Biomarkers of Recent Cannabis Use in Blood, Oral Fluid and Breath.

Proving driving under the influence of cannabis (DUIC) is difficult. Establishing a biomarker of recent use to supplement behavioral observations may be a useful alternative strategy. We determined whether cannabinoid concentrations in blood, oral fluid (OF) or breath could identify use within the past 3 h-likely the period of the greatest impairment. In a randomized trial, 191 frequent (≥4/week) and occasional (<4/week) cannabis users smoked one cannabis (placebo [0.02%], or 5.9% or 13.4% Δ9-tetrahydrocannabinol [THC]) cigarette ad libitum. Blood, OF and breath samples were collected prior to and up to 6 h after smoking. Samples were analyzed for 10 cannabinoids in OF, 8 in blood and THC in breath. Frequent users had more residual THC in blood and were more likely to be categorized as 'recently used' prior to smoking; this did not occur in OF. Per se limits ranging from undetectable to 5 ng/mL THC in blood offered limited usefulness as biomarkers of recent use. Cannabinol (CBN, cutoff = 1 ng/mL) in blood offered 100% specificity but only 31.4% sensitivity, resulting in 100% positive predictive value (PPV) and 94.0% negative predictive value (NPV) at 4.3% prevalence; however, CBN may vary by cannabis chemovar. A 10 ng/mL THC cutoff in OF exhibited the overall highest performance to detect its use within 3 h (99.7% specificity, 82.4% sensitivity, 92.5% PPV and 99.2% NPV) but was still detectable in 23.2% of participants ∼4.4 h post-smoking, limiting specificity at later time points. OF THC may be a helpful indicator of recent cannabis intake, but this does not equate to impairment. Behavioral assessment of impairment is still required to determine DUIC. This study only involved cannabis inhalation, and additional research evaluating alternative routes of ingestion (i.e., oral) is needed.

Optimizing biologic sequencing in metastatic colorectal cancer: first line and beyond.

Significant advances in the treatment of metastatic colorectal cancer (mcrc) since the early 2000s have led to improved clinical outcomes, including overall survival (os). When fluorouracil was the sole treatment agent for mcrc, os in phase iii studies was approximately 12 months. Now, in 2019, the median os (mos) in the most recent mcrc clinical trials has been approaching 3 years. The biologic agents that target the vascular endothelial growth factor (vegf), epithelial growth factor receptor (egfr), human epidermal growth factor receptor 2 (her2), PD-1, ctla-4, ntrk, and braf pathways play important roles in the mcrc treatment algorithm, given their significant-sometimes dramatic-activity. Emerging data indicate that the choice of a specific biologic at a particular time (line of treatment) for specific patient populations (based on tumour characteristics) is critical. In the present review, we discuss the available evidence for optimal biologic sequencing in the management of mcrc.

Blocking FcRn in humans reduces circulating IgG levels and inhibits IgG immune complex-mediated immune responses.

The neonatal crystallizable fragment receptor (FcRn) functions as an intracellular protection receptor for immunoglobulin G (IgG). Recently, several clinical studies have reported the lowering of circulating monomeric IgG levels through FcRn blockade for the potential treatment of autoimmune diseases. Many autoimmune diseases, however, are derived from the effects of IgG immune complexes (ICs). We generated, characterized, and assessed the effects of SYNT001, a FcRn-blocking monoclonal antibody, in mice, nonhuman primates (NHPs), and humans. SYNT001 decreased all IgG subtypes and IgG ICs in the circulation of humans, as we show in a first-in-human phase 1, single ascending dose study. In addition, IgG IC induction of inflammatory pathways was dependent on FcRn and inhibited by SYNT001. These studies expand the role of FcRn in humans by showing that it controls not only IgG protection from catabolism but also inflammatory pathways associated with IgG ICs involved in a variety of autoimmune diseases.

Identifying Spatial Variation Along the HIV Care Continuum: The Role of Distance to Care on Retention and Viral Suppression.

Distance to HIV care may be associated with retention in care (RIC) and viral suppression (VS). RIC (≥ 2 HIV visits or labs ≥ 90 days apart in 12 months), prescribed antiretroviral therapy (ART), VS (< 200 copies/mL at last visit) and distance to care were estimated among 3623 DC Cohort participants receiving HIV care in 13 outpatient clinics in Washington, DC in 2015. Logistic regression models and geospatial statistics were computed. RIC was 73%; 97% were on ART, among whom 77% had VS. ZIP code-level clusters of low RIC and high VS were found in Northwest DC, and low VS in Southeast DC. Those traveling ≥ 5 miles had 30% lower RIC (adjusted odds ratio (aOR) 0.71, 95% CI 0.58, 0.86) and lower VS (OR 0.70, 95% CI 0.52, 0.94). Geospatial clustering of RIC and VS was observed, and distance may be a barrier to optimal HIV care outcomes.

Real-time gait analysis with accelerometer-based smart shoes.

In this paper, we present the evaluation of a new smart shoe capable of performing gait analysis in real time. The system is exclusively based on accelerometers which minimizes the power consumption. The estimated parameters are activity class (rest/walk/run), step cadence, ground contact time, foot impact (zone, strength, and balance), forward distance, and speed. The different parameters have been validated with a customized database of 26 subjects on a treadmill and video data labeled manually. Key measures for running analysis such as the cadence is retrieved with a maximum error of 2%, and the ground contact time with an average error of 3.25%. The classification of the foot impact zone achieves a precision between 72% and 91% depending of the running style. The presented algorithm has been licensed to ICON Health & Fitness Inc. for their line of wearables under the brand iFit.

The transcriptome of human oocytes is related to age and ovarian reserve.

STUDY QUESTION: How does the human oocyte transcriptome change with age and ovarian reserve? SUMMARY ANSWER: Specific sets of human oocyte messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs) are affected independently by age and ovarian reserve. WHAT IS KNOWN ALREADY: Although it is well established that the ovarian reserve diminishes with increasing age, and that a woman's age is correlated with lower oocyte quality, the interplay of a diminished reserve and age on oocyte developmental competence is not clear. After maturation, oocytes are mostly transcriptionally quiescent, and developmental competence prior to embryonic genome activationrelies on maternal RNA and proteins. STUDY DESIGN, SIZE, DURATION: A total of 36 vitrified/warmed MII oocytes from 30 women undergoing oocyte donation were included in this study, processed and analyzed individually. PARTICIPANTS/MATERIALS, SETTING, METHODS: Total RNA from each oocyte was independently isolated, amplified, labeled, and hybridized on HTA 2.0 arrays (Affymetrix). Data were analyzed using TAC software, in four groups, each including nine oocytes, according to the woman's age and antral follicular count (AFC) (mean ± SD): Young with High AFC (YH; age 21 ± 1 years and 24 ± 3 follicles); Old with High AFC (OH; age 32 ± 2 years and 29 ± 7 follicles); Young with Low AFC (YL; age 24 ± 2 years and 8 ± 2 follicles); Old with Low AFC (OL; age 34 ± 1 years and 7 ± 1 follicles). qPCR was performed to validate arrays. MAIN RESULTS AND THE ROLE OF CHANCE: We identified a set of 30 differentially expressed mRNAs when comparing oocytes from women with different ages and AFC. In addition, 168 non-coding RNAs (ncRNAs) were differentially expressed in relation to age and/or AFC. Few mRNAs have been identified as differentially expressed transcripts, and among ncRNAs, a set of Piwi-interacting RNAs clusters (piRNAs-c) and precursor microRNAs (pre-miRNAs) were identified as increased in high AFC and old groups, respectively. Our results indicate that age and ovarian reserve are associated with specific ncRNA profiles, suggesting that oocyte quality might be mediated by ncRNA pathways. LARGE SCALE DATA: Data can be found via GEO accession number GSE87201. LIMITATIONS, REASONS FOR CAUTION: The oldest woman included in the study was 35 years old, thus our results cannot readily be extrapolated to women older than 35 or infertile women. WIDER IMPLICATIONS OF THE FINDINGS: We show, for the first time, that several non-coding RNAs, usually regulating DNA transcription, are differentially expressed in relation to age and/or ovarian reserve. Interestingly, the mRNA transcriptome of in vivo matured oocytes remains remarkably stable across ages and ovarian reserve, suggesting the possibility that changes in the non-coding transcriptome might regulate some post-transcriptional/translational mechanisms which might, in turn, affect oocyte developmental competence. STUDY FUNDING AND COMPETING INTEREST(S): This work was supported by intramural funding of Clinica EUGIN and by the Secretary for Universities and Research of the Ministry of Economy and Knowledge of the Government of Catalonia. J.H. and A.S. are employees of Affymetrix, otherwise there are no competing interests.

Efficacy and safety of follitropin alfa/lutropin alfa in ART: a randomized controlled trial in poor ovarian responders.

STUDY QUESTION: How does the efficacy and safety of a fixed-ratio combination of recombinant human FSH plus recombinant human LH (follitropin alfa plus lutropin alfa; r-hFSH/r-hLH) compare with that of r-hFSH monotherapy for controlled ovarian stimulation (COS) in patients with poor ovarian response (POR)? SUMMARY ANSWER: The primary and secondary efficacy endpoints were comparable between treatment groups and the safety profile of both treatment regimens was favourable. WHAT IS KNOWN ALREADY: Although meta-analyses of clinical trials have suggested some beneficial effect on reproductive outcomes with r-hLH supplementation in patients with POR, the definitions of POR were heterogeneous and limit the comparability across studies. STUDY DESIGN, SIZE, DURATION: Phase III, single-blind, active-comparator, randomized, parallel-group clinical trial. Patients were followed for a single ART cycle. A total of 939 women were randomized (1:1) to receive either r-hFSH/r-hLH or r-hFSH. Randomization, stratified by study site and participant age, was conducted via an interactive voice response system. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women classified as having POR, based on criteria incorporating the ESHRE Bologna criteria, were down-regulated with a long GnRH agonist protocol and following successful down-regulation were randomized (1:1) to COS with r-hFSH/r-hLH or r-hFSH alone. The primary efficacy endpoint was the number of oocytes retrieved following COS. Safety endpoints included the incidence of adverse events, including ovarian hyperstimulation syndrome (OHSS). Post hoc analyses investigated safety outcomes and correlations between live birth and baseline characteristics (age and number of oocytes retrieved in previous ART treatment cycles or serum anti-Müllerian hormone (AMH)). The significance of the treatment effect was tested by generalized linear models (Poisson regression for counts and logistic regression for binary endpoints) adjusting for age and country. MAIN RESULTS AND THE ROLE OF CHANCE: Of 949 subjects achieving down-regulation, 939 were randomized to r-hFSH/r-hLH (n = 477) or r-hFSH (n = 462) and received treatment. Efficacy assessment: In the intention-to-treat (ITT) population, the mean (SD) number of oocytes retrieved (primary endpoint) was 3.3 (2.71) in the r-hFSH/r-hLH group compared with 3.6 (2.82) in the r-hFSH group (between-group difference not statistically significant). The observed difference between treatment groups (r-hFSH/r-hLH and r-hFSH, respectively) for efficacy outcomes decreased over the course of pregnancy (biochemical pregnancy rate: 17.3% versus 23.9%; clinical pregnancy rate: 14.1% versus 16.8%; ongoing pregnancy rate: 11.0% versus 12.4%; and live birth rate: 10.6% versus 11.7%). An interaction (identified post hoc) between baseline characteristics related to POR and treatment effect was noted for live birth, with r-hFSH/r-hLH associated with a higher live birth rate for patients with moderate or severe POR, whereas r-hFSH was associated with a higher live birth rate for those with mild POR. A post hoc logistic regression analysis indicated that the incidence of total pregnancy outcome failure was lower in the r-hFSH/r-hLH group (6.7%) compared with the r-hFSH group (12.4%) with an odds ratio of 0.52 (95% CI 0.33, 0.82; P = 0.005). Safety assessment: The overall proportion of patients with treatment-emergent adverse events (TEAEs) occurring during or after r-hFSH/r-hLH or r-hFSH use (stimulation or post-stimulation phase) was 19.9% and 26.8%, respectively. There was no consistent pattern of TEAEs associated with either treatment. LIMITATIONS, REASONS FOR CAUTION: Despite using inclusion criteria for POR incorporating the ESHRE Bologna criteria, further investigation is needed to determine the impact of the heterogeneity of POR in the Bologna patient population. The observed correlation between baseline clinical characteristics related to POR and live birth rate, as well as the observed differences between groups regarding total pregnancy outcome failure were from post hoc analyses, and the study was not powered for these endpoints. In addition, the attrition rate for pregnancy outcomes in this trial may not reflect general medical practice. Furthermore, as the patient population was predominantly White these results might not be applicable to other ethnicities. WIDER IMPLICATIONS OF THE FINDINGS: In the population of women with POR investigated in this study, although the number of oocytes retrieved was similar following stimulation with either a fixed-ratio combination of r-hFSH/r-hLH or r-hFSH monotherapy, post hoc analyses showed that there was a lower rate of total pregnancy outcome failure in patients receiving r-hFSH/r-hLH, in addition to a higher live birth rate in patients with moderate and severe POR. These findings are clinically relevant and require additional investigation. The benefit:risk balance of treatment with either r-hFSH/r-hLH or r-hFSH remains positive. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by Merck KGaA, Darmstadt, Germany. P.H. has received honoraria for lectures and unrestricted research grants from Ferring, Merck KGaA and MSD. D.R. is a former employee of EMD Serono, a business of Merck KGaA, Darmstadt, Germany. J.S., J.H. and W.C. are employees of EMD Serono Research and Development Institute, a business of Merck KGaA, Darmstadt, Germany. T.D.'H. and S.L. are employees of Merck KGaA, Darmstadt, Germany. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT02047227; EudraCT Number: 2013-003817-16. TRIAL REGISTRATION DATE: ClinicalTrials.gov: 24 January 2014; EudraCT: 19 December 2013. DATE OF FIRST PATIENT'S ENROLMENT: 30 January 2014.

Prognostic significance of baseline fatigue for overall survival: A patient-level meta-analysis of 43 oncology clinical trials with 3915 patients.

We have previously identified a single-item measure for baseline overall quality of life (QOL) as a strong prognostic factor for survival, and that fatigue was an important component of patient QOL. To explore whether patient-reported fatigue was supplemental or redundant to the prognostic information of overall QOL, we performed a patient-level pooled analysis of 43 North Central Cancer Treatment Group (NCCTG) and Mayo Clinic Cancer Center (MCCC) oncology clinical trials assessing the effect of baseline fatigue on overall survival (OS). 3,915 patients participating in 43 trials provided data at baseline for fatigue on a single-item 0-100 point scale. OS was tested for association with clinically deficient fatigue (CDF, score 0-50, n = 1,497) versus not clinically deficient fatigue (nCDF, score 51-100, n = 2,418). We explored whether fatigue contributed to overall survival in the presence of performance status and overall QOL. We used Cox proportional hazards models that adjusted for the effects of overall QOL, performance score, race, disease site, age and gender. Baseline fatigue was a strong predictor of OS for the entire patient cohort (CDF vs. nCDF: 31.5 months vs > 83.9 months, p < 0.0001). The effect sizes of fatigue on survival were more variable across different disease sites than was seen for overall QOL (GI, esophageal, head and neck, prostate, lung, breast and others). After controlling for covariates, including performance status and overall QOL, baseline fatigue remained a strong prognostic factor in multivariate models (CDF vs. nCDF: HR = 1.23, p = 0.02). Baseline fatigue is a strong and independent prognostic factor for OS over and above performance status (PS) and overall QOL in a wide variety of oncology patient populations. Single-item measures of overall QOL and fatigue can help to identify vulnerable subpopulations among cancer patients. We recommend these single-item measures for routine inclusion as a stratification factor or key covariate in the design and analysis of oncology treatment trials.

Phenotypic differentiation is associated with divergent sexual selection among closely related barn swallow populations.

Sexual selection plays a key role in the diversification of numerous animal clades and may accelerate trait divergence during speciation. However, much of our understanding of this process comes from phylogenetic comparative studies, which rely on surrogate measures such as dimorphism that may not represent selection in wild populations. In this study, we assess sexual selection pressures for multiple male visual signals across four barn swallow (Hirundo rustica) populations. Our sample encompassed 2400 linear km and two described subspecies: European H. r. rustica (in the Czech Republic and Romania) and eastern Mediterranean H. r. transitiva (in Israel), as well as a potential area of contact (in Turkey). We demonstrate significant phenotypic differentiation in four sexual signalling axes, despite very low-level genomic divergence and no comparable divergence in an ecological trait. Moreover, the direction of phenotypic divergence is consistent with differences in sexual selection pressures among subspecies. Thus, H. r. transitiva, which have the darkest ventral plumage of any population, experience directional selection for darker plumage. Similarly, H. r. rustica, which have the longest tail feathers of any population, experience directional selection for elongated tail feathers and disruptive selection for ventral plumage saturation. These results suggest that sexual selection is the primary driver of phenotypic differentiation in this species. Our findings add to growing evidence of phenotypic divergence with gene flow. However, to our knowledge, this is the first study to relate direct measures of the strength and targets of sexual selection to phenotypic divergence among closely related wild populations.

Genome-wide differentiation in closely related populations: the roles of selection and geographic isolation.

Population divergence in geographic isolation is due to a combination of factors. Natural and sexual selection may be important in shaping patterns of population differentiation, a pattern referred to as 'isolation by adaptation' (IBA). IBA can be complementary to the well-known pattern of 'isolation by distance' (IBD), in which the divergence of closely related populations (via any evolutionary process) is associated with geographic isolation. The barn swallow Hirundo rustica complex comprises six closely related subspecies, where divergent sexual selection is associated with phenotypic differentiation among allopatric populations. To investigate the relative contributions of selection and geographic distance to genome-wide differentiation, we compared genotypic and phenotypic variation from 350 barn swallows sampled across eight populations (28 pairwise comparisons) from four different subspecies. We report a draft whole-genome sequence for H. rustica, to which we aligned a set of 9493 single nucleotide polymorphisms (SNPs). Using statistical approaches to control for spatial autocorrelation of phenotypic variables and geographic distance, we find that divergence in traits related to migratory behaviour and sexual signalling, as well as geographic distance, together explain over 70% of genome-wide divergence among populations. Controlling for IBD, we find 42% of genomewide divergence is attributable to IBA through pairwise differences in traits related to migratory behaviour and sexual signalling alone. By (i) combining these results with prior studies of how selection shapes morphological differentiation and (ii) accounting for spatial autocorrelation, we infer that morphological adaptation plays a large role in shaping population-level differentiation in this group of closely related populations.

Chronic anti-phencyclidine monoclonal antibody therapy decreases phencyclidine-induced in utero fetal mortality in pregnant rats.

Illicit drug use during pregnancy is a serious social and public health problem inflicting an array of deleterious effects on both mother and offspring. We investigated the hypothesis that a murine anti-phencyclidine (PCP) monoclonal antibody (mAb6B5; K(D)=1.3 nM) can safely protect mother and fetus from PCP-induced adverse health effects in pregnant rats. Pregnant Sprague-Dawley rats (n=4-5) were intravenously administered bolus injections of PCP (1mg/kg) on multiple days during pregnancy. They were also chronically treated with anti-PCP mAb6B5 at 45 mg/kg as a PCP antagonist. This dose provided one mAb-PCP binding site for every four PCP molecules. Therapeutic and safety study endpoints included pregnancy outcome (litter size, number of live vs. dead pups), maternal hemodynamic status and locomotor activity. Maternal hemodynamic changes (i.e., blood pressure and heart rate) and locomotor activity were measured in dams from gestation days 6-21 (one day antepartum) using a radiotelemetry-tracking device with a femoral arterial pressure catheter. This mAb6B5 treatment regimen significantly (p=0.008) reduced the number of PCP-induced in utero fetal deaths (odds ratio=3.2; 95%CI 1.3 to 7.9) and significantly (p<0.05) reduced acute PCP-induced maternal locomotor effects in the second trimester. Maternal hemodynamic responses to PCP were not significantly affected by mAb6B5 treatment. In conclusion, these data suggest that anti-PCP mAb treatments administered during pregnancy can safely protect a mother and her fetus(es) from PCP-related morbidity and mortality even when the mAb dose is too low to significantly prevent other PCP-induced maternal pharmacological effects.

Rheolytic Thrombectomy with or without Adjunctive Indwelling Pharmacolysis in Patients Presenting with Acute Pulmonary Embolism Presenting with Right Heart Strain and/or Pulseless Electrical Activity.

Purpose. To evaluate the safety and efficacy of the Possis rheolytic thrombectomy with or without indwelling catheter-directed pharmacolysis for the treatment of massive pulmonary embolus in patients presenting with right heart strain and/or a pulseless electrical activity (PEA). Materials and Methods. Retrospective review of patients undergoing pulmonary pharmacolysis was performed (07/2004-06/2009). Pre- and posttreatment Miller index scoring weres calculated and compared. Patients were evaluated for tPA doses, ICU stay, hospital stay, and survival by Kaplan-Meier analysis. Results. 11 patients with massive PE were found, with 10/11 presenting with a Miller score of >17 (range: 16-27, mean: 23.2). CTPA and/or echocardiographic evidence of right heart strain was found in 10/11 patients. 3 (27%) patients presented with a PEA event. Two (18%) patients had a contraindication to pharmacolysis and were treated with mechanical thrombectomy alone. The intraprocedural mortality was 9% (n = 1/11). Of the 10 patients who survived the initial treatment, 7 patients underwent standard mechanical thrombectomy initially, while 5 received power pulse spray mechanical thrombectomy. Eight of these 10 patients underwent adjunctive indwelling catheter-directed thrombolysis. The mean catheter-directed infusion duration was 18 hours (range of 12-26 hours). The average intraprocedural, infusion, and total doses of tPA were 7 mg, 19.7 mg, and 26.7 mg, respectively. There was a 91% (10/11) technical success rate. The failure was the single mortality. Average reduction in Miller score was 9.5 or 41% (P = 0.009), obstructive index of 6.4 or 47% (P = 0.03), and perfusion index of 2.7 or 28% (P = 0.05). Average ICU and hospital stay were 7.4 days (range 2-27 days) and 21.3 days (range 6-60 days), respectively. Intent to treat survival was 90% at 6, 12, and 18 months. Conclusion. Rheolytic thrombectomy with or without adjunctive catheter-directed thrombolysis provides a safe and effective method for treatment of acute PE in patients who present with right heart strain and/or a PEA event.

Improving prediction of malignancy of cytologically indeterminate thyroid nodules.

BACKGROUND: Fine-needle aspiration (FNA) is essential in the investigation of thyroid nodules. The British Thyroid Association guidelines recommend clarification of whether follicular nodules are probable follicular neoplasms that require surgical excision. This study assessed the value of the subclassification of cytologically indeterminate thyroid nodules into either follicular neoplasms or other pathology. METHODS: The cytology reports of all thyroid FNAs performed between November 2005 and December 2007 at a single institution reported as Thy 3 (follicular lesions) were reviewed. They were reclassified as Thy 3A (probable follicular neoplasm) or Thy 3B (probable non-neoplastic lesion), and subsequently correlated with final clinical outcome to determine the predictive value of this subclassification. RESULTS: Forty-nine specimens were categorized as Thy 3A and 55 as Thy 3B. Of excised lesions, 14 (29 per cent) of 48 Thy 3A and 4 (10 per cent) of 42 Thy 3B nodules were malignant. If Thy 3A were to predict malignancy and Thy 3B benign disease, the sensitivity of the classification was 88 per cent, with a specificity of 55 per cent and negative predictive value of 91 per cent. CONCLUSION: Subclassification of Thy 3 nodules into Thy 3A and Thy 3B improves the assessment of risk for thyroid malignancy.

Robotic anterior pelvic exenteration for bladder cancer in the female: outcomes and comparisons to their male counterparts.

BACKGROUND: Recent small case series have now been reported for robotic-assisted laparoscopic radical cystectomy. The majority of these series have reported techniques and outcomes in a predominantly male patient population. The application of such novel techniques to female cystectomy and anterior exenterative procedures has not been well documented and described. In this paper, we report our initial experience with robotic anterior pelvic exenteration in the female with bladder cancer evaluating perioperative and pathologic outcomes of this novel procedure and comparing the outcomes to those observed in their male counterparts. METHODS: Fifty patients underwent a robotic radical cystectomy and extracorporeal diversion for clinically localized bladder cancer: 40 male patients (robotic radical cystoprostatetctomy) and 10 women (robotic anterior pelvic exenteration). Outcome measures evaluated in this series included operative variables, hospital recovery, pathologic outcomes, and complication rate. RESULTS: Mean age of female patients was 68.4 years and of male patients was 62.8. Mean operating room time was 4.6 hours, and mean surgical blood loss was 215 mL. On surgical pathology, 5 patients were <=pT2, 3 patients pT3, and 2 patients N+. In no case was there a positive surgical margin, though in 1 case there was inadvertent entry into the bladder. Mean number of lymph nodes removed was 19 (range, 12-34). Mean time to flatus was 1.9 days, time to bowel movement 2.4 days, and time to discharge 4.9 days. These outcomes were comparable to the male patients, particularly the 20 male patients undergoing robotic radical cystoprostatectomy during the same time period. CONCLUSIONS: In our experience, the robotic anterior exenteration has been readily adapted to the surgical treatment of bladder cancer with similar outcomes to those observed in male patients undergoing a robotic radical cystoprostatectomy. The approach appears to achieve the clinical and oncologic goals of radical cystectomy in both the female and male patient.

Rule based processing of the CD4000, CD3200 and CD Sapphire analyser output using the Cerner Discern Expert Module.

The latest version of our Laboratory Information System haematology laboratory expert system that handles the output of Abbott Cell-Dyn Sapphires, CD4000s and a CD3200 full blood count analyser in three high-volume haematology laboratories is described. The three hospital laboratories use Cerner Millennium Version 2007.02 software and the expert system uses Cerner Millennium Discern Expert rules and some small Cerner Command Language in-house programs. The entire expert system is totally integrated with the area-wide database and has been built and maintained by haematology staff members, as has the haematology database. Using patient demographic data, analyser numeric results, analyser error and morphology flags and previous results for the patient, this expert system decides whether to validate the main full blood count indices and white cell differential, or if the analyser results warrant further operator intervention/investigation before verifying, whether a blood film is required for microscopic review and if abnormal results require phoning to the staff treating the patient. The principles of this expert system can be generalized to different haematology analysers and haematology laboratories that have different workflows and different software.

Impact of model perfumes on surfactant and mixed surfactant self-assembly.

The impact of some model perfumes on surfactant self-assembly has been investigated, using small-angle neutron scattering. A range of different model perfumes, with differing degrees of hydrophilicity/hydrophobicity, have been explored, and in order of increasing hydrophobicity include phenyl ethanol (PE), rose oxide (RO), limonene (LM), linalool (LL), and dihydrogen mercenol (DHM). The effect of their solubilization on the nonionic surfactant micelles of dodecaethylene monododecyl ether (C12EO12) and on the mixed surfactant aggregates of C12EO12 and the cationic dialkyl chain surfactant dihexadecyl dimethyl ammonium bromide (DHDAB) has been quantified. For PE and LL the effect of their solubilization on the micelle, mixed micelle/lamellar and lamellar regimes of the C12EO12/DHDAB mixtures, has also been determined. For the C12EO12 and mixed DHDAB/C12EO12 micelles PE is solubilized predominantly at the hydrophilic/hydrophobic interface, whereas the more hydrophobic perfumes, from RO to DHM, are solubilized predominantly in the hydrophobic core of the micelles. For the C12EO12 micelles, with increasing perfume concentration, the more hydrophobic perfumes (RO to DHM) promote micellar growth. Relatively modest growth is observed for RO and LM, whereas substantial growth is observed for LL and DHM. In contrast, for the addition of PE the C12EO12 micelles remain as relatively small globular micelles, with no significant growth. For the C12EO12/DHDAB mixed micelles, the pattern of behavior with the addition of perfume is broadly similar, except that the micellar growth with increasing perfume concentration for the more hydrophobic perfumes is less pronounced. In the Lbeta (Lv) region of the DHDAB-rich C12EO12/DHDAB phase diagram, the addition of PE results in a less structured (less rigid) lamellar phase, and ultimately a shift toward a structure more consistent with a sponge or bicontinuous phase. In the mixed L1/Lbeta region of the phase diagram PE induces a slight shift in the coexistence from Lbeta toward L1. The addition of LL to the Lbeta (Lv) region of the DHDAB-rich C12EO12/DHDAB phase diagram also results in a reduction in the lamellar structure (less rigid lamellae), and a shift toward a structure more consistent with a sponge or bicontinuous phase, or a coexisting phase of small vesicles. For the mixed L1/Lbeta region of the phase diagram LL induces a shift toward a greater L beta component.

Molecular dynamics study of surface-tethered S(CH2CH2O)6CH3: helix formation and thermal disorder.

We present the results of a molecular dynamics study of a set of surface-tethered S(CH2CH2O)6CH3 chains. In this study, we analyze helix formation, in addition to thermal disorder, and find that spontaneous helix formation and details of helix morphology depend on charge partitioning ascribed to oxygen and the methylene groups. The effects of varying surface coverage as well as chain-surface interaction strength indicate that a set of approximately 7/2 helical structures oriented predominantly normal to the surface are formed at near full coverage. This occurs even though thermal disorder clearly precludes a description based on the concept of a perfect crystalline monolayer. Thermal fluctuations in chain morphology in the vicinity of the terminal methyl groups lead to the exposure of oxygen to the external environment. We also find that the persistence of compact helix-containing domains at partial surface coverage results in the formation of well-defined cavities or void regions that expose the bare surface, even in the presence of strong chain-surface attractive interactions.

Robot-assisted laparoscopic anterior pelvic exenteration for bladder cancer in the female patient.

INTRODUCTION: Recent small case series have now been reported for robotic-assisted laparoscopic radical cystectomy. Herein, we describe our approach and initial experience with robotic-assisted laparoscopic anterior pelvic exenteration in the female patient with bladder cancer. METHODS: We describe the technique of robotic-assisted laparoscopic anterior pelvic exenteration. The classic da Vinci or the da Vinci S robotic platform is utilized for the procedure. In our experience, 12 women underwent robotic-assisted laparoscopic anterior pelvic exenteration and extracorporeal urinary diversion for clinically localized bladder cancer. RESULTS: Mean age was 67.9 years (range 61-79 years). Nine patients underwent ileal conduit diversion and three patients underwent an orthotopic neobladder. In all cases, the urinary diversion was performed extracorporeally. Mean operating room time was 4.6 h; mean surgical blood loss was 221 mL. On surgical pathology, seven patients were =pT2, three patients were pT3, and two patients were N+. In no case was there positive surgical margins, and in one case there was inadvertent entry into the bladder. Mean number of lymph nodes removed was 19 (range 12-34). Mean time to flatus was 1.9 days and to bowel movement 2.4 days, and time to discharge 4.8 days. Six patients were discharged on postoperative day 4, four patients on postoperative day 5, one on postoperative day 6, and one on postoperative day 8. There were two postoperative complications (17%) in two patients. CONCLUSIONS: Our initial experience with robotic-assisted laparoscopic anterior pelvic exenteration appears to be favorable with acceptable operative, pathologic, and short-term clinical outcomes. Certainly, larger experiences are required to adequately evaluate and validate this procedure as an appropriate surgical and oncologic option.