Potential, pitfalls, and prospects of food allergy diagnostics with recombinant allergens or synthetic sequential epitopes.
This article aims to critically review developments in food allergy diagnostics with regard to the verification of specific IgE antibodies and the identification of the responsible allergens. Results of IgE-binding tests with food extracts are hampered by cross-reactive proteins, low-quality test agents, or both. Specificity can be increased by defining adequate cutoff values, whereas sensitivity can be improved by using high-quality test agents. IgE-binding tests with purified allergens enabled reliable quantification of allergen-specific IgE titers, with higher levels found in individuals with food allergy compared with individuals without food allergy. However, the overlap in individual test reactivity between allergic and nonallergic subjects complicates interpretation. Recombinant allergens and synthetic sequential epitopes enabled detection of sensitization profiles, with IgE specific to several allergens and substructures now being suggested as markers of severity, persistence, or both. However, high-power quantitative studies with larger numbers of patients are required to confirm these markers. IgE-binding tests merely indicate sensitization, whereas the final proof of clinical relevance still relies on family/case history, physical examinations, and provocation tests. Novel technologies promise superior diagnostics. Microarray technology permits simultaneous measurement of multiple IgE reactivities regarding specificity, abundance, reactivity, or interaction. Improved functional tests might enable reliable estimation of the clinical relevance of IgE sensitizations at justifiable expenses.


Outcomes for adult outpatients with depression under prepaid or fee-for-service financing.
To compare change over time in symptoms of depression and limitations in role and physical functioning of patients receiving prepaid or fee-for-service care within and across clinician specialties. Observational study of change in outcomes over 2 years for 617 depressed patients of psychiatrists, psychologists, other therapists, and general medical clinicians in three urban sites in the United States. Psychiatrists treated psychologically sicker patients than other clinicians in all payment types. Among psychiatrists' patients, those initially receiving prepaid care acquired new limitations in role/physical functioning over time, while those receiving fee-for-service care did not. This finding was most striking in independent practice associations but varied by site and organization. Patients of psychiatrists were more likely to use antidepressant medication than were patients of other clinicians, but among psychiatrists' patients, there was a sharp decline over time in the use of such medication in prepaid compared with fee-for-service care. Outcomes did not differ by payment type for depressed patients of other specialty groups, or overall. Depressed patients of psychiatrists merit policy interest owing to their high levels of psychological sickness. For these patients, functioning outcomes were poorer in some prepaid organizations. The nonexperimental evidence favors (but cannot prove) an explanation based on care received, such as a reduction in medications, rather than on preexisting sickness differences.


Potential and limitations of a gamma 34.5 mutant of herpes simplex 1 as a gene therapy vector in the CNS.
Direct injection of viral vectors into the central nervous system has become a valuable technique for exploring the function of neurological systems and is a potential therapy for neural disease. To this end a number of herpes simplex virus (HSV)-derived vectors are currently being developed for the introduction of foreign DNA into the brain. In this study a non-neurovirulent HSV 17+ mutant, variant 1716, deleted in the gamma 34.5 gene and expressing the marker gene lacZ under the control of the latency-associated transcripts promoter was injected stereotactically into the central nervous system of two strains of rat (AO and PVG). We show (1) that transgene expression was low at the site of injection, in the striatum, at all times studied (12 h to 30 days after injection); (2) dramatically more transgene expression was observed at distant sites which contain neurons projecting directly to the site of injection, with maximal expression at these sites being at 1-2 days; (3) immunostaining with a polyclonal anti-HSV antibody and with an antibody which detects a 65 kDa HSV DNA binding protein (the product of the UL42 gene of the virus) demonstrated that viral gene products could be detected at the injection site as early as 12 h and up to 1 week after injection. Moreover these could also be detected at several secondary sites not all of which have direct connections with the injection site. These findings suggest that gamma 34.5 negative vectors have potential for gene transfer but may require further attenuation to limit viral antigen expression before they can be used successfully for gene therapy in the brain.


Efficacy and limitations of a specific immunotherapy in chronic hepatitis B.
This controlled study aimed to evaluate the efficacy and potential side effects of hepatitis B virus (HBV) vaccination as active immunotherapy in HBV-related chronic hepatitis. The 118 included patients were 'naive' subjects who had never received any previous anti-HBV therapy, showed detectable serum HBV DNA and had biopsy-proven chronic hepatitis. In a 12-month follow-up they were given either five intramuscular injections of 20 microg of a preS2/S (GenHevac B, Pasteur-Mérieux) (n = 46) or an S vaccine (Recombivax Merck & Co.) (n = 34) or no treatment as a control (n = 37). The efficacy of vaccination was evaluated by testing for serum HBV DNA negativation using a standard liquid hybridization assay. Three months after the first three vaccine injections, the percentage of serum HBV DNA negativation was higher in the vaccine groups (16.3%) than in the control group (2.7%) (P = 0.033, by the chi2 Pearson test) and was more frequently observed in patients who had pretreatment viremia >200 pg/ml (none in the control group vs. 16.7% in the vaccinated groups) (P = 0.025). After 12 months follow-up and five vaccine injections, there was no difference in the rate of serum HBV DNA negativation between vaccinated and unvaccinated subjects but HBV vaccines significantly decreased the HBV viral load between the sixth and twelfth months (P = 0.04) in contrast with the control group. The rate of HBe/anti-HBe seroconversion after 6 months of follow-up occurred only in eight (13.3%) vaccinated patients and in one (3.6%) of the controls. Disappearance of serum HBsAg was not observed in any of the patients. This controlled study offers direct evidence that the HBV vaccine may decrease HBV replication in chronic hepatitis B patients. It also emphasizes the need for reinforced immunization strategies as well as combination therapies.


Japanese phase II study of 90Y-ibritumomab tiuxetan in patients with relapsed or refractory indolent B-cell lymphoma.
There is no data about the efficacy and safety of radioimmunotherapy with 90Y-ibritumomab tiuxetan in patients with relapsed or refractory indolent B-cell lymphoma pretreated with rituximab-containing chemotherapy. We focused on this in a Japanese phase II study. Radioimmunotherapy with 90Y-ibritumomab tiuxetan (11.1 and 14.8 MBq) was evaluated in patients with 100-149x10(9) and >150x10(9) platelets/L, respectively. The primary endpoint was the overall response rate. Forty patients were treated with 90Y-ibritumomab tiuxetan (18 with 11.1 MBq/kg and 22 with 14.8 MBq/kg). Thirty-five patients (88%) had been pretreated with rituximab, including 27 (68%) pretreated with rituximab-containing chemotherapy. The overall response rate was 83% (33/40; 95% confidence interval, 67-93%), and the complete response rate was 68% (27/40; 95% confidence interval, 51-81%). The overall response rates in patients pretreated with rituximab-containing chemotherapy and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were 83% (19/23) and 94% (17/18), respectively. The median progression-free survival time of the 40 patients who received 90Y-ibritumomab tiuxetan was 9.6 months. Toxicity was primarily hematological and mostly transient. No grade 4 non-hematological toxicity was observed. In conclusion, radioimmunotherapy with 90Y-ibritumomab tiuxetan is safe and highly effective in patients with relapsed or refractory indolent B-cell lymphoma, including those pretreated with rituximab-containing chemotherapy. (ClinicalTrials.gov number NCT00220285).


PAS kinase promotes cell survival and growth through activation of Rho1.
In Saccharomyces cerevisiae, phosphorylation of Ugp1 by either of the yeast PASK family protein kinases (yPASK), Psk1 or Psk2, directs this metabolic enzyme to deliver glucose to the periphery for synthesis of the cell wall. However, we isolated PSK1 and PSK2 in a high-copy suppressor screen of a temperature-sensitive mutant of target of rapamycin 2 (TOR2). Posttranslational activation of yPASK, either by cell integrity stress or by growth on nonfermentative carbon sources, also suppressed the growth defect resulting from tor2 mutation. Although suppression of the tor2 mutant growth phenotype by activation of the kinase activity of yPASK required phosphorylation of the metabolic enzyme Ugp1 on serine 11, this resulted in the formation of a complex that induced Rho1 activation, rather than required the glucose partitioning function of Ugp1. In addition to phosphorylated Ugp1, this complex contained Rom2, a Rho1 guanine nucleotide exchange factor, and Ssd1, an mRNA-binding protein. Activation of yPASK-dependent Ugp1 phosphorylation, therefore, enables two processes that are required for cell growth and stress resistance: synthesis of the cell wall through partitioning glucose to the periphery and the formation of the signaling complex with Rom2 and Ssd1 to promote Rho1-dependent polarized cell growth. This complex may integrate metabolic and signaling responses required for cell growth and survival in suboptimal conditions.


Relation of the fourth-order statistical invariants of velocity gradient tensor in isotropic turbulence.
We show by direct numerical simulations (DNSs) that in different types of isotropic turbulence, the fourth-order statistical invariants have approximately a linear relation, which can be represented by a straight line in the phase plane, passing two extreme states: the Gaussian state and the restricted Euler state. Also, each DNS case corresponds to an equilibrium region that is roughly Reynolds-dependent. In addition, both the time reversal and the compressibility effect lead to nonequilibrium transition processes in this phase plane. This observation adds a new restriction on the mean-field theory.


Elemental mapping and microimaging by x-ray capillary optics.
Recently, many experiments have highlighted the advantage of using polycapillary optics for x-ray fluorescence studies. We have developed a special confocal scheme for micro x-ray fluorescence measurements that enables us to obtain not only elemental mapping of the sample but also simultaneously its own x-ray imaging. We have designed the prototype of a compact x-ray spectrometer characterized by a spatial resolution of less than 100 microm for fluorescence and less than 10 microm for imaging. A couple of polycapillary lenses in a confocal configuration together with a silicon drift detector allow elemental studies of extended samples (approximately 3 mm) to be performed, while a CCD camera makes it possible to record an image of the same samples with 6 microm spatial resolution, which is limited only by the pixel size of the camera. By inserting a compound refractive lens between the sample and the CCD camera, we hope to develop an x-ray microscope for more enlarged images of the samples under test.


The complex dynamics of wishful thinking: the critical positivity ratio.
We examine critically the claims made by Fredrickson and Losada (2005) concerning the construct known as the "positivity ratio." We find no theoretical or empirical justification for the use of differential equations drawn from fluid dynamics, a subfield of physics, to describe changes in human emotions over time; furthermore, we demonstrate that the purported application of these equations contains numerous fundamental conceptual and mathematical errors. The lack of relevance of these equations and their incorrect application lead us to conclude that Fredrickson and Losada's claim to have demonstrated the existence of a critical minimum positivity ratio of 2.9013 is entirely unfounded. More generally, we urge future researchers to exercise caution in the use of advanced mathematical tools, such as nonlinear dynamics, and in particular to verify that the elementary conditions for their valid application have been met.


Local Effects of Ring Topology Observed in Polymer Conformation and Dynamics by Neutron Scattering-A Review.
The physical properties of polymers depend on a range of both structural and chemical parameters, and in particular, on molecular topology. Apparently simple changes such as joining chains at a point to form stars or simply joining the two ends to form a ring can profoundly alter molecular conformation and dynamics, and hence properties. Cyclic polymers, as they do not have free ends, represent the simplest model system where reptation is completely suppressed. As a consequence, there exists a considerable literature and several reviews focused on high molecular weight cyclics where long range dynamics described by the reptation model comes into play. However, this is only one area of interest. Consideration of the conformation and dynamics of rings and chains, and of their mixtures, over molecular weights ranging from tens of repeat units up to and beyond the onset of entanglements and in both solution and melts has provided a rich literature for theory and simulation. Experimental work, particularly neutron scattering, has been limited by the difficulty of synthesizing well-characterized ring samples, and deuterated analogues. Here in the context of the broader literature we review investigations of local conformation and dynamics of linear and cyclic polymers, concentrating on poly(dimethyl siloxane) (PDMS) and covering a wide range of generally less high molar masses. Experimental data from small angle neutron scattering (SANS) and quasi-elastic neutron scattering (QENS), including Neutron Spin Echo (NSE), are compared to theory and computational predictions.


Age-related variation in foraging behaviour in the wandering albatross at South Georgia: no evidence for senescence.
Age-related variation in demographic rates is now widely documented in wild vertebrate systems, and has significant consequences for population and evolutionary dynamics. However, the mechanisms underpinning such variation, particularly in later life, are less well understood. Foraging efficiency is a key determinant of fitness, with implications for individual life history trade-offs. A variety of faculties known to decline in old age, such as muscular function and visual acuity, are likely to influence foraging performance. We examine age-related variation in the foraging behaviour of a long-lived, wide-ranging oceanic seabird, the wandering albatross Diomedea exulans. Using miniaturised tracking technologies, we compared foraging trip characteristics of birds breeding at Bird Island, South Georgia. Based on movement and immersion data collected during the incubation phase of a single breeding season, and from extensive tracking data collected in previous years from different stages of the breeding cycle, we found limited evidence for age-related variation in commonly reported trip parameters, and failed to detect signs of senescent decline. Our results contrast with the limited number of past studies that have examined foraging behaviour in later life, since these have documented changes in performance consistent with senescence. This highlights the importance of studies across different wild animal populations to gain a broader perspective on the processes driving variation in ageing rates.


Combined scanning transmission X-ray and electron microscopy for the characterization of bacterial endospores.
Endospores (also referred to as bacterial spores) are bacterial structures formed by several bacterial species of the phylum Firmicutes. Spores form as a response to environmental stress. These structures exhibit remarkable resistance to harsh environmental conditions such as exposure to heat, desiccation, and chemical oxidants. The spores include several layers of protein and peptidoglycan that surround a core harboring DNA as well as high concentrations of calcium and dipicolinic acid (DPA). A combination of scanning transmission X-ray microscopy, scanning transmission electron microscopy, and energy dispersive spectroscopy was used for the direct quantitative characterization of bacterial spores. The concentration and localization of DPA, Ca(2+) , and other elements were determined and compared for the core and cortex of spores from two distinct genera: Bacillus subtilis and Desulfotomaculum reducens. This micro-spectroscopic approach is uniquely suited for the direct study of individual bacterial spores, while classical molecular and biochemical methods access only bulk characteristics.


Electrical injuries: a 20-year review.
Electrical injuries continue to present problems with devastating complications and long-term socioeconomic impact. The purpose of this study is to review one institution's experience with electrical injuries. From 1982 to 2002, there were 700 electric injury admissions. A computerized burn registry was used for data collection and analysis. Of these injuries, 263 were high voltage (> or =1000 V), 143 were low voltage (<1000 V), 277 were electric arc flash burns, and 17 were lightning injuries. Mortality was highest in the lightning strikes (17.6%) compared with the high voltage (5.3%) and low voltage (2.8%) injuries, and mortality was least in electric arc injuries without passage of current through the patient (1.1%). Complications were most common in the high-voltage group. Mean length of stay was longest in this group (18.9 +/- 1.4 days), and the patients in this group also required the most operations (3 +/- 0.2). Work-related activity was responsible for the majority of these high-voltage injuries, with the most common occupations being linemen and electricians. These patients tended to be younger men in the prime of their working lives. Electrical injuries continue to make up an important subgroup of patients admitted to burn centers. High-voltage injuries in particular have far reaching social and economic impact largely because of the patient population at greatest risk, that is, younger men at the height of their earning potential. Injury prevention, although appropriate, remains difficult in this group because of occupation-related risk.


A generic model for a single strain mosquito-transmitted disease with memory on the host and the vector.
In the present investigation, three mathematical models on a common single strain mosquito-transmitted diseases are considered. The first one is based on ordinary differential equations, and other two models are based on fractional order differential equations. The proposed models are validated using published monthly dengue incidence data from two provinces of Venezuela during the period 1999-2002. We estimate several parameters of these models like the order of the fractional derivatives (in case of two fractional order systems), the biting rate of mosquito, two probabilities of infection, mosquito recruitment and mortality rates, etc., from the data. The basic reproduction number, R0, for the ODE system is estimated using the data. For two fractional order systems, an upper bound for, R0, is derived and its value is obtained using the published data. The force of infection, and the effective reproduction number, R(t), for the three models are estimated using the data. Sensitivity analysis of the mosquito memory parameter with some important responses is worked out. We use Akaike Information Criterion (AIC) to identify the best model among the three proposed models. It is observed that the model with memory in both the host, and the vector population provides a better agreement with epidemic data. Finally, we provide a control strategy for the vector-borne disease, dengue, using the memory of the host, and the vector.


Emotion regulation deficits in persons with body-focused repetitive behavior disorders.
Conceptualizations of emotion dysregulation (ED) and body-focused repetitive behavior disorders (BFRBDs) imply that ED may be a central component of BFRBDs as well as a factor that distinguishes BFRBDs from non-impairing, subclinical body-focused repetitive behaviors (BFRBs). The current study empirically tested these observations. One hundred thirty-eight undergraduates (of 1900 who completed a screening survey) completed self-report measures assessing four emotion regulation (ER) deficits hypothesized to underlie ED (alexithymia, maladaptive emotional reactivity, experiential avoidance, and response inhibition when distressed); 34 of these participants had BFRBDs, 64 had subclinical BFRBs, and 42 were unaffected by BFRBs. Results indicated that participants with BFRBDs reported higher levels of maladaptive emotional reactivity, experiential avoidance, and response inhibition when distressed than participants with subclinical BFRBs and participants unaffected by BFRBs. These results held even when controlling for comorbidity and total number of reported BFRBs. Participants did not differ on alexithymia. Limitations of the current study include the BFRB groups' different distributions of BFRB types (e.g., hair pulling versus skin picking), the sample's demographic uniformity, and the fact that negative affectivity was not controlled when exploring BFRB group differences on ER deficits. Future research should improve on these limitations. The current results suggest that ED is a factor that differentiates BFRBDs from subclinical BFRBs. Such results may be useful for generating hypotheses regarding mechanisms responsible for BFRBs' development into BFRBDs. Furthermore, these results may provide insight into factors that explain the efficacy of more contemporary behavioral treatments for BFRBDs.


[General clinical and laboratory and instrumental characteristics of the chronic nonbapterial prostatite with the inflammatory component in men of the first period of mature age].
To investigate the course of CNPIC in young men treated with general and local ozone therapy. 306 patients underwent standard treatment concurrently with local and systemic ozone therapy. Clinical-laboratory and instrumental parameters were evaluated before and after treatment. In addition, the blood flow of the prostate, prostatic urethra and skin at the projection point of the prostate was studied. Standard treatment of CNPIC with the concurrent use of general and local ozone therapy resulted in a reduction of pain intensity and severity of dysuria, improvement of the sexual function and quality of life of men. There was an increase in blood flow in the arteries and veins of the prostate, a decrease in the prostate size and volume. The study findings showed an almost twofold decrease of the mean values of the CNPIC clinical index during treatment. In the prostate secretion, the leukocyte count decreased from 29.29+/-0.67 to 4.75+/-0.15. A statistically significant (p<0.001) decrease in all sizes of the prostate was observed: height (upper) from 40.99+/-0.22 to 39.13+/-0.21 mm, width (transverse dimension) from 41.94+/-0.21 to 39.94+/-0.22 mm, and thickness (anteroposterior size) from 30.52+/-0.20 to 29.15+/-0.18 mm. Prostate volume also decreased from 27.78+/-0.42 to 24.10+/-0.36 cm (p<0.001).


Psychological interventions for women with non-metastatic breast cancer.
Breast cancer is the most common cancer affecting women worldwide. It is a distressing diagnosis and, as a result, considerable research has examined the psychological sequelae of being diagnosed and treated for breast cancer. Breast cancer is associated with increased rates of depression and anxiety and reduced quality of life. As a consequence, multiple studies have explored the impact of psychological interventions on the psychological distress experienced after a diagnosis of breast cancer. To assess the effects of psychological interventions on psychological morbidities, quality of life and survival among women with non-metastatic breast cancer. We searched the following databases up to 16 May 2013: the Cochrane Breast Cancer Group Specialised Register, CENTRAL, MEDLINE, EMBASE, CINAHL and PsycINFO; and reference lists of articles. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) search portal and ClinicalTrials.gov for ongoing trials in addition to handsearching. Randomised controlled trials that assessed the effectiveness of psychological interventions for non-metastatic breast cancer in women. Two review authors independently appraised and extracted data from eligible trials. Any disagreement was resolved by discussion. Extracted data included information about participants, methods, the intervention and outcome. Twenty-eight randomised controlled trials comprising 3940 participants were included. The most frequent reasons for exclusion were non-randomised trials and the inclusion of women with metastatic disease. A wide range of interventions were evaluated, with 24 trials investigating a cognitive behavioural therapy and four trials investigating psychotherapy compared to control. Pooled standardised mean differences (SMD) from baseline indicated less depression (SMD -1.01, 95% confidence interval (CI) -1.83 to -0.18; P = 0.02; 7 studies, 637 participants, I(2) = 95%, low quality evidence), anxiety (SMD -0.48, 95% CI -0.76 to -0.21; P = 0.0006; 8 studies, 776 participants, I(2) = 64%, low quality evidence) and mood disturbance (SMD -0.28, 95% CI -0.43 to -0.13; P = 0.0003; 8 studies, 1536 participants, I(2) = 47%, moderate quality evidence) for the cognitive behavioural therapy group than the control group. For quality of life, only an individually-delivered cognitive behavioural intervention showed significantly better quality of life than the control with an SMD of 0.65 (95% CI 0.07 to 1.23; P = 0.03; 3 studies, 141 participants, I(2) = 41%, very low quality evidence). Pooled data from two group-delivered studies showed a non-significant overall survival benefit favouring cognitive behavioural therapy compared to control (pooled hazard ratio (HR) 0.76, 95% CI 0.25 to 2.32; P = 0.63; 530 participants, I(2) = 84%, low quality evidence). Four studies compared psychotherapy to control with one to two studies reporting on each outcome. The four studies were assessed as high risk of bias and provided limited evidence of the efficacy of psychotherapy. Adverse events were not reported in any of the included studies. A psychological intervention, namely cognitive behavioural therapy, produced favourable effects on some psychological outcomes, in particular anxiety, depression and mood disturbance. However, the evidence for survival improvement is still lacking. These findings are open to criticism because of the notable heterogeneity across the included studies and the shortcomings of the included studies.


Simultaneous computed tomography-guided biopsy and radiofrequency ablation of solitary pulmonary malignancy in high-risk patients.
In recent years experience has been accumulated in percutaneous radiofrequency ablation (RFA) of lung malignancies in nonsurgical patients. In this study, we retrospectively evaluated a simultaneous diagnostic and therapeutic approach including CT-guided biopsy followed immediately by RFA of solitary malignant pulmonary lesions. CT-guided transthoracic core needle biopsy of solitary pulmonary lesions suspicious for malignancy was performed and histology was proven based on immediate frozen sections. RFA probes were placed into the pulmonary tumors under CT guidance and the ablation was performed subsequently. The procedure-related morbidity was analyzed. Follow-up included a CT scan and pulmonary function parameters. A total of 33 CT-guided biopsies and subsequent RFA within a single procedure were performed. Morbidity of CT-guided biopsy included pulmonary hemorrhage (24%) and a mild pneumothorax (12%) without need for further interventions. The RFA procedure was not aggravated by the previous biopsy. The rate of pneumothorax requiring chest tube following RFA was 21%. Local tumor control was achieved in 77% with a median follow-up of 12 months. The morbidity of the CT-guided biopsy had no statistical impact on the local recurrence rate. The simultaneous diagnostic and therapeutic approach including CT-guided biopsy followed immediately by RFA of solitary malignant pulmonary lesions is a safe procedure. The potential of this combined approach is to avoid unnecessary therapies and to perform adequate therapies based on histology. Taking the local control rate into account, this approach should only be performed in those patients who are unable to undergo or who refuse surgery.


Experimental comparison of a Shack-Hartmann sensor and a phase-shifting interferometer for large-optics metrology applications.
We performed a direct side-by-side comparison of a Shack-Hartmann wave-front sensor and a phase-shifting interferometer for the purpose of characterizing large optics. An expansion telescope of our own design allowed us to measure the surface figure of a 400-mm-square mirror with both instruments simultaneously. The Shack-Hartmann sensor produced data that closely matched the interferometer data over spatial scales appropriate for the lenslet spacing, and much of the <20-nm rms systematic difference between the two measurements was due to diffraction artifacts that were present in the interferometer data but not in the Shack-Hartmann sensor data. The results suggest that Shack-Hartmann sensors could replace phase-shifting interferometers for many applications, with particular advantages for large-optic metrology.


Suppressor of Cytokine Signaling 3 Expression Induced by Varicella-Zoster Virus Infection Results in the Modulation of Virus Replication.
Varicella-zoster virus (VZV) is an important viral pathogen that is responsible for causing varicella (chickenpox) and herpes zoster (shingles). VZV has been shown to suppress early anti-viral innate immune responses, but the exact mechanisms are not yet well understood. Here we demonstrate that host control of VZV is impaired by the expression of suppressor of cytokine signaling (SOCS)3. We used three different cell types to characterize VZV-induced anti-viral and inflammatory responses. Infection of human fibroblasts (MRC-5) and human macrophages (THP-1) with VZV triggered upregulation of anti-viral responsive gene expression (IFN-α, IFN-β) in the early phases of infection, followed by the waning of these IFNs in the late phases of infection. Conversely, VZV infection in keratinocytes (HaCaT) resulted in a persistent increase in type I IFN gene expression. Interestingly, increase in SOCS1 and 3 expressions coincided with a reduction in phosphorylation of the signal transducer and activator of transcription protein 3 (STAT3) in VZV-infected MRC-5 cells. Furthermore, VZV infection increased the production of pro-inflammatory cytokines, including interleukin (IL)-6, -8, and IFN-γ-inducible protein 10 (IP-10). Knockdown of SOCS3 inhibited viral replication and enhanced secretion levels of IL-6, whereas overexpression of SOCS3 did not affect viral replication efficiency and host response. In conclusion, our data suggest that VZV infection induces SOCS3 expression, resulting in modulation of type I IFN signaling and viral replication.


Racism, ideology, and affirmative action revisited: the antecedents and consequences of "principled objections" to affirmative action.
In 2 studies, the antecedents and consequences of "principled objections" to affirmative action (specific, "race-neutral" reasons for opposing the policy) among Whites were examined. In Study 1. data from a probability sample of Los Angeles adults indicated the following: (a) that principled-objection endorsement was driven not merely by race-neutral values but also by dominance-related concerns like racism; (b) that principled objections mediated the effects of group dominance; and (c) that education strengthened-rather than attenuated-the relationship between dominance-related concerns and principled objections. whereas it left the relationship between race-neutral values and the latter essentially unchanged. In Study 2, the education findings were conceptually replicated in a panel study of undergraduates: The completion of additional years of college boosted the correlation between racism and principled objections, whereas it had no effect on the predictive power of conservatism. These results provide support for a general group-dominance approach, which suggests that factors like racism continue to shape White opposition to race-targeted policies.


Awareness and uptake of the Pap smear among market women in Lagos, Nigeria.
Our study evaluates the effect of an educational programme on awareness and uptake of the cervical cancer screening test (Pap smear) by women in a model market in Lagos, Nigeria. This was a quasi-experimental study using a multistage sampling technique. A total of 350 women were divided into two groups. A baseline survey on awareness of the Pap test and screening practices was carried out using pre-tested, interviewer administered, structured questionnaires. Participants in the intervention group received sessions of community based health information on cervical cancer screening tests while participants in the control group received health information on hypertension. Subsequently, participants in both groups were reassessed to evaluate the effect of the educational programme on the Pap test and cervical screening uptake. Data were analysed with the Epi-info version 6.04. Awareness about the Pap test was low at baseline; only 6.9% and 12.0% of participants in the intervention and control groups, respectively, had heard of Pap smears. Furthermore, less than 10% had correct information on the use of the Pap test. Post-intervention, there was a significant and proportional increase in the knowledge of the Pap test in the intervention group (P<0.05). However, uptake of the test was quite low in the intervention and control groups both pre- and post-intervention and there was no significant change in uptake. We concluded that essential schemes are required to enhance access to screening, as knowledge alone is insufficient to promote acceptance and use of cervical cytological screening tests.


The Importance of Melatonin and Mitochondria Interaction in Mood Disorders and Schizophrenia: A Current Assessment.
Mitochondria play a critical role in regulating cellular functions, such as redox signaling, calcium homeostasis, and apoptosis. Also, mitochondria are crucial for neurogenesis and neuronal functions. Melatonin is an indole analog hormone, which is generally produced by the pineal gland. It plays a vital role in circadian rhythm and act as a powerful antioxidant by scavenging free radicals, immunomodulators, and anticancer agents. Schizophrenia and mood disorders are the two major psychiatric disorders. Disturbances of sleep and circadian rhythms are well-known symptoms of schizophrenia and mood disorders (bipolar disorder, major depression). Since melatonin has a regulator effect on circadian rhythm and sleep quality, it has a close interaction with schizophrenia and mood disorders. Herein, we aimed to summarize the effects of melatonin on mitochondrial activity in schizophrenia and mood disorders.


Novel high-affinity and selective biaromatic 4-substituted gamma-hydroxybutyric acid (GHB) analogues as GHB ligands: design, synthesis, and binding studies.
Gamma-hydroxybutyrate (GHB) is a metabolite of gamma-aminobutyric acid (GABA) and has been proposed to function as a neurotransmitter or neuromodulator. GHB is used in the treatment of narcolepsy and is a drug of abuse. GHB binds to both GABA(B) receptors and specific high-affinity GHB sites in brain, of which the latter have not been linked unequivocally to function, but are speculated to be GHB receptors. In this study, a series of biaromatic 4-substituted GHB analogues, including 4'-phenethylphenyl, 4'-styrylphenyl, and 4'-benzyloxyphenyl GHB analogues, were synthesized and characterized pharmacologically in a [3H](E,RS)-(6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylidene)acetic acid ([3H]NCS-382) binding assay and in GABA(A) and GABA(B) receptor binding assays. The compounds were selective for the high-affinity GHB binding sites and several displayed Ki values below 100 nM. The affinity of the 4-[4'-(2-iodobenzyloxy)phenyl] GHB analogue 17b was shown to reside predominantly with the R-enantiomer (Ki = 22 nM), which has higher affinity than previously reported GHB ligands.


Developing a standardized definition for disease "flare" in rheumatoid arthritis (OMERACT 9 Special Interest Group).
Traditional outcome measures in randomized controlled trials (RCT) include well-established response criteria as well as ACR EULAR responses using Disease Activity Score 44 (DAS44)/DAS28 to assess improvement; however, a measure to assess worsening of disease has yet to be developed. This special interest group (SIG) was established to develop an evidence-based, consensus-driven standard definition of "flare" in rheumatoid arthritis (RA). At OMERACT 8, the need for a standardized definition of RA flare was recognized; interested individuals developed a proposal to form a SIG. A literature review was performed to identify publications and abstracts with flare definitions applied in RA, JIA, and lupus RCT as well as concerning patient perspectives on disease worsening. A SIG was held at OMERACT 9 with breakout sessions for patients and investigators. The RA flare SIG was attended by about 120 participants, including 11 patients. Patients and investigators held separate breakout sessions to discuss various aspects of disease worsening. The following consensus was obtained at OMERACT 9: a working definition of flare should indicate worsening of disease activity (88%), persistence, and duration as critical elements (77%), and consideration of change or increase in therapy (74%). A working definition of RA flare was developed based on these votes: flare is any worsening of disease activity that would, if persistent, in most cases lead to initiation or change of therapy; and a flare represents a cluster of symptoms of sufficient duration and intensity to require initiation, change, or increase in therapy. Using this working definition, evaluation of candidate domains will be conducted via Delphi exercise and further informed by patient focus groups. Validation of candidate definitions in appropriate RCT will be required.


Magnetic manipulation of actin orientation, polymerization, and gliding on myosin using superparamagnetic iron oxide particles.
The actin cytoskeleton controls cell shape, motility, as well as intracellular molecular trafficking. The ability to remotely manipulate actin is therefore highly desirable as a tool to probe and manipulate biological processes at the molecular level. We demonstrate actin manipulation by labeling actin filaments with superparamagnetic iron oxide particles (IOPs) and applying a uniform magnetic field to affect actin orientation, polymerization and gliding on myosin. We show for the first time magnetic manipulation of magnetizable actin filaments at the molecular level while gliding on a bed of myosin molecules and during polymerization. A model for the magnetic alignment and guiding mechanism is proposed based on the torque from the induced molecular anisotropy due to interactions between neighboring IOPs distributed along magnetically labeled actin molecules.


The nuclear higher-order structure defined by the set of topological relationships between DNA and the nuclear matrix is species-specific in hepatocytes.
During the interphase the nuclear DNA of metazoan cells is organized in supercoiled loops anchored to constituents of a nuclear substructure or compartment known as the nuclear matrix. The stable interactions between DNA and the nuclear matrix (NM) correspond to a set of topological relationships that define a nuclear higher-order structure (NHOS). Current evidence suggests that the NHOS is cell-type-specific. Biophysical evidence and theoretical models suggest that thermodynamic and structural constraints drive the actualization of DNA-NM interactions. However, if the topological relationships between DNA and the NM were the subject of any biological constraint with functional significance then they must be adaptive and thus be positively selected by natural selection and they should be reasonably conserved, at least within closely related species. We carried out a coarse-grained, comparative evaluation of the DNA-NM topological relationships in primary hepatocytes from two closely related mammals: rat and mouse, by determining the relative position to the NM of a limited set of target sequences corresponding to highly-conserved genomic regions that also represent a sample of distinct chromosome territories within the interphase nucleus. Our results indicate that the pattern of topological relationships between DNA and the NM is not conserved between the hepatocytes of the two closely related species, suggesting that the NHOS, like the karyotype, is species-specific.


CYP2D6 is primarily responsible for the metabolism of clomiphene.
Clomiphene is a first line treatment for anovulation, a common cause of infertility. Response to clomiphene is variable and unpredictable. Tamoxifen is structurally related to clomiphene, and also shows considerable variation in response. CYP2D6 and CYP3A4 are major contributors to the metabolism of tamoxifen. The aim of the present work was to define the role of CYP2D6 and CYP3A4 in the in vitro metabolism of enclomiphene, regarded by some as the more active isomer of clomiphene. Enclomiphene (25 microM) was incubated with human liver microsomes (from 4 extensive (EM) and 1 poor metaboliser with respect to CYP2D6) and with microsomes from lymphoblastoid cells expressing CYP2D6. Microsomes from all the EM livers and recombinant CYP2D6 metabolised enclomiphene (the disappearance of drug ranged from 40-60%). No metabolism was detected in microsomes from the PM liver. Quinidine (1 microM) completely inhibited the metabolism of enclomiphene by all the EM livers and by recombinant CYP2D6 (p<0.001, one way ANOVA). Ketoconazole (2 microM) had no significant effect on enclomiphene metabolism in 3 out of the 4 EM livers. The extent of enclomiphene metabolism was correlated with the amount of CYP2D6 present (p<0.001, Pearson correlation test). The findings indicate that CYP2D6 is primarily responsible for the metabolism of enclomiphene.


The Psychology of Existential Risk: Moral Judgments about Human Extinction.
The 21st century will likely see growing risks of human extinction, but currently, relatively small resources are invested in reducing such existential risks. Using three samples (UK general public, US general public, and UK students; total N = 2,507), we study how laypeople reason about human extinction. We find that people think that human extinction needs to be prevented. Strikingly, however, they do not think that an extinction catastrophe would be uniquely bad relative to near-extinction catastrophes, which allow for recovery. More people find extinction uniquely bad when (a) asked to consider the extinction of an animal species rather than humans, (b) asked to consider a case where human extinction is associated with less direct harm, and (c) they are explicitly prompted to consider long-term consequences of the catastrophes. We conclude that an important reason why people do not find extinction uniquely bad is that they focus on the immediate death and suffering that the catastrophes cause for fellow humans, rather than on the long-term consequences. Finally, we find that (d) laypeople-in line with prominent philosophical arguments-think that the quality of the future is relevant: they do find extinction uniquely bad when this means forgoing a utopian future.


Impact of surface water conditions on preservative leaching and aquatic toxicity from treated wood products.
New alternative wood preservatives contain higher levels of copper (Cu) which can promote aquatic toxicity in natural water systems. Earlier work focused on evaluating toxicity using laboratory generated leaching solutions. In this study, the impact on preservative leaching and aquatic toxicity from treated wood products was evaluated using natural surface waters including waters from two rivers, three lakes, two wetlands, and one seawater, in addition to synthetic moderate hard water and deionized water. Blocks of wood treated with Cu based alternatives such as alkaline copper quaternary (ACQ) and copper boron azole (CBA), along with chromated copper arsenate (CCA)-treated wood, were leached under quiescent conditions, and total Cu, labile Cu, and heavy metal toxicity were measured. Results show that ACQ- and CBA-treated wood leach approximately 10 and 20 times more total Cu relative to CCA-treated wood and that the presence of organic and inorganic ligands in natural waters lowered the labile fraction of Cu relative to that from laboratory generated leaching solutions. Aquatic toxicity was found to correlate with the labile Cu fraction, and hence, the aquatic toxicity of the treated wood leachates was lower in natural waters in comparison to laboratory leaching solutions. The results of the present study suggest that studies designed to evaluate the impacts of treated wood should therefore consider the role of complexation in reducing the labile Cu fraction and its potential role in decreasing toxicity.


Serial acquisition of data to predict one-year mortality rate after acute myocardial infarction.
Eight hundred sixty-six patients with acute myocardial infarction (AMI) were enrolled in a prospective study to determine optimal predictors of long-term prognosis. During 12-month (mean) follow-up there were 65 cardiac deaths and 21 nonfatal repeat AMIs. Twenty-nine variables (from the history, physical examination, serum chemistries, ambulatory monitor, radionuclide ventriculogram and exercise test) were arranged into in 5 sequential groups according to the time at which results became available during hospitalization. Multivariate analysis (logistic regression) and receiver-operator characteristic curves were used to assess improvement in prediction of mortality or repeat AMI by addition of each group of variables. The first group of independent predictors included rales, left bundle branch block and symptom status at 1 month before admission. Addition of information from ambulatory monitoring or serum chemistry did not improve prediction. Radionuclide ejection fraction made a statistically significant, independent contribution to mortality prediction. Of the final group the only exercise test variable that contributed independently to prediction was whether the patients took the test. However, receiver-operator characteristic curves showed that improvement in sensitivity and specificity by addition of information from the radionuclide scan and exercise test was clinically insignificant. Our results imply that costly tests after AMI should be reserved for specific indications and not applied universally for prognosis. Although these tests were highly predictive individually, each test generally added little to preexisting prognostic information.


Inspiratory muscle forces and endurance in maximum resistive loading.
The ability of the respiratory muscles to sustain ventilation against increasing inspiratory resistive loads was measured in 10 normal subjects. All subjects reached a maximum rating of perceived respiratory effort and at maximum resistance showed signs of respiratory failure (CO2 retention, O2 desaturation, and rib cage and abdominal paradox). The maximum resistance achieved varied widely (range 73-660 cmH2O X l-1 X s). The increase in O2 uptake (delta Vo2) associated with loading was linearly related to the integrated mouth pressure (IMP): delta Vo2 = 0.028 X IMP + 19 ml/min (r = 0.88, P less than 0.001). Maximum delta Vo2 was 142 ml/min +/- SD 68 ml/min. There were significant (P less than 0.05) relationships between the maximum voluntary inspiratory pressure against an occluded airway (MIP) and both maximum IMP (r = 0.80) and maximum delta Vo2 (r = 0.76). In five subjects, three imposed breathing patterns were used to examine the effect of different patterns of respiratory muscle force deployment. Increasing inspiratory duration (TI) from 1.5 to 3.0 and 6.0 s, at the same frequency of breathing (5.5 breaths/min) reduced peak inspiratory pressure and increased the maximum resistance tolerated (190, 269, and 366 cmH2O X l-1 X s, respectively) and maximum IMP (2043, 2473, and 2913 cmH2O X s X min-1, but the effect on maximum delta Vo2 was less consistent (166, 237, and 180 ml/min). The ventilatory endurance capacity and the maximum O2 uptake of the respiratory muscles are related to the strength of the inspiratory muscles, but are also modified through the pattern of force deployment.


Spontaneous Loss of Virulence in Natural Populations of Listeria monocytogenes.
The pathogenesis of Listeria monocytogenes depends on the ability of this bacterium to escape from the phagosome of the host cells via the action of the pore-forming toxin listeriolysin O (LLO). Expression of the LLO-encoding gene (hly) requires the transcriptional activator PrfA, and both hly and prfA genes are essential for L. monocytogenes virulence. Here, we used the hemolytic activity of LLO as a phenotypic marker to screen for spontaneous virulence-attenuating mutations in L. monocytogenes Sixty nonhemolytic isolates were identified among a collection of 57,820 confirmed L. monocytogenes strains isolated from a variety of sources (0.1%). In most cases (56/60; 93.3%), the nonhemolytic phenotype resulted from nonsense, missense, or frameshift mutations in prfA Five strains carried hly mutations leading to a single amino acid substitution (G299V) or a premature stop codon causing strong virulence attenuation in mice. In one strain, both hly and gshF (encoding a glutathione synthase required for full PrfA activity) were missing due to genomic rearrangements likely caused by a transposable element. The PrfA/LLO loss-of-function (PrfA-/LLO-) mutants belonged to phylogenetically diverse clades of L. monocytogenes, and most were identified among nonclinical strains (57/60). Consistent with the rare occurrence of loss-of-virulence mutations, we show that prfA and hly are under purifying selection. Although occurring at a low frequency, PrfA-/LLO- mutational events in L. monocytogenes lead to niche restriction and open an evolutionary path for obligate saprophytism in this facultative intracellular pathogen.


Predictors of posttraumatic stress disorder, depression, and suicidal ideation among Canadian Forces personnel in a National Canadian Military Health Survey.
Despite efforts to elucidate the relationship between traumatic event exposure and adverse mental health outcomes, our ability to understand why only some trauma-exposed individuals become emotionally affected remains challenged. The aim of the current study is to determine the relations between social support, religiosity, and number of lifetime traumatic events experienced on past-12 month posttraumatic stress disorder (PTSD), depression, and suicidal ideation (SI) in a nationally representative sample of Canadian Forces personnel. The current study used data from the Canadian Community Health Survey Cycle 1.2 - Canadian Forces Supplement. The impact of a number of predictive and mediating factors was assessed using structural equation modeling. Social support and number of lifetime traumatic events experienced were significant predictors of past-year PTSD, depression, and SI; however PTSD did not mediate the relationship between number of traumatic events and SI nor between social support and SI. Conversely, depression mediated the relationship between number of traumatic events and SI. Possible mechanisms for these findings and their implications are discussed.


Sex differences in sub-clinical psychosis--results from a community study over 30 years.
Sex differences in schizophrenia have long been reported. They are found within almost all aspects of the disease, from incidence and prevalence, age of onset, symptomatology, and course to its psycho-social outcome. Many sex-related hypotheses have been developed about the biology, psychology, or sociology of that disease. A further approach to study sex differences would be to examine such differences in sub-clinical psychotic states as well. If factors related to full-blown psychosis were equally meaningful over the entire psychosis continuum, we should expect that "true" sex differences could also be identified in sub-clinical psychosis. Here, we studied sex differences in sub-clinical psychosis within a community cohort in Zurich, Switzerland. This population was followed for over 30 years and included males and females between the ages of 20/21 and 49/50. We applied two different measures of sub-clinical psychosis representing schizotypal signs and schizophrenia nuclear symptoms. Using cross-sectional and longitudinal analyses, we found no significant sex differences in sub-clinical psychosis over time with respect to age of onset, symptomatology, course, or psycho-social outcome. Thus it appears that sex differences in psychosis manifest themselves at the high end of the continuum (full-blown schizophrenia) rather than within the sub-threshold range. Possibly males and females have separate thresholds for certain symptoms because they are differently vulnerable or exposed to various risk factors.


Photoacoustic probes for nondestructive testing and biomedical applications.
Fiber-optic photoacoustic sources for nondestructive testing and biomedical applications are described. The photoacoustic sources consist of a pulsed laser, a fiber-optic cable, and a generation head. The generation head is a miniature hermetically sealed chamber, which can be embedded into solid structures or immersed in liquid media. The face of the chamber acts as a target for laser irradiation. Bulk ultrasonic waves generated inside of the target are transmitted into the medium. The proposed systems offer wide ultrasonic range (0.5-15 MHz), easy control over directivity of the ultrasonic beam, high efficiency of generation, and the ability to operate in a harsh environment. Sources with different radiation patterns with respect to the optical axis of the fiber, such as normal, sideways, as well as focused, have been devised. We present a proof-of-concept experiment using these sources in combination with fiber-optic ultrasonic receivers.


Screening tools for HIV-associated neurocognitive disorders among adults living with HIV in sub-Saharan Africa: A scoping review.
Background: People living with HIV are at risk of developing HIV-associated neurocognitive disorders (HAND) which adversely affects their quality of life. Routine screening of HAND in HIV care is recommended to identify clinically important changes in cognitive functioning and allow for early interventions. However, HAND detection in routine clinical practice has never been reported in sub-Saharan Africa (SSA), partly due to a lack of adequately standardized screening tools. This review was conducted to identify the commonly used screening tools for HAND in SSA and document their psychometric properties and diagnostic accuracy. Methods: We searched Ovid Medline, PsycINFO and Web of Sciences databases for empirical studies published from 1/1/1980 to 31/8/2018 on HAND among adults living with HIV in SSA. Results: We identified 14 eligible studies, of which 9 were from South Africa. The International HIV Dementia Scale (IHDS) was the most frequently reported tool, being used in more than half of the studies. However most studies only reported the diagnostic accuracy of this and other tools, with specificity ranging from 37% to 81% and sensitivity ranging from 45% to 100%. Appropriate data on construct validity and reliability of tools was rarely documented. Although most tools performed well in screening for severe forms of HAND, they lacked sensitivity and specificity for mild forms of HAND. NeuroScreen, one of the newer tools, yielded good diagnostic accuracy in its initial evaluation in South Africa (81% to 93% sensitivity and 71% to 81% specificity). Conclusions: This review identified a lack of adequately standardized and contextually relevant HAND screening tools in SSA. Most screening tools for HAND used in SSA possess inadequate psychometric properties and diagnostic accuracy. There is a need for further validation of existing tools and development of new HAND screening tools in SSA.


Interleukin-2 downregulates hepatitis B virus gene expression in transgenic mice by a posttranscriptional mechanism.
We have recently demonstrated that tumor necrosis factor alpha (TNF-alpha) and interleukin-2 (IL-2) downregulate the hepatic steady-state content of hepatitis B virus (HBV) mRNA in vivo in HBV-transgenic mice and that the IL-2 effect is mediated by TNF-alpha. In the current study, we demonstrate that IL-2-induced downregulation of hepatic HBV 2.1-kb mRNA is not due to changes in the transcription rate or the intranuclear maturation or export of this transcript but that it is selectively and profoundly depleted from the cytoplasm of the liver cells in vivo following IL-2 administration. Collectively, these results suggest that IL-2 alters the steady-state content of hepatic HBV mRNA by a posttranscriptional mechanism in vivo, that this effect is mediated by TNF-alpha, and that it probably reflects increased cytoplasmic degradation of the viral transcript.


Biomechanical evaluation of a novel pedicle screw-based interspinous spacer: A finite element analysis.
Interspinous spacers have been designed to provide a minimally invasive surgical technique for patients with lumbar spinal stenosis or foraminal stenosis. A novel pedicle screw-based interspinous spacer has been developed in this study, and the aim of this finite element experiment was to investigate the biomechanical differences between the pedicle screw-based interspinous spacer (M-rod system) and the typical interspinous spacer (Coflex-F™). A validated finite element model of an intact lumbar spine was used to analyze the insertions of the Coflex-F™, titanium alloy M-rod (M-Ti), and polyetheretherketone M-rod (M-PEEK), independently. The range of motion (ROM) between each vertebrae, stiffness of the implanted level, the peak stress at the intervertebral discs, and the contact forces on spinous process were analyzed. Of all three devices, the Coflex-F™ provided the largest restrictions in extension, flexion and lateral bending. For intervertebral disc, the peak stress at the implanted segment decreased by 81% in the Coflex-F™, 60.2% in the M-Ti and 46.7% in the M-PEEK when compared to the intact model. For the adjacent segments, while the Coflex-F™ caused considerable increases in the ROM and disc stress, the M-PEEK only had small changes.


Aberrant hormone production from ovarian neoplasms: strategies for diagnosis and therapy.
Syndromes involving peptide or nonsex steroid hormone secretion due to aberrantly located tumors are rare. We report a collected series of 16 patients with ectopic hormone production from ovarian neoplasms, including 3 patients recently encountered at our institution as well as 13 additional cases identified in the recent literature. These tumors included 2 insulin-producing ovarian carcinoids, 1 ACTH-producing pituitary adenoma within a benign ovarian cystic teratoma, 2 cortisol-producing ovarian neoplasms, 8 gastrin-producing ovarian cystadenomata or cystadenocarcinomata, and 3 thyroxine-producing ovarian strumal carcinoids. All patients presented with syndromes of hormone excess. Only 62% of all tumors were localized preoperatively. Following ovarian resection, 87% of patients remained disease-free with a median follow-up period of 1.5 years. In addition to ovariectomy, 8 additional unnecessary ablative procedures were performed in 7 patients. These included distal pancreatectomy, pancreaticoduodenectomy, adrenalectomy, total gastrectomy, selective vagotomy, and subtotal thyroidectomy. Failure to localize the ovarian neoplasm preoperatively was associated with a significantly higher risk of subsequent unnecessary ablative procedures. Because of the potential for the ovary to act as a source of aberrant hormone secretion, we recommend complete preoperative evaluation of the pelvis in female patients presenting with nonlocalizable endocrine tumors.


Genetic counselors: translating genomic science into clinical practice.
In a time of emerging genetic tests and technologies, genetic counselors are faced with the challenge of translating complex genomic data into information that will aid their client's ability to learn about, understand, make, and cope with decisions relating to genetic diagnoses. The first of two companion articles in this issue examines the role of the genetic counselor, particularly in counseling individuals at risk for or diagnosed with breast cancer, in an era of high-tech health care and gene patents.


Robustness analysis of biochemical network models.
Biological systems that have been experimentally verified to be robust to significant changes in their environments require mathematical models that are themselves robust. In this context, a necessary condition for model robustness is that the model dynamics should not be sensitive to small variations in the model's parameters. Robustness analysis problems of this type have been extensively studied in the field of robust control theory and have been found to be very difficult to solve in general. The authors describe how some tools from robust control theory and nonlinear optimisation can be used to analyse the robustness of a recently proposed model of the molecular network underlying adenosine 3',5'-cyclic monophosphate (cAMP) oscillations observed in fields of chemotactic Dictyostelium cells. The network model, which consists of a system of seven coupled nonlinear differential equations, accurately reproduces the spontaneous oscillations in cAMP observed during the early development of D. discoideum. The analysis by the authors reveals, however, that very small variations in the model parameters can effectively destroy the required oscillatory dynamics. A biological interpretation of the analysis results is that correct functioning of a particular positive feedback loop in the proposed model is crucial to maintaining the required oscillatory dynamics.


Male and non-English-speaking patients with fracture have poorer knowledge of osteoporosis.
Prior fracture is a strong independent risk factor for subsequent fracture. To date, few studies have examined the level of osteoporosis knowledge specifically in the population of patients who have sustained a fracture. This study was designed to assess the knowledge of osteoporosis among patients who sustained a fracture and who were forty years of age or older, as well as to identify what social factors and health and fracture characteristics determine the level of osteoporosis knowledge in this population. Patients who had sustained a fracture and were attending fracture clinics at two Toronto hospitals were identified and invited to fill out a questionnaire during their visit. This questionnaire included questions that could be answered by checking "true," "false," or "don't know" and that were designed to assess the patient's knowledge of osteoporosis. The questionnaire also included questions about the respondent's background. Of 259 patients identified as eligible for the study, 204 (78.8%) agreed to participate. The mean number of correct responses was 16.5 (55%) out of thirty responses. Variables significantly associated with greater numbers of correct responses were female sex, English as a first language, being currently employed, exercising regularly, and having received information from a health-care provider or from a newspaper or magazine. The level of osteoporosis knowledge was fairly low among the surveyed patients, indicating that more education is needed. This study also highlighted certain characteristics (i.e., male sex, English as a second language, being unemployed, and not exercising) that are associated with a lower level of knowledge. Our results can help target certain groups for osteoporosis educational initiatives, especially ethnic groups whose first language is not English, so as to appropriately reduce the risk of future fractures in this high-risk population.


Prevalence and prognostic impact of kidney disease on heart failure patients.
The aim was to determine the prevalence of different degrees of kidney dysfunction and to examine their association with short-term and long-term outcomes in a large unselected contemporary heart failure population and some of its subgroups. We examined to what extent the different cardiac conditions and their severity contribute to the prognostic value of kidney dysfunction in heart failure. We studied 47 716 patients in the Swedish Heart Failure Registry. Patients were divided into five renal function strata based on estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration equation. The adjusted association between kidney function and outcome was examined by Cox regression. 51% of the patients had eGFR <60 mL/min/1.73 m(2) and 11% had eGFR <30. There was increasing mortality with decreasing kidney function regardless of age, presence of diabetes, New York Heart Association NYHA class, duration of heart failure and haemoglobin levels. The risk HR (95% CI) persisted after adjusting for differences in baseline characteristics, severity of heart disease, and medical treatment: eGFR 60-89: 0.86 (0.79 to 0.95); eGFR 30-59: 1.13 (1.03 to 1.24); eGFR 15-29: 1.85 (1.67 to 2.07); and eGFR <15: 2.96 ([2.53 to -3.47)], compared with eGFR ≥90. Kidney dysfunction is common and strongly associated with short-term and long-term outcomes in patients with heart failure. This strong association was evident in all age groups, regardless of NYHA class, duration of heart failure, haemoglobin level, and presence/absence of diabetes mellitus. After adjusting for differences in baseline data, aetiology and severity of heart disease and treatment, the strong association remained.


An indirect comparison of dabigatran, rivaroxaban and apixaban for atrial fibrillation.
New oral anticoagulant drugs are emerging as alternatives to warfarin for the prevention of stroke in patients with non-valvular atrial fibrillation. Two agents are direct factor Xa inhibitors (rivaroxaban and apixaban), and the third is a direct thrombin inhibitor (dabigatran). They have been separately compared to warfarin in large randomised trials. Our objective was to indirectly compare the three agents to each other for major efficacy and safety outcomes. Studies were assessed for comparability and the odds ratios of selected outcomes for each anticoagulant versus one another were estimated indirectly. The three cohorts differed significantly in terms of CHADS(2) score and the number of individuals with a past history of stroke, transient ischemic attack or systemic embolism. The estimated odds ratio of stroke or systemic embolism was 1.35 for rivaroxaban vs dabigatran 150 mg (p=0.04), 0.97 for rivaroxaban versus dabigatran 110 mg (p=0.81), 1.22 for apixaban versus dabigatran 150 mg (p=0.18), 0.88 for apixaban versus dabigatran 110 mg (p=0.34) and 0.90 for apixaban versus rivaroxaban (p=0.43). The estimated odds ratio of major bleeding was 1.10 for rivaroxaban versus dabigatran 150 mg (p=0.36), 1.28 for rivaroxaban versus dabigatran 110 mg (p=0.02), 0.74 for apixaban versus dabigatran 150 mg (p=0.004), 0.87 for apixaban versus dabigatran 110 mg (p=0.17) and 0.68 for apixaban versus rivaroxaban (p<0.001). In conclusion, the available data indicate no significant difference in efficacy between dabigatran 150 mg and apixaban for the prevention of stroke or systemic embolism in patients with non-valvular atrial fibrillation. It appears however that apixaban is associated with less major bleeding than dabigatran 150 mg or rivaroxaban and that rivaroxaban is less effective than dabigatran 150 mg in preventing stroke or systemic embolism. Such an indirect comparison should be used only to generate hypotheses which need to be tested in a dedicated randomised trial comparing the three drugs directly.


Three-dimensional acousto-optic imaging in biological tissues with parallel signal processing.
An original acousto-optic method is described that allows one to reveal optical contrasts through biological tissues that are several centimeters thick with a millimeter-sized resolution. This technique is based on the interaction of scattered laser light with a focused ultrasonic field. The modulation depth of the optical speckle is related to local optical properties of the sample. Our parallel-processing approach to the demodulation of the speckle improves the observed degree of modulation by 2 orders of magnitude and quickly yields a good statistical value. Optically absorbing objects were imaged inside 35-mm-thick biological tissues.


THE EFFECT OF HEMOLYTIC SUBSTANCES ON WHITE CELL RESPIRATION.
Substances such as saponin, the bile salts, etc., which produce lysis of red cells also produce cytolysis of white cells from rabbit peritoneal exudates, the arbitrary criterion of their cytolytic effect being their ability to depress the O(2) consumption of the leucocytes. The amount of cytolysis increases regularly as the amount of the added lysin is increased, and sufficiently large quantities of saponin, sodium taurocholate, sodium glycocholate, or sodium oleate are capable of virtually abolishing the O(2) consumption altogether. At the same time, it can be shown that a lysin such as saponin is used up in combining with the white cells in much the same way as it is used up in combining with red cells, and the reduction in oxygen consumption appears to be roughly proportional to the amount so combined. The action of these lytic substances on white cells, in fact, is very similar to their action on red cells, due allowance being made for the fact that the cytolysis of the white cell is probably not an all-or-none process like hemolysis. White cell respiration is also depressed in hypotonic solutions, the respiration being virtually linear with the tonicity.


Performance-limiting nanoscale trap clusters at grain junctions in halide perovskites.
Halide perovskite materials have promising performance characteristics for low-cost optoelectronic applications. Photovoltaic devices fabricated from perovskite absorbers have reached power conversion efficiencies above 25 per cent in single-junction devices and 28 per cent in tandem devices1,2. This strong performance (albeit below the practical limits of about 30 per cent and 35 per cent, respectively3) is surprising in thin films processed from solution at low-temperature, a method that generally produces abundant crystalline defects4. Although point defects often induce only shallow electronic states in the perovskite bandgap that do not affect performance5, perovskite devices still have many states deep within the bandgap that trap charge carriers and cause them to recombine non-radiatively. These deep trap states thus induce local variations in photoluminescence and limit the device performance6. The origin and distribution of these trap states are unknown, but they have been associated with light-induced halide segregation in mixed-halide perovskite compositions7 and with local strain8, both of which make devices less stable9. Here we use photoemission electron microscopy to image the trap distribution in state-of-the-art halide perovskite films. Instead of a relatively uniform distribution within regions of poor photoluminescence efficiency, we observe discrete, nanoscale trap clusters. By correlating microscopy measurements with scanning electron analytical techniques, we find that these trap clusters appear at the interfaces between crystallographically and compositionally distinct entities. Finally, by generating time-resolved photoemission sequences of the photo-excited carrier trapping process10,11, we reveal a hole-trapping character with the kinetics limited by diffusion of holes to the local trap clusters. Our approach shows that managing structure and composition on the nanoscale will be essential for optimal performance of halide perovskite devices.


Pre-exposure prophylaxis for men and transgender women who have sex with men in Brazil: opportunities and challenges.
The World Health Organization recently released guidelines on the use of pre-exposure prophylaxis (PrEP) for prevention of HIV infection among men and transgender women (TGW) who have sex with men based on results of randomized clinical trials. The aim of this commentary is to discuss the opportunities and challenges of incorporating PrEP into the Brazilian continuum of HIV care and prevention for men who have sex with men (MSM) and TGW. Key aspects of the AIDS epidemic among MSM and TGW in Brazil and the comprehensive Brazilian response to the epidemic are presented. The universal access to health care provided through the Brazilian Unified Health System (SUS) and the range of prevention and care services already available countrywide to HIV-positive individuals and at-risk MSM and TGW are identified as the main facilitators for the implementation of PrEP. Limited PrEP awareness among MSM, TGW and health care providers, low HIV testing frequency and low HIV risk perception among MSM and TGW represent the core challenges to be addressed. Data generated by demonstration projects in Brazil will provide an important contribution to PrEP rollout in Brazil. The implementation of PrEP in Brazil is feasible. A synergistic rollout of treatment as prevention and PrEP will maximize public health and individual benefits of the country's comprehensive response to the AIDS epidemic.


Speckle dynamics resulting from multiple interfering beams.
The space-time intensity covariance function for illuminating an object giving rise to fully developed speckle is considered in the case where the object is illuminated with two spatially separated beams, or with a multitude of equidistant but spatially separated spots. Specifically, and to the best of our knowledge for the first time, we obtain the result that the larger speckles will be covered by a fine structure that, in general, translates at a different velocity from that of the larger speckles. In particular, closed-form analytical expressions are found for the space- and time-lagged covariance of irradiance as well as the corresponding power spectrum for each of the two spatially separated, N equidistant separated illuminating beams. The present analysis is valid not only for free-space propagation but also for an arbitrary real ABCD optical system. Finally, the corresponding statistical signal properties, including the power spectrum, are derived and discussed for the (practical) case where the comprehensive speckle field is spatially filtered by a gratinglike structure.


Benzyl isothiocyanate is the chief or sole anthelmintic in papaya seed extracts.
Papaya (Carica papaya) seeds were extracted in an aqueous buffer or in organic solvents, fractionated by chromatography on silica and aliquots tested for anthelmintic activity by viability assays using Caenorhabditis elegans. For all preparations and fractions tested, anthelmintic activity and benzyl isothiocyanate content correlated positively. Aqueous extracts prepared from heat-treated seeds had no anthelmintic activity or benzyl isothiocyanate content although both appeared when these extracts were incubated with a myrosinase-containing fraction prepared from papaya seeds. A 10 h incubation of crude seed extracts at room temperature led to a decrease in anthelmintic activity and fractionated samples showed a lower benzyl isothiocyanate content relative to non-incubated controls. Benzyl thiocyanate, benzyl cyanide, and benzonitrile were not detected in any preparations and cyanogenic glucosides. which were present, could not account for the anthelmintic activity detected. Thus, our results are best explained if benzyl isothiocyanate is the predominant or sole anthelmintic agent in papaya seed extracts regardless of how seeds are extracted.


Enhancement of contrast regions in suboptimal ultrasound images with application to echocardiography.
In this paper we propose a novel feature-based contrast enhancement approach to enhance the quality of noisy ultrasound (US) images. Our approach uses a phase-based feature detection algorithm, followed by sparse surface interpolation and subsequent nonlinear postprocessing. We first exploited the intensity-invariant property of phase-based acoustic feature detection to select a set of relevant image features in the data. Then, an approximation to the low-frequency components of the sparse set of selected features was obtained using a fast surface interpolation algorithm. Finally, a nonlinear postprocessing step was applied. Results of applying the method to echocardiographic sequences (2-D + T) are presented. The results demonstrate that the method can successfully enhance the intensity of the interesting features in the image. Better balanced contrasted images are obtained, which is important and useful both for manual processing and assessment by a clinician, and for computer analysis of the sequence. An evaluation protocol is proposed in the case of echocardiographic data and quantitative results are presented. We show that the correction is consistent over time and does not introduce any temporal artefacts.


Bilateral fractures of transverse processus: a diagnostic sign of overrun?
Injuries caused by traffic accidents can be complex and extensive. Due to the highly dynamic course of actions, reconstructive questions may be challenging to investigators. Differentiation of a single collision from an overrun is a central question. We hypothesized that the existence of spine fractures such as spinous and transverse processus fractures may be helpful to distinguish both. The postmortem CT-data of pedestrian fatalities were analyzed in a retrospective manner. A group finally assessed as being overrun (n=13; 7 m, 6 f, 18-86 y, mean 65 y) and a control group being hit but not overrun (n=11; 7 m, 4 f, 31-89 y, mean 61 y) were compared. Secondarily, the CT results were compared to the localization of fractures detected in routine autopsy. Cases in the overrun group showed 1-31 fractures of processus (mean 14.6) and 9 cases presented with bilateral fractures of partly opposite transverse processus. In the control group there were 6 cases without any fractures and 5 cases showed 1-9 injuries (mean 1.7). There were no bilateral fractures of transverse processus in the control group. Autopsy only detected fractures of spinous processus in 4 cases from the overrun group. Bilateral fractures of transverse processus are a possible sign for an overrun. Unilateral fractures of the transverse processus are not specific. Post-mortem CT is more sensitive for the evaluation of vertebral processus than conventional autopsy.


Expression profiling of constitutive mast cells reveals a unique identity within the immune system.
Mast cells are evolutionarily ancient sentinel cells. Like basophils, mast cells express the high-affinity receptor for immunoglobulin E (IgE) and have been linked to host defense and diverse immune-system-mediated diseases. To better characterize the function of these cells, we assessed the transcriptional profiles of mast cells isolated from peripheral connective tissues and basophils isolated from spleen and blood. We found that mast cells were transcriptionally distinct, clustering independently from all other profiled cells, and that mast cells demonstrated considerably greater heterogeneity across tissues than previously appreciated. We observed minimal homology between mast cells and basophils, which shared more overlap with other circulating granulocytes than with mast cells. The derivation of mast-cell and basophil transcriptional signatures underscores their differential capacities to detect environmental signals and influence the inflammatory milieu.


Antibacterial and photochemical properties of cellulose nanofiber-titania nanocomposites loaded with two different types of antibiotic medicines.
Nanocomposite dermal drug delivery systems based on cellulose nanofibers with grafted titania nanoparticles loaded by two antibiotic medicines from different classes, i.e. tetracycline (TC) and phosphomycin (Phos), were successfully produced by a "green chemistry" approach in aqueous media. The influence of a different surface binding mechanism between the drug molecule and modified cellulose nanofibers on the release of the drug and, as a result, on antimicrobial properties against common pathogens Gram-positive, Staphylococcus aureus and Gram-negative Escherichia coli was investigated. The disk diffusion method and broth culture tests using varying concentrations of drugs loaded to nanocomposites were carried out to investigate the antibacterial effects. The influence of UV irradiation on the stability of the obtained nanocomposites and their antibacterial properties after irradiation were also investigated, showing enhanced stability especially for the TC loaded materials. These findings suggest that the obtained nanocomposites are promising materials for the development of potentially useful antimicrobial patches.


A Stakeholder Analysis of Schistosomiasis Diagnostic Landscape in South-West Nigeria: Insights for Diagnostics Co-creation.
Background: Schistosomiasis, one of the neglected tropical diseases, is a water-based parasitic disease of public health importance. Currently, tests for Schistosoma haematobium infection either demonstrate poor specificity, are expensive or too laborious for use in endemic countries, creating a need for more sensitive, cheaper, and easy to use devices for the diagnosis of schistosomiasis. To ensure engagement during the process of device development; and effective acceptance and use after the introduction of diagnostics devices for S. haematobium, there is a need to involve stakeholders with varying power, interest, and stakes in device co-creation, as well as those relevant for later use situation in the diagnostic landscape. The main goal of this study is to identify and analyze relevant stakeholders for co-creation using a power-interest matrix. Materials and Methods: The study was based on an action research methodology using a case study approach. A contextual inquiry approach consisting of 2 stages: stakeholder identification and interview; and stakeholder analysis was used. The field part of the study was carried out in Oyo State, Nigeria using a multistage cluster purposive sampling technique based on the category of stakeholders to be interviewed predicated on the organizational structure within the state and communities. A mix of qualitative research techniques was used. Identified themes related to power and interest were mapped and analyzed. Results: We identified 17 characteristics of stakeholders across 7 categories of stakeholders important for schistosomiasis diagnostics. Most of the stakeholders were important for both the co-creation and adoption phase of the device development for diagnostics. However, not all stakeholders were relevant to co-creation. Key Stakeholders relevant for diagnostics co-creation demonstrated significant social power, organization power, and legitimate power bases. Most of the stakeholders showed significant interest in the device to be created. Discussion: The power and interest of these stakeholders reveal some insight into how each stakeholder may be engaged for both co-creation and device usage. The involvement of relevant actors who will also be important for co-creation and implementation, will simplify the engagement process for the critical stakeholders, increase the ability to manage the process, and increase diagnostic device acceptability.


Elevated protein kinase C betaII is an early promotive event in colon carcinogenesis.
Protein kinase C (PKC) has been implicated in colon carcinogenesis in humans and in rodent models. However, little is known about the specific role of individual PKC isozymes in this process. We recently demonstrated that elevated expression of PKC betaII in the colonic epithelium induces hyperproliferation in vivo (N. R. Murray et al., J. Cell Biol., 145: 699-711, 1999). Because hyperproliferation is a major risk factor for colon cancer, we assessed whether specific alterations in PKC betaII expression occur during azoxymethane-induced colon carcinogenesis in mice. An increase in PKC betaII expression was observed in preneoplastic lesions (aberrant crypt foci, 3.7-fold) compared with saline-treated animals, and in colon tumors (7.8-fold; P = 0.011) compared with uninvolved colonic epithelium. In contrast, PKC alpha and PKC betaI (a splicing variant of PKC betaII) expression was slightly decreased in aberrant crypt foci and dramatically reduced in colon tumors. Quantitative reverse transcription-PCR analysis revealed that PKC mRNA levels do not directly correlate with PKC protein levels, indicating that PKC isozyme expression is likely regulated at the posttranscriptional/translational level. Finally, transgenic mice expressing elevated PKC betaII in the colonic epithelium exhibit a trend toward increased colon tumor formation after exposure to azoxymethane. Taken together, our results demonstrate that elevated expression of PKC betaII is an important early, promotive event that plays a role in colon cancer development.


Serenoa repens induces growth arrest and apoptosis of human multiple myeloma cells via inactivation of STAT 3 signaling.
Serenoa repens, a palm species native to the Southeastern United States, is one of the widely used phytotherapeutic agents in benign prostatic hyperplasia. In this study, we found for the first time that Serenoa repens induced growth arrest of a variety of human leukemia cells including U266 and RPMI 8226 multiple myeloma cells as measured by mitochondrial-dependent conversion of the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. TUNEL assays showed that Serenoa repens induced apoptosis of U266 cells in a time- and dose-dependent manner. Serenoa repens also increased the expression of cleaved-PARP or p27 protein in different human leukemia cell lines. In addition, we found that Serenoa repens down-regulated basal level of phosphorylated form of signal transducer and activator of transcription 3 (STAT 3) and Interleukin-6 induced level of phosphorylated form of STAT 3 and extracellular signal-related kinase (ERK) were also reduced after Serenoa repens treatment in U266 cells. Furthermore, we found that inhibition of STAT 3 signaling by Serenoa repens or Janus family of tyrosine kinase (JAK) inhibitor of AG490 enhanced the ability of docetaxel to inhibit the growth of U266 and RPMI 8226 cells, as measured by trypan blue exclusion test. These results indicate that Serenoa repens might be useful for the treatment of individuals with multiple myeloma.


Serological cross-reaction between O-antigens of Shigella dysenteriae type 4 and an environmental Escherichia albertii isolate.
An environmental freshwater bacterial isolate, DM104, appearing as Shigella-like colonies on selective agar plates was found to show strong and specific serological cross-reactivity with Shigella dysenteriae type 4. Biochemical identification according to the analytical profile index, molecular serotyping by restriction of the amplified O-antigen gene cluster (rfb-RFLP), together with phylogenetic analysis of the 16S rRNA gene and multi-locus sequence analysis, identified the isolate as Escherichia albertii. rfb-RFLP of DM104, revealed a profile different from that of S. dysenteriae type 4. However, western blot analysis of extracted lipopolysaccharides demonstrated strong cross-reactivity with S. dysenteriae type 4 using specific monovalent antisera and a lipopolysaccharide gel banding profile similar to that of S. dysenteriae type 4. The observed O-antigen cross-reaction between an E. albertii isolate and S. dysenteriae extends our knowledge of the extent of O-antigen cross-reaction within the Escherichia/Shigella group of organisms, and offers the possibility of using DM104 and similar cross-reacting strains as shigellosis vaccine candidates.


Formulation and Optimization of Candesartan Cilexetil Nano Lipid Carrier: In Vitro and In Vivo Evaluation.
The objective of this study was to formulate and optimize Candesartan Cilexetil (CC) loaded nanostructured lipid carriers (NLCs) for enhanced oral bioavailability. Glycerol monostearate (GMS), Oleic acid, Tween 80 and Span 40 were selected as a solid lipid, liquid lipid, surfactant and co- surfactant, respectively. The CC-NLCs were prepared by hot emulsion probe sonication technique and optimized using experimental design approach. The formulated CC-NLCs were evaluated for various physicochemical parameters and further optimized formulation (CC-NLC-Opt) was assessed for in vivo pharmacokinetic and pharmacodynamic activity. The optimized formulation (CC-NLC-Opt) showed particle size (183.5±5.89nm), PDI (0.228±0.13), zeta potential (-28.2±0.99mV), and entrapment efficiency (88.9±3.69%). The comparative in vitro release study revealed that CC-NLC-Opt showed significantly better (p<0.05) release and enhanced permeation as compared to CC-suspension. The in vivo pharmacokinetic study gave many folds increase in oral bioavailability than CC suspension, which was further confirmed by antihypertensive activity in a murine model. Thus, the results of ex vivo permeation, pharmacokinetic study and pharmacodynamics study suggest the potential of CC-NLCs for improved oral delivery.


Thrombosis in a cavernous left-sided inferior vena cava. An unusual abdominal mass.
A 19-year-old man had an abdominal mass and swelling of the left thigh. The presumptive diagnosis was lymphoma. On exploration the mass proved to be a thrombosed multiloculated "cavernous transformation" of a venous structure, presumably the inferior vena cava, which on postoperative cavogram was shown to be otherwise absent. The venous system of the left lower extremity showed phlebographic evidence of old thrombosis, but that of the right lower extremity was normal. The patient did well without further treatment, despite some residual swelling of the left thigh. To our knowledge, this precise combination of inferior vena cava anomalies has not been encountered before; certainly not presenting as a mass.


Corneal transduction by intra-stromal injection of AAV vectors in vivo in the mouse and ex vivo in human explants.
The cornea is a transparent, avascular tissue that acts as the major refractive surface of the eye. Corneal transparency, assured by the inner stroma, is vital for this role. Disruption in stromal transparency can occur in some inherited or acquired diseases. As a consequence, light entering the eye is blocked or distorted, leading to decreased visual acuity. Possible treatment for restoring transparency could be via viral-based gene therapy. The stroma is particularly amenable to this strategy due to its immunoprivileged nature and low turnover rate. We assayed the potential of AAV vectors to transduce keratocytes following intra-stromal injection in vivo in the mouse cornea and ex vivo in human explants. In murine and human corneas, we transduced the entire stroma using a single injection, preferentially targeted keratocytes and achieved long-term gene transfer (up to 17 months in vivo in mice). Of the serotypes tested, AAV2/8 was the most promising for gene transfer in both mouse and man. Furthermore, transgene expression could be transiently increased following aggression to the cornea.


Rhythmicity facilitates pitch discrimination: Differential roles of low and high frequency neural oscillations.
Previous studies indicate that temporal predictability can enhance timing and intensity perception, but it is not known whether it also enhances pitch perception, despite pitch being a fundamental perceptual attribute of sound. Here we investigate this in the context of rhythmic regularity, a form of predictable temporal structure common in sound streams, including music and speech. It is known that neural oscillations in low (delta: 1-3 Hz) and high (beta: 15-25 Hz) frequency bands entrain to rhythms in phase and power, respectively, but it is not clear why both low and high frequency bands entrain to external rhythms, and whether they and their coupling serve different perceptual functions. Participants discriminated near-threshold pitch deviations (targets) embedded in either rhythmic (regular/isochronous) or arrhythmic (irregular/non-isochronous) tone sequences. Psychophysically, we found superior pitch discrimination performance for target tones in rhythmic compared to arrhythmic sequences. Electroencephalography recordings from auditory cortex showed that delta phase, beta power modulation, and delta-beta coupling were all modulated by rhythmic regularity. Importantly, trial-by-trial neural-behavioural correlational analyses showed that, prior to a target, the depth of U-shaped beta power modulation predicted pitch discrimination sensitivity whereas cross-frequency coupling strength predicted reaction time. These novel findings suggest that delta phase might reflect rhythmic temporal expectation, beta power temporal attention, and delta-beta coupling auditory-motor communication. Together, low and high frequency auditory neural oscillations reflect different perceptual functions that work in concert for tracking rhythmic regularity and proactively facilitate pitch perception.


Electromagnetic energy transport in finite photonic structures.
We have derived, for oblique propagation, an equation relating the averaged energy flux density to energy fluxes arising in the process of scattering by a lossless finite photonic structure. The latter fluxes include those associated with the dispersion relation of the structure, reflection, and interference between the incident and reflected waves. We have also derived an explicit relation between the energy flux density and the group velocity, which provides a simple and systematical procedure for studying theoretically and experimentally the properties of the energy transport through a wide variety of finite photonic structures. Such a relation may be regarded as a generalization of the corresponding one for infinite periodic systems to finite photonic structures. A finite, N-period, photonic crystal was used to illustrate the usefulness of our results.


Brokering health policy: coalitions, parties, and interest group influence.
Assuming a position as broker between disconnected interests is one way for an interest group to influence the making of federal health policy. This study demonstrates how groups use their connections with political parties and lobbying coalitions to augment their brokerage positions and enhance their influence over policy making. Evidence is drawn from statistical analysis of 263 interviews with health policy elites and a qualitative case study of the debate over the Medicare Prescription Drug, Improvement, and Modernization Act of 2003. The results explain, in part, how interest groups play their brokerage roles as dispersed actors in a decentralized system, rather than as central mediators that intervene in a wide range of policy disputes.


HIV/AIDS stigma and utilization of voluntary counselling and testing in Nigeria.
Despite the recognition of stigma as a hindrance to public health treatment and prevention there are gaps in evidence on the relationship between HIV stigma and VCT services utilization in Nigeria. The purpose of this study was to examine a community's perceptions, feelings and attitudes towards people living with HIV/AIDS and how this is associated with access to utilization of voluntary counselling and treatment in Nigeria. A cross-sectional random study of Nigerians, using a mixed-method approach was carried out in two distinct ethnic areas of the country. Both quantitative and qualitative methods (mixed-methods) were used to collect data in Osun State (Yoruba ethnic group) in the South-West and Imo State (Igbo ethnic group) in the South East. Multivariate logistic regression was the model used to examine the association of interest. It is shown that Nigerian public attitudes to HIV/AIDS and those infected with the disease are negative. The markers for stigma on the overall stigma index are significant predictors of utilization of voluntary counselling and testing. As the sum of negative feelings increases, there is less likelihood to using voluntary counselling and testing (VCT) and vice versa. Current national efforts at addressing the AIDS pandemic can only be successful when the issue of AIDS is de-stigmatized and is made a critical part of those efforts. One way to do this is through well-designed messages that should be posted in the media, community halls, health centers and other public places aimed at humanizing the disease and those affected and infected by it.