Assessment of biocompatibility of 3D printed photopolymers using zebrafish embryo toxicity assays.
3D printing has emerged as a rapid and cost-efficient manufacturing technique to enable the fabrication of bespoke, complex prototypes. If the technology is to have a significant impact in biomedical applications, such as drug discovery and molecular diagnostics, the devices produced must be biologically compatible to enable their use with established reference assays and protocols. In this work we demonstrate that we can adapt the Fish Embryo Test (FET) as a new method to quantify the toxicity of 3D printed microfluidic devices. We assessed the biocompatibility of four commercially available 3D printing polymers (VisiJetCrystal EX200, Watershed 11122XC, Fototec SLA 7150 Clear and ABSplus P-430), through the observation of key developmental markers in the developing zebrafish embryos. Results show all of the photopolymers to be highly toxic to the embryos, resulting in fatality, although we do demonstrate that post-printing treatment of Fototec 7150 makes it suitable for zebrafish culture within the FET.


Prosecution-retained versus court-appointed experts: comparing and contrasting risk assessment reports in preventative detention hearings.
The goal of this study was to compare the risk assessment reports of prosecution-retained (n = 43) and court-appointed experts (n = 68) within the context of preventative detention hearings on variables ranging from the information within the assessment reports (e.g., length) to the conclusions drawn in terms of risk and treatment amenability (e.g., categorical statements of risk). A separate section also focused specifically on psychopathy. Court-appointed expert assessments were significantly longer (d = 0.40, 95% confidence interval [CI] [0.01, 0.78]) and contained more information pertaining to risk factors (odds ratio [OR] = 4.48, 95% CI [1.21, 16.61]) and risk management (OR = 3.15, 95% CI [1.20, 8.25]). Both types of experts communicated risk assessment results in categorical terms and were highly likely to utilize actuarial scales. Less than half of all assessments contained information on dynamic or protective factors. Other than providing a total psychopathy score, the assessments contained very little additional information about the implications of this score for risk management or treatment amenability. Although the results indicate that risk assessment reports between prosecution-retained and court-appointed experts were more similar than they were different, it is also evident that, overall, reports should contain more information on dynamic risk factors and risk management in order to be useful in the context of preventative detention hearings.


Making Home Sweet and Sturdy: Toxoplasma gondii ppGalNAc-Ts Glycosylate in Hierarchical Order and Confer Cyst Wall Rigidity.
The protozoan intracellular parasite Toxoplasma gondii forms latent cysts in the central nervous system (CNS) and persists for the lifetime of the host. This cyst is cloaked with a glycosylated structure called the cyst wall. Previously, we demonstrated that a mucin-like glycoprotein, CST1, localizes to the cyst wall and confers structural rigidity on brain cysts in a mucin-like domain-dependent manner. The mucin-like domain of CST1 is composed of 20 units of threonine-rich tandem repeats that are O-GalNAc glycosylated. A family of enzymes termed polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts) initiates O-GalNAc glycosylation. To identify which isoforms of ppGalNAc-Ts are responsible for the glycosylation of the CST1 mucin-like domain and to evaluate the function of each ppGalNAc-T in the overall glycosylation of the cyst wall, all five ppGalNAc-T isoforms were deleted individually from the T. gondii genome. The ppGalNAc-T2 and -T3 deletion mutants produced various glycosylation defects on the cyst wall, implying that many cyst wall glycoproteins are glycosylated by T2 and T3. Both T2 and T3 glycosylate the CST1 mucin-like domain, and this glycosylation is necessary for CST1 to confer structural rigidity on the cyst wall. We established that T2 is required for the initial glycosylation of the mucin-like domain and that T3 is responsible for the sequential glycosylation on neighboring acceptor sites, demonstrating hierarchical glycosylation by two distinct initiating and filling-in ppGalNAc-Ts in an intact organism. Toxoplasma gondii is an obligate intracellular parasite that infects a third of the world's population. It can cause severe congenital disease and devastating encephalitis in immunocompromised individuals. We identified two glycosyltransferases, ppGalNAc-T2 and -T3, which are responsible for glycosylating cyst wall proteins in a hierarchical fashion. This glycosylation confers structural rigidity on the brain cyst. Our studies provide new insights into the mechanisms of O-GalNAc glycosylation in T. gondii.


Secretion of alpha-amylase by the embryonic chick pancreas in vitro.
Pancreases taken from chick embryos secrete amylase in vitro when stimulated by cholinergic drugs. Rates of secretion increase with developmental age. The pancreas isolated together with the duodenal loop from the 8 day embryo is already capable of secretion in vitro. It is therefore concluded that the pancreas acquires the ability to secrete digestive enzymes more than 10 days before the beginning of the prominent biochemical and morphological changes associated with the maturation of the gland.


Coupled-mode equations for nonlinear directional couplers.
We point out some inconsistencies in the usual coupledmode formulation employed to model the nonlinear behavior of symmetric directional couplers. In particular, we show that special care is required when neglecting some of the nonlinear terms in the equations.


The Golgi apparatus remains associated with microtubule organizing centers during myogenesis.
In vitro myogenesis involves a dramatic reorganization of the microtubular network, characterized principally by the relocalization of microtubule nucleating sites at the surface of the nuclei in myotubes, in marked contrast with the classical pericentriolar localization observed in myoblasts (Tassin, A. M., B. Maro, and M. Bornens, 1985, J. Cell Biol., 100:35-46). Since a spatial relationship between the Golgi apparatus and the centrosome is observed in most animal cells, we have decided to follow the fate of the Golgi apparatus during myogenesis by an immunocytochemical approach, using wheat germ agglutinin and an affinity-purified anti-galactosyltransferase. We show that Golgi apparatus in myotubes displays a perinuclear distribution which is strikingly different from the polarized juxtanuclear organization observed in myoblasts. As a result, the Golgi apparatus in myotubes is situated close to the microtubule organizing center (MTOC), the cis-side being situated at a fixed distance from the nuclear envelope, a situation which suggests the existence of a structural association between the Golgi apparatus and the nuclear periphery. This is supported by experiments of microtubule depolymerization by nocodazole, in which a minimal effect was observed on Golgi apparatus localization in myotubes in contrast with the dramatic scattering observed in myoblasts. In both cell types, electron microscopy reveals that microtubule disruption generates individual dictyosomes; this suggests that the connecting structures between dictyosomes are principally affected. This structural dependency of the Golgi apparatus upon microtubules is not apparently accompanied by a reverse dependency of MTOC structure or function upon Golgi apparatus activity. Golgi apparatus modification by monensin, as effective in myotubes as in myoblasts, is without apparent effect on MTOC localization or activity and on microtubule stability. The main result of our study is to show that in a cell type where the MTOC is dissociated from centrioles and where antero-posterior polarity has disappeared, the association between the Golgi apparatus and the MTOC is maintained. The significance of such a tight association is discussed.


Sex-related differences in access to care among patients with premature acute coronary syndrome.
Access to care may be implicated in disparities between men and women in death after acute coronary syndrome, especially among younger adults. We aimed to assess sex-related differences in access to care among patients with premature acute coronary syndrome and to identify clinical and gender-related determinants of access to care. We studied 1123 patients (18-55 yr) admitted to hospital for acute coronary syndrome and enrolled in the GENESIS-PRAXY cohort study. Outcome measures were door-to-electrocardiography, door-to-needle and door-to-balloon times, as well as proportions of patients undergoing cardiac catheterization, reperfusion or nonprimary percutaneous coronary intervention. We performed univariable and multivariable logistic regression analyses to identify clinical and gender-related determinants of timely procedures and use of invasive procedures. Women were less likely than men to receive care within benchmark times for electrocardiography (≤ 10 min: 29% v. 38%, p = 0.02) or fibrinolysis (≤ 30 min: 32% v. 57%, p = 0.01). Women with ST-segment elevation myocardial infarction (MI) were less likely than men to undergo reperfusion therapy (primary percutaneous coronary intervention or fibrinolysis) (83% v. 91%, p = 0.01), and women with non-ST-segment elevation MI or unstable angina were less likely to undergo nonprimary percutaneous coronary intervention (48% v. 66%, p < 0.001). Clinical determinants of poorer access to care included anxiety, increased number of risk factors and absence of chest pain. Gender-related determinants included feminine traits of personality and responsibility for housework. Among younger adults with acute coronary syndrome, women and men had different access to care. Moreover, fewer than half of men and women with ST-segment elevation MI received timely primary coronary intervention. Our results also highlight that men and women with no chest pain and those with anxiety, several traditional risk factors and feminine personality traits were at particularly increased risk of poorer access to care.


Pharmacokinetics of Sulfadoxine and Pyrimethamine for Intermittent Preventive Treatment of Malaria During Pregnancy and After Delivery.
Sulfadoxine/pyrimethamine is recommended for intermittent preventative treatment of malaria during pregnancy. Data from 98 women during pregnancy and 77 after delivery in four African countries were analyzed using nonlinear mixed-effects modeling to characterize the effects of pregnancy, postpartum duration, and other covariates such as body weight and hematocrit on sulfadoxine/pyrimethamine pharmacokinetic properties. During pregnancy, clearance increased 3-fold for sulfadoxine but decreased by 18% for pyrimethamine. Postpartum sulfadoxine clearance decreased gradually over 13 weeks. This finding, together with hematocrit-based scaling of plasma to whole-blood concentrations and allometric scaling of pharmacokinetics parameters with body weight, enabled site-specific differences in the pharmacokinetic profiles to be reduced significantly but not eliminated. Further research is necessary to explain residual site-specific differences and elucidate whether dose-optimization, to address the 3-fold increase in clearance of sulfadoxine in pregnant women, is necessary, viable, and safe with the current fixed dose combination of sulfadoxine/pyrimethamine.


Unravelling the Mechanisms of Gold-Silver Core-Shell Nanostructure Formation by in Situ TEM Using an Advanced Liquid Cell Design.
The growth of silver shells on gold nanorods is investigated by in situ liquid cell transmission electron microscopy using an advanced liquid cell architecture. The design is based on microwells in which the liquid is confined between a thin Si3N4 membrane on one side and a few-layer graphene cap on the other side. A well-defined specimen thickness and an ultraflat cell top allow for the application of high-resolution TEM and the application of analytical TEM techniques on the same sample. The combination of high-resolution data with chemical information is validated by radically new insights into the growth of silver shells on cetrimonium bromide stabilized gold nanorods. It is shown that silver bromide particles already formed in the stock solution play an important role in the exchange of silver ions. The Ag shell growth can be directly correlated with the layer-by-layer dissolution of AgBr nanocrystals, which can be controlled by the electron flux density via distinctly generated chemical species in the solvent. The derived model framework is confirmed by in situ UV-vis absorption spectroscopy evaluating the blue shift in the longitudinal surface plasmon resonance of anisotropic NRs in a complementary batch experiment.


A multistage approach to improve performance of computer-aided detection of pulmonary embolisms depicted on CT images: preliminary investigation.
This study developed a computer-aided detection (CAD) scheme for pulmonary embolism (PE) detection and investigated several approaches to improve CAD performance. In the study, 20 computed tomography examinations with various lung diseases were selected, which include 44 verified PE lesions. The proposed CAD scheme consists of five basic steps: 1) lung segmentation; 2) PE candidate extraction using an intensity mask and tobogganing region growing; 3) PE candidate feature extraction; 4) false-positive (FP) reduction using an artificial neural network (ANN); and 5) a multifeature-based k-nearest neighbor for positive/negative classification. In this study, we also investigated the following additional methods to improve CAD performance: 1) grouping 2-D detected features into a single 3-D object; 2) selecting features with a genetic algorithm (GA); and 3) limiting the number of allowed suspicious lesions to be cued in one examination. The results showed that 1) CAD scheme using tobogganing, an ANN, and grouping method achieved the maximum detection sensitivity of 79.2%; 2) the maximum scoring method achieved the superior performance over other scoring fusion methods; 3) GA was able to delete "redundant" features and further improve CAD performance; and 4) limiting the maximum number of cued lesions in an examination reduced FP rate by 5.3 times. Combining these approaches, CAD scheme achieved 63.2% detection sensitivity with 18.4 FP lesions per examination. The study suggested that performance of CAD schemes for PE detection depends on many factors that include 1) optimizing the 2-D region grouping and scoring methods; 2) selecting the optimal feature set; and 3) limiting the number of allowed cueing lesions per examination.


Outcomes of Pregnancies With Maternal/Paternal Exposure in the Tofacitinib Safety Databases for Ulcerative Colitis.
Active inflammatory bowel disease increases the risk of adverse pregnancy outcomes. Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). As a small molecule, tofacitinib is likely to cross the placental barrier; however, information on the effects of tofacitinib on pregnancy outcomes is limited. We report pregnancy and newborn outcomes among patients in UC clinical studies with prenatal (maternal/paternal) exposure to tofacitinib. Pregnancies with maternal/paternal exposure to tofacitinib were identified and outcomes reported in 5 tofacitinib UC interventional studies (up to March 2017). Outcomes from tofacitinib rheumatoid arthritis (RA), psoriasis, and psoriatic arthritis interventional studies, and RA noninterventional postapproval safety studies, spontaneous adverse event reporting, and registry data are also reported. Of 1157 patients enrolled in the UC interventional studies, 301 were women of childbearing age. Eleven cases of maternal exposure and 14 cases of paternal exposure to tofacitinib (doses of 5 mg or 10 mg twice daily) before/at the time of conception or during pregnancy were identified. Outcomes included 15 healthy newborns, no fetal deaths, no neonatal deaths, no congenital malformations, 2 spontaneous abortions, and 2 medical terminations. Outcomes across other tofacitinib studies and postmarketing cases were consistent, with a healthy newborn being the most common outcome and no fetal deaths. Based on the limited data available, pregnancy and newborn outcomes among patients with prenatal (maternal/paternal) exposure to tofacitinib in UC studies appear similar to those reported for other tofacitinib clinical study populations and the general population.


Higher postoperative pain and increased morphine consumption follow pre- rather than post-incisional single dose epidural morphine.
Neuraxial administration of morphine is an effective way of controlling postoperative pain and reducing analgesic consumption. Some animal models have demonstrated that preemptive administration of neuraxial narcotics reduces pain, while others have revealed the contrary. In addition, there have been no consistent results in clinical settings. This double-blind, randomized study compared the effects of pre- vs. post-incisional administration of neuraxial morphine on postoperative pain perception and analgesic requirements over 48 hours following laparotomy for open colectomy under standardized general anesthesia. Twenty patients received epidural morphine (3 mg) before the incision and saline after wound closure (MO1 group), and twenty patients received epidural saline before the incision and morphine after wound closure (MO2 group). Postoperatively, all patients received morphine boluses (1.5 mg) via intravenous patient-controlled analgesia (IV-PCA) and rescue doses of intramuscular diclofenac (75 mg) every 6 hours, as needed. MO1 patients used significantly (P<0.05) more morphine than the MO2 group during the first 24 postoperative hours and activated the PCA device more frequently throughout the 48-hour study period. The MO1 group was characterized by significantly (P<0.05) higher self-rated pain scores than the MO2 group throughout the study. The self-rated levels of sedation and satisfaction of the MO2 patients were also consistently better (P<0.05) than those of the MO1 patients, especially during the second postoperative day. Pre-incisional epidural morphine in patients undergoing open colonic surgery under general anesthesia was associated with more postoperative pain, a greater need for analgesics, and poorer patient satisfaction compared to post-incisional morphine administration.


Feedforward inhibition is randomly wired from individual granule cells onto CA3 pyramidal cells.
Feedforward inhibition (FFI) between the dentate gyrus (DG) and CA3 sparsifies and shapes memory- and spatial navigation-related activities. However, our understanding of this prototypical FFI circuit lacks essential details, as the wiring of FFI is not yet mapped between individual DG granule cells (GCs) and CA3 pyramidal cells (PCs). Importantly, theoretically opposite network contributions are possible depending on whether the directly excited PCs are differently inhibited than the non-excited PCs. Therefore, to better understand FFI wiring schemes, we compared the prevalence of disynaptic inhibitory postsynaptic events (diIPSCs) between pairs of individually recorded GC axons or somas and PCs, some of which were connected by monosynaptic excitation, while others were not. If FFI wiring is specific, diIPSCs are expected only in connected PCs; whereas diIPSCs should not be present in these PCs if FFI is laterally wired from individual GCs. However, we found single GC-elicited diIPSCs with similar probabilities irrespective of the presence of monosynaptic excitation. This observation suggests that the wiring of FFI between individual GCs and PCs is independent of the direct excitation. Therefore, the randomly distributed FFI contributes to the hippocampal signal sparsification by setting the general excitability of the CA3 depending on the overall activity of GCs.


Desensitizing the attention system to distraction while idling: A new latent learning phenomenon in the visual attention domain.
For the good and the bad, the world around us is full of distraction. In particular, onset stimuli that appear abruptly in the scene grab attention, thus disrupting the ongoing task. Different cognitive mechanisms for distractor filtering have been proposed, but prevalent accounts share the idea that filtering is accomplished to shield target processing from interference. Here we provide novel evidence that challenges this view, as passive exposure to a repeating visual onset is sufficient to trigger learning-dependent mechanisms to filter the unwanted stimulation. In other words, our study shows that during passive exposure the cognitive system is capable of learning about the characteristics of the salient yet irrelevant stimulation, and to reduce the responsiveness of the attention system to it, thus significantly decreasing the impact of the distractor upon start of an active task. However, despite passive viewing efficiently attenuates the spatial capture of attention, a short-lived performance cost is found when the distractor is initially encountered within the context of the active task. This cost, which dissipates in a few trials, likely reflects the need to familiarize with the distractor, already seen during passive viewing, in the new context of the active task. Although top-down inhibitory signals can be applied to distractors for the successful completion of goal-directed behavior, our results emphasize the role of more automatic habituation mechanisms for distraction exclusion based on a neural model of the history of the irrelevant stimulation. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Effects of diffraction efficiency on the modulation transfer function of diffractive lenses.
Diffractive lenses differ from conventional optical elements in that they can produce more than one image because of the presence of more than one diffraction order. These spurious, defocused images serve to lower the contrast of the desired image. We show that a quantity that we define as the integrated efficiency serves as a useful figure of merit to describe diffractive lenses. The integrated efficiency is shown to be the limiting value for the optical transfer function; in most cases it serves as an overall scale factor for the transfer function. We discuss both monochromatic and polychromatic applications of the integrated efficiency and provide examples to demonstrate its utility.


Assessment of ACS NSQIP's predictive ability for adverse events after major cancer surgery.
The American College of Surgeons National Surgery Quality Improvement Program (ACS NSQIP) has improved operative outcomes in the USA. However, its applicability to oncologic resections at ACS NSQIP hospitals has not been fully explored. We assessed the ability of factors currently collected by ACS NSQIP to predict adverse operative events after major cancer surgery. Using pre- and intraoperative factors gathered by the 2005-2008 ACS NSQIP, we constructed logistic regression models to determine their ability to predict 30-day mortality, prolonged length of stay (LOS), major complications or increased number of complications in 15,709 patients who underwent major cancer surgery at 211 hospitals. We assessed each model's predictive ability using the c-index. While the mortality rate was relatively low (2.5%), nearly 24% of patients experienced major adverse events. However, up to 43% of patients with prolonged LOS did not have any major complication captured by NSQIP. Furthermore, our model predicting complications showed poor overall predictive ability compared with those predicting mortality and LOS (c-index <0.67 versus 0.80 and 0.73, respectively). When stratified by procedure, the complication model's predictive ability remained less accurate than models predicting 30-day mortality or prolonged LOS. These results remain unchanged after additional sensitivity analyses. Current ACS NSQIP variables show low predictive ability for major complications after major oncologic resections. Addition of some disease- and operation-specific variables may be an important consideration in the further evolution of the NSQIP to allow for more accurate predictions of adverse outcomes for major oncologic resections.


The Social Context of HIV Prevention and Care among Black Men Who Have Sex with Men in Three U.S. Cities: The Neighborhoods and Networks (N2) Cohort Study.
Background: In many parts of the world, stark racial disparities in human immunodeficiency virus (HIV) prevalence, incidence, prevention, and care outcomes persist among gay, bisexual, and other men who have sex with men (MSM), with Black MSM significantly impacted in the United States (U.S.). Individual-level characteristics, including sexual behaviors and socioeconomic status, do not fully account for racial/ethnic disparities in HIV among MSM. We hypothesize that neighborhood contexts and network characteristics influence risk for HIV infection as well as HIV-related prevention and care behaviors. As such, the study design includes the use of real-time geospatial methods and in-depth assessments of multiple network typologies to investigate the impact of neighborhood and network-level factors on HIV prevention and treatment among Black MSM residing in longstanding priority HIV elimination areas in the U.S., namely Chicago, Illinois and in the Deep South (Jackson, Mississippi and New Orleans, Louisiana) (n = 450, n = 50, and n = 100, respectively). We describe the design, sampling methods, data collection, data management methods, and preliminary findings of the ongoing 'Neighborhoods and Networks (N2) Cohort Study'. Methods/Design: N2 employs a prospective longitudinal design. The sample includes Black MSM participants in Chicago recruited via respondent-driven sampling and assessed every six months over two years of follow-up. Participants enrolled in Jackson and New Orleans are being recruited through existing health and community services and assessed every six months over one year of follow-up. Mobility within and between neighborhoods is being assessed using global positioning system (GPS) technology. Social and sexual networks among Black MSM are being studied through egocentric network inventories as well as newer methods of creating meso-level networks that involve social media (Facebook) and mobile phone contacts. Key HIV prevention outcomes such as pre-exposure prophylaxis (PrEP) care engagement, and HIV/STI (sexually transmitted infections) biomarkers will be examined at baseline and follow-up. Results: As of 31 December 2018, a total of 361 men were enrolled across all study sites: 259 in Chicago and 102 in the Deep South (75 in New Orleans and 27 in Jackson). At baseline, participants ranged in age from 17 to 65 years old (mean = 34.3, standard deviation = 5.1) with 123 men (34.1%) self-reported as HIV positive. While HIV treatment levels were similar between sites, men in the Deep South reported higher rates of adherence than men in Chicago (63.3% versus 49.4%, p = 0.03). Sexual risk profiles were mainly the same between men from different study sites, with 22.9% of men in Chicago and 28.9% in the Deep South reporting consistent condom use during vaginal and anal sex (p = 0.26). Regarding their home neighborhoods, men in the Deep South were more likely than those in Chicago to characterize theirs as having a good reputation (43.1% versus 24.7%, p < 0.001) and as being safe (37.3% versus 21.2%, p = 0.002). Conclusions: The focus on Black MSM in the N2 Study will allow for a nuanced exploration of the attitudes, beliefs, behaviors, and practices of a diverse group of Black MSM. The study is also positioned to provide novel insight about neighborhood and network characteristics that influence HIV-related behaviors. A health equity framework ensures that Black MSM are not explicitly or implicitly deemed as deviant, disordered, or the non-reference group. Findings from N2 will provide guidance for the implementation of more impactful HIV prevention interventions that engage a diverse population of Black MSM as we work toward HIV elimination in the U.S.


Peripheral venous catheter care in the emergency department: education and feedback lead to marked improvements.
Peripheral venous catheters (PVCs) can be associated with serious complications. We evaluated the effect of education and feedback on processes related to PVC placement. We implemented an educational intervention in a 72-bed Emergency Department (ED) over 12 months (4 periods, each a quarter). During preimplementation period, we evaluated PVC placement, condition, accurate documentation, and demonstration of aseptic steps for medication infusion. With implementation, ED nurses had formal education, with direct observations and feedback. For postimplementation periods 1 and 2, we continued direct observations and feedback, reducing the number of audits per week. Of 2,568 PVCs evaluated in the ED, accurate documentation on dressing improved from 83 of 803 (10.3%) preimplementation to 300 of 476 (63%) at the end of the study (P < .0001). Correct documentation in ED records improved from 498 of 803 (62%) preimplementation to 409 of 476 (85.9%) at the end of study (P < .0001). We observed 273 attempts to place PVC; of them, 220 (80.6%) were completed. The overall compliance with the procedure steps was very poor preimplementation (n = 3/63, 4.8%) and improved in implementation (n = 17/55, 30.9%) and postimplementation periods 1 (n = 19/60, 31.7%) and 2 (n = 14/42, 33.3%, P < .0001). ED health care workers showed significant improvement in knowledge with education. Education and real-time feedback to ED health care workers are associated with an increased and sustained compliance with processes to reduce the risk of infection from PVCs.


Mobile phone messaging for illicit drug and alcohol dependence: A systematic review of the literature.
Mobile phone use has increased dramatically and concurrent with rapid developments in mobile phone-based health interventions. The integration of text messaging interventions promises to optimise the delivery of care for persons with substance dependence with minimal disruption to clinical workflows. We conducted a systematic review to assess the acceptability, feasibility and clinical impact of text messaging interventions for persons with illicit drug and alcohol dependence. Studies were required to evaluate the use of text messaging as an intervention for persons who met Diagnostic and Statistical Manual of Mental Disorders, 4th edition criterion for a diagnosis of illicit drug and/or alcohol dependence. Authors searched for articles published to date in MEDLINE (pubmed.gov), the Cochrane Library, EMBASE, CINAHL, Google Scholar and PsychINFO. Eleven articles met the search criteria for this review and support the acceptability and feasibility of text messaging interventions for addressing illicit drug and alcohol dependence. Most studies demonstrated improved clinical outcomes, medication adherence and engagement with peer support groups. Text messaging interventions also intervened on multiple therapeutic targets such as appointment attendance, motivation, self-efficacy, relapse prevention and social support. Suggestions for future research are described, including intervention design features, clinician contact, privacy measures and integration of behaviour change theories. Text messaging interventions offer a feasible platform to address a range of substances (i.e. alcohol, methamphetamine, heroin and alcohol), and there is increasing evidence supporting further larger-scale studies. [Tofighi B, Nicholson JM, McNeely J, Muench F, Lee JD. Mobile phone messaging for illicit drug and alcohol dependence: A systematic review of the literature. Drug Alcohol Rev 2017;36:477-491].


Towards a systematic analysis of human short-chain dehydrogenases/reductases (SDR): Ligand identification and structure-activity relationships.
Short-chain dehydrogenases/reductases (SDRs) constitute a large, functionally diverse branch of enzymes within the class of NAD(P)(H) dependent oxidoreductases. In humans, over 80 genes have been identified with distinct metabolic roles in carbohydrate, amino acid, lipid, retinoid and steroid hormone metabolism, frequently associated with inherited genetic defects. Besides metabolic functions, a subset of atypical SDR proteins appears to play critical roles in adapting to redox status or RNA processing, and thereby controlling metabolic pathways. Here we present an update on the human SDR superfamily and a ligand identification strategy using differential scanning fluorimetry (DSF) with a focused library of oxidoreductase and metabolic ligands to identify substrate classes and inhibitor chemotypes. This method is applicable to investigate structure-activity relationships of oxidoreductases and ultimately to better understand their physiological roles.


Meat quality of kudu (Tragelaphus strepsiceros) and impala (Aepyceros melampus): Carcass yield, physical quality and chemical composition of kudu and impala Longissimus dorsi muscle as affected by gender and age.
The meat quality of kudu and impala was compared. Live weight and carcass weight differed between species, genders and age groups. Impala had the highest dressing percentage while kudu had the highest live weight and carcass weight. Kudu had the lowest fat content while female animals had a higher fat and myoglobin content than males. Sub-adults had a higher ash content than adults. Species, gender and age had no effect of pH, drip loss, cooking loss or tenderness although kudu had higher L∗, a∗, b∗ and chroma values than impala. Impala sub-adults had significantly higher insoluble collagen, soluble collagen, total collagen and hydroxyproline content than kudu sub-adults. Kudu had the highest potassium levels while impala had the highest phosphorus levels. Potassium, sodium, iron and copper levels also differed between species.


Prognostic indicators following curative pancreatoduodenectomy for pancreatic carcinoma: A retrospective multivariate analysis of a single centre experience.
Survival after curative resection of pancreatic, ampullary and lower common bile duct cancer remains very poor. The aim of this study was to assess important prognostic factors in patients with resectable pancreatic cancer. From 2006 to 2010, 156 patients underwent pancreatoduodenectomy (PD) for malignancies of pancreatic, ampullary or lower common bile duct in our institution. Based on the inclusion criteria 101 patients were selected in our retrospective statistical analysis. Of these 101 cases of malignancies, 65.4% were located in the pancreatic head, 18.8% in the ampulla and 15.8% in the lower bile duct. 48.5% of patients underwent classical PD, and 51.5% pylorus-preserving pancreatoduodenectomy (PPPD). Clinical and pathological data were collected, Kaplan-Meier method and Cox proportional hazard models were used to evaluate prognostic factors. Multivariate analysis revealed that blood transfusion, vascular invasion, T4 vs T1 stage, and R0 resection margins were significant negative predictors of survival. Conversely, ampullary (vs pancreatic ductal) and adjuvant chemotherapy were significantly associated with longer survival. Lymph node ratio (LNR), in all its forms, was not found to have a significant effect on survival. For all patients, tumor grading (p=0.042), resection margins (p=0.004), T stage (p=0.001), perineural invasion (p=0.029), vascular invasion (p=0.007) and age >65 years (p=0.009) were factors that impacted survival. Surgical resection margins, tumor grade, T stage, perineural invasion, vascular invasion, age >65 and adjuvant chemotherapy are the strongest predictors of survival after surgical resection of pancreatic, ampullary and lower common bile duct cancer. In this series, lymph node ratio did not impact survival.


Demographic variability, vaccination, and the spatiotemporal dynamics of rotavirus epidemics.
Historically, annual rotavirus activity in the United States has started in the southwest in late fall and ended in the northeast 3 months later; this trend has diminished in recent years. Traveling waves of infection or local environmental drivers cannot account for these patterns. A transmission model calibrated against epidemiological data shows that spatiotemporal variation in birth rate can explain the timing of rotavirus epidemics. The recent large-scale introduction of rotavirus vaccination provides a natural experiment to further test the impact of susceptible recruitment on disease dynamics. The model predicts a pattern of reduced and lagged epidemics postvaccination, closely matching the observed dynamics. Armed with this validated model, we explore the relative importance of direct and indirect protection, a key issue in determining the worldwide benefits of vaccination.


[A case report of childhood systemic lupus erythematosus complicated with lupus cystitis].
The patient was a 13-year-old girl. In August 2000, she presented with a fever, together with diarrhea, vomiting, arthralgia, nasal bleeding and malaise, and was examined by another physician. Because her platelet count was low, and there were positive reactions for anti-nuclear antibodies, anti-DNA antibodies and platelet-associated IgG, idiopathic thrombopenic purpura, and systemic lupus erythematosus (SLE) was suspected. From January 2001, when she caught measles, she reported abdominal pain, and urinalysis indicated urinary protein and occult blood, and the left kidney was found hydronephrotic. At the same time left ureter stenosis and dilatation were demonstrated. Symptoms were disappeared by hydration and treatment with NSAIDs, but 2 months later fever and erythematous patches seen on both cheeks led to the proper diagnosis of SLE, and she was admitted to our hospital. Intravenous pyelography revealed hydronephrosis on left kidney, constriction and dilatation of the left ureter, and intracystic endoscopy showed erythema at the orifice of the left ureter. The pathological examination indicated the presence of vasculitis, and finally lupus cystitis was diagnosed. Intravenous cyclophosphamide (IVCY)-pulse therapy was introduced to a total of 8 times over the period of a year, and maintenance therapy with predonisolone and azathioprin was also used. After completion of the IVCY-pulse therapy, the hydronephrosis and constriction of the ureter were disappeared. No side effects of IVCY-pulses were observed, and the patient is now in remission. We reported a case of childhood SLE complicated with lupus cystitis and successfully treated by IVCY-pulse therapy and maintenance predonisolone and azathioprin.


Inhibition by wheat sprout (Triticum aestivum) juice of bisphenol A-induced oxidative stress in young women.
For health of future generation, fertile young women should be monitored for exposure of endocrine disrupting chemicals (EDCs). Among EDCs, bisphenol A (BPA) is suggested to induce reactive oxygen species (ROS) which play an important role in pathologies of female diseases such as endometriosis. On the other hand, previous studies suggested that sprouts of wheat (Triticum aestivum) have antimutagenicity and antioxidant activity. We performed the 2 weeks intervention of wheat sprout juice (100ml/day) to investigate its effects on BPA-exposure and -oxidative toxicity in young women (N=14, age=24.4±4.0). Geometrical mean of urinary BPA levels was 1.81 (GSTD, 4.34)μg/g creatinine. We observed that irregular meals significantly increased levels of urinary BPA approximate 3 times (p=0.03). In addition, we found BPA-induced oxidative stress is correlated with levels of 8-hydroxydeoxyguanosine (8-OHdG) or malondialdehyde (MDA) levels (p=0.18 or 0.03, respectively). We also observed a continuous reduction of urinary BPA during the wheat sprout intervention (p=0.02). In summary, our data suggested potential detoxification of wheat sprouts on BPA-toxicity via antioxidative and interference of absorption, distribution, metabolism and excretion (ADME)-mediated mechanisms in young women.


Single-step polarization holographic method for programmable microlens arrays.
Optical microsystems have become important tools for imaging, optofluidics, and sensor applications. Here we show a versatile method to create microlens arrays (MAs) exploiting spatial-light-modulator-assisted polarization holography, which enables an efficiency of diffraction up to 100%. We demonstrate the large flexibility of the proposed approach by codifying mixed MAs, i.e., composed of spherical and cylindrical lenses with different focal lengths, either positive or negative. Reconfigurable MAs with 70% total diffraction efficiency have been recorded on a photosensitive polymer that exhibits linear photoinduced birefringence with long time stability as well as optical and thermal reversibility. The good quality of the MA has been shown by a digital holographic test.


Synthesis, Nicotinic Acetylcholine Receptor Binding, and in Vitro and in Vivo Pharmacological Properties of 2'-Fluoro-(substituted thiophenyl)deschloroepibatidine Analogues.
The synthesis, nAChR in vitro and in vivo pharmacological properties of 2'-fluoro-3'-(substituted thiophenyl)deschloroepibatidine analogues (5a-f, 6a-d, and 7a-c) are presented herein. All had subnanomolar affinity at α4β2*-nAChRs. Contrary to lead structure epibatidine, a potent nAChR agonist, all were potent α4β2- and α3β4-AChR antagonists in an in vitro functional assay. In vivo, the compounds were also nAChR antagonists with various degrees of agonist activity. Compounds 5e, 5f, 6a, 6c, 6d, and 7c had no agonist effects in the tail-flick, hot-plate, hypothermia, or spontaneous activity tests, whereas 5a-d, 7a and 7b did not have agonist activity in the tail-flick and hot-plate tests but, like varenicline, were agonists in the hypothermia and spontaneous activity tests. Compound 6b had agonist activity in all four in vivo tests. All the compounds were antagonists of nicotine-induced antinociception in the tail-flick test, and all except 5c, 5d, 5f, and 6b were antagonists of nicotine-induced antinociception in the hot-plate test. Compound 7c, which had a Ki = 0.86 nM in the binding assay similar potency at α4β2/α3β4 with selectivity relative to α7 nAChRs, had an AD50 value of 0.001 μg/kg in the tail-flick test with no agonist activity in the in vitro or in vivo test had one of the more interesting profiles.


Antigen receptors on immature, but not mature, B and T cells are coupled to cytosolic phospholipase A2 activation: expression and activation of cytosolic phospholipase A2 correlate with lymphocyte maturation.
The Ag receptors on mature B and T cells are not coupled to the activation of cytosolic phospholipase A2 (cPLA2) and arachidonic acid release. Moreover, phorbol esters such as PMA, which can activate cPLA2 via mitogen-activated protein (MAP) kinase in most cell types, also failed to induce the release of arachidonate from mature cells, suggesting that the cPLA2 pathway may not be functional in mature lymphocytes. Interestingly, Western blot analysis revealed that cPLA2, which had previously been thought to be expressed ubiquitously, is not expressed in mature B or T cells and that cytosolic phospholipase A2 expression could not be up-regulated in lymphocytes following culture with a range of cytokines most likely to be involved in an immune response such as IL-1 alpha, IL-3, or TNF-alpha. In contrast, cPLA2 was shown to be expressed and activated in thymocytes and immature B cells under conditions in which ligation of the Ag receptors led to growth arrest and/or apoptosis. Taken together, these data suggest that cPLA2 does not play a role in Ag receptor-mediated lymphocyte activation, but may be involved in the molecular mechanisms underlying lymphocyte maturation and/or self tolerance by clonal deletion.


N-WASP deficiency reveals distinct pathways for cell surface projections and microbial actin-based motility.
The Wiskott-Aldrich syndrome protein (WASP) family of molecules integrates upstream signalling events with changes in the actin cytoskeleton. N-WASP has been implicated both in the formation of cell-surface projections (filopodia) required for cell movement and in the actin-based motility of intracellular pathogens. To examine N-WASP function we have used homologous recombination to inactivate the gene encoding murine N-WASP. Whereas N-WASP-deficient embryos survive beyond gastrulation and initiate organogenesis, they have marked developmental delay and die before embryonic day 12. N-WASP is not required for the actin-based movement of the intracellular pathogen Listeria but is absolutely required for the motility of Shigella and vaccinia virus. Despite these distinct defects in bacterial and viral motility, N-WASP-deficient fibroblasts spread by using lamellipodia and can protrude filopodia. These results imply a crucial and non-redundant role for N-WASP in murine embryogenesis and in the actin-based motility of certain pathogens but not in the general formation of actin-containing structures.


A unified stochastic modelling framework for the spread of nosocomial infections.
Over the last years, a number of stochastic models have been proposed for analysing the spread of nosocomial infections in hospital settings. These models often account for a number of factors governing the spread dynamics: spontaneous patient colonization, patient-staff contamination/colonization, environmental contamination, patient cohorting or healthcare workers (HCWs) hand-washing compliance levels. For each model, tailor-designed methods are implemented in order to analyse the dynamics of the nosocomial outbreak, usually by means of studying quantities of interest such as the reproduction number of each agent in the hospital ward, which is usually computed by means of stochastic simulations or deterministic approximations. In this work, we propose a highly versatile stochastic modelling framework that can account for all these factors simultaneously, and which allows one to exactly analyse the reproduction number of each agent at the hospital ward during a nosocomial outbreak. By means of five representative case studies, we show how this unified modelling framework comprehends, as particular cases, many of the existing models in the literature. We implement various numerical studies via which we (i) highlight the importance of maintaining high hand-hygiene compliance levels by HCWs, (ii) support infection control strategies including to improve environmental cleaning during an outbreak and (iii) show the potential of some HCWs to act as super-spreaders during nosocomial outbreaks.


Electrophysiology of flounder intestinal mucosa. I. Conductance properties of the cellular and paracellular pathways.
We evaluated the conductances for ion flow across the cellular and paracellular pathways of flounder intestine using microelectrode techniques and ion-replacement studies. Apical membrane conductance properties are dominated by the presence of Ba-sensitive K channels. An elevated mucosal solution K concentration, [K]m, depolarized the apical membrane potential (psi a) and, at [K]m less than 40 mM, the K dependence of psi a was abolished by 1-2 mM mucosal Ba. The basolateral membrane displayed Cl conductance behavior, as evidenced by depolarization of the basolateral membrane potential (psi b) with reduced serosal Cl concentrations, [Cl]s. psi b was unaffected by changes in [K]s or [Na]s. From the effect of mucosal Ba on transepithelial K selectivity, we estimated that paracellular conductance (Gp) normally accounts for 96% of transepithelial conductance (Gt). The high Gp attenuates the contribution of the cellular pathway to psi t while permitting the apical K and basolateral Cl conductances to influence the electrical potential differences across both membranes. Thus, psi a and psi b (approximately 60 mV, inside negative) lie between the equilibrium potentials for K (76 mV) and Cl (40 mV), thereby establishing driving forces for K secretion across the apical membrane and Cl absorption across the basolateral membrane. Equivalent circuit analysis suggests that apical conductance (Ga approximately equal to 5 mS/cm2) is sufficient to account for the observed rate of K secretion, but that basolateral conductance (Gb approximately equal to 1.5 mS/cm2) would account for only 50% of net Cl absorption. This, together with our failure to detect a basolateral K conductance, suggests that Cl absorption across this barrier involves KCl co-transport.


Sarcopenia: An emphasis on occlusion training and dietary protein.
Demographics reveal that the world's population aged 60 years and older will triple from 600 million in 2000 to more 2 billion by the year 2050. To remain independent and healthy, an important factor to consider is the maintenance of skeletal muscle, as the elderly seem to become prone to a progressive loss of skeletal muscle with aging, termed sarcopenia. Interventions should focus on resistance training and optimal nutrition. Low intensity occlusion training may provide a mode of resistance training more applicable to the elderly, due to the lower loads used. Furthermore, an emphasis must be placed on high quality protein adequately distributed throughout the day to maximize protein synthesis. The use of drug therapy may be of some benefit, but it appears exercise and diet likely plays a more prominent role in the preservation of muscle mass and strength than administration of synthetic hormones.


Panuveitis With Exudative Retinal Detachments After Vaccination Against Human Papilloma Virus.
A 20-year-old white woman presented with bilateral acute visual loss (visual acuity: 20/60), panuveitis, and exudative retinal detachments 3 weeks after a second dose of quadrivalent human papillomavirus (HPV4) vaccine. She was treated with oral prednisolone for 6 weeks and responded rapidly. By week 4, vision had normalized and clinical signs resolved. Uveitis after HPV4 vaccination has been reported in two cases. Although the differential diagnosis includes Harada disease, temporal correlation with HPV4 and definitive response to a short course of treatment implicate the vaccine in this case. Vaccine-induced uveitis is rare and difficult to distinguish from coincidental autoimmune disease.


Determine the operational boundary of a pilot-scale single-stage partial nitritation/anammox system with granular sludge.
The partial nitritation/anammox (PN/A) process has been applied to ammonium-rich wastewater treatment, but the operational boundary has not been well determined for long-term stability. This pilot-scale study was targeted at a single-stage PN/A process using a sequencing batch reactor (SBR) (volume: 53 m(3)) and granulated activated sludge. The maximum nitrogen removal rate reached 0.83 kg N/(m(3)·d). Microbial analysis suggested that ammonium oxidizing bacteria were mainly present in small sludge flocs while anammox bacteria were prone to grow in large sludge granules. The PN/A performance was enhanced when dissolved oxygen (DO) was increased from 0.25 to 0.76 mg/L, and deteriorated at DO higher than 1.15 mg/L. The PN/A was inhibited at free ammonia (FA) over 77.0 mg/L. High DO or FA concentrations inhibited anammox activity and further induced high and inhibitory nitrite concentrations. Therefore, appropriate DO and FA concentrations should be controlled to achieve single-stage PN/A in SBRs.


Quantitative determination of nuclear pore complexes in cycling cells with differing DNA content.
The number of pore complexes per nucleus was determined for a wide variety of cultured cells selected for their variable DNA content over a range of 1-5,6000. The pore number was compared to DNA content, nuclear surface area, and nuclear volume. Values for pore frequency (pores/square micrometer) were relatively constant in the species studied. When the pore to DNA ratio was plotted against the DNA content, there was a remarkable correlation which decreased exponentially for the cells of vertebrae origin. Exceptions were the heteroploid mammalian cells which had the same ratio as the diploid mammalian cells despite higher DNA content. The results are interpreted to mean that neither the nuclear surface, the nuclear volume, nor the DNA content alone determines the pore number of the nucleus, but rather an as yet undetermined combination of different factors. The surface and volume of vertebrate nuclei do not decrease with decreasing DNA content below a given value. The following speculation is suggested to account for the anomalous size changes of the nucleus relative to DNA content in vertebrates. Species with small DNA complements have a relatively large proportion of active chromatin which determines the limits of the physical parameters of the nucleus. The amount of active chromatin maybe the same for at least the vertebrates with low DNA content, At high DNA content, the nuclear parameters may be determined by the relatively high proportion of inactive condensed chromatin which increases the nuclear surface and volume.


Evidence for Exaptation of the Marchantia polymorpha M20D Peptidase MpILR1 into the Tracheophyte Auxin Regulatory Pathway.
Auxin homeostasis is tightly regulated by several mechanisms, including conjugation of the hormone to specific moieties, such as amino acids or sugar. The inactive phytohormone conjugate is stored in large pools in plants and hydrolyzed to regain full activity. Many conjugate hydrolases (M20D metallopeptidases) have been identified and characterized throughout the plant kingdom. We have traced this regulatory gene family back to liverwort (Marchantia polymorpha), a member of the most ancient extant land plant lineage, which emerged approximately 475 million years ago. We have isolated and characterized a single hydrolase homologue, dubbed M. polymorpha IAA-Leucine Resistant1 (MpILR1), from liverwort. MpILR1 can hydrolyze two auxin (indole acetic acid [IAA]) substrates (IAA-Leucine and IPA-Alanine) at very low levels of activity, but it cannot hydrolyze the two native auxin conjugates of liverwort (IAA-Glycine and IAA-Valine). We conclude from these results that liverwort likely does not employ active auxin conjugate hydrolysis as a regulatory mechanism and that conjugate homeostasis likely takes place in liverwort by passive background degradation. Furthermore, we present evidence that MpILR1 was probably exapted by tracheophytes over evolutionary time into the auxin regulatory pathway.


Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) for chronic insomnia disorder ('CANSLEEP' trial): protocol for a randomised, placebo-controlled, double-blinded, proof-of-concept trial.
Insomnia is a highly prevalent and costly condition that is associated with increased health risks and healthcare utilisation. Anecdotally, cannabis use is frequently reported by consumers to promote sleep. However, there is limited research on the effects of cannabis on sleep and daytime function in people with insomnia disorder using objective measures. This proof-of-concept study will evaluate the effects of a single dose of an oral cannabis-based medicine on sleep and daytime function in participants with chronic insomnia disorder. A randomised, crossover, placebo-controlled, single-dose study design will be used to test the safety and efficacy of an oral oil solution ('ETC120') containing 10 mg Δ9-tetrahydrocannabinol (THC) and 200 mg cannabidiol (CBD) in 20 participants diagnosed with chronic insomnia disorder. Participants aged 35-60 years will be recruited over an 18-month period commencing August 2019. Each participant will receive both the active drug and matched placebo, in a counterbalanced order, during two overnight study assessment visits, with at least a 1-week washout period between each visit. The primary outcomes are total sleep time and wake after sleep onset assessed via polysomnography. In addition, 256-channel high-density electroencephalography and source modelling using structural brain MRI will be used to comprehensively examine brain activation during sleep and wake periods on ETC120 versus placebo. Next-day cognitive function, alertness and simulated driving performance will also be investigated. Ethics approval was received from Bellberry Human Research Ethics Committee (2018-04-284). The findings will be disseminated in a peer-reviewed open-access journal and at academic conferences. ANZCTRN12619000714189.


Challenges associated with delivering education to patients after heart surgery.
The aim of this report is to provide a detailed description of the challenges that arose throughout the implementation of an individualized patient education intervention delivered to patients during their home recovery following heart surgery. The intervention was delivered at two points in time by telephone to patients following heart bypass and/or valvular replacement. The individualized patient education intervention was found to be effective in reducing the rate and number of complications developed during the first three months following hospital discharge. However, throughout the implementation of this intervention, specific challenges arose that included: onset of symptoms that interfered with intervention delivery, patient's request for information beyond the scope of the teaching interaction, and the need to provide continued support to the therapist. These challenges were addressed throughout the course of the study and the strategies are currently being implemented into the planned knowledge translation activities associated with this intervention.


In vivo flow territory mapping of major brain feeding arteries.
The ability to visualize the perfusion territories of major feeding arteries to the brain is important for many clinical applications. Since the work of Duret in 1874 on vascularization of the brain, many textbooks and atlases have shown schematic drawings of the supply areas of the major cerebral arteries. Recent postmortem studies demonstrated that the variability of the cerebral vascular territories is significantly greater than previously assumed. The aim of the present study was to investigate in vivo, the variability of flow territories of major brain feeding arteries. Flow territory mapping of the anterior (internal carotid arteries) and posterior (basilar artery) circulation was performed in 115 (58 +/- 9 years of age) subjects with selective arterial spin labeling MRI. Flow territory maps for the entire population indicated significant variation in flow territories. However, when the subjects are further categorized into groups with a complete circle of Willis, with a missing A1 segment and with a unilateral or bilateral fetal-type posterior cerebral artery, the results showed considerably lower variation within groups. It is therefore concluded that, the variation observed from the entire population is mainly caused by anatomical variants of the circle of Willis. To relate focal brain lesions to underlying flow territories in individual cases, knowledge of the anatomy of the circle of Willis is essential.


A prospective, randomized clinical trial to compare the effect of hyperbaric to normobaric hyperoxia on cerebral metabolism, intracranial pressure, and oxygen toxicity in severe traumatic brain injury.
Oxygen delivered in supraphysiological amounts is currently under investigation as a therapy for severe traumatic brain injury (TBI). Hyperoxia can be delivered to the brain under normobaric as well as hyperbaric conditions. In this study the authors directly compare hyperbaric oxygen (HBO2) and normobaric hyperoxia (NBH) treatment effects. Sixty-nine patients who had sustained severe TBIs (mean Glasgow Coma Scale Score 5.8) were prospectively randomized to 1 of 3 groups within 24 hours of injury: 1) HBO2, 60 minutes of HBO(2) at 1.5 ATA; 2) NBH, 3 hours of 100% fraction of inspired oxygen at 1 ATA; and 3) control, standard care. Treatments occurred once every 24 hours for 3 consecutive days. Brain tissue PO(2), microdialysis, and intracranial pressure were continuously monitored. Cerebral blood flow (CBF), arteriovenous differences in oxygen, cerebral metabolic rate of oxygen (CMRO2), CSF lactate and F2-isoprostane concentrations, and bronchial alveolar lavage (BAL) fluid interleukin (IL)-8 and IL-6 assays were obtained pretreatment and 1 and 6 hours posttreatment. Mixed-effects linear modeling was used to statistically test differences among the treatment arms as well as changes from pretreatment to posttreatment. In comparison with values in the control group, the brain tissue PO2 levels were significantly increased during treatment in both the HBO2 (mean +/- SEM, 223 +/- 29 mm Hg) and NBH (86 +/- 12 mm Hg) groups (p < 0.0001) and following HBO2 until the next treatment session (p = 0.003). Hyperbaric O2 significantly increased CBF and CMRO2 for 6 hours (p < or = 0.01). Cerebrospinal fluid lactate concentrations decreased posttreatment in both the HBO2 and NBH groups (p < 0.05). The dialysate lactate levels in patients who had received HBO2 decreased for 5 hours posttreatment (p = 0.017). Microdialysis lactate/pyruvate (L/P) ratios were significantly decreased posttreatment in both HBO2 and NBH groups (p < 0.05). Cerebral blood flow, CMRO2, microdialysate lactate, and the L/P ratio had significantly greater improvement when a brain tissue PO2 > or = 200 mm Hg was achieved during treatment (p < 0.01). Intracranial pressure was significantly lower after HBO2 until the next treatment session (p < 0.001) in comparison with levels in the control group. The treatment effect persisted over all 3 days. No increase was seen in the CSF F2-isoprostane levels, microdialysate glycerol, and BAL inflammatory markers, which were used to monitor potential O2 toxicity. Hyperbaric O2 has a more robust posttreatment effect than NBH on oxidative cerebral metabolism related to its ability to produce a brain tissue PO2 > or = 200 mm Hg. However, it appears that O2 treatment for severe TBI is not an all or nothing phenomenon but represents a graduated effect. No signs of pulmonary or cerebral O2 toxicity were present.


Sexual harassment victimization, school belonging, and depressive symptoms among LGBTQ adolescents: Temporal insights.
Peer victimization and the associated poor outcomes among lesbian, gay, bisexual, transgender, and questioning (LGBTQ) youth have been the focus of countless studies. School climate is a factor that has garnered significant attention. Perceptions of school contexts may even be mechanisms that define how victimization relates to poor outcomes. However, there is a lack of rigorous scholarship that could demonstrate directionality and therefore further augment our understanding of these relations. Specifically, it is not clear if victimization is strictly an antecedent to mental health issues like depressive symptoms. This longitudinal study examined the associations among sexual harassment victimization, school belonging, and depressive symptoms among LGBTQ high school students (n = 404). Self-report measures were completed at 3 time points across 3 school years in 6 Midwest high schools. Structural equation modeling indicated that peer victimization was an antecedent to depressive symptoms, and that school belonging mediated the association. Implications and future directions are discussed. (PsycINFO Database Record


Analytical determination of reflection-peak wavelengths of chirped sampled fiber Bragg gratings.
An analytical expression for calculating the position of the reflection-peak wavelength of a chirped sampled fiber Bragg grating (C-SFBG) is obtained for what is believed to be the first time. Using Fourier theory, the chirped sampling function of the C-SFBG is expanded, and an equivalent local Bragg period is then obtained to derive the expression of the peak wavelength. The calculated results based on the expression are in excellent agreement with the numerical reflection spectra obtained by the conventional transfer-matrix method.


Evaluation of physical activity programmes for the elderly - exploring the lessons from other sectors and examining the general characteristics of the programmes.
In Portugal, there are several physical activity (PA) programmes for elderly people developed by the local government. The importance of these programmes has been increasing since the evidence has shown that this type of health promotion interventions may reduce the deleterious effects of the ageing process. However, no study has already identified the general characteristics of these programmes nor if they use any scheme to assess the quality of the service provided. A widely-used scheme is the EFQM Excellence Model, which will be in the core of our present work. Thus, the main aims of this preliminary study were 1) to identify the general characteristics of the PA programmes developed by the Portuguese Local Public Administration 2) to determine the extent of implementation of quality initiatives in these programmes. Data were collected by an on-line questionnaire sent to all Continental Municipalities (n = 278). Categorical data were expressed as absolute counts and percentages. Continuous data were expressed as the mean and SD. An open-ended question was analysed using qualitative content analysis with QSR NVivo software. Associations between categorical variables were tested by the use of contingency tables and the calculation of chi-square tests. Significance level was set at p ≤ 0.05. Results showed: i) a total of 125 PA programmes were identified in the 18 districts of the Portugal mainland; ii) the main goal of the majority (95.2%) was the participants' health promotion; iii) different characteristics of the programmes were found according to different regions of the country; iv) certain characteristics of the programmes were associated to the existence of other features; v) only one PA programme developed quality initiatives. In conclusion, although there are many PA programmes for elderly people spread throughout the country, aiming at improving the health of participants, the overwhelming majority does not adopt quality control initiatives. Considering that the quality of a service increases customer satisfaction, the continuous quality improvement of the PA programmes for elderly people should therefore be implemented since they can be useful and critical for elderly satisfaction and adherence.


A phase I study of bolus versus continuous infusion of the anti-CD19 immunotoxin, IgG-HD37-dgA, in patients with B-cell lymphoma.
IgG-HD37-SMPT-dgA is a deglycosylated ricin A chain (dgA)-containing immunotoxin (IT) prepared by conjugating the monoclonal murine (MoAb) anti-CD19 antibody, HD37, to dgA using the heterobifunctional hindered disulfide linker, N-succinimidyl-oxycarbonyl-alpha-methyl-alpha-(2-pyridyldithio) toluene (SMPT). In this report, we have used two regimens for the administration of IgG-HD37-SMPT-dgA to patients with non-Hodgkin's lymphoma (NHL) in two concomitant phase I trials. One trial examined four intermittent bolus infusions administered at 48-hour intervals. The other studied a continuous infusion (CI) administered over the same 8-day period. In the intermittent bolus regimen, the maximum tolerated dose (MTD) was 16 mg/m2/8 d and the dose-limiting toxicity (DLT) consisted of vascular leak syndrome (VLS), aphasia, and evidence of rhabdomyolysis encountered at 24 mg/m2/8 d. Using the CI regimen, the MTD was defined by VLS at 19.2 mg/m2/8 d. At the MTD of both regimens, a novel toxicity, consisting of acrocyanosis with reversible superficial distal digital skin necrosis in the absence of overt evidence of systemic vasculitis, occurred in 3 patients. Of 23 evaluable patients on the bolus schedule, there was 1 persisting complete response (CR; > 40 months) and 1 partial response (PR). Of 9 evaluable patients on the continuous infusion regimen, there was 1 PR. Pharmacokinetic parameters for the bolus regimen at the MTD showed a mean maximum serum concentration (Cmax) of 1,209 +/- 430 ng/mL, with a median T1/2 beta for all courses of 18.2 hours (range, 10.0 to 80.0 hours), a volume of distribution (Vd) of 10.9 L (range, 3.1 to 34.5 L), and a clearance (CL) of 0.45 L/h (range, 0.13 to 2.3 L/h). For the CI regimen at MTD, the mean Cmax was 963 +/- 473 ng/mL, with a median T1/2 beta for all courses of 22.8 hours (range, 24.1 to 30.6 hours), a Vd of 9.4 L (range, 4.4 to 19.5 L), and a CL of 0.32 L/h (range, 0.12 to 0.55 L/h). Twenty-five percent of the patients on the bolus infusion regimen and 30% on the CI regimen made antibody against mouse Ig (HAMA) and/or ricin A chain antibody (HARA). We conclude that this IT can be administered safely and that both regimens achieve comparable peak serum concentrations at the MTD; these concentrations are similar to those achieved previously using other regimens with IgG-dgA ITs at their respective MTDs. Thus, toxicity is related to the serum level of the IT and does not differ with different targeting MoAbs.


Epithelial RNase H2 Maintains Genome Integrity and Prevents Intestinal Tumorigenesis in Mice.
RNase H2 is a holoenzyme, composed of 3 subunits (ribonuclease H2 subunits A, B, and C), that cleaves RNA:DNA hybrids and removes mis-incorporated ribonucleotides from genomic DNA through ribonucleotide excision repair. Ribonucleotide incorporation by eukaryotic DNA polymerases occurs during every round of genome duplication and produces the most frequent type of naturally occurring DNA lesion. We investigated whether intestinal epithelial proliferation requires RNase H2 function and whether RNase H2 activity is disrupted during intestinal carcinogenesis. We generated mice with epithelial-specific deletion of ribonuclease H2 subunit B (H2bΔIEC) and mice that also had deletion of tumor-suppressor protein p53 (H2b/p53ΔIEC); we compared phenotypes with those of littermate H2bfl/fl or H2b/p53fl/fl (control) mice at young and old ages. Intestinal tissues were collected and analyzed by histology. We isolated epithelial cells, generated intestinal organoids, and performed RNA sequence analyses. Mutation signatures of spontaneous tumors from H2b/p53ΔIEC mice were characterized by exome sequencing. We collected colorectal tumor specimens from 467 patients, measured levels of ribonuclease H2 subunit B, and associated these with patient survival times and transcriptome data. The H2bΔIEC mice had DNA damage to intestinal epithelial cells and proliferative exhaustion of the intestinal stem cell compartment compared with controls and H2b/p53ΔIEC mice. However, H2b/p53ΔIEC mice spontaneously developed small intestine and colon carcinomas. DNA from these tumors contained T>G base substitutions at GTG trinucleotides. Analyses of transcriptomes of human colorectal tumors associated lower levels of RNase H2 with shorter survival times. In analyses of mice with disruption of the ribonuclease H2 subunit B gene and colorectal tumors from patients, we provide evidence that RNase H2 functions as a colorectal tumor suppressor. H2b/p53ΔIEC mice can be used to study the roles of RNase H2 in tissue-specific carcinogenesis.


VEGF profiling and angiogenesis in human microtissues.
Owing to its dual impact on tissue engineering (neovascularization of tissue implants) and cancer treatment (prevention of tumor-induced vascularization), management and elucidation of vascularization phenomena remain clinical priorities. Using a variety of primary human cells and (neoplastic) cell lines assembled in microtissues by gravity-enforced self-aggregation in hanging drops we (i) studied size and age-dependent VEGF production of microtissues in comparison to isogenic monolayer cultures, (ii) characterized the self-organization and VEGF-production potential of mixed-cell spheroids, (iii) analyzed VEGF-dependent capillary formation of human umbilical vein endothelial cells (HUVECs) cells coated onto several human primary cell spheroids, and (iv) profiled endostatin action on vascularization in human microtissues. Precise understanding of vascularization in human microtissues may foster advances in clinical tissue implant engineering, tumor treatment, as well as drug discovery and drug-function analysis.


A kinetic model of bone marrow neutrophil production that characterizes late phenotypic maturation.
Acute inflammatory stimuli rapidly mobilize neutrophils from the bone marrow by shortening postmitotic maturation time and releasing younger neutrophils; however, the kinetics of this change in maturation time remains unknown. We propose a kinetic model that examines the rate of change in neutrophil average age at exit from the bone marrow during active mobilization to quantify this response and use this model to examine the temporal profile of late neutrophil phenotypic maturation. Total and CD10(-)/CD16(low) circulating neutrophils were quantified in cardiac surgery patients during extracorporeal circulation (ECC). Net growth in the circulating neutrophil pool occurred during the procedural (0.04 +/- 0.02 x 10(9) x l(-1) x min(-1)), warming (0.14 +/- 0.02 x 10(9) x l(-1) x min(-1)), and weaning (0.12 +/- 0.06 x 10(9) x l(-1) x min(-1)) phases of ECC. When applied to our differential equation mathematical model, these results predict that neutrophil average age at exit from the bone marrow decreased continually during ECC, resulting in average neutrophil release 8.44 +/- 2.20 h earlier during the weaning phase than at the beginning of ECC sampling. Modeling of concurrent changes in CD10(-)/CD16(low) neutrophil numbers indicates that CD10 expression is directly related to neutrophil mean age and predicts that the proportion of mobilizable postmitotic neutrophils that are CD10(+) increases from 64 to 81% during these sampled 8.4 h of maturation.


Impacts of temperature, morpholine, and chronic radiation on the embryonic development of round whitefish (Prosopium cylindraceum).
During incubation, round whitefish embryos may experience fluctuating or elevated temperatures from natural (e.g., seasonal temperature changes) and/or anthropogenic sources. Anthropogenic sources like once-through cooling discharges from nuclear power plants can also expose embryos to chemicals (e.g., morpholine) and/or radiation. To examine the effects of these potential stressors on embryogenesis, round whitefish were incubated under fluctuating or constant temperatures, with morpholine or 137 Cs gamma rays. We report the percentage of prehatch and posthatch mortality, developmental rate, hatch dynamics, and morphometrics at 4 development stages. Embryos reared at constant temperatures had delayed developmental stage onset and median hatch, higher mortality at constant 8 °C, and lower mortality at ≤5 °C, compared with embryos reared under seasonal temperature regimes. Embryos incubated with ≥500 mg L-1 morpholine (>200× regulatory limits) had advanced hatch, reduced body size, and increased prehatch (100% at 1000 mg L-1 ) and posthatch (≈95% at 500 mg L-1 ) mortality compared with controls. Relative to controls, embryos irradiated with ≥0.16 mGy/d had larger body mass early in development, and all irradiated embryos had decreased posthatch mortality; the lowest dose was >300× discharge limits. Our study suggests that fluctuating or elevated temperatures and high-dose morpholine can alter development rate, hatch dynamics, and growth, and/or increase mortality compared with embryos reared at constant temperatures of ≤5 °C; conversely, low-dose irradiation had transient developmental effects but may benefit early posthatch survival. Environ Toxicol Chem 2018;37:2593-2608. © 2018 SETAC.


Development and validation of a clinical prediction score for poor postoperative pain control following elective spine surgery.
Thirty percent to sixty-four percent of patients experience poorly controlled pain following spine surgery, leading to patient dissatisfaction and poor outcomes. Identification of at-risk patients before surgery could facilitate patient education and personalized clinical care pathways to improve postoperative pain management. Accordingly, the aim of this study was to develop and internally validate a prediction score for poorly controlled postoperative pain in patients undergoing elective spine surgery. A retrospective cohort study was performed in adult patients (≥ 18 years old) consecutively enrolled in the Canadian Spine Outcomes and Research Network registry. All patients underwent elective cervical or thoracolumbar spine surgery and were admitted to the hospital. Poorly controlled postoperative pain was defined as a mean numeric rating scale score for pain at rest of > 4 during the first 24 hours after surgery. Univariable analysis followed by multivariable logistic regression on 25 candidate variables, selected through a systematic review and expert consensus, was used to develop a prediction model using a random 70% sample of the data. The model was transformed into an eight-tier risk-based score that was further simplified into the three-tier Calgary Postoperative Pain After Spine Surgery (CAPPS) score to maximize clinical utility. The CAPPS score was validated using the remaining 30% of the data. Overall, 57% of 1300 spine surgery patients experienced poorly controlled pain during the first 24 hours after surgery. Seven significant variables associated with poor pain control were incorporated into a prediction model: younger age, female sex, preoperative daily use of opioid medication, higher preoperative neck or back pain intensity, higher Patient Health Questionnaire-9 depression score, surgery involving ≥ 3 motion segments, and fusion surgery. Notably, minimally invasive surgery, body mass index, and revision surgery were not associated with poorly controlled pain. The model was discriminative (C-statistic 0.74, 95% CI 0.71-0.77) and calibrated (Hosmer-Lemeshow goodness-of-fit, p = 0.99) at predicting the outcome. Low-, high-, and extreme-risk groups stratified using the CAPPS score had 32%, 63%, and 85% predicted probability of experiencing poorly controlled pain, respectively, which was mirrored closely by the observed incidence of 37%, 62%, and 81% in the validation cohort. Inadequate pain control is common after spine surgery. The internally validated CAPPS score based on 7 easily acquired variables accurately predicted the probability of experiencing poorly controlled pain after spine surgery.


Migration and HIV infection in Malawi.
To evaluate the assumption that moving heightens HIV infection by examining the time-order between migration and HIV infection and investigate differences in HIV infection by migration destination and permanence. We employ four waves of longitudinal data (2004-2010) for 4265 men and women from a household-based study in rural Malawi and a follow-up of migrants (2013). Using these data, we examine HIV status prior to migration. Migrants are disaggregated by destination (rural, town, and urban) and duration (return and permanent); all compared with individuals who consistently resided in the rural origin ('nonmigrants'). HIV-positive individuals have significantly greater odds of migration than those who are HIV negative [odds ratio 2.75; 95% confidence interval (CI) 1.89-4.01]. Being HIV positive significantly increases the relative risk (RR) that respondent will be a rural-urban migrant [RR ratio (RRR) 6.28; 95% CI 1.77-22.26), rural-town migrant (RRR 3.62; 95% CI 1.24-10.54), and a rural-rural migrant (RRR 4.09; 95% CI 1.68-9.97), instead of a nonmigrant. Being HIV positive significantly increases the RR that a respondent will move and return to the village of origin (RRR 2.58; 95% CI 1.82-3.66) and become a permanent migrant (RRR 3.21; 95% CI 1.77-5.82) instead of not migrating. HIV-positive status has a profound impact on mobility: HIV infection leads to significantly higher mobility through all forms of migration captured in our study. These findings emphasize that migration is more than just an independent risk factor for HIV infection: greater prevalence of HIV among migrants is partly due to selection of HIV-positive individuals into migration.


Influence of the Tumor Microenvironment on Cancer Cells Metabolic Reprogramming.
As with castles, tumor cells are fortified by surrounding non-malignant cells, such as cancer-associated fibroblasts, immune cells, but also nerve fibers and extracellular matrix. In most cancers, this fortification creates a considerable solid pressure which limits oxygen and nutrient delivery to the tumor cells and causes a hypoxic and nutritional stress. Consequently, tumor cells have to adapt their metabolism to survive and proliferate in this harsh microenvironment. To satisfy their need in energy and biomass, tumor cells develop new capacities to benefit from metabolites of the microenvironment, either by their uptake through the macropinocytosis process or through metabolite transporters, or by a cross-talk with stromal cells and capture of extracellular vesicles that are released by the neighboring cells. However, the microenvironments of primary tumor and metastatic niches differ tremendously in their cellular/acellular components and available nutrients. Therefore, cancer cells must develop a metabolic flexibility conferring on them the ability to satisfy their biomass and energetic demands at both primary and metastasis sites. In this review, we propose a brief overview of how proliferating cancer cells take advantage of their surrounding microenvironment to satisfy their high metabolic demand at both primary and metastasis sites.


A comparison of nursing tasks undertaken by regulated nurses and nursing support workers: a work sampling study.
The aim of this study was to determine which tasks unregulated nursing support staff spend their work time undertaking and to determine differences between the work undertaken by licensed/regulated nurses on units which have nursing support workers and those on units which do not. Acute hospital nursing teams often include nursing support staff; little is known about what kinds of tasks these unregulated support workers do and how it affects the work tasks of their licensed/regulated team members. Cross-sectional analysis of nurse work sampling data. Data collection took place between March-October 2013. The proportion of time spent on 25 work activities by nursing support staff and licensed/regulated nursing staff was compared. Logistic regression models estimated whether nursing support staff or licensed/regulated nurses were more likely to conduct direct and indirect patient care tasks and whether licensed/regulated nurses on units with nursing support staff were more likely to conduct direct or indirect tasks compared with those on units without nursing support workers. Nursing support staff spent the majority of their time engaged in direct care tasks, e.g. admission and assessment, hygiene and mobility. Although licensed/regulated nurses were less likely to undertake direct care tasks compared with support workers, those who worked on units with support workers undertook more direct care compared with those who worked on units without support workers. Nursing support workers were given tasks that required substantial amounts of patient interaction. These staff may be associated with an increase in direct care tasks for licensed/regulated nurses, who may duplicate the direct care done by nursing support workers.


Venous and arterial changes in pulmonary veno-occlusive disease, mitral stenosis and fibrosing mediastinitis.
The pathogenesis of pulmonary veno-occlusive disease (PVOD) is not known. The diagnosis of PVOD frequently relies on its histological changes since it is often difficult to distinguish clinically from primary pulmonary hypertension. This study carried out a systematic analysis of the pulmonary venous and arterial remodelling that occurs in PVOD (n=5) and compared these changes to two other diseases affecting the pulmonary veins, mitral stenosis (MS; n=6) and fibrosing mediastinitis (FM; n=2), using established morphometric techniques. In PVOD, pronounced intimal and adventitial thickening were noted in veins of all sizes and arterialization of veins >50 microm external diameter was found. Similar changes were evident in the arterial wall, but intimal thickening was less severe than in the veins and medial thickening was more pronounced in arteries <300 microm external diameter. Eccentric intimal fibrosis of the veins was also noted for the first time in PVOD, although this feature occurred less frequently (approximately one third) than in MS. Less pronounced structural remodelling was also encountered in the veins in cases of MS and FM. The severity of the venous changes in PVOD may aid its diagnosis and lend insight into its pathogenesis. However, the similarity of the vascular changes in each form of venous hypertension also suggests that pathology alone may not always differentiate between these disease states. The similarity of the vascular changes in the three forms of venous hypertension suggests that, as in pulmonary artery hypertension, pressure, per se, is one of the triggers to vascular remodelling.


Heat processing effect of luteolin on anti-metastasis activity of human glioblastoma cells U87.
Among the flavonoïds, luteolin is a flavone that has been identified in many plants. It is known for its apoptotic potential with damage to DNA and cell cycle blockage. Many studies have shown that luteolin has anti-oxidant, anti-inflammatory, and anti-cancer activities. However, it is known that heat treatment (boiling, cooking, and treating with microwaves …) can influence the structure of flavonoïds, which often leads to changes in their activities. The present study was conducted to study the effect of heated luteolin on anti-tumor activity of glioblastoma cells U87. Glioblastoma cell viability was evaluated by MTT assay. Adhesion assay was performed on different protein matrices (collagen type 1, vitronectin, fibronectin, and poly-L-lysine); migration assay was determined by modified Boyden chambers and videomicroscopy, and finally, angiogenesis was tested in vitro by capillary network formation on Matrigel™. The results obtained show that the thermal treatment significantly reduces its cytotoxic activity and ability to inhibit cell adhesion to different protein matrices. It was also found that the heat processed significantly reduced the ability of luteolin to inhibit cell migration, cell invasion, and endothelial cell angiogenesis (HMEC-1). This suggests that heat treated luteolin has a lower anti-tumor potential than native luteolin. Graphical abstract .


Diversity of the neglected and underutilized crop species of importance in Benin.
Many of the plant species that are cultivated for food across the world are neglected and underutilized. To assess their diversity in Benin and identify the priority species and establish their research needs, a survey was conducted in 50 villages distributed throughout the country. The study revealed 41 neglected and underutilized crop species (NUCS) among which 19 were identified as of priority base on 10 criteria among which included their extent and degree of consumption. Reasons for neglect vary with the producers and the agricultural technicians. Market surveys revealed that NUCS are important source of household incomes and substantially contribute to poverty reduction. Review of the literature available revealed that most of the species are rich in nutrients and have some proven medicinal values and the promotion of their use would help in combating malnutrition and improving the health status of the local populations. The knowledge gaps and research needs are immense on most of the species identified as no concrete scientific data is nationally available. In terms of research, almost all has to be done starting from basic ethnobotanical investigation. The results will help the scientists and students willing to conduct research on NUCS in Benin to better orient their research programs.


THE HISTOLOGIGAL LESIONS OF ACUTE GLANDERS IN MAN AND OF EXPERIMENTAL GLANDERS IN THE GUINEA-PIG.
The glanders nodule in the class of cases studied by us is in no sense analogous to the miliary tubercle in its histogenesis, and our studies afford no support to Baumgarten's views. The primary effect of the bacillus of glanders on a tissue we found to be not a production of epithelioid cells, which undergo necrosis and invasion by leucocytes, as happens in the cases in which the bacillus of tuberculosis is concerned, but to be the production of primary necrosis of the tissue, followed by inflammatory exudation, often of a suppurative character. Degenerative changes rapidly ensue in the inflammatory products. These conclusions are in harmony with the observations of Tedeschi, above referred to.


Lymphoma after solid organ transplantation: risk, response to therapy, and survival at a transplantation center.
We studied the incidence, risk factors, treatment, and outcomes of post-transplantation lymphoproliferative disorder (PTLD) that occurred at the University of Michigan since 1964. We identified 7,040 patients who received solid organ transplantation (SOT) and post-transplantation immunosuppressive therapy. Seventy-eight patients developed PTLD. Diffuse large B-cell lymphoma (n = 43), polymorphic PTLD (n = 10), Hodgkin's lymphoma (n = 7), Burkitts lymphoma (n = 6), plasmacytoma (n = 5), and mucosa-associated lymphoid tissue lymphoma (n = 3) were all over-represented in the SOT population compared with a population sample from the Surveillance, Epidemiology, and End Results (SEER) database; follicular lymphoma (n = 0) was underrepresented. Negative pretransplantation Epstein-Barr virus (EBV) serology was a risk factor for PTLD. Available histologic analysis of tumor tissue showed that 75% were CD20 positive and that 62% were EBV positive; EBV-positive tumors occurred sooner after SOT than EBV-negative tumors (mean, 29 v 66 months). Extralymphatic disease (79%), poor performance status (68%), elevated lactate dehydrogenase (LDH; 71%), and advanced stage (68%) disease were all common at the time of lymphoma diagnosis. Two thirds of patients had a complete response when treated with cyclophosphamide, doxorubicin, vincristine, and prednisone-like chemotherapy (either with or without rituximab). Median overall survival in all patients with PTLD was 8.23 years (95% CI, 2.28 to 30.0 years). EBV-naïve patients who receive a donor organ from an EBV-infected donor are in the highest-risk situation for PTLD development. Most of these lymphomas are CD20 positive. Follicular lymphoma is unusual. With treatment, survival of patients with PTLD was indistinguishable from that of the SEER population sample.


Use of host factors to identify people at high risk for cutaneous malignant melanoma .
To determine which host characteristics are risk factors for cutaneous malignant melanoma in order to aim prevention and early detection programs at people at high risk. Case-control study. Southern Ontario. The 583 case subjects were aged 20 to 69 years and had had malignant melanoma newly diagnosed between Oct. 1, 1984, and Sept. 30, 1986. The 608 control subjects were randomly selected from a list of residents in the study area and were stratum matched for age, sex and municipality. Through in-person interviews the interviewer ascertained exposure to putative external risk factors and assessed skin colour and number of nevi on the arm, and the subject reported his or her natural hair colour at age 20 years, eye colour, skin reaction to repeated sun exposure, and freckle and whole-body nevus densities. Although all the host factors mentioned were significantly associated with melanoma risk when considered separately, only hair colour, skin reaction to repeated sun exposure, and self-reported freckle and nevus densities remained significant after backward logistic regression analysis. The odds ratio for melanoma was estimated to be 10.7 in people who had many nevi compared with those who had none (95% confidence interval [CI] 6.6 to 17.4), 4.0 in people who had red hair compared with those who had black hair (95% CI 1.9 to 8.2), 1.9 in people who had many freckles compared with those who had none or few (95% CI 1.3 to 2.8) and 1.4 respectively in people who burned and had a subsequent increase in tan and those who burned and had no increase in tan after repeated sun exposure compared with those who did not burn [corrected]. Four risk factors for malignant melanoma have been identified. Prospective evaluation of their predictive value should be done. In the meantime, however, these factors should be used to identify people apparently at high risk for malignant melanoma, who can then be targeted for early detection and prevention programs.


Osmotic-pressure-controlled concentration of colloidal particles in thin-shelled capsules.
Colloidal crystals are promising structures for photonic applications requiring dynamic control over optical properties. However, for ease of processing and reconfigurability, the crystals should be encapsulated to form 'ink' capsules rather than confined in a thin film. Here we demonstrate a class of encapsulated colloidal photonic structures whose optical properties can be controlled through osmotic pressure. The ordering and separation of the particles within the microfluidically created capsules can be tuned by changing the colloidal concentration through osmotic pressure-induced control of the size of the individual capsules, modulating photonic stop band. The rubber capsules exhibit a reversible change in the diffracted colour, depending on osmotic pressure, a property we call osmochromaticity. The high encapsulation efficiency and capsule uniformity of this microfluidic approach, combined with the highly reconfigurable shapes and the broad control over photonic properties, make this class of structures particularly suitable for photonic applications such as electronic inks and reflective displays.


Skill Assessment for Coupled Biological/Physical Models of Marine Systems.
Coupled biological/physical models of marine systems serve many purposes including the synthesis of information, hypothesis generation, and as a tool for numerical experimentation. However, marine system models are increasingly used for prediction to support high-stakes decision-making. In such applications it is imperative that a rigorous model skill assessment is conducted so that the model's capabilities are tested and understood. Herein, we review several metrics and approaches useful to evaluate model skill. The definition of skill and the determination of the skill level necessary for a given application is context specific and no single metric is likely to reveal all aspects of model skill. Thus, we recommend the use of several metrics, in concert, to provide a more thorough appraisal. The routine application and presentation of rigorous skill assessment metrics will also serve the broader interests of the modeling community, ultimately resulting in improved forecasting abilities as well as helping us recognize our limitations.


A cost-utility analysis of multivitamin and multimineral supplements in men and women aged 65 years and over.
As people age there is a progressive dysregulation of the immune system that may lead to an increased risk of infections, which may precipitate hospital admission in people with chronic heart or respiratory diseases. Mineral and vitamin supplementation in older people could therefore influence infections in older people. However, the evidence from the available randomised controlled trials (RCTs) is mixed. The aim of the study was to assess the relative efficiency of multivitamin and multimineral supplementation compared with no supplementation. Cost-utility analysis alongside an RCT. Participants aged 65 years or over from six general practices in Grampian, Scotland, were studied. They were randomised to one tablet daily of either a multivitamin and multimineral supplement or matching placebo. Exclusion criteria were use of mineral, vitamin or fish oil supplements in the previous 3 months (1 month for water soluble vitamins), vitamin B12 injection in the last 3 months. Nine hundred and ten participants were recruited (454 placebo and 456 supplementation). Use of health service resources and costs were similar between the two groups. The supplementation arm was more costly although this was not statistically significant ( pound15 per person, 95% CI-3.75 to 34.95). After adjusting for minimisation and baseline EQ-5D scores supplementation was associated with fewer QALYs per person (-0.018, 95% CI-0.04 to 0.002). It was highly unlikely that supplementation would be considered cost effective. The evidence from this study suggests that it is highly unlikely that supplementation could be considered cost effective.


Metals in Cannabis Vaporizer Aerosols: Sources, Possible Mechanisms, and Exposure Profiles.
In recent years, cannabis vaporizer cartridges have increased in popularity and availability, and there are concerns regarding exposure to heavy-metal compounds from their use. The physical components of the cartridge devices themselves have been implicated as a potential source of metal exposure, but it is not known if these metals migrate into the inhalable vapor. This study analyzes the components of vaporizer cartridges for 10 different metals and also collects aerosol mixtures from 13 randomly purchased commercially available cannabis cartridges from Washington State to compare their elemental profiles. Results indicate that chromium, copper, nickel, as well as smaller amounts of lead, manganese, and tin migrate into the cannabis oil and inhaled vapor phase, resulting in a possible acute intake of an amount of inhaled metals above the regulatory standard of multiple governmental bodies. Noncartridge heating methods of cannabis flower and concentrate were compared, and results indicate that the heating device itself is a source of metal contamination. As safety and compliance testing regulations evolve, it will be important to include more than the standard As, Cd, Hg, and Pb to the list of regulated metals.