Optimisation of aeration for activated sludge treatment with simultaneous nitrification denitrification.
Following a promising study at pilot scale a new aeration control law has been implemented at a full scale wastewater treatment plant displaying a conventional activated sludge process. The new control law is based on the direct measurements of ammonium and nitrate concentration in the biological tank by ion selective electrodes. This control law features a cascade of two Predictive Function Controls and calculates an optimal air flow rate to be provided to the biomass through fine bubble diffusers. The results obtained at the full scale plant confirmed the high performance of this control strategy allowing to substantially reduce the amount of diffused air while providing an easy means to manage the effluent quality to the plant operator.


Periodical cicadas as resource pulses in North American forests.
Resource pulses are occasional events of ephemeral resource superabundance that occur in many ecosystems. Aboveground consumers in diverse communities often respond strongly to resource pulses, but few studies have investigated the belowground consequences of resource pulses in natural ecosystems. This study shows that resource pulses of 17-year periodical cicadas (Magicicada spp.) directly increase microbial biomass and nitrogen availability in forest soils, with indirect effects on growth and reproduction in forest plants. These findings suggest that pulses of periodical cicadas create "bottom-up cascades," resulting in strong and reciprocal links between the aboveground and belowground components of a North American forest ecosystem.


Long-term effect of diuretic-based therapy on fatal outcomes in subjects with isolated systolic hypertension with and without diabetes.
Diuretic-based antihypertensive therapy is associated with the development of diabetes but with improved clinical outcomes. It has been proposed that the duration of clinical trials has been too short to detect the adverse effects of diabetes. We assessed the long-term mortality rate of subjects in the Systolic Hypertension in the Elderly Program (n = 4,732) who were randomized to stepped-care therapy with 12.5 to 25.0 mg/day of chlorthalidone or matching placebo. If blood pressure remained above the goal, atenolol or matching placebo was added. At a mean follow-up of 14.3 years, cardiovascular (CV) mortality rate was significantly lower in the chlorthalidone group (19%) than in the placebo group (22%; adjusted hazard ratio [HR] 0.854, 95% confidence interval [CI] 0.751 to 0.972). Diabetes at baseline (n = 799) was associated with increased CV mortality rate (adjusted HR 1.659, 95% CI 1.413 to 1.949) and total mortality rate (adjusted HR 1.510, 95% CI 1.347 to 1.693). Diabetes that developed during the trial among subjects on placebo (n = 169) was also associated with increased CV adverse outcome (adjusted HR 1.562, 95% CI 1.117 to 2.184) and total mortality rate (adjusted HR 1.348, 95% CI 1.051 to 1.727). However, diabetes that developed among subjects during diuretic therapy (n = 258) did not have significant associations with CV mortality rate (adjusted HR 1.043, 95% CI 0.745 to 1.459) or total mortality rate (adjusted HR 1.151, 95% CI 0.925 to 1.433). Diuretic treatment in subjects who had diabetes was strongly associated with lower long-term CV mortality rate (adjusted HR 0.688, 95% CI 0.526 to 0.848) and total mortality rate (adjusted HR 0.805, 95% CI 0.680 to 0.952). Thus, chlorthalidone-based treatment improved long-term outcomes, especially among subjects who had diabetes. Subjects who had diabetes associated with chlorthalidone had no significant increase in CV events and had a better prognosis than did those who had preexisting diabetes.


Assessing local health needs in primary care: understanding and experience in three English districts.
Assessing the health needs of a local population has been promoted as a key component in effective targeting of healthcare services and quality improvement. The understanding and experience of assessing health needs in general practice were investigated in three English districts. To identify the issues surrounding the potential for assessing health needs in primary care. Postal survey of 347 general practices in three health authorities. Telephone interviews with a random stratified sample of 35 general practitioners. Although most practices identified assessing health needs as important, it is clear that this identification was typically based on an understanding of assessing needs as primarily focused on individual patient care, based on clinical priorities and involving practice held data. Most practices had not undertaken local consultation, whatever their understanding of assessing health needs. The few practices which had completed population oriented, proactive assessment of needs considered it to have led to tangible improvements in clinical or practice management. Overall, there was apparent confusion over the nature and purpose of assessing needs, although the principled aims and objectives of a population oriented, proactive component to primary care were generally upheld. The need for additional resources and support was identified. In four out of the five cases where specifically population based assessment of health needs had been undertaken, the local public health department had been involved. The value of the concept of assessing health needs in primary care holds considerable uncertainty and ambivalence. The findings from this study show that any attempts to promote assessing needs into primary care which focus either primarily or exclusively on the provision of "education" are unduly simplistic. More fundamental questions about the perceived relevance and opportunities for assessing health needs should be considered if primary care groups are to meet future commissioning challenges.


Optimized synthesis and indium complex formation with the bifunctional chelator NODIA-Me.
The bifunctional chelator NODIA-Me holds promise for radiopharmaceutical development. NODIA-Me is based on the macrocycle TACN (1,4,7-triazacyclononane) and incorporates two additional methylimidazole arms for metal chelation and an acetic acid residue for bioconjugation. The original two step synthesis was less than optimal due to low yields and the requirement of semi-preparative RP-HPLC purifications. Here, the overall yield for the preparation of NODIA-Me was improved two- to five-fold via two synthetic routes using different protection/deprotection techniques. This way, it was possible (1) to prepare of NODIA-Me on multi-gram scale and (2) to avoid time-consuming HPLC purifications. Inspired by recent results with nat/68Ga3+, preliminary studies on the radiolabeling properties and complex formation of NODIA-Me with nat/111In3+ were performed. Quantitative radiochemical yields were achieved at ambient temperature providing molar activities of ∼30 MBq nmol-1, which could be increased to ∼240 MBq nmol-1 at 95 °C. At r.t., pH 5.5 was optimal for 111In-labeling, but quantitative yields were also achieved in the pH range from 5.5 to 8.2, when the reaction temperature was increased. Stability tests of 111In complexes in vitro revealed high kinetic stabilities in serum and ligand challenge experiments, which is a consequence of the formation of rigid 1 : 1 indium chelates as shown by NMR studies in solution. In summary, the new synthetic routes afford the BFC NODIA-Me in high yields and on large scale. Further, 111In complexation experiments broaden the scope of our chelating system for radiopharmaceutical applications.


The enhancement of clinical competence through caring science.
This theoretical research attempts to create a new basis for dialogue between two independent research fields that are connected by an inseparable link. The first, nursing science, is a body of professional knowledge, while the second, caring as an independent body of pure knowledge, conducts basic research with an aspiration towards applicability. This theoretical research uses the guidelines of the Buberian dialogue, which provides new meaning to the concept of clinical competence. The results emphasise the need to adopt abstract knowledge into the nursing field in order to improve the graduate's clinical capabilities. The combination of assessing clinical capability in a judgmental manner together with the dialogical humanistic approach of caring science may create a genuine platform and meeting event as a maturing process, which is intended to promote educational goals, which subsequently receive new meaning, that is, a different type of assessment. However, this assessment cannot be measured since a wide range of ethical moral aspects regarding both the student and the patient will have to be included. Nevertheless, this dialogue between nursing science and caring science can implement evidence on the basis of trust and can be used as a dialogical tool for evaluating clinical skills with the goal of empowering the educational field in nursing. Consequently, this clinical competence is called 'caring maturing means', and the goal is to convert the learning process into a meaningful event with the aim of improvement.


The Impact of Environment and Occupation on the Health and Safety of Active Duty Air Force Members: Database Development and De-Identification.
Preparing data for medical research can be challenging, detail oriented, and time consuming. Transcription errors, missing or nonsensical data, and records not applicable to the study population may hamper progress and, if unaddressed, can lead to erroneous conclusions. In addition, study data may be housed in multiple disparate databases and complex formats. Merging methods may be incomplete to obtain temporally synchronized data elements. We created a comprehensive database to explore the general hypothesis that environmental and occupational factors influence health outcomes and risk-taking behavior among active duty Air Force personnel. Several databases containing demographics, medical records, health survey responses, and safety incident reports were cleaned, validated, and linked to form a comprehensive, relational database. The final step involved removing and transforming personally identifiable information to form a Health Insurance Portability and Accountability Act compliant limited database. Initial data consisted of over 62.8 million records containing 221 variables. When completed, approximately 23.9 million clean and valid records with 214 variables remained. With a clean, robust database, future analysis aims to identify high-risk career fields for targeted interventions or uncover potential protective factors in low-risk career fields.


Perturbation of gene expression of the chromatin remodeling pathway in premature newborns at risk for bronchopulmonary dysplasia.
One-third to one-half of all infants born before the 28th week of gestation develop bronchopulmonary dysplasia (BPD). Inflammatory regulators appear to be involved in the pathogenesis of BPD, possibly beginning in fetal life. To evaluate the feasibility of using expression profiling in umbilical cord tissue to discover molecular signatures for developmental staging and for determining risk of BPD, we conducted a cross-sectional study of infants born at less than 28 weeks of gestation (n = 54). Sections of umbilical cord were obtained at birth from 20 infants who later developed BPD and from 34 of their peers who did not develop BPD. Umbilical cord expression profiles at birth exhibited systematic differences in bioenergetic pathways with respect to gestational age. Infants who subsequently developed BPD had distinct signatures involving chromatin remodeling and histone acetylation pathways, which have previously been implicated in several adult onset lung diseases. These findings are consistent with prior work on inflammatory processes and bioenergetics in prematurity. This study of gene expression of the newborn umbilical cord implicates the chromatin remodeling pathways in those premature infants who subsequently develop BPD. Larger sample sizes will be required to generate prognostic markers from umbilical cord profiles.


The development of anti-immunoglobulin antibodies in rhesus monkeys repeatedly exposed to Schistosoma japonicum.
The development of anti-immunoglobulin (Ig) antibodies in rhesus monkeys repeatedly exposed to Schistosoma japonicum cercariae was studied. Anti-Ig developed in all 8 monkeys exposed 5 times to cercariae of the Formosan strain, while none of 4 monkeys exposed once to the Philippine strain developed such antibodies in the same period. All monkeys developing anti-Ig had specificities for IgA, 6 of 8 for IgM and IgG, and 7 of 8 for rabbit Ig. The persistence of anti-Ig was greatly extended in the monkeys exposed initially to the Formosan strain and then challenged with the Philippine strain. A single monkey exposed once to the Philippine strain developed anti-IgA and anti-rabbit Ig 85 weeks postinfection. No relationship between host reaction to trapped eggs and the development of anti-Ig was discerned. The results suggest that immunization protocols designed for humans be carefully examined for their potential immunopathological side effects.


A simple prognostic scoring system for newly diagnosed cytogenetically normal acute myeloid leukemia: retrospective analysis of 530 patients.
We retrospectively analyzed the data of 337 patients with cytogenetically normal (CN) acute myeloid leukemia (AML), aged ≤ 65 years (training set). A prognostic index score (PIS) was calculated by totaling the score derived from the regression coefficients of each clinical variable, significantly associated with prognosis by multivariate analysis. The variables that were independent prognostic factors for event-free survival (EFS) and overall survival (OS) in the training set were: age ≥ 50 years, secondary AML and white blood cell count (WBC) ≥ 20 × 10(9)/L. The patients of the training set were stratified into three groups: low-, intermediate- and high-risk. The median EFS was 25, 12 and 7 months in the low-, intermediate- and high-risk groups (p < 0.0001), respectively. The median OS was not reached in the low-risk group and was 19 and 10 months in the intermediate- and high-risk groups (p < 0.0001). This PIS was validated in a series of 193 patients with CN-AML. The median EFS was 66, 16, and 3 months (p < 0.0001) and the median OS was 66, 16, and 5 months in the three risk groups, respectively (p < 0.0001). This PIS may be useful for clinical decision-making in CN-AML and may be prospectively integrated with the newest biological markers which at present are not routinely assessed and need prognostic validation.


The relationships between sarcopenic skeletal muscle loss during ageing and macronutrient metabolism, obesity and onset of diabetes.
Skeletal muscle is integral to the metabolism and utilisation of macronutrients; however, substantial muscle loss and morphological changes occur with ageing. These are associated with loss of muscle function and accelerate rapidly from the age of 60 years, leading to the conditions of sarcopenia and frailty. As the relationship between muscle ageing and macronutrient metabolism and utilisation has seen limited research to date, this review focuses on the interactions between skeletal muscle changes during ageing, metabolism and utilisation of fat, carbohydrates and overall energy expenditure.Skeletal muscle contributes less to resting energy expenditure during ageing, potentially contributing to onset of obesity from middle age. Age-related changes to skeletal muscle lead to glucose dysregulation, with consequent reduction in glycaemic control, increased insulin resistance and ultimately onset of type-2 diabetes. Recent studies indicate that high total fat and SFA intake are detrimental to skeletal muscle, while higher intakes of PUFA are protective. Age-associated changes in skeletal muscle may also reduce total fatty acid utilisation.In conclusion, further research is needed to understand the relationships between macronutrient metabolism and utilisation and age-related changes to skeletal muscle. No dietary recommendations exist specifically for skeletal muscle health during ageing, but we advise individuals to follow healthy eating guidelines, by consuming sufficient protein, fruit and vegetables, and limited SFA and to maintain physically active lifestyles. Clinicians responsible for managing type-2 diabetes need to be aware of growing evidence relating age-related skeletal muscle changes to diabetes onset and progression.


Competing ParA structures space bacterial plasmids equally over the nucleoid.
Low copy number plasmids in bacteria require segregation for stable inheritance through cell division. This is often achieved by a parABC locus, comprising an ATPase ParA, DNA-binding protein ParB and a parC region, encoding ParB-binding sites. These minimal components space plasmids equally over the nucleoid, yet the underlying mechanism is not understood. Here we investigate a model where ParA-ATP can dynamically associate to the nucleoid and is hydrolyzed by plasmid-associated ParB, thereby creating nucleoid-bound, self-organizing ParA concentration gradients. We show mathematically that differences between competing ParA concentrations on either side of a plasmid can specify regular plasmid positioning. Such positioning can be achieved regardless of the exact mechanism of plasmid movement, including plasmid diffusion with ParA-mediated immobilization or directed plasmid motion induced by ParB/parC-stimulated ParA structure disassembly. However, we find experimentally that parABC from Escherichia coli plasmid pB171 increases plasmid mobility, inconsistent with diffusion/immobilization. Instead our observations favor directed plasmid motion. Our model predicts less oscillatory ParA dynamics than previously believed, a prediction we verify experimentally. We also show that ParA localization and plasmid positioning depend on the underlying nucleoid morphology, indicating that the chromosomal architecture constrains ParA structure formation. Our directed motion model unifies previously contradictory models for plasmid segregation and provides a robust mechanistic basis for self-organized plasmid spacing that may be widely applicable.


Environmental Inequality and Pollution Advantage among Immigrants in the United States.
Environmental inequality scholarship has paid little attention to the disproportional exposure of immigrants in the United States (U.S.) to unfavorable environmental conditions. This study investigates whether new international migrants in the U.S. are exposed to environmental hazards and how this pattern varies among immigrant subpopulations (e.g., Hispanics, Asian, European). We combine sociodemographic information from the American Community Survey with toxicity-weighted chemical concentrations (Toxics Release Inventory) to model the relationship between toxin exposure and the relative population of recent immigrants across Public Use Microdata Areas (PUMAs, n=2,054) during 2005-2011. Results from spatial panel models show that immigrants tend to be less exposed to toxins, suggesting resilience instead of vulnerability. This pattern was pronounced among immigrants from Europe and Latin America (excluding Mexico). However, our results revealed that Mexican immigrants are disproportionately exposed to environmental hazards in wealthy regions.


Enhanced x-ray irradiation-induced cancer cell damage by gold nanoparticles treated by a new synthesis method of polyethylene glycol modification.
We explored a very interesting gold nanoparticle system-pegylated gold in colloidal solution-and analyzed its uptake by mice colorectal adenocarcinoma CT26 tumor cells and the impact on the cell's response to x-ray irradiation. We found that exposure to polyethylene glycol (PEG) modified ('pegylated') 4.7 ± 2.6 nm gold nanoparticles synthesized by a novel synchrotron-based method enhances the response of CT26 cells to x-ray irradiation. Transmission electron microscopy (TEM) and confocal microscopy revealed that substantial amounts of such nanoparticles are taken up and absorbed by the cells and this conclusion is supported by quantitative induced coupled plasma (ICP) results. Standard tests indicated that the internalized particles are highly biocompatible but strongly enhance the cell damage induced by x-ray irradiation. Synchrotron radiation Fourier transform infrared (SR-FTIR) spectromicroscopy analyzed the chemical aspects of this phenomenon: the appearance of C = O stretching bond spectral features could be used as a marker for cell damage and confirmed the enhancement of the radiation-induced toxicity for cells.


Coactivation of different neurons within an isofrequency lamina of the inferior colliculus elicits enhanced auditory cortical activation.
The phenomenal success of the cochlear implant (CI) is attributed to its ability to provide sufficient temporal and spectral cues for speech understanding. Unfortunately, the CI is ineffective for those without a functional auditory nerve or an implantable cochlea required for CI implementation. As an alternative, our group developed and implanted in deaf patients a new auditory midbrain implant (AMI) to stimulate the central nucleus of the inferior colliculus (ICC). Although the AMI can provide frequency cues, it appears to insufficiently transmit temporal cues for speech understanding. The three-dimensional ICC consists of two-dimensional isofrequency laminae. The single-shank AMI only stimulates one site in any given ICC lamina and does not exhibit enhanced activity (i.e., louder percepts or lower thresholds) for repeated pulses on the same site with intervals <2-5 ms, as occurs for CI pulse or acoustic click stimulation. This enhanced activation, related to short-term temporal integration, is important for tracking the rapid temporal fluctuations of a speech signal. Therefore, we investigated the effects of coactivation of different regions within an ICC lamina on primary auditory cortex activity in ketamine-anesthetized guinea pigs. Interestingly, our findings reveal an enhancement mechanism for integrating converging inputs from an ICC lamina on a fast scale (<6-ms window) that is compromised when stimulating just a single ICC location. Coactivation of two ICC regions also reduces the strong and long-term (>100 ms) suppressive effects induced by repeated stimulation of just a single location. Improving AMI performance may require at least two shanks implanted along the tonotopic gradient of the ICC that enables coactivation of multiple regions along an ICC lamina with the appropriate interstimulus delays.


Comparison of Incidence and Outcomes of Cardiogenic Shock Complicating Posterior (Inferior) Versus Anterior ST-Elevation Myocardial Infarction.
Cardiogenic shock (CS) is a catastrophic consequence of ST-elevation myocardial infarction (STEMI). CS has been reported to be associated less often with inferior wall (IWMI) than anterior wall STEMI (AWMI). We queried the National Inpatient Sample databases from January 2010 to September 2015 to identify all patients aged ≥18 years admitted with AWMI or IWMI. Patients with a concomitant diagnosis of CS were then identified. Complex samples multivariable logistic regression models were used to compare the incidence, management, and in-hospital mortality of CS complicating IWMI versus AWMI. The incidence of CS was lower in IWMI (9.5%) versus AWMI (14.1%), adjusted OR (aOR) 0.84 (95% confidence interval [CI] 0.81 to 0.87). Revascularization rates with either percutaneous coronary intervention or coronary artery bypass grafting were similar in CS complicating IWMI versus AWMI (80.9% vs 80.3%; aOR 1.05; 95% CI 0.97 to 1.14). The reported use of percutaneous mechanical circulatory support devices was lower in patients with CS-IWMI versus CS-AWMI (44.7% vs 61.0%; aOR 0.55; 95% CI 0.52 to 0.59). In-hospital mortality was modestly lower in patients with CS complicating IWMI versus AWMI (30.3% vs 31.9%; aOR, 0.80; 95% CI 0.75 to 0.86). Use of percutaneous mechanical circulatory support was not associated with lower in-hospital mortality in either CS-AWMI (30.0% vs 34.7; aOR 1.04; 95% CI 0.94 to 1.14) or CS-IWMI (31.0% vs 29.8%; aOR 1.20; 95% CI 1.08 to 1.33). In conclusion, the incidence of CS in the contemporary era is lower in patients with IWMI compared with those with AWMI. CS complicating STEMI is associated with higher in-hospital mortality in AWMI versus IWMI, and outcomes were not different with or without percutaneous circulatory support.


Using Targeted Resequencing for Identification of Candidate Genes and SNPs for a QTL Affecting the pH Value of Chicken Meat.
Using targeted genetical genomics, a quantitative trait locus (QTL) affecting the initial postmortem pH value of chicken breast muscle (Pectoralis major) on chromosome 1 (GGA1) recently was fine-mapped. Thirteen genes were present in the QTL region of approximately 1 Mb. In this study, 10 birds that were inferred to be homozygous for either the high (QQ) or low (qq) QTL allele were selected for resequencing. After enrichment for 1 Mb around the QTL region, >500 × coverage for the QTL region in each of the 10 birds was obtained. In total 5056 single-nucleotide polymorphisms (SNPs) were identified for which the genotypes were consistent with one of the QTL genotypes. We used custom tools to identify putative causal mutations in the mapped QTL region from these SNPs. Four nonsynonymous SNPs differentiating the two QTL genotype groups were identified within four local genes (PRDX4, EIF2S3, PCYT1B, and E1BTD2). Although these are likely candidate SNPs to explain the QTL effect, 54 additional consensus SNPs were detected within gene-related regions (untranslated regions, splicing sites CpG island, and promoter regions) for the QQ birds and 71 for the qq birds. These could also play a role explaining the observed QTL effect. The results provide an important step for prioritizing among a large amount of candidate mutations and significantly contribute to the understanding of the genetic mechanisms affecting the initial postmortem pH value of chicken muscle.


Evaluation of neuropsychological functions in patients with Friedreich ataxia before and after cognitive therapy.
Friedreich ataxia (FA) is a neurodegenerative disease characterized by progressive nervous system damage resulting in severe disability. Cognitive functions and mood disorders in FA have been studied little and with conflicting results. The aim of this study was to investigate cognitive functions and mood disorders in FA subjects and the role of cognitive rehabilitation therapy (sequential treatments) performed during a scheduled study period. The executive functions of 24 subjects with FA were evaluated over one year during three separate periods of in-hospital rehabilitation. The neuropsychological evaluations performed before and after cognitive therapy did not reveal differences in the mean test scores of the MMSE, the Rey 15-item Memorization Test for long-term memory, Raven's Colored Progressive Matrices, the Phonemic Verbal Fluency Test, the Symbol Digit Modalities Test, or the Zung scale. The mean scores of the Stroop color-word interference task and of the Rey 15-item Memorization Test for short-term memory were increased at the final evaluation. This finding of long-lasting stability of neuropsychological test scores is noteworthy, as it suggests that one-year cognitive rehabilitation therapy (sequential treatments) may at least contribute to reducing cognitive decline. A cognitive rehabilitation therapy in addition to the conventional neuromotor rehabilitation treatment may improve the management of subjects with FA.


Detection of intracellular bacterial communities in human urinary tract infection.
Urinary tract infections (UTIs) are one of the most common bacterial infections and are predominantly caused by uropathogenic Escherichia coli (UPEC). While UTIs are typically considered extracellular infections, it has been recently demonstrated that UPEC bind to, invade, and replicate within the murine bladder urothelium to form intracellular bacterial communities (IBCs). These IBCs dissociate and bacteria flux out of bladder facet cells, some with filamentous morphology, and ultimately establish quiescent intracellular reservoirs that can seed recurrent infection. This IBC pathogenic cycle has not yet been investigated in humans. In this study we sought to determine whether evidence of an IBC pathway could be found in urine specimens from women with acute UTI. We collected midstream, clean-catch urine specimens from 80 young healthy women with acute uncomplicated cystitis and 20 asymptomatic women with a history of UTI. Investigators were blinded to culture results and clinical history. Samples were analyzed by light microscopy, immunofluorescence, and electron microscopy for evidence of exfoliated IBCs and filamentous bacteria. Evidence of IBCs was found in 14 of 80 (18%) urines from women with UTI. Filamentous bacteria were found in 33 of 80 (41%) urines from women with UTI. None of the 20 urines from the asymptomatic comparative group showed evidence of IBCs or filaments. Filamentous bacteria were present in all 14 of the urines with IBCs compared to 19 (29%) of 66 samples with no evidence of IBCs (p < 0.001). Of 65 urines from patients with E. coli infections, 14 (22%) had evidence of IBCs and 29 (45%) had filamentous bacteria, while none of the gram-positive infections had IBCs or filamentous bacteria. The presence of exfoliated IBCs and filamentous bacteria in the urines of women with acute cystitis suggests that the IBC pathogenic pathway characterized in the murine model may occur in humans. The findings support the occurrence of an intracellular bacterial niche in some women with cystitis that may have important implications for UTI recurrence and treatment.


Vitamin D, calcium and dairy intake, and risk of oesophageal adenocarcinoma and its precursor conditions.
Evidence is accumulating that vitamin D may be protective against carcinogenesis, although exceptions have been observed for some digestive tract neoplasms. The aim of the present study was to explore the association between dietary vitamin D and related nutrients and the risk of oesophageal adenocarcinoma and its precursor conditions, Barrett's oesophagus and reflux oesophagitis. In an all-Ireland case-control study conducted between March 2002 and July 2005, 218 oesophageal adenocarcinoma patients, 212 Barrett's oesophagus patients, 208 reflux oesophagitis patients and 252 population-based controls completed a 101-item FFQ, and provided lifestyle and demographic information. Multiple logistic regression analysis was applied to examine the association between dietary intake and disease risk. Oesophageal adenocarcinoma risk was significantly greater for individuals with the highest compared with the lowest tertile of vitamin D intake (OR 1·99, 95 % CI 1·03, 3·86; P for trend = 0·02). The direct association could not be attributed to a particular vitamin D food source. Vitamin D intake was unrelated to Barrett's oesophagus and reflux oesophagitis risk. No significant associations were observed for Ca or dairy intake and oesophageal adenocarcinoma, Barrett's oesophagus or reflux oesophagitis development. High vitamin D intake may increase oesophageal adenocarcinoma risk but is not related to reflux oesophagitis and Barrett's oesophagus. Ca and dairy product intake did not influence the development of these oesophageal lesions. These findings suggest that there may be population subgroups at an increased risk of oesophageal adenocarcinoma if advice to improve vitamin D intake from foods is implemented. Limited work has been conducted in this area, and further research is required.


Integration of antifouling and antibacterial properties in salt-responsive hydrogels with surface regeneration capacity.
The development of new antimicrobial materials and strategies is of importance for many biomedical and industrial applications. In this work, we report a new strategy to integrate distinct antimicrobial, antifouling, and stimuli-responsive properties into a single hydrogel to realize bacteria resistance, killing, and releasing functions. To achieve this design, we conjugated salt-responsive anti-polyelectrolyte polyDVBAPS (poly(3-(dimethyl(4-vinylbenzyl)ammonio)propyl sulfonate)) with antifouling polyHEAA (poly(N-hydroxyethyl acrylamide)) and antimicrobial AgNPs (silver nanoparticles) to form a hybrid hydrogel of polyDVBAPS-g-polyHEAA@AgNPs, among which polyHEAA functions as a general antifouling background to prevent bacteria adsorption on the surface, AgNPs act as antimicrobial agents to kill bacteria on the surface, and polyDVBAPS uses its unique salt-responsive, anti-polyelectrolyte property to release adherent bacteria from the surface. In this design, polyDVBAPS-g-polyHEAA@AgNPs hydrogels not only effectively resist bacteria attachment and kill the adherent bacteria, but also regenerate the antifouling surface of the hydrogel by releasing the adhered bacteria to keep the surface free from bacteria. The polyDVBAPS-g-polyHEAA@AgNPs hydrogels exhibited high surface resistance to bacteria adsorption (<106 cells per cm2) for up to 4 days, high antibacterial activity by killing ∼99% of attached bacteria of both E. coli and S. aureus, and surface regeneration ability by releasing >96% of adherent live or dead bacteria from the surface upon a simple treatment of 1.0 M NaCl solution for 10 min. Upon the release of AgNPs, AgNPs were reloaded into the hydrogel again to achieve multiple antifouling, bactericidal, and regenerative properties. This work demonstrates a new design for a new multifunctional hydrogel to effectively achieve antimicrobial, antifouling, and surface regeneration properties, making this hydrogel very promising for antimicrobial applications.


Fast analyses and designs of long-period fiber grating devices with cosine-class apodizations by using Fourier mode coupling theory.
This paper presents an analytical approach to fast analyzing and designing long-period fiber grating (LPFG) devices with cosine-class apodizations by using the Fourier mode coupling (FMC) theory. The LPFG devices include LPFGs, LPFG-based in-fiber Mach-Zehnder and Michelson interferometers, which are apodized with the cosine-class windows of cosine, raised-cosine, Hamming, and Blackman. The analytic models (AMs) of the apodized LPFG devices are derived from the FMC theory, which are compared with the preferred transfer matrix (TM) method to confirm their efficiencies and accuracies. The AM-based analyses are achieved and verified to be accurate and efficient enough. The AM-based analysis efficiency is improved over 1318 times versus the TM-based one. Based on the analytic models, an analytic design algorithm is proposed and then applied to designing these LPFG devices, which has the complexity of O(N) and is far faster than the existing design methods.


Breast cancer screening in Tel Aviv.
Optimal breast cancer screening includes both physical examination and mammography. In anticipation of the addition of routine mammographic screening to Israel's 25-year-old early breast cancer detection program, we examined the demographic characteristics of almost one thousand women attending a breast cancer screening examination in Tel Aviv for the first time. The specific objective of the survey was to see whether women attending screening were those who stood a good chance of benefiting from it. Only half the women were aged 40 or older, and there was a preponderance of women of Western origin. Almost half had a breast-related complaint at the time of the visit. Targeted public education and appropriate administrative measures are necessary to ensure that women who can benefit from screening attend screening clinics and that clinics are not filled to capacity by women needing diagnostic evaluation and followup rather than routine screening. Tel Aviv general practitioners appeared to be aware of the advantages of breast cancer screening.


Isolation and characterization of polycyclic aromatic hydrocarbon-degrading Mycobacterium isolates from soil.
Bioremediation of soils contaminated with wood preservatives containing polycyclic aromatic hydrocarbons (PAHs) is desired because of their toxic, mutagenic, and carcinogenic properties. Creosote wood preservative-contaminated soils at the Champion International Superfund Site in Libby, Montana currently undergo bioremediation in a prepared-bed land treatment unit (LTU) process. Microbes isolated from these LTU soils rapidly mineralized the (14)C-labeled PAH pyrene in the LTU soil. Gram staining, electron microscopy, and 16S rDNA-sequencing revealed that three of these bacteria, JLS, KMS, and MCS, were Mycobacterium strains. The phylogeny of the 16S rDNA showed that they were distinct from other Mycobacterium isolates with PAH-degrading activities. Catalase and superoxide dismutase (SOD) isozyme profiles confirmed that each isolate was distinct from each other and from the PAH-degrading mycobacterium, Mycobacterium vanbaalenii sp. nov, isolated from a petroleum-contaminated soil. We find that dioxygenase genes nidA and nidB are present in each of the Libby Mycobacterium isolates and are adjacent to each other in the sequence nidB-nidA, an order that is unique to the PAH-degrading mycobacteria.


Guidelines for perioperative care in elective rectal/pelvic surgery: Enhanced Recovery After Surgery (ERAS®) Society recommendations.
This review aims to present a consensus for optimal perioperative care in rectal/pelvic surgery, and to provide graded recommendations for items for an evidenced-based enhanced recovery protocol. Studies were selected with particular attention paid to meta-analyses, randomized controlled trials and large prospective cohorts. For each item of the perioperative treatment pathway, available English-language literature was examined, reviewed and graded. A consensus recommendation was reached after critical appraisal of the literature by the group. For most of the protocol items, recommendations are based on good-quality trials or meta-analyses of good-quality trials (evidence grade: high or moderate). Based on the evidence available for each item of the multimodal perioperative care pathway, the Enhanced Recovery After Surgery (ERAS) Society, European Society for Clinical Nutrition and Metabolism (ESPEN) and International Association for Surgical Metabolism and Nutrition (IASMEN) present a comprehensive evidence-based consensus review of perioperative care for rectal surgery.


Maternal Deprivation Influences Pup Ultrasonic Vocalizations of C57BL/6J Mice.
Maternal deprivation (MD) is frequently used as an early life stress model in rodents to investigate behavioral and neurological responses under stressful conditions. However, the effect of MD on the early postnatal development of rodents, which is when multiple neural systems become established, is rarely investigated due to methodological limitations. Ultrasonic vocalizations (USVs) are one of the few responses produced by neonatal rodents that can be quantitatively analyzed, and the quantification of USVs is regarded as a novel approach to investigate possible alterations in the neurobehavioral and emotional development of infant rodents under stress. To investigate the effect of MD on pup mice, we subjected C57BL/6J mice to MD and recorded the USVs of pups on postnatal days 1, 3, 7, 8, and 14. To determine whether the effect of MD on USVs was acute or cumulative, pre- and post-separation USV groups were included; sex differences in pup USV emission were also investigated. Our results suggest that (i) USV activity was high on postnatal days 3-8; (ii) the MD effect on USVs was acute, and a cumulative effect was not found; (iii) the MD mice vocalized more and longer than the controls at a lower frequency, and the effect was closely related to age; and (iv) female pups were more susceptible than males to the effect of MD on USV number and duration between postnatal days 3-8.


Role of Ets-1 in erythroid differentiation.
Members of the Ets gene family are known to be expressed in the hematopoietic tissue and some of them play a pivotal role in normal hematopoietic cell development. Ets-1 gene expression was analyzed in Friend Leukemia Cells (FLC) induced to erythroid differentiation by DMSO. We show that the level of Ets-1 protein and its binding activity decreases in FLC along erythroid differentiation of primary human progenitors. The same behavior was observed during normal erythroid differentiation. Moreover, FLC constitutively expressing Ets-1 show a decrease in TfR gene expression, globin mRNA and hemoglobin synthesis. These data indicate that a decrease in Ets-1 binding activity is required for a normal erythroid maturation and that a deregulated expression of this transcription factor may interfere with terminal erythroid differentiation.


Molecular epidemiology of norovirus in Edinburgh healthcare facilities, Scotland 2007-2011.
Norovirus (NoV) is a leading cause of outbreaks of gastroenteritis worldwide, and a major burden for healthcare facilities. This study investigated the NoV genotypes responsible for outbreaks in Edinburgh healthcare facilities between June 2008 and July 2011, and studied their temporal distribution to enable a better understanding of the epidemiology of the outbreaks. A total of 287 samples positive for NoV genogroup II (GII) RNA by reverse transcription-polymerase chain reaction (RT-PCR) during routine diagnostic testing were investigated. Nested RT-PCR (nRT-PCR) and sequencing was used to genotype the NoV strains. Overall, a total of 69 NoV strains belonging to six different genoclusters (GII.1, GII.2, GII.3, GII.4, GII.6, GII.13) were detected. The predominant genotype was GII.4 that included four variants, GII.4 2006a, GII.4 2006b, GII.4 2007 and GII.4 2010. Importantly, increases in NoV activity coincided with the emergence of new GII.4 strains, highlighting the need for an active surveillance system to allow the rapid identification of new strains.


Antipeptide antibodies directed to the C-terminal part of ammodytoxin A react with the PLA2 subunit of crotoxin and neutralize its pharmacological activity.
Crotoxin and ammodytoxin A are snake venom neurotoxic phospholipases A2. Polyclonal antibodies against three synthetic peptides selected from the C-terminal part of the primary structure of ammodytoxin A were tested by ELISA for their interaction with crotoxin and its subunits, CA and CB. All three antipeptide antibodies reacted specifically with corresponding parts of ammodytoxin A and CB, either native or reduced. Conversely, polyclonal antibodies produced against ammodytoxin A and CB reacted strongly with all three peptides, suggesting that they constitute at least a part of natural epitopes in both proteins. All antipeptide antibodies reacted also with the corresponding peptides derived from CB by cyanogen bromide cleavage. The biological activity of the immune complexes was tested. No significant change in the enzymatic activity of CB, ammodytoxin A or crotoxin was observed with any of the three antipeptide antibodies. These antibodies were, however, able to protect mice against the lethal potency of CB and to prolong survival time of mice injected with crotoxin. These antipeptide antibodies were assayed in vitro for their protective effect against the action of CB or crotoxin on synaptosomes from Torpedo marmorata electric organ. They partly inhibited the acetylcholine release induced by both proteins. These results indicate that the C-terminal part of CB is likely to be involved in the pharmacological action of crotoxin.


[The Cannulation of the Arteriovenous Fistula in the Presence of a Stent: Precautions, Risks, and Possibilities].
A proper management and tailored interventions represented two fundamental steps to ensure a long-term use of the arteriovenous fistula (AVF). AVF failure can be attributed to various factors, with stenosis being the most common cause. Different techniques are employed for treating complications, but percutaneous endovascular procedures are the most widely used. In addition to angioplasty (PTA), the possibility of utilizing stents, particularly stent grafts (SG), has further improved outcomes. However, the insertion of these devices involves commitment to a segment of the vessel, which may vary in length, making the indication necessitate a careful evaluation. The positioning of a stent graft indeed limits the space for needle insertion, and on the other hand, the cannulation of the device is considered off-label according to technical specification. This work addresses the issue of puncturing these devices. Alongside a rapid overview, we describe a clinical case of continuous cannulation of a multiply stented AVF, for over 9 years, which opens up the discussion about the possibility of long-term cannulation through proper planning.


Is population flow an unintended consequence of alcohol management plans?
The aim of this study was to gauge whether, and to what extent, population flow occurred as a result of the implementation of alcohol management plans in Indigenous communities. Alcohol management plans involving carriage limits and dry places were introduced into 15 Queensland Indigenous communities between 2002-2004. Controls on alcohol availability were further tightened between 2008-2010, seeing the closure of eight mainly remote community taverns/canteens. A retrospective observational study was undertaken using data from the Queensland Injury Surveillance Unit. Population flow was measured by changing patterns of alcohol-related injuries in a mining region near dry Indigenous communities following the introduction of alcohol management plans and a control mining region distant from Indigenous communities with alcohol management plans. Data were analysed using descriptive and inferential statistics. Logistic regression was used for the comparison of the characteristics between the emergency department presentations. The rates of alcohol-related injury presentations per 1000/population were calculated and age-standardised to the Australian population. Between the five-year periods 2003-2007 and 2008-2012, alcohol-related injury presentations to the Mount Isa emergency department trebled from an age-adjusted average annual rate of 9·5/1000 in the region's population to 27·1/1000 population. In the control region, alcohol-related emergency department injury presentations did not increase to the same degree with age-adjusted average annual rates of 1·42/1000 and 2·21/1000, respectively. The 10-year pattern of emergency department presentations for alcohol-related injuries increased significantly in the Mount Isa region compared with the control region. Further research should investigate the impacts of population flow related to Indigenous community alcohol management plans. Although initiatives such as alcohol management plans have been implemented to reduce alcohol use and related consequences in Indigenous communities, there needs to be a greater consideration of the impact of these policies in nearby towns in the future.


A tool set to map allosteric networks through the NMR chemical shift covariance analysis.
Allostery is an essential regulatory mechanism of biological function. Allosteric sites are also pharmacologically relevant as they are often targeted with higher selectivity than orthosteric sites. However, a comprehensive map of allosteric sites poses experimental challenges because allostery is driven not only by structural changes, but also by modulations in dynamics that typically remain elusive to classical structure determination methods. An avenue to overcome these challenges is provided by the NMR chemical shift covariance analysis (CHESCA), as chemical shifts are exquisitely sensitive to redistributions in dynamic conformational ensembles. Here, we propose a set of complementary CHESCA algorithms designed to reliably detect allosteric networks with minimal occurrences of false positives or negatives. The proposed CHESCA toolset was tested for two allosteric proteins (PKA and EPAC) and is expected to complement traditional comparative structural analyses in the comprehensive identification of functionally relevant allosteric sites, including those in otherwise elusive partially unstructured regions.


PML suppresses oncogenic transformation of NIH/3T3 cells by activated neu.
The chromosomal translocation t(15;17)(q22;q12) is a consistent feature of acute promyelocytic leukemia (APL) that results in the disruption of genes for the zinc finger transcription factor PML and the retinoic acid receptor alpha (RAR alpha). We have previously shown that PML is a growth suppressor and is able to suppress transformation of NIH/3T3 by activated neu oncogene. In the study presented here, the full-length PML cDNA was transfected into B104-1-1 cells (NIH/3T3 cells transformed by the activated neu oncogene) by retrovirally mediated gene transfer. We found that expression of PML could reverse phenotypes of B104-1-1 including morphology, contact-limiting properties, and growth rate in both transient-expression and stable transfectants. We also demonstrated that PML is able to suppress clonogenicity of B104-1-1 in soft agar assay and tumorigenicity in nude mice. These results strongly support our previous finding that PML is a transformation or growth suppressor. Our results further demonstrate that expression of PML in B104-1-1 cells has little effect on cell cycle distribution. Western blot analysis demonstrated that suppression of neu expression in B104-1-1 by PML was insignificant in the transient transfection experiment but significant in the PML stable transfectants. This study suggests that PML may suppress neu expression and block signaling events associated with activated neu. This study supports our hypothesis that disruption of the normal function of PML, a growth or transformation suppressor, is a critical event in APL leukomogenesis.


A matrix-located processing peptidase of plant mitochondria.
Nuclear-encoded mitochondrial precursor proteins are proteolytically processed inside the mitochondrion after import. The general mitochondrial processing activity in plant mitochondria has been shown to be integrated into the cytochrome bc1 complex of the respiratory chain. Here we investigate the occurrence of an additional, matrix-located processing activity by incubation of the precursors of the soybean mitochondrial proteins, alternative oxidase, the FAd subunit of the ATP synthetase and the tobacco F1 beta subunit of the ATP synthase, with the membrane and soluble components of mitochondria isolated from soybean cotyledons and spinach leaves. A matrix-located peptidase specifically processed the precursors to the predicted mature form in a reaction which was sensitive to orthophenanthroline, a characteristic inhibitor of mitochondrial processing peptidase (MPP). The specificity of the matrix peptidase was illustrated by the inhibition of processing of the alternative oxidase precursor in both soybean and spinach matrix extracts upon altering a single amino acid residue in the targeting presequence (-2 Arg to Gly). Additionally, there was no evidence for general proteolysis of precursor proteins incubated with the matrix. The purity of the matrix fractions was ascertained by spectrophotometric and immunological analyses. The results demonstrate that there is a specific processing activity in the matrix of soybean and spinach in addition to the previously well characterized membrane-bound MPP integrated into the cytochrome bcl complex of the respiratory chain.


Performance on verbal and low-verbal false belief tasks: evidence from children with Williams syndrome.
Previous studies that have investigated the relationship between performance on theory of mind (ToM) tasks and verbal abilities in individuals with Williams syndrome (WS) have reported contradictory findings with some showing that language abilities aid performance on ToM tasks while others have found that participants with WS fail these tasks because of their verbal demands. The current study investigated this relationship again comparing performance on a classical change-location task to two newly developed low-verbal tasks, one change-location task and one unexpected content task. Thirty children with WS (aged 5-17;01 years) and 30 typically developing (TD) children (aged between 2;10 years and 9;09 years), who were matched for vocabulary comprehension scores were included in the study. Although performance in the WS group was significantly poorer compared to the TD group on all three tasks, performance was not predicted by their receptive vocabulary or grammatical ability scores. In addition, ToM abilities in both groups depended on the cognitive demands of the task at hand. This finding shows that performance on ToM tasks in WS is not necessarily hindered by their delayed language abilities but rather by the task administered. This could potentially affect the diagnosis of developmental disorders, such as Autism Spectrum Disorders, and comparison of ToM abilities across developmental disorders. Readers of this article should be able to (1) describe the current state of theory of mind research in Williams syndrome, (2) identify which cognitive abilities might explain performance on theory of mind tasks in both typically developing children and in children with Williams syndrome, and (3) interpret the importance of task demands when assessing children's theory of mind abilities.


Motivational Pathways to STEM Career Choices: Using Expectancy-Value Perspective to Understand Individual and Gender Differences in STEM Fields.
The United States has made a significant effort and investment in STEM education, yet the size and the composition of the STEM workforce continues to fail to meet demand. It is thus important to understand the barriers and factors that influence individual educational and career choices. In this article, we conduct a literature review of the current knowledge surrounding individual and gender differences in STEM educational and career choices, using expectancy-value theory as a guiding framework. The overarching goal of this paper is to provide both a well-defined theoretical framework and complementary empirical evidence for linking specific sociocultural, contextual, biological, and psychological factors to individual and gender differences in STEM interests and choices. Knowledge gained through this review will eventually guide future research and interventions designed to enhance individual motivation and capacity to pursue STEM careers, particularly for females who are interested in STEM but may be constrained by misinformation or stereotypes.


Behavioral Health Coverage In The Individual Market Increased After ACA Parity Requirements.
As of January 1, 2014, the Affordable Care Act designated mental health and substance use services as an essential health benefit in Marketplace plans and extended parity protections to the individual and small-group markets. We analyzed documents for seventy-eight individual and small-group plans in 2014 (after parity provisions took effect) and sixty comparison plans in 2013 (the year before parity provisions took effect) to understand the degree to which coverage for mental health and substance use care improved relative to medical/surgical benefits. The results suggest that plan issuers did what the provisions required them to do. Although in 2013 a lower proportion of plans covered mental health or substance use care, compared to medical/surgical care, in 2014 the proportions were the same. If essential health benefit requirements were to be removed and mental health and substance use coverage becomes similar to that in 2013, as many as 20 percent of the plans in our sample would not cover these conditions. To determine whether increases in behavioral health coverage will result in improved access to behavioral health services requires complementary data on the size of provider networks and use of services.


Surface waves over periodically-spaced rectangular strips.
Frequency- and time-domain measurements have been made on surfaces composed from parallel periodically-spaced rectangular strips (width: 0.0126 m, height: 0.0253 m) on an acoustically hard surface. The edge-to-edge spacing between the strips has been varied between 0.003 and 0.06 m. Frequency domain predictions show that when the spacing is small, these surfaces may be regarded as locally reacting rigid-framed hard-backed slit-pore layers with an effective depth slightly larger than the strip height, but when the spacing is comparable to the strip height or greater, the surfaces behave as periodically rough surfaces. Both frequency- and time-domain results show that surface waves of comparable magnitudes are created over the range of strip spacings studied but the frequency content of the acoustically induced surface waves decreases as the mean spacing is increased. It is found that surface wave dispersion is better predicted by the deduced effective impedance spectrum than by the slit-pore layer impedance model.


Differential gene expression in anatomical compartments of the human eye.
The human eye is composed of multiple compartments, diverse in form, function, and embryologic origin, that work in concert to provide us with our sense of sight. We set out to systematically characterize the global gene expression patterns that specify the distinctive characteristics of the various eye compartments. We used DNA microarrays representing approximately 30,000 human genes to analyze gene expression in the cornea, lens, iris, ciliary body, retina, and optic nerve. The distinctive patterns of expression in each compartment could be interpreted in relation to the physiology and cellular composition of each tissue. Notably, the sets of genes selectively expressed in the retina and in the lens were particularly large and diverse. Genes with roles in immune defense, particularly complement components, were expressed at especially high levels in the anterior segment tissues. We also found consistent differences between the gene expression patterns of the macula and peripheral retina, paralleling the differences in cell layer densities between these regions. Based on the hypothesis that genes responsible for diseases that affect a particular eye compartment are likely to be selectively expressed in that compartment, we compared our gene expression signatures with genetic mapping studies to identify candidate genes for diseases affecting the cornea, lens, and retina. Through genome-scale gene expression profiling, we were able to discover distinct gene expression 'signatures' for each eye compartment and identified candidate disease genes that can serve as a reference database for investigating the physiology and pathophysiology of the eye.


Diets benefiting health and climate relate to longevity in northern Sweden.
Diets combining adequate nutritional quality and low climate impact are highly needed for human and planet health. We aimed to 1) evaluate nutrient density indexes' ability to predict mortality, and 2) assess the effects of diets varying in nutrient density and climate impact on total mortality. Dietary data from 49,124 women and 47,651 men aged 35-65 y in the population-based prospective study Västerbotten Intervention Programme (Sweden) were used. Greenhouse gas emissions (GHGEs) were estimated using data from life cycle assessments. Fifteen variants of nutrient density indexes were evaluated and the index that best predicted mortality was used to estimate participants' nutrient density. GHGEs and nutrient density were adjusted for energy intakes. Total mortality risk was estimated by Cox proportional hazards models for 4 groups of women and men, respectively, i.e., higher nutrient density, lower climate impact (HNutr/LClim); higher nutrient density, higher climate impact (HNutr/HClim); lower nutrient density, lower climate impact (LNutr/LClim); and lower nutrient density, higher climate impact (LNutr/HClim-reference group). NRF11.3, a Sweden-adapted variant of the Nutrient Rich Foods index, was identified to have the best ability to predict mortality in the study population. Median follow-up times for women and men were 16.0 and 14.7 y, respectively. For women a significantly lower mortality risk was found for HNutr/LClim (HR: 0.87; 95% CI: 0.79, 0.96; P = 0.008) and HNutr/HClim (HR: 0.87; 95% CI: 0.78, 0.97; P = 0.011) than for LNutr/HClim. Among men LNutr/LClim had a significantly higher mortality risk (HR: 1.10; 95% CI: 1.01, 1.21; P = 0.033) than LNutr/HClim. Diets beneficial for both health and climate are feasible and associated with lower mortality risk in women. Further studies are needed to understand how men may transition into diets that are more sustainable from a combined health and climate perspective.


Molecular biology of hepatitis B virus infection.
Human hepatitis B virus (HBV) is the prototype of a family of small DNA viruses that productively infect hepatocytes, the major cell of the liver, and replicate by reverse transcription of a terminally redundant viral RNA, the pregenome. Upon infection, the circular, partially double-stranded virion DNA is converted in the nucleus to a covalently closed circular DNA (cccDNA) that assembles into a minichromosome, the template for viral mRNA synthesis. Infection of hepatocytes is non-cytopathic. Infection of the liver may be either transient (<6 months) or chronic and lifelong, depending on the ability of the host immune response to clear the infection. Chronic infections can cause immune-mediated liver damage progressing to cirrhosis and hepatocellular carcinoma (HCC). The mechanisms of carcinogenesis are unclear. Antiviral therapies with nucleoside analog inhibitors of viral DNA synthesis delay sequelae, but cannot cure HBV infections due to the persistence of cccDNA in hepatocytes.


Self-management for people with multiple sclerosis: report from the first international consensus conference, november 15, 2010.
People with multiple sclerosis (MS) must manage the day-to-day effects of the disease on their lives. Self-management interventions may be helpful in this challenge. An international, multidisciplinary consensus conference was held on November 15, 2010, by the University of Washington's Rehabilitation Research and Training Center for Multiple Sclerosis (MS RRTC), with funding from the Consortium of Multiple Sclerosis Centers (CMSC) and the National Institute on Disability and Rehabilitation Research (NIDRR), to discuss the concept of self-management for people with MS. The specific goals of the consensus conference were as follows: 1) review the current research on self-management and related issues in chronic disability and specifically in MS; 2) review optimal research methodologies, outcome measurement tools, program planning frameworks, and dissemination strategies for self-management research; and 3) establish recommendations on the next steps necessary to develop, adapt, and test self-management interventions for people with MS. The consensus conference and this document are the initial steps toward achieving the stated goals. Participants in the consensus conference concluded that it is necessary to: 1) define an empirically based conceptual model of self-management for people with MS; 2) establish reliable and valid self-management outcome measures; 3) use best practices to validate models of self-management interventions; and 4) plan dissemination and knowledge translation of interventions once their effectiveness is established.


Darunavir-based dual therapy in HIV experienced patients.
We assessed the virological response of DRV/r-based dual therapy in drug-experienced patients included in the Italian antiretroviral resistance database (ARCA). Patients included in the study were treated with DRV/r in association with raltegravir (RAL), etravirine (ETV) or maraviroc (MAR) following treatment failure(s) and with a resistance test and at least one follow-up visit available. Observation was censored at last visit under dual therapy and survival analysis and proportional hazard models were used, taking virological failure (confirmed >50 c/mL HIV-RNA) as the end-point. Of the total 221 patients included, 149 (67.4%) started DRV/r with RAL, 45 (20.4%) with ETV, 27 (12.2%) with MAR. Patients characteristics at the start of dual regimen were as follows: mean number of previous regimens, nine (IQR: 5-13); non-B subtype, 17 (7.7%); median CD4 count, 347 (IQR: 246-544); undetectable viral load, 74 (33.5%). Full DRV/r resistance was detected in one (0.5%, HIV-DB interpretation system), 13 (5.9%, ANRS) and 17 patients (7.7%, Rega). 69 virological failures (31.2%) were observed during follow-up. At survival analysis, the overall proportion of failure was 29.2% at one year and 33.8% at two years. The proportion of failure was lower in patients starting with undetectable versus detectable viral load (13.3% and 25.2% versus 37.4% and 38.8% at one and two years, respectively, p=0.001 for both analyses) and in patients treated with DRV 600 BID versus 800 QD (HR: 0, 56; 95% CI 0.31-0.99; p<0.05). By regimen, patients treated with DRV/r-RAL showed a non-significant lower proportion of failure (27.7% at one year, 32.0% at two years) if compared with DRV/r-MAR (35.9%, 47.1%) and DRV/r-ETV (34.1%, 34.1% at one and two years). In the adjusted proportional model, no significant difference among the three regimens was detected. A significant lower risk of failure was associated with higher overall GSS (HIV-DB HR: 0.53, 95% CI 0.32-0.88, p=0.014; Rega 0.60, 0.40-0.88, p<0.01; ANRS 0.55, 0.34-0.90, p=0.017), while a higher risk of failure was associated with detectable HIV-RNA (3.02, 1.70-5.72, p<0.001). Among experienced patients, the best candidates to dual-therapy regimens including DRV/r are those with undetectable viral load and higher GSS. The association with RAL is the most commonly used but no clear advantage with respect to ETV or MAR was observed in our dataset, possibly due to the limited sample size.


Ischemia-hyperpnea test is useful to detect patients with fibromyalgia syndrome.
To demonstrate the prevalence of neuromuscular hyperexcitability in Fibromyalgia Syndrome (FMS) by electromyography ischaemia-hyperpnea test (IHT) and its correlation with clinical and clinimetric parameters. One hundred and forty-five FMS patients underwent IHT to evaluate neuromuscular hyperexcitability and were evaluated for pain (numeric Rating Scale and Regional Pain Scale), tenderness (tender points), disability [Fibromyalgia Impact Questionnaire (FIQ), Health Assessment Questionnaire (HAQ)], quality of life (QOL) [Short Form 36 (SF36)], mood [Hospital Anxiety and Depression Scale (HADS)], sleep [numeric rating scale (NRS)], and fatigue [Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT)]. Of the 145 patients, 95 were tested positive by IHT, and 33 and 17 patients were negative and borderline, respectively. By comparing the three groups, IHT positive patients had lower age and lower SF36 vitality (V), social activities (SA), and mental summary index (MSI) than negative patients (p<0.05). By comparing positive versus negative patients and by comparing positive and borderline patients versus negative patients, it was found that FACIT was higher, whereas age, SF36 V, SA, mental health (MH), and MSI were lower (p<0.05). FMS patients present a high prevalence of neuromuscular hyperexcitability, as assessed by IHT. IHT positive patients have poor QOL and higher fatigue than IHT negative patients. Thus, IHT positivity could identify FMS patients with a more severe disease.


Cryogenic methods for the spectroscopy of large, biomolecular ions.
Determining the conformation of biological molecules is key for understanding their function. The recent combination of mass spectrometry, cryogenic ion traps, and laser spectroscopy is providing new methods to interrogate individual conformations of peptides and proteins that have advantages over classical techniques of structure determination. This chapter provides an overview of these new state-of-the-art methods and illustrates several specific applications. After reviewing the fundamentals of ion production, trapping, cooling, and spectroscopic detection, we review how different combinations of these techniques have been implemented in various laboratories around the world. We then focus on applications of cryogenic ion spectroscopy from two specific laboratories to illustrate the potential of this general approach. Finally, we outline ways in which these powerful new techniques could be further improved.


Emerging Biofabrication Techniques: A Review on Natural Polymers for Biomedical Applications.
Natural polymers have been widely used for biomedical applications in recent decades. They offer the advantages of resembling the extracellular matrix of native tissues and retaining biochemical cues and properties necessary to enhance their biocompatibility, so they usually improve the cellular attachment and behavior and avoid immunological reactions. Moreover, they offer a rapid degradability through natural enzymatic or chemical processes. However, natural polymers present poor mechanical strength, which frequently makes the manipulation processes difficult. Recent advances in biofabrication, 3D printing, microfluidics, and cell-electrospinning allow the manufacturing of complex natural polymer matrixes with biophysical and structural properties similar to those of the extracellular matrix. In addition, these techniques offer the possibility of incorporating different cell lines into the fabrication process, a revolutionary strategy broadly explored in recent years to produce cell-laden scaffolds that can better mimic the properties of functional tissues. In this review, the use of 3D printing, microfluidics, and electrospinning approaches has been extensively investigated for the biofabrication of naturally derived polymer scaffolds with encapsulated cells intended for biomedical applications (e.g., cell therapies, bone and dental grafts, cardiovascular or musculoskeletal tissue regeneration, and wound healing).


Reprint of: Recent advances in cytomegalovirus: an update on pharmacologic and cellular therapies.
The 2015 Tandem American Society for Blood and Marrow Transplantation/Center for International Blood and Marrow Transplant Meetings provide an opportunity to review the current status and future perspectives on therapy for cytomegalovirus (CMV) infection in the setting of hematopoietic stem cell transplantation (HSCT). After many years during which we have seen few tangible advances in terms of new antiviral drugs, we are now experiencing an exciting period of late-stage drug development, characterized by a series of phase III trials incorporating a variety of novel agents. These trials have the potential to shift our current standard therapeutic strategies, which generally involve pre-emptive therapy based on sensitive molecular surveillance, towards the prophylactic approaches we see more generally with other herpes viruses such as herpes simplex and varicella zoster. This comes at a time when the promise of extensive preclinical research has been translated into encouraging clinical responses with several cellular immunotherapy strategies, which have also been moved towards definitive late-stage clinical trials. How these approaches will be integrated with the new wave of antiviral drugs remains open to conjecture. Although most of the focus of these cellular immunotherapy studies has been on adaptive immunity, and in particular T cells, an increasing awareness of the possible role of other cellular subsets in controlling CMV infection has developed. In particular, the role of natural killer (NK) cells is being revisited, along with that of γδ T cells. Depletion of NK cells in mice results in higher titers of murine CMV in tissues and increased mortality, whereas NK cell deficiency in humans has been linked to severe CMV disease. We will review recent progress in these areas.


Coordination of CuB in reduced and CO-liganded states of cytochrome bo3 from Escherichia coli. Is chloride ion a cofactor?
The ubiquinol oxidase cytochrome bo3 from Escherichia coli is one of the respiratory heme-copper oxidases which catalyze the reduction of O2 to water linked to translocation of protons across the bacterial or mitochondrial membrane. We have studied the structure of the CuB site in the binuclear heme-copper center of O2 reduction by EXAFS spectroscopy in the fully reduced state of this enzyme, as well as in the reduced CO-liganded states where CO is bound either to the heme iron or to CuB. We find that, in the reduced enzyme, CuB is coordinated by one weakly bound and two strongly bound histidine imidazoles at Cu-N distances of 2.10 and 1.92 A, respectively, and that an additional feature at 2.54 A is due to a highly ordered water molecule that might be weakly associated with the copper. Unexpectedly, the binding of CO to heme iron is found to result in a major conformational change at CuB, which now binds only two equidistant histidine imidazoles at 1.95 A and a chloride ion at 2. 25 A, with elimination of the water molecule and one of the histidines. Attempts to remove the chloride from the enzyme by extensive dialysis did not change this finding, nor did substitution of chloride with bromide. Photolysis of CO bound to the heme iron is known to cause the CO to bind to CuB in a very fast reaction and to remain bound to CuB at low temperatures. In this state, we indeed find the CO to be bound to CuB at a Cu-C distance of 1.85 A, with chloride still bound at 2.25 A and the two histidine imidazoles at a Cu-N distance of 2.01 A. These results suggest that reduction of the binuclear site weakens the bond between CuB and one of its three histidine imidazole ligands, and that binding of CO to the reduced binuclear site causes a major structural change in CuB in which one histidine ligand is lost and replaced by a chloride ion. Whether chloride is a cofactor in this enzyme is discussed.


Factor and reliability analysis of a brief scale to measure motivation to change lifestyle for dementia risk reduction in the UK: the MOCHAD-10.
Modifying lifestyle risk factors for dementia is a public health priority. Motivation for change is integral to the modification of health-related risk behaviours. This study investigates the psychometric properties of the previously validated tool entitled 'Motivation to Change Lifestyle and Health Behaviours for Dementia Risk Reduction Scale' (MCLHB-DRR) for use in the UK. A sample of 3,948 individuals aged 50 and over completed the 27-item MCLHB-DRR online. The psychometric properties of the scale were explored via Exploratory Principal Axis Factoring (PAF) with Oblimin rotation. Confirmatory Factor Analysis (CFA) was used to confirm the factor structure using chi-square (χ2), the goodness-of-fit index (GFI), the comparative fit index (CFI), the root mean square error of approximation (RMSEA) and Root Mean Square Residual (RMR) as fit indices to evaluate the model fit. Internal consistency (Cronbach α) was measured for the final scale version. Exploratory Factor Analysis (EFA) resulted in a parsimonious 10-item, two-factor structure (5 items each, factor loadings > 0.3) that explained 52.83% of total variance. Based on the Pattern Matrix, Factor 1 was labelled "Positive Cues to Action" and Factor 2 was labelled "Negative Cues to Action". After addressing some errors in covariances, CFA showed a good fit where all fit indices were larger than 0.90 (GFI = 0.968, CFI = 0.938) and smaller than 0.08 (RMSEA = 0.072, RMR = 0.041). The standardized coefficients of Factor 1 and Factor 2 ranged from 0.30 to 0.73 and were all statistically significant (p < 0.001). The final scale showed moderate to high reliability scores (Factor 1 α = 0.809; Factor 2 α = 0.701; Overall α = 0.785). The new MOCHAD-10 (Motivation to Change Behaviour for Dementia Risk Reduction Scale) is a short, reliable and robust two-factor, 10-item clinical tool for use in preventative health care and research to evaluate motivation to change lifestyle for dementia risk reduction.


Divided attention and the matching law: sample duration affects sensitivity to reinforcement allocation.
Previously, we have shown that changes in pigeons' divided attention performance resulting from changes in relative reinforcement are well described by the generalized matching law. In the present experiment, we examined whether sensitivity of performance to variations in relative reinforcement would be dependent upon sample duration. Pigeons responded on a delayed matching-to-sample procedure with compound samples (color + line orientation) and element comparison stimuli (two colors or two line orientations). Relative reinforcement for accurate matches on the two types of comparison trials varied across conditions. Sample duration was short (i.e., 0.75 sec) for half of the trials in a session and longer (i.e., 2.25 sec) for the other half. Sensitivity of accuracy to changes in relative reinforcement was greater with the longer sample than with the shorter sample, suggesting that differential reinforcement alters the allocation of attending to the elements of compound stimuli. Continued examination of the applicability of well-established theories of goal-directed behavior to the allocation of attention may provide further insights into what is variously referred to as goal-directed, voluntary, endogenous, or top-down control of attention.


Transcranial motor evoked potential waveform changes in corrective fusion for adolescent idiopathic scoliosis.
OBJECTIVE Corrective surgery for spinal deformities can lead to neurological complications. Several reports have described spinal cord monitoring in surgery for spinal deformity, but only a few have included patients younger than 20 years with adolescent idiopathic scoliosis (AIS). The goal of this study was to evaluate the characteristics of cases with intraoperative transcranial motor evoked potential (Tc-MEP) waveform deterioration during posterior corrective fusion for AIS. METHODS A prospective database was reviewed, comprising 68 patients with AIS who were treated with posterior corrective fusion in a prospective database. A total of 864 muscles in the lower extremities were chosen for monitoring, and acceptable baseline responses were obtained from 819 muscles (95%). Intraoperative Tc-MEP waveform deterioration was defined as a decrease in intraoperative amplitude of ≥ 70% of the control waveform. Age, Cobb angle, flexibility, operative time, estimated blood loss (EBL), intraoperative body temperature, blood pressure, number of levels fused, and correction rate were examined in patients with and without waveform deterioration. RESULTS The patients (3 males and 65 females) had an average age of 14.4 years (range 11-19 years). The mean Cobb angles before and after surgery were 52.9° and 11.9°, respectively, giving a correction rate of 77.4%. Fourteen patients (20%) exhibited an intraoperative waveform change, and these occurred during incision (14%), after screw fixation (7%), during the rotation maneuver (64%), during placement of the second rod after the rotation maneuver (7%), and after intervertebral compression (7%). Most waveform changes recovered after decreased correction or rest. No patient had a motor deficit postoperatively. In multivariate analysis, EBL (OR 1.001, p = 0.085) and number of levels fused (OR 1.535, p = 0.045) were associated with waveform deterioration. CONCLUSIONS Waveform deterioration commonly occurred during rotation maneuvers and more frequently in patients with a larger preoperative Cobb angle. The significant relationships of EBL and number of levels fused with waveform deterioration suggest that these surgical invasions may be involved in waveform deterioration.


Cetuximab attenuates metastasis and u-PAR expression in non-small cell lung cancer: u-PAR and E-cadherin are novel biomarkers of cetuximab sensitivity.
Cetuximab, which blocks ligand binding to epidermal growth factor receptor (EGFR), is currently being studied as a novel treatment for non-small cell lung cancer (NSCLC). However, its mechanisms of action toward metastasis, and markers of drug sensitivity, have not been fully elucidated. This study was conducted to (a) determine the effect of Cetuximab on invasion and NSCLC-metastasis; (b) investigate urokinase-type plasminogen activator receptor (u-PAR), a major molecule promoting invasion and metastasis, as a target molecule; (c) delineate molecular mediators of Cetuximab-induced metastasis inhibition; and (d) identify biomarkers of drug sensitivity in NSCLC. Cetuximab treatment resulted in reduced growth and Matrigel invasion of H1395 and A549 NSCLC cell lines, in parallel with reduced u-PAR mRNA and protein. u-PAR down-regulation was brought about by suppressing the binding of JunD and c-Jun to u-PAR promoter motif -190/-171 in vivo, and an inhibition of MAP/ERK kinase signaling. Furthermore, Cetuximab inhibited NSCLC proliferation and metastasis to distant organs in vivo as indicated by the chicken embryo metastasis assay. Low E-cadherin and high u-PAR, but not EGFR, was associated with resistance to Cetuximab in seven NSCLC cell lines. Furthermore, siRNA knockdown of u-PAR led to a resensitization to Cetuximab. Moreover, low E-cadherin and high u-PAR was found in 63% of resected tumor tissues of NSCLC patients progressing under Cetuximab therapy. This is the first study to show u-PAR as a target and marker of sensitivity to Cetuximab, and to delineate novel mechanisms leading to metastasis suppression of NSCLC by Cetuximab.


Patient preference for radial versus femoral vascular access for elective coronary procedures: The PREVAS study.
To explore patient preference for vascular access site in percutaneous coronary procedures, the perceived importance of benefits and risks of transradial access (TRA) and transfemoral access (TFA) were assessed. In addition, direct preference for vascular access and preference for shared decision making (SDM) were evaluated. TRA has gained significant ground on TFA during the last decades. Surveys on patient preference have mostly been performed in dedicated TRA trials. In the PREVAS study (Clinicaltrials.gov: NCT02625493) a stated preference elicitation method best-worst scaling (BWS) was used to determine patient preference for six treatment attributes: bleeding, switch of access-site, postprocedural vessel quality, mobilization and comfort, and over-night stay. Based on software-generated treatment scenarios, 142 patients indicated which characteristics they perceived most and least important in treatment choice. Best-minus-Worst scores and attribute importance were calculated. Bleeding risk was considered most important (attribute importance 31.3%), followed by length of hospitalization (22.6%), and mobilization(20.2%). Most patients preferred the approach of their current procedure (85.9%); however, 71.1% of patients with experience with both access routes favored TRA (P < 0.001). Most patients (38.0%) appreciated SDM, balanced between patient and cardiologist. Patients appreciate lower bleeding risk and early ambulation, factors favoring TRA. Previous experience with a single access route has a major impact on preference, while experience with both routes generally resulted in preference for TRA. Most patients prefer balanced SDM. © 2017 The Authors Catheterization and Cardiovascular Interventions Published by Wiley Periodicals, Inc.


The athlete's heart: a contemporary appraisal of the 'Morganroth hypothesis'.
As early as 1975, Morganroth and colleagues hypothesized that the cardiac morphological adaptation observed in athletes corresponded with the nature of the haemodynamic stimulus imposed on the ventricles during repeated exercise bouts. Endurance training purportedly leads to an eccentric form of cardiac hypertrophy, principally characterized by increased left ventricular (LV) cavity dimension, and thus LV mass (LVM), as a consequence of prolonged repetitive volume overload. In contrast, strength training is supposedly associated with a concentric form of hypertrophy where increased ventricular wall thickness, with no change in cavity size, underpins the elevated LVM as a consequence of the pressure overload produced during strenuous resistive exercise. The 'Morganroth hypothesis' has been broadly adopted in the scientific and medical literature, partly as a consequence of a large body of cross-sectional evidence suggesting that endurance athletes have greater cavity dimensions than control subjects or resistance athletes. However, in conflict with the 'Morganroth hypothesis', several studies suggest that LV wall thickness is increased more in endurance-, than strength-trained athletes and others have reported no morphological changes in resistance-trained athletes. Such controversial data may reflect variability in the training stimuli, with little obvious attempt to quantify these issues in previous research. Further reflection on the 'Morganroth hypothesis' may also be pertinent as more sensitive technologies, such as magnetic resonance imaging, are now being employed for the assessment of cardiac morphology. Finally, the process of scaling (or normalizing) cardiac size for between-subject differences in body size and composition has further complicated the description and understanding of cardiac morphology in athletes. Specifically, it is possible that the increased LVM observed in some athletes may merely reflect a 'larger than normal' body size. These considerations emphasise the limitations of the predominance of cross-sectional comparisons in the available literature, which assume that differences between groups are due to a training effect per se rather than other between-subject differences. The small number of longitudinal training studies undertaken in athletes suggest that individuals with athlete's heart can exhibit further cardiac adaptation in response to training resumption. Longitudinal training studies undertaken in previously sedentary subjects generally indicate that exercise results in enlargement of LV cavity size, increases in wall thickness or LVM following training. However, there are currently limited longitudinal data available to comment on the effects of different modalities of exercise training on LV cavity dimension and wall thickness. In summary, significant caveats related to cross-sectional literature, the relative insensitivity of echocardiographic measurements and the paucity of evidence from longitudinal exercise training studies, warrant ongoing research to verify the 'Morganroth hypothesis'.


Lung structure and function of infants with recurrent wheeze when asymptomatic.
Infants with recurrent wheeze have repeated episodes of airways obstruction; however, relatively little is known about the structure and function of their lungs when not symptomatic. The current authors evaluated whether infants with recurrent wheeze have smaller airway lumens or thickened airway walls, as well as decreased airway function. High-resolution computed tomography images 1 mm thick were obtained at three anatomic locations at an elevated lung volume and at functional residual capacity. Forced expiratory flows were also measured in subjects with recurrent wheeze. Airway lumen, wall areas and lung tissue density were not significantly different for recurrent wheeze (n = 17) and control (n = 14) subjects; however, subjects with recurrent wheeze had lower forced expiratory flows than predicted. Similar findings were obtained when subjects were grouped by exposure to tobacco smoke. These findings indicate that infants with recurrent wheeze, as well as exposure to tobacco smoke, have lower airway function when not symptomatic. The lower forced expiratory flows may result from a degree of airway narrowing that could not be resolved with the methodology employed or from other mechanisms, such as more collapsible airways or decreased pulmonary elastic recoil.


Microsecond molecular dynamics simulations of intrinsically disordered proteins involved in the oxidative stress response.
Intrinsically disordered proteins (IDPs) are abundant in cells and have central roles in protein-protein interaction networks. Interactions between the IDP Prothymosin alpha (ProTα) and the Neh2 domain of Nuclear factor erythroid 2-related factor 2 (Nrf2), with a common binding partner, Kelch-like ECH-associated protein 1(Keap1), are essential for regulating cellular response to oxidative stress. Misregulation of this pathway can lead to neurodegenerative diseases, premature aging and cancer. In order to understand the mechanisms these two disordered proteins employ to bind to Keap1, we performed extensive 0.5-1.0 microsecond atomistic molecular dynamics (MD) simulations and isothermal titration calorimetry experiments to investigate the structure/dynamics of free-state ProTα and Neh2 and their thermodynamics of bindings. The results show that in their free states, both ProTα and Neh2 have propensities to form bound-state-like β-turn structures but to different extents. We also found that, for both proteins, residues outside the Keap1-binding motifs may play important roles in stabilizing the bound-state-like structures. Based on our findings, we propose that the binding of disordered ProTα and Neh2 to Keap1 occurs synergistically via preformed structural elements (PSEs) and coupled folding and binding, with a heavy bias towards PSEs, particularly for Neh2. Our results provide insights into the molecular mechanisms Neh2 and ProTα bind to Keap1, information that is useful for developing therapeutics to enhance the oxidative stress response.


Inflection in inactive lateral rectus muscle: evidence suggesting focal mechanical effects of connective tissues.
Paths of inactive lateral rectus (LR) muscles were studied to investigate putative roles of orbital fat and intrinsic muscle stiffness suggested to be alternatives to connective tissue pulleys as determinants of pulling direction. Surface coil orbital magnetic resonance imaging was performed in axial planes in adult humans: seven with chronic unilateral LR paralysis, three with nonparalytic concomitant esotropia of similar angle, and 15 healthy controls. Fixation was controlled using targets placed at a broad range of horizontal positions. Paralyzed LRs exhibited marked atrophy compared with functional contralateral LRs and LRs of orthotropic and esotropic subjects without LR paralysis. The normal LR exhibited a gradual 18.8 degrees +/- 4.5 degrees (mean +/- SD) lateral inflection 14.4 +/- 2.6 mm posterior to the globe center, bowing the LR away from the orbital center. The paralyzed LR exhibited a significantly (P < 0.002) larger and typically more discrete 29.2 degrees +/- 8.8 degrees lateral inflection, similar to that observed in concomitant esotropia in maximal adduction. Average position of this inflection was 11 to 14 mm posterior to the globe center in all three subject groups, but in LR palsy only the inflection of the paralyzed LR-0.17 mm further posterior per degree of abduction (linear fit, R = 0.85)-depended on horizontal gaze. The behavior of the paralyzed LR inflection was consistent with LR pulley anatomy. Sharper lateral inflection in the flaccid rather than the tense LR seems inconsistent with intrinsic muscle stiffness or diffuse orbital fat pressure but suggests the influence of discrete connective tissue.


Melatonin antagonizes hypoxia-mediated glioblastoma cell migration and invasion via inhibition of HIF-1α.
Hypoxia is a crucial factor in tumor aggressiveness and resistance to therapy, especially in glioblastoma. Our previous results have shown that melatonin exerts antimigratory and anti-invasive action in glioblastoma cells under normoxia. However, the effect of melatonin on migration and invasion of glioblastoma cells under hypoxic condition remains poorly understood. Here, we show that melatonin strongly reduced hypoxia-mediated invasion and migration of U251 and U87 glioblastoma cells. In addition, we found that melatonin significantly blocked HIF-1α protein expression and suppressed the expression of downstream target genes, matrix metalloproteinase 2 (MMP-2) and vascular endothelial growth factor (VEGF). Furthermore, melatonin destabilized hypoxia-induced HIF-1α protein via its antioxidant activity against ROS produced by glioblastoma cells in response to hypoxia. Along with this, HIF-1α silencing by small interfering RNA markedly inhibited glioblastoma cell migration and invasion, and this appeared to be associated with MMP-2 and VEGF under hypoxia. Taken together, our findings suggest that melatonin suppresses hypoxia-induced glioblastoma cell migration and invasion via inhibition of HIF-1α. Considering the fact that overexpression of the HIF-1α protein is often detected in glioblastoma multiforme, melatonin may prove to be a potent therapeutic agent for this tumor.


Identifying Affinity Classes of Inorganic Materials Binding Sequences via a Graph-Based Model.
Rapid advances in bionanotechnology have recently generated growing interest in identifying peptides that bind to inorganic materials and classifying them based on their inorganic material affinities. However, there are some distinct characteristics of inorganic materials binding sequence data that limit the performance of many widely-used classification methods when applied to this problem. In this paper, we propose a novel framework to predict the affinity classes of peptide sequences with respect to an associated inorganic material. We first generate a large set of simulated peptide sequences based on an amino acid transition matrix tailored for the specific inorganic material. Then the probability of test sequences belonging to a specific affinity class is calculated by minimizing an objective function. In addition, the objective function is minimized through iterative propagation of probability estimates among sequences and sequence clusters. Results of computational experiments on two real inorganic material binding sequence data sets show that the proposed framework is highly effective for identifying the affinity classes of inorganic material binding sequences. Moreover, the experiments on the structural classification of proteins (SCOP) data set shows that the proposed framework is general and can be applied to traditional protein sequences.


Rapid cost decrease of renewables and storage accelerates the decarbonization of China's power system.
The costs for solar photovoltaics, wind, and battery storage have dropped markedly since 2010, however, many recent studies and reports around the world have not adequately captured such dramatic decrease. Those costs are projected to decline further in the near future, bringing new prospects for the widespread penetration of renewables and extensive power-sector decarbonization that previous policy discussions did not fully consider. Here we show if cost trends for renewables continue, 62% of China's electricity could come from non-fossil sources by 2030 at a cost that is 11% lower than achieved through a business-as-usual approach. Further, China's power sector could cut half of its 2015 carbon emissions at a cost about 6% lower compared to business-as-usual conditions.


Studies of chinese original quiet sitting by using functional magnetic resonance imaging.
Since different meditations may activate different regions in brain, we can use functional magnetic resonance imaging (fMRI) to investigate it. Chinese original quiet sitting is mainly one kind of traditional Chinese meditation. It contains two different parts: a short period of keeping phrase and intake spiritual energy, and a long period of relaxation with no further action. In this paper, both those two stages were studied by fMRI. We performed two different paradigms and found the accurate positions in the brain. The pineal gland and the hypothalamus showed positive activation during the first and second stages of this meditation. The BOLD (Blood Oxygenation Level Dependent) signal changes had also been found.


Diagnosis of perioperative myocardial infarction with measurement of cardiac troponin I.
Perioperative myocardial infarction is the most common cause of morbidity and mortality in patients who have had noncardiac surgery, but its diagnosis can be difficult. The present study was designed to determine whether the measurement of serum levels of cardiac troponin I, a highly sensitive and specific marker for cardiac injury, would help establish the diagnosis of myocardial infarction. We obtained preoperative measurements of MB creatine kinase, total creatine kinase, and cardiac troponin I, in addition to base-line electrocardiograms and two-dimensional echocardiograms, in 96 patients undergoing vascular surgery and 12 undergoing spinal surgery. Blood samples were obtained every 6 hours for at least the first 36 hours after surgery, and electrocardiograms were obtained daily; a second echocardiogram was obtained approximately three days after surgery. The appearance of a new abnormality in segmental-wall motion on the postoperative echocardiogram (that is, an abnormality that had not been seen on the preoperative echocardiogram) was considered to be indicative of perioperative infarction. Eight patients who underwent vascular surgery had new abnormalities in segmental-wall motion and received a diagnosis of perioperative infarction. All eight had elevations of cardiac troponin I, and six had elevations of MB creatine kinase. Of the 100 patients without perioperative infarction detected by echocardiography, 19 had elevations of MB creatine kinase, and 1 had a slight elevation of cardiac troponin I. The measurement of cardiac troponin I is a sensitive and specific method for the diagnosis of perioperative myocardial infarction. It avoids the high incidence of false diagnoses associated with the use of MB creatine kinase as a diagnostic marker.