Relationship Quality Among Older Cohabitors: A Comparison to Remarrieds.
Later life marital patterns have undergone shifts over the past few decades, including a rapid growth of cohabiting unions. Despite the increase in older adult cohabitation, research on this population has been slow to keep up. Intimate relationships are linked to well-being and relationship quality is especially important because high-quality relationships offer a number of benefits for well-being, whereas poor-quality relationships often are detrimental. This study compares cohabiting and remarried individuals on two measures of relationship quality. Using data from the 2010 and 2012 Health and Retirement Study, I investigate the positive and negative relationship quality of cohabitors relative to their remarried counterparts and whether the association of union type and relationship quality varies by race. Across both positive and negative relationship quality, I found few differences between cohabiting and remarried individuals. Black cohabitors report higher positive relationship quality than remarrieds, whereas White cohabitors and remarrieds do not differ. These findings suggest that cohabiting unions and remarriages are comparable among White older adults, but that Black cohabitors may gain more in terms of positive relationship quality than their remarried counterparts.


The economic benefits of supported employment for persons with mental illness.
BACKGROUND: Policies and programs that emphasize employment for persons with mental illness are often promoted with the goals of improving economic self-sufficiency and reducing dependence on public welfare programs. At present, there is little empirical evidence about the actual effect of vocational interventions on economic self-sufficiency or on use of public benefits by persons with mental illness. STUDY AIMS: This study provides a preliminary look at how participating in supported employment, a form of vocational rehabilitation emphasizing ongoing support in competitive jobs, affects the amount that participants earn from work and the total amount of income they receive from all sources. Further, we examine the extent to which receiving public benefits affects the amount earned from private employment, taking into consideration other factors that might be associated with benefit status. METHODS: Data are from a randomized trial of supported employment interventions. This analysis followed 137 of those study participants with severe mental illness for 18 months after they enrolled in either of two supported employment programs. Income from various sources was estimated based on interviews with study participants upon study entry and at six-month intervals thereafter. Changes in income from work, government and other sources were analyzed using paired Wilcoxon matched-pairs signed-ranks tests and t-tests. Using ordinary least-squares regression, we analyzed the effect of benefit status on changes in earnings, taking into account diagnosis, work history, education, program type, site of program, psychiatric symptoms, global functioning and previous earnings. RESULTS: Estimated total income increased by an average of $134 (US) per month after enrolling in supported employment. More than three-quarters of this increase was from government sources, such as Social Security and educational grants. The increase in government income was largely due to participants applying for and getting cash benefits for the first time. Social Security payments for those receiving benefits before enrollment did not change significantly. A small group of persons (n = 22) who did not receive Social Security benefits before or after enrolment earned significantly more from competitive employment after enrolling than did those who received benefits. This finding persisted after taking into acount differences in work history, clinical and functional variables and education. LIMITATIONS: Because of the relatively small sample size and the lack of continuous measures of income these results should be considered preliminary. CONCLUSIONS: Supported employment, one of the more effective forms of vocational rehabilitation for persons with mental illness, did not reduce dependence on government support. Receiving government benefits was associated with lower earnings from work. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: These findings suggest that most persons in treatment for severe mental illness need continued public financial support even after enrolling in vocational rehabilitation programs. IMPLICATIONS FOR HEALTH POLICY FORMULATION: Undoubtedly increased labor force participation can benefit persons with mental illness in a number of ways. However, policy makers should be careful about justifying increased access to vocational programs on the basis of reduced spending for income support. Further, targeting such programs only to persons receiving income support may overlook the clients who can benefit most: those who are not currently receiving benefits. IMPLICATIONS FOR FURTHER RESEARCH: Policy makers need a better understanding of how vocational interventions and income support programs affect the income and well-being of persons with mental illness. Studies similar to this one should be repeated with larger, more diverse samples that will allow use of instrumental variables statistical techniques.


Malaria in pregnancy in the Asia-Pacific region.
Most pregnant women at risk of for infection with Plasmodium vivax live in the Asia-Pacific region. However, malaria in pregnancy is not recognised as a priority by many governments, policy makers, and donors in this region. Robust data for the true burden of malaria throughout pregnancy are scarce. Nevertheless, when women have little immunity, each infection is potentially fatal to the mother, fetus, or both. WHO recommendations for the control of malaria in pregnancy are largely based on the situation in Africa, but strategies in the Asia-Pacific region are complicated by heterogeneous transmission settings, coexistence of multidrug-resistant Plasmodium falciparum and Plasmodium vivax parasites, and different vectors. Most knowledge of the epidemiology, effect, treatment, and prevention of malaria in pregnancy in the Asia-Pacific region comes from India, Papua New Guinea, and Thailand. Improved estimates of the morbidity and mortality of malaria in pregnancy are urgently needed. When malaria in pregnancy cannot be prevented, accurate diagnosis and prompt treatment are needed to avert dangerous symptomatic disease and to reduce effects on fetuses.


Involvement of epigenetics and EMT-related miRNA in arsenic-induced neoplastic transformation and their potential clinical use.
Exposure to toxicants leads to cumulative molecular changes that overtime increase a subject's risk of developing urothelial carcinoma. To assess the impact of arsenic exposure at a time progressive manner, we developed and characterized a cell culture model and tested a panel of miRNAs in urine samples from arsenic-exposed subjects, urothelial carcinoma patients, and controls. To prepare an in vitro model, we chronically exposed an immortalized normal human bladder cell line (HUC1) to arsenic. Growth of the HUC1 cells was increased in a time-dependent manner after arsenic treatment and cellular morphology was changed. In a soft agar assay, colonies were observed only in arsenic-treated cells, and the number of colonies gradually increased with longer periods of treatment. Similarly, invaded cells in an invasion assay were observed only in arsenic-treated cells. Withdrawal of arsenic treatment for 2.5 months did not reverse the tumorigenic properties of arsenic-treated cells. Western blot analysis demonstrated decreased PTEN and increased AKT and mTOR in arsenic-treated HUC1 cells. Levels of miR-200a, miR-200b, and miR-200c were downregulated in arsenic-exposed HUC1 cells by quantitative RT-PCR. Furthermore, in human urine, miR-200c and miR-205 were inversely associated with arsenic exposure (P = 0.005 and 0.009, respectively). Expression of miR-205 discriminated cancer cases from controls with high sensitivity and specificity (AUC = 0.845). Our study suggests that exposure to arsenic rapidly induces a multifaceted dedifferentiation program and miR-205 has potential to be used as a marker of arsenic exposure as well as a maker of early urothelial carcinoma detection.


Dye-sensitized photocathodes for H2 evolution.
The arguments for converting sunlight and H2O to H2 to provide cleaner fuels and chemicals are very powerful. However, there is still no efficient means of direct solar energy conversion to H2 on a large scale despite a large research effort worldwide. This review describes strategies to develop robust devices which exploit the selectivity of a molecular catalyst but avoids the use of sacrificial electron donors by adsorbing them onto an electrode surface. By assembling the photocathodes with photoanodes, the electrons provided by water oxidation are used to reduce H+ to H2. By separating the functions of light absorption, charge transport and catalysis between the colloidal semiconductor and molecular components, the activity of each can be optimised. However, the complexity of the system requires advanced experimental techniques to evaluate the performance. Current understanding of the factors governing electron transfer across the interface between the semiconductor, dye and catalyst is described and future directions and challenges for this field are outlined.


Another Record: Ocean Warming Continues through 2021 despite La Niña Conditions.
The increased concentration of greenhouse gases in the atmosphere from human activities traps heat within the climate system and increases ocean heat content (OHC). Here, we provide the first analysis of recent OHC changes through 2021 from two international groups. The world ocean, in 2021, was the hottest ever recorded by humans, and the 2021 annual OHC value is even higher than last year's record value by 14 ± 11 ZJ (1 zetta J = 1021 J) using the IAP/CAS dataset and by 16 ± 10 ZJ using NCEI/NOAA dataset. The long-term ocean warming is larger in the Atlantic and Southern Oceans than in other regions and is mainly attributed, via climate model simulations, to an increase in anthropogenic greenhouse gas concentrations. The year-to-year variation of OHC is primarily tied to the El Niño-Southern Oscillation (ENSO). In the seven maritime domains of the Indian, Tropical Atlantic, North Atlantic, Northwest Pacific, North Pacific, Southern oceans, and the Mediterranean Sea, robust warming is observed but with distinct inter-annual to decadal variability. Four out of seven domains showed record-high heat content in 2021. The anomalous global and regional ocean warming established in this study should be incorporated into climate risk assessments, adaptation, and mitigation.


Singlet order conversion and parahydrogen-induced hyperpolarization of 13C nuclei in near-equivalent spin systems.
We have demonstrated two radiofrequency pulse methods which convert the nuclear singlet order of proton spin pairs into the magnetisation of nearby 13C nuclei. These irradiation schemes work well in the near-equivalence regime of the three-spin system, which applies when the difference in the two 1H-13C couplings is much smaller than the 1H-1H coupling. We use pulse sequences to generate thermally polarized singlet states in a reproducible manner, and study the singlet-to-magnetisation transfer step. Preliminary results demonstrate a parahydrogen-enhanced 13C polarization level of at least 9%, providing a signal enhancement factor of more than 9000, using 50% enriched parahydrogen.


Examining the absorption of post-internship medical officers into the public sector at county-level in devolved Kenya: a qualitative case study.
After Kenya's decentralization and constitutional changes in 2013, 47 devolved county governments are responsible for workforce planning and recruitment including for doctors/medical officers (MO). Data from the Ministry of Health suggested that less than half of these MOs are being absorbed by the public sector between 2015 and 2018. We aimed to examine how post-internship MOs are absorbed into the public sector at the county-level, as part of a broader project focusing on Kenya's human resources for health. We employed a qualitative case study design informed by a simplified health labour market framework. Data included interviews with 30 MOs who finished their internship after 2018, 10 consultants who have supervised MOs, and 51 county/sub-county-level managers who are involved in MOs' planning and recruitment. A thematic analysis approach was used to examine recruitment processes, outcomes as well as perceived demand and supply. We found that Kenya has a large mismatch between supply and demand for MOs. An increasing number of medical schools are offering training in medicine while the demand for MOs in the county-level public sector has not been increasing at the same pace due to fiscal resource constraints and preference for other workforce cadres. The local Department of Health put in requests and participate in interviews but do not lead the recruitment process and respondents suggested that it can be subject to political interference and corruption. The imbalance of supply and demand is leading to unemployment, underemployment and migration of post-internship MOs with further impacts on MOs' wages and contract conditions, especially in the private sector. The mismatched supply and demand of MO accompanied by problematic recruitment processes led to many MOs not being absorbed by the public sector and subsequent unemployment and underemployment. Although Kenya has ambitious workforce norms, it may need to take a more pragmatic approach and initiate constructive policy dialogue with stakeholders spanning the education, public and private health sectors to better align MO training, recruitment and management.


Dense plasma effects on nuclear reaction rates.
Plasma density effects can cause an exponential change in charged particle nuclear reaction rates important in stellar evolution. Reaction rates in dense plasma, with emphasis on quantum aspects, are examined here using path integral Monte Carlo calculations. Quantum mechanics causes a reduction in the many body enhancement of the reaction rate compared to the value for a classical system. This can be attributed to the "quantum smearing" of the short range Coulomb interaction resulting in reduced repulsion between the reacting pair and surrounding particles. Electron screening and ion exchange effects are also examined, with screening reducing and exchange slightly increasing the many body enhancement.


Total reproductive values for females and for males in sexual diploids are not equal.
A very simple mathematical exposition of reproductive value in an age- and sex-structured sexual diploid population employs reproductive value as the probability that a random gene in a distant generation traces its ancestry to a given individual or set of individuals today. Although the total reproductive values of all females and that of all males are not in general equal, but instead proportional to the average age of a new mother and a new father, respectively, Fisher׳s equal-investment conclusion for the sex ratio remains valid because the total reproductive value of age-zero females equals the total reproductive value of age-zero males. However, the conclusion is seen to require an extra assumption, namely stability of the age-distribution.


Serum cholesterol concentration of mice selected for litter size and its relationship to litter size and testis mass.
This study assessed the genetic relationship between litter size and serum cholesterol concentration and between litter size and testis mass in mice. Mice were from a long-term experiment in which selection had occurred for 21 generations in three replicated lines per criterion of selection (LS = selection to increase litter size based on number born; LC = unselected control). Thereafter, random mating within lines was practiced. Serum cholesterol concentrations were evaluated in female and male mice from two replicates at Generation 29 and one replicate at Generation 30. Body weights and blood samples were collected from primiparous females 8 d after weaning their pups. Data from males were collected as they came out of breeding cages. In addition, the testes were excised, stripped clean of connective tissue and the epididymides, and weighed. Means for body mass of females and males, serum cholesterol, number born, and testis mass were as follows: 35.2 vs 32.5 g (P < .09), 33.9 vs 30.7 g (P < .08), 117.5 vs 110.5 mg/dL (P < .08), 14.0 vs 10.3 pups (P < .04), and 126 vs 122 mg, respectively, for LS and LC. Serum cholesterol was greater in males than in females (133.3 vs 95.1 mg/dL; P < .001), but there was no interaction between sex and selection criterion. Serum cholesterol concentration was not correlated phenotypically to number born or body mass, but it had a small negative relationship with testis mass. Therefore, we concluded that selection for litter size tended to increase serum cholesterol in addition to the increase in number born but did not change testis mass.


Axenic amastigote cultivation and in vitro development of Leishmania orientalis.
Leishmania (Mundinia) orientalis is a recently described new species that causes leishmaniasis in Thailand. To facilitate characterization of this new species, an in vitro culture system to generate L. orientalis axenic amastigotes was developed. In vitro culture conditions of the axenic culture-derived amastigotes were optimized by manipulation of temperature and pH. Four criteria were used to evaluate the resulting L. orientalis axenic amastigotes, i.e., morphology, zymographic analysis of nucleases, cyclic transformation, and infectivity to the human monocytic cell line (THP-1) cells. Results revealed that the best culture condition for L. orientalis axenic amastigotes was Grace's insect medium supplemented with FCS 20%, 2% human urine, 1% BME vitamins, and 25 μg/ml gentamicin sulfate, pH 5.5 at 35 °C. For promastigotes, the condition was M199 medium, 10% FCS supplemented with 2% human urine, 1% BME vitamins, and 25 μg/ml gentamicin sulfate, pH 6.8 at 26 °C. Morphological characterization revealed six main stages of the parasites including amastigotes, procyclic promastigotes, nectomonad promastigotes, leptomonad promastigotes, metacyclic promastigotes, and paramastigotes. Also, changes in morphology during the cycle were accompanied by changes in zymographic profiles of nucleases. The developmental cycle of L. orientalis in vitro was complete in 12 days using both culture systems. The infectivity to THP-1 macrophages and intracellular growth of the axenic amastigotes was similar to that of THP-1 derived intracellular amastigotes. These results confirmed the successful axenic cultivation of L. orientalis amastigotes. The axenic amastigotes and promastigotes can be used for further study on infection in permissive vectors and animals.


Chaperones mainly suppress primary nucleation during formation of functional amyloid required for bacterial biofilm formation.
Unlike misfolding in neurodegenerative diseases, aggregation of functional amyloids involved in bacterial biofilm, e.g. CsgA (E. coli) and FapC (Pseudomonas), is carefully regulated. However, it is unclear whether functional aggregation is inhibited by chaperones targeting pathological misfolding and if so by what mechanism. Here we analyze how four entirely different human chaperones or protein modulators (transthyretin, S100A9, Bri2 BRICHOS and DNAJB6) and bacterial CsgC affect CsgA and FapC fibrillation. CsgA is more susceptible to inhibition than FapC and the chaperones vary considerably in the efficiency of their inhibition. However, mechanistic analysis reveals that all predominantly target primary nucleation rather than elongation or secondary nucleation, while stoichiometric considerations suggest that DNAJB6 and CsgC target nuclei rather than monomers. Inhibition efficiency broadly scales with the chaperones' affinity for monomeric CsgA and FapC. The chaperones tend to target the most aggregation-prone regions of CsgA, but do not display such tendencies towards the more complex FapC sequence. Importantly, the most efficient inhibitors (Bri2 BRICHOS and DNAJB6) significantly reduce bacterial biofilm formation. This commonality of chaperone action may reflect the simplicity of functional amyloid formation, driven largely by primary nucleation, as well as the ability of non-bacterial chaperones to deploy their proteostatic capacities across biological kingdoms.


Genomes of coral dinoflagellate symbionts highlight evolutionary adaptations conducive to a symbiotic lifestyle.
Despite half a century of research, the biology of dinoflagellates remains enigmatic: they defy many functional and genetic traits attributed to typical eukaryotic cells. Genomic approaches to study dinoflagellates are often stymied due to their large, multi-gigabase genomes. Members of the genus Symbiodinium are photosynthetic endosymbionts of stony corals that provide the foundation of coral reef ecosystems. Their smaller genome sizes provide an opportunity to interrogate evolution and functionality of dinoflagellate genomes and endosymbiosis. We sequenced the genome of the ancestral Symbiodinium microadriaticum and compared it to the genomes of the more derived Symbiodinium minutum and Symbiodinium kawagutii and eukaryote model systems as well as transcriptomes from other dinoflagellates. Comparative analyses of genome and transcriptome protein sets show that all dinoflagellates, not only Symbiodinium, possess significantly more transmembrane transporters involved in the exchange of amino acids, lipids, and glycerol than other eukaryotes. Importantly, we find that only Symbiodinium harbor an extensive transporter repertoire associated with the provisioning of carbon and nitrogen. Analyses of these transporters show species-specific expansions, which provides a genomic basis to explain differential compatibilities to an array of hosts and environments, and highlights the putative importance of gene duplications as an evolutionary mechanism in dinoflagellates and Symbiodinium.


Effects of early feeding on growth velocity and overweight/obesity in a cohort of HIV unexposed South African infants and children.
South Africa has the highest prevalence of overweight/obesity in Sub-Saharan Africa. Assessing the effect of modifiable factors such as early infant feeding on growth velocity and overweight/obesity is therefore important. This paper aimed to assess the effect of infant feeding in the transitional period (12 weeks) on 12-24 week growth velocity amongst HIV unexposed children using WHO growth velocity standards and on the age and sex adjusted body mass index (BMI) Z-score distribution at 2 years. Data were from 3 sites in South Africa participating in the PROMISE-EBF trial. We calculated growth velocity Z-scores using the WHO growth standards and assessed feeding practices using 24-hour and 7-day recall data. We used quantile regression to study the associations between 12 week infant feeding and 12-24 week weight velocity (WVZ) with BMI-for-age Z-score at 2 years. We included the internal sample quantiles (70th and 90th centiles) that approximated the reference cut-offs of +2 (corresponding to overweight) and +3 (corresponding to obesity) of the 2 year BMI-for-age Z-scores. At the 2-year visit, 641 children were analysed (median age 22 months, IQR: 17-26 months). Thirty percent were overweight while 8.7% were obese. Children not breastfed at 12 weeks had higher 12-24 week mean WVZ and were more overweight and obese at 2 years. In the quantile regression, children not breastfed at 12 weeks had a 0.37 (95% CI 0.07, 0.66) increment in BMI-for-age Z-score at the 50th sample quantile compared to breast-fed children. This difference in BMI-for-age Z-score increased to 0.46 (95% CI 0.18, 0.74) at the 70th quantile and 0.68 (95% CI 0.41, 0.94) at the 90th quantile . The 12-24 week WVZ had a uniform independent effect across the same quantiles. This study demonstrates that the first 6 months of life is a critical period in the development of childhood overweight and obesity. Interventions targeted at modifiable factors such as early infant feeding practices may reduce the risks of rapid weight gain and subsequent childhood overweight/obesity.


Pathogen-induced human TH17 cells produce IFN-γ or IL-10 and are regulated by IL-1β.
IL-17-producing CD4+ T helper cells (TH17) have been extensively investigated in mouse models of autoimmunity. However, the requirements for differentiation and the properties of pathogen-induced human TH17 cells remain poorly defined. Using an approach that combines the in vitro priming of naive T cells with the ex vivo analysis of memory T cells, we describe here two types of human TH17 cells with distinct effector function and differentiation requirements. Candida albicans-specific TH17 cells produced IL-17 and IFN-γ, but no IL-10, whereas Staphylococcus aureus-specific TH17 cells produced IL-17 and could produce IL-10 upon restimulation. IL-6, IL-23 and IL-1β contributed to TH17 differentiation induced by both pathogens, but IL-1β was essential in C. albicans-induced TH17 differentiation to counteract the inhibitory activity of IL-12 and to prime IL-17/IFN-γ double-producing cells. In addition, IL-1β inhibited IL-10 production in differentiating and in memory TH17 cells, whereas blockade of IL-1β in vivo led to increased IL-10 production by memory TH17 cells. We also show that, after restimulation, TH17 cells transiently downregulated IL-17 production through a mechanism that involved IL-2-induced activation of STAT5 and decreased expression of ROR-γt. Taken together these findings demonstrate that by eliciting different cytokines C. albicans and S. aureus prime TH17 cells that produce either IFN-γ or IL-10, and identify IL-1β and IL-2 as pro- and anti-inflammatory regulators of TH17 cells both at priming and in the effector phase.


Implants and sinus-inlay graft in a 1-stage procedure in severely atrophied maxillae: prosthodontic aspects in a 3-year follow-up study.
The aim of this 3-year prospective study was to evaluate the prosthetic treatment in 2 groups of maxillary edentulous patients with similar age and gender distribution: a study group of 39 patients treated with intra-sinus block bone grafts and implants in a 1-stage procedure, and a control (reference) group of 37 patients treated with implants and no grafting. In the study group, bone volumes were regarded as insufficient for implant treatment unless a bone grafting procedure was performed (posterior alveolar bone height was less than 5 mm). Self-tapping Nobel Biocare implants were used in both groups of patients. In the study group, 35 fixed partial dentures and 4 overdentures were placed, and in the control group 34 fixed partial dentures and 3 overdentures were placed. All patients were followed for at least 3 years. The 3-year follow-up examination included examination of a number of clinical parameters as well as the type of abutment and evaluation of stability of prosthesis retention screws and abutment screws. During the follow-up period, 2 patients were lost from the study group and 4 patients from the control group, giving a total of 70 patients available for examination after 3 years (8% dropout rate). Both the amount of plaque and gingival bleeding were significantly lower in the study group than in the control group. The presence of attached gingiva was 25% in the study group and 35% in the control group. The number of angulated abutments was significantly higher in the study group than in the control group. There was no significant difference in the number of prosthetic complications in the 2 groups of patients. Neither was there any significant difference in prosthesis screw or abutment screw stability between the 2 groups. The type of abutment did not significantly influence the stability of prosthesis retention screws or abutment screws in either of the groups. However, prosthesis screw stability was significantly greater than abutment screw stability in both groups of patients. It can be concluded that the prosthetic outcome was similar in the 2 groups of patients, regardless of whether or not a bone grafting procedure was used.


Emerin inhibits Lmo7 binding to the Pax3 and MyoD promoters and expression of myoblast proliferation genes.
X-linked Emery-Dreifuss muscular dystrophy (X-EDMD) is caused by mutations in the inner nuclear membrane protein emerin. Previous studies have shown that emerin binds to and inhibits the activity of LIM domain only 7 (Lmo7), a transcription factor that regulates the expression of genes implicated in X-EDMD. Here, we analyzed Lmo7 function in C2C12 myoblast differentiation and its regulation by emerin. We found that Lmo7 was required for proper myoblast differentiation. Lmo7-downregulated myoblasts exhibited reduced expression of Pax3, Pax7, Myf5 and MyoD, whereas overexpression of GFP-Lmo7 increased the expression of MyoD and Myf5. Upon myotube formation, Lmo7 shuttled from the nucleus to the cytoplasm, concomitant with reduced expression of MyoD, Pax3 and Myf5. Importantly, we show that Lmo7 bound the Pax3, MyoD and Myf5 promoters both in C2C12 myoblasts and in vitro. Because emerin inhibited Lmo7 activity, we tested whether emerin competed with the MyoD promoter for binding to Lmo7 or whether emerin sequestered promoter-bound Lmo7 to the nuclear periphery. Supporting the competition model, emerin binding to Lmo7 inhibited Lmo7 binding to and activation of the MyoD and Pax3 promoters. These findings support the hypothesis that the functional interaction between emerin and Lmo7 is crucial for temporally regulating the expression of key myogenic differentiation genes.


[Significance of molecular network regulation of microRNA for studies on mechanisms of acu-moxibustion therapy].
Bioinformatics analysis of the molecular network regulation is the main content of systems biology, may reveal the complex life phenomena from interactions among molecules and will bring about a far-reaching impact on our current understanding about life activities of organism. MicroRNAs (functional RNAs) can regulate mRNA transcription through inhibition of post-transcriptional protein-coding gene expression, target degradation, etc., and are extensively involved in various biological processes in the cells. It is generally held that the therapeutic effect of acu-moxibustion intervention involves multi-channels, multi-targets, and multi-levels of both peripheral and central nervous systems of the body but has not been fully revealed, being similar with functional forms of molecular regulatory networks. Thus, it is necessary to introduce new ideas and methods for studying the underlying mechanism of acu-moxibustion therapy. The molecular regulatory networks of microRNA would provide a new way for revealing the mechanism of acu-moxibustion interventions.


A robot trace maker: modeling the fossil evidence of early invertebrate behavior.
The study of trace fossils, the fossilized remains of animal behavior, reveals interesting parallels with recent research in behavior-based robotics. This article reports robot simulations of the meandering foraging trails left by early invertebrates that demonstrate that such trails can be generated by mechanisms similar to those used for robot wall-following. We conclude with the suggestion that the capacity for intelligent behavior shown by many behavior-based robots is similar to that of animals of the late Precambrian and early Cambrian periods approximately 530 to 565 million years ago.


Developing the criteria for evaluating quality of individualization in homeopathic clinical trial reporting: a preliminary study.
This study describes the development of a preliminary version of an instrument that attempts to assess the quality of reports of individualized homeopathic prescriptions in clinical trials and observational studies. A multidisciplinary panel of 15 judges produced an initial version of the instrument through iterative Delphi rounds and pilot-tested the instrument on five clinical trials. Later they assessed, under blind conditions, the individualization quality of 40 randomly-selected research reports. The final version of the instrument included six criteria. These items were scored consistently by all the raters regardless of background. The instrument appeared to have adequate face and content validity, acceptable internal consistency or reliability (Cronbach's α 0.606 - 0.725), significant discriminant validity (F = 398.7; P < 0.000 1), moderate interrater reliability (Fleiss κ 0.533), agreeable test-retest reliability (Cohen's κ 0.765 - 0.934), moderate sensitivity (0.4; 95% confidence interval 0.253-0.566), and high specificity (1.0; 95% confidence interval 0.891-1.000). The initial data suggest that this instrument may be a promising systematic tool amendable for further development.


Pharmacotherapy of chronic spontaneous urticaria.
Urticaria, by definition, is a disease presenting with wheals, angioedema or both. In patients with recurrent angioedema without wheals, urticaria needs to be distinguished from bradykinin-mediated angioedema, for example, hereditary angioedema or ACE inhibitor-induced angioedema. Urticaria is comprised of acute and chronic forms. The latter group of chronic urticaria has many different subtypes needing partly different therapeutic approaches. However, all therapeutic approaches for symptomatic treatment center on reducing mast cell-mediator-release and preventing its effect. The current guidelines recommend non-sedating, second generation H1-antihistamines (nsAHs) as the first-line treatment. If needed, nsAHs are to be used at higher doses (up to fourfold the standard dose), and Omalizumab, Montelukast or Cyclosporin A (not in preferred order) are recommended as third-line options. Many alternative treatments have been reported but not tested in randomized controlled trials. These include among others dapsone, H2-antihistamines, anticoagulants and methotrexate. Some therapies should no longer be used according to current guidelines, since studies have shown their inefficacy or because new safety concerns have emerged. This mainly refers to the formally propagated use of sedating antihistamines at night, which change REM-sleeping-patterns and learning curves and have been shown in head-to-head trials to not be superior in efficacy to non-sedating antihistamines.


Chlorpyrifos bioassay and resistance monitoring of San Joaquin Valley California citricola scale populations.
The responses to chlorpyrifos of six populations of citricola scale, Coccus pseudomagnoliarum (Kuwana) (Hemiptera: Coccidae), were tested using a leaf dip bioassay, and two- to nine-fold resistances were found. LC50 responses of nymphs ranged from 7.5 to 68.9 ppm and LC90 responses ranged from 20 to 222 ppm chlorpyrifos. A population tested monthly during August-October showed up to 3.5-fold differences in LC50 responses but no differences in LC90 responses as scale size increased. A diagnostic concentration of 178 ppm chlorpyrifos was used to test 93 populations from throughout the San Joaquin Valley California during 2006-2009 by using a leaf dip bioassay. Of the populations tested, 41% showed > 20% survival after exposure to the diagnostic concentration of chlorpyrifos, indicating resistance problems. Research is needed to relate the level of survival of the scales in the bioassay to the field efficacy of the insecticide. Tulare County citrus growers applied a higher number of organophosphate and carbamate insecticides during the 15-yr period from 1994 to 2008, and these orchards showed a higher average scale survival of chlorpyrifos and a higher number of locations with resistant scale compared with the other San Joaquin Valley counties. Chlorpyrifos resistance is a significant issue for citricola scale management because biological control is ineffective in the San Joaquin Valley and the alternative neonicotinoid and insect growth regulator (IGR) insecticides require more frequent application.


Prenatal dog-keeping practices vary by race: speculations on implications for disparities in childhood health and disease.
There is consistent evidence demonstrating that pet-keeping, particularly of dogs, is beneficial to human health. We explored relationships between maternal race and prenatal dog-keeping, accounting for measures of socioeconomic status that could affect the choice of owning a pet, in a demographically diverse, unselected birth cohort. Self-reported data on mothers' race, socioeconomic characteristics and dog-keeping practices were obtained during prenatal interviews and analyzed cross-sectionally. Robust methods of covariate balancing via propensity score analysis were utilized to examine if race (Black vs White), independent of other participant traits, influenced prenatal dog-keeping. A birth cohort study conducted in a health care system in metropolitan Detroit, Michigan between September 2003 and November 2007. 1065 pregnant women (n=775 or 72.8% Black), between ages 21 and 45, receiving prenatal care. Participant's self-report of race/ethnicity and prenatal dog-keeping, which was defined as her owning or caring for > or =1 dog for more than 1 week at her home since learning of her pregnancy, regardless of whether the dog was kept inside or outside of her home. In total, 294 women (27.6%) reported prenatal dog-keeping. Prenatal dog-keeping was significantly lower among Black women as compared to White women (20.9% vs 45.5%, P<.001), and remained significantly different even after propensity score analysis was applied. Findings suggest that there are persistent racial differences in dog-keeping not fully explained by measures of socioeconomic status. Racial differences in prenatal dog-keeping may contribute to childhood health disparities.


Review of the pharmaceutical properties and clinical effects of the topical NSAID formulation, diclofenac epolamine.
Topical formulations of non-steroidal anti-inflammatory drugs (NSAIDs), in particular diclofenac (DI), have become popular for treating various acute and chronic painful inflammatory conditions. To perform a literature review of (1) the use of topical NSAIDs; (2) the pharmaceutical, pharmacokinetic and pharmacodynamic properties of a medicated plaster (patch) containing diclofenac epolamine (DI-EP, Flector Tissugel, Flector patch) compared with other formulations of topical NSAIDs; and (3) evaluation of the clinical findings from studies with this novel DI-EP patch. (1) Pharmacokinetic studies involved determination of DI from DI-EP and separately epolamine (EP) and the epoxide metabolite (N-oxide-EP) in laboratory animals and humans; the latter being the major metabolite in humans. About 2% of DI is absorbed by the skin in humans and is excreted in the urine. Maximum plasma concentrations of 17.4 ng/mL DI are reached at 5.4 hours (approximate steady state conditions); the plasma elimination half-time (t(1/2)) being 26.4 hours. Low systemic levels of DI and EP are produced from DI-EP. Pronounced accumulation of DI occurs in the muscle layers and in synovial fluids of arthritic patients; (2) No significant toxicity occurs from EP nor N-oxide-EP, while that of oral DI-EP was similar to that from DI; and (3) In acute musculoskeletal conditions (sprains, tendonitis and sports injuries) and osteoarthritis DI-EP patches control pain and signs of joint or physical injury compared with placebo controls by 3-5 days with almost complete pain relief at 14 days. DI-EP was shown to have equivalent therapeutic effect to another DI diethylammonium gel formulation (Voltaren Emulgel). There were no reports of serious adverse events in the gastro-intestinal (GI) tract, kidneys or liver from DI-EP. Mild GI symptoms and skin reactions occur in 2 and 10% of patients, respectively. The patch delivery of DI in DI-EP affords controlled delivery of the active drug in contrast to that from application of gels or ointments of NSAIDs.


Climate and Health Co-Benefits in Low-Income Countries: A Case Study of Carbon Financed Water Filters in Kenya and a Call for Independent Monitoring.
The recent global climate agreement in Paris aims to mitigate greenhouse gas emissions while fostering sustainable development and establishes an international trading mechanism to meet this goal. Currently, carbon offset program implementers are allowed to collect their own monitoring data to determine the number of carbon credits to be awarded. We summarize reasons for mandating independent monitoring of greenhouse gas emission reduction projects. In support of our policy recommendations, we describe a case study of a program designed to earn carbon credits by distributing almost one million drinking water filters in rural Kenya to avert the use of fuel for boiling water. We compare results from an assessment conducted by our research team in the program area among households with pregnant women or caregivers in rural villages with low piped water access with the reported program monitoring data and discuss the implications. Our assessment in Kenya found lower levels of household water filter usage than the internal program monitoring reported estimates used to determine carbon credits; we found 19% (n = 4,041) of households reported filter usage 2-3 years after filter distribution compared to the program stated usage rate of 81% (n = 14,988) 2.7 years after filter distribution. Although carbon financing could be a financially sustainable approach to scale up water treatment and improve health in low-income settings, these results suggest program effectiveness will remain uncertain in the absence of requiring monitoring data be collected by third-party organizations. Independent monitoring should be a key requirement for carbon credit verification in future international carbon trading mechanisms to ensure programs achieve benefits in line with sustainable development goals. Citation: Pickering AJ, Arnold BF, Dentz HN, Colford JM Jr., Null C. 2017. Climate and health co-benefits in low-income countries: a case study of carbon financed water filters in Kenya and a call for independent monitoring. Environ Health Perspect 125:278-283; http://dx.doi.org/10.1289/EHP342.


Use of assistive technology devices in mainstream schools: students' perspective.
The use and nonuse of assistive technology devices in school by students with physical disabilities was investigated, and the students' experiences in using these devices is described. We used a mixed-methods approach with predominantly qualitative methods to collect and analyze data, which included observations of and interviews with 20 students with physical disabilities and the number and type of assistive technology devices provided. It is vital that devices be integrated into educational practice and that students experience immediate benefits for their function in everyday school activities without detrimental effects on their social participation. The latter was often more important than being able to perform activities independently. The students adopted both a functional and a psychosocial perspective of their devices, and providers should neglect neither. Children and youth need both verbal information and practical experience using devices to be able to make informed decisions.


Efficacy of Bifidobacterium infantis 35624 in patients with irritable bowel syndrome: a meta-analysis.
The treatment of irritable bowel syndrome (IBS) is a challenge because its cause remains unknown. Previous clinical trials to examine the efficacy of probiotic Bifidobacterium infantis 35624 (B. infantis) in patients with IBS have shown inconsistent findings. This study aimed to assess the combined effect of B. infantis on reducing the symptom severity of IBS based on the published data. A meta-analysis was conducted using fixed-effect models to estimate the combined effect of B. infantis on primary outcomes, which included abdominal pain, bloating/distention, and bowel habit satisfaction. A systematic review was performed based on PubMed, Cochrane Library, and EMBASE databases to identify the randomized controlled trials comparing probiotic B. infantis with placebo in treating IBS symptoms, published up until 31 December 2016. The standardized mean difference (SMD) method was used to combine data since scales to measure the efficacy of probiotics were different among studies. A total of five studies were identified as suitable for inclusion, including three studies with single probiotic B. infantis and two studies with composite probiotics containing B. infantis. Treatment with single probiotic B. infantis didn't impact on abdominal pain, bloating/distention, or bowel habit satisfaction among IBS patients. However, patients who received composite probiotics containing B. infantis had significantly reduced abdominal pain (SMD, 0.22; 95% CI, 0.03-0.41) and bloating/distention (SMD, 0.30; 95% CI, 0.04-0.56). After combining the data from six studies, the improvement of bloating/distention among IBS patients remained significant (SMD, 0.21; 95% CI, 0.07-0.35). Composite probiotics containing B. infantis might be an effective therapeutic option for IBS patients, which could significantly alleviate the symptoms of IBS without significant adverse effects. However, the efficacy of single probiotic B. infantis on IBS has not been confirmed yet, which needs to be further validated by more large-sized randomized clinical trials.


Opportunities to improve the cost-effectiveness of treatment for hypertension.
The cost-effectiveness of treatment for hypertension depends on the pretreatment level of blood pressure, age and sex of the patient, presence of other cardiovascular risk factors, long-term control of blood pressure, and the annual costs of treatment. Treatment of very mild hypertension (diastolic blood pressure, 90-94 mm Hg), even if the benefits do exceed the risks, does not appear to be particularly cost-effective. Opportunities to improve the cost-effectiveness of hypertension management lie in 1) avoidance of patient mislabeling by careful documentation of blood pressures on multiple occasions in the office and during usual activities outside the office before the diagnosis is made and treatment is begun; 2) efforts to increase adherence to scheduled visits and medication regimens; 3) attempts to step-down dosages or discontinue medications after periods of good blood pressure control; 4) explicit consideration of costs, as well as benefits, in decisions on the needed frequency of office visits, choice of medications, and use of laboratory tests; and 5) efforts to improve practice efficiency. Future practice guidelines for hypertension management should take these factors into account and should make trade-offs between benefits, risks, and costs explicit for specific types of patients.


The genome of the model beetle and pest Tribolium castaneum.
Tribolium castaneum is a member of the most species-rich eukaryotic order, a powerful model organism for the study of generalized insect development, and an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved the ability to interact with a diverse chemical environment, as shown by large expansions in odorant and gustatory receptors, as well as P450 and other detoxification enzymes. Development in Tribolium is more representative of other insects than is Drosophila, a fact reflected in gene content and function. For example, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, some being expressed in the growth zone crucial for axial elongation in short-germ development. Systemic RNA interference in T. castaneum functions differently from that in Caenorhabditis elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.


Circadian Period Modulation and Masking Effects Induced by Repetitive Light Pulses in Locomotor Rhythms of the Cricket, Gryllus bimaculatus.
Effects of 15 min light pulses given at various intervals (every 1, 2, 4, 6, 8 and 12 hr) under constant darkness on the locomotor rhythm were investigated in the adult male cricket, Gryllus bimaculatus. A single pulse per 24 hr induced period modulation in a circadian phase dependent manner, yielding a period modulation curve (PMC): the 15 min light pulse lengthened the period in the early subjective night (CT11-16) and shortened it during the late subjective night to the early subjective day (CT20-5). Frequent light pulses modulated the freerunning period of the rhythm dependent on the interval of the pulses: when compared with the freerunning period in DD (23.74 +/- 0.03 hr) the period was significantly shorter in intervals of 2 and 4 hr, but lengthened when the interval was 1 and 12 hr. Frequent light pulses also resulted in entrainment of the rhythm to run with the period of 24 hr and the ratio of the entrained animals varied from 12% to 72% depending on the interval of the light pulses. The period modulation and the entrainment by the repetitive light pulses could be interpreted according to the PMC. In about 15% of animals, the light pulses induced a rhythm dissociation, suggesting that the bilaterally paired circadian pacemakers have their own sensitivity to the entraining photic information. The light pulse caused a masking effect, i.e., an intense burst of activity. The magnitude of the light induced responses was dependent on the circadian phase. The strongest masking effect was observed in the subjective night. The phase of the prominent period modulation and of the marked masking effects well coincides with the previously reported sensitive phase of the photoreceptive system.


Cancer detection rates of different prostate biopsy regimens in patients with renal failure.
We aimed to evaluate the cancer detection rates of 6-, 10-, 12-core biopsy regimens and the optimal biopsy protocol for prostate cancer diagnosis in patients with renal failure. A total of 122 consecutive patients with renal failure underwent biopsy with age-specific prostate-specific antigen (PSA) levels up to 20 ng/mL. The 12-core biopsy technique (sextant biopsy + lateral base, lateral mid-zone, lateral apex, bilaterally) performed to all patients. Pathology results were examined separately for each sextant, 10-core that exclude parasagittal mid-zones from 12-cores (10a), 10-core that exclude apex zones from 12-cores (10b) and 12-core biopsy regimens. Of 122 patients, 37 (30.3%) were positive for prostate cancer. The cancer detection rates for sextant, 10a, 10b and 12 cores were 17.2%, 29%, 23.7% and 30.7%, respectively. Biopsy techniques of 10a, 10b and 12 cores increased the cancer detection rates by 40%, 27.5% and 43.2% among the sextant technique, respectively. Biopsy techniques of 10a and 12 cores increased the cancer detection rates by 17.1% and 21.6% among 10b biopsy technique, respectively. There were no statistical differences between 12 core and 10a core about cancer detection rate. Adding lateral cores to sextant biopsy improves the cancer detection rates. In our study, 12-core biopsy technique increases the cancer detection rate by 5.4% among 10a core but that was not statistically different. On the other hand, 12-core biopsy technique includes all biopsy regimens. We therefore suggest 12-core biopsy or minimum 10-core strategy incorporating six peripheral biopsies with elevated age- specific PSA levels up to 20 ng/mL in patients with renal failure.


Requirement for the transcription factor LSIRF/IRF4 for mature B and T lymphocyte function.
Lymphocyte-specific interferon regulatory factor (LSIRF) (now called IRF4) is a transcription factor expressed only in lymphocytes. Mice deficient in IRF4 showed normal distribution of B and T lymphocyes at 4 to 5 weeks of age but developed progressive generalized lymphadenopathy. IRF4-deficient mice exhibited a profound reduction in serum immunoglobulin concentrations and did not mount detectable antibody responses. T lymphocyte function was also impaired in vivo; these mice could not generate cytotoxic or antitumor responses. Thus, IRF4 is essential for the function and homeostasis of both mature B and mature T lymphocytes.


Long-term health-related quality of life improvements among patients treated with lurasidone: results from the open-label extension of a switch trial in schizophrenia.
Long-term improvement of health-related quality of life (HRQoL) in schizophrenia may improve adherence and reduce relapse and rehospitalization. This analysis examines long-term changes in HRQoL among patients with schizophrenia switched to lurasidone from other antipsychotics. Patients who completed an open-label 6-week switch study continued on lurasidone for an additional 24-weeks. HRQoL was measured using the self-reported Personal Evaluation of Transitions in Treatment (PETiT) scale and Short-Form 12 (SF-12) questionnaire. The PETiT assessed HRQoL via total and domain scores (adherence-related attitude and psychosocial functioning). The SF-12 assessed patients' mental and physical component summary scores (MCS and PCS). Mean changes from the initial baseline were calculated at extension baseline and extension endpoint using analysis of covariance models. Analyses were further stratified by prior antipsychotic medication and responder status; responders were defined as having a ≥20 % improvement in Positive and Negative Syndrome Scale during the first 6-weeks of treatment. The analysis included 144 patients with PETIT or SF-12 data who received ≥1 dose of lurasidone. Mean (standard deviation) PETiT total score improved significantly from 34.9 (9.3) at baseline to 39.5 (8.9) at extension baseline and 39.1 (9.0) at extension endpoint, representing improvements of 4.5 (7.9) and 5.1 (7.2) points, respectively (both p < 0.001). Significant improvements in adherence-related attitude and psychosocial functioning were observed at extension baseline and extension endpoint (all p < 0.001). Improvement in SF-12 MCS score was observed at extension baseline and endpoint, and PCS score at extension endpoint (all p < 0.01). Patients who switched from quetiapine and aripiprazole showed significant improvement of PETiT total score and adherence-related attitude at extension baseline and extension endpoint. In addition, patients who switched from quetiapine, risperidone, aripiprazole, or ziprasidone showed significant improvement in MCS scores from baseline to extension endpoint. Responders to lurasidone demonstrated greater improvement in PETiT total, psychosocial functioning, and MCS scores at extension baseline than nonresponders. After switching to lurasidone, patients with schizophrenia experienced HRQoL improvements that were sustained for an additional 24 weeks of treatment. Further study is warranted to understand the implications of these improvements in terms of employment, adherence, relapse, and rehospitalization. Clinical trials.gov identifier NCT01143090 (June 10th, 2010).


Prediction of soft-tissue injuries in Schatzker II tibial plateau fractures based on measurements of plain radiographs.
Split-depression fractures of the lateral tibial plateau (Schatzker II) are associated with a significant risk of capsuloligamentous and meniscal injury. We hypothesized that the amount of fracture depression and widening on anteroposterior (AP) plain radiographs would correlate with the incidence of injury to these structures on magnetic resonance imaging (MRI). Sixty-two consecutive patients with Schatzker II tibial plateau fractures had a knee x-ray series and MRI preoperatively. AP plain radiographs were measured for lateral joint line depression and condylar widening, and MRIs were evaluated for injury to soft-tissue structures around the knee. For each structure, the threshold of depression and widening that led to the greatest disparity in soft-tissue injury was determined. Multiple logistic regressions were applied to calculate whether depression and/or widening above the thresholds were predictive for injury to individual soft-tissue structures. When depression was greater than 6 mm and widening was greater than 5 mm, lateral meniscal injury occurred in 83% of fractures, compared with 50% of fractures with less displacement (p < 0.05). When either depression or widening was at least 8 mm, medial meniscal injury occurred more frequently (depression 53%, p < 0.05; widening 78%, p < 0.05; versus neither 15%). Lateral collateral ligament and posterior cruciate ligament tears were not seen with minimally displaced fractures (< 4 mm), but the incidence of injury approached 30% with increasing displacement. Due to the limited availability of MRI in some centers, correlation of lateral condylar depression and widening, as measured on plain radiographs, to injury of various soft-tissue structures may be extremely helpful in planning open or arthroscopic treatment methods. Using these guidelines, Schatzker II fractures with depression or widening approaching 5 mm deserve heightened vigilance in diagnosing and treating these concomitant soft-tissue injuries.


Effect of smoking and comorbidities on survival in idiopathic pulmonary fibrosis.
Cigarette smoking has been associated with the risk of idiopathic pulmonary fibrosis (IPF). Certain comorbidities have been associated with reduced survival although some studies have indicated that current smokers have a longer survival than ex-smokers. Comorbidities in relation to smoking history have not been previously analyzed. Retrospective data was collected and patients were categorized according to gender and smoking habits. Comorbidities and medications were collected. Predictive values for mortality were identified by COX proportional hazard analyses. We examined 45 non-smokers (53.3% female), 66 ex-smokers (9.1% female) and 17 current smokers (17.6% female) with IPF. Current smokers were younger at baseline (58.1 ± 8.74 years) compared to non-smokers (71.4 ± 8.74, p < 0.001) and ex-smokers (72.5 ±7.95, p <0.001). Median survival of non-smokers and current smokers was longer (55.0 and 52.0 months, respectively) than that of ex-smokers (36.0 months) (p=0.028 and 0.034, respectively). In age and severity adjusted analyses, smoking was not related to survival. Cardiovascular diseases (CVD) (72.7 %) were the most common comorbidities, current smokers had more chronic obstructive pulmonary disease (COPD) and lung cancer compared to ex-smokers (p<0.001). CVD, COPD and use of insulin were related to poorer survival in adjusted analyses. Smoking seems to influence the course of disease in IPF since current smokers developed the disease at a younger age in comparison to non-smokers and ex-smokers. No significant differences in the major comorbidities were detected between IPF patients with different smoking histories. The mechanism through which smoking influences IPF progression requires further investigation.


The emergence of different resistance mechanisms toward nucleoside inhibitors is explained by the properties of the wild type HIV-1 reverse transcriptase.
Nucleoside reverse transcriptase inhibitors (NRTIs) represent one of the main drug families used against AIDS. Once incorporated in DNA, they act as chain terminators, due to the lack of a 3'-hydroxyl group. As for the other anti-human immunodeficiency virus type 1 drugs, their efficiency is limited by the emergence of resistant viral strains. Unexpectedly, previous studies indicated that resistance toward NRTIs is achieved via two distinct and generally exclusive mechanisms. Resistance mutations either decrease the efficiency of NRTIs incorporation or increase their excision from the extended primer. To understand the emergence of different resistance mechanisms toward a single inhibitor class, we compared the incorporation and the pyrophosphorolysis of several NRTIs using wild type reverse transcriptase (WT RT). We found that the efficiency of discrimination or excision by pyrophosphorolysis in the presence of nucleotides of a given NRTI is a key determinant in the emergence of one or the other resistance pathway. Indeed, our results suggest that the pathway by which RT become resistant toward a given NRTI can be predicted by studying the inhibition of WT RT, because the resistance mutations do not confer new properties to the mutant enzyme, but rather exacerbate pre-existing properties of the WT enzyme. They also help to understand the low cross-resistance toward d4T observed with the 3'-azido-3'-deoxythymidine (AZT or zidovudine)-resistant RT.


The force of impacting rain.
Drop impacts are difficult to characterize due to their transient, non-stationary nature. We discuss the force generated during such impacts, a key quantity for animals, plants, roofs or soil erosion. Although a millimetric drop has a modest weight, it can generate collision forces on the order of thousand times this weight. We measure and discuss this amplification, considering natural parameters such as drop radius and density, impact speed and response time of the substrate. We finally imagine two kinds of devices allowing us to deduce the size of the raindrop from impact forces.


Biology of Muscle Atrophy and of its Recovery by FES in Aging and Mobility Impairments: Roots and By-Products.
There is something in our genome that dictates life expectancy and there is nothing that can be done to avoid this; indeed, there is not yet any record of a person who has cheated death. Our physical prowess can vacillate substantially in our lifetime according to our activity levels and nutritional status and we may fight aging, but we will inevitably lose. We have presented strong evidence that the atrophy which accompanies aging is to some extent caused by loss of innervation. We compared muscle biopsies of sedentary seniors to those of life long active seniors, and show that these groups indeed have a different distribution of muscle fiber diameter and fiber type. The senior sportsmen have many more slow fiber-type groupings than the sedentary people which provides strong evidence of denervation-reinnervation events in muscle fibers. It appears that activity maintains the motoneurons and the muscle fibers. Premature or accelerated aging of muscle may occur as the result of many chronic diseases. One extreme case is provided by irreversible damage of the Conus and Cauda Equina, a spinal cord injury (SCI) sequela in which the human leg muscles may be completely and permanently disconnected from the nervous system with the almost complete disappearance of muscle fibers within 3-5 years from SCI. In cases of this extreme example of muscle degeneration, we have used 2D Muscle Color CT to gather data supporting the idea that electrical stimulation of denervated muscles can retain and even regain muscle. We show here that, if people are compliant, atrophy can be reversed. A further example of activity-related muscle adaptation is provided by the fact that mitochondrial distribution and density are significantly changed by functional electrical stimulation in horse muscle biopsies relative to those not receiving treatment. All together, the data indicate that FES is a good way to modify behaviors of muscle fibers by increasing the contraction load per day. Indeed, it should be possible to defer the muscle decline that occurs in aging people and in those who have become unable to participate in physical activities. Thus, FES should be considered for use in rehabilitation centers, nursing facilities and in critical care units when patients are completely inactive even for short periods of time.


Graphical calibration curves and the integrated calibration index (ICI) for survival models.
In the context of survival analysis, calibration refers to the agreement between predicted probabilities and observed event rates or frequencies of the outcome within a given duration of time. We aimed to describe and evaluate methods for graphically assessing the calibration of survival models. We focus on hazard regression models and restricted cubic splines in conjunction with a Cox proportional hazards model. We also describe modifications of the Integrated Calibration Index, of E50 and of E90. In this context, this is the average (respectively, median or 90th percentile) absolute difference between predicted survival probabilities and smoothed survival frequencies. We conducted a series of Monte Carlo simulations to evaluate the performance of these calibration measures when the underlying model has been correctly specified and under different types of model mis-specification. We illustrate the utility of calibration curves and the three calibration metrics by using them to compare the calibration of a Cox proportional hazards regression model with that of a random survival forest for predicting mortality in patients hospitalized with heart failure. Under a correctly specified regression model, differences between the two methods for constructing calibration curves were minimal, although the performance of the method based on restricted cubic splines tended to be slightly better. In contrast, under a mis-specified model, the smoothed calibration curved constructed using hazard regression tended to be closer to the true calibration curve. The use of calibration curves and of these numeric calibration metrics permits for a comprehensive comparison of the calibration of competing survival models.


Nausea and vomiting of pregnancy: an evolutionary hypothesis.
Nausea and vomiting of pregnancy, "morning sickness", is a common contemporary complaint. Many pregnant patients note alterations in smell and taste which can precipitate "morning sickness", symptoms that characterize early gestation. Epidemiologic studies suggest that pregnancies accompanied by "morning sickness" have better outcomes than asymptomatic pregnancies. The intimate connection between immunogenetic identity, chemoidentity, and chemocommunication by olfactory mechanisms suggests a relationship between maternal symptoms and maternal accommodation of paternal antigens contained in the fetoplacental unit. Most mammalian species utilize olfaction to reduce inbreeding and thus do not require an intimate placental connection between mother and fetus. The evolution of Homo sapiens included prolonged periods of small, genetically homogeneous foraging groups which limited selection of genetically heterogeneous mates. Adaptation to this circumstance included a reduction of olfactory precision in mate selection and a more intimate association between mother and fetus, the hemochorial placenta.


Analysis of the experience of Cuban physicians in a Brazilian metropolis in accordance with the Paideia Method.
We had hoped that the Mais Médicos Program (More Doctors Program) would have generated several changes and reflections in each municipality in which it was deployed. In order to observe those changes, we sought to analyze the experience of Cuban physicians in the Mais Médicos program from an actor-centered perspective, based on the Paideia Method - an approach that seeks to enhance the ability of the subjects to analyze and intervene in their practice. We performed semi-structured interviews to analyze our research object that consisted in the experience of those actors included professionally in the Mais Médicos program in a metropolis with unique characteristics. In order to assess the interviews, we applied Content Analysis followed by Thematic Analysis. From the discourse of the actors, of which illustrative excerpts are transcribed in this article, we can affirm that the program's potential surpassed any initial barriers, presenting itself as fine-tuning instrument for replacing the biomedical model in line with the Paideia Method.


Prototypes of self-powered radiation detectors employing intrinsic high-energy current.
The authors experimentally investigate the effect of direct energy conversion of x-rays via selfpowered Auger- and photocurrent, potentially suitable to practical radiation detection and dosimetry in medical applications. Experimental results are compared to computational predictions. The detector the authors consider is a thin-film multilayer device, composed of alternating disparate electrically conductive and insulating layers. This paper focuses on the experiments while a companion paper introduces the fundamental concepts of high-energy current (HEC) detectors. The energy of ionizing radiation is directly converted to detector signal via electric current induced by high-energy secondary electrons generated in the detector material by the incident primary radiation. The HEC electrons also ionize the dielectric and the resultant charge carriers are selfcollected due to the contact potential of the disparate electrodes. Thus, an electric current is induced in the conductors in two different ways without the need for externally applied bias voltage or amplification. Thus, generated signal in turn is digitized by a data acquisition system. To determine the fundamental properties of the HEC detector and to demonstrate its feasibility for medical applications, the authors used a planar geometry composed of multilayer microstructures. Various detectors with up to seven conducting layers with different combinations of materials (250 μm Al, 35 μm Cu, 100 μm Pb) and air gaps (100 μm) were exposed to nearly plane-parallel 60-120 kVp x-ray beams. For the experimental design and verification, the authors performed coupled electron-photon radiation transport computations. The detector signal was measured using a commercial data acquisition system with 24 bits dynamic range, 0.4 fC sensitivity, and 0.9 ms sampling time. Measured signals for the prototype detector varied depending on the number of layers, material type, and incident photon energy, and it was in the range of 30-150 nA/cm(2) for unit air kerma (1 Gy), which is viable for practical applications. The experiments had an excellent agreement with the computations. Within the examined range of 60-120 kVp, the energy dependence of the HEC (normalized to the x-ray tube output) was relatively small. Based on the experimental results for 100 ms sampling time, it would be possible to measure the time dependence of x-ray beams for x-ray tube current of 0.1 mA or higher. Significant advantages of the HEC device are that generation of its signal does not require external power supply, it can be made in any size and shape, including flexible curvilinear forms, and it is inexpensive. It remains to be determined, which of the potential applications in medical dosimetry (both in vivo and external), or radiation protection would benefit from such selfpowered detectors.


Acupuncture for shoulder pain.
There are many commonly employed forms of treatment for shoulder disorders. This review of acupuncture is one in a series of reviews of varying interventions for shoulder disorders including adhesive capsulitis (frozen shoulder), rotator cuff disease and osteoarthritis. Acupuncture to treat musculoskeletal pain is being used increasingly to confer an analgesic effect and to date its use in shoulder disorder has not been evaluated in a systematic review. To determine the efficacy and safety of acupuncture in the treatment of adults with shoulder pain. The Cochrane Controlled Trials Register, MEDLINE, EMBASE and CINAHL were searched from inception to December 2003, and reference lists from relevant trials were reviewed. Randomised and quasi-randomised trials, in all languages, of acupuncture compared to placebo or another intervention in adults with shoulder pain. Specific exclusions were duration of shoulder pain less than three weeks, rheumatoid arthritis, polymyalgia rheumatica, cervically referred pain and fracture. Two reviewers independently extracted trial and outcome data. For continuous outcome measures where the standard deviations were not reported it was either calculated from the raw data or converted from the standard error of the mean. If neither of these was reported, authors were contacted. Where results were reported as median and range, the trial was not included in the meta-analysis, but presented in Additional Tables. Effect sizes were calculated and combined in a pooled analysis if the study end-points population and intervention were homogenous. Results are presented separately for rotator cuff disease, adhesive capsulitis, full thickness rotator cuff tear and mixed diagnoses, and, where possible, combined in meta-analysis to indicate effect of acupuncture across all shoulder disorders. Nine trials of varying methodological quality met the inclusion criteria. For all trials there was poor description of interventions. Varying placebos were used in the different trials. Two trials assessed short-term success (post intervention) of acupuncture for rotator cuff disease and could be combined in meta analysis. There was no significant difference in short-term improvement associated with acupuncture when compared to placebo, but due to small sample sizes this may be explained by Type II error. Acupuncture was of benefit over placebo in improving the Constant Murley Score (a measure of shoulder function) at four weeks (WMD 17.3 (7.79, 26.81)). However, by four months, the difference between the acupuncture and placebo groups, whilst still statistically significant, was no longer likely to be clinically significant (WMD 3.53 (0.74, 6.32)). The Constant Murley Score is graded out of 100, hence a change of 3.53 is unlikely to be of substantial benefit. The results of a small pilot study demonstrated some benefit of both traditional and ear acupuncture plus mobilization over mobilization alone. There was no difference in adverse events related to acupuncture when compared to placebo, however this was assessed by only one trial Due to a small number of clinical and methodologically diverse trials, little can be concluded from this review. There is little evidence to support or refute the use of acupuncture for shoulder pain although there may be short-term benefit with respect to pain and function. There is a need for further well designed clinical trials.


A computerized decision support system improves the accuracy of temperature capture from nursing personnel at the bedside.
To assess the effect of a computerized decision support system (CDSS) on the accuracy of patient temperature recording at the bed side. This is a randomized, controlled trial comparing nurses assigned to an intervention group that received CDSS whenever they attempted to store a low temperature (</= 96.4 degrees F) or a control group that received no CDSS. The computer recorded temperatures that would trigger reminders equally in both control and intervention groups. It also logged the reactions of nurses who received reminders and whether they retook the patient's temperature or chose to store the original low value. We analyzed the temperature data over a 10-month period tracking a total of 44339 temperatures taken by the control group and 45823 temperatures taken by the intervention group. We showed a 51% relative reduction in the number of erroneous low temperatures stored by the intervention versus the control group. CDSS are effective with nursing personnel in improving the accuracy of temperature capture at the bedside.


Prediction and imitation in speech.
It has been suggested that intra- and inter-speaker variability in speech are correlated. Interlocutors have been shown to converge on various phonetic dimensions. In addition, speakers imitate the phonetic properties of voices they are exposed to in shadowing, repetition, and even passive listening tasks. We review three theoretical accounts of speech imitation and convergence phenomena: (i) the Episodic Theory (ET) of speech perception and production (Goldinger, 1998); (ii) the Motor Theory (MT) of speech perception (Liberman and Whalen, 2000; Galantucci et al., 2006); (iii) Communication Accommodation Theory (CAT; Giles and Coupland, 1991; Giles et al., 1991). We argue that no account is able to explain all the available evidence. In particular, there is a need to integrate low-level, mechanistic accounts (like ET and MT), and higher-level accounts (like CAT). We propose that this is possible within the framework of an integrated theory of production and comprehension (Pickering and Garrod, 2013). Similarly to both ET and MT, this theory assumes parity between production and perception. Uniquely, however, it posits that listeners simulate speakers' utterances by computing forward-model predictions at many different levels, which are then compared to the incoming phonetic input. In our account phonetic imitation can be achieved via the same mechanism that is responsible for sensorimotor adaptation; i.e., the correction of prediction errors. In addition, the model assumes that the degree to which sensory prediction errors lead to motor adjustments is context-dependent. The notion of context subsumes both the preceding linguistic input and non-linguistic attributes of the situation (e.g., the speaker's and listener's social identities, their conversational roles, the listener's intention to imitate).


Quantitative T-wave analysis predicts 1 year prognosis and benefit from early invasive treatment in the FRISC II study population.
To investigate the prognostic value of T-wave abnormalities in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS), and whether such ECG changes may predict benefit from an early coronary angiography. Although ST-segment changes are considered the most important ECG feature in NSTE-ACS, T-wave abnormalities are the most common ECG finding. We hypothesize that a new quantitative approach to T-wave analysis could improve the prognostic value of this ECG abnormality. Quantitative T-wave analysis was performed on the admission ECG in 1609 patients with NSTE-ACS. Nine different categories of T-wave abnormality were analysed for their prognostic value concerning clinical outcome in patients not randomized to early coronary angiography. Also, the presence of one category (i.e. T-wave abnormality in > or =6 leads) was analysed for its predictive value concerning benefit from early coronary angiography. The combined study endpoint was death or myocardial infarction at 1 year follow-up. Patients with > or =6 leads with abnormal T-waves and concomitant ST-segment depression had a higher risk when not receiving early coronary angiography (24 vs. 12%, respectively; P=0.003), but could be brought to the same level of risk as the remaining patients with this treatment. For non-invasively treated patients five different categories of T-wave abnormality were significantly associated with an adverse outcome. New quantitative T-wave analysis of the admission ECG gives additional predictive information concerning clinical outcome and identifies patients who benefit from early coronary angiography.


Large atypical cells of lymphomatoid papulosis are CD56-negative: a study of 18 cases.
Histologically, diffuse dermal infiltrates of large atypical lymphocytes can be seen in lesions as indolent as type C lymphomatoid papulosis (LyP) to ones as aggressive as NK/T-cell lymphoma. While lesions of lymphomatoid papulosis are definitionally positive for CD30, their ability to express CD56 has not been formally studied. The objective of the current study was to determine whether or not the large atypical cells of LyP express the natural killer cell marker, CD56. Biopsies from 18 patients with LyP were studied with monoclonal antibodies to CD30, CD56, CD8, and TIA-1. These included four type C LyP lesions. Clinical information was obtained by chart review and included extent of LyP lesions, presence/absence of disease at follow-up, and any associated hematologic malignancies,. None of the biopsies exhibited CD56 positivity within the large atypical cells of LyP. While some biopsies demonstrated CD56-positive, small, presumably reactive, lymphocytes within the infiltrate, their presence did not correlate with extent of disease, persistence of disease, or propensity for an associated non-LyP hematologic malignancy. The large atypical cells of types A and C LyP do not exhibit positivity for CD56, and thus a panel of antibodies that includes CD30 and CD56 can readily distinguish between the benign end of the spectrum of CD30-positive lymphoproliferations and aggressive NK/T-cell lymphoma.


Synthesis of monoalkylidene diketopiperazines and application to the synthesis of barettin.
The synthesis of barettin, a selective serotonin receptor inhibitor and potent antibiofouling natural product, is described. The synthesis starts with the diketopiperazine nucleus intact and the side chains are installed using iterative aldol condensations. The route represents a general strategy for synthesis of a wide array of mono-alkylidene diketopiperazine structures, including those derived from non-canonical amino acid residues.


Timing of organogenesis support basal position of turtles in the amniote tree of life.
The phylogenetic position of turtles is the most disputed aspect in the reconstruction of the land vertebrate tree of life. This controversy has arisen after many different kinds and revisions of investigations of molecular and morphological data. Three main hypotheses of living sister-groups of turtles have resulted from them: all reptiles, crocodiles + birds or squamates + tuatara. Although embryology has played a major role in morphological studies of vertebrate phylogeny, data on developmental timing have never been examined to explore and test the alternative phylogenetic hypotheses. We conducted a comprehensive study of published and new embryological data comprising 15 turtle and eight tetrapod species belonging to other taxa, integrating for the first time data on the side-necked turtle clade. The timing of events in organogenesis of diverse character complexes in all body regions is not uniform across amniotes and can be analysed using a parsimony-based method. Changes in the relative timing of particular events diagnose many clades of amniotes and include a phylogenetic signal. A basal position of turtles to the living saurian clades is clearly supported by timing of organogenesis data. The clear signal of a basal position of turtles provided by heterochronic data implies significant convergence in either molecular, adult morphological or developmental timing characters, as only one of the alternative solutions to the phylogenetic conundrum can be right. The development of a standard reference series of embryological events in amniotes as presented here should enable future improvements and expansion of sampling and thus the examination of other hypotheses about phylogeny and patterns of the evolution of land vertebrate development.


Differences in intensity and specificity of hypersensitive response induction in Nicotiana spp. by INF1, INF2A, and INF2B of Phytophthora infestans.
Elicitins form a family of structurally related proteins that induce the hypersensitive response (HR) in plants, particularly Nicotiana spp. The elicitin family is composed of several classes. Most species of the plant-pathogenic oomycete genus Phytophthora produce the well-characterized 10-kDa canonical elicitins (class I), such as INF1 of the potato and tomato pathogen Phytophthora infestans. Two genes, inf2A and inf2B, encoding a distinct class (class III) of elicitin-like proteins, also occur in P. infestans. Unlike secreted class I elicitins, class III elicitins are thought to be cell-surface-anchored polypeptides. Molecular characterization of the inf2 genes indicated that they are widespread in Phytophthora spp. and occur as a small gene family. In addition, Southern blot and Northern blot hybridizations using gene-specific probes showed that inf2A and inf2B genes and transcripts can be detected in 17 different P. infestans isolates. Functional secreted expression in plant cells of the elicitin domain of the infl and inf2 genes was conducted using a binary Potato virus X (PVX) vector (agroinfection) and Agrobacterium tumefaciens transient transformation assays (agroinfiltration), and resulted in HR-like necrotic symptoms and induction of defense response genes in tobacco. However, comparative analyses of elicitor activity of INF1, INF2A, and INF2B revealed significant differences in intensity, specificity, and consistency of HR induction. Whereas INF1 induced the HR in Nicotiana benthamiana, INF2A induced weak symptoms and INF2B induced no symptoms on this plant. Nonetheless, similar to INF1, HR induction by INF2A in N. benthamiana required the ubiquitin ligase-associated protein SGT1. Overall, these results suggest that variation in the resistance of Nicotiana spp. to P. infestans is shadowed by variation in the response to INF elicitins. The ability of tobacco, but not N. benthamiana, to respond to INF2B could explain differences in resistance to P. infestans observed for these two species.


Comparative study of conventional colonoscopy, magnifying chromoendoscopy, and magnifying narrow-band imaging systems in the differential diagnosis of small colonic polyps between trainee and experienced endoscopist.
Removal of colorectal neoplastic polyps can reduce the incidence of colorectal cancers. It is important to distinguish neoplastic from nonneoplastic polyps. We compared the ability of a trainee and an experienced endoscopist in distinguishing between neoplastic polyps and nonneoplastic polyps by conventional white-light, magnifying narrow-band imaging (NBI), and magnifying chromoendoscopy. One hundred and sixty-three small colorectal polyps from 104 patients were studied. All polyps were diagnosed by trainees and experienced endoscopists using conventional white-light, magnifying NBI, and magnifying chromoendoscopy. The kappa values of interobserver agreement between trainees and experienced endoscopists were evaluated before this study. Sensitivity, specificity, and diagnostic accuracy were assessed by reference to histopathology. The first 50 polyps were diagnosed by the trainee as the first stage and the rest 113 polyps were diagnosed as the second stage. Magnifying NBI and magnifying chromoendoscopy were significant better than conventional white-light by the experienced endoscopist (diagnostic accuracy: NBI 85.3%, chromoendoscopy 87.7%, conventional view 74.8%). No significant differences were found for the trainee. The kappa values (0.77 approximately 0.85) were good for each endoscopic modality for the experienced endoscopist. However, only NBI and chromoendoscopy had acceptable kappa values (0.40 approximately 0.48) for the trainee. The trainee improved diagnostic accuracy in the second stage, but not yielded the level of the experienced endoscopist. Magnifying NBI and magnifying chromoendoscopy had a better interobserver agreement than conventional white-light among trainees and experienced endoscopists. The trainee needs learning time to improve diagnostic ability, even using a new modality such as magnifying NBI.


Depression in advanced cancer.
Depression is one of the most common psychiatric diseases seen in patients with advanced cancer. It is not only an independent predictor of poor survival in advanced cancer but also reduces quality of life, reduces compliance with treatment and prolongs hospitalization. Yet all too often depression is under diagnosed and under treated in this population. A literature review was undertaken using extensive electronic and hand searches. Whilst it is true that the diagnostic and treatment challenges facing healthcare professionals in this area are considerable one must not forget that depression in advanced cancer is treatable and validated assessment tools have been developed to facilitate diagnosis. This review article provides the reader with a comprehensive review of the current evidence in this field with particular focus on assessment and treatment. Depression is under diagnosed and under treated - there are valid screening and assessment tools available which will allow appropriate management of this important and debilitating symptom.


Interhemispheric difference of pallidal local field potential activity in cervical dystonia.
Cervical dystonia (CD) produces involuntary neck muscle contractions that result in abnormal and often asymmetrical postures of the head and neck. Basal ganglia oscillatory activity in the 3-12 Hz band correlating with involuntary muscle activity suggests a role in the pathophysiology of primary dystonia. Despite the asymmetrical postures seen with CD, no comparison of interhemispheric differences of pallidal local field potential (LFP) activity has been reported. The aim of this study was to examine the interhemispheric differences of LFP power in globus pallidus interna (GPi) in CD patients and compare these with their predominant head excursion identified as torticollis, laterocollis and retrocollis. LFPs were recorded from bilateral GPi in 11 patients with CD using microelectrodes during deep brain stimulation surgery. LFP power was measured in right and left GPi separately. The mean percentage of total GPi LFP power in 4-30 Hz frequency band on each brain side was determined and related to their predominant CD symptoms. Interhemispheric difference in the mean percentage of LFP power in 4-12 Hz and 13-30 Hz band frequencies was found in patients with torticollis and laterocollis regardless of excursion direction. However, patients with retrocollis did not show interhemispheric difference in LFP activity in any band frequency. Interhemispheric differences in synchronisation of pallidal LFP activity in 4-12 Hz and 13-30 Hz bands are related to the CD clinical condition, suggesting that these frequencies are important in the pathophysiology of dystonia.


Insights into the regulation of DMSP synthesis in the diatom Thalassiosira pseudonana through APR activity, proteomics and gene expression analyses on cells acclimating to changes in salinity, light and nitrogen.
Despite the importance of dimethylsulphoniopropionate (DMSP) in the global sulphur cycle and climate regulation, the biological pathways underpinning its synthesis in marine phytoplankton remain poorly understood. The intracellular concentration of DMSP increases with increased salinity, increased light intensity and nitrogen starvation in the diatom Thalassiosira pseudonana. We used these conditions to investigate DMSP synthesis at the cellular level via analysis of enzyme activity, gene expression and proteome comparison. The activity of the key sulphur assimilatory enzyme, adenosine 5'-phosphosulphate reductase was not coordinated with increasing intracellular DMSP concentration. Under all three treatments coordination in the expression of sulphur assimilation genes was limited to increases in sulphite reductase transcripts. Similarly, proteomic 2D gel analysis only revealed an increase in phosphoenolpyruvate carboxylase following increases in DMSP concentration. Our findings suggest that increased sulphur assimilation might not be required for increased DMSP synthesis, instead the availability of carbon and nitrogen substrates may be important in the regulation of this pathway. This contrasts with the regulation of sulphur metabolism in higher plants, which generally involves up-regulation of several sulphur assimilatory enzymes. In T. pseudonana changes relating to sulphur metabolism were specific to the individual treatments and, given that little coordination was seen in transcript and protein responses across the three growth conditions, different patterns of regulation might be responsible for the increase in DMSP concentration seen under each treatment.


Quantitative spectrally resolved imaging through a spectrograph.
A grating spectrograph can be used for spectrally selective two-dimensional imaging if it is operated with a broad entrance slit. The resulting intensity distribution in its exit plane is a one-dimensional convolution of the spatial and spectral distributions of incident light. We present a dedicated deconvolution filter to reconstruct the spatial image from the spectrograph output. The algorithm is illustrated on Raman imaging of an underexpanded dry air jet. Recorded Raman images correspond to density maps convolved with the Raman spectrum of air; the latter essentially acts as a blurring function for the density map. The deconvolution filter combines the individual images recorded in the O2 and N2 Raman bands into a single image of relative air density.


Identification of Escherichia coli O157:H7 genomic regions conserved in strains with a genotype associated with human infection.
Beta-glucuronidase-negative, sorbitol-nonfermenting isolates of Shiga toxin-producing Escherichia coli O157 comprise part of a clone complex of related enterohemorrhagic E. coli isolates. High-resolution genotyping shows that the O157 populations have diverged into two different lineages that appear to have different ecologies. To identify genomic regions unique to the most common human-associated genotype, suppression subtractive hybridization was used to identify DNA sequences present in two clinical strains representing the human lineage I O157:H7 strains but absent from two bovine-derived lineage II strains. PCR assays were then used to test for the presence of these regions in 10 lineage I strains and 20 lineage II strains. Twelve conserved regions of genomic difference for lineage I (CRD(I)) were identified that were each present in at least seven of the lineage I strains but absent in most of the lineage II strains tested. The boundaries of the lineage I conserved regions were further delimited by PCR. Eleven of these CRD(I) were associated with E. coli Sakai S-loops 14, 16, 69, 72, 78, 82, 83, 91 to 93, 153, and 286, and the final CRD(I) was located on the pO157 virulence plasmid. Several potential virulence factors were identified within these regions, including a putative hemolysin-activating protein, an iron transport system, and several possible regulatory genes. Cluster analysis based on lineage I conserved regions showed that the presence/absence of these regions was congruent with the inferred phylogeny of the strains.


Fibroblast growth factor receptor (FGFR) 3. Alternative splicing in immunoglobulin-like domain III creates a receptor highly specific for acidic FGF/FGF-1.
Fibroblast growth factors (FGF) regulate the growth and differentiation of cells through complex combinatorial signaling pathways. There are nine ligands that interact with a family of four tyrosine kinase FGF receptors (FGFR). Diversity in FGF signaling is determined in part by the affinity of specific ligand-receptor pairs. Alternative splicing in the FGFR ligand binding domain generates additional receptor isoforms with novel ligand affinities. For example, splicing events in the ligand binding domain of FGFR2 dramatically increases its affinity for keratinocyte growth factor (KGF/FGF-7). We have identified an alternatively spliced form of the FGFR3 mRNA, corresponding to known splice variants of FGFRs 1 and 2. We demonstrate both by binding studies on genetically engineered soluble receptors and by the mitogenic response of growth factor-dependent cell lines that this splice variant of FGFR3 (FGFR3 IIIb), by binding only acidic FGF (aFGF/FGF-1), has the most restricted ligand binding properties of any FGFR thus far described. Furthermore, by constructing a chimeric receptor that contains the homologous exon from FGFR2, we demonstrate that this single domain from FGFR2 is sufficient to confer upon FGFR3 the ability to bind KGF/FGF-7. The uniquely limited repertoire of ligands that interact with this receptor suggests that a novel ligand for FGFR3 IIIb exists.


Rathke cleft cysts: correlation of enhanced MR and surgical findings.
To describe the gadolinium-enhanced MR findings of Rathke cleft cyst correlate them with the surgical findings, and define those preoperative findings that differentiate this lesion from other sellar and juxtasellar tumors. We studied 18 patients who were diagnosed as having Rathke cleft cyst pathologically. These patients were imaged with T1- and T2-weighted coronal and sagittal spin-echo sequences. Fifteen of these patients received gadopentetate dimeglumine. In eight patients, the cyst showed low intensity on T1-weighted images and high intensity on T2-weighted images. At surgery, the cyst fluid was cerebrospinal fluid-like or light brown in five patients, motor oil-like in one patient, and milky in two patients. In 10 patients, cysts showed isointensity to high intensity on T1-weighted images and had various intensity on T2-weighted images. All 10 contained milky fluid. In three patients the intensity of fluid was heterogeneous. A waxy nodule was found in two patients. The position of the normal pituitary gland confirmed by surgery in all cases coincided with enhancement on MR imaging. The variable position of the normal pituitary gland was clearly identified in the sagittal images. The cyst walls showed no enhancement by gadopentetate dimeglumine. Because Rathke cleft cysts show variable intensities on MR, the diagnosis is often difficult when based on MR signal intensity values alone. MR imaging with gadopentetate dimeglumine does assist in the diagnosis of Rathke cleft cysts. Diagnostic clues include the lack of cyst wall enhancement and displacement of the normal pituitary gland.


Computational modelling for the embolization of brain arteriovenous malformations.
Treatment of arteriovenous malformations (AVMs) of the brain often requires the injection of a liquid embolic material to reduce blood flow through the malformation. The type of the liquid and the location of injection have to be carefully planned in a pre-operative manner. We introduce a new model of the interaction of liquid embolic materials with blood for the simulation of their propagation and solidification in the AVM. Solidification is mimicked by an increase of the material's viscosity. Propagation is modelled by using the concept of two-fluids modelling and that of scalar transport. The method is tested on digital phantoms and on one anatomically derived patient AVM case. Simulations showed that intuitive behaviour of the two-fluid system can be confirmed and that two types of glue propagation through the malformation can be reproduced. Distinction between the two types of propagation could be used to identify fistulous and plexiform compartments composing the AVM and to characterize the solidification of the embolic material in them.