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AIM: To provide a detailled analysis of the microvascular burden in patients with diabetes hopitalized for COVD-19. MATERIALS AND METHODS: We analysed data from the French CORONADO initiative and the UK Association of British Clinical Diabetologists (ABCD) COVID-19 audit, two nationwide multicentre studies, and the AMERICADO, a multicentre study conducted in New York area. We assessed the association between risk of all-cause death during hospital stay and the following microvascular complications in patients with diabetes hospitalized for COVID-19: diabetic retinopathy and/or diabetic kidney disease and/or history of diabetic foot ulcer. RESULTS: Among 2951 CORONADO, 3387 ABCD COVID-19 audit and 9327 AMERICADO participants, microvascular diabetic complications status was ascertained for 1314 (44.5%), 1809 (53.4%) and 7367 (79.0%) patients, respectively: 1010, 1059 and 1800, respectively, had ≥1 severe microvascular complication(s) and 304, 750 and 5567, respectively, were free of any complications. The patients with isolated diabetic kidney disease had an increased risk of all-cause death during hospital stay: odds ratio [OR] 2.53 (95% confidence interval [CI] 1.66-3.83), OR 1.24 (95% CI 1.00-1.56) and OR 1.66 (95% CI 1.40-1.95) in the CORONADO, the ABCD COVID-19 national audit and the AMERICADO studies, respectively. After adjustment for age, sex, hypertension and cardiovascular disease (CVD), compared to those without microvascular complications, patients with microvascular complications had an increased risk of all-cause death during hospital stay in the CORONADO, the ABCD COVID-19 diabetes national audit and the AMERICADO studies: adjusted OR (adj OR) 2.57 (95% CI 1.69-3.92), adj OR 1.22 (95% CI 1.00-1.52) and adj OR 1.33 (95% CI 1.15-1.53), respectively. In meta-analysis of the three studies, compared to patients free of complications, those with microvascular complications had an unadjusted OR for all-cause death during hospital stay of 2.05 (95% CI 1.42-2.97

BACKGROUND: It is not clear whether pre-existing macrovascular complications (ischemic heart disease, stroke or peripheral artery disease) are associated with health outcomes in people with diabetes mellitus hospitalized for COVID-19. METHODS: We conducted cohort studies of adults with pre-existing diabetes hospitalized for COVID-19 infection in the UK, France, and Spain during the early phase of the pandemic (between March 2020-October 2020). Logistic regression models adjusted for demographic factors and other comorbidities were used to determine associations between previous macrovascular disease and relevant clinical outcomes: mortality, intensive care unit (ICU) admission and use of invasive mechanical ventilation (IMV) during the hospitalization. Output from individual logistic regression models for each cohort was combined in a meta-analysis. RESULTS: Complete data were available for 4,106 (60.4%) individuals. Of these, 1,652 (40.2%) had any prior macrovascular disease of whom 28.5% of patients died. Mortality was higher for people with compared to those without previous macrovascular disease (37.7% vs 22.4%). The combined crude odds ratio (OR) for previous macrovascular disease and mortality for all four cohorts was 2.12 (95% CI 1.83-2.45 with an I2 of 60%, reduced after adjustments for age, sex, type of diabetes, hypertension, microvascular disease, ethnicity, and BMI to adjusted OR 1.53 [95% CI 1.29-1.81]) for the three cohorts. Further analysis revealed that ischemic heart disease and cerebrovascular disease were the main contributors of adverse outcomes. However, proportions of people admitted to ICU (adjOR 0.48 [95% CI 0.31-0.75], I2 60%) and the use of IMV during hospitalization (adjOR 0.52 [95% CI 0.40-0.68], I2 37%) were significantly lower for people with previous macrovascular disease. CONCLUSIONS: This large multinational study of people with diabetes mellitus hospitalized for COVID-19 demonstrates that previous macrovascular disease is associated

Background: The measurement of anatomical structures is critical in plastic and reconstructive surgery. However, few detailed and standardized measurements have been widely used in the periorbital region. This study aimed to evaluate the feasibility of a novel detailed and standardized protocol with 2D and 3D technologies, and explore the relationship between them and direct measurements. Methods: Fifty healthy Caucasians (100 eyes) between 20 and 68 years old were recruited and captured for 3D photographs by VECTRA M3 3D Imaging System. Subsequently, 24 landmarks were located on each 3D photographs following a standardized protocol, and then 19 linear and 3 angular periorbital variables were measured. Furthermore, two-dimensional (2D) and direct measurements were conducted on each subject and compared with 3D measurements and one another. Results: The grand r means across all measurements were 0.77, 0.78, and 0.88 for direct vs. 2D values, direct vs. 3D values, and 3D vs. 2D values, respectively. The mean absolute differences were 1 mm (ranging from 0.2 mm to 3.7 mm) between direct and 3D measurements, 1 mm (ranging from 0.04 mm to 2.4 mm) between direct and 2D measurements, and 1 mm and 6.6 degrees (ranging from 0.04 mm or 0.5 degrees to 3 mm or 12.8 degrees) between 2D and 3D measurements. Conclusions: This study verified the feasibility of this detailed and standardized landmark localization protocol for assessing the periorbital morphology with 2D and 3D technologies. This protocol may work as a bridge communicating with all studies involving any of the three technologies in the future. (C) 2020 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Background: People with diabetes and coronavirus disease 2019 (COVID-19) have a significantly greater risk of death and/or intensive care unit (ICU) admission. The Association of British Clinical Diabetologists (ABCD) recently audited outcomes for people hospitalised in the UK with diabetes and COVID-19. Methods: The ABCD COVID-19 and diabetes audit was a retrospective audit of patients admitted to UK hospitals with diabetes and COVID-19 between March and December 2020. Data related to patients admitted in Wales were compared with patients admitted in England and Scotland. Results: In Wales, 40/82 (48.7%) patients with diabetes had COVID-19-related mortality compared with 1,149/2,916 (39.1%) in the UK group (p=0.08). The Welsh cohort were more likely to be Caucasian, have a higher body mass index and HbA1c, be diagnosed with diabetic retinopathy and prescribed a sodium-glucose co-transporter 2 inhibitor or insulin than those in England and Scotland. Patients admitted to the ICU in Wales were more likely to be male and have type 2 diabetes. Conclusions: Patients admitted to hospital with diabetes and COVID-19 in Wales had a poorer outcome compared with England and Scotland. This disparity may reflect social inequality, differences in cardiovascular risk factors and/or differences in diabetes medications between hospitalised patients in Wales and the UK.

We describe the rationale, aims and objectives and the methodology of data collection for the ABCD nationwide audit of individuals admitted to hospital with coronavirus (SARS-CoV-2; COVID-19) and diabetes. The audit was inspired and undertaken by the urgent need to understand the clinical course of COVID-19 in patients with diabetes admitted to hospital in the UK during the pandemic. We wished to understand the clinical behaviour of diabetes per se, post hospital admission and the factors with may be associated with admission to the Intensive Care Unit (ICU) and death due to COVID-19. This was a clinically-led audit. We used existing infrastructure and expertise to collect data using an electronic tool specifically designed and piloted by the steering group members. The clinical variables were chosen to fulfil the main aim of this audit as stated above, and factors influencing the clinical course of COVID-19 in individuals with both type 1 and type 2 diabetes at the time of admission to hospital and during the whole length of stay, until discharge or death from COVID-19. The data collected so far represent a large, multicentre audit with more than 3,500 admissions during the pandemic. We plan to continue collecting additional data and publish ongoing reports of interest to diabetes clinicians with the aim of enhancing knowledge and understanding and thereby improving clinical care of, and outcomes for, people with diabetes who are admitted to hospital with COVID-19 in the UK.

AIMS/HYPOTHESIS: The aim of this work was to describe the clinical characteristics of adults with type 1 diabetes admitted to hospital and the risk factors associated with severe coronavirus disease-2019 (COVID-19) in the UK. METHODS: A retrospective cohort study was performed using data collected through a nationwide audit of people admitted to hospital with diabetes and COVID-19, conducted by the Association of British Clinical Diabetologists from March to October 2020. Prespecified demographic, clinical, medication and laboratory data were collected from the electronic and paper medical record systems of the participating hospitals by local clinicians. The primary outcome of the study, severe COVID-19, was defined as death in hospital and/or admission to the adult intensive care unit (AICU). Logistic regression models were used to generate age-adjusted ORs. RESULTS: Forty UK centres submitted data. The final dataset included 196 adults who were admitted to hospital and had both type 1 diabetes and COVID-19 on admission (male sex 55%, white 70%, with mean [SD] age 62 [19] years, BMI 28.3 [7.3] kg/m2 and last recorded HbA1c 76 [31] mmol/mol [9.1 (5.0)%]). The prevalence of pre-existing microvascular disease and macrovascular disease was 56% and 39%, respectively. The prevalence of diabetic ketoacidosis on admission was 29%. A total of 68 patients (35%) died or were admitted to AICU. The proportions of people that died were 7%, 38% and 38% of those aged <55, 55-74 and ≥75 years, respectively. BMI, serum creatinine levels and having one or more microvascular complications were positively associated with the primary outcome after adjusting for age. CONCLUSIONS/INTERPRETATION: In people with type 1 diabetes and COVID-19 who were admitted to hospital in the UK, higher BMI, poorer renal function and presence of microvascular complications were associated with greater risk of death and/or admission to AICU. Risk of severe COVID-19 is reassuringly very low in people with t

Background Several randomized trials have compared the patency of coronary artery bypass conduits. All of the published studies, however, have performed pairwise comparisons and a comprehensive evaluation of the patency rates of all conduits has yet to be published. We set out to investigate the angiographic patency rates of all conduits used in coronary bypass surgery by performing a network meta-analysis of the current available randomized evidence. Methods and Results A systematic literature search was conducted for randomized controlled trials comparing the angiographic patency rate of the conventionally harvested saphenous vein, the no-touch saphenous vein, the radial artery (RA), the right internal thoracic artery, or the gastroepiploic artery. The primary outcome was graft occlusion. A total of 4160 studies were retrieved of which 14 were included with 3651 grafts analyzed. The weighted mean angiographic follow-up was 5.1 years. Compared with the conventionally harvested saphenous vein, both the RA (incidence rate ratio [IRR] 0.54; 95% CI, 0.35-0.82) and the no-touch saphenous vein (IRR 0.55; 95% CI, 0.39-0.78) were associated with lower graft occlusion. The RA ranked as the best conduit (rank score for RA 0.87 versus 0.85 for no-touch saphenous vein, 0.23 for right internal thoracic artery, 0.29 for gastroepiploic artery, and 0.25 for the conventionally harvested saphenous vein). Conclusions Compared with the conventionally harvested saphenous vein, only the RA and no-touch saphenous vein grafts are associated with significantly lower graft occlusion rates. The RA ranks as the best conduit. Registration URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42020164492.

Background: The measurement of anatomical structures is critical in plastic and reconstructive surgery. However, few detailed and standardized measurements have been widely used in the periorbital region. This study aimed to evaluate the feasibility of a novel detailed and standardized protocol with 2D and 3D technologies, and explore the relationship between them and direct measurements. Methods: Fifty healthy Caucasians (100 eyes) between 20 and 68 years old were recruited and captured for 3D photographs by VECTRA M3 3D Imaging System. Subsequently, 24 landmarks were located on each 3D photographs following a standardized protocol, and then 19 linear and 3 angular periorbital variables were measured. Furthermore, two-dimensional (2D) and direct measurements were conducted on each subject and compared with 3D measurements and one another. Results: The grand r means across all measurements were 0.77, 0.78, and 0.88 for direct vs. 2D values, direct vs. 3D values, and 3D vs. 2D values, respectively. The mean absolute differences were 1 mm (ranging from 0.2 mm to 3.7 mm) between direct and 3D measurements, 1 mm (ranging from 0.04 mm to 2.4 mm) between direct and 2D measurements, and 1 mm and 6.6 degrees (ranging from 0.04 mm or 0.5 degrees to 3 mm or 12.8 degrees) between 2D and 3D measurements. Conclusions: This study verified the feasibility of this detailed and standardized landmark localization protocol for assessing the periorbital morphology with 2D and 3D technologies. This protocol may work as a bridge communicating with all studies involving any of the three technologies in the future. (C) 2020 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Fire causes dramatic energy and matter exchanges between biosphere and atmosphere on a regional to global scale. Predicting fires, however, is hindered by the complex interplay of fire, climate, and vegetation. Paleo-fire records provide critical information beyond instrumental records that cover only the past few decades and may be used to assess the role of fire in large-scale and long-term environmental changes. Here we present a 22,000-year multiproxy record of fire regime from a sediment core retrieved offshore South Java, Indonesia. We use microcharcoal in combination with two molecular markers of burning, levoglucosan and polycyclic aromatic hydrocarbons, to reconstruct fire occurrence as well as fire intensity in the past. We show that fire occurrence and intensity were high during the Last Glacial Maximum (LGM; around 21,000 years ago) and low during the Heinrich Stadial 1 and the early Holocene. Both fire regime and vegetation in tropical regions with high annual rainfall were primarily controlled by rainfall seasonality. However, fire additionally stabilized the savannah (rainforest)-dominated ecosystem during the LGM (early Holocene) but caused transitions between the two vegetation types during the deglaciation and the late Holocene.

An aerobic denitrification strain, Pseudomonas balearica RAD-17, was identified and showed efficient inorganic nitrogen removal ability. The average NO3–-N, NO2–-N, and total ammonium nitrogen (TAN) removal rate (>95% removal efficiency) in a batch test was 6.22 mg/(L·∙h), 6.30 mg/(L·∙h), and 1.56 mg/(L·∙h), respectively. Meanwhile, optimal incubate conditions were obtained through single factor experiments. For nitrogen removal pathways, the transcriptional results proved that respiratory nitrate reductases encoded by napA, which was primarily performed in aerobic denitrification and cell assimilation, were conducted by gluS and gluD genes for ammonium metabolism. In addition, adding the strain RAD-17 into actual wastewater showed obvious higher denitrification performance than in the no inoculum group (84.22% vs. 22.54%), and the maximum cell abundance achieved 28.5 ± 4.5% in a ratio of total cell numbers. Overall, the efficient nitrogen removal performance plus strong environmental fitness makes the strain RAD-17 a potential alternative for RAS (recirculating aquaculture system) effluent treatment. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

An aerobic denitrification strain, Pseudomonas balearica RAD-17, was identified and showed efficient inorganic nitrogen removal ability. The average NO3–-N, NO2–-N, and total ammonium nitrogen (TAN) removal rate (>95% removal efficiency) in a batch test was 6.22 mg/(L·∙h), 6.30 mg/(L·∙h), and 1.56 mg/(L·∙h), respectively. Meanwhile, optimal incubate conditions were obtained through single factor experiments. For nitrogen removal pathways, the transcriptional results proved that respiratory nitrate reductases encoded by napA, which was primarily performed in aerobic denitrification and cell assimilation, were conducted by gluS and gluD genes for ammonium metabolism. In addition, adding the strain RAD-17 into actual wastewater showed obvious higher denitrification performance than in the no inoculum group (84.22% vs. 22.54%), and the maximum cell abundance achieved 28.5 ± 4.5% in a ratio of total cell numbers. Overall, the efficient nitrogen removal performance plus strong environmental fitness makes the strain RAD-17 a potential alternative for RAS (recirculating aquaculture system) effluent treatment. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

The authors regret that on page 68, Table 3, the number of observed cases, the PAR, and the attributable cases of breast cancer in the rows for both men and women were mistakenly presented. These values should be the same as those for women. In Table 3, the column heading ‘EAC’ should be changed to ‘AC’. In the title of Table 3, ‘***No confidence intervals.’ Should be deleted. Tables 1, 3, 4, and 5 are all missing a footnote to indicate ‘postmenopausal breast cancer’. In the last paragraph on page 70, the text should read ‘and 180 to 900 colon cancer cases’. The original text erroneously states ‘colorectal’. In the author list on page 65, the superscript for ‘the ComPARe Study Team’ should be ‘1’ instead of ‘c, 1’. A corrected Table 3 is attached with this corrigendum. The authors would like to apologize for any inconvenience caused. [Table presented]

Fire causes dramatic energy and matter exchanges between biosphere and atmosphere on a regional to global scale. Predicting fires, however, is hindered by the complex interplay of fire, climate, and vegetation. Paleo‐fire records provide critical information beyond instrumental records that cover only the past few decades and may be used to assess the role of fire in large‐scale and long‐term environmental changes. Here we present a 22,000‐year multiproxy record of fire regime from a sediment core retrieved offshore South Java, Indonesia. We use microcharcoal in combination with two molecular markers of burning, levoglucosan and polycyclic aromatic hydrocarbons, to reconstruct fire occurrence as well as fire intensity in the past. We show that fire occurrence and intensity were high during the Last Glacial Maximum (LGM; around 21,000 years ago) and low during the Heinrich Stadial 1 and the early Holocene. Both fire regime and vegetation in tropical regions with high annual rainfall were primarily controlled by rainfall seasonality. However, fire additionally stabilized the savannah (rainforest)‐dominated ecosystem during the LGM (early Holocene) but caused transitions between the two vegetation types during the deglaciation and the late Holocene.

This research thesis clarifies the negotiation process of Chinese young homosexual males between the heteronormative urban public space and their homosexual identity by focusing on their daily practice in space. Based on an empirical study in the city of Guangzhou, this research adopts methods of in-depth interview and photography. Post90s urban gay men have higher acceptance towards homosexual identity and lower acceptance towards conducting homosexual behaviour or visiting homosexual place in urban public space. They have different levels of awareness towards the heteronormativity of the urban public space. They also notice the suppression brought by such heteronormativity to their identity cognition pathway. As a compromise, they instead satisfy homosexual needs in an understated way to avoid identity exposure. Meanwhile, they transform part of homosexual social life to the relatively free and less heteronormative digital space that is more private and accessible for their group. Also, they value the geographical space such as restaurants, cafes, malls and squares, as it provides public places to develop online connections. Besides, concepts like “gay cruising” “gay neighbourhood” and “space for performance” in western research are discussed in the condition associated with the reality of China.

An aerobic denitrification strain, Pseudomonas balearica RAD-17, was identified and showed efficient inorganic nitrogen removal ability. The average NO3–-N, NO2–-N, and total ammonium nitrogen (TAN) removal rate (>95% removal efficiency) in a batch test was 6.22 mg/(L·∙h), 6.30 mg/(L·∙h), and 1.56 mg/(L·∙h), respectively. Meanwhile, optimal incubate conditions were obtained through single factor experiments. For nitrogen removal pathways, the transcriptional results proved that respiratory nitrate reductases encoded by napA, which was primarily performed in aerobic denitrification and cell assimilation, were conducted by gluS and gluD genes for ammonium metabolism. In addition, adding the strain RAD-17 into actual wastewater showed obvious higher denitrification performance than in the no inoculum group (84.22% vs. 22.54%), and the maximum cell abundance achieved 28.5 ± 4.5% in a ratio of total cell numbers. Overall, the efficient nitrogen removal performance plus strong environmental fitness makes the strain RAD-17 a potential alternative for RAS (recirculating aquaculture system) effluent treatment. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Fire causes dramatic energy and matter exchanges between biosphere and atmosphere on a regional to global scale. Predicting fires, however, is hindered by the complex interplay of fire, climate, and vegetation. Paleo‐fire records provide critical information beyond instrumental records that cover only the past few decades and may be used to assess the role of fire in large‐scale and long‐term environmental changes. Here we present a 22,000‐year multiproxy record of fire regime from a sediment core retrieved offshore South Java, Indonesia. We use microcharcoal in combination with two molecular markers of burning, levoglucosan and polycyclic aromatic hydrocarbons, to reconstruct fire occurrence as well as fire intensity in the past. We show that fire occurrence and intensity were high during the Last Glacial Maximum (LGM; around 21,000 years ago) and low during the Heinrich Stadial 1 and the early Holocene. Both fire regime and vegetation in tropical regions with high annual rainfall were primarily controlled by rainfall seasonality. However, fire additionally stabilized the savannah (rainforest)‐dominated ecosystem during the LGM (early Holocene) but caused transitions between the two vegetation types during the deglaciation and the late Holocene.

This research thesis clarifies the negotiation process of Chinese young homosexual males between the heteronormative urban public space and their homosexual identity by focusing on their daily practice in space. Based on an empirical study in the city of Guangzhou, this research adopts methods of in-depth interview and photography. Post90s urban gay men have higher acceptance towards homosexual identity and lower acceptance towards conducting homosexual behaviour or visiting homosexual place in urban public space. They have different levels of awareness towards the heteronormativity of the urban public space. They also notice the suppression brought by such heteronormativity to their identity cognition pathway. As a compromise, they instead satisfy homosexual needs in an understated way to avoid identity exposure. Meanwhile, they transform part of homosexual social life to the relatively free and less heteronormative digital space that is more private and accessible for their group. Also, they value the geographical space such as restaurants, cafes, malls and squares, as it provides public places to develop online connections. Besides, concepts like “gay cruising” “gay neighbourhood” and “space for performance” in western research are discussed in the condition associated with the reality of China.

Whether hemodiafiltration (HDF) is better than conventional hemodialysis (HD) in improving left ventricular hypertrophy (LVH), defined as reduction of the left ventricular mass index (LVMi) and increasing the ejection fraction (EF), is unclear. A systematic literature search was performed. Primary outcome was the mean difference between pre- and post-procedural LVMi. Secondary outcome was the mean difference in EF. Seven studies with a total of 845 patients were included. The pooled mean difference between pre-and post-procedural LVMi was −8.0 g/m2 (95% confidence interval [CI] −13.1, −2.8). On subgroup analysis, the mean differences between pre- and post-procedural LVMi for HD and HDF were −6.7 g/m2 (95% CI −14.5, 1.1) and −9.3 g/m2 (95% CI −16.3, −2.3), respectively (P for subgroups =.62). Pooled mean difference between pre- and post-procedural EF was 2.4% (95% CI −1.8, 6.5). On subgroup analysis, the mean differences between pre- and post-procedural EF for HD and HDF were 3.6% (95% CI −2.7, 9.8) and 2.0% (95% CI 2.9, 6.8), respectively (P for subgroups =.68). On meta-regression, age (Beta −0.35 ± 0.05, P <.001) and longer dialysis duration (Beta −0.12 ± 0.02, P <.001) were associated with lower mean difference between pre-and post-procedural EF. No significant effects on changes in LVMi and EF were observed with HDF compared with conventional HD.

Novel approaches for digital data storage are imperative, as storage capacities are drastically being outpaced by the exponential growth in data generation. Optical data storage represents the most promising alternative to traditional magnetic and solid-state data storage. In this paper, a novel and energy efficient approach to optical data storage using rare-earth ion doped inorganic insulators is demonstrated. In particular, the nanocrystalline alkaline earth halide BaFCl:Sm is shown to provide great potential for multilevel optical data storage. Proof-of-concept demonstrations reveal for the first time that these phosphors could be used for rewritable, multilevel optical data storage on the physical dimensions of a single nanocrystal. Multilevel information storage is based on the very efficient and reversible conversion of Sm3+ to Sm2+ ions upon exposure to UV-C light. The stored information is then read-out using confocal optics by employing the photoluminescence of the Sm2+ ions in the nanocrystals, with the signal strength depending on the UV-C fluence used during the write step. The latter serves as the mechanism for multilevel data storage in the individual nanocrystals, as demonstrated in this paper. This data storage platform has the potential to be extended to 2D and 3D memory for storage densities that could potentially approach petabyte/cm3 levels.

Introduction The Canadian Population Attributable Risk of Cancer project aims to quantify the number and proportion of cancer cases incident in Canada, now and projected to 2042, that could be prevented through changes in the prevalence of modifiable exposures associated with cancer. The broad risk factor categories of interest include tobacco, diet, energy imbalance, infectious diseases, hormonal therapies and environmental factors such as air pollution and resi

BACKGROUND: Physical activity has emerged as an important lifestyle factor for primary prevention of numerous diseases, including postmenopausal breast cancer. No study to date has assessed the acute and long-term effects of year-long aerobic exercise programs differing in prescribed exercise volume on physical activity and sedentary time in postmenopausal women. Therefore, we aimed to examine the effects of two moderate-vigorous intensity exercise doses on total, light and moderate-vigorous intensity physical activity times, and sedentary time in postmenopausal women during the year-long intervention and one year later. METHODS: The Breast Cancer and Exercise Trial in Alberta (BETA) was a two-center, two-arm, 12-month randomized controlled trial that included 400 previously inactive postmenopausal women randomized to either 150 (MODERATE) or 300 (HIGH) minutes/week of aerobic exercise. Physical activity and sedentary time were assessed at baseline, 6- (intervention mid-point), 12- (prior to end of intervention) and 24-months (follow-up) with waist-mounted accelerometers (Actigraph GTX3®). Self-reported activity and sedentary time at baseline, 12- and 24-months was also assessed (Past Year Total Physical Activity Questionnaire and SIT-Q). Intention-to-treat analyses were conducted using linear mixed models and adjusted for baseline variables. RESULTS: Both physical activity interventions led to increases in objective and subjective measures of total and moderate-vigorous intensity/recreational physical activity time, coupled with decreases in sedentary time, at 6- and 12-months compared to baseline. Additionally, greater increases in accelerometry-derived total physical activity time at 6- and 12-months, and self-reported recreational activity time at 12-months, compared to baseline were noted in the HIGH versus MODERATE groups. Decreases in total, light and moderate-vigorous intensity physical activity time, and an increase in sedentary time, in both groups were no

Traditional optical fibers are insensitive to magnetic fields, however many applications would benefit from fiber-based magnetometry devices. In this work, we demonstrate a magnetically sensitive optical fiber by doping nanodiamonds containing nitrogen vacancy centers into tellurite glass fibers. The fabrication process provides a robust and isolated sensing platform as the magnetic sensors are fixed in the tellurite glass matrix. Using optically detected magnetic resonance from the doped nanodiamonds, we demonstrate detection of local magnetic fields via side excitation and longitudinal collection. This is a first step towards intrinsically magneto-sensitive fiber devices with future applications in medical magneto-endoscopy and remote mineral exploration sensing.

We present results demonstrating the prospects of samarium-doped nanocrystals for use in ultra-high capacity multilevel optical data storage. Optical data storage is demonstrated through fluorescence tuning of MeFCl:Sm (Me: Ba, Sr) in the deep UV with a 7 orders of magnitude linear dynamic range.

Contains fulltext : 171367.pdf (Publisher’s version ) (Open Access), Genome-wide association and fine-mapping studies in 14 autoimmune diseases (AID) have implicated more than 250 loci in one or more of these diseases. As more than 90% of AID-associated SNPs are intergenic or intronic, pinpointing the causal genes is challenging. We performed a systematic analysis to link 460 SNPs that are associated with 14 AID to causal genes using transcriptomic data from 629 blood samples. We were able to link 71 (39%) of the AID-SNPs to two or more nearby genes, providing evidence that for part of the AID loci multiple causal genes exist. While 54 of the AID loci are shared by one or more AID, 17% of them do not share candidate causal genes. In addition to finding novel genes such as ULK3, we also implicate novel disease mechanisms and pathways like autophagy in celiac disease pathogenesis. Furthermore, 42 of the AID SNPs specifically affected the expression of 53 non-coding RNA genes. To further understand how the non-coding genome contributes to AID, the SNPs were linked to functional regulatory elements, which suggest a model where AID genes are regulated by network of chromatin looping/non-coding RNAs interactions. The looping model also explains how a causal candidate gene is not necessarily the gene closest to the AID SNP, which was the case in nearly 50% of cases.

Genome-wide association and fine-mapping studies in 14 autoimmune diseases (AID) have implicated more than 250 loci in one or more of these diseases. As more than 90% of AID-associated SNPs are intergenic or intronic, pinpointing the causal genes is challenging. We performed a systematic analysis to link 460 SNPs that are associated with 14 AID to causal genes using transcriptomic data from 629 blood samples. We were able to link 71 (39%) of the AID-SNPs to two or more nearby genes, providing evidence that for part of the AID loci multiple causal genes exist. While 54 of the AID loci are shared by one or more AID, 17% of them do not share candidate causal genes. In addition to finding novel genes such as ULK3, we also implicate novel disease mechanisms and pathways like autophagy in celiac disease pathogenesis. Furthermore, 42 of the AID SNPs specifically affected the expression of 53 non-coding RNA genes. To further understand how the non-coding genome contributes to AID, the SNPs were linked to functional regulatory elements, which suggest a model where AID genes are regulated by network of chromatin looping/non-coding RNAs interactions. The looping model also explains how a causal candidate gene is not necessarily the gene closest to the AID SNP, which was the case in nearly 50% of cases.

Contains fulltext : 171367.pdf (Publisher’s version ) (Open Access), Genome-wide association and fine-mapping studies in 14 autoimmune diseases (AID) have implicated more than 250 loci in one or more of these diseases. As more than 90% of AID-associated SNPs are intergenic or intronic, pinpointing the causal genes is challenging. We performed a systematic analysis to link 460 SNPs that are associated with 14 AID to causal genes using transcriptomic data from 629 blood samples. We were able to link 71 (39%) of the AID-SNPs to two or more nearby genes, providing evidence that for part of the AID loci multiple causal genes exist. While 54 of the AID loci are shared by one or more AID, 17% of them do not share candidate causal genes. In addition to finding novel genes such as ULK3, we also implicate novel disease mechanisms and pathways like autophagy in celiac disease pathogenesis. Furthermore, 42 of the AID SNPs specifically affected the expression of 53 non-coding RNA genes. To further understand how the non-coding genome contributes to AID, the SNPs were linked to functional regulatory elements, which suggest a model where AID genes are regulated by network of chromatin looping/non-coding RNAs interactions. The looping model also explains how a causal candidate gene is not necessarily the gene closest to the AID SNP, which was the case in nearly 50% of cases.

Contains fulltext : 171367.pdf (Publisher’s version ) (Open Access), Genome-wide association and fine-mapping studies in 14 autoimmune diseases (AID) have implicated more than 250 loci in one or more of these diseases. As more than 90% of AID-associated SNPs are intergenic or intronic, pinpointing the causal genes is challenging. We performed a systematic analysis to link 460 SNPs that are associated with 14 AID to causal genes using transcriptomic data from 629 blood samples. We were able to link 71 (39%) of the AID-SNPs to two or more nearby genes, providing evidence that for part of the AID loci multiple causal genes exist. While 54 of the AID loci are shared by one or more AID, 17% of them do not share candidate causal genes. In addition to finding novel genes such as ULK3, we also implicate novel disease mechanisms and pathways like autophagy in celiac disease pathogenesis. Furthermore, 42 of the AID SNPs specifically affected the expression of 53 non-coding RNA genes. To further understand how the non-coding genome contributes to AID, the SNPs were linked to functional regulatory elements, which suggest a model where AID genes are regulated by network of chromatin looping/non-coding RNAs interactions. The looping model also explains how a causal candidate gene is not necessarily the gene closest to the AID SNP, which was the case in nearly 50% of cases.

© 2015, Springer Science+Business Media New York. Quantum image retrieval is an exhaustive work due to exponential measurements. Casting aside the background of image processing, quantum image is a pure many-body state, and the retrieval task is a physical process named as quantum state tomography. Tomography of a special class of states, permutationally symmetric states, just needs quadratic measurement scales with the number of qubits. In order to take advantage of this result, we propose a method to map the main energy of the image to these states. First, we deduce that n+1 permutationally symmetric states can be constructed as bases of 2n Hilbert space (n qubits) at least. Second, we execute Schmidt decomposition by continually bipartite splitting of the quantum image (state). At last, we select n+1 maximum coefficients, do base transformation to map these coefficients to new bases (permutationally symmetric states). By these means, the quantum image with high retrieval performance can be gotten.

© 2015, Springer Science+Business Media New York. Quantum image retrieval is an exhaustive work due to exponential measurements. Casting aside the background of image processing, quantum image is a pure many-body state, and the retrieval task is a physical process named as quantum state tomography. Tomography of a special class of states, permutationally symmetric states, just needs quadratic measurement scales with the number of qubits. In order to take advantage of this result, we propose a method to map the main energy of the image to these states. First, we deduce that n+1 permutationally symmetric states can be constructed as bases of 2n Hilbert space (n qubits) at least. Second, we execute Schmidt decomposition by continually bipartite splitting of the quantum image (state). At last, we select n+1 maximum coefficients, do base transformation to map these coefficients to new bases (permutationally symmetric states). By these means, the quantum image with high retrieval performance can be gotten.

Contains fulltext : 152267.pdf (publisher's version ) (Open Access), BACKGROUND: The impact of signal-dependent transcription factors, such as glucocorticoid receptor and nuclear factor kappa-b, on the three-dimensional organization of chromatin remains a topic of discussion. The possible scenarios range from remodeling of higher order chromatin architecture by activated transcription factors to recruitment of activated transcription factors to pre-established long-range interactions. RESULTS: Using circular chromosome conformation capture coupled with next generation sequencing and high-resolution chromatin interaction analysis by paired-end tag sequencing of P300, we observed agonist-induced changes in long-range chromatin interactions, and uncovered interconnected enhancer-enhancer hubs spanning up to one megabase. The vast majority of activated glucocorticoid receptor and nuclear factor kappa-b appeared to join pre-existing P300 enhancer hubs without affecting the chromatin conformation. In contrast, binding of the activated transcription factors to loci with their consensus response elements led to the increased formation of an active epigenetic state of enhancers and a significant increase in long-range interactions within pre-existing enhancer networks. De novo enhancers or ligand-responsive enhancer hubs preferentially interacted with ligand-induced genes. CONCLUSIONS: We demonstrate that, at a subset of genomic loci, ligand-mediated induction leads to active enhancer formation and an increase in long-range interactions, facilitating efficient regulation of target genes. Therefore, our data suggest an active role of signal-dependent transcription factors in chromatin and long-range interaction remodeling.

We have developed a technique for creating high quality tellurite microspheres with embedded nanodiamonds (NDs) containing nitrogen-vacancy (NV) centres. This hybrid method allows fluorescence of the NVs in the NDs to be directly, rather than evanescently, coupled to the whispering gallery modes of the tellurite microspheres at room temperature. As a demonstration of its sensing potential, shifting of the resonance peaks is also demonstrated by coating a sphere surface with a liquid layer. This new approach is a robust way of creating cavities for use in quantum and sensing applications.

Contains fulltext : 152267.pdf (publisher's version ) (Open Access), BACKGROUND: The impact of signal-dependent transcription factors, such as glucocorticoid receptor and nuclear factor kappa-b, on the three-dimensional organization of chromatin remains a topic of discussion. The possible scenarios range from remodeling of higher order chromatin architecture by activated transcription factors to recruitment of activated transcription factors to pre-established long-range interactions. RESULTS: Using circular chromosome conformation capture coupled with next generation sequencing and high-resolution chromatin interaction analysis by paired-end tag sequencing of P300, we observed agonist-induced changes in long-range chromatin interactions, and uncovered interconnected enhancer-enhancer hubs spanning up to one megabase. The vast majority of activated glucocorticoid receptor and nuclear factor kappa-b appeared to join pre-existing P300 enhancer hubs without affecting the chromatin conformation. In contrast, binding of the activated transcription factors to loci with their consensus response elements led to the increased formation of an active epigenetic state of enhancers and a significant increase in long-range interactions within pre-existing enhancer networks. De novo enhancers or ligand-responsive enhancer hubs preferentially interacted with ligand-induced genes. CONCLUSIONS: We demonstrate that, at a subset of genomic loci, ligand-mediated induction leads to active enhancer formation and an increase in long-range interactions, facilitating efficient regulation of target genes. Therefore, our data suggest an active role of signal-dependent transcription factors in chromatin and long-range interaction remodeling.

Contains fulltext : 152267.pdf (publisher's version ) (Open Access), BACKGROUND: The impact of signal-dependent transcription factors, such as glucocorticoid receptor and nuclear factor kappa-b, on the three-dimensional organization of chromatin remains a topic of discussion. The possible scenarios range from remodeling of higher order chromatin architecture by activated transcription factors to recruitment of activated transcription factors to pre-established long-range interactions. RESULTS: Using circular chromosome conformation capture coupled with next generation sequencing and high-resolution chromatin interaction analysis by paired-end tag sequencing of P300, we observed agonist-induced changes in long-range chromatin interactions, and uncovered interconnected enhancer-enhancer hubs spanning up to one megabase. The vast majority of activated glucocorticoid receptor and nuclear factor kappa-b appeared to join pre-existing P300 enhancer hubs without affecting the chromatin conformation. In contrast, binding of the activated transcription factors to loci with their consensus response elements led to the increased formation of an active epigenetic state of enhancers and a significant increase in long-range interactions within pre-existing enhancer networks. De novo enhancers or ligand-responsive enhancer hubs preferentially interacted with ligand-induced genes. CONCLUSIONS: We demonstrate that, at a subset of genomic loci, ligand-mediated induction leads to active enhancer formation and an increase in long-range interactions, facilitating efficient regulation of target genes. Therefore, our data suggest an active role of signal-dependent transcription factors in chromatin and long-range interaction remodeling.

Objectives: To study the dynamics of HIV drug resistance (HIVDR) and its association with virologic and immunologic failure as well as mortality among patients on combination antiretroviral therapy (cART) in China. Design: Werecruited 365 patients on cART in two rural Chinese counties in 2003-2004 and followed them every 6 months until May 2010. Methods: Virologic failure, HIVDR, immunologic failure and death were documented. We used Kaplan-Meier and the proportional hazards models to identify the timing of the events, and risk factors for mortality. Results: At the end of study, patients had been followed for 1974.3 person-years, a median of 6.1 years. HIVDR mutations were found in 235 (64.4%) patients and 75 died (20.5%, 3.8/100 person-years). Median time from cART to detection of virologic failure was 17.5 months, to HIVDR 36.6 months and to immunologic failure 55.2 months (∼18-month median interval between each adverse milestone). Being male, having a baseline CD4+ cell count of less than 50 cells/μl and HIVDR were associated with higher mortality. Patients who developed HIVDR in the first year of treatment had higher mortality than those developing HIVDR later (adjusted hazard ratio 1.90, 95% confidence interval 1.01-3.48). Conclusion: HIVDR was common and was associated with higher mortality among Chinese patients on cART, particular when HIVDR was detected early in therapy. Our study reinforces the importance of improving patient adherence to cART in order to delay the emergence of HIVDR and obviate the need to switch to costly second-line drug regimens too early. © 2013 Creative Common License.

Background: Highly active antiretroviral therapy (HAART) has significantly decreased mortality among Chinese HIV patients. However, emerging HIV drug resistance (HIVDR) poses a growing threat to the long-term success and durability of HAART. Methods: Three cross-sectional surveys were conducted across the country from 2004 to 2006, respectively. Patients completed a questionnaire and provided blood for CD4 cell count, HIV viral load (VL), and HIV resistance genotyping. Factors associated with HIVDR were identified by logistic regression. Results: 3667 unique patients were included across the three surveys. Among 2826 treatment-experienced patients, median duration of treatment was 17.4 (IQR 8.6-28.4) months and HIVDR was identified in 543 (19.2%). Factors significantly associated with HIVDR included ART drug distribution location, CD4 cell count, initial HAART regimen, self-reported medication adherence, and province. Conclusions: Virologic failure increased over time on therapy but a significant proportion of patients in failure had no resistance mutations identified, suggesting that treatment adherence is suboptimal and must be emphasized. Due to the significantly higher risk of HIVDR in certain provinces, additional steps to reduce HIVDR should be taken. © 2013 Xing et al.

Background:A critical indicator of the future success of highly active antiretroviral therapy (HAART) is the incidence of HIV drug resistance, which has not been studied in China on the national scale.Methods:HIV drug resistance baseline survey was conducted in the eight provinces with the largest numbers of patients on HAART in 2009, and a prospective cohort study with 12-month follow-up was completed in 2010. Patients completed an interviewer-administrated questionnaire and provided blood for CD4+ T-lymphocyte count (CD4 count), HIV viral load (VL), and HIV drug resistance genotyping. Factors associated with incidence of HIVDR were identified by Cox regression analysis.Results:The overall prevalence of HIV RNA ≥1000 copies/ml and HIVDR at baseline was 12.4% and 5.6%, respectively. Incidence of HIVDR in the one year follow-up was 3.5 per 100 person years. Independently associated factors were started treatment with a didanosine-based regimen, received care at township hospital or village clinic, low baseline CD4 counts, and high baseline VL.Conclusions:The incidence of HIVDR in China was higher than that of some developed countries. China urgently needs to provide comprehensive education and training to doctors at village clinics and township hospitals to improve quality community-based care and treatment. © 2013 Xing et al.

In multicellular organisms, transcription regulation is one of the central mechanisms modelling lineage differentiation and cell-fate determination. Transcription requires dynamic chromatin configurations between promoters and their corresponding distal regulatory elements. It is believed that their communication occurs within large discrete foci of aggregated RNA polymerases termed transcription factories in three-dimensional nuclear space. However, the dynamic nature of chromatin connectivity has not been characterized at the genome-wide level. Here, through a chromatin interaction analysis with paired-end tagging approach using an antibody that primarily recognizes the pre-initiation complexes of RNA polymerase II, we explore the transcriptional interactomes of three mouse cells of progressive lineage commitment, including pluripotent embryonic stem cells, neural stem cells and neurosphere stem/progenitor cells. Our global chromatin connectivity maps reveal approximately 40,000 long-range interactions, suggest precise enhancer-promoter associations and delineate cell-type-specific chromatin structures. Analysis of the complex regulatory repertoire shows that there are extensive colocalizations among promoters and distal-acting enhancers. Most of the enhancers associate with promoters located beyond their nearest active genes, indicating that the linear juxtaposition is not the only guiding principle driving enhancer target selection. Although promoter-enhancer interactions exhibit high cell-type specificity, promoters involved in interactions are found to be generally common and mostly active among different cells. Chromatin connectivity networks reveal that the pivotal genes of reprogramming functions are transcribed within physical proximity to each other in embryonic stem cells, linking chromatin architecture to coordinated gene expression. Our study sets the stage for the full-scale dissection of spatial and temporal genome structures and their roles in orche

Disrupted-in-Schizophrenia-1 (DISC1) is a genetic susceptibility locus for major mental illness, including schizophrenia and depression. The Disc1 protein was recently shown to interact with the Wnt signaling protein, DIX domain containing 1 (Dixdc1). Both proteins participate in neural progenitor proliferation dependent on Wnt signaling, and in neural migration independently of Wnt signaling. Interestingly, their effect on neural progenitor proliferation is additive. By analogy to Disc1, mutations in Dixdc1 may lead to abnormal behavior in mice, and to schizophrenia or depression in humans. To explore this hypothesis further, we generated mice mutant at the Dixdc1 locus and analyzed their behavior. Dixdc1(-/-) mice had normal prepulse inhibition, but displayed decreased spontaneous locomotor activity, abnormal behavior in the elevated plus maze and deficits in startle reactivity. Our results suggest that Dixdc1(-/-) mice will be a useful tool to elucidate molecular pathophysiology involving Disc1 in major mental illnesses.

Disrupted-in-Schizophrenia-1 (DISC1) is a genetic susceptibility locus for major mental illness, including schizophrenia and depression. The Disc1 protein was recently shown to interact with the Wnt signaling protein, DIX domain containing 1 (Dixdc1). Both proteins participate in neural progenitor proliferation dependent on Wnt signaling, and in neural migration independently of Wnt signaling. Interestingly, their effect on neural progenitor proliferation is additive. By analogy to Disc1, mutations in Dixdc1 may lead to abnormal behavior in mice, and to schizophrenia or depression in humans. To explore this hypothesis further, we generated mice mutant at the Dixdc1 locus and analyzed their behavior. Dixdc1(-/-) mice had normal prepulse inhibition, but displayed decreased spontaneous locomotor activity, abnormal behavior in the elevated plus maze and deficits in startle reactivity. Our results suggest that Dixdc1(-/-) mice will be a useful tool to elucidate molecular pathophysiology involving Disc1 in major mental illnesses.

In this paper we consider the problem of distributed tracking with consensus on a time-varying graph with noisy communications links and sensing constraints. We develop a framework to handle the time-varying network topology in which not every node has local observations to generate own local tracking estimates. Our approach introduces the concepts of active node set and connectivity graph to characterize such a network, and by merging these two, an effective network graph is obtained. Then we propose a distributed tracking-with-consensus algorithm for such a network model. We establish the conditions on the connectivity graph so that distributed consensus can be achieved in the presence of noisy communication links when the effective network graph is time-varying. We also discuss how this problem is motivated by the problem of distributed tracking of space-borne Objects of Interests (OoI's) in a hybrid space surveillance network (SSN) formed by both ground and satellite nodes. Simulation results of the proposed distributed tracking with consensus algorithm are given for a two-dimensional hybrid sensor network. They show that our algorithm performs almost the same as the distributed local Kalman filtering with centralized fusion on a noisy time-varying graphs with incomplete data while the proposed algorithm has the additional advantages of flexibility and scalability., 5th International Conference on Information and Automation for Sustainability (ICIAFs), Colombo, Sri Lanka, Dec. 2010. U.S. Government or Federal Rights License

The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.

Certain environmental microorganisms can cause severe human infections, even in the absence of an obvious requirement for transition through an animal host for replication ("accidental virulence"). To understand this process, we compared eleven isolate genomes of Burkholderia pseudomallei (Bp), a tropical soil microbe and causative agent of the human and animal disease melioidosis. We found evidence for the existence of several new genes in the Bp reference genome, identifying 282 novel genes supported by at least two independent lines of supporting evidence (mRNA transcripts, database homologs, and presence of ribosomal binding sites) and 81 novel genes supported by all three lines. Within the Bp core genome, 211 genes exhibited significant levels of positive selection (4.5%), distributed across many cellular pathways including carbohydrate and secondary metabolism. Functional experiments revealed that certain positively selected genes might enhance mammalian virulence by interacting with host cellular pathways or utilizing host nutrients. Evolutionary modifications improving Bp environmental fitness may thus have indirectly facilitated the ability of Bp to colonize and survive in mammalian hosts. These findings improve our understanding of the pathogenesis of melioidosis, and establish Bp as a model system for studying the genetics of accidental virulence.