Polycyclic Aromatic Hydrocarbons (PAHs) in Wildfire Smoke Accumulate on Indoor Materials and Create Postsmoke Event Exposure Pathways.

Wildfire smoke contains PAHs that, after infiltrating indoors, accumulate on indoor materials through particle deposition and partitioning from air. We report the magnitude and persistence of select surface associated PAHs on three common indoor materials: glass, cotton, and mechanical air filter media. Materials were loaded with PAHs through both spiking with standards and exposure to a wildfire smoke proxy. Loaded materials were aged indoors over ∼4 months to determine PAH persistence. For materials spiked with standards, total PAH decay rates were 0.010 ± 0.002, 0.025 ± 0.005, and 0.051 ± 0.009 day-1, for mechanical air filter media, glass, and cotton, respectively. PAH decay on smoke-exposed samples is consistent with that predicated by decay constants from spiked materials. Decay curves of smoke loaded samples show that PAH surface concentrations are elevated above background for ∼40 days after the smoke clears. Cleaning processes efficiently remove PAHs, with reductions of 71% and 62% after cleaning smoke-exposed glass with ethanol and a commercial cleaner, respectively. Laundering smoke-exposed cotton in a washing machine and heated drying removed 48% of PAHs. An exposure assessment indicates that both inhalation and dermal PAH exposure pathways may be relevant following wildfire smoke events.

Characterization of Volatile Organic Compound Emissions and CO2 Uptake from Eco-roof Plants.

Vegetation plays an important role in biosphere-atmosphere exchange, including emission of biogenic volatile organic compounds (BVOCs) that influence the formation of secondary pollutants. Gaps exist in our knowledge of BVOC emissions from succulent plants, which are often selected for urban greening on building roofs and walls. In this study, we characterize the CO2 uptake and BVOC emission of eight succulents and one moss using proton transfer reaction - time of flight - mass spectrometry in controlled laboratory experiments. CO2 uptake ranged 0 to 0.16 µmol [g DW (leaf dry weight)]-1 s-1 and net BVOC emission ranges -0.10 to 3.11 µg [g DW]-1 h-1. Specific BVOCs emitted or removed varied across plants studied; methanol was the dominant BVOC emitted, and acetaldehyde had the largest removal. Isoprene and monoterpene emissions of studied plants were generally low compared to other urban trees and shrubs, ranging 0 to 0.092 µg [g DW]-1 h-1 and 0 to 0.44 µg [g DW]-1 h-1, respectively. Calculated ozone formation potentials (OFP) of the succulents and moss range 4×10-7 - 4×10-4 g O3 [g DW]-1 d-1. Results of this study can inform selection of plants used in urban greening. For example, on a per leaf mass basis, Phedimus takesimensis and Crassula ovata have OFP lower than many plants presently classified as low OFP and may be promising candidates for greening in urban areas with ozone exceedances.

Per-Person and Whole-Building VOC Emission Factors in an Occupied School with Gas-Phase Air Cleaning.

Using real-time measurements of CO2 and volatile organic compounds (VOCs) in the air handler of an occupied middle school, we quantified source strengths for 249 VOCs and apportioned the source to the building, occupants and their activities, outdoor air, or recirculation air. For VOCs quantified in this study, there is a source to the outdoors of 8.6 ± 1.8 g/h in building exhaust air, of which 5.9 ± 1.7 g/h can be attributed to indoor sources (the building and occupants and their activities). The corresponding whole-building area emission factor from indoor sources is 1020 ± 300 µg/(m2 h), including reactive VOCs like isoprene and monoterpenes (33 ± 5.1 and 29 ± 5.7 µg/(m2 h), respectively). Per-person emission factors are calculated for compounds associated with occupants and their activities, e.g., monoterpenes are emitted at a rate of 280 ± 80 µg/(person h). The air handler included carbon scrubbing, reducing supply air concentrations of 125 compounds by 38 ± 19% (mean ± std. dev.) with a net removal of 2.4 ± 0.4 g/h of organic compounds from the building. This carbon scrubber reduces steady-state indoor concentrations of organics by 65 µg/m3 and the contribution of indoor sources of VOCs to the outdoor environment by ∼40%. These data inform the design and operation of buildings to reduce human exposure to VOCs inside buildings. These data indicate the potential for gas-phase air cleaning to improve both indoor air quality and reduce VOC emissions from buildings to the outdoor environment.

Impact of renin-angiotensin-aldosterone system inhibition on mortality in critically ill COVID-19 patients with pre-existing hypertension: a prospective cohort study.

BACKGROUND: The influence of renin-angiotensin-aldosterone system (RAAS) inhibitors on the critically ill COVID-19 patients with pre-existing hypertension remains uncertain. This study examined the impact of previous use of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) on the critically ill COVID-19 patients. METHODS: Data from an international, prospective, observational cohort study involving 354 hospitals spanning 54 countries were included. A cohort of 737 COVID-19 patients with pre-existing hypertension admitted to intensive care units (ICUs) in 2020 were targeted. Multi-state survival analysis was performed to evaluate in-hospital mortality and hospital length of stay up to 90 days following ICU admission. RESULTS: A total of 737 patients were included-538 (73%) with pre-existing hypertension had received ACEi/ARBs before ICU admission, while 199 (27%) had not. Cox proportional hazards model showed that previous ACEi/ARB use was associated with a decreased hazard of in-hospital death (HR, 0.74, 95% CI 0.58-0.94). Sensitivity analysis adjusted for propensity scores showed similar results for hazards of death. The average length of hospital stay was longer in ACEi/ARB group with 21.2 days (95% CI 19.7-22.8 days) in ICU and 6.7 days (5.9-7.6 days) in general ward compared to non-ACEi/ARB group with 16.2 days (14.1-18.6 days) and 6.4 days (5.1-7.9 days), respectively. When analysed separately, results for ACEi or ARB patient groups were similar for both death and discharge. CONCLUSIONS: In critically ill COVID-19 patients with comorbid hypertension, use of ACEi/ARBs prior to ICU admission was associated with a reduced risk of in-hospital mortality following adjustment for baseline characteristics although patients with ACEi/ARB showed longer length of hospital stay. Clinical trial registration The registration number: ACTRN12620000421932; The date of registration: 30, March 2020; The URL of the registration: https://www.australianclinicaltrials.gov.au/anzctr/trial/ACTRN12620000421932 .

The genetic architecture of sexual dimorphism in the moss Ceratodon purpureus.

A central problem in evolutionary biology is to identify the forces that maintain genetic variation for fitness in natural populations. Sexual antagonism, in which selection favours different variants in males and females, can slow the transit of a polymorphism through a population or can actively maintain fitness variation. The amount of sexually antagonistic variation to be expected depends in part on the genetic architecture of sexual dimorphism, about which we know relatively little. Here, we used a multivariate quantitative genetic approach to examine the genetic architecture of sexual dimorphism in a scent-based fertilization syndrome of the moss Ceratodon purpureus. We found sexual dimorphism in numerous traits, consistent with a history of sexually antagonistic selection. The cross-sex genetic correlations (rmf) were generally heterogeneous with many values indistinguishable from zero, which typically suggests that genetic constraints do not limit the response to sexually antagonistic selection. However, we detected no differentiation between the female- and male-specific trait (co)variance matrices (Gf and Gm, respectively), meaning the evolution of sexual dimorphism may be constrained. The cross-sex cross-trait covariance matrix B contained both symmetric and asymmetric elements, indicating that the response to sexually antagonistic or sexually concordant selection, and the constraint to sexual dimorphism, are highly dependent on the traits experiencing selection. The patterns of genetic variances and covariances among these fitness components is consistent with partly sex-specific genetic architectures having evolved in order to partially resolve multivariate genetic constraints (i.e. sexual conflict), enabling the sexes to evolve towards their sex-specific multivariate trait optima.

Impact of Cognitive Tasks on CO2 and Isoprene Emissions from Humans.

The human body emits a wide range of chemicals, including CO2 and isoprene. To examine the impact of cognitive tasks on human emission rates of CO2 and isoprene, we conducted an across-subject, counterbalanced study in a controlled chamber involving 16 adults. The chamber replicated an office environment. In groups of four, participants engaged in 30 min each of cognitive tasks (stressed activity) and watching nature documentaries (relaxed activity). Measured biomarkers indicated higher stress levels were achieved during the stressed activity. Per-person CO2 emission rates were greater for stressed than relaxed activity (30.3 ± 2.1 vs 27.0 ± 1.7 g/h/p, p = 0.0044, mean ± standard deviation). Isoprene emission rates were also elevated under stressed versus relaxed activity (154 ± 25 µg/h/p vs 116 ± 20 µg/h/p, p = 0.041). The chamber temperature was held constant at 26.2 ± 0.49 °C; incidental variation in temperature did not explain the variance in emission rates. Isoprene emission rates increased linearly with salivary α-amylase levels (r2 = 0.6, p = 0.02). These results imply the possibility of considering cognitive tasks when determining building ventilation rates. They also present the possibility of monitoring indicators of cognitive tasks of occupants through measurement of air quality.

High-Efficiency Air Cleaning Reduces Indoor Traffic-Related Air Pollution and Alters Indoor Air Chemistry in a Near-Roadway School.

Schools in proximity to roadways expose students to traffic-related air pollution (TRAP). We investigate impacts of air-cleaning on indoor TRAP levels and indoor chemistry in a renovated school adjacent an interstate highway. We monitor air pollutants pre- and post-renovation and quantify efficiency of particle (MERV8 and 16 filters) and gas (functionalized activated carbon) air-cleaning. Time-resolved measurements show air-cleaning systems are effective, with in situ particle removal efficiency >94% across 10 nm to 10 µm. Activated carbon removed BTEX and NO2 with variability in removal efficiency. Over eight months of monitoring, NO2 removal efficiency was 96% initially and decreased to 61%; and BTEX removal efficiency was >80% or increased to >80%. Air-cleaning reduced indoor TRAP to below or near urban background. Air-cleaning systems suppressed indoor chemistry by reducing indoor levels of oxidants (NO2, O3) and reactive organics of indoor origin. When the air cleaning system was inactive, our data show that indoor SOA formation within the school was elevated. Loss rates of NO2 and O3 through the air-cleaning system were ∼1.5-2.4 h-1 and ∼2.3 h-1, respectively. Air-cleaning was 83% and 69% efficient, respectively, in removing monoterpenes and isoprene. By suppressing precursors, scaling calculations show air-cleaning prevented ∼3.4 mg/h of indoor SOA formation due to indoor ozone-monoterpene chemistry. For comparison, we estimate that filtration removed ∼130 mg/h of PM0.01-0.3.

Investigating honesty-humility and impulsivity as predictors of aggression in children and youth.

Among adult and adolescent populations, the personality trait of honesty-humility (HH) has been linked to aggression. For example, adults low in HH have been found to exhibit higher levels of workplace delinquency and revenge motivation, and adolescent low in HH are more likely to bully others. However, there is a paucity of research examining this relationship in children and youth, and how these relationships develop over time. The current study addressed these gaps in the literature by assessing whether HH and impulsivity are independently associated with aggression in children Grades 3 through 8 (N = 1201). Using data from the two waves of a longitudinal project, autoregressive crossed-lagged path analysis was used to examine the bidirectional relationships between HH, impulsivity, and aggression over a 1-year period. Results revealed significant bidirectional relationships between HH and aggression, such that lower scores of HH at Time 1 were associated with higher scores of aggression at Time 2 and vice versa. Similarly, higher scores of impulsivity at Time 1 were associated with higher scores of aggression at Time 2 and vice versa. In addition, these relationships were strongest in boys and at higher ages. Consistent with research in other populations, these results indicate that low HH and high impulsivity are linked to aggression in children and youth. Further, our results demonstrate that HH and impulsivity bidirectionally impact aggression as one age, suggesting a need for early intervention.

Viability and development of Ascaridia galli eggs recovered in artificial media followed by storage under different conditions.

Eggs oviposited by Ascaridia galli females in artificial media are commonly used as a source of infective material. We investigated the rate of egg production by cultured mature females (n = 223), and changes in egg viability under different storage and incubation conditions. Eggs recovered after 1, 2 or 3 days of culture were subjected to either (1) storage in water at 4°C (1, 4 or 8 weeks) followed by incubation in 0.1 N H2SO4 at 26°C (2, 4 or 6 weeks); or (2) prolonged storage at 4°C (up to 14 weeks). Egg development and viability was assessed by morphology coupled with a viability dye exclusion test of hatched larvae. Of the 6,044 eggs recovered per mature female 49.2, 38.5 and 12.3% were recovered on days 1, 2 and 3 of worm incubation respectively with similar initial viability (≥99%) between days. Eggs recovered on different days had only minor differences in viability after storage. The prolonged storage period at 4°C significantly affected both viability and embryonation ability resulting in decline in viability of 5.7-6.2% per week. A smaller but significant decline in egg (2.0%) and hatched larval (1.4%) viability per week of incubation at 26°C was also observed. We conclude that storage and incubation conditions, not the day of egg recovery, are the main factors affecting A. galli egg viability. Our findings indicate that under aerobic conditions storage at 26°C may be preferable to 4°C whereas other studies indicate that under anaerobic conditions storage at 4°C is preferable.

Measuring the Building Envelope Penetration Factor for Ambient Nitrogen Oxides.

Much of human exposure to nitrogen oxides (NOx) of ambient origin occurs indoors. Reactions with materials inside building envelopes are expected to influence the amount of ambient NOx that infiltrates indoors. However, envelope penetration factors for ambient NOx constituents have never been measured. Here, we develop and apply methods to measure the penetration factor and indoor loss rates for ambient NOx constituents using time-resolved measurements in an unoccupied apartment unit. Multiple test methods and parameter estimation approaches were tested, including natural and artificial indoor NOx elevation with and without accounting for indoor oxidation reactions. Twelve of 16 tests yielded successful estimates of penetration factors and indoor loss rates. The penetration factor for NO was confirmed to be ∼1 and the mean (±s.d.) NO2 penetration factor was 0.72 ± 0.06 with a mean relative uncertainty of ∼15%. The mean (±s.d.) indoor NO2 loss rate was 0.27 ± 0.12 h-1, ranging 0.06-0.47 h-1, with strong correlations with indoor relative and absolute humidity. Indoor NO loss rates were strongly correlated with the estimated ozone concentration in infiltrating air. Results suggest that envelope penetration factors and loss rates for NOx constituents can be reasonably estimated across a wide range of conditions using these approaches.

Force versus fury: Sex differences in the relationships among physical and psychological threat potential, the facial width-to-height ratio, and judgements of aggressiveness.

Individuals with larger facial width-to-height ratios (FWHRs) are judged as more threatening, and engage in more threat-related behavior, than do individuals with smaller FWHRs. Here we identified components of threat potential that are related to the FWHR. In Study 1, the FWHR was correlated positively with physical threat potential (bicep size) in women and with both physical and psychological (anger proneness) threat potential in men. Behavioral aggression was measured in a subset of these participants using the Point Subtraction Aggression Paradigm (costly aggression) and a Money Allocation Task (non-costly aggression). Psychological (but not physical) threat potential predicted non-costly aggression and physical (but not psychological) threat potential predicted costly aggression. In Study 2, a separate set of participants judged the anger proneness, strength, or aggressiveness of male participants photographed in Study 1. Participants' judgements of all three characteristics were associated with the FWHR, and there were sex differences in how aggressiveness was conceptualized (for women, aggressiveness was associated with anger proneness, for men, aggressiveness was associated with strength). These results are consistent with the hypothesis that the FWHR may be an adaptation to cue the threat potential of men.

The Point Subtraction Aggression Paradigm as a laboratory tool for investigating the neuroendocrinology of aggression and competition.

A contribution to a special issue on Hormones and Human Competition.The ease of measuring steroids in saliva has led to an increase in investigating their role in competition and aggression in laboratory settings and using behavioral measures of aggression. We review here the Point-Subtraction-Aggression-Paradigm (PSAP) as a measure of costly aggression and we compare and contrast the PSAP to other aggression measures. We describe our use of the PSAP, highlighting how it can be modified to investigate a broad array of experimental questions. We review studies that have investigated neuroendocrine function and the PSAP, and we conclude that across studies the relationship between fluctuations in testosterone and PSAP aggression scores are directionally positive, and are likely specific to men. Investigations of other neuroendocrine measures and the PSAP are fewer, limiting conclusions that can be drawn for other hormones. We provide two versions of the PSAP that can be used with E-PRIME® software for researchers interested in this measure for their laboratories.

Enhanced chlorhexidine skin penetration with 1,8-cineole.

BACKGROUND: Chlorhexidine (CHG) penetrates poorly into skin. The purpose of this study was to compare the depth of CHG skin permeation from solutions containing either 2% (w/v) CHG and 70% (v/v) isopropyl alcohol (IPA) or 2% (w/v) CHG, 70% (v/v) IPA and 2% (v/v) 1,8-cineole. METHODS: An ex-vivo study using Franz diffusion cells was carried out. Full thickness human skin was mounted onto the cells and a CHG solution, with or without 2% (v/v) 1,8-cineole was applied to the skin surface. After twenty-four hours the skin was sectioned horizontally in 100 µm slices to a depth of 2000 µm and the concentration of CHG in each section quantified using high performance liquid chromatography (HPLC). The data were analysed with repeated measures analysis of variance. RESULTS: The concentration of CHG in the skin on average was significantly higher (33.3% [95%, CI 1.5% - 74.9%]) when a CHG solution which contained 1,8-cineole was applied to the skin compared to a CHG solution which did not contain this terpene (P = 0.042). CONCLUSIONS: Enhanced delivery of CHG can be achieved in the presence of 1,8-cineole, which is the major component of eucalyptus oil. This may reduce the numbers of microorganisms located in the deeper layers of the skin which potentially could decrease the risk of surgical site infection.

Pre-treatment lymphocytopaenia is an adverse prognostic biomarker in muscle-invasive and advanced bladder cancer.

BACKGROUND: Pre-treatment lymphocytopaenia may result from cytokines secreted by the tumour microenvironment in association with aggressive tumour biology. We sought to establish the prognostic significance of lymphocytopaenia in muscle-invasive and advanced bladder cancer. PATIENTS AND METHODS: Seventy-four patients with muscle-invasive bladder cancer treated with radical chemoradiotherapy and 131 patients with advanced bladder cancer treated with palliative chemotherapy were included in the study. The absolute lymphocyte count on the first day of treatment was recorded. Invasive local or systemic recurrence in the muscle-invasive bladder cancer cohort and all-cause mortality in the advanced bladder cancer cohort were defined as survival end points. Receiver operating characteristic (ROC) curve analysis was utilized to determine the cut-off for defining lymphocytopaenia in the muscle-invasive bladder cancer cohort followed by multivariable analysis in a model evaluating the following variables: anaemia, neutrophilia, tumour stage, hydronephrosis and neoadjuvant chemotherapy. Subsequently, lymphocytopaenia was assessed in a multivariable model of the advanced bladder cancer cohort analysing the following prognostic variables: neutrophilia, anaemia, performance status and presence of bone or visceral metastases. A further analysis was carried out evaluating absolute lymphocyte count as a continuous variable. RESULTS: An absolute lymphocyte count of 1.5 × 10(9)/l was determined as the cut-off on ROC curve analysis in the muscle-invasive bladder cancer cohort, and multivariate analysis revealed that only lymphocytopaenia was predictive for inferior outcome in this cohort. In the advanced bladder cancer cohort, lymphocytopaenia [hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.1-2.4; P = 0.02] and performance status (HR 1.7, 95% CI 1.0-2.7; P = 0.047) were adverse prognostic factors in the binary variable multivariate model. Absolute lymphocyte count was the sole significant factor when analysed as a continuous variable (HR 0.66, 95% CI 0.5-0.87; P = 0.003). CONCLUSION: Pre-treatment lymphocytopaenia is an independent adverse prognostic factor in both muscle-invasive and advanced bladder cancer. It may be a manifestation of cancer-induced immune suppression driving tumour progression.

Distinct immune signatures in the colon of Crohn's disease and ankylosing spondylitis patients in the absence of inflammation.

Crohn's disease (CD) is an inflammatory bowel disease characterized by patchy inflammation of the gastrointestinal tract. Ankylosing spondylitis (AS) is primarily characterized by inflammation of the lower vertebral column, and many patients with AS present with inflammatory gut symptoms. Genome-wide association studies have highlighted significant overlap in short nucleotide polymorphisms for both diseases. We hypothesized that patients with CD and AS have a common intestinal immune signature, characterized by inflammatory T cells, compared with healthy people. We designed a pilot study to determine both the feasibility of defining complex immune signatures from primary tissue, and differences in the local immune signature of people with inflammatory diseases compared with healthy people. Intestinal biopsies were obtained by colonoscopy from healthy patients, non-inflamed regions of CD patients and AS patients with inflammatory gut symptoms. A flow cytometry platform was developed measuring polyfunctional T-cell populations based on cytokines, surface molecules and transcription factors. There was overlap in the immune signature of people with CD or AS, characterized by changes in the frequency of regulatory T cells, compared with healthy people. There were significant differences in frequencies of other polyfunctional T-cell populations-CD patients had an increased frequency of T cells producing interleukin-22 (IL-22) and interferon-γ, whereas AS patients had an increased frequency of T cells producing IL-2; compared with healthy people. These data indicate that the local immune signature could be described in these patients and that distinct immune mechanisms may underlie disease progression.

Azathioprine is effective for oral involvement in Crohn's disease but not for orofacial granulomatosis alone.

BACKGROUND: There have been no previous reports assessing the effectiveness of azathioprine (AZA) in the treatment of orofacial granulomatosis (OFG). This report is a review of patients receiving AZA for active OFG with or without concomitant gut Crohn's disease (CD) in a specialist tertiary referral centre. METHODS: Clinical response was defined by Global Physician Assessment at 4-, 12- and 24-month follow-up and a standardised oral disease activity score (ODAS). RESULTS: Sixty of 215 patients seen with OFG in our clinic over a 12-year period were treated with AZA. Of these, 22 had concomitant CD. The proportion of patients responding to AZA with a diagnosis of CD/OFG vs. OFG only at 4, 12 and 24 months were 54% vs. 21% (P = 0.03), 59% vs. 21% (P = 0.003) and 41% vs. 24% (P = 0.16), respectively. A statistically significant difference was seen between starting and follow-up ODAS scores at 4 months in the CD/OFG group which was not observed in the OFG only group. Factors predicting a need for AZA included a diagnosis of intestinal CD, sulcal swelling, sulcal ulcers and upper lip involvement. The factor predicting response to treatment was a diagnosis of CD at 12 months of follow-up. No difference in the number of adverse effects was observed between the two groups of patients. CONCLUSIONS: AZA is significantly more effective in the treatment of oral disease with a concurrent diagnosis of CD rather than in the treatment of OFG alone.

Multi-platform assessment of transcriptional profiling technologies utilizing a precise probe mapping methodology.

BACKGROUND: The arrival of RNA-seq as a high-throughput method competitive to the established microarray technologies has necessarily driven a need for comparative evaluation. To date, cross-platform comparisons of these technologies have been relatively few in number of platforms analyzed and were typically gene name annotation oriented. Here, we present a more extensive and yet precise assessment to elucidate differences and similarities in performance of numerous aspects including dynamic range, fidelity of raw signal and fold-change with sample titration, and concordance with qRT-PCR (TaqMan). To ensure that these results were not confounded by incompatible comparisons, we introduce the concept of probe mapping directed "transcript pattern". A transcript pattern identifies probe(set)s across platforms that target a common set of transcripts for a specific gene. Thus, three levels of data were examined: entire data sets, data derived from a subset of 15,442 RefSeq genes common across platforms, and data derived from the transcript pattern defined subset of 7,034 RefSeq genes. RESULTS: In general, there were substantial core similarities between all 6 platforms evaluated; but, to varying degrees, the two RNA-seq protocols outperformed three of the four microarray platforms in most categories. Notably, a fourth microarray platform, Agilent with a modified protocol, was comparable, or marginally superior, to the RNA-seq protocols within these same assessments, especially in regards to fold-change evaluation. Furthermore, these 3 platforms (Agilent and two RNA-seq methods) demonstrated over 80% fold-change concordance with the gold standard qRT-PCR (TaqMan). CONCLUSIONS: This study suggests that microarrays can perform on nearly equal footing with RNA-seq, in certain key features, specifically when the dynamic range is comparable. Furthermore, the concept of a transcript pattern has been introduced that may minimize potential confounding factors of multi-platform comparison and may be useful for similar evaluations.

Antimicrobial activity and skin permeation of iodine present in an iodine-impregnated surgical incise drape.

OBJECTIVES: The antimicrobial efficacy of an iodine-impregnated incise drape against MRSA was evaluated in a skin model. The permeation of iodine from this drape into the skin was also assessed. METHODS: The antimicrobial efficacy was evaluated in ex vivo studies following application of the surgical incise drape for various times on the surface of donor skin, which was inoculated with either 1 × 10(3) or 1 × 10(6) cfu MRSA/cm(2) skin and mounted on Franz diffusion cells. In some experiments the MRSA-inoculated skin was pre-incubated for 18 h at room temperature prior to applying the drape. Permeation of iodine into the skin using this model was also determined following application of the incise drape for 6 h. RESULTS: The iodine-impregnated drape demonstrated antimicrobial activity compared with the non-use of drape. This reached significance when a high inoculum of MRSA was applied with no pre-incubation period and when a low inoculum of MRSA was applied with a pre-incubation period (P = 0.002 and P = 0.014, respectively). Furthermore, in experiments wherein a high inoculum of MRSA was applied with no pre-incubation period, the iodine-impregnated drape demonstrated superior antimicrobial activity compared with the use of a non-antimicrobial drape (P < 0.001). MIC and MBC values of iodine were attained to 1500 µm below the skin surface. CONCLUSIONS: The iodine-impregnated surgical incise drape had detectable antimicrobial activity. Furthermore, iodine penetrated into the deeper layers of the skin. This property should suppress microbial regrowth at and around a surgical incision site, making its use preferable to the use of a standard drape or non-use of a drape.

AZD3514, an oral selective androgen receptor down-regulator in patients with castration-resistant prostate cancer - results of two parallel first-in-human phase I studies.

BACKGROUND: AZD3514 is a first-in-class, orally bio-available, androgen-dependent and -independent androgen receptor inhibitor and selective androgen-receptor down-regulator (SARD). METHODS: In study 1 and 2, castration-resistant prostate cancer (CRPC) patients (pts) were initially recruited into a once daily (QD) oral schedule (A). In study 1, pharmacokinetic assessments led to twice daily (BID) dosing (schedule B) to increase exposure. Study 2 explored a once daily schedule. RESULTS: In study 1, 49 pts were treated with escalating doses of AZD3514 (A 35 pts, B 14 pts). Starting doses were 100 mg (A) and 1000 mg (B). The AZD3514 formulation was switched from capsules to tablets at 1000 mg QD. 2000 mg BID was considered non-tolerable due to grade (G) 2 toxicities (nausea [N], vomiting [V]). No adverse events (AEs) met the dose-limiting toxicity (DLT) definition. Thirteen pts received AZD3514 in study 2, with starting doses of 250 mg QD. The most frequent drug-related AEs were N: G1/2 in 55/70 pts (79 %); G3 in 1 pt (1.4 %); & V: G1/2 in 34/70 pts (49 %) & G3 in 1 pt (1.4 %). PSA declines (≥50 %) were documented in 9/70 patients (13 %). Objective soft tissue responses per RECIST1.1 were observed in 4/24 (17 %) pts in study 1. CONCLUSION: AZD3514 has moderate anti-tumour activity in pts with advanced CRPC but with significant levels of nausea and vomiting. However, anti-tumour activity as judged by significant PSA declines, objective responses and durable disease stabilisations, provides the rationale for future development of SARD compounds.

Multipartite entangled spatial modes of ultracold atoms generated and controlled by quantum measurement.

We show that the effect of measurement backaction results in the generation of multiple many-body spatial modes of ultracold atoms trapped in an optical lattice, when scattered light is detected. The multipartite mode entanglement properties and their nontrivial spatial overlap can be varied by tuning the optical geometry in a single setup. This can be used to engineer quantum states and dynamics of matter fields. We provide examples of multimode generalizations of parametric down-conversion, Dicke, and other states; investigate the entanglement properties of such states; and show how they can be transformed into a class of generalized squeezed states. Furthermore, we propose how these modes can be used to detect and measure entanglement in quantum gases.