A transgenic approach to control hemipteran insects by expressing insecticidal genes under phloem-specific promoters.
The first generation transgenic crops used strong constitutive promoters for transgene expression. However, tissue-specific expression is desirable for more precise targeting of transgenes. Moreover, piercing/sucking insects, which are generally resistant to insecticidal Bacillus thuringiensis (Bt) proteins, have emerged as a major pests since the introduction of transgenic crops expressing these toxins. Phloem-specific promoters isolated from Banana bunchy top virus (BBTV) were used for the expression of two insecticidal proteins, Hadronyche versuta (Blue Mountains funnel-web spider) neurotoxin (Hvt) and onion leaf lectin, in tobacco (Nicotiana tabacum). Here we demonstrate that transgenic plants expressing Hvt alone or in combination with onion leaf lectin are resistant to Phenacoccus solenopsis (cotton mealybug), Myzus persicae (green peach aphids) and Bemisia tabaci (silver leaf whitefly). The expression of both proteins under different phloem-specific promoters resulted in close to 100% mortality and provided more rapid protection than Hvt alone. Our results suggest the employment of the Hvt and onion leaf lectin transgenic constructs at the commercial level will reduce the use of chemical pesticides for control of hemipteran insect pests.


Can resource-use traits predict native vs. exotic plant success in carbon amended soils?
Productivity in desert ecosystems is primarily limited by water followed by nitrogen availability. In the deserts of southern California, nitrogen additions have increased invasive annual plant abundance. Similar findings from other ecosystems have led to a general acceptance that invasive plants, especially annual grasses, are nitrophilous. Consequently, reductions of soil nitrogen via carbon amendments have been conducted by many researchers in a variety of ecosystems in order to disproportionately lower invasive species abundance, but with mixed success. Recent studies suggest that resource-use traits may predict the efficacy of such resource manipulations; however, this theory remains largely untested. We report findings from a carbon amendment experiment that utilized two levels of sucrose additions that were aimed at achieving soil carbon to nitrogen ratios of 50:1 and 100:1 in labile sources. Carbon amendments were applied once each year, for three years, corresponding with the first large precipitation event of each wet season. Plant functional traits measured on the three invasive and 11 native herbaceous species that were most common at the study site showed that exotic and native species did not differ in traits associated with nitrogen use. In fact, plant abundance measures such as density, cover, and biomass showed that carbon amendments were capable of decreasing both native and invasive species. We found that early-germinating species were the most impacted by decreased soil nitrogen resulting from amendments. Because invasive annuals typically germinate earlier and exhibit a rapid phenology compared to most natives, these species are expected to be more competitive than native annuals yet more susceptible to early-season carbon amendments. However, desert annual communities can exhibit high interannual variability in species composition and abundance. Therefore, the relative abundance of native and invasive species at the time of application is critical to the success of carbon amendments at our study site. For land management purposes, carbon amendments remain relatively impractical and may only be useful at small scales or in conjunction with other invasive species removal techniques.


Diagnosis and perioperative management of ruptured AAA mimicking symptomatic groin hernia.
Ruptured abdominal aortic aneurysm (RAAA) can infrequently present as symptomatic groin hernia. This misleading form of presentation often leads to erroneous preoperative management resulting in poor survival. Two patients with RAAA mimicking symptomatic groin hernia underwent different preoperative managements pointing out the importance of the principles of hypotensive haemostasis in the scope of this emergency scenario. Computed Tomography Angiography (CTA) remains the recommended diagnostic tool-for both safe diagnosis of the ruptured aneurysm and precise preoperative planning. Endovascular aortic repair of the RAAA-if feasible-is the treatment of choice. This rare form of RAAA manifestation should call physicians attention-especially in patients with known abdominal aortic aneurysms in their preceding medical history.


Endocytosis and intracellular processing of tissue-type plasminogen activator by rat liver cells in vivo.
Endocytosis of tissue-type plasminogen activator (t-PA) by different types of rat liver cells was studied in immunocytochemically labelled cryosections as well as in biochemical experiments. For morphological localization of the ligand in different endocytic compartments involved in its catabolism, rat livers were fixed at various times (1-24 min) after injection of t-PA. Late-endosomal and lysosomal compartments were identified by double-labelling the sections with antibodies to the lysosomal proteins glycoprotein Igp 120 and cathepsin D. In liver t-PA was localized in sinusoidal endothelial cells (EC), parenchymal cells (PC) and to some extent in Kupffer cells (KC), indicating that it is internalized and degraded in all three cell types. In specimens fixed 6 min after injection PC, EC and KC were found to contribute to 69, 24 and 7% respectively of total t-PA endocytosed. The transfer from late endosomes to lysosomes was found to be faster in EC than in PC. The morphological findings were supported by studies of the endocytic mechanisms employing isolated perfused livers and primary hepatocytes. The presence of monensin, an inhibitor of lysosomal protein degradation, reduced the amount of t-PA degraded to about 50% of the control values. The catalytic site seems not to be required for the catabolism of t-PA in hepatic cells. The inhibition of t-PA by D-phenylalanyl-L-prolylarginyl-chloromethane did not influence receptor recognition and catabolic processing, as determined in morphological studies using labelled cryosections, in binding studies employing liver cell membranes and primary hepatocytes, as well as in liver-perfusion experiments.


CD47 blockade augmentation of trastuzumab antitumor efficacy dependent on antibody-dependent cellular phagocytosis.
The HER2-specific monoclonal antibody (mAb), trastuzumab, has been the mainstay of therapy for HER2+ breast cancer (BC) for approximately 20 years. However, its therapeutic mechanism of action (MOA) remains unclear, with antitumor responses to trastuzumab remaining heterogeneous and metastatic HER2+ BC remaining incurable. Consequently, understanding its MOA could enable rational strategies to enhance its efficacy. Using both murine and human versions of trastuzumab, we found its antitumor activity dependent on Fcγ receptor stimulation of tumor-associated macrophages (TAMs) and antibody-dependent cellular phagocytosis (ADCP), but not cellular cytotoxicity (ADCC). Trastuzumab also stimulated TAM activation and expansion, but did not require adaptive immunity, natural killer cells, and/or neutrophils. Moreover, inhibition of the innate immune ADCP checkpoint, CD47, significantly enhanced trastuzumab-mediated ADCP and TAM expansion and activation, resulting in the emergence of a unique hyperphagocytic macrophage population, improved antitumor responses, and prolonged survival. In addition, we found that tumor-associated CD47 expression was inversely associated with survival in HER2+ BC patients and that human HER2+ BC xenografts treated with trastuzumab plus CD47 inhibition underwent complete tumor regression. Collectively, our study identifies trastuzumab-mediated ADCP as an important antitumor MOA that may be clinically enabled by CD47 blockade to augment therapeutic efficacy.


Gammaretroviral pol sequences act in cis to direct polysome loading and NXF1/NXT-dependent protein production by gag-encoded RNA.
All retroviruses synthesize essential proteins via alternatively spliced mRNAs. Retrovirus genera, though, exploit different mechanisms to coordinate the synthesis of proteins from alternatively spliced mRNAs. The best studied of these retroviral, post-transcriptional effectors are the trans-acting Rev protein of lentiviruses and the cis-acting constitutive transport element (CTE) of the betaretrovirus Mason-Pfizer monkey virus (MPMV). How members of the gammaretrovirus genus translate protein from unspliced RNA has not been elucidated. The mechanism by which two gammaretroviruses, XMRV and MLV, synthesize the Gag polyprotein (Pr65Gag) from full-length, unspliced mRNA was investigated here. The yield of Pr65Gag from a gag-only expression plasmid was found to be at least 30-fold less than that from an otherwise isogenic gag-pol expression plasmid. A frameshift mutation disrupting the pol open reading frame within the gag-pol expression plasmid did not decrease Pr65Gag production and 398 silent nucleotide changes engineered into gag rendered Pr65Gag synthesis pol-independent. These results are consistent with pol-encoded RNA acting in cis to promote Pr65Gag translation. Two independently-acting pol fragments were identified by screening 17 pol deletion mutations. To determine the mechanism by which pol promoted Pr65Gag synthesis, gag RNA in total and cytoplasmic fractions was quantitated by northern blot and by RT-PCR. The pol sequences caused, maximally, three-fold increase in total or cytoplasmic gag mRNA. Instead, pol sequences increased gag mRNA association with polyribosomes ~100-fold, a magnitude sufficient to explain the increase in Pr65Gag translation efficiency. The MPMV CTE, an NXF1-binding element, substituted for pol in promoting Pr65Gag synthesis. A pol RNA stem-loop resembling the CTE promoted Pr65Gag synthesis. Over-expression of NXF1 and NXT, host factors that bind to the MPMV CTE, synergized with pol to promote gammaretroviral gag RNA loading onto polysomes and to increase Pr65Gag synthesis. Conversely, Gag polyprotein synthesis was decreased by NXF1 knockdown. Finally, overexpression of SRp20, a shuttling protein that binds to NXF1 and promotes NXF1 binding to RNA, also increased gag RNA loading onto polysomes and increased Pr65Gag synthesis. These experiments demonstrate that gammaretroviral pol sequences act in cis to recruit NXF1 and SRp20 to promote polysome loading of gag RNA and, thereby license the synthesis of Pr65Gag from unspliced mRNA.


Protocol for a double-blind randomised placebo-controlled trial of lithium carbonate in patients with amyotrophic lateral sclerosis (LiCALS) [Eudract number: 2008-006891-31].
Amyotrophic lateral sclerosis is a rapidly progressive neurodegenerative disorder characterised by loss of motor neurons leading to severe weakness and death from respiratory failure within 3-5 years. Riluzole prolongs survival in ALS. A published report has suggested a dramatic effect of lithium carbonate on survival. 44 patients were studied, with 16 randomly selected to take LiCO3 and riluzole and 28 allocated to take riluzole alone. In the group treated with lithium, no patients had died (i.e., 100% survival) at the end of the study (15 months from entry), compared to 71% surviving in the riluzole-only group. Although the trial can be criticised on several grounds, there is a substantial rationale from other laboratory studies that lithium is worth investigating therapeutically in amyotrophic lateral sclerosis. LiCALS is a multi-centre double-blind randomised parallel group controlled trial of the efficacy, safety, and tolerability of lithium carbonate (LiCO3) at doses to achieve stable 'therapeutic' plasma levels (0.4-0.8 mmol/L), plus standard treatment, versus matched placebo plus standard treatment, in patients with amyotrophic lateral sclerosis. The study will be based in the UK, in partnership with the MND Association and DeNDRoN (the Dementias and Neurodegnerative Diseases Clinical Research Network). 220 patients will be recruited. All patients will be on the standard treatment for ALS of riluzole 100 mg daily. The primary outcome measure will be death from any cause at 18 months defined from the date of randomisation. Secondary outcome measures will be changes in three functional rating scales, the ALS Functional Rating Scale-Revised, The EuroQOL (EQ-5D), and the Hospital Anxiety and Depression Scale.Eligible patients will have El Escorial Possible, Laboratory-supported Probable, Probable or Definite amyotrophic lateral sclerosis with disease duration between 6 months and 36 months (inclusive), vital capacity ≥ 60% of predicted within 1 month prior to randomisation and age at least18 years. Patient recruitment began in June 2009 and the last patient is expected to complete the trial protocol in November 2011. Current controlled trials ISRCTN83178718.


Comparison of LABORAS with static incapacitance testing for assessing spontaneous pain behaviour in surgically-induced murine osteoarthritis.
Evoked responses following mechanical or thermal stimulation are typically used to assess pain behaviour in murine osteoarthritis (OA). However, there is no consensus on how best to measure spontaneous pain behaviour. OA by partial meniscectomy (PMX), or sham surgery was performed in 10-week old C57BL/6 male mice. Collagen-induced arthritis (CIA) was induced in 10 week old DBA1 male mice. Spontaneous pain behaviour, either at the time of active inflammatory disease (CIA), or over the 12 weeks after induction of OA, was assessed by static incapacitance testing (measuring percentage of weight placed through each hindlimb), and Laboratory Animal Behaviour Observation Registration and Analysis System (LABORAS) (translating cage vibrations of singly house animals into specific activities). Data were analysed by repeated measures two way ANOVA with post hoc testing comparing experimental groups with either sham operated or naïve controls. By incapacitance testing, two phases of painful behaviour were evident after PMX: a transient, post-operative phase, which resolved within one week, and a late OA pain phase starting 8 weeks post surgery and reaching statistical significance at week 12 (95% CI: sham 89.51-98.19, PMX 76.18-98.16). LABORAS, was able to detect pain behaviour in mice with CIA, but no statistically significant pain behaviour was observed in OA mice either post operatively (once analgesia had been controlled for) or at any later time points for any activity compared with the sham group. Static incapacitance testing is superior to LABORAS for measuring spontaneous pain behaviour in surgically induced murine OA.


Health status, health behaviour and healthcare use among migrants in the UK: evidence from mothers in the Millennium Cohort Study.
The health of migrants in the UK and their access to healthcare is of considerable policy interest. There is evidence of ethnic inequalities in health and access to and use of healthcare but insufficient consideration of the importance of birth abroad and length of residence in the UK. This study examines indicators of health status, behaviour and healthcare use among mothers of infants in the Millennium Cohort Study, according to whether born in the UK or abroad, individual ethnic grouping, and length of residence. Our findings show there are both positive and negative health indicators associated with ethnicity, birth abroad, and length of residence and presenting results on a single factor in isolation could lead to a misinterpretation of associations. For mothers ethnicity has an important relationship with most health indicators independent of country of birth, length of residence and socio-demographic circumstances. Once adjusted for ethnicity and socio-demographic variables, association with birth abroad disappears for most health outcomes suggesting that there may not be an independent migrant penalty in health. There is a linear trend in decreasing health status with increasing length of residence but no independent association between length of residence and healthcare use. This suggests that while there are continuing barriers to good health for migrants in the receiving society as shown in other studies, factors important for one health outcome may not apply to another. Our findings challenge linear acculturation models for migrants' health in showing that a linear trend in improving socio-economic circumstances for mothers in some ethnic groups is not always associated with better health outcomes or changes in health behaviour. Our results point to a need for a comprehensive collection of information and analysis for all categories of migrants for understanding patterns of and factors underlying health and use of healthcare.


How accurately are height, weight and leg length reported by the elderly, and how closely are they related to measurements recorded in childhood?
This paper examines (1) the accuracy of self-reported height, leg length and weight in a group of subjects aged 56-78; (2) whether recent measurement of height and weight influences the accuracy of self-reporting and (3) associations between childhood and adult height, leg length and BMI measured in old age. All 3182 surviving members of the Boyd Orr cohort were sent postal questionnaires in 1997-1998 and a sub-sample (294) was also clinically examined. Self-reported height was overestimated and body mass index (BMI), based on reported height and weight, underestimated. The mean difference between self-report and measured values were for height: 2.1 cm in males and 1.7 cm in females; for BMI the difference was -1.3 kg/m(2) in males and -1.2 kg/m(2) in females. Shorter individuals and older subjects tended to over-report their height more than others. The overweight under-reported their weight to a greater extent. Recent measurement appeared to decrease over-reporting of height but not weight. Correlations between self-report and measured height and BMI were generally over 0.90, but weaker for leg length (r = 0.70 in males and 0.71 in females). Adult height and leg length were quite closely related to their relative values in childhood (correlation coefficients ranged from 0.66 to 0.84), but associations between adult and childhood BMI were weak (r = 0.19 in males and 0.21 in females). Self-reported measures of height and weight may be used in studies of the elderly although systematic reporting errors may bias effect estimates. As overweight individuals tend to under-report and the short and underweight tend to over-report, studies investigating associations of disease with height and weight using self-reported measures will underestimate effects. The weak associations between childhood and adult BMI indicate that associations between childhood adiposity and adult cardiovascular disease found in this cohort may reflect the specific effect of childhood overweight, rather than its persistence into adulthood. This suggests that avoidance of adiposity may be as important in childhood as in adulthood.


Outcomes following erosions of the artificial urinary sphincter.
Artificial urinary sphincter urethral cuff erosion occurs in up to 5.0% of cases, presenting a complex management problem. We examine our experience with the eroded AUS, relating to preoperative risk factors, operative management and outcomes. We reviewed the medical records of 637 patients undergoing bulbar urethral AUS implantation from 1990 to 2003 for demographic and surgical variables. Of the 637 records reviewed, 46 patients underwent 54 explantations of the AUS device for erosions, including 13 who had the primary implant performed at our institution and 33 being referred for management of erosion after implantation elsewhere. Our institution erosion rate was 2.2%. Mean followup after AUS reimplant following erosion was 27.8 months (range 1 to 180). Comorbidities were more prevalent in patients with erosions included hypertension (p = 0.006), coronary artery disease (p = 0.03), prior radiation therapy (p = 0.006) and prior AUS revisions (p = 0.0001). A majority of patients had persistent mild incontinence (0 to 1 pad daily in 29 or 56.8%), moderate (1 to 3 pads daily in 9 or 17.4%) and severe (more than 3 pads daily in 6 or 11.8%) incontinence after secondary AUS implantation. Patients who underwent reimplantation after AUS cuff erosions have a significantly higher rate of second erosions (in 16, 34.8%) within an average of 6.7 months (range 3 to 24), including our own 11.8% institutional rate (in 4). Our study suggests that patients with comorbidities including hypertension, coronary artery disease, prior radiation therapy and prior AUS revisions are more likely to have erosions of their AUS. Nevertheless, continence can still be salvaged using various strategies which optimize use of the remaining healthy urethral tissue.


Optical and mechanical design of a "zipper" photonic crystal optomechanical cavity.
Design of a doubly-clamped beam structure capable of localizing mechanical and optical energy at the nanoscale is presented. The optical design is based upon photonic crystal concepts in which patterning of a nanoscale-cross-section beam can result in strong optical localization to an effective optical mode volume of 0.2 cubic wavelengths ( (lambdac)(3)). By placing two identical nanobeams within the near field of each other, strong optomechanical coupling can be realized for differential motion between the beams. Current designs for thin film silicon nitride beams at a wavelength of lambda?= 1.5 microm indicate that such structures can simultaneously realize an optical Q-factor of 7x10(6), motional mass m(u) approximately 40 picograms, mechanical mode frequency Omega(M)/2pi approximately 170 MHz, and an optomechanical coupling factor (g(OM) identical with domega(c)/dx = omega(c)/L(OM)) with effective length L(OM) approximately lambda= 1.5 microm.


Stability and instability for low refractive-index-contrast particle trapping in a dual-beam optical trap.
A dual-beam optical trap is used to trap and manipulate dielectric particles. When the refractive index of these particles is comparable to that of the surrounding medium, equilibrium trapping locations within the system shift from stable to unstable depending on fiber separation and particle size. This is due to to the relationship between gradient and scattering forces. We experimentally and computationally study the transitions between stable and unstable trapping of poly(methyl methacrylate) beads for a range of parameters relevant to experimental setups involving giant unilamellar vesicles. We present stability maps for various fiber separations and particle sizes, and find that careful attention to particle size and configuration is necessary to obtain reproducible quantitative results for soft matter stretching experiments.


Circadian clock gene variants and their link with chronotype, chrononutrition, sleeping patterns and obesity in the European prospective investigation into cancer and nutrition (EPIC) study.
The circadian clock is involved in the control of daily rhythms and is related to the individual's chronotype, i.e., the morningness-eveneningness preference. Knowledge is limited on the relationship between circadian genes, chronotype, sleeping patterns, chronutrition and obesity. The aim was to explore these associations within the EPIC-Spain cohort study. There were 3183 subjects with information on twelve genetic variants of six genes (PER1, PER2, PER3, CRY1, NR1D1, CLOCK). Their association was evaluated with: chronotype and sleeping duration/quality (assessed by questionnaires), chrononutrition (number of meals and timing of intake assessed by a diet history), and also anthropometric measures of obesity at early and late adulthood (in two points in time), such as weight and waist circumference (assessed by physical measurements). Multivariable logistic and linear regression as well as additive genetic models were applied. Odds ratios (ORs), β coefficients, and p-values corrected for multiple comparisons were estimated. Genetic risk scores (GRS) were built to test gene-outcome associations further. At nominal significance level, the variant rs2735611 (PER1 gene) was associated with a 11.6% decrease in long-term weight gain (per-allele β = -0.12), whereas three CLOCK gene variants (rs12649507, rs3749474 and rs4864548), were associated with a ∼20% decrease in waist circumference gain (per-allele β ∼ -0.19). These and other associations with body measures did not hold after multiple testing correction, except waist-to-hip ratio and rs1801260, rs2070062 and rs4580704 (CLOCK gene). Associations with chrononutrition variables, chronotype and sleep duration/quality failed to reach statistical significance. Conversely, a weighted GRS was associated with the evening/late chronotype and with all other outcomes (p < 0.05). The chronotype-GRS was associated with an increased overweight/obesity risk (vs normal weight) in both early and late adulthood (OR = 2.2; p = 0.004, and OR = 2.1; p = 0.02, respectively). Genetic variants of some circadian clock genes could explain the link between genetic susceptibility to the individual's chronotype and obesity risk.


Ion channel formation by zervamicin-IIB. A molecular modelling study.
Zervamicin-IIB (Zrv-IIB) is a 16 residue peptaibol which forms voltage-activated, multiple conductance level channels in planar lipid bilayers. A molecular model of Zrv-IIB channels is presented. The structure of monomeric Zrv-IIB is based upon the crystal structure of Zervamicin-Leu. The helical backbone is kinked by a hydroxyproline residue at position 10. Zrv-IIB channels are modelled as helix bundles of from 4 to 8 parallel helices surrounding a central pore. The monomers are packed with their C-terminal helical segments in close contact, and the bundles are stabilized by hydrogen bonds between glutamine 11 and hydroxyproline 10 of adjacent helices. Interaction energy profiles for movement of three different probes species (K+, Cl- and water) through the central pore are analyzed. The conformations of: (a) the sidechain of glutamine 3; (b) the hydroxyl group of hydroxyproline 10; and (c) the C-terminal hydroxyl group are "optimized" in order to maximize favourable interactions between the channel and the probes, resulting in favourable interaction energy profiles for all three. This suggests that conformational flexibility of polar sidechains enables the channel lining to mimic an aqueous environment.


Comparison of ramosetron and ondansetron for the treatment of established postoperative nausea and vomiting after laparoscopic surgery: a prospective, randomized, double-blinded multicenter trial.
Postoperative nausea and vomiting (PONV) is a common complication after surgery, which increases physical and psychological discomfort and delays recovery. The aim of this study was to test the hypothesis that ramosetron is comparable to ondansetron for the treatment of established PONV after laparoscopic surgery using a prospective, randomized, double-blinded, noninferiority study. Patients who had at least two risk factors of PONV and underwent laparoscopic surgery under general anesthesia were assessed for eligibility. Patients who developed PONV within the first 2 h after anesthesia received ondansetron (4 mg) or ramosetron (0.3 mg) intravenously in a randomized double-blind manner. Patients were then observed for 24 h after drug administration. The incidence of nausea and vomiting, severity of nausea, rescue antiemetic necessity, and adverse effects at 0-2 or 2-24 h after drug administration was evaluated. The primary endpoint was the rate of patients exhibiting a complete response, defined as no emesis and no further rescue antiemetic medication for 24 h after drug administration. Among the 583 patients, 210 (36.0%) developed PONV and were randomized to either the ondansetron (n=105) or ramosetron (n=105) group. Patient's characteristics were similar between the groups. The complete response rate was 44.1% in the ondansetron group and 52.9% in the ramosetron group after 24 h of initial antiemetic administration. The incidence of adverse events was not different between the groups. We found evidence to support the noninferiority of ramosetron (0.3 mg) compared to ondansetron (4 mg) for the treatment of established PONV in moderate to high-risk patients undergoing laparoscopic surgery.


Effect of Crop Rotations on Rotylenchulus reniformis Population Structure.
Rotylenchulus reniformis is a highly variable nematode species and an economically important pest in many cotton fields across the south-eastern United States. Rotation with resistant or poor host crops is a method for management of reniform nematode. We studied the effect of six planting schemes covering four 120-day planting cycles on the predominant genotype of R. reniformis. Rotations used were: (i) cotton to corn; (ii) susceptible soybean to corn; (iii) resistant soybean to cotton; (iv) corn to cotton; (v) continuous susceptible soybean; (vi) continuous cotton. After each 120-day cycle, amplified fragment length polymorphisms (AFLPs) produced from four primer pairs were used to determine the effect of crop rotation on the predominant genotype of reniform nematode. A total of 279 polymorphic bands were scored using four primer combinations. Distinct changes in genotype composition were observed following rotations with resistant soybean or corn. Rotations involving soybean (susceptible and resistant) had the greatest effect on population structure. The characterization of field population variability of reniform nematode and of population responses to host plants used in rotations can help extend the durability of resistant varieties and can help identify effective rotation schemes.


Does Twitter Affect Stock Market Decisions? Financial Sentiment Analysis During Pandemics: A Comparative Study of the H1N1 and the COVID-19 Periods.
Investors are constantly aware of the behaviour of stock markets. This affects their emotions and motivates them to buy or sell shares. Financial sentiment analysis allows us to understand the effect of social media reactions and emotions on the stock market and vice versa. In this research, we analyse Twitter data and important worldwide financial indices to answer the following question: How does the polarity generated by Twitter posts influence the behaviour of financial indices during pandemics? This study is based on the financial sentiment analysis of influential Twitter accounts and its relationship with the behaviour of important financial indices. To carry out this analysis, we used fundamental and technical financial analysis combined with a lexicon-based approach on financial Twitter accounts. We calculated the correlations between the polarities of financial market indicators and posts on Twitter by applying a date shift on tweets. In addition, correlations were identified days before and after the existing posts on financial Twitter accounts. Our findings show that the markets reacted 0 to 10 days after the information was shared and disseminated on Twitter during the COVID-19 pandemic and 0 to 15 days after the information was shared and disseminated on Twitter during the H1N1 pandemic. We identified an inverse relationship: Twitter accounts presented reactions to financial market behaviour within a period of 0 to 11 days during the H1N1 pandemic and 0 to 6 days during the COVID-19 pandemic. We also found that our method is better at detecting highly shifted correlations by using SenticNet compared with other lexicons. With SenticNet, it is possible to detect correlations even on the same day as the Twitter posts. The most influential Twitter accounts during the period of the pandemic were The New York Times, Bloomberg, CNN News and Investing.com, presenting a very high correlation between sentiments on Twitter and stock market behaviour. The combination of a lexicon-based approach is enhanced by a shifted correlation analysis, as latent or hidden correlations can be found in data.


The ethical review of health care quality improvement initiatives: findings from the field.
Questions have been raised about whether and how health care quality improvement (QI) initiatives ought to be reviewed to address possible ethical issues associated with them. These questions have focused primarily on whether some QI initiatives meet the regulatory criteria for human subject research and should therefore be regulated and reviewed as such. Based on surveys of health care system professionals conducting QI initiatives and hospital CEOs, this issue brief finds that QI initiatives are routinely reviewed by a variety of internal mechanisms prior to implementation, although rarely through an institutional review board or another independent body charged specifically with ethical oversight of QI initiatives. Further research, the authors say, is needed to achieve a better understanding of how review mechanisms for QI initiatives are structured, including information on who reviews these activities, how they are reviewed, and whether such processes include an ethical assessment of the proposed QI initiative.


Surveillance of human and swine adenovirus, human norovirus and swine circovirus in water samples in Santa Catarina, Brazil.
Animal and human wastewater can potentially contaminate water sources and the treatment of drinking water may not effectively remove all contaminants, especially viruses. The purpose of the present study was to evaluate the viral contamination of water used for human and animal consumption in the city of Concórdia, located in southern Brazil. Porcine circovirus type 2 (PCV2), porcine adenovirus (PAdV), human adenovirus (HAdV) and human norovirus (NoV) were searched for using quantitative polymerase chain reaction (qPCR). HAdV-positive samples were tested for viral infectivity by plaque assay. The qPCR results showed that PAdV, PCV2 and HAdV genetic material were present in all sampling sites. NoV was absent in all samples. The presence of genetic material from PAdV and PCV2 was detected in 30% and 45% of the 36 analyzed samples, respectively, with an average of 10(2) gc mL(-1) for PAdV and 10(4) gc mL(-1) for PCV2. HAdV was present in 100% of the samples, with an average of 10(4) gc mL(-1). However, in plaque assay, only 36% of the samples were positive. As viable particles of HAdV were found in drinking water, these results confirm that swine manure and human sewage impact surface water and groundwater, endangering water quality and indicating a potential risk to public health.


Towards the TIGER International Framework for Recommendations of Core Competencies in Health Informatics 2.0: Extending the Scope and the Roles.
This paper describes the methodology and developments towards the TIGER International Recommendation Framework of Core Competencies in Health Informatics 2.0. This Framework is meant to augment the scope from nursing towards a series of six other professional roles, i.e. direct patient care, health information management, executives, chief information officers, engineers and health IT specialists and researchers and educators. Health informatics core competency areas were compiled from various sources that had integrated the literature and were grouped into consistent clusters. The relevance of these core competency areas was rated in a survey by 718 professional experts from 51 countries. Furthermore, 22 local case studies illustrated the competencies and gave insight into examples of local educational practice. The Framework contributes to the overall discourse on how to shape health informatics education to improve quality and safety of care by enabling useful and successful health information systems.


Resistant Hypertension after Hypertensive Intracerebral Hemorrhage Is Associated with More Medical Interventions and Longer Hospital Stays without Affecting Outcome.
Hypertension (HTN) is the most common cause of spontaneous intracerebral hemorrhage (ICH). The aim of this study is to investigate the role of resistant HTN in patients with ICH. We conducted a retrospective study of all consecutive ICH admissions at our medical center from November 2013 to October 2015. The clinical features of patients with resistant HTN (requiring four or more antihypertensive agents to keep systolic blood pressure <140 mm Hg) were compared with those with responsive HTN (requiring three or fewer agents). Of the 152 patients with hypertensive ICH, 48 (31.6%) had resistant HTN. Resistant HTN was independently associated with higher body mass index and proteinuria. Compared to the responsive group, patients with resistant HTN had higher initial blood pressures and greater requirement for ventilator support, hematoma evacuation, hypertonic saline therapy, and nicardipine infusion. Resistant HTN increases length of stay (LOS) in the intensive care unit (ICU) (4.2 vs 2.1 days; p = 0.007) and in the hospital (11.5 vs 7.0 days; p = 0.003). Multivariate regression analysis showed that the rate of systolic blood pressure >140 mm Hg and duration of nicardipine infusion were independently associated with LOS in the ICU. There was no significant difference in hematoma expansion and functional outcome at hospital discharge between the two groups. Resistant HTN in patients with ICH is associated with more medical interventions and longer LOS without effecting outcome at hospital discharge.


Tiliroside, a dietary glycosidic flavonoid, inhibits TRAF-6/NF-κB/p38-mediated neuroinflammation in activated BV2 microglia.
Tiliroside is a dietary glycosidic flavonoid which has shown in vivo anti-inflammatory activity. This study is aimed at evaluating the effect of tiliroside on neuroinflammation in BV2 microglia, and to identify its molecular targets of anti-neuroinflammatory action. BV2 cells were stimulated with LPS+IFNγ in the presence or absence of tiliroside. TNFα, IL-6, nitrite and PGE2 production was determined with ELISA, Griess assay and enzyme immunoassay, respectively. iNOS, COX-2, phospho-p65, phospho-IκBα, phospho-IKKα, phospho-p38, phospho-MK2, phosopho-MKK3/6 and TRAF-6 were determined by western blot analysis. NF-κB activity was also investigated using a reporter gene assay in HEK293 cells. LPS-induced microglia ROS production was tested using the DCFDA method, while HO-1 and Nrf2 activation was determined with western blot. Tiliroside significantly suppressed TNFα, IL-6, nitrite and PGE2 production, as well as iNOS and COX-2 protein expression from LPS+IFNγ-activated BV2 microglia. Further mechanistic studies showed that tiliroside inhibited neuroinflammation by targeting important steps in the NF-κB and p38 signalling in LPS+IFNγ-activated BV2 cells. This compound also inhibited LPS-induced TRAF-6 protein expression in BV2 cells. Antioxidant activity of tiliroside in BV2 cells was demonstrated through attenuation of LPS+IFNγ-induced ROS production and activation of HO-1/Nrf2 antioxidant system. Tiliroside inhibits neuroinflammation in BV2 microglia through a mechanism involving TRAF-6-mediated activation of NF-κB and p38 MAPK signalling pathways. These activities are possibly due, in part, to the antioxidant property of this compound. Tiliroside is a potential novel natural compound for inhibiting neuroinflammation in neurodegenerative disorders.


The divergent fates of primitive hydrospheric water on Earth and Mars.
Despite active transport into Earth's mantle, water has been present on our planet's surface for most of geological time. Yet water disappeared from the Martian surface soon after its formation. Although some of the water on Mars was lost to space via photolysis following the collapse of the planet's magnetic field, the widespread serpentinization of Martian crust suggests that metamorphic hydration reactions played a critical part in the sequestration of the crust. Here we quantify the relative volumes of water that could be removed from each planet's surface via the burial and metamorphism of hydrated mafic crusts, and calculate mineral transition-induced bulk-density changes at conditions of elevated pressure and temperature for each. The metamorphic mineral assemblages in relatively FeO-rich Martian lavas can hold about 25 per cent more structurally bound water than those in metamorphosed terrestrial basalts, and can retain it at greater depths within Mars. Our calculations suggest that in excess of 9 per cent by volume of the Martian mantle may contain hydrous mineral species as a consequence of surface reactions, compared to about 4 per cent by volume of Earth's mantle. Furthermore, neither primitive nor evolved hydrated Martian crust show noticeably different bulk densities compared to their anhydrous equivalents, in contrast to hydrous mafic terrestrial crust, which transforms to denser eclogite upon dehydration. This would have allowed efficient overplating and burial of early Martian crust in a stagnant-lid tectonic regime, in which the lithosphere comprised a single tectonic plate, with only the warmer, lower crust involved in mantle convection. This provided an important sink for hydrospheric water and a mechanism for oxidizing the Martian mantle. Conversely, relatively buoyant mafic crust and hotter geothermal gradients on Earth reduced the potential for upper-mantle hydration early in its geological history, leading to water being retained close to its surface, and thus creating conditions conducive for the evolution of complex multicellular life.


Failure to cleave measles virus fusion protein in lymphoid cells.
The host-directed cleavage of measles virus fusion protein on infected lymphoid cells was studied to understand the mechanism of viral persistence in lymphoid cells in vivo. Several lymphoblastoid cell lines were infected with measles virus, and the viral glycoproteins expressed on the cell's surface were radiolabeled and analyzed for cleavage of fusion (F(0)) to F(1) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Daudi and Ramos lymphoblastoid cells were deficient in their ability to cleave measles virus fusion protein and correspondingly produced low titers of infectious measles virus, Daudi cells being more defective than Ramos cells. In contrast, other lymphoblastoid cells studied, Victor, Raji, Wi-L2, RPMI 8866, and Seraphine, cleaved the fusion polypeptide and made significantly more infectious virus. Despite their defect in cleaving F protein, Daudi cells were able to assemble and release (noninfectious) measles virus particles into the fluid phase. The deficit in Daudi cells was corrected by fusing infected Daudi cells with cleavage-competent cells such as Victor or Raji. Furthermore, the cleavage event performed by competent cells could be mimicked at the plasma membrane by treating infected Daudi cells with trypsin, implicating the role of a plasma membrane enzyme in cleaving F(0) to F(1) during measles virus infection. Hence, lymphoid cells deficient in the plasma membrane enzyme required to cleave F protein are permissive for measles virus, maintain viral gene products, produce mostly noninfectious virus, and fail to place the biologic activity F(1) protein on their surfaces.


The Keloid Disorder: Heterogeneity, Histopathology, Mechanisms and Models.
Keloids constitute an abnormal fibroproliferative wound healing response in which raised scar tissue grows excessively and invasively beyond the original wound borders. This review provides a comprehensive overview of several important themes in keloid research: namely keloid histopathology, heterogeneity, pathogenesis, and model systems. Although keloidal collagen versus nodules and α-SMA-immunoreactivity have been considered pathognomonic for keloids versus hypertrophic scars, conflicting results have been reported which will be discussed together with other histopathological keloid characteristics. Importantly, histopathological keloid abnormalities are also present in the keloid epidermis. Heterogeneity between and within keloids exists which is often not considered when interpreting results and may explain discrepancies between studies. At least two distinct keloid phenotypes exist, the superficial-spreading/flat keloids and the bulging/raised keloids. Within keloids, the periphery is often seen as the actively growing margin compared to the more quiescent center, although the opposite has also been reported. Interestingly, the normal skin directly surrounding keloids also shows partial keloid characteristics. Keloids are most likely to occur after an inciting stimulus such as (minor and disproportionate) dermal injury or an inflammatory process (environmental factors) at a keloid-prone anatomical site (topological factors) in a genetically predisposed individual (patient-related factors). The specific cellular abnormalities these various patient, topological and environmental factors generate to ultimately result in keloid scar formation are discussed. Existing keloid models can largely be divided into in vivo and in vitro systems including a number of subdivisions: human/animal, explant/culture, homotypic/heterotypic culture, direct/indirect co-culture, and 3D/monolayer culture. As skin physiology, immunology and wound healing is markedly different in animals and since keloids are exclusive to humans, there is a need for relevant human in vitro models. Of these, the direct co-culture systems that generate full thickness keloid equivalents appear the most promising and will be key to further advance keloid research on its pathogenesis and thereby ultimately advance keloid treatment. Finally, the recent change in keloid nomenclature will be discussed, which has moved away from identifying keloids solely as abnormal scars with a purely cosmetic association toward understanding keloids for the fibroproliferative disorder that they are.


Breadth and magnitude of antibody responses to multiple Plasmodium falciparum merozoite antigens are associated with protection from clinical malaria.
Individuals living in areas where malaria is endemic are repeatedly exposed to many different malaria parasite antigens. Studies on naturally acquired antibody-mediated immunity to clinical malaria have largely focused on the presence of responses to individual antigens and their associations with decreased morbidity. We hypothesized that the breadth (number of important targets to which antibodies were made) and magnitude (antibody level measured in a random serum sample) of the antibody response were important predictors of protection from clinical malaria. We analyzed naturally acquired antibodies to five leading Plasmodium falciparum merozoite-stage vaccine candidate antigens, and schizont extract, in Kenyan children monitored for uncomplicated malaria for 6 months (n = 119). Serum antibody levels to apical membrane antigen 1 (AMA1) and merozoite surface protein antigens (MSP-1 block 2, MSP-2, and MSP-3) were inversely related to the probability of developing malaria, but levels to MSP-1(19) and erythrocyte binding antigen (EBA-175) were not. The risk of malaria was also inversely associated with increasing breadth of antibody specificities, with none of the children who simultaneously had high antibody levels to five or more antigens experiencing a clinical episode (17/119; 15%; P = 0.0006). Particular combinations of antibodies (AMA1, MSP-2, and MSP-3) were more strongly predictive of protection than others. The results were validated in a larger, separate case-control study whose end point was malaria severe enough to warrant hospital admission (n = 387). These findings suggest that under natural exposure, immunity to malaria may result from high titers antibodies to multiple antigenic targets and support the idea of testing combination blood-stage vaccines optimized to induce similar antibody profiles.


Niche differentiation among annually recurrent coastal Marine Group II Euryarchaeota.
Since the discovery of archaeoplankton in 1992, the euryarchaeotal Marine Group II (MGII) remains uncultured and less understood than other planktonic archaea. We characterized the seasonal dynamics of MGII populations in the southern North Sea on a genomic and microscopic level over the course of four years. We recovered 34 metagenome-assembled genomes (MAGs) of MGIIa and MGIIb that corroborated proteorhodopsin-based photoheterotrophic lifestyles. However, MGIIa and MGIIb MAG genome sizes differed considerably (~1.9 vs. ~1.4 Mbp), as did their transporter, peptidase, flagella and sulfate assimilation gene repertoires. MGIIb populations were characteristic of winter samples, whereas MGIIa accounted for up to 23% of the community at the beginning of summer. Both clades consisted of annually recurring, sequence-discrete populations with low intra-population sequence diversity. Oligotyping of filtered cell-size fractions and microscopy consistently suggested that MGII cells were predominantly free-living. Cells were coccoid and ~0.7 µm in diameter, likely resulting in grazing avoidance. Based on multiple lines of evidence, we propose distinct niche adaptations of MGIIa and MGIIb Euryarchaeota populations that are characteristic of summer and winter conditions in the coastal North Sea.


CT-Osteoabsorptiometry (CT-OAM) - a new investigation technique in the field of mummy research.
Introduction: The scientific study of mummies provides an insight into the life of past populations. Using CT-Osteoabsorptiometry (CT-OAM), a noninvasive technique based on conventional CT-data sets, it is possible to visualize the mineral density distribution in the subchondral bone plate, representing the long-term loading conditions of the articulation surface. The objective of the current study was to investigate the applicability of CT-OAM on mummies for the load analysis of joints as a new investigation technique in the field of mummy research. Material and methods: In order to clarify if apparent malpositions of the spinal column have existed during lifetime or occurred post-mortem, we evaluated the long-term loading patterns within the thoracic and lumbar endplates of 8 mummies. Results: The implementation of CT-OAM on mummies for load analysis of joints was feasible. The mineral density distribution within the endplates was not homogenous but followed distinct distribution patterns. In all of the endplates investigated the marginal zones were higher and the central areas lower mineralized, whereby the areas of greatest density were found in the peripheral marginal zones. The vertebra columns without malposition showed within the thoracic endplates an almost even circular allocation of the density maxima, whereas within the lumbar endplates an increased localization of the density maxima dorsomedial, dorsolateral and ventral was observed. The thoracic endplates of the spines with kyphosis did not show an even circular allocation anymore but a concentration of the density maxima in the ventral area and the endplates of the spines with scoliosis exhibited a predominant localization of the density maxima on the concave side. The examined endplates showed characteristic reproducible density patterns consistent with the long-term loading conditions. Conclusions: With help of CT-OAM pathological load distributions can be visualized before macroscopical changes appear and the information obtained can be useful to solve paleopathological and paleoarchaeological questions.


Complete fusion of a transposon and herpesvirus created the Teratorn mobile element in medaka fish.
Mobile genetic elements (e.g., transposable elements and viruses) display significant diversity with various life cycles, but how novel elements emerge remains obscure. Here, we report a giant (180-kb long) transposon, Teratorn, originally identified in the genome of medaka, Oryzias latipes. Teratorn belongs to the piggyBac superfamily and retains the transposition activity. Remarkably, Teratorn is largely derived from a herpesvirus of the Alloherpesviridae family that could infect fish and amphibians. Genomic survey of Teratorn-like elements reveals that some of them exist as a fused form between piggyBac transposon and herpesvirus genome in teleosts, implying the generality of transposon-herpesvirus fusion. We propose that Teratorn was created by a unique fusion of DNA transposon and herpesvirus, leading to life cycle shift. Our study supports the idea that recombination is the key event in generation of novel mobile genetic elements. Teratorn is a large mobile genetic element originally identified in the small teleost fish medaka. Here, the authors show that Teratorn is derived from the fusion of a piggyBac superfamily DNA transposon and an alloherpesvirus and that it is widely found across teleost fish.


Herpes simplex virus glycoproteins gD and gE/gI serve essential but redundant functions during acquisition of the virion envelope in the cytoplasm.
The late stages of assembly of herpes simplex virus (HSV) and other herpesviruses are not well understood. Acquisition of the final virion envelope apparently involves interactions between viral nucleocapsids coated with tegument proteins and the cytoplasmic domains of membrane glycoproteins. This promotes budding of virus particles into cytoplasmic vesicles derived from the trans-Golgi network or endosomes. The identities of viral membrane glycoproteins and tegument proteins involved in these processes are not well known. Here, we report that HSV mutants lacking two viral glycoproteins, gD and gE, accumulated large numbers of unenveloped nucleocapsids in the cytoplasm. These aggregated capsids were immersed in an electron-dense layer that appeared to be tegument. Few or no enveloped virions were observed. More subtle defects were observed with an HSV unable to express gD and gI. A triple mutant lacking gD, gE, and gI exhibited more severe defects in envelopment. We concluded that HSV gD and the gE/gI heterodimeric complex act in a redundant fashion to anchor the virion envelope onto tegument-coated capsids. In the absence of either one of these HSV glycoproteins, envelopment proceeds; however, without both gD and gE, or gE/gI, there is profound inhibition of cytoplasmic envelopment.


SARS-CoV-2, SARS-CoV, and MERS-CoV viral load dynamics, duration of viral shedding, and infectiousness: a systematic review and meta-analysis.
Viral load kinetics and duration of viral shedding are important determinants for disease transmission. We aimed to characterise viral load dynamics, duration of viral RNA shedding, and viable virus shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in various body fluids, and to compare SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) viral dynamics. In this systematic review and meta-analysis, we searched databases, including MEDLINE, Embase, Europe PubMed Central, medRxiv, and bioRxiv, and the grey literature, for research articles published between Jan 1, 2003, and June 6, 2020. We included case series (with five or more participants), cohort studies, and randomised controlled trials that reported SARS-CoV-2, SARS-CoV, or MERS-CoV infection, and reported viral load kinetics, duration of viral shedding, or viable virus. Two authors independently extracted data from published studies, or contacted authors to request data, and assessed study quality and risk of bias using the Joanna Briggs Institute Critical Appraisal Checklist tools. We calculated the mean duration of viral shedding and 95% CIs for every study included and applied the random-effects model to estimate a pooled effect size. We used a weighted meta-regression with an unrestricted maximum likelihood model to assess the effect of potential moderators on the pooled effect size. This study is registered with PROSPERO, CRD42020181914. 79 studies (5340 individuals) on SARS-CoV-2, eight studies (1858 individuals) on SARS-CoV, and 11 studies (799 individuals) on MERS-CoV were included. Mean duration of SARS-CoV-2 RNA shedding was 17·0 days (95% CI 15·5-18·6; 43 studies, 3229 individuals) in upper respiratory tract, 14·6 days (9·3-20·0; seven studies, 260 individuals) in lower respiratory tract, 17·2 days (14·4-20·1; 13 studies, 586 individuals) in stool, and 16·6 days (3·6-29·7; two studies, 108 individuals) in serum samples. Maximum shedding duration was 83 days in the upper respiratory tract, 59 days in the lower respiratory tract, 126 days in stools, and 60 days in serum. Pooled mean SARS-CoV-2 shedding duration was positively associated with age (slope 0·304 [95% CI 0·115-0·493]; p=0·0016). No study detected live virus beyond day 9 of illness, despite persistently high viral loads, which were inferred from cycle threshold values. SARS-CoV-2 viral load in the upper respiratory tract appeared to peak in the first week of illness, whereas that of SARS-CoV peaked at days 10-14 and that of MERS-CoV peaked at days 7-10. Although SARS-CoV-2 RNA shedding in respiratory and stool samples can be prolonged, duration of viable virus is relatively short-lived. SARS-CoV-2 titres in the upper respiratory tract peak in the first week of illness. Early case finding and isolation, and public education on the spectrum of illness and period of infectiousness are key to the effective containment of SARS-CoV-2. None.


Digital PCR for determination of cytochrome P450 2D6 and sulfotransferase 1A1 gene copy number variations.
CYP2D6 and SULT1A1 occasionally show copy number variations (CNVs), with a larger number generally indicating greater enzymic activity. However, those variations are difficult to calculate using standard methods. With digital PCR, a recently introduced method for CNV analysis, DNA molecules are subjected to limited dilution and separated into nano-scale droplets prior to a PCR assay. Absolute quantitation of copy number can then be performed with high accuracy and sensitivity by determining the number of droplets showing an amplified signal for the target gene. This is the first report of analyses of CYP2D6 and SULT1A1 CNVs using a digital PCR method with blood sample from Japanese subject. Primers and probes were synthesized for the target and reference genes, and copy number calculation was performed using a QX200 Droplet Digital PCR System. Our results showed that the copy numbers in CYP2D6*5 hetero, non-CNV, and CYP2D6xN subjects were 1, 2, and 3 to 4, respectively. In addition, in non-CNV and multiplication subjects, the number of copies for SULT1A1 was 2 and 3 to 6, respectively. We found that the present digital PCR method was useful as well as accurate. In the future, a combined genotyping, allele distinction, and copy number calculation technique will be helpful for analysis of enzymic activity.


The Xenopus Irx genes are essential for neural patterning and define the border between prethalamus and thalamus through mutual antagonism with the anterior repressors Fezf and Arx.
The Iroquois (Irx) genes encode homeoproteins conserved during evolution. Vertebrate genomes contain six Irx genes organized in two clusters, IrxA (which harbors Irx1, Irx2 and Irx4) and IrxB (which harbors Irx3, Irx5 and Irx6). To determine the precise role of these genes during development and their putative redundancies, we conducted a comparative expression analysis and a comprehensive loss-of-function study of all the early expressed Irx genes (Irx1-5) using specific morpholinos in Xenopus. We found that the five Irx genes display largely overlapping expression patterns and contribute to neural patterning. All Irx genes are required for proper formation of posterior forebrain, midbrain, hindbrain and, to a lesser an extent, spinal cord. Nevertheless, Irx1 and Irx3 seem to have a predominant role during regionalization of the neural plate. In addition, we find that the common anterior limit of Irx gene expression, which will correspond to the future border between the prethalamus and thalamus, is defined by mutual repression between Fezf and Irx proteins. This mutual repression is likely direct. Finally, we show that Arx, another anteriorly expressed repressor, also contribute to delineate the anterior border of Irx expression.


Uptake of combination antiretroviral therapy and HIV disease progression according to geographical origin in seroconverters in Europe, Canada, and Australia.
We examined differences by geographical origin (GO) in time from HIV seroconversion (SC) to AIDS, death, and initiation of antiretroviral therapy (cART). Data from HIV seroconverter cohorts in Europe, Australia and Canada (CASCADE) was used; GO was classified as: western countries (WE), North Africa and Middle East (NAME), sub-Saharan Africa (SSA), Latin America (LA), and Asia (ASIA). Differences by GO were assessed using Cox models. Administrative censoring date was 30 June 2008. Of 16 941 seroconverters, 15 548 were from WE, 158 NAME, 762 SSA, 349 LA, and 124 ASIA. We found no differences by GO in risks of AIDS (P = .99) and death (P = .12), although seroconverters from NAME (adjusted hazard ratio [aHR]: 0.57; 95% CI: 0.33-.94) and SSA (aHR: 0.74; 95% CI: 0.50-1.10) appeared to have lower mortality than WE. Chances of initiating cART differed by GO (P < .001): seroconverters from SSA were more likely to initiate cART than WE (aHR: 1.48; 95% CI: 1.26-1.74), but not after adjustment for CD4 at SC (aHR: 1.11; 95% CI: 0.88-1.40). In settings with universal access to healthcare, GO does not play a major role in HIV disease progression.


Evaluating current policy for detecting mosaicism in amniotic fluid cultures: implications for current cell counting practices.
Chromosomal mosaicism is one of the most vexing problems for clinical cytogenetic laboratories and personnel time used for analysis at the microscope is one of the principle costs in cytogenetic laboratories. We use data collected from 26 cytogenetic laboratories to evaluate whether the American College of Medical Genetics guidelines for minimum number of cells to count to exclude mosaicism in amniotic fluid specimens is appropriate. An accurate estimate of the number of mosaics that are missed by current cell counting practices is an important step in this process. Thus, we present a new method for estimating the number of mosaics that are missed and we use computer simulation to evaluate this new method. Our results indicate that if the clinical significance of mosaicism is suspected to be minimal for certain cytogenetic anomalies when the percentage of abnormal cells is 15 per cent or less, then it may be sufficient to use a 15-cell counting-rule-for-detection along with a minimum total cell count of 30 regardless of whether abnormal cells or normal cells are in the minority.


Virological response to highly active antiretroviral therapy in patients infected with human immunodeficiency virus type 2 (HIV-2) and in patients dually infected with HIV-1 and HIV-2 in the Gambia and emergence of drug-resistant variants.
Drug design, antiretroviral therapy (ART), and drug resistance studies have focused almost exclusively on human immunodeficiency virus type 1 (HIV-1), resulting in limited information for patients infected with HIV-2 and for those dually infected with HIV-1 and HIV-2. In this study, 20 patients, 12 infected with HIV-2 and 8 dually infected with HIV-1 and HIV-2, all treated with zidovudine (ZDV), lamivudine (3TC), and lopinavir-ritonavir (LPV/r), were followed up longitudinally for about 3 years. For 19/20 patients, viral loads were reduced to undetectable levels; the patient whose viral load remained detectable reported adverse effects associated with LPV/r that had caused him to stop taking all the drugs. HIV-2 strains containing mutations in both the protease and the reverse transcriptase gene that may confer drug resistance were observed in two patients with viral rebound, as early as 130 days (4.3 months) after the initiation of therapy. We conclude that the combination of ZDV, 3TC, and LPV/r is able to provide efficient and durable suppression of HIV-1 and HIV-2 for as long as 3 years in HIV-2-infected and dually infected patients. However, the emergence of HIV-1 and HIV-2 strains containing drug-resistant mutations can compromise the efficacy of this highly active ART.


Stroke in the very elderly: characteristics and outcome in patients aged ≥85 years with a first-ever ischemic stroke.
Epidemiological and clinical features of very elderly patients with stroke are still uncertain. Our aim was to study the patient characteristics and outcomes in the very elderly (aged ≥85 years) with a first-ever ischemic stroke in the National Acute Stroke Israeli Survey (NASIS) registry. The NASIS registry is a nationwide prospective hospital-based study performed triennially (2004, 2007, 2010). Patients with ischemic stroke aged ≥85 years were compared with those 65-84 years old regarding their baseline characteristics, stroke severity, etiology of stroke and stroke outcomes. Logistic regression analyses were used to adjust for potential confounders. Stroke severity was determined according to the National Institute of Health Stroke Scale (NIHSS) score. The proportion of very elderly (≥85 years) patients among the NASIS population increased from 18.3% in 2004 to 19.9% in 2007 and 24.5% in 2010 (p for trend = 0.005). The percentage of women was higher in patients aged ≥85 years (p < 0.0001). Atrial fibrillation, congestive heart disease and prior disability were significantly more common, while diabetes, current smoking and dyslipidemia were less frequent in the very elderly. The very elderly presented with more severe strokes: 36.3% of the ≥85-year-old patients had an NIHSS score ≥11 compared with 22.0% in the younger age group (p < 0.05). There is an increasing proportion of very elderly subjects, mostly women, among first-ever ischemic stroke patients. Current information on age-specific aspects of stroke in the very elderly is crucial to set up successful prevention pathways and implementing well-organized stroke care for this population.


Effect of strength training on enzyme activities and fibre characteristics in human skeletal muscle.
Progressive strength training was performed 3 times a week for 8 weeks by 14 male students (19-31 yrs.). The training program consisted mainly of dynamic exercises for the leg extensors with maximal or close to maximal loads. The training caused significant improvements in dynamic and isometric strength. One repetition maximum in squats increased with 67%, Sargent jump with 22%, and maximal voluntary isometric contraction (MVC) with 13%, respectively. Body weight and leg muscle circumferences remained unchanged after training, whereas total body potassium, lean body mass and calculated total muscle mass increased, suggesting a change in body composition with training. Muscle biopsies were obtained from vastus lateralis for fibre analyses and determination of enzyme activities. There were no changes in muscle fibre composition or fibre area with training. The activities of Mg2+ stimulated ATPase, creatine phosphokinase and phosphofructokinase remained unchanged, whereas myokinase activity was increased after training from (1.41 to 1.52 moles x 10(-4) x g-1 x min-1, p less than 0.05). After training significant correlations (p less than 0.01) were demonstrated between Mg2+ stimulated ATPase activity and % fast twitch fibres (% FT) (r = 0.67), as well as between myokinase activity and % FT (r = 0.86).


Importance of the donor:fullerene intermolecular arrangement for high-efficiency organic photovoltaics.
The performance of organic photovoltaic (OPV) material systems are hypothesized to depend strongly on the intermolecular arrangements at the donor:fullerene interfaces. A review of some of the most efficient polymers utilized in polymer:fullerene PV devices, combined with an analysis of reported polymer donor materials wherein the same conjugated backbone was used with varying alkyl substituents, supports this hypothesis. Specifically, the literature shows that higher-performing donor-acceptor type polymers generally have acceptor moieties that are sterically accessible for interactions with the fullerene derivative, whereas the corresponding donor moieties tend to have branched alkyl substituents that sterically hinder interactions with the fullerene. To further explore the idea that the most beneficial polymer:fullerene arrangement involves the fullerene docking with the acceptor moiety, a family of benzo[1,2-b:4,5-b']dithiophene-thieno[3,4-c]pyrrole-4,6-dione polymers (PBDTTPD derivatives) was synthesized and tested in a variety of PV device types with vastly different aggregation states of the polymer. In agreement with our hypothesis, the PBDTTPD derivative with a more sterically accessible acceptor moiety and a more sterically hindered donor moiety shows the highest performance in bulk-heterojunction, bilayer, and low-polymer concentration PV devices where fullerene derivatives serve as the electron-accepting materials. Furthermore, external quantum efficiency measurements of the charge-transfer state and solid-state two-dimensional (2D) (13)C{(1)H} heteronuclear correlation (HETCOR) NMR analyses support that a specific polymer:fullerene arrangement is present for the highest performing PBDTTPD derivative, in which the fullerene is in closer proximity to the acceptor moiety of the polymer. This work demonstrates that the polymer:fullerene arrangement and resulting intermolecular interactions may be key factors in determining the performance of OPV material systems.


A first principle comparative study of the ionic diffusivity in LiAlO2 and NaAlO2 polymorphs for solid-state battery applications.
Lithium aluminates are attracting increasing attention as battery materials. They are typically used for the coating of electrodes. The diffusive properties of the equilibrium tetragonal phase (γ) are well understood from both an experimental and a theoretical perspective, and the major diffusive mechanism is recognised to be vacancy hopping between neighbouring sites. Investigations of this type are however not reported for other, high-pressure LiAlO2 phases. Moreover, the ionic diffusivity of the Na-based aluminates, manifesting a similar polymorphism to LiAlO2, has never been studied using atomistic techniques. In this work, we address these points, by presenting a comparative density functional theory-based study of these materials, describing the structural properties of the various phases, and evaluating the activation energies for single vacancy hops. While LiAlO2 exhibits a poor ionic conductivity due to a significant degree of covalency of the Al-O bonding, orthorhombic β-NaAlO2 exhibits a significantly lower diffusion barrier. This feature cannot be explained only in terms of the larger equilibrium volume, as the same trend is not observed for the high-pressure trigonal α-LiAlO2 and α-NaAlO2. We utilise here various electronic-structure tools to verify the lower degree of covalency of the Na-O bonds. The electron localisation function, in particular, is shown to be intrinsically correlated to the diffusion pathways of Li and Na ions, and its variation along the path is a qualitative measure of ionic conductivity.


The bisphosphonate ibandronate stimulates reverse cholesterol transport out of monocytoid cells by enhanced ABCA1 transcription.
Nitrogen-containing bisphosphonates used in osteoporosis act by interference with pyrophosphorylated intermediates of the sterol pathway and are internalized by monocytes/macrophages, key players in atherogenesis. We therefore studied the effects of ibandronate on monocytic cholesterol homeostasis. In differentiated human MM6 cells and freshly prepared human PBMCs lipoprotein receptor transcription was quantified by real-time RT-PCR and receptor-mediated cellular cholesterol handling by lipoprotein-driven uptake and efflux assays. Low nanomolar concentrations of ibandronate reduced cellular cholesterol content despite reactive up-regulation of the LDL receptor. Simultaneously, the transcription of the cellular cholesterol exporter ABCA1 was severalfold stimulated, whereas the scavenger receptor CD36 was down-regulated. Thereby, ibandronate decreased the cellular uptake of modified LDL and enhanced the efflux of cholesterol to delipidated HDL. Geranylgeraniol antagonized the stimulation of ABCA1 expression by ibandronate. Ibandronate in low pharmacologic concentrations redirects monocytic cholesterol handling from favouring foam cell formation towards enhanced reverse cholesterol transport.


Uptake of veterinary medicines from soils into plants.
Medicines play an important role in the treatment and prevention of disease. Whereas the side effects on human and animal health resulting directly from treatment have been widely documented, only recently have the occurrence and fate of medicines in the environment and the potential consequences for human health been recognized as an issue warranting consideration. Medicines have been shown to be released to soils and to persist in the environment. This study was performed to investigate the potential for a range of veterinary medicines to be taken up from soil by plants used for human consumption and to assess the potential significance of this exposure route in terms of human health. Soil analyses indicated that, for selected substances, measurable residues of these are likely to occur in soils for at least 5 months following application of manure containing these compounds. Experimental studies on the uptake of veterinary medicines into carrot roots (tubers) and lettuce leaves showed that only florfenicol, levamisole, and trimethoprim were taken up by lettuces, whereas diazinon, enrofloxacin, florfenicol, and trimethoprim were detected in carrot roots. Measured concentrations in plant material were used to model potential adult human exposure to these compounds. Although exposure concentrations were appreciable in a few instances, accounting for approximately 10% of the acceptable daily intake values (ADI), all were lower than the ADI values, indicating that, at least for compounds with properties similar to those considered here, there is little evidence of an appreciable risk. This exposure route may, however, be important when veterinary medicines have a very low ADI, at which they elicit subtle effects over prolonged periods, or when exposure is occurring via a number of routes at once. Although degradation products (produced in the soil or the plant) were not measured, it is possible for some substances that these could increase the risks to consumers.


Characterizing low affinity epibatidine binding to α4β2 nicotinic acetylcholine receptors with ligand depletion and nonspecific binding.
Along with high affinity binding of epibatidine (Kd1≈10 pM) to α4β2 nicotinic acetylcholine receptor (nAChR), low affinity binding of epibatidine (Kd2≈1-10 nM) to an independent binding site has been reported. Studying this low affinity binding is important because it might contribute understanding about the structure and synthesis of α4β2 nAChR. The binding behavior of epibatidine and α4β2 AChR raises a question about interpreting binding data from two independent sites with ligand depletion and nonspecific binding, both of which can affect equilibrium binding of [3H]epibatidine and α4β2 nAChR. If modeled incorrectly, ligand depletion and nonspecific binding lead to inaccurate estimates of binding constants. Fitting total equilibrium binding as a function of total ligand accurately characterizes a single site with ligand depletion and nonspecific binding. The goal of this study was to determine whether this approach is sufficient with two independent high and low affinity sites. Computer simulations of binding revealed complexities beyond fitting total binding for characterizing the second, low affinity site of α4β2 nAChR. First, distinguishing low-affinity specific binding from nonspecific binding was a potential problem with saturation data. Varying the maximum concentration of [3H]epibatidine, simultaneously fitting independently measured nonspecific binding, and varying α4β2 nAChR concentration were effective remedies. Second, ligand depletion helped identify the low affinity site when nonspecific binding was significant in saturation or competition data, contrary to a common belief that ligand depletion always is detrimental. Third, measuring nonspecific binding without α4β2 nAChR distinguished better between nonspecific binding and low-affinity specific binding under some circumstances of competitive binding than did presuming nonspecific binding to be residual [3H]epibatidine binding after adding a large concentration of cold competitor. Fourth, nonspecific binding of a heterologous competitor changed estimates of high and low inhibition constants but did not change the ratio of those estimates. Investigating the low affinity site of α4β2 nAChR with equilibrium binding when ligand depletion and nonspecific binding are present likely needs special attention to experimental design and data interpretation beyond fitting total binding data. Manipulation of maximum ligand and receptor concentrations and intentionally increasing ligand depletion are potentially helpful approaches.


Mortality in patients with multiple sclerosis.
Mortality in patients with multiple sclerosis (MS) is significantly increased compared with the general population. Many questions concerning survival in MS are still unanswered due to the difficulty of comparing information collected at different times and in different geographic areas. The increasing incidence of MS, the improvement in care of the chronically disabled, and different methodologies may explain the lack of coherence among studies' results. Reported times to death from birth and from disease onset/diagnosis are highly variable. Patients older at onset or with primary progressive course have shorter survival; however, data on sex and mortality are contradictory. Changes in sex ratio in MS over time represent one possible explanation. MS is the main cause of death in ≥50% of patients and the incidence of deaths not due to MS varies among countries. Particularly, suicide is substantially increased in patients with MS, and, despite its varying incidence, mainly due to "cultural bias," it should be considered an MS-related cause of death. Recent results of the long-term follow-up study of interferon-β-1b demonstrated a significant reduction of mortality among treated patients. Notwithstanding its long latency, mortality is therefore an unambiguously valid long-term outcome in randomized controlled trials. It usefully combines the net impact of treatment efficacy on longevity and adverse events, which may reduce it.


A G-protein-coupled estrogen receptor is involved in hypothalamic control of energy homeostasis.
Estrogens are involved in the hypothalamic control of multiple homeostatic functions including reproduction, stress responses, energy metabolism, sleep cycles, temperature regulation, and motivated behaviors. The critical role of 17beta-estradiol (E2) is evident in hypoestrogenic states (e.g., postmenopause) in which many of these functions go awry. The actions of E2 in the brain have been attributed to the activation of estrogen receptors alpha and beta through nuclear, cytoplasmic, or membrane actions. However, we have identified a putative membrane-associated estrogen receptor that is coupled to desensitization of GABAB and mu-opioid receptors in guinea pig and mouse hypothalamic proopiomelanocortin neurons. We have synthesized a new nonsteroidal compound, STX, which selectively targets the Galphaq-coupled phospholipase C-protein kinase C-protein kinase A pathway, and have established that STX is more potent than E2 in mediating this desensitization in an ICI 182, 780-sensitive manner in both guinea pig and mouse neurons. Both E2 and STX were fully efficacious in estrogen receptor alpha,beta knock-out mice. Moreover, in vivo treatment with STX, similar to E2, attenuated the weight gain in hypoestrogenic female guinea pigs. Therefore, this membrane-delimited signaling pathway plays a critical role in the control of energy homeostasis and may provide a novel therapeutic target for treatment of postmenopausal symptoms and eating disorders in females.


Reliability of Handheld Optical Coherence Tomography in Children Younger Than Three Years of Age Undergoing Vigabatrin Treatment for Childhood Epilepsy.
Vigabatrin-associated retinal toxicity manifests as reduction in the clinical electroretinogram and retinal nerve fiber layer (RNFL) thinning. This observational investigation of RNFL thickness in young vigabatrin-treated children was to identify intravisit and intervisit reliabilities of peripapillary RNFL thickness measurements performed with Envisu (optical coherence tomography) OCT. Secondarily, a longitudinal assessment investigated the presence and extent of RNFL thinning. We measured the handheld OCT in sedated children to evaluate the RNFL thickness using segmentation software. Intraclass correlation coefficient (ICC) statistics identified intravisit and intervisit reliabilities for RNFL thickness. Twenty-nine children (10.1 ± 6.0 months old) underwent handheld optical coherence tomography (OCT). Fourteen of these completed follow-up assessments. Intravisit reliability was good for the right eye (ICCs = 0.82-0.98) and the left eye (ICCs = 0.75-0.89) for each of the 4 retinal quadrants. Inter-visit ICCs for each of the 4 retinal quadrants were good (ICC = 0.82-0.98). There was no consistent change in RNFL thickness longitudinally. In this pediatric cohort, RNFL thickness measures using handheld OCT provided good reliability within a single visit and between consecutive visits supporting its use as an adjunctive tool in the clinical setting. Further long-term follow-up is required to understand RNFL thickness changes in this specific population and its association with vigabatrin toxicity. The findings of good reliability and clinical feasibility would provide an opportunity for the handheld OCT to monitor reliably for vigabatrin-associated retinal toxicity in children who often show noncompliance to traditional testing approaches.


Fringe positions in double-exposure speckle photography.
Double-exposure records in speckle photography or particle image velocimetry are often evaluated by analysis of the system of Young's diffraction fringes. Fringe spacing, necessary to calculate the displacement, is determined from the positions of fringe maxima or minima. These, however, are influenced by the diffraction halo function and by fringe visibility. A generalized theory of the effects is presented, including position dependent visibility and fringe phase. Evaluations are given for disk-shaped particle images in particle image velocimetry, and for coherent and incoherent speckle photography. Fringe shifts are determined numerically for commonly encountered values of fringe density and visibility thus presenting a basis for rapid assessment of accuracy in metrological experiments.


Cascading effects of mammalian herbivores on ground-dwelling arthropods: Variable responses across arthropod groups, habitats and years.
Large mammalian herbivores are well known to shape the structure and function of ecosystems world-wide, and these effects can in turn cascade through systems to indirectly influence other animal species. A wealth of studies has explored the effects of large mammals on arthropods, but to date they have reported such widely varying results that generalizations have been elusive. Three factors are likely drivers of this variability: the widely varying life-history characteristics of different arthropod groups, the highly variable landscapes that mammalian herbivores commonly inhabit and temporal variation in environmental conditions. Here, we use an 18-year-old exclosure experiment stratified across three distinct coastal prairie habitats in northern California to address the effects of a reintroduced mammalian herbivore, tule elk (Cervus canadensis nannodes) on the composition, richness and abundance of ground-dwelling arthropods over two years with very different precipitation regimes. We found that elk shifted the composition of arthropod communities, increasing the abundance of ants, beetles, spiders and mites, decreasing the abundance of woodlice and bristletails in some but not all habitats types, and having no effect on the abundance of bugs, crickets and springtails. Elk also increased richness and changed the composition of ant genera and beetle morpho-species. Interestingly, the effects of elk on arthropod composition, richness and abundance varied little between years, despite very different precipitation levels, biomass accumulation and thatch height. Elk reduced shrub cover, above-ground herbaceous biomass and thatch height and increased soil compaction, and these changes predicted the abundance and richness of arthropods, although taxonomic groups varied in their responses, presumably due to differences in environmental requirements. Synthesis. Our research highlights the importance of using long-term experiments to assess the cascading effects of large herbivores on the composition of grounddwelling arthropod communities and to identify the mechanisms that indirectly shape arthropod responses to herbivores among variable habitats and years in order to develop a greater understanding of the variable responses of arthropods to large mammalian herbivores.


Mammographic density is related to stroma and stromal proteoglycan expression.
Mammographic density and certain histological changes in breast tissues are both risk factors for breast cancer. However, the relationship between these factors remains uncertain. Previous studies have focused on the histology of the epithelial changes, even though breast stroma is the major tissue compartment by volume. We have previously identified lumican and decorin as abundant small leucine-rich proteoglycans in breast stroma that show altered expression after breast tumorigenesis. In this study we have examined breast biopsies for a relationship between mammographic density and stromal alterations. We reviewed mammograms from women aged 50-69 years who had enrolled in a provincial mammography screening program and had undergone an excision biopsy for an abnormality that was subsequently diagnosed as benign or pre-invasive breast disease. The overall mammographic density was classified into density categories. All biopsy tissue sections were reviewed and tissue blocks from excision margins distant from the diagnostic lesion were selected. Histological composition was assessed in sections stained with haematoxylin and eosin, and the expression of lumican and decorin was assessed by immunohistochemistry; both were quantified by semi-quantitative scoring. Tissue sections corresponding to regions of high in comparison with low mammographic density showed no significant difference in the density of ductal and lobular units but showed significantly higher collagen density and extent of fibrosis. Similarly, the expression of lumican and decorin was significantly increased. Alteration in stromal composition is correlated with increased mammographic density. Although epithelial changes define the eventual pathway for breast cancer development, mammographic density might correspond more directly to alterations in stromal composition.


Renal β-intercalated cells maintain body fluid and electrolyte balance.
Inactivation of the B1 proton pump subunit (ATP6V1B1) in intercalated cells (ICs) leads to type I distal renal tubular acidosis (dRTA), a disease associated with salt- and potassium-losing nephropathy. Here we show that mice deficient in ATP6V1B1 (Atp6v1b1-/- mice) displayed renal loss of NaCl, K+, and water, causing hypovolemia, hypokalemia, and polyuria. We demonstrated that NaCl loss originated from the cortical collecting duct, where activity of both the epithelial sodium channel (ENaC) and the pendrin/Na(+)-driven chloride/bicarbonate exchanger (pendrin/NDCBE) transport system was impaired. ENaC was appropriately increased in the medullary collecting duct, suggesting a localized inhibition in the cortex. We detected high urinary prostaglandin E2 (PGE2) and ATP levels in Atp6v1b1-/- mice. Inhibition of PGE2 synthesis in vivo restored ENaC protein levels specifically in the cortex. It also normalized protein levels of the large conductance calcium-activated potassium channel and the water channel aquaporin 2, and improved polyuria and hypokalemia in mutant mice. Furthermore, pharmacological inactivation of the proton pump in β-ICs induced release of PGE2 through activation of calcium-coupled purinergic receptors. In the present study, we identified ATP-triggered PGE2 paracrine signaling originating from β-ICs as a mechanism in the development of the hydroelectrolytic imbalance associated with dRTA. Our data indicate that in addition to principal cells, ICs are also critical in maintaining sodium balance and, hence, normal vascular volume and blood pressure.


Emerging roles of ATRX in cancer.
ATRX was identified over 20 years ago as the gene responsible for a rare developmental disorder characterized by α-thalassemia and intellectual disability. Similarities to the sucrose nonfermentable SNF2 type chromatin remodelers initially suggested a role in transcriptional regulation. However, over the last years, our knowledge of the epigenetic activities of ATRX has expanded steadily. Recent exciting discoveries have propelled ATRX into the limelight of chromatin and telomere biology, development and cancer research. This review summarizes recent breakthroughs in understanding ATRX function in heterochromatin structure, genome stability and its frequent dysregulation in a variety of cancers.


Three-dimensional dielectric phoxonic crystals with network topology.
We theoretically demonstrate the existence of simultaneous large complete photonic and phononic bandgaps in three-dimensional dielectric phoxonic crystals with a simple cubic lattice. These phoxonic crystals consist of dielectric spheres on the cubic lattice sites connected by thin dielectric cylinders. The simultaneous photonic and phononic bandgaps can exist over a wide range of geometry parameters. The vibration modes corresponding to the phononic bandgap edges are the local torsional resonances of the dielectric spheres and rods. Detailed discussion is presented on the variation of the photonic and phononic bandgaps with the geometry of the structure. Optimal geometry which generates large phoxonic bandgaps is suggested.


Mindfulness-based cognitive therapy for the treatment of current depressive symptoms: a meta-analysis.
Mindfulness-based cognitive therapy (MBCT) appears to be a promising intervention for the prevention of relapse in major depressive disorder, but its efficacy in patients with current depressive symptoms is less clear. Randomized clinical trials of MBCT for adult patients with current depressive symptoms were included (k = 13, N = 1046). Comparison conditions were coded based on whether they were intended to be therapeutic (specific active controls) or not (non-specific controls). MBCT was superior to non-specific controls at post-treatment (k = 10, d = 0.71, 95% confidence interval [CI] [0.47, 0.96]), although not at longest follow-up (k = 2, d = 1.47, [-0.71, 3.65], mean follow-up = 5.70 months across all studies with follow-up). MBCT did not differ from other active therapies at post-treatment (k = 6, d = 0.002, [-0.43, 0.44]) and longest follow-up (k = 4, d = 0.26, [-0.24, 0.75]). There was some evidence that studies with higher methodological quality showed smaller effects at post-treatment, but no evidence that effects varied by inclusion criterion. The impact of publication bias appeared minimal. MBCT seems to be efficacious for samples with current depressive symptoms at post-treatment, although a limited number of studies tested the long-term effects of this therapy.


Vaping in the Workplace: Implications for Employer-Sponsored Tobacco Cessation Programs.
Assess workplace vaping as a trigger for tobacco use; examine interest in and prevalence of vaping cessation programs; determine needs of parents whose children vape. Employees of companies with more than 150 employees, drawn from an opt-in national online panel (N = 1607), ages 18 to 65, completed an online survey in November 2019. Among tobacco users, 46% to 48% reported workplace vaping was a trigger for smoking and vaping, respectively; 7% of former users reported it as a trigger. Quit vaping support is important to 85% of employees; 1/3 of workplaces have such programs, with industry variation. Child vaping results in presenteeism and absenteeism among roughly 1/3 of parents. Workplace vaping is a trigger for smoking and vaping among current and former tobacco users. A gap exists between desired support for vaping cessation and current employer-sponsored cessation programs.


Early and late post-operative arrhythmias after surgical myectomy: 45 years of follow-up.
The aims of this study are to investigate the incidence and determinants of post-operative atrial arrhythmias, conduction disorders and mortality in hypertrophic obstructive cardiomyopathy (HOCM) patients undergoing transaortic myectomy. This retrospective single-center study was conducted in 249 patients (median age 54 years [40-64], 42% female) undergoing transaortic myectomy. Post-operative atrial fibrillation (AF) was reported in 84 patients (33.7%), including 56 patients (22.5%) with de novo AF. Older age (HR = 1.027 (1.003-1.052), p = 0.029) and hypercholesterolemia (HR = 2.296 (1.091-4.832) p = 0.029) were independent predictors for de novo post-operative AF. Late post-operative AF and atrial flutter (AFL) occurred in 18.9% and 6.8% of the patients, respectively. De novo early post-operative AF increased the risk of late post-operative AF (HR = 3.138 (1.450-6.789), p = 0.004). Patients with a right bundle branch block had a higher risk of early-postoperative pacemaker implantation (p = 0.003, HR = 9.771 (2.195-43.505)). Higher age at time of surgery (HR = 1.053 (1.026-1.081), p < 0.001) was a predictor for late mortality (n = 47, 18.9%). Early and late post-operative AF, AFL and other SVTs are common sequelae after myectomy and are associated with older age at surgery, history of AF and early post-operative AF. Early post-operative arrhythmias are not transient and periodic rhythm monitoring is therefore essential to initiate therapy as soon as possible.


Summary of the panel session at the 38th Annual Surgical Symposium of the Association of VA Surgeons: what is the big deal about frailty?
Owing to the phenomenon known as "global graying," elderly-specific conditions, including frailty, will become more prominent among patients undergoing surgery. The concept of frailty, its effect on surgical outcomes, and its assessment and management were discussed during the 38th Annual Surgical Symposium of the Association of VA Surgeons panel session entitled "What's the Big Deal about Frailty?" and held in New Haven, Connecticut, on April 7, 2014. The expert panel discussed the following questions and topics: (1) Why is frailty so important? (2) How do we identify the frail patient prior to the operating room? (3) The current state of the art: preoperative frail evaluation. (4) Preoperative interventions for frailty prior to operation: do they work? (5) Intraoperative management of the frail patient: does anesthesia play a role? (6) Postoperative care of the frail patient: is rescue the issue? This special communication summarizes the panel session topics and provides highlights of the expert panel's discussions and relevant key points regarding care for the geriatric frail surgical patient.


Transient cholinergic enhancement does not significantly affect either the magnitude or selectivity of perceptual learning of visual texture discrimination.
Perceptual learning (PL), often characterized by improvements in perceptual performance with training that are specific to the stimulus conditions used during training, exemplifies experience-dependent cortical plasticity. An improved understanding of how neuromodulatory systems shape PL promises to provide new insights into the mechanisms of plasticity, and by extension how PL can be generated and applied most efficiently. Previous studies have reported enhanced PL in human subjects following administration of drugs that increase signaling through acetylcholine (ACh) receptors, and physiological evidence indicates that ACh sharpens neuronal selectivity, suggesting that this neuromodulator supports PL and its stimulus specificity. Here we explored the effects of enhancing endogenous cholinergic signaling during PL of a visual texture discrimination task. We found that training on this task in the lower visual field yielded significant behavioral improvement at the trained location. However, a single dose of the cholinesterase inhibitor donepezil, administered before training, did not significantly impact either the magnitude or the location specificity of texture discrimination learning compared with placebo. We discuss potential explanations for discrepant findings in the literature regarding the role of ACh in visual PL, including possible differences in plasticity mechanisms in the dorsal and ventral cortical processing streams.


Reliability and Validity of the Checklist for Function-Focused Care in Service Plans.
The purpose of this study was to test the reliability and validity of the Checklist for Function-Focused Care in Service Plans. Function-focused care is a care approach that optimizes function and physical activity during all care interactions. This study used baseline data from the first cohort of the study titled Dissemination and Implementation of Function-Focused Care for Assisted Living Using the Evidence Integration Triangle (FFC-AL-EIT). A total of 242 participants were recruited from 26 assisted living facilities. The majority of participants were White, female, and unmarried. There was support for internal consistency with an alpha coefficient of .96, interrater reliability with a correlation of .80, construct validity based on Rasch analysis and INFIT statistics ranging from 0.69 to 1.29, and a significant association with function-focused care activities. Although there is some support for reliability and validity of the measure, modifications are recommended to add more challenging items.