Lindane degradation by Candida VITJzN04, a newly isolated yeast strain from contaminated soil: kinetic study, enzyme analysis and biodegradation pathway.
A new yeast strain was isolated from sugarcane cultivation field which was able to utilize lindane as sole carbon source for growth in mineral medium. The yeast was identified and named as Candida sp. VITJzN04 based on a polyphasic approach using morphological, biochemical and 18S rDNA, D1/D2 and ITS sequence analysis. The isolated yeast strain efficiently degraded 600 mg L⁻¹ of lindane within 6 days in mineral medium under the optimal conditions (pH 7; temperature 30 °C and inoculum dosage 0.06 g L⁻¹) with the least half-life of 1.17 days and degradation constant of 0.588 per day. Lindane degradation was tested with various kinetic models and results revealed that the reaction could be described best by first-order and pseudo first-order models. In addition, involvement of the enzymes viz. dechlorinase, dehalogenase, dichlorohydroquinone reductive dechlorinase, lignin peroxidase and manganese peroxidase was noted during lindane degradation. Addition of H2O2 in the mineral medium showed 32 % enhancement of lindane degradation within 3 days. Based on the metabolites identified by GC-MS and FTIR analysis, sequential process of lindane degradation by Candida VITJzN04 was proposed. To the best of our knowledge, this is the first report of isolation and characterization of lindane-degrading Candida sp. and elucidation of enzyme systems during the degradation process.


Apolipoprotein E polymorphism and coronary artery disease.
Lipid status and apolipoprotein E phenotypes were tested in 1000 patients who underwent coronary angiography. The same number of factory employees was chosen as a control group. We distinguished between six different apolipoprotein E phenotypes and determined their frequencies in all groups. For the three homozygous phenotypes E3/3, E4/4, and E2/2, the percentage distribution in the group of factory employees was 62.7%, 2.3%, and 0.8%, respectively; for the three heterozygous phenotypes E4/3, E3/2, and E4/2, we determined frequencies of 20.3%, 11.0%, and 3.0%, respectively. In the group of patients with and without signs of coronary atherosclerosis, we observed almost the same frequencies except that heterozygotes (E3/2) occurred significantly more frequently in the group of coronary angiography patients unaffected by coronary sclerosis. Cholesterol and triglyceride values were significantly elevated in patients with coronary artery disease, whereas high density lipoprotein cholesterol levels were not significantly different. The data further suggest that apolipoprotein E2/2 homozygosity, despite the presence of beta-very low density lipoproteins in the plasma of these patients, cannot be considered a biochemical indicator of an increased risk of coronary atherosclerosis. On the other hand, apolipoprotein E3/2 heterozygosity may have a protective effect on the development of early atherosclerosis.


(In)activity-related neuroplasticity in brainstem control of sympathetic outflow: unraveling underlying molecular, cellular, and anatomical mechanisms.
More people die as a result of physical inactivity than any other preventable risk factor including smoking, high cholesterol, and obesity. Cardiovascular disease, the number one cause of death in the United States, tops the list of inactivity-related diseases. Nevertheless, the vast majority of Americans continue to make lifestyle choices that are creating a rapidly growing burden of epidemic size and impact on the United States healthcare system. It is imperative that we improve our understanding of the mechanisms by which physical inactivity increases the incidence of cardiovascular disease and how exercise can prevent or rescue the inactivity phenotype. The current review summarizes research on changes in the brain that contribute to inactivity-related cardiovascular disease. Specifically, we focus on changes in the rostral ventrolateral medulla (RVLM), a critical brain region for basal and reflex control of sympathetic activity. The RVLM is implicated in elevated sympathetic outflow associated with several cardiovascular diseases including hypertension and heart failure. We hypothesize that changes in the RVLM contribute to chronic cardiovascular disease related to physical inactivity. Data obtained from our translational rodent models of chronic, voluntary exercise and inactivity suggest that functional, anatomical, and molecular neuroplasticity enhances glutamatergic neurotransmission in the RVLM of sedentary animals. Collectively, the evidence presented here suggests that changes in the RVLM resulting from sedentary conditions are deleterious and contribute to cardiovascular diseases that have an increased prevalence in sedentary individuals. The mechanisms by which these changes occur over time and their impact are important areas for future study.


Evolution of nanostructured single-phase CoSb3 thin films by low-energy ion beam induced mixing and their thermoelectric performance.
Skutterudites are emerging as potential candidates that show high efficiency and thus provide an ideal platform for research. The properties of nanostructured films of skutterudites are different from those of the corresponding bulk. The present study reports the evolution of nanostructured single-phase CoSb3 fabricated by using low-energy ion irradiation of Co/Sb bilayer films and subsequent annealing at an optimized temperature and their Seebeck coefficients (S). The effects of ion beam parameters with annealing on the phase evolution and nanostructure modifications were studied. An increase in Xe+ ion fluence resulted in complete mixing of Co/Sb on postannealing forming flower-like nanostructures of single phase CoSb3. The temperature-dependent electrical resistivity (ρ) increases with the ion fluence because of defect creation which further increases on postannealing due to surface nanostructuring. The S of these films of CoSb3 is found to be higher and this is attributed to the formation of a uniform layer of nanostructured CoSb3 alloy thin film. The S and Hall coefficients of all these films are negative implying that they are n-type semiconductors.


Evaluation of α-pyrones and pyrimidones as photoaffinity probes for affinity-based protein profiling.
α-Pyrones and pyrimidones are common structural motifs in natural products and bioactive compounds. They also display photochemistry that generates high-energy intermediates that may be capable of protein reactivity. A library of pyrones and pyrimidones was synthesized, and their potential to act as photoaffinity probes for nondirected affinity-based protein profiling in several crude cell lysates was evaluated. Further "proof-of-principle" experiments demonstrate that a pyrimidone tag on an appropriate scaffold is equally capable of proteome labeling as a benzophenone.


Neurochemical and electrophysiological studies on the functional significance of burst firing in serotonergic neurons.
We have previously described a population of 5-hydroxytryptamine neurons which repetitively fires bursts of usually two (but occasionally three or four) action potentials, with a short (<20 ms) interspike interval within a regular low-frequency firing pattern. Here we used a paradigm of electrical stimulation comprising twin pulses (with 7- or 10-ms inter-pulse intervals) to mimic this burst firing pattern, and compared the effects of single- and twin-pulse electrical stimulations in models of pre- and postsynaptic 5-hydroxytryptamine function. Firstly, we measured the effect of direct electrical stimulation (2 Hz for 2 min) of rat brain slices on efflux of preloaded [3H]5-hydroxytryptamine. In this in vitro model, twin-pulse stimulation increased the efflux of tritium by about twice as much as did single-pulse stimulation. This effect was evident in the medial prefrontal cortex (area under the curve: 2. 59+/-0.34 vs 1.28+/-0.22% relative fractional release), as well as in the caudate-putamen (3.93+/-0.65 vs 2.17+/-0.51%) and midbrain raphe nuclei (5.42+/-1.05 vs 2.51+/-0.75%). Secondly, we used in vivo microdialysis to monitor changes in endogenous extracellular 5-hydroxytryptamine in rat medial prefrontal cortex in response to electrical stimulation (3 Hz for 10 min) of the dorsal raphe nucleus. In this model, twin-pulse stimulation of the dorsal raphe nucleus increased 5-hydroxytryptamine by approximately twice as much as did single-pulse stimulation at the same frequency (area under the curve: 50.4+/-9.0 vs 24.2+/-4.4 fmol). Finally, we used in vivo extracellular recording to follow the response of postsynaptic neurons in the rat medial prefrontal cortex to 5-hydroxytryptamine released by dorsal raphe stimulation. Electrical stimulation of the dorsal raphe nucleus (1 Hz) induced a clear-cut poststimulus inhibition in the majority of cortical neurons tested. In these experiments, the duration of poststimulus inhibition following twin-pulse stimulation was markedly longer than that induced by single-pulse stimulation (200+/-21 vs 77+/-18.5 ms). Taken together, the present in vitro and in vivo data suggest that in 5-hydroxytryptamine neurons, short bursts of action potentials will propagate along the axon to the nerve terminal and will enhance both the release of 5-hydroxytryptamine and its postsynaptic effect.


Edema and intrapancreatic trypsinogen activation precede glutathione depletion during caerulein pancreatitis.
Acute pancreatitis is characterized by hyperamylasemia, pancreatic edema, and the presence of activated digestive enzymes within the pancreas. The secretagogue-induced model of acute pancreatitis is also characterized by pancreatic acinar cell vacuolation, subcellular redistribution of lysosomal hydrolases, and a fall in pancreatic glutathione levels. We have performed time-dependence studies to determine the sequence with which these phenomena appear and to establish their cause-and-effect relationship. Evidence of lysosomal enzyme redistribution and trypsinogen activation within the pancreas could be detected within 10-15 min of the onset of supramaximal secretagogue stimulation, while hyperamylasemia (30 min), pancreatic edema (60 min), and acinar cell vacuolation (60 min) occurred at later times. Pancreatic glutathione levels were either unchanged (15 and 30 min) or elevated (60 min) during the early times of supramaximal stimulation and were only noted to be decreased at a later time. These results support the conclusion that intrapancreatic digestive enzyme activation, possibly occurring by a mechanism involving lysosomal hydrolase redistribution, is an early and likely a critical event in the evolution of secretagogue-induced pancreatitis but that glutathione depletion is neither early nor critical to the evolution of this model of pancreatitis.


Comparison of Intralesional Triamcinolone Acetonide, 5-Fluorouracil, and Their Combination in Treatment of Keloids.
Despite the myriad options available, there is no universally accepted treatment for keloids. This study has compared intralesional triamcinolone acetonide, 5-fluorouracil, and their combination in treatment of keloids. In this randomized parallel group study, 60 patients were enrolled and randomly allocated to three groups. Patients received intralesional injections of triamcinolone acetonide (TAC) in Group TAC, 5-fluorouracil (5FU) in Group 5FU and a combination in Group T+F every 3 weeks till 24 weeks or till the keloid resolved. There was a reduction in all parameters at every successive assessment in all three groups. Improvement in terms of height, vascularity and pliability was fastest with 5FU, TAC and T+F group, respectively, which was statistically significant. Decrease in pigmentation was significantly faster with T+F. Reduction in pruritus, however, was significantly faster with 5FU than the other groups, but the difference in reduction of pain among the three groups was not significant. Telangiectasias and skin atrophy were seen most commonly in TAC group, while skin ulceration was a common problem in 5FU group. TAC, 5FU and their combination are all effective in keloid scars. A combination of TAC+5FU seems to offer the balanced benefit of faster and more efficacious response with lesser adverse effects when compared to individual drugs.


Liver needle biopsy in Iraninan pediatric patients: diagnostic significance and pattern of liver diseases.
We aimed at determining the pattern of liver disease in the Iranian children referred to the Medical Center of Children affiliated with the Tehran University of Medical Sciences. In a cross-sectional study conducted over 2 years, 425 liver needle biopsies were sent to the pathology laboratory of our center. Slides were prepared from paraffin-embedded blocks, stained by routine H & E and special stains and were then reviewed. The frequency of each disorder, separately and in combination with the age group or gender of the patients was calculated and compared with other similar studies. The male to female ratio was 1.42:1. The age range was between 1 month and 18 years old and 41.4% were less than 2 years old. The most common histological diagnosis was iron overload due to major thalassemia (17.5%) followed by biliary atresia (9.7%), no significant pathologic change (8.7%), neonatal hepatitis (8.7%), chronic hepatitis (8.5%), cirrhosis (6.5%), metabolic disease (5.5%) and progressive familial intrahepatic cholestasis (5%). RESULTS of the hemosiderosis grading in patients with thalassemia revealed no or minimal, mild, medium, or marked increase in 10%, 27.1%, 10%, 21.4% and 31.5% of the cases, respectively and the degree of iron deposition rose in parallel with age and also the stage of fibrosis (p< 0.05). A liver biopsy is a useful and practical tool for the appropriate diagnosis of pediatric liver diseases. Also, we found that in non thalassemic children, biliary atresia, chronic hepatitis and neonatal hepatitis, in the stated order, are the most prevalent histologic diagnoses in Iranian pediatrics.


Rayleigh-Brillouin scattering to determine one-dimensional temperature and number density profiles of a gas flow field.
Rayleigh-Brillouin spectra for heated nitrogen gas were measured by imaging the output of a Fabry-Perot interferometer onto a CCD array. The spectra were compared with the theoretical 6-moment model of Rayleigh-Brillouin scattering convolved with the Fabry-Perot instrument function. Estimates of the temperature and a dimensionless parameter proportional to the number density of the gas as functions of position in the laser beam were calculated by least-squares deviation fits between theory and experiment.


Haematological status of middle- and long-distance runners.
1. Haematological investigation and blood volume measurements were carried out on forty male middle and long distance runners and twelve non-athletes. 2. The distribution of haemoglobin concentration, packed cell volume, erythrocyte count, total ironbinding capacity, serum and erythrocyte folate and serum vitamin B12 concentrations were essentially the same in atheletes and non-athletes. The mean serum iron concentration was higher in non-athletes than in athletes. There was no difference in the above measurements between athletes taking iron and/or folate and athletes not taking these supplements. 3. Blood volume and total body haemoglogin were on average 20% higher in the atheletes than in the non-athletes. 4. There was no correlation between haemoglobin concentration and blood volume in athletes. The evidence of this study suggests that haemoglobin concentration and blood volume are independently controlled. 5. 2,3-Diphosphoglycerate concentration in the erythrocytes was higher in the athletes than in the non-athletes; the mean values were 15-9 and 14-2 mumol/g of haemoglobin respectively.


Computational study on hydroxybenzotriazoles as reagents for ester hydrolysis.
1-Hydroxybenzotriazole (1) and several of its derivatives (2-5) demonstrate potent esterolytic activity toward activated esters such as p-nitrophenyl diphenyl phosphate (PNPDPP) and p-nitrophenyl hexanoate (PNPH) in cationic micelles at pH 8.2 and 25 degrees C. The deprotonated anionic forms of such reagents act as reactive species in the hydrolysis of ester. To rationalize the origin of their nucleophilic character, a detailed ab initio/DFT computational study has been performed on 1-5 along with additional hydroxybenzotriazole derivatives (6-13). The geometries of 1-hydroxybenzotriazoles (1-13) and their corresponding bases are discussed in detail. All calculations were carried out using different methods, i.e., restricted Hartree-Fock (RHF) and hybrid ab initio/DFT (B3LYP) using 6-31G and 6-31+G basis sets. Free energy of protonation ("fep") of the 1-hydroxybenzotriazoles (1-13), free energy of solvation DeltaG(aq), and the corresponding pK(a) values have been calculated. Solvation-free energies were calculated using density functional theory and the polarizable continuum model. In addition, to examine the reliability of calculated fep, benzaldehyde oxime (14) and 2-methyl propionaldehyde oxime (15) have been computed as reference systems using different methods and basis sets, the experimental feps of which are known. Our experimental finding shows that the compound 4 is the most effective catalyst for the hydrolytic cleavages of PNPDPP and PNPH. This has been predicted from our calculated fep, pK(a), and natural charge analysis results as well. In general, the introduction of electron-withdrawing substituents on 1-hydroxybenzotriazoles facilitates the lowering of pK(a) and fep. As the pK(a) values are lowered, a greater percentage of such hydroxybenzotriazoles remain in their deprotonated, anionic forms at pH 8.2. Since the anionic forms are nucleophilic, pK(a) lowering should enhance their ester cleaving capacity. However, such substitution also decreases the charge density on the catalytically active oxido atom (O(7)). Taking these two factors together, the derivatives are only modestly better nucleophiles in comparison to the parent 1-hydroxybenzotriazole. Interestingly, the introduction of electron-donating groups does not significantly enhance the charge accumulation on the oxido atom (O(7)) of 1-hydroxybenzotriazoles.


Nutritional status: importance in predicting wound-healing after amputation.
Protein-calorie malnutrition, or both, affects the morbidity and mortality of patients undergoing operations. Laboratory assessments of nutritional status consisting of evaluations of serum albumin levels and total lymphocyte counts are valid tests of a patient's nutritional status. In this study we examined the influence of preoperative nutritional status on morbidity in twenty-three diabetic patients who underwent a Syme amputation. All of the patients met Wagner's criteria for a Syme-level amputation, but in only 43 per cent (ten patients) did the amputation heal at this level, which was chosen by Wagner's criteria alone. Of the seven patients who, in addition to meeting Wagner's criteria, had a serum albumin level of at least 3.5 grams per deciliter and a total lymphocyte count of at least 1500 cubic millimeters, in six (86 per cent) the amputation healed at the Syme level. In contrast, the Syme-level amputation healed in only two of the eleven patients who met the criteria of Wagner but who had a serum albumin level of less than 3.5 grams per deciliter and a total lymphocyte count of less than 1500 cubic millimeters.


"Faith, ethics and the Holocaust": the Holocaust survivor's faith and religious behavior and some implications for treatment.
The survivor's religious experiences, both during and after the Holocaust have been underexplored in the psychological literature. This essay concerns itself with the survivor's religious realm as it affects the psychotherapeutic process. it also provides a conceptual framework for helping the therapist understand the significance of religion in the survivor's life. When a survivor's religious framework, his symbolic world, can no longer "make sense" of his life, when he cannot recognize his own identity, his psychological world begins to crumble: Clinical symptoms are thus an attempt to preserve self-cohesion, self-continuity and self-esteem amidst a tottering symbolic world. Treatment should focus on helping the survivor rebuild or create new viable human meaning formations that support self-affirmation.


The resurrection of sacrospinous fixation: unilateral apical sling hysteropexy.
The apical compartment is a keystone in POP treatment. Sacrospinous fixation, suggested half a century ago, today is still one of the most popular and efficient methods of colpo-hysteropexy. However, it has specific side effects: chronic pain syndrome, dyspareunia and а high rate of cystocele de novo. We aimed to evaluate the efficacy and safety of unilateral sacrospinous hysteropexy with a synthetic apical sling combined with anterior subfascial colporrhaphy. Following the suggested technique, 174 women with anterior-apical prolapse underwent surgery. The follow-up period took 12 months. Pre- and postoperative examination included: urogynecological examination (POP-Q), uroflowmetry, ultrasound of the bladder and filling in of validated questionnaires (PFDI-20, PISQ-12). The mean surgery time was 26 ± 7.84 min. No cases of damage of the bladder or rectum or of intraoperative clinically significant bleeding were noted. At the 12-month follow-up, the recurrence rate in the apical compartment was 0.7% (1/147) and in the anterior compartment 7.4% (11/147). The efficacy of the surgery reached 96.5%. During 12 months of follow-up, no cases of mesh exposure or chronic pelvic pain syndrome were detected. The incidence of dyspareunia de novo was observed in just one patient. A unilateral sacrospinous fixation with a synthetic mesh (apical sling) combined with anterior subfascial colporrhaphy enhances the anatomical efficacy of surgery. It also helps to avoid specific side effects of traditional sacrospinous fixation.


Prescription opioids. II. Metabolism and excretion patterns of hydrocodone in urine following controlled single-dose administration.
Hydrocodone (HC) is a highly misused prescription drugs in the USA. Interpretation of urine tests for HC is complicated by its metabolism to two metabolites, hydromorphone (HM) and dihydrocodeine (DHC), which are also available commercially and are misused. Currently, there is interest in including HC and HM in the federal workplace drug-testing programs. This study characterized the disposition of HC in human urine. Twelve healthy, drug-free, adults were administered a single, oral 20 mg immediate-release dose of HC in a controlled clinical setting. Urine specimens were collected at timed intervals for up to 52 h and analyzed by LC-MS-MS (limit of quantitation = 50 ng/mL) with and without enzymatic hydrolysis. All specimens were also analyzed for creatinine and specific gravity (SG). HC and norhydrocodone (NHC) appeared within 2 h followed by HM and DHC. Peak concentrations of HC and metabolites occurred at 3-9 h. Peak hydrolyzed concentrations were in the order: NHC > HC > HM > DHC. Only HM was excreted extensively as a conjugated metabolite. At a cutoff concentration of 50 ng/mL, detection times were ∼28 h for HC, 40 h for NHC, 26 h for HM and 16 h for DHC. Some specimens did not contain HC, but most contained NHC, thereby facilitating interpretation that HC was the administered drug. Creatinine and SG measures were highly correlated. Creatinine corrections of HC urinary data had variable effects of lowering or raising concentrations. These data suggest that drug-testing requirements for HC should include a hydrolysis step and a test for HM.


Distinct signaling profiles of beta1 and beta2 adrenergic receptor ligands toward adenylyl cyclase and mitogen-activated protein kinase reveals the pluridimensionality of efficacy.
Drug efficacy is typically considered an intrinsic property of a ligand/receptor couple. However, recent observations suggest that efficacy may also be influenced by the signaling effectors engaged by a unique receptor. To directly and systematically test this possibility, we assessed the ability of a panel of beta-adrenergic ligands to modulate the activity of two effector systems, the adenylyl cyclase (AC) and the mitogen-activated protein kinase (MAPK), via beta(1) and beta(2) adrenergic receptors. Although some compounds displayed similar efficacies toward the two pathways, others showed complex efficacy profiles. For example, compounds that are inverse agonists for the AC activity were found to be either agonists, neutral antagonists, or inverse agonists for the MAPK pathway. Likewise, agonists for the AC were either agonists or neutral antagonists for MAPK. Given this complexity, we propose a Cartesian representation of the efficacies that takes into account the activities of the different effectors that can be engaged by a given receptor. In addition, compounds considered as nonselective for beta(1) and beta(2) adrenergic receptors, based on their binding affinities, showed distinct relative efficacy profiles toward AC and MAPK, adding a new dimension to the concept of ligand selectivity. Taken together, the results suggest that binding of different ligands promote distinct conformational changes leading to specific signaling outcomes. Our data therefore clearly illustrate that efficacy is a pluridimensional parameter that is not an intrinsic characteristic of a ligand/receptor couple. This should have important implications for the future design of screening assays used in drug discovery campaigns.


Cortical rotation of the Xenopus egg: consequences for the anteroposterior pattern of embryonic dorsal development.
We first review cortical-cytoplasmic rotation, a microtubule-mediated process by which the Xenopus egg, like other amphibian eggs, transforms its polarized cylindrical symmetry into bilateral symmetry within the first cell cycle after fertilization. This transformation, the earliest of many steps leading to dorsal development, involves the displacement of the egg's cortex relative to its cytoplasmic core by 30 degrees in an animal-vegetal direction. As rotation is progressively reduced by microtubule-depolymerizing agents, embryos develop with body axes progressively deleted for dorsal structures at the anterior end. With no rotation, ventralized embryos are formed. In an effort to comprehend this progressive effect on embryonic organization, we go on to review subsequent developmental process depending on rotation, and we propose, with evidence, that reduced rotation leads to a reduced number of vegetal dorsalizing cells, which induce during the blastula stage a Spemann organizer region of smaller than normal size. The reduced organizer then promotes a reduced amount of cell rearrangement (morphogenesis) at gastrulation. Reduced morphogenesis seems the proximate cause of the incompleteness of axial pattern, as shown further by the fact that embryos that are normal until the gastrula stage, if exposed to inhibitors of morphogenesis, develop body axes that are progressively less complete in their anterior dorsal organization the earlier their gastrulation had been blocked. We discuss why axial pattern might depend systematically on morphogenesis.


Developing an educational intervention on dementia diagnosis and management in primary care for the EVIDEM-ED trial.
Dementia syndromes are under-diagnosed and under-treated in primary care. Earlier recognition of and response to dementia syndrome is likely to enhance the quality of life of people with dementia, but general practitioners consistently report limited skills and confidence in diagnosis and management of this condition. Changing clinical practice is difficult, and the challenge for those seeking change it is to find ways of working with the grain of professional knowledge and practice. Assessment of educational needs in a practice has the potential to accommodate variations in individual understanding and competence, learning preferences and skill mix. Educational prescriptions identify questions that need to be answered in order to address a clinical problem. This paper reports the development of an educational needs assessment tool to guide tailored educational interventions designed to enhance early diagnosis and management of dementia in primary care, in the Evidence Based Interventions in Dementia in the Community - Early Diagnosis trial. A multidisciplinary team, including a lay researcher, used an iterative technology development approach to create an educational needs assessment tool, from which educational prescriptions could be written. Workplace learning was tailored to each practice using the educational prescription, and the method was field-tested in five pilot practices. The educational prescriptions appeared acceptable and useful in volunteer practices. The time commitment (no more than four hours, spread out at the practice's discretion) appeared manageable. The pilot group of practices prioritised diagnosis, assessment of carers' needs, quality markers for dementia care in general practice, and the implications of the Mental Capacity Act (2005) for their clinical practice. The content of the educational needs assessment tool seemed to be comprehensive, in that no new topics were identified by practices in the field trial. The educational needs assessment tool took into account practitioners' knowledge of the local health and social care systems, reflected the complexity of the diagnostic and care processes for people with dementia, and acknowledged the complexity of the disease process itself.


Body girth as an alternative to body mass for establishing condition indexes in field studies: a validation in the king penguin.
Body mass and body condition are often tightly linked to animal health and fitness in the wild and thus are key measures for ecophysiologists and behavioral ecologists. In some animals, such as large seabird species, obtaining indexes of structural size is relatively easy, whereas measuring body mass under specific field circumstances may be more of a challenge. Here, we suggest an alternative, easily measurable, and reliable surrogate of body mass in field studies, that is, body girth. Using 234 free-living king penguins (Aptenodytes patagonicus) at various stages of molt and breeding, we measured body girth under the flippers, body mass, and bill and flipper length. We found that body girth was strongly and positively related to body mass in both molting (R(2) = 0.91) and breeding (R(2) = 0.73) birds, with the mean error around our predictions being 6.4%. Body girth appeared to be a reliable proxy measure of body mass because the relationship did not vary according to year and experimenter, bird sex, or stage within breeding groups. Body girth was, however, a weak proxy of body mass in birds at the end of molt, probably because most of those birds had reached a critical depletion of energy stores. Body condition indexes established from ordinary least squares regressions of either body girth or body mass on structural size were highly correlated (r(s) = 0.91), suggesting that body girth was as good as body mass in establishing body condition indexes in king penguins. Body girth may prove a useful proxy to body mass for estimating body condition in field investigations and could likely provide similar information in other penguins and large animals that may be complicated to weigh in the wild.


The herpes simplex virus immediate-early protein ICP0 affects transcription from the viral genome and infected-cell survival in the absence of ICP4 and ICP27.
ICP4, ICP0, and ICP27 are the immediate-early (IE) regulatory proteins of herpes simplex virus that have the greatest effect on viral gene expression and growth. Comparative analysis of viral mutants defective in various subsets of these IE genes should help elucidate how these proteins affect cellular and viral processes. This study focuses on the mutant d97, which is defective for the genes encoding ICP4, ICP0, and ICP27 and expresses the bacterial beta-galactosidase (beta-gal) gene from the ICP0 promoter. Together with the d92 virus (ICP4- ICP27-) and the ICP0-complementing cell line L7, d97 provided a unique opportunity to evaluate ICP0 function in the absence of the regulatory activities specified by ICP4 and ICP27. The pattern of protein synthesis in d97-infected cells was unique relative to other IE gene mutants in that it was similar to that seen in the absence of prior viral protein synthesis, possibly approximating the effect of cellular factors and virion components alone. Inactivation of ICP0 in the absence of ICP4 produced a significant decrease in the levels of the early mRNAs ICP6 and thymidine kinase (tk). There was also a marginal reduction in the levels of the IE ICP22 mRNA, and this was most notable at low multiplicity of infection (MOI). In d97-infected L7 cells, the levels of the viral mRNAs were mostly restored to those observed in infections with d92. Nuclear runoff transcription analysis demonstrated that the presence of ICP0 resulted in an increase in the transcription rates of the analyzed genes. The transcription rates of the early genes were dramatically reduced in the absence of ICP0. At low MOI, the transcription rates of ICP6 and tk were comparable to the rate of transcription of a cellular gene. Relevant to the potential use of d97 as a transfer vector, it was also determined that the absence of ICP0 reduced the cellular toxicity of the virus compared to that of d92. The beta-gal transgene expressed from an IE promoter was detected for up to 14 days postinfection; however, the level of beta-gal expression declined dramatically after 1 day postinfection. In the presence of ICP0, the level of expression of beta-gal was increased; however the infected monolayer was destroyed by 3 days postinfection. Therefore, deletion of ICP0 in the absence of ICP4 and ICP27 reduces toxicity and lowers the level of expression of genes from the viral genome.


MAPK-interacting kinase 2 (MNK2) regulates adipocyte metabolism independently of its catalytic activity.
The mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs) are serine/threonine protein kinases that are activated by the ERK1/2 (extracellular regulated kinase) and p38α/β MAPK pathways. The MNKs have previously been implicated in metabolic disease and shown to mediate diet-induced obesity. In particular, knockout of MNK2 in mice protects from the weight gain induced by a high-fat diet. These and other data suggest that MNK2 regulates the expansion of adipose tissue (AT), a stable, long-term energy reserve that plays an important role in regulating whole-body energy homeostasis. Using the well-established mouse 3T3-L1 in vitro model of adipogenesis, the role of the MNKs in adipocyte differentiation and lipid storage was investigated. Inhibition of MNK activity using specific inhibitors failed to impair adipogenesis or lipid accumulation, suggesting that MNK activity is not required for adipocyte differentiation and does not regulate lipid storage. However, small-interfering RNA (siRNA) knock-down of MNK2 did reduce lipid accumulation and regulated the levels of two major lipogenic transcriptional regulators, ChREBP (carbohydrate response element-binding protein) and LPIN1 (Lipin-1). These factors are responsible for controlling the expression of genes for proteins involved in de novo lipogenesis and triglyceride synthesis. The knock-down of MNK2 also increased the expression of hormone-sensitive lipase which catalyses the breakdown of triglyceride. These findings identify MNK2 as a regulator of adipocyte metabolism, independently of its catalytic activity, and reveal some of the mechanisms by which MNK2 drives AT expansion. The development of an MNK2-targeted therapy may, therefore, be a useful intervention for reducing weight caused by excessive nutrient intake.


Subspecialty training: is it financially worthwhile?
To determine the financial return of additional training in a cognitive-oriented medical subspecialty (rheumatology) and in a procedure-oriented medical subspecialty (gastroenterology) relative to general internal medicine. Analysis of existing data to compare lifetime discounted earnings of physicians in different medical specialties. General internists, gastroenterologists, and rheumatologists were surveyed. Using data from surveys conducted by Medical Economics and the American College of Rheumatology, we constructed lifetime earnings streams that allowed the calculation of the net present values of discounted lifetime earnings in general internal medicine, gastroenterology, and rheumatology. Net present values of lifetime earnings were calculated for each group at two discount rates. Sensitivity analyses were done to estimate how changes in relative income would affect calculations of the net present values. The average net incomes before taxes for general internists, gastroenterologists, and rheumatologists in 1988 were $115,825, $201,875, and $118,056, respectively. At 5% and 10% discount rates, the net present values of the estimated career earnings stream for additional training in gastroenterology relative to general internal medicine were + $1,101,863 and + $512,952, respectively; for additional training in rheumatology relative to general internal medicine, the respective values were - $84,748 and - $92,467. If the incomes of general internists were decreased by 3% and the incomes of gastroenterologists were decreased by 25% to reflect the effect of potential changes due to the resource-based relative value scale (RBRVS), or if gastroenterology training were increased to 3 years and rheumatology fellowship stipends were increased by 30%, large differences would still exist between the groups. Gastroenterologists have an extremely large return on their additional investment in training, but rheumatologists have a negative return. When considered exclusively as a financial decision, fellowship training in a cognitive-oriented medical subspecialty such as rheumatology is a poor investment. Even major changes in reimbursement policies will not affect the relative pecuniary attractiveness of procedure-oriented medical subspecialties.


A rodent version of the Iowa Gambling Task: 7 years of progress.
In the Iowa Gambling Task (IGT) subjects need to find a way to earn money in a context of variable wins and losses, conflicting short-term and long-term pay-off, and uncertainty of outcomes. In 2006, we published the first rodent version of the IGT (r-IGT; Behavior Research Methods 38, 470-478). Here, we discuss emerging ideas on the involvement of different prefrontal-striatal networks in task-progression in the r-IGT, as revealed by our studies thus far. The emotional system, encompassing, among others, the orbitofrontal cortex, infralimbic cortex and nucleus accumbens (shell and core area), may be involved in assessing and anticipating the value of different options in the early stages of the task, i.e., as animals explore and learn task contingencies. The cognitive control system, encompassing, among others, the prelimbic cortex and dorsomedial striatum, may be involved in instrumental goal-directed behavior in later stages of the task, i.e., as behavior toward long-term options is strengthened (reinforced) and behavior toward long-term poor options is weakened (punished). In addition, we suggest two directions for future research: (1) the role of the internal state of the subject in decision-making, and (2) studying differences in task-related costs. Overall, our studies have contributed to understanding the interaction between the emotional system and cognitive control system as crucial to navigating human and non-human animals alike through a world of variable wins and losses, conflicting short-term and long-term pay-offs, and uncertainty of outcomes.


Enhanced spontaneous emission inside hyperbolic metamaterials.
Hyperbolic metamaterials can enhance spontaneous emission, but the radiation-matter coupling is not optimized if the light source is placed outside such media. We demonstrate a 3-fold improvement of the Purcell factor over its outer value and a significant enlargement in bandwidth by including the emitter within a Si/Ag periodic multilayer metamaterial. To extract the plasmonic modes of the structure into the far field we implement two types of 1D grating with triangular and rectangular profile, obtaining a 10-fold radiative enhancement at visible frequencies.


The effect of hospital care on early survival after penetrating trauma.
The effectiveness of emergency medical interventions can be best evaluated using time-to-event statistical methods with time-varying covariates (TVC), but this approach is complicated by uncertainty about the actual times of death. We therefore sought to evaluate the effect of hospital intervention on mortality after penetrating trauma using a method that allowed for interval censoring of the precise times of death. Data on persons with penetrating trauma due to interpersonal assault were combined from the 2008 to 2010 National Trauma Data Bank (NTDB) and the 2004 to 2010 National Violent Death Reporting System (NVDRS). Cox and Weibull proportional hazards models for survival time (t SURV) were estimated, with TVC assumed to have constant effects for specified time intervals following hospital arrival. The Weibull model was repeated with t SURV interval-censored to reflect uncertainty about the precise times of death, using an imputation method to accommodate interval censoring along with TVC. All models showed that mortality was increased by older age, female sex, firearm mechanism, and injuries involving the head/neck or trunk. Uncensored models showed a paradoxical increase in mortality associated with the first hour in a hospital. The interval-censored model showed that mortality was markedly reduced after admission to a hospital, with a hazard ratio (HR) of 0.68 (95% CI 0.63, 0.73) during the first 30 min declining to a HR of 0.01 after 120 min. Admission to a verified level I trauma center (compared to other hospitals in the NTDB) was associated with a further reduction in mortality, with a HR of 0.93 (95% CI 0.82, 0.97). Time-to-event models with TVC and interval censoring can be used to estimate the effect of hospital care on early mortality after penetrating trauma or other acute medical conditions and could potentially be used for interhospital comparisons.


Caring for the older person with cognitive impairment in hospital: Qualitative analysis of nursing personnel reflections on fall events.
To explore nurse and nursing assistant reflections on the care of older patients with cognitive impairment who have experienced a fall. While there are evidence-based clinical guidelines for the prevention and management of falls and for the care of older people with cognitive impairment, the falls rates for older people with cognitive impairment are three times as high as those without. Critical incident technique. Eleven registered and two enrolled nurses and four assistants in nursing working in one subacute and two acute wards within two hospitals of a tertiary level health service in south-east Queensland. Individual semistructured interviews focused on two past events when a patient with cognitive impairment had fallen in hospital: one when there was minimal harm and the second when there was significant harm. Thematic analysis was undertaken. The COREQ checklist was followed. Three themes emerged from 23 reflective accounts of fall events: "direct observation is confounded by multiple observers" and "knowing the person has cognitive impairment is not enough," and "want to rely on the guideline but unsure how to enact it." While participants were aware of the falls prevention policy and techniques available to prevent falls, the implementation of these was challenging due to the complexity of care required by the older person with cognitive impairment. Falls prevention for older people with cognitive impairment is complex and belies the simple application of policy. To reduce falls, nurses can involve the family to support "knowing the patient" to enable prediction of impulsive actions; shift the focus of in-service from lectures to specific case presentations, with collaborative analysis on person-focused strategies to prevent falls in older people with cognitive impairment; and reconsider the sitter role from simple observer to assistant, focused on ambulation and supporting independence in activities of daily living.


A lateral flow paper microarray for rapid allergy point of care diagnostics.
There is a growing need for multiplexed specific IgE tests that can accurately evaluate patient sensitization profiles. However, currently available commercial tests are either single/low-plexed or require sophisticated instrumentation at considerable cost per assay. Here, we present a novel convenient lateral flow microarray-based device that employs a novel dual labelled gold nanoparticle-strategy for rapid and sensitive detection of a panel of 15 specific IgE responses in 35 clinical serum samples. Each gold nanoparticle was conjugated to an optimized ratio of HRP and anti-IgE, allowing significant enzymatic amplification to improve the sensitivity of the assay as compared to commercially available detection reagents. The mean inter-assay variability of the developed LFM assay was 12% CV, and analysis of a cohort of clinical samples (n = 35) revealed good general agreement with ImmunoCAP, yet with a varying performance among allergens (AUC = [0.54-0.88], threshold 1 kU). Due to the rapid and simple procedure, inexpensive materials and read-out by means of a consumer flatbed scanner, the presented assay may provide an interesting low-cost alternative to existing multiplexed methods when thresholds >1 kU are acceptable.


Association of ventilation rates and CO2 concentrations with health and other responses in commercial and institutional buildings.
This paper reviews current literature on the associations of ventilation rates and carbon dioxide concentrations in non-residential and non-industrial buildings (primarily offices) with health and other human outcomes. Twenty studies, with close to 30,000 subjects, investigated the association of ventilation rates with human responses, and 21 studies, with over 30,000 subjects, investigated the association of carbon dioxide concentration with these responses. Almost all studies found that ventilation rates below 10 Ls-1 per person in all building types were associated with statistically significant worsening in one or more health or perceived air quality outcomes. Some studies determined that increases in ventilation rates above 10 Ls-1 per person, up to approximately 20 Ls-1 per person, were associated with further significant decreases in the prevalence of sick building syndrome (SBS) symptoms or with further significant improvements in perceived air quality. The carbon dioxide studies support these findings. About half of the carbon dioxide studies suggest that the risk of sick building syndrome symptoms continued to decrease significantly with decreasing carbon dioxide concentrations below 800 ppm. The ventilation studies reported relative risks of 1.5-2 for respiratory illnesses and 1.1-6 for sick building syndrome symptoms for low compared to high low ventilation rates.


Lunar apatite with terrestrial volatile abundances.
The Moon is thought to be depleted relative to the Earth in volatile elements such as H, Cl and the alkalis. Nevertheless, evidence for lunar explosive volcanism has been used to infer that some lunar magmas exsolved a CO-rich and CO(2)-rich vapour phase before or during eruption. Although there is also evidence for other volatile species on glass spherules, until recently there had been no unambiguous reports of indigenous H in lunar rocks. Here we report quantitative ion microprobe measurements of late-stage apatite from lunar basalt 14053 that document concentrations of H, Cl and S that are indistinguishable from apatites in common terrestrial igneous rocks. These volatile contents could reflect post-magmatic metamorphic volatile addition or growth from a late-stage, interstitial, sulphide-saturated melt that contained approximately 1,600 parts per million H(2)O and approximately 3,500 parts per million Cl. Both metamorphic and igneous models of apatite formation suggest a volatile inventory for at least some lunar materials that is similar to comparable terrestrial materials. One possible implication is that portions of the lunar mantle or crust are more volatile-rich than previously thought.


Nipple-sparing mastectomy in women at high risk of developing breast cancer.
Nipple-sparing mastectomy is a valuable addition to the options available for women at high risk of developing breast cancer. In this review, we summarize current knowledge about the high-risk genes, BRCA1, BRCA2 and TP53 and the associated guidelines with regard to risk-reducing surgery. We consider other genetic risks and high-risk lesions. We discuss the literature on bilateral mastectomy for breast cancer risk-reduction, and the results of nipple-sparing mastectomy in particular. Finally, we report on patient satisfaction with these procedures and the impact that nipple-sparing mastectomy may have on women at high-risk of breast cancer.


Roles of Hox genes in the patterning of the central nervous system of Drosophila.
One of the key aspects of functional nervous systems is the restriction of particular neural subtypes to specific regions, which permits the establishment of differential segment-specific neuromuscular networks. Although Hox genes play a major role in shaping the anterior-posterior body axis during animal development, our understanding of how they act in individual cells to determine particular traits at precise developmental stages is rudimentary. We have used the abdominal leucokinergic neurons (ABLKs) to address this issue. These neurons are generated during both embryonic and postembryonic neurogenesis by the same progenitor neuroblast, and are designated embryonic and postembryonic ABLKs, respectively. We report that the genes of the Bithorax-Complex, Ultrabithorax (Ubx) and abdominal-A (abd-A) are redundantly required to specify the embryonic ABLKs. Moreover, the segment-specific pattern of the postembryonic ABLKs, which are restricted to the most anterior abdominal segments, is controlled by the absence of Abdominal-B (Abd-B), which we found was able to repress the expression of the neuropeptide leucokinin. We discuss this and other examples of how Hox genes generate diversity within the central nervous system of Drosophila.


Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease.
Serum ferritin (SF) levels are commonly elevated in patients with nonalcoholic fatty liver disease (NAFLD) because of systemic inflammation, increased iron stores, or both. The aim of this study was to examine the relationship between elevated SF and NAFLD severity. Demographic, clinical, histologic, laboratory, and anthropometric data were analyzed in 628 adult patients with NAFLD (age, ≥ 18 years) with biopsy-proven NAFLD and an SF measurement within 6 months of their liver biopsy. A threshold SF >1.5 × upper limit of normal (ULN) (i.e., >300 ng/mL in women and >450 ng/mL in men) was significantly associated with male sex, elevated serum alanine aminotransferase, aspartate aminotransferase, iron, transferrin-iron saturation, iron stain grade, and decreased platelets (P < 0.01). Histologic features of NAFLD were more severe among patients with SF >1.5 × ULN, including steatosis, fibrosis, hepatocellular ballooning, and diagnosis of NASH (P < 0.026). On multiple regression analysis, SF >1.5 × ULN was independently associated with advanced hepatic fibrosis (odds ratio [OR], 1.66; 95% confidence interval [CI], 1.05-2.62; P = 0.028) and increased NAFLD Activity Score (NAS) (OR, 1.99; 95% CI, 1.06-3.75; P = 0.033). A SF >1.5 × ULN is associated with hepatic iron deposition, a diagnosis of NASH, and worsened histologic activity and is an independent predictor of advanced hepatic fibrosis among patients with NAFLD. Furthermore, elevated SF is independently associated with higher NAS, even among patients without hepatic iron deposition. We conclude that SF is useful to identify NAFLD patients at risk for NASH and advanced fibrosis.


Domestic dog demographic structure and dynamics relevant to rabies control planning in urban areas in Africa: the case of Iringa, Tanzania.
Mass vaccinations of domestic dogs have been shown to effectively control canine rabies and hence human exposure to rabies. Knowledge of dog population demography is essential for planning effective rabies vaccination programmes; however, such information is still rare for African domestic dog populations, particularly so in urban areas. This study describes the demographic structure and population dynamics of a domestic dog population in an urban sub-Saharan African setting. In July to November 2005, we conducted a full household-level census and a cross-sectional dog demography survey in four urban wards of Iringa Municipality, Tanzania. The achievable vaccination coverage was assessed by a two-stage vaccination campaign, and the proportion of feral dogs was estimated by a mark-recapture transect study. The estimated size of the domestic dog population in Iringa was six times larger than official town records assumed, however, the proportion of feral dogs was estimated to account for less than 1% of the whole population. An average of 13% of all households owned dogs which equalled a dog:human ratio of 1:14, or 0.31 dogs per household or 334 dogs km-2. Dog female:male ratio was 1:1.4. The average age of the population was 2.2 years, 52% of all individuals were less than one year old. But mortality within the first year was high (72%). Females became fertile at the age of 10 months and reportedly remained fertile up to the age of 11 years. The average number of litters whelped per fertile female per year was 0.6 with an average of 5.5 pups born per litter. The population growth was estimated at 10% y-1. Such high birth and death rates result in a rapid replacement of anti-rabies immunised individuals with susceptible ones. This loss in herd immunity needs to be taken into account in the design of rabies control programmes. The very small proportion of truly feral dogs in the population implies that vaccination campaigns aimed at the owned dog population are sufficient to control rabies in urban Iringa, and the same may be valid in other, comparable urban settings.


The use of weighted health-related Quality of Life scores in people with diabetic macular oedema at baseline in a randomized clinical trial.
To examine the relationship between visual acuity in each eye and Quality of Life (QoL) outcomes in people with diabetic macular oedema. Cross sectional retrospective analysis of data collected at baseline in 289 people entered into a randomized clinical trial with diabetic macular oedema which investigated the safety and efficacy of a vascular endothelial growth factor inhibitor, pegaptanib sodium. At the baseline visit, visual acuity was measured through refraction and using retro-illuminated modified Early Treatment Diabetic Retinopathy Study Log MAR charts, and patient health-related QoL was determined using the European Quality of Life EQ-5D-3L and the Visual Functioning Questionnaire-25 (NEI-VFQ25). A regression analysis with QoL score from each vision-related domain as the dependent variable was fitted using linear and quadratic terms of the better and worse eye, age, gender, adjusted for number of concurrent conditions, ethnicity and level of diabetes control. For all vision-related QoL domains from NEI-VFQ25 and EQ-5D-3L except ocular pain, both visual acuity in the better-seeing and the worse-seeing eye gave a significant increase in correlation coefficient over that obtained from clinical and demographic data. The NEI-VFQ25 correlation was most closely associated with a weighted visual acuity measure of 0.75 in the better and 0.25 in the worse eye or 0.60 in the better and 0.40 in the worse eye. We recommend that a weighted visual acuity measure from both eyes is considered in future diabetic macular oedema trials.


Emigration and alcohol consumption among migrant household members staying behind: Evidence from Kyrgyzstan.
Despite the growth of alcohol consumption and international migration in many developing countries, the links between the two remain underexplored. We study the relationship between emigration of household members, receiving remittances (migrant monetary transfers), and alcohol consumption of migrant household members staying behind in Kyrgyzstan, a poor post-socialist country that has recently witnessed both large-scale emigration and a rise in alcohol-related health problems. Using a large longitudinal survey, we find that, among the ethnic majority (Kyrgyz), an increase in migrant remittances is associated with a higher likelihood and frequency of consuming alcohol, as well as an increase in the consumption of beer. Among ethnic Russians, the emigration of family members who do not send remittances back home is associated with an increased likelihood and frequency of alcohol consumption. We discuss possible mechanisms through which emigration and remittances may affect the alcohol consumption of those staying behind, including the relaxation of budget constraints and psychological distress. Overall, our findings suggest that the emigration of household members contribute to a greater alcohol consumption among those staying behind, and highlight the role of remittances and cultural background in understanding the nuances in this relationship.


A GWAS Meta-analysis and Replication Study Identifies a Novel Locus within CLPTM1L/TERT Associated with Nasopharyngeal Carcinoma in Individuals of Chinese Ancestry.
Genetic loci within the major histocompatibility complex (MHC) have been associated with nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-associated cancer, in several GWAS. Results outside this region have varied. We conducted a meta-analysis of four NPC GWAS among Chinese individuals (2,152 cases; 3,740 controls). Forty-three noteworthy findings outside the MHC region were identified and targeted for replication in a pooled analysis of four independent case-control studies across three regions in Asia (4,716 cases; 5,379 controls). A meta-analysis that combined results from the initial GWA and replication studies was performed. In the combined meta-analysis, rs31489, located within the CLPTM1L/TERT region on chromosome 5p15.33, was strongly associated with NPC (OR = 0.81; P value 6.3 × 10(-13)). Our results also provide support for associations reported from published NPC GWAS-rs6774494 (P = 1.5 × 10(-12); located in the MECOM gene region), rs9510787 (P = 5.0 × 10(-10); located in the TNFRSF19 gene region), and rs1412829/rs4977756/rs1063192 (P = 2.8 × 10(-8), P = 7.0 × 10(-7), and P = 8.4 × 10(-7), respectively; located in the CDKN2A/B gene region). We have identified a novel association between genetic variation in the CLPTM1L/TERT region and NPC. Supporting our finding, rs31489 and other SNPs in this region have been reported to be associated with multiple cancer sites, candidate-based studies have reported associations between polymorphisms in this region and NPC, the TERT gene has been shown to be important for telomere maintenance and has been reported to be overexpressed in NPC, and an EBV protein expressed in NPC (LMP1) has been reported to modulate TERT expression/telomerase activity. Our finding suggests that factors involved in telomere length maintenance are involved in NPC pathogenesis.


Mutations in conserved yeast DNA primase domains impair DNA replication in vivo.
To assess the role of eukaryotic DNA primase in vivo, we have produced conditional and lethal point mutations by random in vitro mutagenesis of the PR11 and PR12 genes, which encode the small and large subunits of yeast DNA primase. We replaced the wild-type copies of PRI1 and PRI2 with two pri1 and two pri2 conditional alleles. When shifted to the restrictive temperature, these strains showed altered DNA synthesis and reduced ability to synthesize high molecular weight DNA products, thus providing in vivo evidence for the essential role of DNA primase in eukaryotic DNA replication. Furthermore, mapping of the mutations at the nucleotide level has shown that the two pri1 and two pri2 conditional alleles and one pri2 lethal allele have suffered single base-pair substitutions causing a change in amino acid residues conserved in the corresponding mouse polypeptide.


Intermatrix synthesis: easy technique permitting preparation of polymer-stabilized nanoparticles with desired composition and structure.
The synthesis of polymer-stabilized nanoparticles (PSNPs) can be successfully carried out using intermatrix synthesis (IMS) technique, which consists in sequential loading of the functional groups of a polymer with the desired metal ions followed by nanoparticles (NPs) formation stage. After each metal-loading-NPs-formation cycle, the functional groups of the polymer appear to be regenerated. This allows for repeating the cycles to increase the NPs content or to obtain NPs with different structures and compositions (e.g. core-shell or core-sandwich). This article reports the results on the further development of the IMS technique. The formation of NPs has been shown to proceed by not only the metal reduction reaction (e.g. Cu0-NPs) but also by the precipitation reaction resulting in the IMS of PSNPs of metal salts (e.g. CuS-NPs).


Neonatal infection with species C adenoviruses confirmed in viable cord blood lymphocytes.
Credible but conflicting reports address the frequency of prenatal infection by species C adenovirus. This question is important because these viruses persist in lymphoid cells and suppress double-stranded DNA-break repair. Consequently, prenatal adenovirus infections may generate the aberrant clones of lymphocytes that precede development of childhood acute lymphoblastic leukemia (ALL). The present study was designed to overcome technical limitations of prior work by processing cord blood lymphocytes within a day of collection, and by analyzing sufficient numbers of lymphocytes to detect adenovirus-containing cells at the lower limits determined by our previous studies of tonsil lymphocytes. By this approach, adenoviral DNA was identified in 19 of 517 (3.7%) samples, providing definitive evidence for the occurrence of prenatal infection with species C adenoviruses in a significant fraction of neonates predominantly of African American and Hispanic ancestry. Cord blood samples were also tested for the presence of the ETV6-RUNX1 translocation, the most common genetic abnormality in childhood ALL. Using a nested PCR assay, the ETV6-RUNX1 transcript was detected in four of 196 adenovirus-negative samples and one of 14 adenovirus-positive cord blood samples. These findings indicate that this method will be suitable for determining concordance between adenovirus infection and the leukemia-associated translocations in newborns.


Falls in hospices: a cancer network observational study of fall rates and risk factors.
Falls have been identified as a problem in frail patient populations, but their risk factors have not been studied prospectively in the hospice setting. We calculated fall rates in three hospices in the Yorkshire region, identified risk factors for falls based on previous studies in elderly patients, and then carried out a prospective study of inpatients in two of these hospices. We compared these risk factors in patients who subsequently fell with patients that did not fall during the study period. Information was recorded on 102 admissions. Twelve patients fell, generating 23 falls; six patients fell more than once. Significant risk factors for falling were cognitive impairment, low systolic lying and standing blood pressure, visual impairment and age over 80. Males with these risk factors fell more often than female patients with these risk factors. Strategies to prevent falls in hospice inpatients need to be directed appropriately towards patients with cognitive and visual impairment and low systolic blood pressure.


Escalation of drug use in early-onset cannabis users vs co-twin controls.
Previous studies have reported that early initiation of cannabis (marijuana) use is a significant risk factor for other drug use and drug-related problems. To examine whether the association between early cannabis use and subsequent progression to use of other drugs and drug abuse/dependence persists after controlling for genetic and shared environmental influences. Cross-sectional survey conducted in 1996-2000 among an Australian national volunteer sample of 311 young adult (median age, 30 years) monozygotic and dizygotic same-sex twin pairs discordant for early cannabis use (before age 17 years). Self-reported subsequent nonmedical use of prescription sedatives, hallucinogens, cocaine/other stimulants, and opioids; abuse or dependence on these drugs (including cannabis abuse/dependence); and alcohol dependence. Individuals who used cannabis by age 17 years had odds of other drug use, alcohol dependence, and drug abuse/dependence that were 2.1 to 5.2 times higher than those of their co-twin, who did not use cannabis before age 17 years. Controlling for known risk factors (early-onset alcohol or tobacco use, parental conflict/separation, childhood sexual abuse, conduct disorder, major depression, and social anxiety) had only negligible effects on these results. These associations did not differ significantly between monozygotic and dizygotic twins. Associations between early cannabis use and later drug use and abuse/dependence cannot solely be explained by common predisposing genetic or shared environmental factors. The association may arise from the effects of the peer and social context within which cannabis is used and obtained. In particular, early access to and use of cannabis may reduce perceived barriers against the use of other illegal drugs and provide access to these drugs.


The Relationship of Gender and Self-Efficacy on Social Physique Anxiety among College Students.
The anxiety or fear associated with physique evaluation is defined as Social Physique Anxiety (SPA). Numerous studies have examined this construct, yet a gap exists exploring this phenomenon among current college students with SPA, self-efficacy, and gender concurrently. Therefore, the purposes of this study included quantitatively analyzing the association between SPA, gender, and self-efficacy. Participants included 237 students at a Southeastern university participating in jogging, body conditioning, or weight training courses. Analysis of Variance yielded a significant main effect for self-efficacy as well, as those with lower self-efficacy displayed higher levels of SPA (p< 0.001). Stepwise regression analysis indicated self-efficacy and gender were both significant predictors of SPA. This information could aid in creating interventions designed to decrease the prevalence of SPA and increase levels of self-efficacy among the current college student population.


Altered balance of excitatory and inhibitory learning in a genetically modified mouse model of glutamatergic dysfunction relevant to schizophrenia.
The GluA1 AMPAR subunit (encoded by the Gria1 gene) has been implicated in schizophrenia. Gria1 knockout in mice results in recently experienced stimuli acquiring aberrantly high salience. This suggests that GluA1 may be important for learning that is sensitive to the temporal contiguity between events. To test this, mice were trained on a Pavlovian trace conditioning procedure in which the presentation of an auditory cue and food were separated by a temporal interval. Wild-type mice initially learnt, but with prolonged training came to withhold responding during the trace-conditioned cue, responding less than for another cue that was nonreinforced. Gria1 knockout mice, in contrast, showed sustained performance over training, responding more to the trace-conditioned cue than the nonreinforced cue. Therefore, the trace-conditioned cue acquired inhibitory properties (signalling the absence of food) in wild-type mice, but Gria1 deletion impaired the acquisition of inhibition, thus maintaining the stimulus as an excitatory predictor of food. Furthermore, when there was no trace both groups showed successful learning. These results suggest that cognitive abnormalities in disorders like schizophrenia in which gluatamatergic signalling is implicated may be caused by aberrant salience leading to a change in the nature of the information that is encoded.


The Gene Wiki: community intelligence applied to human gene annotation.
Annotating the function of all human genes is a critical, yet formidable, challenge. Current gene annotation efforts focus on centralized curation resources, but it is increasingly clear that this approach does not scale with the rapid growth of the biomedical literature. The Gene Wiki utilizes an alternative and complementary model based on the principle of community intelligence. Directly integrated within the online encyclopedia, Wikipedia, the goal of this effort is to build a gene-specific review article for every gene in the human genome, where each article is collaboratively written, continuously updated and community reviewed. Previously, we described the creation of Gene Wiki 'stubs' for approximately 9000 human genes. Here, we describe ongoing systematic improvements to these articles to increase their utility. Moreover, we retrospectively examine the community usage and improvement of the Gene Wiki, providing evidence of a critical mass of users and editors. Gene Wiki articles are freely accessible within the Wikipedia web site, and additional links and information are available at http://en.wikipedia.org/wiki/Portal:Gene_Wiki.


Effect of Dedicated In-Person Interpreter on Satisfaction and Efficiency in Otolaryngology Ambulatory Clinic.
In a large academic children's hospital ambulatory clinic, the increasing demand for Spanish interpretation exceeds the Interpreting Services Department capacity, necessitating telephone interpretation. By adding a dedicated Spanish interpreter in the otolaryngology clinic, we aimed to decrease visit times for Spanish-speaking patients and increase satisfaction. Additional aims explored if dedicated Spanish interpreters could increase patients seen per session. A quality improvement initiative investigated baseline state compared to 2 tests of change using video interpretation and dedicated, in-person interpretation. Time permitting, interpreters contacted patients before the visit to decrease missed appointments and late arrivals. Measures included clinic visit times, late arrivals, missed appointments, and family/employee satisfaction scores. Actuarial statistics forecasted if on-site Spanish interpreters would affect patients seen per session and the potential addition of sessions. In-person interpretation reduced visit times for Spanish-speaking patients from 55 to 48 minutes (P = .01) and 57 to 48 minutes for all patients (P < .0001). Nearly 50% of video calls experienced technical difficulties. Families and employees preferred in-person over video and phone interpretation. No-show visits decreased by 25% and late arrivals by 17%. Implementing dedicated Spanish interpreters may increase productivity and enhance family experience. Reducing patient visit time by 9 minutes permits 2 additional patients per clinic session (1560 visits, 390 surgeries per year). Applied institution-wide, the intervention could create 29% more capacity in the ambulatory schedule (31,000 additional visits) and reduce actuarial need for ambulatory sessions in the same clinic space.


Prediction of therapeutic potency of tacrine derivatives as BuChE inhibitors from quantitative structure-activity relationship modelling.
Numerous studies show that tacrine derivatives exhibit increased inhibitory activity against butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE). However, the screening assays for currently available BuChE inhibitors are expensive, time consuming and dependent on the inhibitory compound. It is therefore desirable to develop alternative methods to facilitate the screening of these derivatives in the early phase of drug discovery. In order to develop robust predictive models, three regression methods were chosen in this study: multiple linear regression (MLR), support vector regression (SVR) and multilayer perceptron network (MLP). Eight relevant descriptors were selected on a dataset of 151 molecules using a method based on genetic algorithms. Internal and external validation strategies play an important role. Also, to check the robustness of the selected models, all available validation strategies were used, and all criteria used to validate these models revealed the superiority of the SVR model. The statistical parameters obtained with the SVR model were RMSE = 0.197, r2 = 0.969 and Q2 = 0.964 for the training set, and r2 = 0.906 and Q2 = 0.891 for the test set. Therefore, the model developed in this study provides an excellent prediction of the inhibitory concentration of tacrine derivatives.


Perspectives on modern orthopaedics: use of Adcon-L for epidural scar prevention.
Adcon-L is a biodegradable gel matrix that was recently approved by the Food and Drug Administration for use during single-level posterior lumbar laminectomy or laminotomy procedures. Experimental and clinical studies have suggested that the use of this product will decrease postoperative epidural scarring. However, the relationship between epidural fibrosis and patient outcome remains unclear. If the treating surgeon is of the opinion that there is a need to reduce epidural scar, the use of this product appears worthwhile. However, further studies are needed to evaluate clinical outcome and justify the use of this product on a routine basis.


Monocytes: subsets, origins, fates and functions.
The term mono-cyte suggests this population of cells consists of a single homogenous fraction. However, evidence from a number of laboratories indicates that monocytes are composed of several subsets, which differ in phenotype, size, nuclear morphology, granularity and gene profiles. Most importantly, recent data suggest that monocyte subsets are also functionally distinct. Here we summarize the recent advances in our understanding of monocyte subsets and their origins, fates and functions. The recent past has seen major progress in our understanding of myeloid differentiation. Specifically, the published literature now suggests a dichotomy that starts at the stage of a novel clonotypic bone marrow resident precursor, the macrophage dendritic cell progenitor (MDP). Insights into differential origins of macrophages and dendritic cells, linked with functional specifications, are likely to significantly change our current view of the mononuclear phagocyte system. Contemporary studies have demonstrated that two subsets of monocytes reside in the peripheral circulation. These subsets are surprisingly distinct; with regard to their functions and fates, for example, one subset might be dedicated to generate macrophages upon extravasation from the peripheral circulation, whereas, the other subset under inflammatory conditions may differentiate into inflammatory dendritic cells. The tissue response during pathogenesis seems to differentially mobilize these cells, thereby manipulating the local mononuclear phagocyte composition according to acute needs.


Autonomous vehicles: How perspective-taking accessibility alters moral judgments and consumer purchasing behavior.
In preparation for unavoidable collisions, autonomous vehicle (AV) manufacturers could program their cars with utilitarian ethical algorithms that maximize the number of lives saved during a crash. However, recent research employing hypothetical AV crash scenarios reveals that people are not willing to purchase a utilitarian AV despite judging them to be morally appropriate (Bonnefon, Shariff, & Rahwan, 2016). This important result, indicating evidence for a social dilemma, has not yet been psychologically explored by behavioral scientists. In order to address the psychological underpinnings of this phenomenon, we developed and tested a novel theoretical proposal - perspective-taking accessibility (PT accessibility). Accordingly, we established that providing participants with access to both situational perspectives (AV buyers can be passengers or pedestrians) in crash scenarios, eliminated the behavioral inconsistency between their utilitarian judgments of moral appropriateness and non-utilitarian purchasing behavior. Moreover, our full PT accessibility induced respondents' utilitarian prosocial judgments and purchasing behavior (Experiments 1a and 1b) and consistent utilitarian preferences across judgment tasks (Experiment 2). Crucially, with full PT accessibility, participants' utilitarian purchasing behavior as well as their willingness to buy and ride utilitarian AVs were informed by their utilitarian moral judgments. Full PT accessibility provides the participants with even odds of being a pedestrian or passenger in crash scenarios, and thus impartiality. It could be argued that full PT accessibility is a new type of 'veil of ignorance', which is not based on purposely induced self-interest and uneven risk options (as in Huang, Greene, & Bazerman, 2019), but rather is based on even odds of being a passenger or pedestrian, and therefore with even 50/50 chance to die/live as passenger or pedestrian. Under these circumstances one can measure utilitarian preferences.


Treatment of neurological and psychiatric disorders with deep brain stimulation; raising hopes and future challenges.
The technology of Neural Stimulation in recent years has become the focus of the research and treatment, although it has been around for many years. The potential use of stimulating the brain and nerves ranges from the spinal cord stimulation to the implantations of cochlear and bionic eyes with a large discrepancy between the clinical readiness for these various uses. Electrical high-frequency Deep Brain Stimulation (DBS) was developed as an alternative option to treat a few neurological disorders. However, with advancing in surgical procedures, technologies and safeties, the applications of DBS are expanding not only for therapeutic purposes but also for research. Although the exact mechanisms of action/s are not fully understood, the outcome of the ongoing research and clinical trials are promising. DBS has been used to treat the essential tremor since 1997, Parkinson's disease (PD) since 2002 and dystonia since 2003. It has also been used to treat various disorders, including major depression. The therapeutic effect of DBS in PD is well established but for other diseases such as epilepsy the outcomes are unclear and ambiguous. This article is a succinct review of the literature, focusing on PD, epilepsy and Obsessive Compulsive Disorder (OCD).


Differences in amyloid deposition in primary and recurrent corneal lattice dystrophy type 1.
To report the histopathology of a case of recurrent corneal lattice dystrophy showing altered distribution of the corneal deposits in the recurrent disease compared with the original. Clinical details and histopathology of the primary and repeat corneal grafts are reported. A woman originally presented at age 28 years with reduced visual acuity and classic corneal lattice lines in both corneas and underwent bilateral corneal grafts. Recurrent disease was detected 20 years later as anterior haze and various-sized subepithelial opacities but no stromal lattice lines. Histology of the original corneas demonstrated amyloid deposits throughout the corneal stroma, typical of corneal lattice dystrophy. In the repeat grafts, amyloid deposits were confined to the basement membrane region of the anterior cornea and were almost entirely absent from the stroma of the cornea. Recurrence of corneal lattice dystrophy is widely recognized to occur, but the pathology of the recurrent disease is not well documented in the literature. This case report highlights that there may be a difference in the distribution of the deposits when the disease recurs. We postulate that the reason for this difference may be that donor keratocytes survive long enough in the transplanted cornea to prevent build-up of abnormal keratoepithelin, the product of the mutated gene in type 1 corneal lattice dystrophy. By contrast, the epithelium, being replaced by host epithelium shortly after grafting, is still producing abnormal protein. The differences in the pattern of deposits may have important clinical implications, particularly regarding treatment modalities in recurrent disease.


A bootstrap based analysis pipeline for efficient classification of phylogenetically related animal miRNAs.
Phylogenetically related miRNAs (miRNA families) convey important information of the function and evolution of miRNAs. Due to the special sequence features of miRNAs, pair-wise sequence identity between miRNA precursors alone is often inadequate for unequivocally judging the phylogenetic relationships between miRNAs. Most of the current methods for miRNA classification rely heavily on manual inspection and lack measurements of the reliability of the results. In this study, we designed an analysis pipeline (the Phylogeny-Bootstrap-Cluster (PBC) pipeline) to identify miRNA families based on branch stability in the bootstrap trees derived from overlapping genome-wide miRNA sequence sets. We tested the PBC analysis pipeline with the miRNAs from six animal species, H. sapiens, M. musculus, G. gallus, D. rerio, D. melanogaster, and C. elegans. The resulting classification was compared with the miRNA families defined in miRBase. The two classifications were largely consistent. The PBC analysis pipeline is an efficient method for classifying large numbers of heterogeneous miRNA sequences. It requires minimum human involvement and provides measurements of the reliability of the classification results.


[Use and non-use of pedestrian bridges in Mexico City. The pedestrian perspective].
To analyze the motives for using and not using pedestrian bridges (PB). A cross-sectional survey was conducted of a sample of pedestrian users and non-users of PB; a logistic regression model was used to analyze the motives for use and non-use. The prevalence of non-use was 50.5 % of 813 surveyed pedestrians; the principal reason to use a PB was safety, and not to use it was "laziness". There were significant differences when analyzing the reason of non-use in the age groups 19 to 36 years, adjusted for education and physical characteristics of the PB ([aOR=1.7; 95 % CI=1.06-2.86] and [ORa.1.9; 95 % CI=1.14-3.33], respectively). The results of this study allow us to identify important aspects to consider--from the perspective of the pedestrians--when constructing new PB and improving existing PB to increase use in areas with a high risk of pedestrian injuries.


Enzyme inhibition by hydroamination: design and mechanism of a hybrid carmaphycin-syringolin enone proteasome inhibitor.
Hydroamination reactions involving the addition of an amine to an inactivated alkene are entropically prohibited and require strong chemical catalysts. While this synthetic process is efficient at generating substituted amines, there is no equivalent in small molecule-mediated enzyme inhibition. We report an unusual mechanism of proteasome inhibition that involves a hydroamination reaction of alkene derivatives of the epoxyketone natural product carmaphycin. We show that the carmaphycin enone first forms a hemiketal intermediate with the catalytic Thr1 residue of the proteasome before cyclization by an unanticipated intramolecular alkene hydroamination reaction, resulting in a stable six-membered morpholine ring. The carmaphycin enone electrophile, which does not undergo a 1,4-Michael addition as previously observed with vinyl sulfone and α,β-unsaturated amide-based inhibitors, is partially reversible and gives insight into the design of proteasome inhibitors for cancer chemotherapy.


A line-scan hyperspectral system for high-throughput Raman chemical imaging.
A line-scan hyperspectral system was developed to enable Raman chemical imaging for large sample areas. A custom-designed 785 nm line laser based on a scanning mirror serves as an excitation source. A 45° dichroic beam splitter reflects the laser light to form a 24 cm × 1 mm excitation line normally incident on the sample surface. Raman signals along the laser line are collected by a detection module consisting of a dispersive imaging spectrograph and a CCD camera. A hypercube is accumulated line by line as a motorized table moves the samples transversely through the laser line. The system covers a Raman shift range of -648.7 to 2889.0 cm(-1) and a 23 cm wide area. An example application for authenticating milk powder is presented to demonstrate the system performance. In 4 min the system acquired a 512 × 110 × 1024 hypercube (56 320 spectra) from four, 47 mm diameter Petri dishes containing four powder samples. Chemical images were created for detecting two adulterants (melamine and dicyandiamide) that had been mixed into the milk powder.


Ocean zoning for conservation, fisheries and marine renewable energy: assessing trade-offs and co-location opportunities.
Oceans, particularly coastal areas, are getting busier and within this increasingly human-dominated seascape, marine biodiversity continues to decline. Attempts to maintain and restore marine biodiversity are becoming more spatial, principally through the designation of marine protected areas (MPAs). MPAs compete for space with other uses, and the emergence of new industries, such as marine renewable energy generation, will increase competition for space. Decision makers require guidance on how to zone the ocean to conserve biodiversity, mitigate conflict and accommodate multiple uses. Here we used empirical data and freely available planning software to identified priority areas for multiple ocean zones, which incorporate goals for biodiversity conservation, two types of renewable energy, and three types of fishing. We developed an approached to evaluate trade-offs between industries and we investigated the impacts of co-locating some fishing activities within renewable energy sites. We observed non-linear trade-offs between industries. We also found that different subsectors within those industries experienced very different trade-off curves. Incorporating co-location resulted in significant reductions in cost to the fishing industry, including fisheries that were not co-located. Co-location also altered the optimal location of renewable energy zones with planning solutions. Our findings have broad implications for ocean zoning and marine spatial planning. In particular, they highlight the need to include industry subsectors when assessing trade-offs and they stress the importance of considering co-location opportunities from the outset. Our research reinforces the need for multi-industry ocean-zoning and demonstrates how it can be undertaken within the framework of strategic conservation planning.


QTL mapping of natural variation reveals that the developmental regulator bruno reduces tolerance to P-element transposition in the Drosophila female germline.
Transposable elements (TEs) are obligate genetic parasites that propagate in host genomes by replicating in germline nuclei, thereby ensuring transmission to offspring. This selfish replication not only produces deleterious mutations-in extreme cases, TE mobilization induces genotoxic stress that prohibits the production of viable gametes. Host genomes could reduce these fitness effects in two ways: resistance and tolerance. Resistance to TE propagation is enacted by germline-specific small-RNA-mediated silencing pathways, such as the Piwi-interacting RNA (piRNA) pathway, and is studied extensively. However, it remains entirely unknown whether host genomes may also evolve tolerance by desensitizing gametogenesis to the harmful effects of TEs. In part, the absence of research on tolerance reflects a lack of opportunity, as small-RNA-mediated silencing evolves rapidly after a new TE invades, thereby masking existing variation in tolerance. We have exploited the recent historical invasion of the Drosophila melanogaster genome by P-element DNA transposons in order to study tolerance of TE activity. In the absence of piRNA-mediated silencing, the genotoxic stress imposed by P-elements disrupts oogenesis and, in extreme cases, leads to atrophied ovaries that completely lack germline cells. By performing quantitative trait locus (QTL) mapping on a panel of recombinant inbred lines (RILs) that lack piRNA-mediated silencing of P-elements, we uncovered multiple QTL that are associated with differences in tolerance of oogenesis to P-element transposition. We localized the most significant QTL to a small 230-kb euchromatic region, with the logarithm of the odds (LOD) peak occurring in the bruno locus, which codes for a critical and well-studied developmental regulator of oogenesis. Genetic, cytological, and expression analyses suggest that bruno dosage modulates germline stem cell (GSC) loss in the presence of P-element activity. Our observations reveal segregating variation in TE tolerance for the first time, and implicate gametogenic regulators as a source of tolerant variants in natural populations.


Maize Genomes to Fields: 2014 and 2015 field season genotype, phenotype, environment, and inbred ear image datasets.
Crop improvement relies on analysis of phenotypic, genotypic, and environmental data. Given large, well-integrated, multi-year datasets, diverse queries can be made: Which lines perform best in hot, dry environments? Which alleles of specific genes are required for optimal performance in each environment? Such datasets also can be leveraged to predict cultivar performance, even in uncharacterized environments. The maize Genomes to Fields (G2F) Initiative is a multi-institutional organization of scientists working to generate and analyze such datasets from existing, publicly available inbred lines and hybrids. G2F's genotype by environment project has released 2014 and 2015 datasets to the public, with 2016 and 2017 collected and soon to be made available. Datasets include DNA sequences; traditional phenotype descriptions, as well as detailed ear, cob, and kernel phenotypes quantified by image analysis; weather station measurements; and soil characterizations by site. Data are released as comma separated value spreadsheets accompanied by extensive README text descriptions. For genotypic and phenotypic data, both raw data and a version with outliers removed are reported. For weather data, two versions are reported: a full dataset calibrated against nearby National Weather Service sites and a second calibrated set with outliers and apparent artifacts removed.


China engages global health governance: processes and dilemmas.
Using HIV/AIDS, Severe Acute Respiratory Syndrome (SARS), and avian influenza as case studies, this paper discusses the processes and dilemmas of China's participation in health governance, both at the domestic level and the global level. Globalization has eroded the boundary between public and private health and between domestic and global health governance. In addition, the SARS outbreak of 2002-2003 focused global attention on China's public health. As a rising power with the largest population on earth, China is expected by the international community to play a better and more active role in health management. Since the turn of this century, China has increasingly embraced multilateralism in health governance. This paper argues that China's multilateral cooperation is driven by both necessity and conscious design. International concerns about good governance and its aspiration to become a 'responsible' state have exerted a normative effect on China to change tack. Its interactions with United Nations agencies have triggered a learning process for China to securitize the spread of infectious diseases as a security threat. Conversely, China has utilized multilateralism to gain access to international resources and technical assistance. It is still a matter of debate whether China's cooperative engagement with global health governance can endure, because of the persistent problems of withholding information on disease outbreaks and because of its insistence on the Westphalian notion of sovereignty.


The widening health care gap between high- and low-wage workers.
Rising health care costs affect everyone, but pose a particular problem for low-wage workers and their families. Few of these workers are eligible for public insurance programs or can afford to purchase private insurance, and they are less likely than high-wage workers to work for companies offering health coverage. Using data from the Medical Expenditure Panel Survey, this report finds that, between 1996 and 2003, low-wage workers were more likely than high-wage workers to be uninsured and to spend a proportionally higher share of family income on out-of-pocket health costs. They were less likely to have a usual source of care, less likely to have received preventive services, used fewer health care services overall, and were less likely to use the latest generation of medical technologies (e.g., prescription drugs approved within the prior 20 years). They were also more likely to report worse general and mental health than high-wage workers.


Rescue of anaemia and autoimmune responses in SOD1-deficient mice by transgenic expression of human SOD1 in erythrocytes.
Oxidative stress has been implicated as a cause of various diseases such as anaemia. We found that the SOD1 [Cu,Zn-SOD (superoxide dismutase)] gene deficiency causes anaemia, the production of autoantibodies against RBCs (red blood cells) and renal damage. In the present study, to further understand the role of oxidative stress in the autoimmune response triggered by SOD1 deficiency, we generated mice that had the hSOD1 (human SOD1) transgene under regulation of the GATA-1 promoter, and bred the transgene onto the SOD1(-/-) background (SOD1(-/-);hSOD1(tg/+)). The lifespan of RBCs, levels of intracellular reactive oxygen species, and RBC content in SOD1(-/-);hSOD1(tg/+) mice, were approximately equivalent to those of SOD1(+/+) mice. The production of antibodies against lipid peroxidation products, 4-hydroxy-2-nonenal and acrolein, as well as autoantibodies against RBCs and carbonic anhydrase II were elevated in the SOD1(-/-) mice, but were suppressed in the SOD1(-/-);hSOD1(tg/+) mice. Renal function, as judged by blood urea nitrogen, was improved in the transgenic mice. These results rule out the involvement of a defective immune system in the autoimmune response of SOD1-deficient mice, because SOD1(-/-);hSOD1(tg/+) mice carry the hSOD1 protein only in RBCs. Metabolomic analysis indicated a shift in glucose metabolism to the pentose phosphate pathway and a decrease in the energy charge potential of RBCs in SOD1-deficient mice. We conclude that the increase in reactive oxygen species due to SOD1 deficiency accelerates RBC destruction by affecting carbon metabolism and increasing oxidative modification of lipids and proteins. The resulting oxidation products are antigenic and, consequently, trigger autoantibody production, leading to autoimmune responses.


Assessing Inequalities in Wellbeing at a Neighbourhood Scale in Low-Middle-Income-Country Secondary Cities and Their Implications for Long-Term Livability.
To ensure future sustainability, cities need to consider concepts of livability and resident wellbeing alongside environmental, economic and infrastructure development equity. The current rapid urbanization experienced in many regions is leading to sustainability challenges, but also offers the opportunity to deliver infrastructure supporting the social aspects of cities and the services that underpin them alongside economic growth. Unfortunately, evidence of what is needed to deliver urban wellbeing is largely absent from the global south. This paper contributes to filling this knowledge gap through a novel interdisciplinary mixed methods study undertaken in two rapidly changing cities (one Thai and one Kenyan) using qualitative surveys, subjective wellbeing and stress measurements, and spatial analysis of urban infrastructure distribution. We find the absence of basic infrastructure (including waste removal, water availability and quality) unsurprisingly causes significant stress for city residents. However, once these services are in place, smaller variations (inequalities) in social (crime, tenure) and environmental (noise, air quality) conditions begin to play a greater role in determining differences in subjective wellbeing across a city. Our results indicate that spending time in urban greenspaces can mitigate the stressful impacts of city living even for residents of informal neighborhoods. Our data also highlights the importance of places that enable social interactions supporting wellbeing-whether green or built. These results demonstrate the need for diversity and equity in the provision of public realm spaces to ensure social and spatial justice. These findings strengthen the need to promote long term livability in LMIC urban planning alongside economic growth, environmental sustainability, and resilience.


Implication of rapid thermal annealing-induced cracks on the performance of multiple-quantum-well laser diodes.
We investigated the effects of rapid thermal annealing (RTA)-induced cracks on the diode performance fabricated with GaAs-AlGaAs microstructures. These effects were examined and characterized after quantum-well intermixing within an epitaxial structure capped by either SiO2 or SrF2 layers. The results show clearly that the density of surface crackes strongly depends on the atomic interdiffusion between the well and the barrier layers and on the quality of the dielectric caps as well. Moreover, surface-crack correlation with the RTA process an dielectric deposition parameters, and the cracking effects on diode performance were observed and analyzed in detail. The results demonstrate that diode characteristics can be greatly improved by good surface morphology. Most importantly, we explored an effective way of reducing the density of RTA-induced cracks for the dielectrics grown by plasma-enhanced chemical vapor deposition, which was beneficial for dielectric-cap quantum-well disordering.