef damselfishes. In conspecific contests, juvenile Ambon damselfish, Pomacentrus amboinensis, exhibited no change in aggressive interactions after 4d exposure to higher temperatures. However, after 90d of exposure, fish showed a nonadaptive reduction in aggression at elevated temperatures. Conversely, 4d exposure to higher temperature increased aggression towards conspecifics in the lemon damselfish, Pomacentrus moluccensis. 90d exposure began to reduce this pattern, but overall there was little effect of temperature. Aggression in interspecific contests increased with short-term exposure, but was significantly lower after long-term exposure indicative of acclimation. Our results show how the length of exposure to elevated temperature can affect the outcome of competitive interactions. Furthermore, we illustrate that results from intraspecific contests may not accurately predict interspecific interactions, which will challenge our ability to generalise the effects of warming on competitive interactions.

Facial Blanching After Cosmetic Botulinum Toxin Injection: Case Series.

Case 1 A 32-year-old woman was treated for the first time with onabotulinumtoxinA (BoNT), receiving 10 units in her forehead and 20 units in her glabella. She reported no history of skin disease and had a very active lifestyle. She first noticed blanching while doing a group workout and a friend inquired if she had "hives" on her forehead (Figure 1). She continued to note the blanching during workouts 5 months after injection. Each episode lasted 30 minutes to 2 hours. There were no associated symptoms with the blanching other than minor embarrassment. Given her active lifestyle and frequent blanching, she has elected not to receive further injections.

Upper airway resistance during growth: A longitudinal study of children from 8 to 17 years of age.

OBJECTIVE: To study upper airway breathing in 115 children annually from 8 to 17 years of age with the hypothesis that upper airway respiratory needs increase steadily during growth and show sexual dimorphism. MATERIAL AND METHODS: To calculate nasal resistance, airflow rate (mL/s) and oronasal pressures (cmH2O) were measured during rest breathing in a seated position using the pressure-flow technique. RESULTS: Median values of oronasal pressure ranged at different ages in girls from 0.88 to 1.13 and in boys from 0.92 to 1.44 cmH2O, being 0.95 and 0.93 cmH2O at the age of 17 years, respectively. The gender differences were statistically significant in four age groups (P < .05 by the Mann-Whitney test). Mean values of nasal resistance decreased from 8 to 17 years of age in girls from 4.0 (±3.27) to 2.4 (±2.30) and in boys from 3.3 (±2.48) to 1.5 (±0.81) cmH2O/L/s. However, there was an increase in resistance in 11-year-old girls and 12-year-old boys and at the age of 15 in both genders (P < .05 by paired t-test). CONCLUSIONS: Respiratory efforts stabilize oronasal pressure to maintain vital functions at optimal level. Nasal resistance decreased with age but increased temporarily at the prepubertal and pubertal phases, in accordance with other growth and possibly hormonal changes. When measuring upper airway function for clinical purposes, especially in patients with sleep apnea, asthma, allergies, cleft palate, or maxillary expansion, the measurements need to be compared with age- and gender-specific values obtained from healthy children.

Sunscreen use on the dorsal hands at the beach.

Background. Since skin of the dorsal hands is a known site for the development of cutaneous squamous cell carcinoma, an epidemiologic investigation was needed to determine if beachgoers apply sunscreen to the dorsal aspect of their hands as frequently as they apply it to other skin sites. Aim. The aim of the current study was to compare the use of sunscreen on the dorsal hands to other areas of the body during subtropical late spring and summer sunlight exposure at the beach. Materials and Methods. A cross-sectional survey from a convenience sample of beachgoers was designed to evaluate respondent understanding and protective measures concerning skin cancer on the dorsal hands in an environment with high natural UVR exposure. Results. A total of 214 surveys were completed and analyzed. Less than half of subjects (105, 49%) applied sunscreen to their dorsal hands. Women applied sunscreen to the dorsal hands more than men (55% women versus 40% men, P = 0.04). Higher Fitzpatrick Skin Type respondents were less likely to protect their dorsal hands from ultraviolet radiation (P = 0.001). Conclusions. More public education focused on dorsal hand protection from ultraviolet radiation damage is necessary to reduce the risk for squamous cell carcinomas of the hands.