Systematic variation of the stellar initial mass function in early-type galaxies.

Much of our knowledge of galaxies comes from analysing the radiation emitted by their stars, which depends on the present number of each type of star in the galaxy. The present number depends on the stellar initial mass function (IMF), which describes the distribution of stellar masses when the population formed, and knowledge of it is critical to almost every aspect of galaxy evolution. More than 50 years after the first IMF determination, no consensus has emerged on whether it is universal among different types of galaxies. Previous studies indicated that the IMF and the dark matter fraction in galaxy centres cannot both be universal, but they could not convincingly discriminate between the two possibilities. Only recently were indications found that massive elliptical galaxies may not have the same IMF as the Milky Way. Here we report a study of the two-dimensional stellar kinematics for the large representative ATLAS(3D) sample of nearby early-type galaxies spanning two orders of magnitude in stellar mass, using detailed dynamical models. We find a strong systematic variation in IMF in early-type galaxies as a function of their stellar mass-to-light ratios, producing differences of a factor of up to three in galactic stellar mass. This implies that a galaxy's IMF depends intimately on the galaxy's formation history.

Characteristics of sarcoidosis in Maori and Pacific Islanders.

BACKGROUND AND OBJECTIVE: Ethnicity is strongly associated with variable clinical presentation in sarcoidosis but the association between ethnicity and clinical characteristics has not previously been described in patients of Polynesian ancestry, Maori and Pacific Islander (PI). The objective of this study was to describe the clinical characteristics of sarcoidosis in Maori and PI patients and determine if those were different to European patients. METHODS: A retrospective review of the medical records of 406 patients (69 Maori/PI) attending a specialist interstitial lung disease (ILD) clinic. RESULTS: The population (207 females, mean age at presentation: 36) reflected the current New Zealand census data (2013) with only people of Indian ethnicity over-represented. Parenchymal lung involvement was uncommon in Maori and PI patients (21% Scadding stage 2, 2% stage 3), and no patient had extensive pulmonary fibrosis (stage 4). Computed tomography (CT) patterns of sarcoid parenchymal lung involvement were less commonly reported for Maori/PI. There were no differences in respect of baseline lung function or requirement for treatment. Ocular and skin involvement occurred more frequently in Maori and PI (P = 0.0045, P = 0.03), and erythema nodosum was more common in Caucasians (P = 0.0008). CONCLUSION: People of Polynesian ancestry appear to have less pulmonary and more extra-pulmonary manifestations of sarcoidosis. This adds to our knowledge that sarcoidosis heterogeneity is influenced by ethnicity.

Trap and track: designing self-reporting porous Si photonic crystals for rapid bacteria detection.

The task of rapid detection and identification of bacteria remains a major challenge in both medicine and industry. This work introduces a new concept for the design of self-reporting optical structures that can detect and quantify bacteria in real-time. The sensor is based on a two-dimensional periodic structure of porous Si photonic crystals in which the pore size is adjusted to fit the target bacteria cells (Escherichia coli). Spontaneous bacteria capture within the pores induces measurable changes in the zero-order reflectivity spectrum collected from the periodic structure. Confocal laser microscopy and electron microscopy confirm that the Escherichia coli cells are individually imprisoned within the porous array. A simple model is suggested to correlate the optical readout and the bacteria concentration and its predictions are found to be in good agreement with experimental results. In addition, we demonstrate that sensing scheme can be easily modified to potentially allow monitoring of concentration, growth and physiological state of bacteria cells. This generic platform can be tailored to target different microorganisms by tuning the array periodicity and its surface chemistry for rapid and label-free detection outside the laboratory environment.

Evaluation of hair loss in cats occurring after treatment with a topical flea control product.

BACKGROUND: A formulation containing 39.6% spinetoram resulted in a higher than anticipated number of reports of alopecia at the site of application in the first months following commercial product launch. HYPOTHESIS/OBJECTIVES: To determine the cause of the alopecia using histopathology, including assessment for inflammation, follicular findings of physical trauma (plucking/pulling behaviour) and changes in follicular cycling. ANIMALS: Twenty-four flea-free, male and female adult domestic short hair cats within a private research colony. METHODS: Cats were treated with a single application of 39.6% spinetoram on day 0; personnel were not blinded. Observations of the skin and hair coat began immediately and were repeated at 30 min and 1, 2, 3, 4, 6, 8 and 12 h post-application and then on subsequent days at the same time as initial dosing and at 2, 4, 6, 8 and 12 h after that time, until day 5. If hair thinning or loss was observed, a skin biopsy sample was collected. Two cats not exhibiting abnormalities were biopsied on day 6. RESULTS: Thirty-eight per cent of cats (nine of 24) developed hair thinning and alopecia of sufficient severity within 78 h post-application of the product to warrant skin biopsy. Abnormalities in the skin were limited to the application site and were consistent with physical trauma (pulling or plucking) to the hair. CONCLUSIONS AND CLINICAL IMPORTANCE: Microscopic changes in the hair follicles of affected cats were consistent with self-induced trauma or barbering behaviour. All changes were reversible and paralleled findings associated with well-established, topical flea control products.

The prevalence and predictors of airway hyperresponsiveness in sarcoidosis.

BACKGROUND AND OBJECTIVE: Obstructive airflow limitation is the most common physiological impairment in sarcoidosis. This study determined the prevalence of airway hyperresponsiveness (AHR) in sarcoidosis, the correlation between responses to direct (using histamine) and indirect (using hypertonic saline) bronchial challenge, and the clinical, physiological and radiological predictors of AHR. METHODS: Subjects with sarcoidosis and a baseline forced expiratory volume in 1 s (FEV(1)) >35% predicted underwent hypertonic and histamine challenge, lung function testing and high resolution computed tomography (HRCT) of the chest. AHR was defined as a 15% fall in FEV(1) to hypertonic saline and a 20% fall in FEV(1) to histamine. RESULTS: The 52 subjects had well-preserved lung function (FEV(1) = 2.8 ± 0.7 L, 87% predicted). AHR was detected in 5/47 (11%) to hypertonic saline and 19/43 (44%) to histamine challenge. On univariate analysis, response to histamine challenge was predicted by conglomerate fibrosis (P = 0.02) and reticular pattern (P = 0.03) on HRCT. The baseline % predicted forced expiratory volume in 1 s was significantly inversely associated with AHR on univariate (P = 0.004) and multivariate analysis (P = 0.01) when adjusted by HRCT patterns. CONCLUSIONS: The higher prevalence of AHR using histamine challenge than hypertonic saline challenge and the association with baseline % predicted FEV(1) suggest that the AHR in sarcoidosis may reflect the consequences of airway remodelling following inflammation.

Field study to investigate the effectiveness and safety of a novel orally administered combination drug product containing milbemycin oxime and lotilaner (Credelio® Plus) for the prevention of heartworm disease (Dirofilaria immitis) in client-owned dogs in the USA.

BACKGROUND: Dirofilaria immitis, a globally distributed filarial parasite of dogs, is known to cause serious or fatal cardiopulmonary disease. Client-owned dogs were enrolled in a clinical field study in the USA to evaluate the clinical effectiveness and field safety of an orally administered combination investigational product (IP) containing milbemycin oxime and lotilaner (Credelio® Plus) as compared to a control product (CP) for the prevention of heartworm disease when administered monthly for 11 consecutive months. METHODS: In this 11-month field study, 319 dogs ≥ 8 weeks old confirmed to be heartworm-negative were enrolled from eight geographically distinct US veterinary clinics, including sites in the southern USA and Mississippi River Valley. The dogs were treated with either the IP combination product at 0.75-1.53 mg/kg milbemycin oxime and 20-41.5 mg/kg lotilaner (n = 159) or the CP (Sentinel® Flavor Tabs®; milbemycin oxime/lufenuron) at the label-recommended dose rate (n = 158.) On day 330, effectiveness was evaluated in each dog using antigen and microfilarial (modified Knott's) testing to assess the establishment of any patent adult heartworm infections. RESULTS: All dogs treated with the IP combination product and the CP tested negative (100% prevention) for heartworm infection on day 330. The IP combination product tablets containing milbemycin oxime and lotilaner were well tolerated based on the safety assessments in all treated dogs. CONCLUSIONS: This multi-site clinical study using client-owned dogs demonstrated that monthly use of flavored, chewable tablets containing a combination of milbemycin oxime and lotilaner administered orally under end use conditions is safe for dogs. None of the enrolled dogs developed heartworm infections. Eleven consecutive monthly treatments of the IP provided 100% prevention of heartworm disease caused by D. immitis.

Effectiveness of Credelio® Plus, a novel chewable tablet containing milbemycin oxime and lotilaner for the treatment of larval and immature adult stages of Toxocara canis in experimentally infected dogs.

BACKGROUND: The ascarid, Toxocara canis, is a common and important zoonotic intestinal nematode parasite that infects dogs globally. An effective treatment that kills any pre-patent stages of immature T. canis could additionally reduce or eliminate the development of patent infections that can result in clinical disease in infected dogs and would further reduce environmental contamination of eggs. Two randomized, blinded, GCP-compliant, pivotal laboratory dose confirmation studies were conducted to assess the effectiveness and safety of a new novel combination of lotilaner and milbemycin oxime tablets (Credelio Plus) administered orally to dogs that were experimentally infected with immature (L4 or immature adult [L5]) stages of T. canis. METHODS: The commercial tablet formulation of Credelio Plus® was administered in a time frame relative to inoculation with infective eggs. This allowed for effectiveness to be assessed against each specific immature stage of T. canis. In each study, dogs were randomized and allocated to one of four treatment groups. Each treatment group contained ten dogs that had been experimentally inoculated on Day 0 with infective T. canis eggs and then were dosed once on Day 14 or Day 24 using either placebo tablets or Credelio Plus tablets (IP) to provide minimum dosages of 0.75 mg/kg of milbemycin oxime and 20 mg/kg of lotilaner. All dogs were necropsied 5 or 6 days after their respective treatment. At necropsy, all nematodes recovered from the gastrointestinal tract were counted by species and stage. RESULTS: In both dose confirmation studies using geometric mean worm counts, effectiveness of Credelio Plus was ≥ 98.6% and ≥ 96.8% against L4 larval stage T. canis and immature adult [L5] T. canis in both studies, respectively. CONCLUSIONS: These studies demonstrated that the Credelio Plus combination tablet administered orally to dogs was highly efficacious against experimental infections with L4 and immature adult [L5] stages of T. canis.

Community-acquired methicillin-resistant Staphylococcus aureus emerging as an important cause of necrotizing fasciitis.

BACKGROUND: Necrotizing fasciitis (NF) is an uncommon fulminant soft tissue infection characterized by extensive fascial necrosis. Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) isolates producing the Panton-Valentine leukocidin (PVL) cytotoxin have been associated with serious necrotizing infections, but NF caused by CA-MRSA has been described only recently. We reviewed our NF experience at Denver Health Medical Center, where CA-MRSA accounts for more than 50% of community S. aureus clinical isolates. METHODS: Patients treated for NF from January 2004 to February 2006 were identified by review of pathology records and diagnostic codes, and their medical records were reviewed. Isolates of MRSA from monomicrobial NF underwent testing for the PVL gene and pulsed-field gel electrophoresis to determine relatedness to CA-MRSA strains. RESULTS: Five of 30 NF cases during the study period, all involving the extremities, were caused by MRSA. Monomicrobial MRSA NF accounted for three cases, with all of the patients reporting a distinct "spider bite" lesion 2-3 days prior to admission. The median age was 32 years (range 28-55 years). Resistance to erythromycin and levofloxacin was present in four isolates. None of the isolates displayed inducible clindamycin resistance. Within 12 hours of admission, all patients received empiric antibiotics to which their isolate was susceptible. Patients required a median of six surgical procedures (range 2-7 operations). All patients survived. The MRSA isolates tested positive for PVL and had the USA 300 CA-MRSA deoxyribonucleic acid banding pattern. CONCLUSIONS: Community-acquired MRSA is an important cause of NF in our region, accounting for > 15% of NF cases. This infection was associated with significant morbidity necessitating multiple surgical interventions. Given the propensity of PVL-positive CA-MRSA to cause severe necrotizing infections, it is reasonable to administer empiric MRSA coverage for NF in endemic locations.

Demographic profile of families and children in the Study to Explore Early Development (SEED): Case-control study of autism spectrum disorder.

BACKGROUND: The Study to Explore Early Development (SEED) is designed to enhance knowledge of autism spectrum disorder characteristics and etiologies. OBJECTIVE: This paper describes the demographic profile of enrolled families and examines sociodemographic differences between children with autism spectrum disorder and children with other developmental problems or who are typically developing. METHODS: This multi-site case-control study used health, education, and birth certificate records to identify and enroll children aged 2-5 years into one of three groups: 1) cases (children with autism spectrum disorder), 2) developmental delay or disorder controls, or 3) general population controls. Study group classification was based on sampling source, prior diagnoses, and study screening tests and developmental evaluations. The child's primary caregiver provided demographic characteristics through a telephone (or occasionally face-to-face) interview. Groups were compared using ANOVA, chi-squared test, or multinomial logistic regression as appropriate. RESULTS: Of 2768 study children, sizeable proportions were born to mothers of non-White race (31.7%), Hispanic ethnicity (11.4%), and foreign birth (17.6%); 33.0% of households had incomes below the US median. The autism spectrum disorder and population control groups differed significantly on nearly all sociodemographic parameters. In contrast, the autism spectrum disorder and developmental delay or disorder groups had generally similar sociodemographic characteristics. CONCLUSIONS: SEED enrolled a sociodemographically diverse sample, which will allow further, in-depth exploration of sociodemographic differences between study groups and provide novel opportunities to explore sociodemographic influences on etiologic risk factor associations with autism spectrum disorder and phenotypic subtypes.

Elder physical abuse.

Physical abuse of the elderly is a significant public health concern. The true prevalence of all types is unknown, and under-reporting is known to be significant. The geriatric population is projected to increase dramatically over the next 10 years, and the number of abused individuals is projected to increase also. It is critical that health care providers feel competent in addressing physical elder abuse. This article presents cases illustrating the variety of presenting symptoms that may be attributed to physical elder abuse.

Assessment of owner-administered monthly treatments with oral spinosad or topical spot-on fipronil/(S)-methoprene in controlling fleas and associated pruritus in dogs.

Monitoring of the performance of flea control products under conditions of natural challenge is valuable in assessing continued effectiveness and determining the ongoing relevance of laboratory studies. A multi-clinic, investigator-blinded study was undertaken in client-owned dogs to investigate and compare the flea control provided by 3 consecutive monthly treatments of oral spinosad (SPN) or fipronil/(S)-methoprene topical (FSM) spot-on. The first household dog meeting enrollment criteria and with at least 10 fleas (whole-body flea count) served as the index dog in a household against which primary objectives were set. Stratification was based on pruritus scores at the enrollment visit and on single or multiple pet household. Index pets were randomized to treatment with either SPN or FSM, dispensed on day 0 for at-home administration by owners. All other household dogs and cats, maximum 4 pets per household, were dispensed the same treatment as the index dog (spinetoram was dispensed for cats in SPN households). Subsequent treatments were dispensed when index dogs were returned for whole-body flea counts and pruritus-scoring at visits on days 30 and 60, with final assessments on day 90 (±5 days on each occasion). Primary endpoints were the number of flea-free index dogs in each group one month after the final treatment, the reduction in owner-reported pruritus, and the reduction from baseline mean flea counts. One hundred twenty eight index dogs were enrolled (65 in the SPN arm; 63 in the FSM arm) at 10 clinics in FL (6), NC (2), LA (1), and TX (1). On day 0, geometric mean flea counts were 57.7 (range: 10-1469) and 44.8 (10-717) for the SPN and FSM groups, respectively. On Day 90, 55 of 58 (95%) and 21 of 55 (38%) index dogs completing the study were flea-free in SPN and FSM groups, respectively; mean SPN pruritus scores declined to 0.92 (6.67 on day 0), and to 3.83 (6.33 on day 0) for FSM; geometric mean flea counts (% control) were 0.08 (99.9%) and 5.19 (88.4%), for SPN and FSM groups, respectively. Between-treatment differences were highly statistically significant (p<0.0001). In conclusion, SPN provided reliable flea control in client-owned dogs, regardless of challenge level.

Mathematical modeling of drug release from nanostructured porous Si: combining carrier erosion and hindered drug diffusion for predicting release kinetics.

A novel, empirical, macroscopic model is developed to describe the release of a model anticancer drug, Mitoxantrone, from native and chemically modified porous Si (PSi) thin films. Drug release from these carriers results from a combination of two mechanisms, i.e. out-diffusion of the drug molecules and erosion of the Si scaffold. Thus, the proposed mathematical model adapts the Crank model to lump the effects of temporal changes in molecular interactions and carrier scaffold erosion into a comprehensive model of hindered drug diffusion from nanoscale porous systems. Careful characterization of pore size, porosity, surface area, drug loading, as well as Si scaffold degradation profiles, measured over the same time-scale as drug release, are incorporated into the model parameter estimation. A comparison of the experimental and model results shows accurate representation of the data, emphasizing the reliability of the model. The proposed model shows that drug diffusivity values significantly vary with time for the two studied carriers, which are ascribed to the distinctive role of the prevailing physical mechanisms in each system. Finally, secondary validation of the proposed model is demonstrated by showing adequate fit to published data of the release of dexamethasone from similar mesoporous Si carriers.

Screening strategies for autism spectrum disorders in pediatric primary care.

BACKGROUND: Two strategies have been proposed for early identification of children with autism spectrum disorders (ASD): (1) using a general screening tool followed by an ASD-specific screening tool for those who screen positive on the former or (2) using an ASD-specific tool for all children. The relative yield of these two strategies has not been examined. OBJECTIVES: This study compared the number of children identified at risk for ASD at their well child visits between the ages of 18 and 30 months using a general developmental screening tool and an autism-specific screening tool. METHODS: The Parents' Evaluation of Developmental Status (PEDS) was used as the general developmental screening tool and the Modified Checklist for Autism in Toddlers (M-CHAT) was used as the autism-specific tool. These tools were administered concurrently to 152 children. RESULTS: Cross tabulations and chi tests were used to determine the utility of the PEDS as the first step of a two-part screen for ASD. Of those who screened positive for developmental concerns on the PEDS (n = 38), 16% screened positive for ASD on the M-CHAT; of those who did not screen positive for developmental concerns on the PEDS (n = 114), 14% screened positive for ASD on the M-CHAT (p = .79). CONCLUSION: The PEDS missed the majority of children who screened positive for ASD on the M-CHAT, suggesting that these two tools tap into very different domains of developmental concerns. The findings support the use of an ASD-specific tool for all children in conjunction with regular standardized developmental screening.

Lower occurrence of idiopathic pulmonary fibrosis in Maori and Pacific Islanders.

OBJECTIVE: Idiopathic pulmonary fibrosis (IPF), a chronic fibro-proliferative interstitial pneumonia, has not been reported to occur more frequently in any particular race. We have observed that our patients with IPF comprise a proportionately lower number of Maori and Pacific Islanders and set out to evaluate this further. METHODS: Retrospective analysis of an IPF database from a single tertiary respiratory institution was undertaken. Demographic and survival data were collected. Ethnicity was compared with 2001 New Zealand census data from the same catchment area. RESULTS: Eighty-seven cases of IPF were identified. Overall median survival was 46 months. Ethnicity data were available for 84 of the 87 cases. 76/84 (90%) were European, 6/84 (7%) were Asian or Indian, 2/84 (2%) were Maori, and 0/84 (0%) were Pacific Islanders. For Maori and Pacific Islanders, this represented a significant trend in difference when compared with ethnicity data from the hospital catchment population (P < 0.001). CONCLUSIONS: Our department is the tertiary referral centre for pulmonary disease in the upper North Island of New Zealand, and therefore referral centre bias is likely to be low. The preliminary observation that the occurrence of IPF is lower in those of Maori or Polynesian ethnicity warrants further study. This may, in part, help in our understanding of the pathogenic mechanisms in IPF.