Yield-related salinity tolerance traits identified in a nested association mapping (NAM) population of wild barley.
Producing sufficient food for nine billion people by 2050 will be constrained by soil salinity, especially in irrigated systems. To improve crop yield, greater understanding of the genetic control of traits contributing to salinity tolerance in the field is needed. Here, we exploit natural variation in exotic germplasm by taking a genome-wide association approach to a new nested association mapping population of barley called HEB-25. The large population (1,336 genotypes) allowed cross-validation of loci, which, along with two years of phenotypic data collected from plants irrigated with fresh and saline water, improved statistical power. We dissect the genetic architecture of flowering time under high salinity and we present genes putatively affecting this trait and salinity tolerance. In addition, we identify a locus on chromosome 2H where, under saline conditions, lines homozygous for the wild allele yielded 30% more than did lines homozygous for the Barke allele. Introgressing this wild allele into elite cultivars could markedly improve yield under saline conditions.


Trends in mental health of an adolescent medicine clinic patient population.
The correlation between exposure to forms of violence and development of mental disorders in victims is well established. The purpose of this paper was to identify mental health problems in an adolescent medicine clinic population in Lexington, KY and to investigate potential correlation of mental disorders with psychosocial factors. Data were gathered from the charts of 169 adolescent clinic patients (age 10-22) seen in the clinic for mental health care and analyzed using Excel. Of the patient population, 68% were urban, whereas 32% were rural. In terms of gender, 40% of the patients were male and 60% were female, 80% were white, 13% black, and 7% had other racial background(s). The most prevalent mental disorders in this group were depression 32.12%, 13% with generalized anxiety disorder, 8.2% with an attention deficit disorder (including ADHD), and 5.76% with an adjustment disorder. The abovementioned demographic trends showed that depression continues to be the most common mental health problem in this population regardless of gender, ethnic origin, or economic status. This finding highlights the need for availability of mental health support to this patient population. Further work is needed to spotlight the most significant psychosocial factors and root causes of mental health conditions in this age group.


A SMYD3 Small-Molecule Inhibitor Impairing Cancer Cell Growth.
SMYD3 is a histone lysine methyltransferase that plays an important role in transcriptional activation as a member of an RNA polymerase complex, and its oncogenic role has been described in different cancer types. We studied the expression and activity of SMYD3 in a preclinical model of colorectal cancer (CRC) and found that it is strongly upregulated throughout tumorigenesis both at the mRNA and protein level. Our results also showed that RNAi-mediated SMYD3 ablation impairs CRC cell proliferation indicating that SMYD3 is required for proper cancer cell growth. These data, together with the importance of lysine methyltransferases as a target for drug discovery, prompted us to carry out a virtual screening to identify new SMYD3 inhibitors by testing several candidate small molecules. Here we report that one of these compounds (BCI-121) induces a significant reduction in SMYD3 activity both in vitro and in CRC cells, as suggested by the analysis of global H3K4me2/3 and H4K5me levels. Of note, the extent of cell growth inhibition by BCI-121 was similar to that observed upon SMYD3 genetic ablation. Most of the results described above were obtained in CRC; however, when we extended our observations to tumor cell lines of different origin, we found that SMYD3 inhibitors are also effective in other cancer types, such as lung, pancreatic, prostate, and ovarian. These results represent the proof of principle that SMYD3 is a druggable target and suggest that new compounds capable of inhibiting its activity may prove useful as novel therapeutic agents in cancer treatment.


Current challenges in health information technology-related patient safety.
We identify and describe nine key, short-term, challenges to help healthcare organizations, health information technology developers, researchers, policymakers, and funders focus their efforts on health information technology-related patient safety. Categorized according to the stage of the health information technology lifecycle where they appear, these challenges relate to (1) developing models, methods, and tools to enable risk assessment; (2) developing standard user interface design features and functions; (3) ensuring the safety of software in an interfaced, network-enabled clinical environment; (4) implementing a method for unambiguous patient identification (1-4 Design and Development stage); (5) developing and implementing decision support which improves safety; (6) identifying practices to safely manage information technology system transitions (5 and 6 Implementation and Use stage); (7) developing real-time methods to enable automated surveillance and monitoring of system performance and safety; (8) establishing the cultural and legal framework/safe harbor to allow sharing information about hazards and adverse events; and (9) developing models and methods for consumers/patients to improve health information technology safety (7-9 Monitoring, Evaluation, and Optimization stage). These challenges represent key "to-do's" that must be completed before we can expect to have safe, reliable, and efficient health information technology-based systems required to care for patients.


Expression of XB130 in human ductal breast cancer.
XB130 is involved in gene regulation, cell proliferation, cell survival, cell migration, and tumorigenesis. In the present study, we first evaluated the expression of the XB130 and its prognostic significance in breast cancer. Then we evaluated whether XB130 could be a target for therapy in breast cancer. Immunohistochemistry was used to assess the level of XB130 protein in surgically resected, formalin-fixed, paraffin-embedded breast cancer specimens. Associations between XB130 and the postoperative prognosis of patients with breast cancer were evaluated. We evaluated the effect of XB130 inhibited by RNA interference on proliferation, invasion and apoptosis in vitro in a metastatic subclone of MCF-7 breast cancer cell line (LM-MCF-7). The effect of XB130 silencing alone or in combination with gemcitabine on LM-MCF-7 cells apoptosis was also investigated. XB130 protein was present in the cytoplasm of malignant cells, and not in the normal breast tissues. There was correlation between the presence of XB130 in tumour cells and lymph node status, tumor classification and clinical stage. XB130 expression level was significantly associated with recurrence-free and overall survival. Furthermore, multivariate Cox regression analyses revealed that positive XB130 was an independent risk factor for overall survival and recurrence free survival. XB130 silencing alone inhibits tumor growth and induces apoptosis in the LM-MCF-7 cells. Depletion of the XB130 in combination with gemcitabine resulted in marked apoptotic and necrotic cell death in LM-MCF-7 cells. XB130 could be useful as a prognostic marker of recurrence-free and overall survival in invasive breast cancer, as well as for the response to chemotherapy.


Oxygen-enabled control of Dzyaloshinskii-Moriya Interaction in ultra-thin magnetic films.
The search for chiral magnetic textures in systems lacking spatial inversion symmetry has attracted a massive amount of interest in the recent years with the real space observation of novel exotic magnetic phases such as skyrmions lattices, but also domain walls and spin spirals with a defined chirality. The electrical control of these textures offers thrilling perspectives in terms of fast and robust ultrahigh density data manipulation. A powerful ingredient commonly used to stabilize chiral magnetic states is the so-called Dzyaloshinskii-Moriya interaction (DMI) arising from spin-orbit coupling in inversion asymmetric magnets. Such a large antisymmetric exchange has been obtained at interfaces between heavy metals and transition metal ferromagnets, resulting in spin spirals and nanoskyrmion lattices. Here, using relativistic first-principles calculations, we demonstrate that the magnitude and sign of DMI can be entirely controlled by tuning the oxygen coverage of the magnetic film, therefore enabling the smart design of chiral magnetism in ultra-thin films. We anticipate that these results extend to other electronegative ions and suggest the possibility of electrical tuning of exotic magnetic phases.


Retinal Explant of the Adult Mouse Retina as an Ex Vivo Model for Studying Retinal Neurovascular Diseases.
One of the challenges in retina research is studying the cross-talk between different retinal cells such as retinal neurons, glial cells, and vascular cells. Isolating, culturing, and sustaining retinal neurons in vitro have technical and biological limitations. Culturing retinal explants may overcome these limitations and offer a unique ex vivo model to study the cross-talk between various retinal cells with well-controlled biochemical parameters and independent of the vascular system. Moreover, retinal explants are an effective screening tool for studying novel pharmacological interventions in various retinal vascular and neurodegenerative diseases such as diabetic retinopathy. Here, we describe a detailed protocol for retinal explants' isolation and culture for an extended period. The manuscript also presents some of the technical problems during this procedure that may affect the desired outcomes and reproducibility of the retinal explant culture. The immunostaining of the retinal vessels, glial cells, and neurons demonstrated intact retinal capillaries and neuroglial cells after 2 weeks from the beginning of the retinal explant culture. This establishes retinal explants as a reliable tool for studying changes in the retinal vasculature and neuroglial cells under conditions that mimic retinal diseases such as diabetic retinopathy.


Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis.
BACKGROUND/AIMS--The course of primary sclerosing cholangitis (PSC) is highly variable and unpredictable. This study describes the natural history and outcome of PSC. These data were used to construct a prognostic model for patients with PSC. METHODS--A total of 305 Swedish patients with PSC were studied. The median follow up time was 63 (1-194) months and all patients could be traced for follow up. Some 79 patients died or had a liver transplant. The prognostic significance of clinical, biochemical, and histological findings at the time of diagnosis were evaluated using multivariate analysis. RESULTS--The estimated median survival from time of diagnosis to death or liver transplantation was 12 years. Cholangiocarcinoma was found in 24 (8%) of the patients and 134 (44%) of the patients were asymptomatic at the time of diagnosis. The estimated survival rate was significantly higher in the asymptomatic group (p < 0.001). However, 29 (22%) of the asymptomatic patients became symptomatic during the study period. It was found that age, serum bilirubin concentration, and histological stage at the time of diagnosis were independent predictors of a bad prognosis. These variables were used to construct a prognostic model. CONCLUSIONS--This prognostic model developed from a large homogeneous population of PSC patients should be of value for the timing of transplantation and patient counselling in PSC.


Dental visits and self-assessment of dental health status in the adult Danish population.
The purpose of the present investigation was to study dental visits and self-assessment of dental health status in the adult Danish population. The study group comprised 5151 persons (86.7% of the original sample) who were interviewed in order to determine living conditions. Questions on dental visits and self-assessment of dental health status were included. 61% of the adult Danish population in the age group 20-69 had regular dental visits. Dental visit habits varied according to urbanization, age, sex and social group. Among well off persons 85% had regular dental visits as opposed to only 40% in the disadvantaged social group. Well off persons and persons with regular dental visits more often claimed good dental health than persons in the disadvantaged social group and among the non-regular visitors. In the higher social group 13% reported to have removable dentures in contrast to 51% in the disadvantaged social group. To isolate determinants of dental visits a multiple dummy-regression analysis was performed. Nearly 50% of the variation in dental visit habits was explained by the variables: urbanization, sex, age, perceived dental health status, education, work in exhausting jobs, income, social background and perceived psychological problems. Efforts to bring a greater part of the adult population in Denmark in contact with the dental health service system should consider these findings.


The Mononuclear Phagocytic System. Generation of Diversity.
We are living through an unprecedented accumulation of data on gene expression by macrophages, reflecting their origin, distribution, and localization within all organs of the body. While the extensive heterogeneity of the cells of the mononuclear phagocyte system is evident, the functional significance of their diversity remains incomplete, nor is the mechanism of diversification understood. In this essay we review some of the implications of what we know, and draw attention to issues to be clarified in further research, taking advantage of the powerful genetic, cellular, and molecular tools now available. Our thesis is that macrophage specialization and functions go far beyond immunobiology, while remaining an essential contributor to innate as well as adaptive immunity.


A dominant mutant of inner centromere protein (INCENP), a chromosomal protein, disrupts prometaphase congression and cytokinesis.
INCENP is a tightly bound chromosomal protein that transfers to the spindle midzone at the metaphase/anaphase transition. Here, we show that an INCENP truncation mutant (INCENP382-839) associates with microtubules but does not bind to chromosomes, and coats the entire spindle throughout mitosis. Furthermore, an INCENP truncation mutant (INCENP43-839) previously shown not to transfer to the spindle at anaphase (Mackay, A.M., D.M. Eckley, C. Chue, and W.C. Earnshaw. 1993. J. Cell Biol. 123:373-385), is shown here to bind chromosomes, but is unable to target to the centromere. Thus, association with the chromosomes, and specifically with centromeres, appears to be essential for INCENP targeting to the correct spindle subdomain at anaphase. An INCENP truncation mutant (INCENP1-405) that targets to centromeres but lacks the microtubule association region acquires strong dominant-negative characteristics. INCENP1-405 interferes with both prometaphase chromosome alignment and the completion of cytokinesis. INCENP1-405 apparently exerts its effect by displacing the endogenous protein from centromeres. These experiments provide evidence of an unexpected link between this chromosomal protein and cytokinesis, and suggest that one function of INCENP may be to integrate the chromosomal and cytoskeletal events of mitosis.


Purification of an exo-beta-D-glucanase from cell-free extracts of Candida utilis.
beta-Glucanase present in cell-free extracts from Candida utilis was isolated and purified 562-fold by procedures that include adsorption on DEAE-Sephadex A-50 and filtration through columns of Sephadex G-50, G-100 and G-200, Bio-Gel P-10, and Concanavalin A-Sepharose 4B. The purified enzyme appeared homogeneous on polyacrylamide-gel electrophoresis and in ultracentrifugation studies (S20,w = 1.74S). The enzyme behaved as an acidic glycoprotein (pI4.1) with 68% carbohydrate and a high content of acidic amino acids. The mol.wt. was estimated to be 20000 from gel filtration and polyacrylamide-gel electrophoresis and 36000 from sedimentation experiments. Studies on the hydrolysis of different substrates showed that the enzyme is an unspecific beta-glucanase able to break down both (1 leads to 3)-eta- and (1 leads to 6)-beta-linkages by an exo-splitting mechanism. Glucono-delta-lactone, Zn2+ and Hg2+ inhibited the enzyme activity.


Is there a relation between clinical scores and serum ion levels after MoM-THA? One year results in 383 implants.
Adverse reaction to metal debris is the major cause of the high revision rates of metal on metal hip implants with femoral head size ≥ 36mm. Health authorities recommend regular surveillance even for asymptomatic individuals. The main investigations used are Co+ and Cr+ serum levels, x-rays and, eventually, ultrasound and MARS-MRI. Clinic is also assessed. The aim of this study is to identify if there is a relation between ion levels and the clinical scores in order to evaluate the outcome and plan the correct management after this type of implant. 383 subjects were included and divided in 3 groups (serum ion levels >, < and >60 µg/L). Co+, Cr+, HHS and OHS results of 1 2017 were analysed in order to show a correlation between ion levels and clinical scores . Clinical scores were similar in group 1 and 2. Differences were observed comparing the group 1 and 2 with group 3 for both variables. Surveillance algorithms have been introduced by health authorities. Nevertheless, the indication to revision surgery is not simple especially in those cases in which a discrepancy between clinic and investigations is present. In this study clinical scores seem to be less important than ion levels in the evaluation of outcomes and in order to plan the correct management in the majority of cases. Larger studies are needed to highlight the real importance of clinical scores in the decision making after these type of implants.


Do attitude and area influence health? A multilevel approach to health inequalities.
This paper demonstrates an area effect on health and suggests improvements in research practice for work in this field. We use an area classification which can be related clearly to factors that influence the health of individuals and take account of people's differing propensities to draw influence from their area. Multilevel analysis demonstrates that the degree of deindustrialisation which an area experienced in Britain, in the 1980s, has an independent association with the health of resident individuals. A significant relationship between a person's attitude to their community and their health is shown to be independent of individual and area characteristics. We conclude that both individual and area characteristics influence health.


Chemopreventive effects of Cuminum cyminum in chemically induced forestomach and uterine cervix tumors in murine model systems.
Lately, a strong correlation has been established between diet and cancer. For ages, cumin has been a part of the diet. It is a popular spice regularly used as a flavoring agent in a number of ethnic cousins. In the present study, cancer chemopreventive potentials of different doses of a cumin seed-mixed diet were evaluated against benzo(a)pyrene [B(a)P]-induced forestomach tumorigenesis and 3-methylcholanthrene (MCA)-induced uterine cervix tumorigenesis. Results showed a significant inhibition of stomach tumor burden (tumors per mouse) by cumin. Tumor burden was 7.33 +/- 2.10 in the B(a)P-treated control group, whereas it reduced to 3.10 +/- 0.57 (P < 0.001) by a 2.5% dose and 3.11 +/- 0.60 (P <0.001) by a 5% dose of cumin seeds. Cervical carcinoma incidence, compared with the MCA-treated control group (66.67%), reduced to 27.27% (P < 0.05) by a diet of 5% cumin seeds and to 12.50% (P < 0.05) by a diet of 7.5% cumin seeds. The effect of 2.5 and 5% cumin seed-mixed diets was also examined on carcinogen/xenobiotic metabolizing phase I and phase II enzymes, antioxidant enzymes, glutathione content, lactate dehydrogenase (LDH), and lipid peroxidation in the liver of Swiss albino mice. Levels of cytochrome P-450 (cyt P-450) and cytochrome b5 (cyt b(5)) were significantly augmented (P < 0.05) by the 2.5% dose of cumin seed diet. The levels of cyt P-450 reductase and cyt b(5) reductase were increased (significance level being from P < 0.05 to P < 0.01) by both doses of cumin. Among the phase II enzymes, glutathione S-transferase specific activity increased (P < 0.005) by the 5% dose, whereas that of DT-diaphorase increased significantly (P < 0.05) by both doses used (2.5 and 5%). In the antioxidant system, significant elevation of the specific activities of superoxide dismutase (P < 0.01) and catalase (P < 0.05) was observed with the 5% dose of cumin. The activities of glutathione peroxidase and glutathione reductase remained unaltered by both doses of cumin. The level of reduced glutathione measured as nonprotein sulfhydryl content was elevated (significance level being from P < 0.05 to P < 0.01) by both doses of cumin. Lipid peroxidation measured as formation of MDA production showed significant inhibition (P < 0.05 to P < 0.01) by both doses of cumin. LDH activity remained unaltered by both doses of cumin. The results strongly suggest the cancer chemopreventive potentials of cumin seed and could be attributed to its ability to modulate carcinogen metabolism.


Lactation and postpartum infertility: the use-effectiveness of natural family planning (NFP) after term pregnancy.
The use-effectiveness of natural methods of family planning in lactation is evaluated by comparing the incidence of unplanned pregnancies in a group of nursing mothers practising these methods with the incidences reported previously in surveys of breastfeeding women using no contraception. The complexity of the physiological processes involved in the resumption of ovulation after term pregnancy is discussed in relation to NFP and the problems encountered by its users in the context of normal family life. The serum prolactin and gonadotrophin levels are correlated with the postpartum interval and nursing status of the participants and discussed in relation to NFP after childbirth.


Sexual and reproductive health needs assessment with deaf people in Ghana: Methodological challenges and ethical concerns.
Deafness is a complex and multifaceted phenomenon. The different ways of perceiving and understanding deafness have practical implications for research with deaf people. Whilst the deaf community is not homogenous, it is generally distinct from the hearing population. Consequently, the appropriateness of applying research methods and informed concern processes designed for the hearing population in research with deaf people has been questioned. This article reflected on some methodological challenges and ethical concerns arising from conducting a sexual and reproductive health needs assessment with deaf people in Ghana. The aim was to provide some perspectives on some of the challenges associated with doing research with deaf people. The study was a two phase, sequential, mixed methods design, consisting of three focus groups to assist in the development of a survey and then the implementation of the survey for needs assessment data collection. The number of participants in the study was 179, consisting of 26 focus group participants: 7 executives of the Ghana National Association of the Deaf (GNAD), 10 male adults, and 9 female adults. There were 152 survey respondents (students, women and men) and one key informant. All participants, except the key informant, were deaf people. The application of traditional research methods to studies involving deaf participants presents numerous methodological and ethical dilemmas associated mainly with deaf people's unique cultural and linguistic characteristics. Research methods should not be taken as universal guidelines for conducting research in all settings because of differences in settings.


The short-term effectiveness of full-contact custom-made foot orthoses and prefabricated shoe inserts on lower-extremity musculoskeletal pain: a randomized clinical trial.
Foot orthoses are commonly dispensed for musculoskeletal complaints of the foot and lower limb. Few randomized clinical trials evaluate the clinical effectiveness of foot orthoses. In this randomized clinical trial with a crossover design, 42 participants wore custom orthoses and prefabricated inserts in their regular footwear for 4 weeks each, consecutively. Twenty-seven participants received prefabricated inserts first and 13 received custom orthoses first. A numeric pain rating scale (possible score, 0-10) was used to measure participant pain. Statistically and clinically important decreases in pain were reported after 3 weeks by participants wearing custom orthoses first (-1.39 pain units, t(12) = 2.70, P = .02). Participants who wore prefabricated inserts first reported no statistically significant change in pain. When the alternative intervention was introduced, participants now wearing prefabricated inserts had greater pain after 1 and 2 weeks (1.1 pain units, t(12) = 3.09, P = .01 and 0.9 pain units, t(12) = 2.65, P = .02, respectively). Participants now wearing custom orthoses did not demonstrate significantly lower pain at any week compared with the second baseline but did have significantly lower pain scores compared with their initial baseline scores (-0.81 pain units, t(12) = 2.31, P = .03). Full-contact custom-made foot orthoses provide symptomatic relief after 3 weeks of use for patients with lower-extremity musculoskeletal pain if they are prescribed as the initial treatment.


Seroprevalence of anti-Toxoplasma gondii antibodies in Egyptian sheep and goats.
Toxoplasmosis is a zoonotic disease that affects a wide range of animals, including small ruminants. Sheep and goats are considered as biological indicators for the contamination of the environment with Toxoplasma gondii oocysts. In addition, in countries such as Egypt, where sheep and goat meat is frequently consumed, T. gondii infection in small ruminants may also pose a public health risk. To establish baseline estimates of the prevalence of T. gondii infection in Egyptian small ruminants, we used an indirect immunofluorescence assay (IFA) and an enzyme-linked immunosorbent assay (ELISA) to assess the seroprevalence in 398 sheep from four Egyptian governorates (Cairo, Giza, Dakahlia and Sharkia) and in 100 goats from Dakahlia. The positive and negative agreements of both tests were calculated and the true prevalence was estimated using a Bayesian approach. The true prevalence of antibodies to T. gondii as determined by both tests was higher in Egyptian goats (62%) than in sheep for each province (between 4.1 and 26%). Sheep slaughtered at the Cairo abattoir had the lowest true prevalence (4.1%), while true prevalences in Dakahlia, Giza and Sharkia governorates (26%, 23% and 12%, respectively) were substantially higher. The high prevalence of antibodies to T. gondii may indicate an important role of goat and sheep in the transmission of human toxoplasmosis in Egypt, given the habit of eating undercooked grilled mutton.


Modulation of ethanol state-dependent learning by dorsal hippocampal NMDA receptors in mice.
The possible role of N-methyl-D-aspartate (NMDA) receptors of dorsal hippocampus on ethanol state-dependent learning was studied in adult male mice (Pasteur Institute, Iran). As a model of memory, a single-trial step-down passive avoidance task was used. All animals were bilaterally implanted with cannulae into the CA1 regions of dorsal hippocampi. Results show that intraperitoneal (i.p.) administration of ethanol (0.5 and 1 g/kg) 30 min before training impaired memory performance in animals when tested 24h later. Pretest administration of the same doses of ethanol-induced state-dependent retrieval of the memory acquired under pretraining ethanol (1 g/kg, i.p.) influence. Pretest intra-CA1 microinjection of NMDA (0.001, 0.01, and 0.1 microg/mouse) by itself had no effect on memory retrieval and ethanol-induced amnesia. However, pretest intra-CA1 administration of the same doses of NMDA with an ineffective dose of ethanol (0.25 g/kg, i.p.) significantly restored the retrieval and potentiated ethanol state-dependent learning. On the other hand, pretest administration of a competitive NMDA receptor antagonist D-AP5 (D-(-)-2-Amino-5-phosphonopentanoic acid) (0.01, 0.1, and 1 microg/mouse, intra-CA1) or a noncompetitive NMDA receptor antagonist MK-801 maleate [(5S, 10R)-(+)-5-Methyl-10, 11-dihydro-5H-dibenzo [a, d] cyclohepten-5, 10-imine maleate] (0.25, 0.5, and 1 g/mouse, intra-CA1) 5 min before the administration of ethanol (1 g/kg, i.p.) significantly inhibited ethanol state-dependent learning. Intra-CA1 pretest administration of D-AP5 (0.01, 0.1, and 1 microg/mouse) or MK-801 maleate [5S, 10R)-(+)-5-Methyl-10, 11-dihydro-5H-dibenzo [a, d] cyclohepten-5, 10-imine maleate] (0.25, 0.5, and 1 microg/mouse) alone did not affect memory retention. It may be concluded that dorsal hippocampal NMDA receptors are involved in mediating ethanol state-dependent learning.


Safe patient care - safety culture and risk management in otorhinolaryngology.
Safety culture is positioned at the heart of an organization's vulnerability to error because of its role in framing organizational awareness to risk and in providing and sustaining effective strategies of risk management. Safety related attitudes of leadership and management play a crucial role in the development of a mature safety culture ("top-down process"). A type marker for organizational culture and thus a predictor for an organization's maturity in respect to safety is information flow and in particular an organization's general way of coping with information that suggests anomaly. As all values and beliefs, relationships, learning, and other aspects of organizational safety culture are about sharing and processing information, safety culture has been termed "informed culture". An informed culture is free of blame and open for information provided by incidents. "Incident reporting systems" are the backbone of a reporting culture, where good information flow is likely to support and encourage other kinds of cooperative behavior, such as problem solving, innovation, and inter-departmental bridging. Another facet of an informed culture is the free flow of information during perioperative patient care. The World Health Organization's safe surgery checklist" is the most prevalent example of a standardized information exchange aimed at preventing patient harm due to information deficit. In routine tasks mandatory standard operating procedures have gained widespread acceptance in guaranteeing the highest possible process quality. Technical and non-technical skills of healthcare professionals are the decisive human resource for an efficient and safe delivery of patient care and the avoidance of errors. The systematic enhancement of staff qualification by providing training opportunities can be a major investment in patient safety. In recent years several otorhinolaryngology departments have started to incorporate stimulation based team trainings into their curriculum.


Blinatumomab consolidation and maintenance therapy in adults with relapsed/refractory B-precursor acute lymphoblastic leukemia.
In a phase 3 clinical study of heavily pretreated adults with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL), overall survival (OS) following blinatumomab, a BiTE (bispecific T-cell engager) immunooncology therapy, was significantly improved vs chemotherapy following induction (cycles 1 to 2). Here we report the efficacy and safety of those who received additional cycles of blinatumomab. Blinatumomab was administered as a continuous IV infusion for 4 weeks in a 6-week cycle. Patients who achieved a bone marrow response (≤5% blasts) or complete remission (full, partial, or incomplete hematological recovery) during induction could receive additional cycles of blinatumomab. OS and relapse-free survival (RFS) for consolidation (cycles 3 to 5) vs no consolidation, and maintenance (cycles ≥6) vs no maintenance were analyzed using Simon-Makuch and Mantel-Byar odds ratios. Of 267 patients who received blinatumomab induction, 86 (32%) entered consolidation and 36 (13%) entered maintenance. Evidence of longer OS was demonstrated among the maintenance group compared with no-maintenance (median OS [95% confidence interval, CI]: not reached for maintenance vs 15.5 months for no maintenance). Median RFS (months; 95% CI) was numerically longer among maintenance group (14.5; 7.1 to 21.9) compared with no-maintenance (9.8; 8.5 to 11.1). A lower incidence of adverse events was seen during maintenance (72.2%) compared with induction (97.2%) and consolidation (86.1%). Adults with R/R ALL who achieved remission following blinatumomab induction had longer survival on continuation therapy than those who discontinued blinatumomab early, supporting the use of blinatumomab as long-term therapy. No new safety signals were reported. This trial was registered at www.clinicaltrials.gov as #NCT02013167.


Millennium Development Goal 1: poverty, hunger and decent work in Southeast Asia.
This article considers three questions: 1) what progress has been made in achieving MDG1 targets?; 2) what challenges remain?; and 3) what more could and should be done? To examine these questions, the article assesses the progress of Southeast Asia in seeking to achieve MDG1. It argues that the region is 'on track' to achieve MDG 1 targets, although significant challenges such as inequality remain. Economic growth, significant structural change and incorporation into global value chains have contributed to MDG progress. However, this is a double-edged sword as exposure to global economic turbulence can increase. The longer-term reduction of poverty, inequality and social exclusion is a question of empowerment of local producers within value chains-a shift in economic power and control through pro-poor strategies strong enough to effect substantive structural change. The article outlines key concepts; identifies the main characteristics of Southeast Asian poverty; outlines what more needs to be done; and concludes by reprising the article's findings and weighing the prospects for 2010-15 and beyond.


Increased levels of apoptosis in the prefusion neural folds underlie the craniofacial disorder, Treacher Collins syndrome.
Treacher Collins syndrome (TCS) is an autosomal dominant disorder of human craniofacial development that results from loss-of-function mutations in the gene TCOF1. Although this gene has been demonstrated to encode the nucleolar phosphoprotein treacle, the developmental mechanism underlying TCS remains elusive, particularly as expression studies have shown that the murine orthologue, Tcof1, is widely expressed. To investigate the molecular pathogenesis of TCS, we replaced exon 1 of Tcof1 with a neomycin-resistance cassette via homologous recombination in embryonic stem cells. Tcof1 heterozygous mice die perinatally as a result of severe craniofacial anomalies that include agenesis of the nasal passages, abnormal development of the maxilla, exencephaly and anophthalmia. These defects arise due to a massive increase in the levels of apoptosis in the prefusion neural folds, which are the site of the highest levels of Tcof1 expression. Our results demonstrate that TCS arises from haploinsufficiency of a protein that plays a crucial role in craniofacial development and indicate that correct dosage of treacle is essential for survival of cephalic neural crest cells.


Correlates of compliance among chiropractic patients treated for low back pain.
To test Becker's revision of the Health Belief Model in predicting adherence to a chiropractic regimen, 50 patients diagnosed with recurrent acute lumbago were interviewed regarding health beliefs. All subjects had initiated treatment 12 months before the onset of research. This enabled the calculation of a compliance score for each patient, expressed as the percentage of appointments kept to appointments recommended over a 1-yr period. Posttreatment health beliefs were correlated with the compliance measure. From the four dimensions of the model tested, two categories showed variables having significant associations with appointment keeping. Intention to comply was strongly correlated with compliance (P less than 0.01). However, contrary to the model, subjects' estimates of disability were negatively related with adherence to the program (P less than 0.05). It was suggested that patients reporting high levels of disability showed forced compliance. Clinical applications derived from these results are included to aid chiropractors in the prediction and management of compliance.


The limited role of splenectomy in patients with leukemia.
Splenectomy is a valuable method of management of approximately 80 per cent of patients with hairy cell leukemia who have hypersplenic complications develop; operation can be performed with minimal morality and morbidity. Removal of the spleen also provides useful palliation in patients with chronic lymphocytic leukemia who have symptomatic splenomegaly or autoimmune hemolytic anemia; success is less predictable when operation is performed for thrombocytopenia. Splenectomy is linked with a high mortality and is of little benefit in patients with chronic granulocytic leukemia except when operation is performed as a prerequisite to bone marrow transplantation. Several patients with acute leukemia who have signs of splenic infarction and intra-abdominal bleeding develop had a short survival period after splenectomy.


A comprehensive review of ultrasonic assisted extraction (UAE) for bioactive components: Principles, advantages, equipment, and combined technologies.
The increasing focus on health and well-being has sparked a rising interest in bioactive components in the food, pharmaceutical, and nutraceutical industries. These components are gaining popularity due to their potential benefits for overall health. The growing interest has resulted in a continuous rise in demand for bioactive components, leading to the exploration of both edible and non-edible sources to obtain these valuable substances. Traditional extraction methods like solvent extraction, distillation, and pressing have certain drawbacks, including lower extraction efficiency, reduced yield, and the use of significant amounts of solvents or resources. Furthermore, certain extraction methods necessitate high temperatures, which can adversely affect certain bioactive components. Consequently, researchers are exploring non-thermal technologies to develop environmentally friendly and efficient extraction methods. Ultrasonic-assisted extraction (UAE) is recognized as an environmentally friendly and highly efficient extraction technology. The UAE has the potential to minimize or eliminate the need for organic solvents, thereby reducing its impact on the environment. Additionally, UAE has been found to significantly enhance the production of target bioactive components, making it an attractive method in the industry. The emergence of ultrasonic assisted extraction equipment (UAEE) has presented novel opportunities for research in chemistry, biology, pharmaceuticals, food, and other related fields. However, there is still a need for further investigation into the main components and working modes of UAEE, as current understanding in this area remains limited. Therefore, additional research and exploration are necessary to enhance our knowledge and optimize the application of UAEE. The core aim of this review is to gain a comprehensive understanding of the principles, benefits and impact on bioactive components of UAE, explore the different types of equipment used in this technique, examine the various working modes and control parameters employed in UAE, and provide a detailed overview of the blending of UAE with other emerging extraction technologies. In conclusion, the future development of UAEE is envisioned to focus on achieving increased efficiency, reduced costs, enhanced safety, and improved reliability. These key areas of advancement aim to optimize the performance and practicality of UAEE, making it a more efficient, cost-effective, and reliable extraction technology.


Fetal tubuloglomerular feedback in an ovine model of mild maternal renal disease.
Fetuses of pregnant ewes, which were subtotally nephrectomized prior to mating, were studied to assess whether mild maternal renal impairment would affect fetal tubuloglomerular feedback (TGF) under control conditions and after the inhibition of macula densa-derived nitric oxide (NO). Based on previous observations we hypothesized that, the TGF curve of fetuses of subtotally nephrectomized (STNx) ewes would resemble that of a volume expanded fetus with a high production rate of NO and that inhibition of neuronal nitric oxide synthase (nNOS) would increase the sensitivity of the TGF system in these fetuses. Renal function studies were performed on anaesthetized fetal sheep (133-140 days gestation; term ~150 days; Isoflurane 2-4% in oxygen). Fetuses were removed from the uterus and placed in a water bath (39.5°C) while maintaining umbilical blood flow. Glomerular filtration rate (GFR) and urine flow rate were markedly increased in fetuses of STNx ewes compared to fetuses of untreated ewes. Interestingly, and contrary to our hypothesis, the fetuses of STNx ewes exhibited no difference in TGF sensitivity in the presence or absence of 7-nitroindazole (7NI; nNOS inhibitor), compared to fetuses of untreated ewes, although sensitivity and reactivity increased in both groups after 7NI. There was however, a decrease in the stop flow pressure and net filtration pressure with an increase in the filtration coefficient (Kf). These factors suggest that maternal renal impairment drives the glomerular hypertrophy which has previously been found to be present in the neonatal period. Thus, we conclude that at ~138 days gestation, the fetal kidney has matured functionally and fetuses of STNx ewes are able to maintain fluid and electrolyte homeostasis even in the presence of increased transplacental flux.


pH of endophagosomes controls association of their membranes with Vps34 and PtdIns(3)P levels.
Phagocytosis of filamentous bacteria occurs through tubular phagocytic cups (tPCs) and takes many minutes to engulf these filaments into phagosomes. Contravening the canonical phagocytic pathway, tPCs mature by fusing with endosomes. Using this model, we observed the sequential recruitment of early and late endolysosomal markers to the elongating tPCs. Surprisingly, the regulatory early endosomal lipid phosphatidylinositol-3-phosphate (PtdIns(3)P) persists on tPCs as long as their luminal pH remains neutral. Interestingly, by manipulating cellular pH, we determined that PtdIns(3)P behaves similarly in canonical phagosomes as well as endosomes. We found that this is the product of a pH-based mechanism that induces the dissociation of the Vps34 class III phosphatidylinositol-3-kinase from these organelles as they acidify. The detachment of Vps34 stops the production of PtdIns(3)P, allowing for the turnover of this lipid by PIKfyve. Given that PtdIns(3)P-dependent signaling is important for multiple cellular pathways, this mechanism for pH-dependent regulation of Vps34 could be at the center of many PtdIns(3)P-dependent cellular processes.


Novel Molecular Markers for Breast Cancer.
The use of molecular biomarkers assures that breast cancer (BC) patients receive optimal treatment. Established biomarkers, such as estrogen receptor, progesterone receptor, HER2, and Ki67, have been playing significant roles in the subcategorization of BC to predict the prognosis and decide the specific therapy to each patient. Antihormonal therapy using 4-hydroxytamoxifen or aromatase inhibitors have been employed in patients whose tumor cells express hormone receptors, while monoclonal antibody to HER2 has been administered to HER2-positive BCs. Although new therapeutic agents have been developed in the past few decades, many patients still die of the disease due to relapse; thus, novel molecular markers that predict therapeutic failure and those that can be targets for specific therapy are expected. We have chosen four of such molecules by reviewing recent publications, which are cyclin E, B-Myb, Twist, and DMP1β. The oncogenicity of these molecules has been demonstrated in vivo and/or in vitro through studies using transgenic mice or siRNAs, and their expressions have been shown to be associated with shortened overall or disease-free survival of BC patients. The former three molecules have been shown to accelerate epithelial-mesenchymal transition that is often associated with cancer stem cell-ness and metastasis; all these four can be novel therapeutic targets as well. Thus, large prospective studies employing immunohistochemistry will be needed to establish the predictive values of these molecules in patients with BC.


Non-Helicobacter pylori bacterial flora during acid-suppressive therapy: differential findings in gastric juice and gastric mucosa.
Intragastric growth of non-Helicobacter pylori bacteria commonly occurs during acid-suppressive therapy. The long-term clinical consequences are still unclear. To investigate the luminal and mucosal bacterial growth during gastric acid inhibition, in relation to the type and duration of acid-inhibitory treatment, as well as to concomitant H. pylori infection. A total of 145 patients on continuous acid inhibition with either proton pump inhibitors (n=109) or histamine2-receptor antagonists (H(2)RAs, n=36) for gastro-oesophageal reflux disease, and 75 dyspeptic patients without acid inhibition (control group) were included. At endoscopy, fasting gastric juice was obtained for pH measurement and bacteriological culture. Gastric biopsy specimens were examined for detection of H. pylori (immunohistochemistry) and of non-H. pylori bacteria (modified Giemsa stain-positive and immunohistochemistry-negative at the same location). Non-H. pylori flora was detected in the gastric juice of 92 (41.8%) patients and in the gastric mucosa of 109 (49.6%) patients. In gastric juice, prevalence rate for non-H. pylori bacteria was higher in patients taking proton pump inhibitors than controls and those taking H(2)RAs (58.7% vs. 22.6% and vs. 30.6%, P < 0.0001 and P < 0.003, respectively), but did not differ statistically between H(2)RAs and controls. In gastric mucosa, prevalence rates for non-H. pylori bacteria were higher in patients taking proton pump inhibitors and H(2)RAs than in the controls (antrum: 46.9% and 48.6% vs. 25%, P < 0.05 for both; corpus: 52.2% and 56.8% vs. 23.7%, P < 0.001 for both), but did not differ between proton pump inhibitors and H(2)RAs. Both luminal and mucosal growth of non-H. pylori bacteria were significantly greater in H. pylori-positive than -negative patients taking proton pump inhibitors (P < 0.05 for both). Luminal growth of non-H. pylori flora increased with the intragastric pH level, whilst mucosal bacterial growth increased with the duration of acid inhibition. Non-H. pylori flora not only contaminates the gastric juice but also colonizes the gastric mucosa of a large proportion of patients treated long-term with acid inhibition. The relationship between H. pylori and non-H. pylori bacteria in the pathogenesis of atrophic gastritis and gastric cancer needs further elucidation.


[Automatic injectors in magnetic resonance imaging and computed tomography: pilot study on hygienic aspects].
To evaluate hygienic conditions using automatic injectors in magnetic resonance imaging (MRI) and computed tomography (CT) during clinical routine. The surfaces of medical devices (e. g., control console) and the palms of the technical and medical staff were microbiologically analyzed by taking imprints before and after hygienic education. In addition, the injector syringes for contrast medium (CM) and saline were checked for microbiological contamination following multiple (MRI: 14 h; CT 8 h) and single use. Furthermore, the potential of retrograde contamination from the patient along the tube was analyzed. A bacterial contamination with typical dermal bacteria was documented for the surfaces of the medical devices, the palms of the technical and medical staff, and the injection syringes following multiple use (MRI: 10/10 CM syringes, 6/10 saline syringes; CT: 8/10 CM syringes, 5/10 saline syringes). Correct hand disinfection in combination with single use of syringes avoided bacterial colonization. Retrograde bacterial contamination from the patient was not observed. Regular hygienic teaching sessions for technical and medical staff in MRI and CT departments using automatic injectors should be mandatory. Furthermore, the multiple use of syringes should be avoided until investigations addressing the potential of bacterial contamination are performed.


Evaluation of a data warehouse in an academic health sciences center.
A data warehouse can provide significant benefits to a health care organization if successfully designed and implemented. The Clinical Data Repository (CDR) at the University of Virginia Health Sciences Center improves access to needed data for clinical research and effective decision making at many levels of the organization. We conducted an evaluation of the CDR using a survey questionnaire and interviews of key executive leaders. Our results suggest factors that influence the initial decision to use an information resource, examine the impact of communication channels, and highlight key issues that determine the continued use and ultimate success of a healthcare data warehouse.


Right iliac arteriovenous fistula due to aneurysm rupture and left iliac artery aneurysm: hybrid treatment.
An arteriovenous fistula (AVF) is an uncommon sequela of spontaneous arterial aneurysm rupture into the adjacent venous system. We describe the case of a 74-year-old patient who underwent endovascular treatment of a right iliac AVF caused by a ruptured common iliac artery (CIA) aneurysm and a distal left CIA aneurysm. Surgery preserved the lumbar and inferior mesenteric arteries because of the need to simultaneously exclude the hypogastric arteries. Dynamic fluid balance phenomena provoked by closure of the AVF are described. The patient had a benign postoperative course with normalization of the severe hemodynamic changes presented prior to the intervention and resolution of respiratory symptoms attributed to pulmonary arterial hypertension.


Herpes simplex virus type-1 glycoprotein D gene: nucleotide sequence and expression in Escherichia coli.
The protein coding region of the herpes simplex virus type-1 glycoprotein D (gD) gene was mapped, and the nucleotide sequence was determined. The predicted amino acid sequence of the gD polypeptide was found to contain a number of features in common with other virus glycoproteins. Insertion of this protein coding region into a bacterial expressor plasmid enabled synthesis in Escherichia coli of an immunoreactive gD-related polypeptide. The potential of this system for preparation of a type-common herpes simplex virus vaccine is discussed.


Probing the Cleaning of Polymeric Coatings by Nanostructured Fluids: A QCM-D Study.
Complex fluids composed of water, an organic solvent, and a surfactant have been recently employed as cleaning systems to remove hydrophobic materials, such as polymeric coatings, from solid surfaces. The simultaneous presence of surfactants and an organic solvent with good affinity for the polymer was proven necessary for the polymer's removal, but the comprehension of the cleaning mechanism is poorly understood. In this Article, we investigated the mechanism of removal, highlighting the specific role of each component in the interaction with the polymer film. In particular, the results from quartz crystal microbalance with dissipation monitoring (QCM-D) were compared with those obtained by using confocal microscopy to follow in situ the effect of a nanostructured fluid, i.e., a ternary formulation containing water, 2-butanone (MEK) as a good solvent for the polymer, and a nonionic surfactant (C9-11 ethoxylated alcohol, BR) on acrylic copolymer films (Paraloid B72). The results indicate a two-step process: (i) the penetration of the good solvent across the film causes the swelling of the polymer, the weakening of polymer-polymer interactions, and an increase of molecular mobility, followed by (ii) the slow adsorption of amphiphilic aggregates promoting the film detachment from the solid substrate. A different behavior is observed in the presence of similar formulations containing an anionic surfactant (sodium dodecyl sulfate, SDS), where the adsorption of SDS micelles on the surface of the polymeric film hinders solvent access into the polymer layer, rather than promoting its detachment from the solid substrate.


The meaning and significance of self-management among socioeconomically vulnerable older adults.
The aim of this study was to describe and contrast perceptions of self-management among socioeconomically vulnerable and nonvulnerable older adults. We used in-depth, in-home interviews guided by identity theory. Analyses included reviewing audiotapes, creating and comparing field notes, coding transcripts, and identifying themes based on case summaries. Interviews took place in patients' homes. Participants were 23 vulnerable older adults with incomes at or below 200% of the federal poverty level and no private insurance and 12 older adults with private health insurance. The vulnerable sample had lower educational attainment and lower health literacy than the privately insured sample. Keeping doctor visits and taking prescription medications largely defined self-management for the vulnerable sample but were just two of a number of roles noted by the privately insured group, who expressed health promotion as the key to healthy aging. The vulnerable interviewees relayed few examples of healthy aging and did not have expectations for healthful aging. In contrast, the privately insured interviewees gave examples and had expectations of living long and healthfully into old age. Improved understanding of the role of social context in expectations regarding aging, and awareness of and priorities for self-management, could lead to improvements in self-management support and thus chronic care outcomes.


Summative interaction between astaxanthin, Ginkgo biloba extract (EGb761) and vitamin C in suppression of respiratory inflammation: a comparison with ibuprofen.
In this study, combinations of Ginkgo biloba leaf extract (EGb761) plus the carotenoid antioxidant astaxanthin (ASX) and vitamin C were evaluated for a summative dose effect in the inhibition of asthma-associated inflammation in asthmatic guinea-pigs. Ovalbumin-sensitized Hartley guinea-pigs challenged with ovalbumin aerosol to induce asthma, were administered EGb761, ASX, vitamin C or ibuprofen. Following killing, bronchoalveolar lavage (BAL) fluid was evaluated for inflammatory cell infiltrates and lung tissue cyclic nucleotide content. Each parameter measured was significantly altered to a greater degree by drug combinations, than by each component acting independently. An optimal combination was identified that included astaxanthin (10 mg/kg), vitamin C (200 mg/kg) and EGb761 (10 mg/kg), resulting in counts of eosinophils and neutrophils each 1.6-fold lower; macrophages 1.8-fold lower, cAMP 1.4-fold higher; and cGMP 2.04-fold higher than levels in untreated, asthmatic animals (p < 0.05). In conclusion, EGb761, ASX and vitamin C are shown here to interact summatively to suppress inflammation with efficacy equal to or better than ibuprofen, a widely used non-steroidal antiinflammatory drug (NSAID). Such combinations of non-toxic phytochemicals constitute powerful tools for the prevention of onset of acute and chronic inflammatory disease if consumed regularly by healthy individuals; and may also augment the effectiveness of therapy for those with established illness.


Accepting Immunotherapy After Multiline Treatment Failure: An Exploration of the Anxiety and Depression in Patients with Advanced Cancer Experience.
Tumor immunotherapy is a promising therapeutic strategy for patients with advanced cancers, and some tumors have profound and durable tumor regression. However, immunotherapy is still in the clinical trial stage with elusive long-term effects and complications as a new strategy. It is unclear whether patients possess an accurate understanding of the clinical benefits associated with these agents. To investigate the anxiety and depression of patients with advanced cancer who received immunotherapy using programmed death-1 or programmed death-ligand 1 after multiline treatment failure, explore the influencing factors, and provide a reference for clinical medical staff and psychological support for patients. The Hospital Anxiety and Depression Scale was used to calculate the anxiety and depression scores before and after 1, 2, and 3 courses of treatment, respectively. The patients with anxiety and depression were counted. Purposive sampling was used to conduct face-to-face semi-structured interviews with 21 patients to find out the reasons. The obtained data were analyzed and collated using Colaizzi's phenomenological method. One hundred and twenty-six patients with advanced cancers were included in the study. Before and after 1, 2 and 3 courses of treatment, 18.26%, 23.0%, 50% and 54% of patients suffered from anxiety and depression, respectively. The proportion of patients with anxiety and depression during immunotherapy kept increasing, mainly due to therapeutic efficacy below expectation, lack of timely information after treatment, lack of awareness of treatment and drugs, and lack of family and social support. Patients with advanced tumors after multiline treatment failure are susceptible to anxiety and depression during immunotherapy. It is necessary to test the emotional state of patients in time and carry out early intervention. Nursing staffs and medical staffs should adopt personalized measures to meet the psychological needs of patients.


National evaluation for calving ease, gestation length and birth weight by linear and threshold model methodologies.
Data included 393,097 calving ease, 129,520 gestation length, and 412,484 birth weight records on 412,484 Gelbvieh cattle. Additionally, pedigrees were available on 72,123 animals. Included in the models were effects of sex and age of dam, treated as fixed, as well as direct, maternal genetic and permanent environmental effects and effects of contemporary group (herd-year-season), treated as random. In all analyses, birth weight and gestation length were treated as continuous traits. Calving ease (CE) was treated either as a continuous trait in a mixed linear model (LM), or as a categorical trait in linear-threshold models (LTM). Solutions in TM obtained by empirical Bayes (TMEB) and Monte Carlo (TMMC) methodologies were compared with those by LM. Due to the computational cost, only 10,000 samples were obtained for TMMC. For calving ease, correlations between LM and TMEB were 0.86 and 0.78 for direct and maternal genetic effects, respectively. The same correlations but between TMEB and TMMC were 1.00 and 0.98, respectively. The correlations between LM and TMMC were 0.85 and 0.75, respectively. The correlations for the linear traits were above.97 between LM and TMEB but as low as 0.91 between LM and TMMC, suggesting insufficient convergence of TMMC. Computing time required was about 2 hrs, 5 hrs, and 6 days for LM, TMEB and TMMC, respectively, and memory requirements were 169, 171, and 445 megabytes, respectively. Bayesian implementation of threshold model is simple, can be extended to multiple categorical traits, and allows easy calculation of accuracies; however, computing time is prohibitively long for large models.


Internists' career choice towards primary care: a cross-sectional survey.
Swiss primary care (PC) is facing workforce shortage. Up to 2011 this workforce was supplied by two board certifications: general medicine and internal medicine. To strengthen them against subspecialties, they were unified into one: general internal medicine. However, since unification general practitioners' career options are no longer restrained by early commitment to PC. This may lead to a decrease of future primary care physicians (PCPs). To gain insights in timing and factors influencing career choice of internists, we addressed a cross sectional survey to all board certified internists in the years 2000-2010 (n = 1462). Main measures were: final career choice (PCPs, hospital internists or subspecialists), timing and factors influencing career choice, and attractiveness of PCP career during medical school and residency. Response rate was 53.2%, 44.8% were female and median age was 45 years old. Final career choice was PCP for 39.1% of participants, 15.0% chose to become hospital internists, 41.8% became subspecialists and 4.0% other. Timing of career choice significantly differed between groups. Most of the subspecialists have chosen their career during residency (65.3%), while only 21.9% of the PCPs chose during residency. Work experience in an academic hospital was negatively associated with becoming PCP (P < 0.001). Family influence on career choice was more frequently reported among PCPs and chiefs' influence more reported among non-PCPs (P < 0.001). Fifty-nine percent of the participants considered a career as PCP to be attractive during medical school, this proportion decreased over time. Timing of career choice of PCPs and subspecialists strongly differed. PCPs opted late for their career and potentially modifiable external factors seem to contribute to their decision. This stresses the importance of fostering attractiveness of PC during medical school as well as during and after residency and of tailored residency positions for future PCPs in the hospital-dominated new general internal medicine training.


A kinetic molecular model of the reversible unfolding and refolding of titin under force extension.
Molecular elasticity is a physicomechanical property that is associated with a select number of polypeptides and proteins, such as the giant muscle protein, titin, and the extracellular matrix protein, tenascin. Both proteins have been the subject of atomic force microscopy (AFM), laser tweezer, and other in vitro methods for examining the effects of force extension on the globular (FNIII/Ig-like) domains that comprise each protein. In this report we present a time-dependent method for simulating AFM force extension and its effect on FNIII/Ig domain unfolding and refolding. This method treats the unfolding and refolding process as a standard three-state protein folding model (U right arrow over left arrow T right arrow over left arrow F, where U is the unfolded state, T is the transition or intermediate state, and F is the fully folded state), and integrates this approach within the wormlike chain (WLC) concept. We simulated the effect of AFM tip extension on a hypothetical titin molecule comprised of 30 globular domains (Ig or FNIII) and 25% Pro-Glu-Val-Lys (PEVK) content, and analyzed the unfolding and refolding processes as a function of AFM tip extension, extension rate, and variation in PEVK content. In general, we find that the use of a three-state protein-folding kinetic-based model and the implicit inclusion of PEVK domains can accurately reproduce the experimental force-extension curves observed for both titin and tenascin proteins. Furthermore, our simulation data indicate that PEVK domains exhibit extensibility behavior, assist in the unfolding and refolding of FNIII/Ig domains in the titin molecule, and act as a force "buffer" for the FNIII/Ig domains, particularly at low and moderate extension forces.


Brain flow changes before and after deep brain stimulation of the subthalamic nucleus in Parkinson's disease.
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) markedly improves motor symptoms and reduces medication needs in Parkinson's disease (PD) patients. However, its effect on brain function has remained unclear. We used SPECT and the tracer ECD to measure regional cerebral blood flow before and 6 months after DBS of the STN in 22 PD patients and 13 healthy controls. PD patients were divided into good and poor responders to DBS, if changes in "off" UPDRS motor scores after surgery were >60% or <40%, respectively. Statistical analysis was performed using the SPM99 software. At baseline, all PD patients showed significant perfusion reductions in cortical areas (premotor frontal, parietal, and occipital). After DBS, changes were normalized only in the good responders, while cortical defects in the poor responders were unchanged. No flow decrements were detected in basal ganglia and thalamus in both groups, suggesting that DBS does not have a "lesion-like" effect. We conclude that good surgery outcome is associated with normalization of cortical flow abnormalities in PD.


Cryptic dispersal networks shape biodiversity in an invaded landscape.
Species interact with the physical world in complex ways, and life-history strategies could cause species to differ in how they experience the connectedness of the same landscape. As a consequence, dispersal limitation might be present but not captured by distance-based measures of connectivity. To test these ideas, we surveyed plant communities that live on discrete patches of serpentine habitat embedded within an invaded nonserpentine habitat matrix. Species in these communities differ in dispersal mode (gravity, animal, or wind); thus we used satellite imagery to quantify landscape features that might differentially influence connectivity for some dispersal- mode groups over others (surface streams, animal paths). Our data yielded two key insights: first, dispersal limitation appeared to be absent using a conventional distance-based measure of connectivity, but emerged after considering forms of landscape connectivity relevant to each dispersal mode. Second, the landscape variables that emerged as most important to each dispersal mode were generally consistent with our predictions based on species' putative dispersal vectors, but also included unexpected interactive effects. For example, the richness of animal-dispersed species was positively associated with animal connectivity when patches were close in space, but when patches were isolated, animals had a strong negative effect. This finding alludes to the reduced ability of animals to disperse seeds between suitable patches in invaded landscapes because of increased inter-patch distances. Real landscapes include complex spatial flows of energy and matter, which, as our work demonstrates, sets up ecological opportunity for organisms to differ in how they disperse in a common landscape.


Impact of design parameters on bileaflet mechanical heart valve flow dynamics.
One significant problem encountered during surgery to implant mechanical heart valve prostheses is the propensity for thrombus formation near the valve leaflet and housing. This may be caused by the high shear stresses present in the leakage jet flows through small gaps between leaflets and the valve housing during the valve closure phase. A two-dimensional (2D) study was undertaken to demonstrate that design changes in bileaflet mechanical valves result in notable changes in the flow-induced stresses and prediction of platelet activation. A Cartesian grid technique was used for the 2D simulation of blood flow through two models of bileaflet mechanical valves, and their flow patterns, closure characteristics and platelet activation potential were compared. A local mesh refinement algorithm allowed efficient and fast flow computations with mesh adaptation based on the gradients of the flow field in the gap between the leaflet and housing at the instant of valve closure. Leaflet motion was calculated dynamically, based on the fluid forces acting on it. Platelets were modeled and tracked as point particles by a Lagrangian particle tracking method which incorporated the hemodynamic forces on the particles. A comparison of results showed that the velocity, wall shear stress and simulated platelet activation parameter were lower in the valve model, with a smaller angle of leaflet traverse between the fully open to the fully closed position. The parameters were also affected to a lesser extent by local changes in the leaflet and housing geometry. Computational simulations can be used to examine local design changes to help minimize the fluid-induced stresses that may play a key role in thrombus initiation with the implanted mechanical valves.


Non-alcoholic fatty liver disease in 2016.
Non-alcoholic fatty liver disease is the commonest cause of liver disease worldwide, and is rapidly becoming the leading indication for liver transplantation. Original articles, reviews and meta-analyses, guidelines. NAFLD strongly correlates with obesity and insulin resistance; currently, the best management strategy is weight loss and treatment of the metabolic syndrome. Recent data suggest that the presence of fibrosis and not non-alcoholic steatohepatitis (NASH) is the predictor of clinical outcome. Many phase 2 and 3 trials are underway. Drugs hoped to be effective are obeticholic acid, elafibranor, glucagon-like peptide-1 analogues and CCR2/5 inhibitors. Improved understanding of the pathophysiology of NAFLD should help us identify which patients progress to significant liver disease and to develop therapies to target this population.


Narrative and prosodic skills in children and adolescents with Down syndrome and typically developing children.
Children with Down Syndrome (DS) show difficulties in language development, in both basic and complex abilities, as narratives. Less is known about the prosodic competence in DS, but the few available studies highlighted the presence of some deficits. Considering the importance of narratives and prosody in communication, the main aim of this study is to investigate these two competencies in participants with DS. 13 children with DS participated (Mean age: 13;04, years; months). Their narrative and prosodic abilities, collected through a storytelling task, were compared with those of two control groups of typically developing (TD) children, one matched for nonverbal mental age (MA, Mean age: 5;03) and the other matched for the mean length of utterance (MLU, Mean age: 5;05). For the narrative competence, we considered both the macrostructural (i.e. quantity of information and story structure) and the microstructural level (i.e. verbal productivity, lexical diversity, syntactic complexity). For the prosodic competence, we took into account acoustic measures linked to intonation (i.e. mean fundamental frequency (f0), pitch range, final speech profile, and speed of speech). The results of the Mann-Whitney test showed that participants with DS produced stories comparable to those of TD children in nearly all the variables considered, except for the syntactic complexity when compared with children of the same MA. Differences between participants with DS and TD children were found in the f0 and the final pitch profile used. Considering the small size of the samples, these preliminary results should be taken with caution. Nonetheless, this study confirms the presence of difficulties in the prosody of speech and in the syntactic competence of children with DS. These difficulties could have consequences on the possibility to communicate efficiently and should be taken into account in rehabilitation programmes.


Suprascapular neuropathy. Results of non-operative treatment.
We retrospectively reviewed the results of non-operative treatment of suprascapular neuropathy in fifteen patients seen between November 1983 and February 1991. The clinical diagnosis was confirmed with electrodiagnostic studies. The treatment consisted of a program of physical therapy to improve the range of motion of the shoulder and to strengthen the surrounding muscles. The average duration of follow-up was three years and eleven months (range, one year to eight years and ten months). The latest evaluation included electrodiagnostic studies of the affected extremity and dynamic isokinetic testing of both upper extremities. The result was excellent for five patients and good for seven. The three remaining patients had operative treatment because of persistent symptoms; one of these patients had an excellent result, one had a good result, and one had a poor result. The results suggest that, in the absence of a well defined lesion producing mechanical compression of the suprascapular nerve, suprascapular neuropathy should be treated non-operatively.


INCA: a computational platform for isotopically non-stationary metabolic flux analysis.
13C flux analysis studies have become an essential component of metabolic engineering research. The scope of these studies has gradually expanded to include both isotopically steady-state and transient labeling experiments, the latter of which are uniquely applicable to photosynthetic organisms and slow-to-label mammalian cell cultures. Isotopomer network compartmental analysis (INCA) is the first publicly available software package that can perform both steady-state metabolic flux analysis and isotopically non-stationary metabolic flux analysis. The software provides a framework for comprehensive analysis of metabolic networks using mass balances and elementary metabolite unit balances. The generation of balance equations and their computational solution is completely automated and can be performed on networks of arbitrary complexity.


Transcription of the trpR gene of Escherichia coli: an autogeneously regulated system studied by direct measurements of mRNA levels in vivo.
The expression of the trpR gene of Escherichia coli was investigated by measuring trpR messenger RNA levels in vivo under various physiological conditions. Trp repressor, when present, led to significant decreases in the amount of trpR message produced; this effect was enhanced by providing excess L-tryptophan to the system. In the absence of Trp repressor, no changes in trpR message levels were observed under any of the conditions employed. Sedimentation profiles of trpR mRNA revealed a single species under all circumstances. These results suggest that autogenous repression alone acts to regulate transcription of the trpR gene. The activity of the trpR promoter in vivo was evaluated using a trpR-lacZ operon fusion. Very good agreement was found between relative promoter activity and trpR message levels under all experimental conditions.


Demonstration of two protein kinases in extracts of Legionella micdadei.
Protein kinases I (PK I) and II (PK II) were purified 253- and 13.5-fold, respectively, from an extract of sonically disrupted cells of Legionella micdadei by ion-exchange chromatography on QAE-Sephadex, by histone affinity chromatography, and by HPLC-gel filtration chromatography. Both enzymes catalysed the phosphorylation of calf thymus histones, with a Km of 2.7 mg ml-1 for PK I and 2.9 mg ml-1 for PK II. Histone H2b was the best protein kinase substrate for both PK I and PK II. The pH optima were 6.8 and 7.0 for PK I and PK II respectively. The Km for ATP was 0.29 mM for PK I and 0.33 mM for PK II. PK II activity was stimulated by either cAMP or cGMP, whereas PK I was inhibited by both cyclic nucleotides. The activity of PK I was unaffected by addition of calmodulin, diacylglycerol and mixtures of Ca2+ and acidic phospholipids, but these additions increased PK II activity threefold. The activity of PK II was stimulated by spermine and spermidine, but PK I was inhibited by these compounds. PK I and PK II were both strongly inhibited by heparin.


Non-proximity resonant tunneling in multi-core photonic band gap fibers: An efficient mechanism for engineering highly-selective ultra-narrow band pass splitters.
The objective of the present investigation is to demonstrate the possibility of designing compact ultra-narrow band-pass filters based on the phenomenon of non-proximity resonant tunneling in multi-core photonic band gap fibers (PBGFs). The proposed PBGF consists of three identical air-cores separated by two defected air-holes which act as highly-selective resonators. With a fine adjustment of the design parameters associated with the resonant-air-holes, phase matching at two distinct wavelengths can be achieved, thus enabling very narrow-band resonant directional coupling between the input and the two output cores. The validation of the proposed design is ensured with an accurate PBGF analysis based on finite element modal and beam propagation algorithms. Typical characteristics of the proposed device over a single polarization are: reasonable short coupling length of 2.7 mm, dual bandpass transmission response at wavelengths of 1.339 and 1.357 mum, with corresponding full width at half maximum bandwidths of 1.2 nm and 1.1 nm respectively, and a relatively high transmission of 95% at the exact resonance wavelengths. The proposed ultra-narrow band-pass filter can be employed in various applications such as all-fiber bandpass/bandstop filtering and resonant sensors.


Prevalence of the antiphospholipid syndrome and its effect on survival in 679 Chinese patients with systemic lupus erythematosus: a cohort study.
In this work we evaluate the prevalence of the antiphospholipid syndrome (APS) and its impact on survival in Chinese patients with systemic lupus erythematosus (SLE). We studied a prospective cohort of southern Chinese patients who fulfilled ≥4 American College of Rheumatology criteria for SLE. The cumulative rate of survival over time was calculated by the Kaplan-Meier method. APS was defined by the 2006 updated consensus criteria. We evaluated the prevalence and manifestations of APS, and compared the survival of patients with and without APS. We followed 679 patients with SLE (92% women; age of onset, 32.5 ± 14 yr) for 9.7 ± 7.3 years. Sixty-eight (10%) patients died and 33 (4.9%) patients were lost to follow-up. Forty-four (6.5%) patients met the criteria for APS, manifested by the following: ischemic stroke (55%), deep venous thrombosis (32%), obstetric morbidity (14%), cardiovascular events (9%), and peripheral vascular disease (9%). Nine (9/44 [20%]) APS patients died, which was more frequent than the non-APS patients (59/635 [9%]; p = 0.02). The cumulative mortality of patients with APS was 4.6% at 5 years, 7.8% at 10 years, and 22.2% at 15 years, which was not significantly higher than that of non-APS patients (5.4% at 5 years, 9.2% at 10 years, and 11.3% at 15 years; p = 0.14). However, if we considered only patients with APS caused by arterial thrombosis, the presence of APS was significantly associated with mortality (hazard ratio, 2.29; 95% confidence interval, 1.13-4.64; p = 0.02). We conclude that the presence of APS increases the mortality risk of Chinese patients with SLE, which is mainly contributed by arterial thrombotic events. 1) APS is infrequent in southern Chinese patients with SLE compared to white patients. 2) Arterial thrombosis is a more common manifestation of APS than venous thrombosis in Chinese SLE patients. 3) APS related to arterial thrombosis is associated with increased mortality in Chinese patients with SLE.


Very small embryonic-like stem cells: characterization, developmental origin, and biological significance.
Bone marrow (BM) was, for many years, primarily envisioned as the "home organ" of hematopoietic stem cells (HSC). Augmenting evidence demonstrates, however, that BM, in addition to HSC, also contains a heterogeneous population of non-HSC. Recently, our group identified in BM and other adult tissues a population of very small embryonic-like stem cells (VSELs), which express several markers characteristic for pluripotent stem cells that are characteristic for epiblast/germ line-derived stem cells. Thus, we hypothesize that VSELs are a population of epiblast-derived cells that are deposited during early gastrulation in developing tissues/organs and play an important role in turnover of tissue-specific/committed stem cells. In this context, VSELs deposited in BM can give rise to long-term repopulating HSC. VSELs could be also mobilized into peripheral blood (PB), and the number of these cells circulating in PB increases during stress and tissue/organ injuries. Finally, we envision that in pathological situations VSELs are involved in development of some malignancies (e.g., teratomas, germinal tumors).


Phenolic contents and antioxidant activities of major Australian red wines throughout the winemaking process.
Three Australian red wine types (Shiraz, Cabernet Sauvignon, and Merlot) were analyzed for antioxidant activity and a range of phenolic component contents using various spectral methods. More than half of the total phenolic compounds were tannins, whereas monomeric anthocyanins and flavonols were present in much lesser amounts (<10%). The evolution of phenolic contents and the respective antioxidant activities in wine samples from all stages of winemaking showed progressive changes toward those of commercial wines. The antioxidant activity of the wines in DPPH and ABTS assays was positively correlated with total phenolic contents and tannins. Comparisons of the three wine varieties based on their individual phenolic component groups and antioxidant activities showed limited differences between the different varieties. However, when all of the variables were combined in a principal component analysis, variety differentiation was observed. The three varieties of red wines all contained similar and high concentrations of antioxidants despite differences in grape variety/maturity and winemaking process, suggesting that related health benefits would accrue from all of the red wines studied.


Physical characteristics and chemical composition of Lesser Rhea (Pterocnemia pennata) eggs from farmed populations.
1. Eggs from 4 farmed populations of Lesser Rhea (Pterocnemia pennata) were studied to determine their physical and chemical characteristics. 2. None of the physical variables (weight of whole egg, yolk, albumen and shell; proportion of yolk based on egg content; proportion of shell based on entire egg weight; volume; density) showed significant differences between populations. 3. Among chemical variables, moisture, both saturated fatty acids (palmitic 16:0 and stearic 18:0), one monounsaturated fatty acid (palmitoleic 16:1), and one polyunsaturated fatty acid (arachidonic 20:4), did not differ between populations, whereas other variables (protein, lipid and ash contents; fatty acids: oleic 18:1, linoleic 18:2, linolenic 18:3; PUFA; PUFA/SFA; cholesterol) differed significantly.


Real-time sensors for indoor air monitoring and challenges ahead in deploying them to urban buildings.
Household air pollution is ranked the 9(th) largest Global Burden of Disease risk (Forouzanfar et al., The Lancet 2015). People, particularly urban dwellers, typically spend over 90% of their daily time indoors, where levels of air pollution often surpass those of outdoor environments. Indoor air quality (IAQ) standards and approaches for assessment and control of indoor air require measurements of pollutant concentrations and thermal comfort using conventional instruments. However, the outcomes of such measurements are usually averages over long integrated time periods, which become available after the exposure has already occurred. Moreover, conventional monitoring is generally incapable of addressing temporal and spatial heterogeneity of indoor air pollution, or providing information on peak exposures that occur when specific indoor sources are in operation. This article provides a review of new air pollution sensing methods to determine IAQ and discusses how real-time sensing could bring a paradigm shift in controlling the concentration of key air pollutants in billions of urban houses worldwide. We also show that besides the opportunities, challenges still remain in terms of maturing technologies, or data mining and their interpretation. Moreover, we discuss further research and essential development needed to close gaps between what is available today and needed tomorrow. In particular, we demonstrate that awareness of IAQ risks and availability of appropriate regulation are lagging behind the technologies.


The accuracy of Japanese claims data in identifying breast cancer cases.
In use of a claims database for a study, an inaccurate diagnosis of breast cancer based on claims data may lead to invalid study results. The aim of this study was to assess the accuracy of definitions for identifying breast cancer cases from the Japanese claims database. The study cohort consisted of women with no prior cancer-related history, from the claims data at a single institution between January 1 and December 31, 2011. We developed 14 definitions for identifying breast cancer based on claims data, using a combination of diagnosis codes and treatment procedure codes. We calculated the sensitivity, specificity, and positive predictive value (PPV) of each definition, compared to cases identified from the standardized hospital-based cancer registry as a standard reference. A total of 50056 women were included in the study cohort from the claims database. We identified 633 breast cancer cases from the cancer registry. Of 14 definitions, 12 exhibited higher sensitivity than 90%, while the others exhibited lower sensitivity than 40%. The specificities of all definitions were high (≥ 99%), and the PPVs were between 65.8 and 90.7%. We selected the most optimal definition obtained from combinations of diagnosis and cancer treatment codes (surgery, chemotherapy, medication, radiation procedure), which had high values for sensitivity (90.4%), specificity (99.8%), and PPV (87.3%). Definitions obtained via combinations of the diagnosis codes and procedure codes could be used to accurately identify breast cancer cases from the claims database. Further studies in a multi-institutional setting are planned to confirm our results.


Isolation and characterization of a new gram-negative, acetone-degrading, nitrate-reducing bacterium from soil, Paracoccus solventivorans sp. nov.
An acetone-degrading, nitrate-reducing, coccoid to rod-shaped bacterium, strain L1, was isolated from soil on the site of a natural gas company. Cells of the logarithmic growth phase reacted gram positive, while those of the stationary growth phase were gram negative. Single organisms were 0.4 to 0.5 by 0.9 to 1.5 microns in size, nonmotile, and non-spore forming and had poly-beta-hydroxybutyrate inclusions. The doubling time of strain L1 on acetone-CO2-nitrate at the optimal pH of 7 to 8 and the optimal temperature of 30 to 37 degrees C was 12 h. More than 0.2% NaCl or 10 mM thiosulfate inhibited growth. For oxygen or nitrate respiration, acetone and a few organic chemicals were utilized as carbon sources whereas many others could not be used (for details, see Results). Bicarbonate (or CO2) was essential for growth on acetone but not for growth on acetoacetate. The growth yields for acetone-CO2 and acetoacetate were 28.3 and 27.3 g/mol, respectively. With acetone as the carbon source, poly-beta-hydroxybutyrate accounted for up to 40% of the cellular dry weight. The DNA of strain L1 had a G + C content of 68.5 mol% (as determined by high-performance liquid chromatography of nucleotides) or 70 mol% (as determined by the TM method). The sequence of the gene coding for the 16S rRNA led to the classification of strain L1 in the paracoccus group of the alpha subclass of the Proteobacteria. The new isolate is named Paracoccus solventivorans sp. nov. DSM 6637.


Effects of aircraft noise exposure on saliva cortisol near airports in France.
Saliva cortisol is a possible marker of noise-induced stress and could then mediate the relation observed between exposure to aircraft or road traffic noise and cardiovascular diseases. However, the association between transportation noise and cortisol levels is still unclear. The objective of the study was to investigate the variability of saliva cortisol concentration as an indicator of disturbed hypothalamus-pituitary-adrenal (HPA) axis regulation in relation to long-term aircraft noise exposure. Saliva samples were taken when awakening and before going to bed for 1244 participants older than 18 years of age. Information about health, socioeconomic and lifestyle factors was also collected by means of a face-to-face questionnaire performed at home by an interviewer. Aircraft noise exposure was assessed for each participant's home address using noise maps. Linear regression models were used to evaluate the effects of aircraft noise exposure on the morning and evening cortisol levels and on the daily variation of cortisol per hour. This study suggests a modification of the cortisol circadian rhythm in relation to aircraft noise exposure. This exposure was associated with a smaller variation of cortisol levels over the day, with unchanged morning cortisol levels, but higher cortisol levels in the evening. These findings provide some support for a psychological stress induced by aircraft noise exposure, resulting in HPA dysregulation and a flattened cortisol rhythm, thus contributing to cardiovascular diseases.


Commentary on "Rapid identification of Streptococcus and Enterococcus species using diffuse reflectance-absorbance Fourier transform infrared spectroscopy and artificial neural networks".
This is an invited review/commentary by the first and last authors of a paper that was the most cited in FEMS Microbiology Letters for 1996, presently showing in excess of 150 citations at Web of Science, and over 200 at Google Scholar. It was the first paper in which diffuse reflectance absorbance FT-IR spectroscopy was used with a supervised learning method in the form of artificial neural networks, and showed that this combination could succeed in discriminating a series of closely related, clinically relevant, Gram-positive bacterial strains.


Measurement of gain tilt and its contribution to composite second-order distortion in the analog-digital transmission systems with Er/Yb fiber amplifiers.
Fiber-optic-based analog or digital community antenna television systems experience composite second-order (CSO) distortion caused by the interaction between the gain tilt of the doped fiber amplifier and the laser chirp due to modulation. The gain tilt for an analog-digital transmission system with a high-power erbium/ytterbium-codoped fiber amplifier has been experimentally measured and its contribution to the CSO distortion of the system is evaluated. The results are in good agreement when compared with the direct measurement of the CSO distortion of the transmission system with and without the amplifier. The dependence of the gain tilt on the modulation frequency and wavelength of the input light is also investigated.


Retention-release characteristics of triclocarban and triclosan in biosolids, soils, and biosolids-amended soils.
Transport models that incorporate retention/release characteristics of organic compounds in soils and sediments typically assume that organic-carbon normalized partition coefficients (K(OC)) apply to all solid matrices and that the partitioning process is completely reversible. Partition coefficients (K(d)) (from which the K(OC) was calculated), and retention/release characteristics of triclocarban (TCC) and triclosan (TCS) in biosolids, soils, and biosolids-amended soils were determined. Four soils of different physicochemical properties amended with biosolids at 10 g/kg, together with unamended soils, and several biosolids were separately spiked with either [(14)C]TCC or [(14)C]TCS for the various determinations. The hysteresis coefficient values of the two compounds were consistently <1 in all three solid matrices, suggesting strong hysteresis. Multiple desorption steps (24 h each) over several days revealed incomplete desorption of the two compounds from all three solid matrices. The K(d) values determined in biosolids (log K(d) 3.34 +/- 0.13 for TCC and 3.76 +/- 0.39 for TCS) were greater than those determined in soils (log K(d) 1.71 +/- 0.09 for TCC and 2.25 +/- 0.26 for TCS) and biosolids-amended soils (log K(d)1.90 +/- 0.16 for TCC and 2.31 +/- 0.19 for TCS), however, the K(OC) values of all three solid matrices were similar (log K(OC) of 3.82 +/- 0.16 for TCC and 4.26 +/- 0.31 for TCS). Thus, it was concluded that a single or a narrow range of K(OC) values for TCC and TCS may be appropriate to describe retention of the compounds in soils and sediments. However, models that assume complete reversibility of the retention/release processes of the compounds in soils and sediments may not adequately describe the retention/release characteristics of the compounds in soils and sediments, especially when the chemicals are biosolids borne.


To mesh or not to mesh: a review of pelvic organ reconstructive surgery.
Pelvic organ prolapse (POP) is a major health issue with a lifetime risk of undergoing at least one surgical intervention estimated at close to 10%. In the 1990s, the risk of reoperation after primary standard vaginal procedure was estimated to be as high as 30% to 50%. In order to reduce the risk of relapse, gynecological surgeons started to use mesh implants in pelvic organ reconstructive surgery with the emergence of new complications. Recent studies have nevertheless shown that the risk of POP recurrence requiring reoperation is lower than previously estimated, being closer to 10% rather than 30%. The development of mesh surgery - actively promoted by the marketing industry - was tremendous during the past decade, and preceded any studies supporting its benefit for our patients. Randomized trials comparing the use of mesh to native tissue repair in POP surgery have now shown better anatomical but similar functional outcomes, and meshes are associated with more complications, in particular for transvaginal mesh implants. POP is not a life-threatening condition, but a functional problem that impairs quality of life for women. The old adage "primum non nocere" is particularly appropriate when dealing with this condition which requires no treatment when asymptomatic. It is currently admitted that a certain degree of POP is physiological with aging when situated above the landmark of the hymen. Treatment should be individualized and the use of mesh needs to be selective and appropriate. Mesh implants are probably an important tool in pelvic reconstructive surgery, but the ideal implant has yet to be found. The indications for its use still require caution and discernment. This review explores the reasons behind the introduction of mesh augmentation in POP surgery, and aims to clarify the risks, benefits, and the recognized indications for its use.


Development and validation of a luminescence-based, medium-throughput assay for drug screening in Schistosoma mansoni.
Schistosomiasis, one of the world's greatest neglected tropical diseases, is responsible for over 280,000 human deaths per annum. Praziquantel, developed in the 1970s, has high efficacy, excellent tolerability, few and transient side effects, simple administration procedures and competitive cost and it is currently the only recommended drug for treatment of human schistosomiasis. The use of a single drug to treat a population of over 200 million infected people appears particularly alarming when considering the threat of drug resistance. Quantitative, objective and validated methods for the screening of compound collections are needed for the discovery of novel anti-schistosomal drugs. The present work describes the development and validation of a luminescence-based, medium-throughput assay for the detection of schistosomula viability through quantitation of ATP, a good indicator of metabolically active cells in culture. This validated method is demonstrated to be fast, highly reliable, sensitive and automation-friendly. The optimized assay was used for the screening of a small compound library on S. mansoni schistosomula, showing that the proposed method is suitable for a medium-throughput semi-automated screening. Interestingly, the pilot screening identified hits previously reported to have some anti-parasitic activity, further supporting the validity of this assay for anthelminthic drug discovery. The developed and validated schistosomula viability luminescence-based assay was shown to be successful and suitable for the identification of novel compounds potentially exploitable in future schistosomiasis therapies.


Effects of mixing between short-chain and branched-chain alcohols in protonated clusters.
The previous analysis of the neat protonated branched-chain alcohol clusters revealed the impact of steric repulsion and dispersion of the bulky alkyl group on the hydrogen-bonded (H-bonded) structures and their temperature-dependence. To further understand the influence of the alkyl groups in H-bonded clusters, we studied the mixing of the two extremes of alcohols, methanol (MeOH) and tert-butyl alcohol (t-BuOH), with an excess proton. Infrared spectroscopy and a structural search of first principles calculations on the size-selected clusters H+(MeOH)m(t-BuOH)t (m + t = 4 and 5) were conducted. Temperature-dependence of the dominant H-bonded structures was explored by the Ar-tagging technique and quantum harmonic superposition approach. By introducing the dispersion-corrected density functional theory methods, it was shown that the effects of dispersion due to the bulky alkyl groups in the mixed clusters cannot be ignored for t≥ 2. The computational results qualitatively depicted the characteristics of the observed IR spectra, but overestimation of the temperature-dependence with dispersion correction was clearly seen due to the unbalanced correction between linear H-bonded structures and compact cyclic ones. These results demonstrate the importance of extensive investigation and benchmarks on different levels of theory, and that a properly sampled structure database is crucial to evaluate theoretical models.