eggNOG 5.0: a hierarchical, functionally and phylogenetically annotated orthology resource based on 5090 organisms and 2502 viruses.
eggNOG is a public database of orthology relationships, gene evolutionary histories and functional annotations. Here, we present version 5.0, featuring a major update of the underlying genome sets, which have been expanded to 4445 representative bacteria and 168 archaea derived from 25 038 genomes, as well as 477 eukaryotic organisms and 2502 viral proteomes that were selected for diversity and filtered by genome quality. In total, 4.4M orthologous groups (OGs) distributed across 379 taxonomic levels were computed together with their associated sequence alignments, phylogenies, HMM models and functional descriptors. Precomputed evolutionary analysis provides fine-grained resolution of duplication/speciation events within each OG. Our benchmarks show that, despite doubling the amount of genomes, the quality of orthology assignments and functional annotations (80% coverage) has persisted without significant changes across this update. Finally, we improved eggNOG online services for fast functional annotation and orthology prediction of custom genomics or metagenomics datasets. All precomputed data are publicly available for downloading or via API queries at http://eggnog.embl.de.


Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia.
Developmental dyslexia (DD) is a learning disorder affecting the ability to read, with a heritability of 40-60%. A notable part of this heritability remains unexplained, and large genetic studies are warranted to identify new susceptibility genes and clarify the genetic bases of dyslexia. We carried out a genome-wide association study (GWAS) on 2274 dyslexia cases and 6272 controls, testing associations at the single variant, gene, and pathway level, and estimating heritability using single-nucleotide polymorphism (SNP) data. We also calculated polygenic scores (PGSs) based on large-scale GWAS data for different neuropsychiatric disorders and cortical brain measures, educational attainment, and fluid intelligence, testing them for association with dyslexia status in our sample. We observed statistically significant (p < 2.8 × 10-6) enrichment of associations at the gene level, for LOC388780 (20p13; uncharacterized gene), and for VEPH1 (3q25), a gene implicated in brain development. We estimated an SNP-based heritability of 20-25% for DD, and observed significant associations of dyslexia risk with PGSs for attention deficit hyperactivity disorder (at pT = 0.05 in the training GWAS: OR = 1.23[1.16; 1.30] per standard deviation increase; p = 8 × 10-13), bipolar disorder (1.53[1.44; 1.63]; p = 1 × 10-43), schizophrenia (1.36[1.28; 1.45]; p = 4 × 10-22), psychiatric cross-disorder susceptibility (1.23[1.16; 1.30]; p = 3 × 10-12), cortical thickness of the transverse temporal gyrus (0.90[0.86; 0.96]; p = 5 × 10-4), educational attainment (0.86[0.82; 0.91]; p = 2 × 10-7), and intelligence (0.72[0.68; 0.76]; p = 9 × 10-29). This study suggests an important contribution of common genetic variants to dyslexia risk, and novel genomic overlaps with psychiatric conditions like bipolar disorder, schizophrenia, and cross-disorder susceptibility. Moreover, it revealed the presence of shared genetic foundations with a neural correlate previously implicated in dyslexia by neuroimaging evidence.


Five-year cost-effectiveness analysis of the European Fans in Training (EuroFIT) physical activity intervention for men versus no intervention.
Increasing physical activity reduces the risk of chronic illness including Type 2 diabetes, cardiovascular disease and certain types of cancer. Lifestyle interventions can increase physical activity but few successfully engage men. This study aims to investigate the 5 year cost-effectiveness of EuroFIT, a program to improve physical activity tailored specifically for male football (soccer) fans compared to a no intervention comparison group. We developed a Markov cohort model in which the impact of improving physical activity on five chronic health conditions (colorectal cancer, Type 2 diabetes, coronary heart disease, stroke and depression) and mortality was modelled. We estimated costs from a societal perspective and expressed benefits as quality adjusted life years (QALYs). We obtained data from a 4-country (England, Netherlands, Portugal and Norway) pragmatic randomised controlled trial evaluating EuroFIT, epidemiological and cohort studies, and meta-analyses. We performed deterministic and probabilistic sensitivity analyses to assess the impact of uncertainty in the model's parameter values on the cost-effectiveness results. We used Monte Carlo simulations to estimate uncertainty and presented this using cost-effectiveness acceptability curves (CEACs). We tested the robustness of the base case analysis using five scenario analyses. Average costs over 5 years per person receiving EuroFIT were €14,663 and per person receiving no intervention €14,598. Mean QALYs over 5 years were 4.05 per person for EuroFIT and 4.04 for no intervention. Thus, the average incremental cost per person receiving EuroFIT was €65 compared to no intervention, while the average QALY gain was 0.01. This resulted in an ICER of €5206 per QALY gained. CEACs show that the probability of EuroFIT being cost-effective compared to no intervention is 0.53, 0.56 and 0.58 at thresholds of €10,000, €22,000 and €34,000 per QALY gained, respectively. When using a time horizon of 10 years, the results suggest that EuroFIT is more effective and less expensive compared to (i.e. dominant over) no intervention with a probability of cost-effectiveness of 0.63 at a threshold of €22,000 per QALY gained. We conclude the EuroFIT intervention is not cost-effective compared to no intervention over a period of 5 years from a societal perspective, but is more effective and less expensive (i.e. dominant) after 10 years. We thus suggest that EuroFIT can potentially improve public health in a cost-effective manner in the long term.


Educating students in a university museum environment: the Adler Museum of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg.
Museums are now very much part of the mainstream of education and are no longer regarded as peripheral to education. They increasingly serve in South Africa as formal partners in education at primary and secondary level. University museums particularly have a formal role to play in tertiary education, with most university collections having been established to further the teaching of a faculty or school. The Adler Museum of Medicine plays an important educational role within the Faculty of Health Sciences at the University of the Witwatersrand, Johannesburg (Wits) and is also increasingly used by schools. As the curricula for South African schools were changed after the first democratic election in 1994, and outcome-based education implemented in this country, more and more educators established contact with museums in particular learning areas of the curricula. In South Africa, there are three areas of the school syllabi which this particular Museum can directly address: great discoveries, technological advances and traditional healing and indigenous knowledge.


Maribacter litoralis sp. nov. a marine bacterium isolated from seashore.
A novel Gram-stain-negative, moderately halophilic and aerobic bacterium, designated strain SDRB-Phe2T, was isolated from coastal sediment of the yellow sea in Sindu-ri, Republic of Korea. Cells were oxidase-positive, catalase-positive, rod-shaped and surrounded by a capsule with gliding motility. Colonies were yellow-coloured, circular, pulvinate with entire margins. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain SDRB-Phe2T formed a distinct lineage within the genus Maribacter of the family Flavobacteriaceae. Stain SDRB-Phe2T exhibited 16S rRNA gene sequence similarity values of 97.1-98.9 % to the type strains of Maribacterstanieri, Maribacterspongiicola, Maribacter forsetii, Maribacter dokdonensis, Maribacter aquivivus, Maribactercaenipelagi, Maribacterlitorisediminis, Maribactersedimenticola, Maribacterulvicola, Maribacter confluentis and Maribacter orientalis, and of 94.8-96.7 % to the type strains of the other species of the genus Maribacter. Strain SDRB-Phe2T contained MK-6 as the predominant respiratory quinone and iso-C15 : 1 G, iso-C15 : 0 and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) as the major fatty acids. The polar lipids of strain SDRB-Phe2T were phosphatidylethanolamine, one unidentified amino lipid and two unidentified lipids. The DNA G+C content was 36.2 mol%. DNA-DNA relatedness values of strain SDRB-Phe2T to the type strains of the 11 phylogenetically related species of the genus Maribacter were 21.9-38.6 %. On the basis of the phenotypic features, phylogenetic and DNA-DNA hybridization analyses presented here, strain SDRB-Phe2T (=JCM 32373T=KCTC 62273T=DSM 106042T) represents a novel species of the genus Maribacter, for which the name Maribacterlitoralis sp. nov. is proposed.


Clinical expert guidelines for the management of cough in lung cancer: report of a UK task group on cough.
Cough is a common and distressing symptom in lung cancer patients. The clinical management of cough in lung cancer patients is suboptimal with limited high quality research evidence available. The aim of the present paper is to present a clinical guideline developed in the UK through scrutiny of the literature and expert opinion, in order to aid decision making in clinicians and highlight good practice. Two systematic reviews, one focusing on the management of cough in respiratory illness and one Cochrane review specifically on cancer, were conducted. Also, data from reviews, phase II trials and case studies were synthesized. A panel of experts in the field was also convened in an expert consensus meeting to make sense of the data and make clinical propositions. A pyramid of cough management was developed, starting with the treatment of reversible causes of cough/specific pathology. Initial cough management should focus on peripherally acting and intermittent treatment; more resistant symptoms require the addition of (or replacement by) centrally acting and continuous treatment. The pyramid for the symptomatic management starts from the simpler and most practical regimens (demulcents, simple linctus) to weak opioids to morphine and methadone before considering less well-researched and experimental approaches. The clinical guidelines presented aim to provide a sensible clinical approach to the management of cough in lung cancer. High quality research in this field is urgently required to provide more evidence-based recommendations.


International policy failures: cloning and stem-cell research.
In late 2003, two international bodies were unable to resolve disagreements that involved bioethical issues. First, the United Nations General Assembly failed to pass a treaty on reproductive cloning because of insistence by some countries that the treaty include a ban on cloning for research. In view of the importance of enacting prohibition of reproductive cloning, the two issues should be separated and each argued on its own merits. Relevant objections to separation of the two issues can be refuted. Second, the European Union (EU) failed to agree on conditions for funding stem-cell research because of the diversity of views and policies of the countries of the EU. Because a stalemate was reached, funding decisions in the next programme cycle will be made on an ad hoc basis. Scientists will not have information they need to plan research programmes, suggesting that clear guidelines, even if restrictive, are preferable to vague unpublicised criteria.


Sex and death: are they related? Findings from the Caerphilly Cohort Study.
To examine the relation between frequency of orgasm and mortality. Cohort study with a 10 year follow up. The town of Caerphilly, South Wales, and five adjacent villages. 918 men aged 45-59 at time of recruitment between 1979 and 1983. All deaths and deaths from coronary heart disease. Mortality risk was 50% lower in the group with high orgasmic frequency than in the group with low orgasmic frequency, with evidence of a dose-response relation across the groups. Age adjusted odds ratio for all cause mortality was 2.0 for the group with low frequency of orgasm (95% confidence interval 1.1 to 3.5, test for trend P = 0.02). With adjustment for risk factors this became 1.9 (1.0 to 3.4, test for trend P = 0.04). Death from coronary heart disease and from other causes showed similar associations with frequency of orgasm, although the gradient was most marked for deaths from coronary heart disease. Analysed in terms of actual frequency of orgasm, the odds ratio for total mortality associated with an increase in 100 orgasms per year was 0.64 (0.44 to 0.95). Sexual activity seems to have a protective effect on men's health.


Membrane connectivity estimated by digital image analysis of HER2 immunohistochemistry is concordant with visual scoring and fluorescence in situ hybridization results: algorithm evaluation on breast cancer tissue microarrays.
The human epidermal growth factor receptor 2 (HER2) is an established biomarker for management of patients with breast cancer. While conventional testing of HER2 protein expression is based on semi-quantitative visual scoring of the immunohistochemistry (IHC) result, efforts to reduce inter-observer variation and to produce continuous estimates of the IHC data are potentiated by digital image analysis technologies. HER2 IHC was performed on the tissue microarrays (TMAs) of 195 patients with an early ductal carcinoma of the breast. Digital images of the IHC slides were obtained by Aperio ScanScope GL Slide Scanner. Membrane connectivity algorithm (HER2-CONNECT, Visiopharm) was used for digital image analysis (DA). A pathologist evaluated the images on the screen twice (visual evaluations: VE1 and VE2). HER2 fluorescence in situ hybridization (FISH) was performed on the corresponding sections of the TMAs. The agreement between the IHC HER2 scores, obtained by VE1, VE2, and DA was tested for individual TMA spots and patient's maximum TMA spot values (VE1max, VE2max, DAmax). The latter were compared with the FISH data. Correlation of the continuous variable of the membrane connectivity estimate with the FISH data was tested. The pathologist intra-observer agreement (VE1 and VE2) on HER2 IHC score was almost perfect: kappa 0.91 (by spot) and 0.88 (by patient). The agreement between visual evaluation and digital image analysis was almost perfect at the spot level (kappa 0.86 and 0.87, with VE1 and VE2 respectively) and at the patient level (kappa 0.80 and 0.86, with VE1max and VE2max, respectively). The DA was more accurate than VE in detection of FISH-positive patients by recruiting 3 or 2 additional FISH-positive patients to the IHC score 2+ category from the IHC 0/1+ category by VE1max or VE2max, respectively. The DA continuous variable of the membrane connectivity correlated with the FISH data (HER2 and CEP17 copy numbers, and HER2/CEP17 ratio). HER2 IHC digital image analysis based on membrane connectivity estimate was in almost perfect agreement with the visual evaluation of the pathologist and more accurate in detection of HER2 FISH-positive patients. Most immediate benefit of integrating the DA algorithm into the routine pathology HER2 testing may be obtained by alerting/reassuring pathologists of potentially misinterpreted IHC 0/1+ versus 2+ cases.


Association Between Ambient Air Pollution Exposure and Spontaneous Pneumothorax Occurrence.
Spontaneous pneumothorax is hypothesized to be associated with air pollution exposure based on pathophysiological mechanisms involving airway inflammation. Therefore, we analyzed the association between daily concentrations of air pollutants [sulfur dioxide, nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O3), particulate matter (PM) less than 2.5 μm in diameter (PM2.5), PM less than 10 μm in diameter (PM10), and coarse PM (PM10-2.5)] and the number of spontaneous pneumothorax-related hospital visits. We analyzed a subset of data from the National Health Insurance Service-National Sample Cohort, a nationally representative dynamic cohort based on health insurance claims data in Korea. Using time series analysis with the Poisson generalized additive model, we evaluated hospital visit data of over 100,000 male cohort members residing in Seoul from 2007 to 2010. We identified 516 hospital visits due to spontaneous pneumothorax. In a single-pollutant model, an interquartile range increase of PM and CO exposure at lag day 1 was associated with spontaneous pneumothorax hospital visits (relative risk, 95% confidence interval: PM2.5: 1.10 (1.01, 1.21); PM10: 1.09 (1.01, 1.18); PM10-2.5: 1.06 (1.00, 1.12); CO: 1.11 (1.01, 1.23)). For lag day 2, NO2 and PM exposure was associated with pneumothorax hospital visits (NO2: 1.15 (1.01, 1.32); PM10: 1.10 (1.02, 1.18); PM10-2.5: 1.07 (1.02, 1.13)). In a multipollutant model, the association was consistent for PM. The number of hospital visits due to spontaneous pneumothorax increased with air pollution exposure, especially with PM. Our finding suggests that air pollution is a possible predisposing factor for spontaneous pneumothorax.


Tumor heterogeneity, clonal evolution, and therapy resistance: an opportunity for multitargeting therapy.
Heterogeneity within the cell population is a feature of many tumors. This lack of cellular homogeneity may originate from a number of sources, including differential nutrient status due to the de novo microcirculations of tumors, to infiltration of normal cells into the tumor, and to the hierarchical natures of the cell populations from which cancers arise. Tumors are thought to arise from one or more tumor initiating cells (TIC) within the population and to found hierarchies of progenitors and more differentiated cancer cells. TIC are often derived from tissue stem cells and these cancer stem cells are characterized by resistance to most cytotoxic treatments and by a high metastatic rate. Many of the properties of tumor populations, including the ability to express mutated oncogenes and to evolve new features such as treatment resistance and invasive and metastatic potential appear to depend on the molecular chaperone Hsp90. We discuss the potential of targeting the heterogeneous cell population with Hsp90 inhibitory drugs and its potential ability to inactivate TIC and to block the evolution of new phenotypes in cancer.


Resistance in Selected Corn Hybrids to Meloidogyne arenaria and M. incognita.
A total of 33 corn hybrids were evaluated in a series of greenhouse and field trials to determine if they differed in resistance to either Meloidogyne incognita race 3 or M. arenaria race 1. Reproduction of M. incognita race 3 and M. arenaria race 1 on the hybrids was also compared. Reproduction of M. arenaria differed among corn hybrids after 58 to 65 days in greenhouse experiments; however, reproduction was similar among hybrids in the field experiment. No hybrids were consistently resistant to M. incognita. Two isolates of M. arenaria and two of M. incognita were evaluated in the greenhouse trials, and no evidence of isolate-dependent resistance was observed. Meloidogyne incognita reproduced better than M. arenaria on the hybrids in this study. A survey of 102 corn fields from 11 counties throughout southern Georgia was conducted to determine the relative frequency of M. incognita and M. arenaria. Meloidogyne species were found in 34 of the fields surveyed, and 93.9% of these were identified as M. incognita. The frequency of occurrence of M. incognita was 99.6% if the previous crop was cotton and 84.6% if the previous crop was peanut. Pratylenchus spp. were extracted from all intact corn root systems examined.


Improved diagnostic and real-time pcr in rapid screening for Salmonella in the poultry food chain.
The goal of this study was to improve the diagnostic applicability of genus- and serovar- (S. Enteritidis and S. Typhimurium) specific PCR systems in screening faecal and caecal samples of poultry, poultry feed and poultrymeat for Salmonella, by keeping the opportunity to obtain Salmonella cultures from positive samples. Peptone broth pre-enrichment cultures of the samples were tested by PCR. In faecal and caecal samples from broiler chicks a strong inhibitory action was frequently observed. This could be reduced markedly by the addition of bovine serum albumin (BSA) acting as amplification facilitator. The results of testing pre-enrichment cultures from artificially contaminated faecal, poultry feed and poultrymeat samples (using S. Enteritidis, S. Typhimurium and S. Hadar as contaminants) suggest that the sensitivity of the above systems is 10(1)-10(2) CFU g(-1) sample. The testing of 95 caecal samples from slaughtered chicks resulted in 49% culture-positive and 76% PCR-positive samples. The suitability of a generic real-time PCR for testing faecal samples of poultry was also studied. Its detection limit for these samples was found to be lower than that of the diagnostic PCR system. Both methods reduced the time required for Salmonella detection to 24-30 h, and the advantage of the real-time PCR was its increased sensitivity. We have established a diagnostic and a real-time PCR system for rapid and reliable genus- and serovar- (S. Enteritidis and S. Typhimurium) specific detection of Salmonella for monitoring purposes in the poultry food chain. Sensitivity is equal to, or higher than, that of the standard bacterial culture method, and the method still provides the Salmonella culture if needed.


Surfactant-Directed Synthesis of Mesoporous Pd Films with Perpendicular Mesochannels as Efficient Electrocatalysts.
Palladium (Pd) films with perpendicularly aligned mesochannels are expected to provide fascinating electrocatalytic properties due to their low diffusion resistance and the full utilization of their large surface area. There have been no studies on such mesoporous metal films, because of the difficulties in controlling both the vertical alignment of the molecular template and the crystal growth in the metallic pore walls. Here we report an effective approach for the synthesis of mesoporous Pd films with mesochannels perpendicularly aligned to the substrate by an elaborated electrochemical deposition. The films show a superior electrocatalytic activity by taking full advantage of the perpendicularly aligned mesochannels.


Microglial Implication in Parkinson's Disease: Loss of Beneficial Physiological Roles or Gain of Inflammatory Functions?
Microglia, often described as the brain-resident macrophages, play crucial roles in central nervous system development, maintenance, plasticity, and adaptation to the environment. Both aging and chronic stress promote microglial morphological and functional changes, which can lead to the development of brain pathologies including Parkinson's disease (PD). Indeed, aging, and chronic stress represent main environmental risk factors for PD. In these conditions, microglia are known to undergo different morphological and functional changes. Inflammation is an important component of PD and disequilibrium between pro- and anti-inflammatory microglial functions might constitute a crucial component of PD onset and progression. Cumulated data also suggest that, during PD, microglia might lose beneficial functions and gain detrimental ones, in addition to mediating inflammation. In this mini-review, we aim to summarize the literature discussing the functional and morphological changes that microglia undergo in PD pathophysiology and upon exposure to its two main environmental risk factors, aging, and chronic stress.


Large-scale community echocardiographic screening reveals a major burden of undiagnosed valvular heart disease in older people: the OxVALVE Population Cohort Study.
Valvular heart disease (VHD) is expected to become more common as the population ages. However, current estimates of its natural history and prevalence are based on historical studies with potential sources of bias. We conducted a cross-sectional analysis of the clinical and epidemiological characteristics of VHD identified at recruitment of a large cohort of older people. We enrolled 2500 individuals aged ≥65 years from a primary care population and screened for undiagnosed VHD using transthoracic echocardiography. Newly identified (predominantly mild) VHD was detected in 51% of participants. The most common abnormalities were aortic sclerosis (34%), mitral regurgitation (22%), and aortic regurgitation (15%). Aortic stenosis was present in 1.3%. The likelihood of undiagnosed VHD was two-fold higher in the two most deprived socioeconomic quintiles than in the most affluent quintile, and three-fold higher in individuals with atrial fibrillation. Clinically significant (moderate or severe) undiagnosed VHD was identified in 6.4%. In addition, 4.9% of the cohort had pre-existing VHD (a total prevalence of 11.3%). Projecting these findings using population data, we estimate that the prevalence of clinically significant VHD will double before 2050. Previously undetected VHD affects 1 in 2 of the elderly population and is more common in lower socioeconomic classes. These unique data demonstrate the contemporary clinical and epidemiological characteristics of VHD in a large population-based cohort of older people and confirm the scale of the emerging epidemic of VHD, with widespread implications for clinicians and healthcare resources.


Pattern formation by graded and uniform signals in the early Drosophila embryo.
The early Drosophila embryo is patterned by graded distributions of maternal transcription factors. Recent studies revealed that pattern formation by these graded signals depends on uniformly expressed transcriptional activators, such as Zelda. Removal of Zelda influences both the timing and the spatial expression domains for most of the genes controlled by maternal gradients. We demonstrate that some of these patterning defects, which range from temporal delay to loss of expression, can be rationalized with the use of a mathematical model based on cooperative binding of graded and uniform factors. This model makes a number of predictions, which we confirm experimentally by analyzing the expression of short gastrulation (sog), a gene that is controlled by a combination of the Dorsal morphogen gradient and Zelda. The proposed model suggests a general mechanism for the formation of nested gene expression domains, which is a hallmark of tissue patterning by morphogen gradients. According to this mechanism, the differential effects of a morphogen on its target genes can depend on their differential sensitivity to uniform factors.


A culinary twist of a two-course meals-on-wheels menu in a cluster-randomized controlled trial influencing health-related quality of life in nursing home residents.
Meals-on-wheels in nursing homes are sensory diminished because of the packaging and reheating of the food, which creates less appetite stimulation and an impaired meal experience for nursing home residents. This background is crucial since nursing home residents are a frail and often malnourished group that is physiologically affected by sensory, physical and mental alterations. The study aimed to increase health-related quality of life in nursing home residents receiving meals-on-wheels using an intervention menu with favourite meals that added a culinary twist and were sensory improved by chefs. A double-blinded cluster-randomized controlled trial with two arms, one group receives an intervention menu, and the other group receives a non-optimized menu. The intervention menu included popular meals-on-wheels (a main meal for dinner and a starter/dessert before or after dinner with culinary improvements). The participants received the same meals without culinary improvements in the control group. Health-related quality of life (EQ5D3L) was the primary outcome of the study. Secondary outcomes were mental and nutritional status and muscle strength. The measurements were assessed at a baseline and end visit (12 weeks after baseline visit). Fifty-two nursing home residents were included in the study (There are 20 in the intervention group and 32 in the control group). Following the principle of intention-to-treat, a significant decreasing effect (p-value 0.026) was found between the groups on health-related quality of life. The treated group experienced the largest decrease from the baseline to the end visit. The intervention group had a significant decrease in the second item on Satisfaction With Food-related Life (SWFL2) (I am very pleased with my food). No changes were found either within or between the groups, on the rest of the measured parameters. Nursing home residents are a target group experiencing natural aggravation, why the health-related quality of life might be difficult to improve using a culinary meal intervention. The decreasing effect of Satisfaction With Food-related Life found in the intervention group could be related to these older adults being too unfamiliar with the culinary twist added to the intervention menu. The study was registered on ClinTrials.gov (Identifier NCT03133364).


Ocean circulation: its effects on seasonal sea-ice simulations.
A diagnostic ice-ocean model of the Arctic, Greenland, and Norwegian seas is constructed and used to examine the role of ocean circulation in seasonal sea-ice simulations. The model includes lateral ice motion and three-dimensional ocean circulation. The ocean portion of the model is weakly forced by observed temperature and salinity data. Simulation results show that including modeled ocean circulation in seasonal sea-ice simulations substantially improves the predicted ice drift and ice margin location. Simulations that do not include lateral ocean movment predict a much less realistic ice edge.


Comparison of single and boosted protease inhibitor versus nonnucleoside reverse transcriptase inhibitor-containing cART regimens in antiretroviral-naïve patients starting cART after January 1, 2000.
Few published studies have considered both the short- and long-term virologic or immunologic response to combination antiretroviral therapy (cART) and the impact of different cART strategies. To compare time to initial virologic (<500 copies/mL) or immunologic (>200/mm3 cell increase) response in antiretroviral-naïve patients starting either a single protease inhibitor (PI; n = 183), a ritonavir-boosted PI regimen (n = 197), or a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based cART regimen (n = 447) after January 1, 2000, and the odds of lack of virologic or immunologic response at 3 years after starting cART. Cox proportional hazards models and logistic regression. After adjustment, compared to patients taking an NNRTI-regimen, patients taking a single-PI regimen were significantly less likely to achieve a viral load (VL) <500 copies/mL (relative hazard [RH] 0.74, 95% CI 0.54-0.84, p = .0005); there was no difference between the boosted-PI regimen and the NNRTI regimen (p = .72). There were no differences between regimens in the risk of >200/mm3 CD4 cell increase after starting cART (p > .3). At 3 years after starting cART, patients taking a single-PI-based regimen were more likely to not have virologic suppression (<500 copies/mL; odds ratio [OR] 1.60, 95% CI 1.06-2.40, p = .024), while there were no differences in the odds of having an immunologic response (>200/mm3 increase; p > .15). This model was adjusted for CD4 and VL at starting cART, age, prior AIDS diagnosis, year of starting cART, and region of Europe. Compared to patients starting an NNRTI-based regimen, patients starting a single-PI regimen were less likely to be virologically suppressed at 3 years after starting cART. These results should be interpreted with caution, because of the potential biases associated with observational studies. Ultimately, clinical outcomes, such as new AIDS diagnoses or deaths, will be the measure of efficacy of cART regimens, which requires the follow-up of a very large number of patients over many years.


Meeting physical activity guidelines through community-based group exercise: "better bones and balance".
Community-based exercise programs are popular for achieving physical activity among older adults, but the amount of physical activity obtained through such programs is unknown. This study quantified the bone-loading forces and levels of cardiovascular activity associated with participation in "Better Bones and Balance" (BBB), a community-based fall- and fracture-prevention program for older adults. Thirty-six postmenopausal women age 73.2 ± 7.6 yr engages in BBB participated in this study. Ground-reaction forces (GRFs) associated with BBB exercises were evaluated using a force platform. Session and weekly totals of minutes of moderate to vigorous physical activity (MVPA) and total time spent above 55% maximum heart rate (HR) were measured using accelerometers and HR monitors, respectively. BBB exercises produced mean 1-leg GRFs of 1.4-2.2 units body weight. Weekly BBB participation was associated with 126 ± 31 min of MVPA. Activity obtained by BBB participation meets recommended guidelines for skeletal and cardiovascular health.


129-derived strains of mice are deficient in DNA polymerase iota and have normal immunoglobulin hypermutation.
Recent studies suggest that DNA polymerase eta (poleta) and DNA polymerase iota (poliota) are involved in somatic hypermutation of immunoglobulin variable genes. To test the role of poliota in generating mutations in an animal model, we first characterized the biochemical properties of murine poliota. Like its human counterpart, murine poliota is extremely error-prone when catalyzing synthesis on a variety of DNA templates in vitro. Interestingly, when filling in a 1 base-pair gap, DNA synthesis and subsequent strand displacement was greatest in the presence of both pols iota and eta. Genomic sequence analysis of Poli led to the serendipitous discovery that 129-derived strains of mice have a nonsense codon mutation in exon 2 that abrogates production of poliota. Analysis of hypermutation in variable genes from 129/SvJ (Poli-/-) and C57BL/6J (Poli+/+) mice revealed that the overall frequency and spectrum of mutation were normal in poliota-deficient mice. Thus, either poliota does not participate in hypermutation, or its role is nonessential and can be readily assumed by another low-fidelity polymerase.


Measures of care fragmentation: Mathematical insights from population genetics.
To identify novel properties of health care fragmentation measures, drawing on insights from mathematically equivalent measures of genetic diversity. We describe mathematical relationships between two measures: (a) Breslau's Usual Provider of Care (UPC), the proportion of care with the most frequently visited provider, analogous to the "frequency of the most frequent allele" at a genetic locus; and (b) Bice-Boxerman's Continuity of Care Index (COCI), a measure of care dispersion across multiple providers, analogous to "Nei's estimator of homozygosity" in genetics. Just as the frequency of the most frequent allele places a tight constraint on homozygosity, the proportion of care with the most frequently visited provider (UPC) places lower and upper bounds on dispersion of care (COCI), and vice versa. This property presents the possibility of a normalized COCI given UPC (NCGU) measure, which reflects a bounded range of care dispersion dependent on the number of visits with the most frequently visited provider. Mathematical aspects of UPC and COCI also suggest thresholds for the minimal number of patient visits to use when studying fragmentation. Applying knowledge from population genetics elucidated relationships between care fragmentation measures and produced novel insights for care fragmentation studies.


Minimally Invasive Function-Preserving Gastrectomy with Sentinel Node Biopsy for Early Gastric Cancer.
Recently, minimally invasive approaches such as endoscopic treatment or laparoscopic gastrectomy for early gastric cancer have made rapid progress. However, the extent of gastrectomy and lymphadenectomy in laparoscopic surgery is radical, similar to that of open gastrectomy for patients with early gastric cancer diagnosed as not indicated for endoscopic treatment. Since it is well known that lymph node metastasis is an important prognostic factor, the standard procedure of gastrectomy with radical lymph node dissection has been performed for the purpose of curative resection. The frequency of lymph node metastases is relatively low in patients with early gastric cancer; therefore, function-preserving gastrectomy, a solution between endoscopic treatment and standard gastrectomy in terms of invasiveness, could be considered to avoid excessive invasive surgery. A prospective multicenter trial and meta-analyses of sentinel node (SN) mapping and biopsy for early gastric cancer demonstrated favorable SN detection rates and accuracy of nodal metastatic status. Personalized function-preserving gastrectomy with limited lymphadenectomy using SN theory will positively impact patients' quality of life (QOL). Specifically, a full-thickness partial gastrectomy by laparoscopic endoscopic cooperative surgery with SN basin dissection could become a reliable technique of minimally invasive gastrectomy for treating patients with clinically node-negative (cN0) early gastric cancer. Key Messages: For early gastric cancer, the development of laparoscopic personalized minimized gastrectomy with SN navigation may improve patients' postoperative QOL.


The value of best-practice guidelines for OSCEs in a postgraduate program in an Australian remote area setting.
Nurses in remote areas of Australia are the primary healthcare professionals, who need to be able to deliver comprehensive and culturally sensitive care to clients, many of whom are Indigenous Australians. Adequate and specific preparation for practice is crucial to the quality of care delivered by remote area nurses (RANs). Objective structured clinical examinations (OSCE) provide an excellent opportunity for student practice in a simulated environment that is safe, authentic, fair and valid when well constructed. Seven integrated best practice guidelines (BPGs), previously developed by project team members to inform OSCEs within educational programs, provided guidance in restructuring the OSCE. This paper provides a detailed analysis of the value of BPGs used in the development, teaching and learning, and evaluation of OSCEs in a rural and remote postgraduate course for RANs. A pre-site visit to the Centre for Remote Health, Alice Springs, Northern Territory, was conducted with modification of the course and previous OSCE according to BPGs. Following delivery of the course and OSCE, evaluations occurred via a mixed method approach. Student surveys (n=15) and focus groups (n=13) and staff interviews (n=5) provided an in-depth analysis of their perceptions of the revised OSCE. Descriptive statistics were used to describe the student sample. The narrative data were transcribed verbatim and analysed using content analysis. Triangulation was achieved with the convergence of the separate data sources focusing on themes and patterns within and between students and tutors. All 15 students and five tutors provided feedback. The majority of student participants had limited experience in working in remote area nursing prior to participation and therefore the opportunities that availed themselves were critical in adequately equipping them with the requisite knowledge, skills and abilities. Three themes emerged from the data: (1) value of common and significant events in OSCE; (2) power of deliberate actions; and (3) learning cultural sensitivity. OSCEs in this setting proved to be a good way for students to learn the skills required by RANs. Overwhelmingly, the modifications using the BPGs were highly valued by students and staff. Three themes emerged and were clearly linked to specific BPGs, indicating the positive impact the BPGs had on the OSCEs and student learning. The authentic content for the scenarios was seen as relevant and motivational for student learning. The practice element of the OSCEs enhanced the learning experience and feedback supported learning. OSCEs developed, taught and assessed using BPGs were highly valued. The BPGs provided an integrated approach with real-life scenarios with a strong cultural perspective - all important features to the RANs' future success in providing individualised care to clients in remote areas of Australia. Further use of BPGs is recommended.


Enhanced preference for high-fat foods following a simulated night shift.
Shift workers are prone to obesity and associated co-morbidities such as diabetes and cardiovascular disease. Sleep restriction associated with shift work results in dramatic endocrine and metabolic effects that predispose shift workers to these adverse health consequences. While sleep restriction has been associated with increased caloric intake, food preference may also play a key role in weight gain associated with shift work. This study examined the impact of an overnight simulated night shift on food preference. Sixteen participants [mean 20.1, standard deviation (SD) 1.4 years; 8 women] underwent a simulated night shift and control condition in a counterbalanced order. On the following morning, participants were provided an opportunity for breakfast that included high- and low-fat food options (mean 64.8% and 6.4% fat, respectively). Participants ate significantly more high-fat breakfast items after the simulated night shift than after the control condition [167.3, standard error of the mean (SEM 28.7) g versus 211.4 (SEM 35.6) g; P=0.012]. The preference for high-fat food was apparent among the majority of individuals following the simulated night shift (81%), but not for the control condition (31%). Shift work and control conditions did not differ, however, in the total amount of food or calories consumed. A simulated night shift leads to preference for high-fat food during a subsequent breakfast opportunity. These results suggest that food choice may contribute to weight-related chronic health problems commonly seen among night shift workers.


Insights into the low adhesive capacity of human T-cadherin from the NMR structure of Its N-terminal extracellular domain.
T-cadherin is unique among the family of type I cadherins, because it lacks transmembrane and cytosolic domains, and attaches to the membrane via a glycophosphoinositol anchor. The N-terminal cadherin repeat of T-cadherin (Tcad1) is approximately 30% identical to E-, N-, and other classical cadherins. However, it lacks many amino acids crucial for their adhesive function of classical cadherins. Among others, Trp-2, which is the key residue forming the canonical strand-exchange dimer, is replaced by an isoleucine. Here, we report the NMR structure of the first cadherin repeat of T-cadherin (Tcad1). Tcad1, as other cadherin domains, adopts a beta-barrel structure with a Greek key folding topology. However, Tcad1 is monomeric in the absence and presence of calcium. Accordingly, lle-2 binds into a hydrophobic pocket on the same protomer and participates in an N-terminal beta-sheet. Specific amino acid replacements compared to classical cadherins reduce the size of the binding pocket for residue 2 and alter the backbone conformation and flexibility around residues 5 and 15 as well as many electrostatic interactions. These modifications apparently stabilize the monomeric form and make it less susceptible to a conformational switch upon calcium binding. The absence of a tendency for homoassociation observed by NMR is consistent with electron microscopy and solid-phase binding data of the full T-cadherin ectodomain (Tcad1-5). The apparent low adhesiveness of T-cadherin suggests that it is likely to be involved in reversible and dynamic cellular adhesion-deadhesion processes, which are consistent with its role in cell growth and migration.


Polymorphisms in bovine immune genes and their associations with somatic cell count and milk production in dairy cattle.
Mastitis, an inflammation of the mammary gland, is a major source of economic loss on dairy farms. The aim of this study was to quantify the associations between two previously identified polymorphisms in the bovine toll-like receptor 2 (TLR2) and chemokine receptor 1 (CXCR1) genes and mammary health indictor traits in (a) 246 lactating dairy cow contemporaries representing five breeds from one research farm and (b) 848 Holstein-Friesian bulls that represent a large proportion of the Irish dairy germplasm. To expand the study, a further 14 polymorphisms in immune genes were included for association studies in the bull population. TLR4-2021 associated (P < 0.05) with both milk protein and fat percentage in late lactation (P < 0.01) within the cow cohort. No association was observed between this polymorphism and either yield or composition of milk within the bull population. CXCR1-777 significantly associated (P < 0.05) with fat yield in the bull population and tended to associate (P < 0.1) with somatic cell score (SCS) in the cows genotyped. CD14-1908 A allele was found to associate with increased (P < 0.05) milk fat and protein yield and also tended to associate with increased (P < 0.1) milk yield. A SERPINA1 haplotype with superior genetic merit for milk protein yield and milk fat percentage (P < 0.05) was also identified. Of the sixteen polymorphisms in seven immune genes genotyped, just CXCR1-777 tended to associate with SCS, albeit only in the on-farm study. The lack of an association between the polymorphisms with SCS in the Holstein-Friesian data set would question the potential importance of these variants in selection for improved mastitis resistance in the Holstein-Friesian cow.


Plasma neutrophil gelatinase-associated lipocalin in kidney transplantation and early renal function prediction.
This prospective observational study aimed to assess the relevance of serial postoperative plasma neutrophil gelatinase-associated lipocalin (NGAL) measurements on prediction of early renal transplant function. Plasma NGAL (pNGAL) was measured (Triage NGAL Test; Biosite Inc., Inverness Medical) in 41 patients scheduled for kidney transplantation from deceased or living donors, immediately before and after surgery, and at 12 hr, day 1, day 3, and day 7. A delayed graft function (DGF) was defined as the need for dialysis during the first week. The results were expressed as median (Q1, Q3). Of the 41 consecutive patients enrolled, all had a high preoperative pNGAL level: 453 ng/mL (382, 595). Fifteen (36.6%) presented a DGF. In patients with DGF, pNGAL was significantly higher at 12 hr (571 [467, 634] vs. 242 [158, 299] ng/mL, P<0.0001) and at day 1 (466 [356, 627] vs. 165 [91, 248] ng/mL, P<0.0001). A pNGAL higher than 400 ng/mL 12 hr after transplantation predicted DGF with a sensitivity of 93.3%, a specificity of 88.5%, and an odds ratio of 63.2 (P=0.0004). This predictive performance was higher than for plasma creatinine. pNGAL level early and accurately predicted DGF after renal transplantation. pNGAL measurements allowed monitoring of the renal function in this striking situation of ischemia-reperfusion aggression. Early identification of patients at risk of DGF, before graft lesions are consolidated, opens the field of a precise monitoring of renal injury and the impact of future protective therapeutics.


Assessing applicability when comparing medical interventions: AHRQ and the Effective Health Care Program.
To describe a systematic approach for identifying, reporting, and synthesizing information to allow consistent and transparent consideration of the applicability of the evidence in a systematic review according to the Population, Intervention, Comparator, Outcome, Setting domains. Comparative effectiveness reviews need to consider whether available evidence is applicable to specific clinical or policy questions to be useful to decision makers. Authors reviewed the literature and developed guidance for the Effective Health Care program. Because applicability depends on the specific questions and needs of the users, it is difficult to devise a valid uniform scale for rating the overall applicability of individual studies or body of evidence. We recommend consulting stakeholders to identify the factors most relevant to applicability for their decisions. Applicability should be considered separately for benefits and harms. Observational studies can help determine whether trial populations and interventions are representative of "real world" practice. Reviewers should describe differences between available evidence and the ideally applicable evidence for the question being asked and offer a qualitative judgment about the importance and potential effect of those differences. Careful consideration of applicability may improve the usefulness of systematic reviews in informing practice and policy.


Evaluation of transcutaneous pulmonoscopy for examination and biopsy of the lungs of ball pythons and determination of preferred biopsy specimen handling and fixation procedures.
To establish a safe and effective technique for the endoscopic examination and biopsy of snake lungs by use of a 2.7-mm rigid endoscope system. Clinical trial. 17 adult ball pythons (Python regius). The right lung of each anesthetized snake was transcutaneously penetrated at a predetermined site. Endoscopic lung examination was objectively scored, and 3 lung biopsies were performed. Tissue samples were evaluated histologically for diagnostic quality. One year later, 11 of the 17 snakes again underwent pulmonoscopy and biopsy; specimens were placed in various fixatives to compare preservation quality. All 17 snakes were euthanatized and necropsied. No major anesthetic, surgical, or biopsy-associated complications were detected in any snake. In 16 of 17 pythons, ease of right lung entry was satisfactory to excellent, and views of the distal portion of the trachea; primary bronchus; intrapulmonary bronchus; cranial lung lobe; and faveolar, semisaccular, and saccular lung regions were considered excellent. In 1 snake, mild hemorrhage caused minor procedural difficulties. After 1 year, pulmonoscopy revealed healing of the previous transcutaneous lung entry and biopsy sites. Important procedure-induced abnormalities were not detected at necropsy. Diagnostic quality of specimens that were shaken from biopsy forceps into physiologic saline (0.9% NaCl) solution before fixation in 2% glutaraldehyde or neutral-buffered 10% formalin was considered good to excellent. By use of a 2.7-mm rigid endoscope, lung examination and biopsy can be performed safely, swiftly, and with ease in ball pythons. Biopsy specimens obtained during this procedure are suitable for histologic examination.


A novel Bruton's tyrosine kinase gene (BTK) invariant splice site mutation in a Malaysian family with X-linked agammaglobulinemia.
X-linked agammaglobulinemia (XLA) is a rare genetic disorder caused by mutations in the Bruton's tyrosine kinase (BTK) gene. These mutations cause defects in early B cell development. A patient with no circulating B cells and low serum immunoglobulin isotypes was studied as were his mother and sister. Monocyte BTK protein expression was evaluated by flow cytometry. The mutation was determined using PCR and followed by sequencing. Flow cytometry showed the patient lacked BTK protein expression in his monocytes while the mother and sister had 62% and 40% of the monocytes showing BTK protein expressions respectively. The patient had a novel base substitution in the first nucleotide of intron 9 in the BTK gene, and the mutation was IVS9+1G<C. This mutation resulted in exon 9 skipping. This defect rendered the patient susceptible to asthma, failure to thrive, recurrent pyogenic infections, otitis media and bronchopneumonia. His mother and sister were heterozygous for this mutation. The combination of flow cytometry and genetic study is necessary in the diagnosis of X-linked agammaglobulinemia and may be used for subsequent genetic counseling, carrier detection and prenatal diagnosis.


Impaired Player-Coach Perceptions of Exertion and Recovery During Match Congestion.
During intensified phases of competition, attunement of exertion and recovery is crucial to maintain performance. Although a mismatch between coach and player perceptions of training load is demonstrated, it is unknown if these discrepancies also exist for match exertion and recovery. To determine match exertion and subsequent recovery and to investigate the extent to which the coach is able to estimate players' match exertion and recovery. Rating of perceived exertion (RPE) and total quality of recovery (TQR) of 14 professional basketball players (age 26.7 ± 3.8 y, height 197.2 ± 9.1 cm, weight 100.3 ± 15.2 kg, body fat 10.3% ± 3.6%) were compared with observations of the coach. During an in-season phase of 15 matches within 6 wk, players gave RPEs after each match. TQR scores were filled out before the first training session after the match. The coach rated observed exertion (ROE) and recovery (TQ-OR) of the players. RPE was lower than ROE (15.6 ± 2.3 and 16.1 ± 1.4; P = .029). Furthermore, TQR was lower than TQ-OR (12.7 ± 3.0 and 15.3 ± 1.3; P < .001). Correlations between coach- and player-perceived exertion and recovery were r = .25 and r = .21, respectively. For recovery within 1 d the correlation was r = .68, but for recovery after 1-2 d no association existed. Players perceive match exertion as hard to very hard and subsequent recovery reasonable. The coach overestimates match exertion and underestimates degree of recovery. Correspondence between coach and players is thus not optimal. This mismatch potentially leads to inadequate planning of training sessions and decreases in performance during fixture congestion in basketball.


Using Oculomotor Features to Predict Changes in Optic Nerve Sheath Diameter and ImPACT Scores From Contact-Sport Athletes.
There is mounting evidence linking the cumulative effects of repetitive head impacts to neuro-degenerative conditions. Robust clinical assessment tools to identify mild traumatic brain injuries are needed to assist with timely diagnosis for return-to-field decisions and appropriately guide rehabilitation. The focus of the present study is to investigate the potential for oculomotor features to complement existing diagnostic tools, such as measurements of Optic Nerve Sheath Diameter (ONSD) and Immediate Post-concussion Assessment and Cognitive Testing (ImPACT). Thirty-one high school American football and soccer athletes were tracked through the course of a sports season. Given the high risk of repetitive head impacts associated with both soccer and football, our hypotheses were that (1) ONSD and ImPACT scores would worsen through the season and (2) oculomotor features would effectively capture both neurophysiological changes reflected by ONSD and neuro-functional status assessed via ImPACT. Oculomotor features were used as input to Linear Mixed-Effects Regression models to predict ONSD and ImPACT scores as outcomes. Prediction accuracy was evaluated to identify explicit relationships between eye movements, ONSD, and ImPACT scores. Significant Pearson correlations were observed between predicted and actual outcomes for ONSD (Raw = 0.70; Normalized = 0.45) and for ImPACT (Raw = 0.86; Normalized = 0.71), demonstrating the capability of oculomotor features to capture neurological changes detected by both ONSD and ImPACT. The most predictive features were found to relate to motor control and visual-motor processing. In future work, oculomotor models, linking neural structures to oculomotor function, can be built to gain extended mechanistic insights into neurophysiological changes observed through seasons of participation in contact sports.


Cosmetic tattoo ink darkening. A complication of Q-switched and pulsed-laser treatment.
High-energy, short-pulse lasers, eg, Q-switched lasers, emitting visible and near-infrared light have recently been developed for removing tattoos, with little risk of scarring. The mechanisms of action, and possible adverse effects other than scarring and hypopigmentation, are not fully understood. We describe five cases of pulsed-laser-induced, immediate, irreversible darkening of cosmetic, white, flesh (skin-color), and pink-red colored tattoos. Irreversible ink darkening can be an insidious complication, because immediate whitening of the skin temporarily obscures the subsequently impressive color change. Among these cases, irreversible ink darkening occurred with Q-switched ruby (694 nm), Q-switched neodymium (Nd):YAG (1064 nm/532 nm), and pulsed green dye (510 nm) lasers. Attempts to remove the darkened ink with further laser treatment failed in two cases, and surgical excision was necessary. In the other three cases, subsequent laser treatments successfully removed the darkened ink. The red cosmetic tattoo ink used in one of the cases was placed in agar in vitro and was converted to a black compound immediately on Q-switched ruby laser exposure. Ferric oxide, a brown-red ingredient commonly used in cosmetic tattoos, was similarly tested and blackened in vitro by Q-switched ruby laser exposures. Although most tattoos are not darkened by laser treatment, short-pulsed lasers over a wide spectrum can cause immediate darkening of some tattoo inks. Patients should be warned of the potential for irreversible cosmetic tattoo darkening, and test-site exposures should be performed prior to treatment. In some cases, subsequent laser treatments may remove the blackened ink. The mechanism probably involves, at least for some tattoos, reduction of ferric oxide (Fe2O3, "rust") to ferrous oxide (FeO, jet black), but the chemical reaction that is involved remains unknown.


An extended cavity femtosecond Cr:LiSAF laser pumped by low cost diode lasers.
We describe an extended cavity femtosecond Cr:LiSAF laser pumped by inexpensive single spatial mode diodes. Using a multi-pass cavity (MPC) to lower the repetition rate and a saturable Bragg reflector (SBR) for mode-locking, pulse energies of 0.75 nJ at a repetition rate of 8.6 MHz are achieved with durations of 39 fs and bandwidths of 20 nm in a prismless configuration. Pulse energies of 0.66 nJ at a repetition rate of 8.4 MHz with durations of 43 fs and bandwidths of 18.5 nm are generated using prisms for dispersion compensation. This laser offers performance approaching that of standard Ti:sapphire lasers at a fraction of the cost.


Gametes or organs? How should we legally classify ovaries used for transplantation in the USA?
Ovarian tissue transplantation is an experimental procedure that can be used to treat both infertility and premature menopause. Working within the current legal framework in the USA, I examine whether ovarian tissue should be legally treated like gametes or organs in the case of ovarian tissue transplantation between two women. One option is to base classification upon its intended use: ovarian tissue used to treat infertility would be classified like gametes, and ovarian tissue used to treat premature menopause would be classified like organs. In the end, however, I argue that this approach will not work because it engenders too many legal, cultural and logistical concerns and that, at least for the near future, we should treat ovarian tissue like gametes.


The potential risk assessment for different arsenic species in the aquatic environment.
The different toxicity characteristics of arsenic species result in discrepant ecological risk. The predicted no-effect concentrations (PNECs) 43.65, 250.18, and 2.00×10(3)μg/L were calculated for As(III), As(V), and dimethylarsinic acid in aqueous phase, respectively. With these PNECs, the ecological risk from arsenic species in Pearl River Delta in China and Kwabrafo stream in Ghana was evaluated. It was found that the risk from As(III) and As(V) in the samples from Pearl River Delta was low, while much high in Kwabrafo stream. This study implies that ecological risk of arsenic should be evaluated basing on its species.


Developing a Blood Cell-Based Diagnostic Test for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Using Peripheral Blood Mononuclear Cells.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by debilitating fatigue that profoundly impacts patients' lives. Diagnosis of ME/CFS remains challenging, with most patients relying on self-report, questionnaires, and subjective measures to receive a diagnosis, and many never receiving a clear diagnosis at all. In this study, a single-cell Raman platform and artificial intelligence are utilized to analyze blood cells from 98 human subjects, including 61 ME/CFS patients of varying disease severity and 37 healthy and disease controls. These results demonstrate that Raman profiles of blood cells can distinguish between healthy individuals, disease controls, and ME/CFS patients with high accuracy (91%), and can further differentiate between mild, moderate, and severe ME/CFS patients (84%). Additionally, specific Raman peaks that correlate with ME/CFS phenotypes and have the potential to provide insights into biological changes and support the development of new therapeutics are identified. This study presents a promising approach for aiding in the diagnosis and management of ME/CFS and can be extended to other unexplained chronic diseases such as long COVID and post-treatment Lyme disease syndrome, which share many of the same symptoms as ME/CFS.


Meta-analysis of field experiments shows no change in racial discrimination in hiring over time.
This study investigates change over time in the level of hiring discrimination in US labor markets. We perform a meta-analysis of every available field experiment of hiring discrimination against African Americans or Latinos (n = 28). Together, these studies represent 55,842 applications submitted for 26,326 positions. We focus on trends since 1989 (n = 24 studies), when field experiments became more common and improved methodologically. Since 1989, whites receive on average 36% more callbacks than African Americans, and 24% more callbacks than Latinos. We observe no change in the level of hiring discrimination against African Americans over the past 25 years, although we find modest evidence of a decline in discrimination against Latinos. Accounting for applicant education, applicant gender, study method, occupational groups, and local labor market conditions does little to alter this result. Contrary to claims of declining discrimination in American society, our estimates suggest that levels of discrimination remain largely unchanged, at least at the point of hire.


A genome-wide screen for promoter methylation in lung cancer identifies novel methylation markers for multiple malignancies.
Promoter hypermethylation coupled with loss of heterozygosity at the same locus results in loss of gene function in many tumor cells. The "rules" governing which genes are methylated during the pathogenesis of individual cancers, how specific methylation profiles are initially established, or what determines tumor type-specific methylation are unknown. However, DNA methylation markers that are highly specific and sensitive for common tumors would be useful for the early detection of cancer, and those required for the malignant phenotype would identify pathways important as therapeutic targets. In an effort to identify new cancer-specific methylation markers, we employed a high-throughput global expression profiling approach in lung cancer cells. We identified 132 genes that have 5' CpG islands, are induced from undetectable levels by 5-aza-2'-deoxycytidine in multiple non-small cell lung cancer cell lines, and are expressed in immortalized human bronchial epithelial cells. As expected, these genes were also expressed in normal lung, but often not in companion primary lung cancers. Methylation analysis of a subset (45/132) of these promoter regions in primary lung cancer (n = 20) and adjacent nonmalignant tissue (n = 20) showed that 31 genes had acquired methylation in the tumors, but did not show methylation in normal lung or peripheral blood cells. We studied the eight most frequently and specifically methylated genes from our lung cancer dataset in breast cancer (n = 37), colon cancer (n = 24), and prostate cancer (n = 24) along with counterpart nonmalignant tissues. We found that seven loci were frequently methylated in both breast and lung cancers, with four showing extensive methylation in all four epithelial tumors. By using a systematic biological screen we identified multiple genes that are methylated with high penetrance in primary lung, breast, colon, and prostate cancers. The cross-tumor methylation pattern we observed for these novel markers suggests that we have identified a partial promoter hypermethylation signature for these common malignancies. These data suggest that while tumors in different tissues vary substantially with respect to gene expression, there may be commonalities in their promoter methylation profiles that represent targets for early detection screening or therapeutic intervention.


Genetic Variation of 25 Y-Chromosomal and 15 Autosomal STR Loci in the Han Chinese Population of Liaoning Province, Northeast China.
In the present study, we investigated the genetic characteristics of 25 Y-chromosomal and 15 autosomal short tandem repeat (STR) loci in 305 unrelated Han Chinese male individuals from Liaoning Province using AmpFISTR® Yfiler® Plus and IdentifilerTM PCR amplification kits. Population comparison was performed between Liaoning Han population and different ethnic groups to better understand the genetic background of the Liaoning Han population. For Y-STR loci, the overall haplotype diversity was 0.9997 and the discrimination capacity was 0.9607. Gene diversity values ranged from 0.4525 (DYS391) to 0.9617 (DYS385). Rst and two multi-dimensional scaling plots showed that minor differences were observed when the Liaoning Han population was compared to the Jilin Han Chinese, Beijing Han Chinese, Liaoning Manchu, Liaoning Mongolian, Liaoning Xibe, Shandong Han Chinese, Jiangsu Han Chinese, Anhui Han Chinese, Guizhou Han Chinese and Liaoning Hui populations; by contrast, major differences were observed when the Shanxi Han Chinese, Yunnan Bai, Jiangxi Han Chinese, Guangdong Han Chinese, Liaoning Korean, Hunan Tujia, Guangxi Zhuang, Gansu Tibetan, Xishuangbanna Dai, South Korean, Japanese and Hunan Miao populations. For autosomal STR loci, DP ranged from 0.9621 (D2S1338) to 0.8177 (TPOX), with PE distributing from 0.7521 (D18S51) to 0.2988 (TH01). A population comparison was performed and no statistically significant differences were detected at any STR loci between Liaoning Han, China Dong, and Shaanxi Han populations. The results showed that the 25 Y-STR and 15 autosomal STR loci in the Liaoning Han population were valuable for forensic applications and human genetics, and Liaoning Han was an independent endogenous ethnicity with a unique subpopulation structure.


Urinary tract infection-like symptom is associated with worse bladder cancer outcomes in the Medicare population: Implications for sex disparities.
To determine the time to bladder cancer diagnosis from initial infection-like symptoms and its impact on cancer outcomes. Using Surveillance, Epidemiology and End Results-Medicare, we designed a retrospective cohort study identifying beneficiaries aged ≥ 66 years diagnosed with bladder cancer from 2007 to 2009. Patients were required to have a hematuria or urinary tract infection claim within 1 year of bladder cancer diagnosis (n = 21 216), and have 2 years of prior Medicare data (n = 18 956) without any precedent hematuria, bladder cancer or urinary tract infection claims (n = 12 195). The number of days to bladder cancer diagnosis was measured, as well as the impact of sex and presenting symptom on time to diagnosis, pathology, and oncological outcomes. The mean time to bladder cancer diagnosis was 72.2 days in women versus 58.9 days in men (P < 0.001). A logistic regression model identified the greatest predictors of ≥ pT2 pathology were both women (odds ratio 2.08, 95% confidence interval 1.70-2.55) and men (odds ratio 1.71, 95% confidence interval 1.49-1.97) presenting with urinary tract infection. Cox proportional hazards analysis identified an increased risk of mortality from bladder cancer and all causes in women presenting with urinary tract infection (hazard ratio 1.37, 95% confidence interval 1.10-1.71, and hazard ratio 1.47, 95% confidence interval 1.28-1.69) compared with women with hematuria. Women have a longer interval from urinary tract infection to diagnosis of bladder cancer. Urinary tract infection presentation can adversely affect time to diagnosis, pathology and survival. Time to diagnosis seems not to be an independent predictor of bladder cancer outcomes.


Biological analysis of human immunodeficiency virus type 1 R5 envelopes amplified from brain and lymph node tissues of AIDS patients with neuropathology reveals two distinct tropism phenotypes and identifies envelopes in the brain that confer an enhanced tropism and fusigenicity for macrophages.
Complete envelope genes were amplified from autopsy brain tissue of five individuals who had died of AIDS and had neurological complications. Lymph node samples were included for two of the patients. Nineteen different envelope clones from the five patients had distinct V1V2 sequences. Thirteen of the envelopes were functional and conferred fusigenicity and infectivity for CD4(+) CCR5(+) cells. Infectivity and cell-cell fusion assays showed that most envelopes used both CCR5 and CCR3. One brain-derived envelope used a broad range of coreceptors, while three other brain envelopes from one individual were restricted to CCR5. However, there was no correlation between tissue of origin and coreceptor use. Envelopes showed two very distinct phenotypes depending on their capacity to infect macrophages and to exploit low levels of CD4 and/or CCR5 for infection. Envelopes that were highly fusigenic and tropic for macrophages were identified in brain tissue from four of the five patients. The enhanced macrophage tropism correlated with reduced sensitivity to inhibition by Q4120, a CD4-specific antibody, but not with sensitivity to the CCR5 inhibitor, TAK779. The highly macrophage-tropic envelopes were able to infect cells expressing low levels of CD4 and/or CCR5. Comparison with several well-characterized macrophage-tropic envelopes showed that the four identified patient envelopes were at the top limit of macrophage tropism. In contrast, all four lymph node-derived envelopes exhibited a non-macrophage-tropic phenotype and required high levels of CD4 for infection. Our data support the presence of envelopes that are highly fusigenic and tropic for macrophages in the brains of patients with neurological complications. These envelopes are able to infect cells that express low levels of CD4 and/or CCR5 and may have adapted for replication in brain macrophages and microglia, which are known to express limited amounts of CD4.


Quantitative FRET measurement by high-speed fluorescence excitation and emission spectrometer.
Förster resonance energy transfer (FRET) is an important method in studying biochemistry reactions. But quantifying FRET rapidly is difficult to do because of crosstalk between free donor, free acceptor and FRET fluorescent signals when only excitation or emission property of a FRET sample is measured. If FRET is studied with excitation-emission matrix (EEM) measurements, because the fluorescence intensity maxima of donor, acceptor, and FRET emissions occupy different regions within the EEM, FRET fluorescence can be easily separated out by linear unmixing. In this paper, we report a novel high-speed Fourier Fluorescence Excitation Emission spectrometer, which simultaneously measures three projections of EEM from a FRET sample, which are excitation, emission and excitation-emission cross-correlation spectra. We demonstrate that these three EEM projections can be measured and unmixed in approximately 1 ms to provide rapid quantitative FRET in the presence of free donors and acceptors. The system can be utilized to enable real-time biochemistry reaction studies.


Effects of Ultraviolet Germicidal Irradiation (UVGI) on N95 Respirator Filtration Performance and Structural Integrity.
The ability to disinfect and reuse disposable N95 filtering facepiece respirators (FFRs) may be needed during a pandemic of an infectious respiratory disease such as influenza. Ultraviolet germicidal irradiation (UVGI) is one possible method for respirator disinfection. However, UV radiation degrades polymers, which presents the possibility that UVGI exposure could degrade the ability of a disposable respirator to protect the worker. To study this, we exposed both sides of material coupons and respirator straps from four models of N95 FFRs to UVGI doses from 120-950 J/cm(2). We then tested the particle penetration, flow resistance, and bursting strengths of the individual respirator coupon layers, and the breaking strength of the respirator straps. We found that UVGI exposure led to a small increase in particle penetration (up to 1.25%) and had little effect on the flow resistance. UVGI exposure had a more pronounced effect on the strengths of the respirator materials. At the higher UVGI doses, the strength of the layers of respirator material was substantially reduced (in some cases, by >90%). The changes in the strengths of the respirator materials varied considerably among the different models of respirators. UVGI had less of an effect on the respirator straps; a dose of 2360 J/cm(2) reduced the breaking strength of the straps by 20-51%. Our results suggest that UVGI could be used to effectively disinfect disposable respirators for reuse, but the maximum number of disinfection cycles will be limited by the respirator model and the UVGI dose required to inactivate the pathogen.


Parameters associated with ventricular arrhythmias in mitral valve prolapse with significant regurgitation.
Mitral valve prolapse (MVP) has been associated with ventricular arrhythmias (VA), but little is known about VA in patients with significant primary mitral regurgitation (MR). Our aim was to describe the prevalence of symptomatic VA in patients with MVP (fibro-elastic deficiency or Barlow's disease) referred for mitral valve (MV) surgery because of moderate-to-severe MR, and to identify clinical, electrocardiographic, standard and advanced echocardiographic parameters associated with VA. 610 consecutive patients (64±12 years, 36% female) were included. Symptomatic VA was defined as symptomatic and frequent premature ventricular contractions (PVC, Lown grade ≥2), non-sustained or sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) without ischaemic aetiology. A total of 67 (11%) patients showed symptomatic VA, of which 3 (4%) had VF, 3 (4%) sustained VT, 27 (40%) non-sustained VT and 34 (51%) frequent PVCs. Patients with VA were significantly younger, more often female and showed T-wave inversions; furthermore, they showed significant MV morphofunctional abnormalities, such as mitral annular disjunction (39% vs 20%, p<0.001), and dilatation (annular diameter 37±5 mm vs 33±6 mm, p<0.001), lower global longitudinal strain (GLS 20.9±3.1% vs 22.0±3.6%, p=0.032) and prolonged mechanical dispersion (45±12 ms vs 38±14 ms, p=0.003) as compared with patients without VA. Female sex, increased MV annular diameter, lower GLS and prolonged mechanical dispersion were identified as independent associates of symptomatic VA. In patients with MVP with moderate-to-severe MR, symptomatic VA are relatively frequent and associated with significant MV annular abnormalities, subtle left ventricular function impairment and heterogeneous contraction. Assessment of these parameters might help decision-making over further diagnostic analyses and improve risk-stratification.


Restoration of circadian behavior by anterior hypothalamic heterografts.
The suprachiasmatic nucleus (SCN) of the anterior hypothalamus (AH) is a circadian oscillator and an important component of the mammalian circadian system. To determine whether the SCN is the dominant circadian pacemaker responsible for generating a species-typical characteristic of circadian rhythms [i.e., period length (tau)], neural transplantation was conducted using fetal AH donors of different species and SCN-lesioned (SCNx) hosts. The circadian behavior of each of the three donor species is clearly distinguishable by its species-typical tau. The extent of SCN pacemaker autonomy was assessed by noting whether the period of the restored circadian rhythm following heterograft transplantation was characteristic of the donor or the host, or whether an atypical circadian period was established. Hamsters rendered arhythmic by SCN ablation were implanted with AH tissue from fetal hamsters (E13-E14, homograft controls) or fetal mice or rats (E15-E17). The AH homografts restored circadian activity rhythms with a tau similar to that of intact hamsters, and fetal mouse AH heterografts restored circadian rhythmicity with a tau similar to that of the donor mouse strain. However, fetal rat AH tissue implanted into SCNx hamsters renewed circadian rhythmicity with a period significantly shorter than either the species-typical tau of the rat donor or the hamster host. In both the mouse and rat AH heterograft experiments, immunocytochemical analysis performed with species-specific monoclonal antibodies revealed extensive fiber outgrowth from the implant into the host hypothalamus, evident up to 7 months postimplantation. The rat implants were consistently larger, more fully vascularized and exhibited less necrosis than the implanted mouse tissue. The histological appearance of the grafts, thus, provides no explantation for the difference in efficacy of the grafts to restore species-typical behavior. However, several interpretations are considered that are consistent with the combined behavioral results observed.


The Use of Avoidance, Adjustment, Interaction and Acceptance Strategies to Handle Participation Restrictions Among Swedish Men with Early Rheumatoid Arthritis.
Living with a chronic disease means learning to live under new circumstances and involves a continuous adaptation to new ways of living. There is increasing knowledge about how people cope with stressful life events and adapt to new life situations. Approximately a third of patients diagnosed with rheumatoid arthritis (RA) are men; however, few studies have described the needs and experiences of men living with RA. The aim of the present study was to explore men's strategies for handling challenges related to participation in everyday life. The present study was associated with the prospective Swedish multicentre early arthritis project (given the Swedish acronym TIRA), which, in 2006-2009, included patients with early RA, contemporarily treated, with a mean disease duration of three years. From this cohort, 25 men, aged 20-63 years, were recruited consecutively. Data were collected in individual interviews, using the critical incident technique. The strategies for dealing with the challenges of RA in everyday life were analysed and categorized using content analysis. Men with RA described four types of strategy for dealing with participation restrictions in everyday life: (i) Adjustment strategies - adjust behaviour, movements, medication, equipment and clothing to find new ways to conduct tasks or activities; (ii) Avoidance strategies - avoid activities, movements, social contacts and sometimes medication; (iii) Interaction strategies - say no, ask for help and work together to handle participation restrictions; and (iv) Acceptance strategies - learn to accept RA, with the pain, the slower work pace and the extended time needed. According to men's lived experiences, a combination of strategies was used to deal with RA, depending on the situation and the experienced restriction. The results provided an understanding of how men with RA manage their disease, to reduce physical, social and emotional challenges. This knowledge may be used further to develop multi-professional interventions and patient education tailored to men with RA.


Does maintained spinal manipulation therapy for chronic nonspecific low back pain result in better long-term outcome?
A prospective single blinded placebo controlled study was conducted. To assess the effectiveness of spinal manipulation therapy (SMT) for the management of chronic nonspecific low back pain (LBP) and to determine the effectiveness of maintenance SMT in long-term reduction of pain and disability levels associated with chronic low back conditions after an initial phase of treatments. SMT is a common treatment option for LBP. Numerous clinical trials have attempted to evaluate its effectiveness for different subgroups of acute and chronic LBP but the efficacy of maintenance SMT in chronic nonspecific LBP has not been studied. Sixty patients, with chronic, nonspecific LBP lasting at least 6 months, were randomized to receive either (1) 12 treatments of sham SMT over a 1-month period, (2) 12 treatments, consisting of SMT over a 1-month period, but no treatments for the subsequent 9 months, or (3) 12 treatments over a 1-month period, along with "maintenance spinal manipulation" every 2 weeks for the following 9 months. To determine any difference among therapies, we measured pain and disability scores, generic health status, and back-specific patient satisfaction at baseline and at 1-, 4-, 7-, and 10-month intervals. Patients in second and third groups experienced significantly lower pain and disability scores than first group at the end of 1-month period (P = 0.0027 and 0.0029, respectively). However, only the third group that was given spinal manipulations (SM) during the follow-up period showed more improvement in pain and disability scores at the 10-month evaluation. In the nonmaintained SMT group, however, the mean pain and disability scores returned back near to their pretreatment level. SMT is effective for the treatment of chronic nonspecific LBP. To obtain long-term benefit, this study suggests maintenance SM after the initial intensive manipulative therapy.


Endothelial dysfunction and inflammatory process in transfusion-dependent patients with beta-thalassemia major.
Beta-thalassemia major is associated with increased cardiovascular risk, although the underlying mechanisms remain unclear. We examined endothelial function and serum levels of inflammatory mediators in transfusion-dependent patients with beta-thalassemia major. The study population consisted of 67 patients with homozygous beta-thalassemia major, (aged 24.6+/-0.7 years) and 71 healthy age and sex matched controls. Forearm blood flow was measured with gauge-strain plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) or to nitrate (NTG%) was expressed as the percentage change of forearm blood flow from baseline to the maximum flow during reactive hyperemia or sublingual nitroglycerin, respectively. Serum levels of interleukin 6 (IL-6), soluble vascular cell adhesion molecule (sVCAM-1) and soluble intercellular adhesion molecule (sICAM-1) were determined with ELISA. Patients had significantly lower levels of total cholesterol (125+/-4.5 vs. 207+/-7 mg/ml, p<0.01), ApoA1 (120+/-3 vs. 129+/-5 mg/ml, p<0.05), ApoB (60.5+/-2 vs. 95+/-4 mg/ml, p<0.01), ApoE (3+/-2 vs. 4+/-0.2 mg/ml, p<0.01) and Lp(a) (7.9+/-1.3 vs. 14.5+/-3.2 mg/ml, p<0.01) than controls. IL-6 levels were significantly higher in patients (3.03+/-0.31 pg/ml) than controls (1.15+/-0.15 pg/ml, p<0.01). Similarly, sVCAM-1 and sICAM-1 levels were significantly higher in patients (513+/-31 and 368+/-25.5 ng/ml, respectively) than controls (333+/-13.8 and 272+/-14.05 ng/ml, respectively, p<0.01 for both). Maximum hyperemic forearm blood flow and RH% were lower in patients (7.1+/-0.3 ml/100 ml tissue/min and 49+/-2.8%, respectively) than controls (8.26+/-0.32 ml/100 ml tissue/min and 86.3+/-5.57%, respectively, p<0.01 for both). Beta-thalassemia major is associated with impaired endothelial function and increased levels of IL-6, sVCAM-1 and sICAM-1, suggesting a potential role of inflammation and endothelial dysfunction in the complications of the disease.


Testing process errors and their harms and consequences reported from family medicine practices: a study of the American Academy of Family Physicians National Research Network.
Little is known about the types and outcomes of testing process errors that occur in primary care. To describe types, predictors and outcomes of testing errors reported by family physicians and office staff. Events were reported anonymously. Each office completed a survey describing their testing processes prior to event reporting. 243 clinicians and office staff of eight family medicine offices. Distribution of error types, associations with potential predictors; predictors of harm and consequences of the errors. Participants submitted 590 event reports with 966 testing process errors. Errors occurred in ordering tests (12.9%), implementing tests (17.9%), reporting results to clinicians (24.6%), clinicians responding to results (6.6%), notifying patient of results (6.8%), general administration (17.6%), communication (5.7%) and other categories (7.8%). Charting or filing errors accounted for 14.5% of errors. Significant associations (p<0.05) existed between error types and type of reporter (clinician or staff), number of labs used by the practice, absence of a results follow-up system and patients' race/ethnicity. Adverse consequences included time lost and financial consequences (22%), delays in care (24%), pain/suffering (11%) and adverse clinical consequence (2%). Patients were unharmed in 54% of events; 18% resulted in some harm, and harm status was unknown for 28%. Using multilevel logistic regression analyses, adverse consequences or harm were more common in events that were clinician-reported, involved patients aged 45-64 years and involved test implementation errors. Minority patients were more likely than white, non-Hispanic patients to suffer adverse consequences or harm. Errors occur throughout the testing process, most commonly involving test implementation and reporting results to clinicians. While significant physical harm was rare, adverse consequences for patients were common. The higher prevalence of harm and adverse consequences for minority patients is a troubling disparity needing further investigation.


Human infants detect other people's interactions based on complex patterns of kinematic information.
Do infants perceive other people's interactions by means of a mechanism that integrates biological motion information across the observed individuals? In support of this view, the present study demonstrates that infants (N = 28, Age = 14 months) discriminate between point light displays representing disrupted and non-disrupted interactions between people, even though the two interaction types are identical at the level of individual point light agents. Moreover, a second experiment (sample 2: N = 28, Age = 14 months) indicated that visual preference in this context is influenced by an audiovisual integration processes that takes into account the presence of an interaction between people. All these results were found exclusively for upright displays--when stimuli were shown upside-down (disrupting biological motion processing), performance was random. Collectively, these findings point to an important role for biological motion in social perception in human infants.


Successful use of talc sclerodesis to control a persistent high-output groin seroma following endovascular abdominal aortic aneurysm repair.
Groin wound lymphatic complications after vascular procedures are accompanied by increased risk of infection, prolonged hospital stay, and greater patient morbidity. High-output groin seromas can be difficult to manage and refractory to established interventions. Although subcutaneous talc has been used to prevent seroma accumulation in other high-risk surgical fields, such as after axillary lymph node dissection, it has not been described in the context of vascular surgery. This article presents the first reported case of a persistent high-output groin seroma after endovascular abdominal aortic aneurysm repair managed successfully with intraoperative application of sterile talc.


Simultaneous prediction of Cryptosporidium parvum oocyst inactivation and bromate formation during ozonation of synthetic waters.
A model was developed to simultaneously assess Cryptosporidium parvum oocyst inactivation and bromate formation during ozonation of synthetic solutions in batch and flow-through reactors. The model incorporated 65 elementary chemical reactions involved in the decomposition of ozone and the oxidation of bromine species and their corresponding rate or equilibrium constants reported in the literature. Ozonation experiments were performed with a laboratory-scale batch reactor to evaluate the model with respect to the rate of ozone decomposition and bromate formation. The model was found to provide a good representation of experimental results when the ozone decomposition initiation reaction with hydroxide ion was assumed to produce superoxide radical instead of the alternatively proposed product hydrogen peroxide. The model was further developed to simulate the performance of a flow-through bubble-diffuser reactor with an external recirculation line. Each compartment of the reactor (bubble column and recirculation line) was assumed to behave as a plug flow reactor as supported by tracer test results, and an empirical correlation was used to represent the rate of ozone gas transfer in the bubble column. Model predictions of the performance of the flow-through ozone bubble-diffuser contactor were in good agreement with experimental results obtained for bromate formation and C. parvum oocyst inactivation under all conditions investigated. Additional model simulations revealed that hydrodynamic conditions had a more pronounced effect on C. parvum oocyst inactivation than on bromate formation. In contrast, pH had a strong effect on bromate formation without affecting the inactivation efficiency of C. parvum oocysts for a given level of exposure to ozone. These findings suggested that bromate formation could be minimized while achieving target inactivation levels for C. parvum oocysts by designing ozone reactors with hydrodynamic conditions approaching that of an ideal plug flow reactor and by lowering the pH of the target water.


Experimental demonstration of accelerated extinction in source-sink metapopulations.
Population extinction is a fundamental ecological process which may be aggravated by the exchange of organisms between productive (source) and unproductive (sink) habitat patches. The extent to which such source-sink exchange affects extinction rates is unknown. We conducted an experiment in which metapopulation effects could be distinguished from source-sink effects in laboratory populations of Daphnia magna. Time-to-extinction in this experiment was maximized at intermediate levels of habitat fragmentation, which is consistent with a minority of theoretical models. These results provided a baseline for comparison with experimental treatments designed to detect effects of concentrating resources in source patches. These treatments showed that source-sink configurations increased population variability (the coefficient of variation in abundance) and extinction hazard compared with homogeneous environments. These results suggest that where environments are spatially heterogeneous, accurate assessments of extinction risk will require understanding the exchange of organisms among population sources and sinks. Such heterogeneity may be the norm rather than the exception because of both the intrinsic heterogeneity naturally exhibited by ecosystems and increasing habitat fragmentation by human activity.


A quantitative definition of hypervalency.
From the inception of Lewis' theory of chemical bonding, hypervalency has remained a point of difficulty that has not been fully resolved by the currently accepted qualitative definition of this term. Therefore, in this work, a quantitative measure of hypervalency has been developed. The only required input is the atomic charge map, which can be obtained from either quantum calculations or from experiment. Using this definition, it is found that well-known species such as O3, CH2N2 and ClO4-, are indeed hypervalent, whilst others such as XeF4, PCl5 and SO42-, are not. Quantitative analysis of known species of general formulae XF nm-, XCl nm-, and XO nm- shows that there are no fundamental differences in chemical bonding for hypervalent and non-hypervalent species. Nevertheless, hypervalency is associated with chemical instability, as well as a high degree of covalent rather than ionic bonding. The implications for accepted Lewis structure conventions are discussed.


Sex- and diet-specific changes of imprinted gene expression and DNA methylation in mouse placenta under a high-fat diet.
Changes in imprinted gene dosage in the placenta may compromise the prenatal control of nutritional resources. Indeed monoallelic behaviour and sensitivity to changes in regional epigenetic state render imprinted genes both vulnerable and adaptable. We investigated whether a high-fat diet (HFD) during pregnancy modified the expression of imprinted genes and local and global DNA methylation patterns in the placenta. Pregnant mice were fed a HFD or a control diet (CD) during the first 15 days of gestation. We compared gene expression patterns in total placenta homogenates, for male and female offspring, by the RT-qPCR analysis of 20 imprinted genes. Sexual dimorphism and sensitivity to diet were observed for nine genes from four clusters on chromosomes 6, 7, 12 and 17. As assessed by in situ hybridization, these changes were not due to variation in the proportions of the placental layers. Bisulphite-sequencing analysis of 30 CpGs within the differentially methylated region (DMR) of the chromosome 17 cluster revealed sex- and diet-specific differential methylation of individual CpGs in two conspicuous subregions. Bioinformatic analysis suggested that these differentially methylated CpGs might lie within recognition elements or binding sites for transcription factors or factors involved in chromatin remodelling. Placental global DNA methylation, as assessed by the LUMA technique, was also sexually dimorphic on the CD, with lower methylation levels in male than in female placentae. The HFD led to global DNA hypomethylation only in female placenta. Bisulphite pyrosequencing showed that neither B1 nor LINE repetitive elements could account for these differences in DNA methylation. A HFD during gestation triggers sex-specific epigenetic alterations within CpG and throughout the genome, together with the deregulation of clusters of imprinted genes important in the control of many cellular, metabolic and physiological functions potentially involved in adaptation and/or evolution. These findings highlight the importance of studying both sexes in epidemiological protocols and dietary interventions.


Facet- and structure-dependent catalytic activity of cuprous oxide/polypyrrole particles towards the efficient reduction of carbon dioxide to methanol.
The preparation of cost-effective, stable catalysts for the selective reduction of carbon dioxide (CO2) to C1 products such as methanol is extremely important because methanol can be used directly as a fuel or it can be converted into other value-added products. However, the catalysts currently used for the reduction of CO2 to methanol exhibit poor selectivity, poor stability and very low faradaic efficiency. Herein, we used low-cost, stable cuprous oxide/polypyrrole (Cu2O/Ppy) particles having structures of octahedra and icosahedra (microflowers) that were prepared on linen texture (LT) papers for the selective reduction of CO2 to form a value-added single C1 product, methanol. The Cu2O/Ppy particles possessing both octahedral and microflower shapes with exposed low-index (111) facets and high-index (311) and (211) facets are denoted as Cu2O(OL-MH)/Ppy particles. The as-prepared Cu2O(OL-MH)/Ppy particles exhibited high catalytic activity and selectivity towards the electrochemical reduction of CO2 at -0.85 V vs. RHE to form methanol, with a faradaic efficiency of 93 ± 1.2% and an average methanol formation rate of 1.61 ± 0.02 μmol m-2 s-1. The X-ray photoelectron spectroscopy (XPS) analysis revealed that the pyrrolic nitrogen atoms present in the Ppy shell played a dominant role as active sites for CO2 molecules. The Raman bands of Ppy and Cu2O did not shift even after being subjected to electrolysis for several hours, suggesting superior stability of the Cu2O(OL-MH)/Ppy particles. The high resolution microscopic, spectroscopic, diffraction and electrochemical analysis results clearly revealed that the Ppy shell protected the Cu2O particles and avoided corrosion, dissolution, and structural and crystal facet changes, leading to greater stability. The low-cost, durable, flexible, and catalytically active Cu2O(OL-MH)/Ppy LT paper holds great potential for catalytic, photocatalytic and energy storage applications.