Comparison of the functional results of single lung transplantation for pulmonary fibrosis and chronic airway obstruction.
Single lung transplantation (SLT) is now a treatment option for patients with both pulmonary fibrosis and advanced chronic airway obstruction. Lung function after transplantation might be expected to be different in these two groups of patients because of the effect of the remaining native lung, but the implications of these differences have not been fully explored. The functional results of a stable population of 20 patients (13 chronic airway obstruction, seven pulmonary fibrosis) after SLT with no evidence of obliterative bronchiolitis were analysed. The differences between the two populations in the interrelations between and determinants of total lung capacity (TLC), subdivisions of lung volume, airway function (spirometry, maximum expiratory flow volume curves, and moments analysis of the spirogram) respiratory mechanics (PV curves and maximal respiratory pressures), CO transfer factor (TLCO) and the distribution of perfusion, ventilation and volume of the transplanted and native lungs were compared. Total lung capacity after SLT (TLCpost) was normal in the patients with pulmonary fibrosis (mean (SE) 103.9 (6.9)% predicted) but remained significantly elevated in patients with airway obstruction (126.4 (4.4)%. Forced expiratory volume in one second (FEV1) and vital capacity (VC) improved to similar values after SLT in both groups with a final VC of 76.8 (5.9)% and 66.7 (3.9)% in patients with fibrosis and airway obstruction, respectively. Maximum expiratory flows were generally lower and moments analysis of the spirogram showed slower lung emptying with significantly greater second and third moments (alpha 2 and alpha 3) in patients with airway obstruction. Relative ventilation and perfusion of the transplanted lung were both greater in both populations but relative ventilation of the transplanted lung was significantly greater in patients treated for airway disease than in those with pulmonary fibrosis. TLCO was also significantly higher in patients who had received a transplant for chronic airway obstruction. These results suggest that differences in the functional results of SLT for airway disease and pulmonary fibrosis are relatively minor. In this series the native hyperinflated lung in chronic airway disease was not more disadvantageous to overall function than the native lung in pulmonary fibrosis. However, tests of lung function based on the terminal portion of the forced spirogram are likely to be less sensitive for the detection of obliterative bronchiolitis in patients who have received a transplant for advanced airway obstruction than in those with pulmonary fibrosis.


Conversion of Tibiotalar Arthrodesis to Total Ankle Arthroplasty.
Conversion of ankle arthrodesis to total ankle arthroplasty remains controversial. Although satisfactory outcomes have been published, not all foot and ankle surgeons performing total ankle arthroplasty have embraced this modality. Twenty-three total ankle arthroplasties were performed in patients who had undergone a prior or an attempted ankle arthrodesis. The mean age at surgery was fifty-nine years (range, forty-one to eighty years), and the mean duration of follow-up was 33.1 months (minimum, twelve months). Indications for the procedure were symptomatic adjacent hindfoot arthritis (twelve patients) or symptomatic tibiotalar or subtalar nonunion (eleven) after tibiotalocalcaneal arthrodesis. We performed concomitant surgical procedures in eighteen ankles (78%), with the most common procedure being prophylactic malleolar fixation (70%). We prospectively evaluated clinical outcomes using the Short Form-36 (SF-36), Short Musculoskeletal Function Assessment (SMFA), and visual analog scale (VAS) for pain and assessed initial weight-bearing radiographs and those made at the most recent follow-up evaluation. The mean VAS pain score (and standard deviation) improved from 65.7 ± 21.8 preoperatively to 18.3 ± 17.6 at the most recent follow-up evaluation (p < 0.001), with five patients being pain-free (VAS score = 0). The mean SMFA bother and function indexes improved from 55 ± 22.9 and 46.7 ± 12.6 preoperatively to 30.6 ± 22.7 and 25.4 ± 17.4 at the most recent follow-up visit (p = 0.001 and p < 0.001, respectively). The mean SF-36 total score improved from 37.7 ± 19.3 to 56.4 ± 23.1 (p = 0.002). The implant survival rate was 87%. Four (20%) of the tibial components and fourteen (70%) of the talar components that were not revised exhibited initial settling and then were seen to be stabilized radiographically without further change in implant position. Three total ankle replacements (13%) showed progressive talar subsidence, prompting revision. Ten patients (43%) had minor complications not requiring repeat surgery. Short-term follow-up after conversion of ankle arthrodesis to total ankle arthroplasty demonstrated pain relief and improved function in a majority of patients. Patients who undergo this surgery frequently require concomitant procedures; we recommend prophylactic malleolar fixation when performing conversion total ankle arthroplasty. The rate of complications, particularly talar component settling and migration, is cause for concern. We do not recommend the procedure for ankle arthrodeses that included distal fibulectomy.


Metabolic dysfunction in women with bipolar disorder: the potential influence of family history of type 2 diabetes mellitus.
Overweight/obesity, insulin resistance (IR), and other types of metabolic dysfunction are common in patients with bipolar disorder (BD); however, the pathophysiological underpinnings of metabolic dysfunction in BD are not fully understood. Family history of type 2 diabetes mellitus (FamHxDM2), which has been shown to have deleterious effects on metabolic function in the general population, may play a role in the metabolic dysfunction observed in BD. Using multivariate analysis of variance, the effects of BD illness and/or FamHxDM2 were examined relative to metabolic biomarkers in 103 women with BD and 36 healthy, age-matched control women. As a group, women with BD had higher levels of fasting plasma insulin (FPI) and fasting plasma glucose (FPG), higher homeostatic assessment of IR (HOMA-IR) scores, body mass index (BMI), waist circumference (WC), and hip circumference (HC) compared to control women. FamHxDM2 was associated with significantly worse metabolic biomarkers among women with BD but not among healthy control women. Among women with BD, there was a significant main effect of FamHxDM2 on FPI, HOMA-IR, BMI, WC, and HC, even after controlling for type of BD illness, duration of medication exposure, and depression severity. Metabolic biomarkers were not influenced by use of weight-liable psychotropic medication (WLM), even after controlling for type of BD illness, duration of medication exposure, and depression severity. Women with BD have overall worse metabolic biomarkers than age-matched control women. The use of WLM, duration of medication use, type of BD illness, and depression severity did not appear to be associated with more pronounced metabolic dysfunction. FamHxDM2 may represent a risk factor for the development of IR in women with BD. Further, focused studies of the endocrine profiles of families of BD patients are needed.


Effects of FOXO genotypes on longevity: a biodemographic analysis.
Based on data from 760 centenarians and 1060 middle-age controls (all Han Chinese), this article contributes biodemographic insights and syntheses concerning the magnitude of effects of the FOXO genotypes on longevity. We also estimate independent and joint effects of the genotypes of FOXO1A and FOXO3A genes on long-term survival, considering carrying or not-carrying the minor allele of the single-nucleotide polymorphism of another relevant gene. We found substantial gender differences in the independent effects; positive effects of FOXO3A and negative effects of FOXO1A largely compensate each other if one carries both, although FOXO3A has a stronger impact. Ten-year follow-up cohort analysis shows that at very advanced ages 92-110, adjusted for various confounders, positive effects of FOXO3A on survival remain statistically significant, but no significant effects of FOXO1A alone; G × G interactions between FOXO1A-209 and FOXO3A-310 or FOXO3A-292 decrease survival likelihood by 32%-36% (p < .05); G × E interactions between FOXO1A-209 and regular exercise increase survival likelihood by 31%-32% (p < .05).


Therapeutic ultrasound for osteoarthritis of the knee or hip.
Osteoarthritis is the most common form of joint disease and the leading cause of pain and physical disability in the elderly. Therapeutic ultrasound is one of several physical therapy modalities suggested for the management of pain and loss of function due to osteoarthritis (OA). To compare therapeutic ultrasound with sham or no specific intervention in terms of effects on pain and function safety outcomes in patients with knee or hip OA. We updated the search in CENTRAL, CINAHL, EMBASE, MEDLINE and PEDro up to 23 July 2009, checked conference proceedings, reference lists, and contacted authors. Studies were included if they were randomised or quasi-randomised controlled trials that compared therapeutic ultrasound with a sham intervention or no intervention in patients with osteoarthritis of the knee or hip. Two independent review authors extracted data using standardized forms. Investigators were contacted to obtain missing outcome information. Standardised mean differences (SMDs) were calculated for pain and function, relative risks for safety outcomes. Trials were combined using inverse-variance random-effects meta-analysis. Compared to the previous version of the review, four additional trials were identified resulting in the inclusion of five small sized trials in a total of 341 patients with knee OA. No trial included patients with hip OA. Two evaluated pulsed ultrasound, two continuous and one evaluated both pulsed and continuous ultrasound as the active treatment. The methodological quality and the quality of reporting was poor and a high degree of heterogeneity among the trials was revealed for function (88%). For pain, there was an effect in favour of ultrasound therapy, which corresponded to a difference in pain scores between ultrasound and control of -1.2 cm on a 10-cm VAS (95% CI -1.9 to -0.6 cm). For function, we found a trend in favour of ultrasound, which corresponded to a difference in function scores of -1.3 units on a standardised WOMAC disability scale ranging from 0 to 10 (95% CI -3.0 to 0.3). Safety was evaluated in two trials including up to 136 patients; no adverse event, serious adverse event or withdrawals due to adverse events occurred in either trial. In contrast to the previous version of this review, our results suggest that therapeutic ultrasound may be beneficial for patients with osteoarthritis of the knee. Because of the low quality of the evidence, we are uncertain about the magnitude of the effects on pain relief and function, however. Therapeutic ultrasound is widely used for its potential benefits on both knee pain and function, which may be clinically relevant. Appropriately designed trials of adequate power are therefore warranted.


Design, construction and performance of a horizontal subsurface flow wetland system in Australia.
Malabugilmah is a remote Aboriginal community located in Clarence Valley, Northern NSW, Australia. In 2006, seven horizontal subsurface flow wetland clusters consisting of 3 m × 2 m wetland cells in series were designed and constructed to treat septic tank effluent to a secondary level (Total Suspended Solids (TSS) < 30 mg/L and Biochemical Oxygen Demand (BOD5) <20 mg/L) and achieve >50% Total Nitrogen (TN) reduction, no net Total Phosphorus (TP) export and ≥99.9% Faecal Coliform (FC) reduction. The wetland cell configuration allowed the wetlands to be located on steeper terrain, enabling effluent to be treated to a secondary level without the use of pumps. In addition to the water quality targets, the wetlands were designed and constructed to satisfy environmental, economic and social needs of the community. The wetland systems were planted with a local Australian wetland tree species which has become well established. Two wetland clusters have been monitored over the last 4 years. The wetlands have demonstrated to be robust over time, providing a high level of secondary treatment over an extended period.


Comparison of the effects of low energy laser and ultrasound in treatment of shoulder myofascial pain syndrome: a randomized single-blinded clinical trial.
Myofascial pain syndrome (MPS) is one of the most prevalent musculoskeletal diseases. MPS impaired quality of life in the patients. There is a lot of controversy about different treatment options which include medical treatments, physical therapy, injections, ultrasound and laser. The effects of laser in MPS are challenging. To assess the effects of laser and ultrasound in treatment of MPS. Randomized single blinded clinical trial Outpatient physical therapy clinic at university hospital Sixty three subjects (females: 46, males: 17), (age range: 17-55 year old) who had a diagnosis of definite MPS were entered in the study. We measured the pain intensity at rest, during activity and at night using Visual Analogue Scale (VAS) questionnaire. The patients also filled the Neck Disability Index (NDI) form and the pain threshold provoked by pressure was determined using algometric assessment. Then, the patients were categorized randomly in groups A, B and C (receiving laser therapy, ultrasound and sham laser therapy, respectively). Six weeks after the initial visit, they were visited again and filled the forms again. Ultrasound was effective in VAS improvement during activity (46%), at rest (39%) and at night (35%). It also improved NDI scores (34%) and algometric assessment (37%). Laser was effective in VAS improving during activity (54%), at night (51%) and at rest (51%) and also improved NDI scores (73%). It was also found effective in algometric assessment improvement (105%). Laser resulted in more NDI score and algometric assessment improvements comparing to ultrasound (p<0.05). This study introduces laser as one of the preferred treatments of myofascial pain syndrome in shoulder.


Membrane-active antimicrobial poly(amino-modified alkyl) β-cyclodextrins synthesized via click reactions.
The emergence of drug-resistant bacteria has led to the high demand for new antibiotics. In this report, we investigated membrane-active antimicrobial β-cyclodextrins. These contain seven amino-modified alkyl groups on a molecule, which act as functional moieties to permeabilize bacterial cell membranes. The polyfunctionalization of cyclodextrins was achieved through a click reaction assisted by microwave irradiation. A survey using derivatives with systematically varied functionalities clarified the unique correlation of the antimicrobial activity of these compounds with their molecular structure and hydrophobicity/hydrophilicity balances. The optimum hydrophobicity for the compounds being membrane-active was specific to bacterial strains and animal cells; this led to specific compounds having selective toxicity against bacteria including multidrug-resistant pathogens. The results demonstrate that cyclodextrin is a versatile molecular scaffold for rationally designed structures and can be used for the development of new antibiotics.


Electrocardiographic arrhythmia risk testing.
Among the most compelling challenges facing cardiologists today is identification of which patients are at highest risk for sudden death. Automatic implantable cardioverter-defibrillators are now indicated in many of these patients, yet the role of noninvasive risk stratification in classifying patients at high risk is not well defined. The purpose of this review is to evaluate the various electrocardiographic (ECG) techniques that appear to have potential in assessment of risk for arrhythmia. The resting ECG (premature ventricular contractions, QRS duration, damage scores, QT dispersion, and ST segment and T wave abnormalities), T wave alternans, late potentials identified on signal-averaged ECGs, and heart rate variability are explored. Unequivocal evidence to support the widespread use of any single noninvasive technique is lacking; further research in this area is needed. It is likely that a combination of risk evaluation techniques will have the greatest predictive power in enabling identification of patients most likely to benefit from device therapy.


Exergy analysis in the assessment of the sustainability of waste gas treatment systems.
This study focuses on the sustainability of different technological options for the treatment of waste gases from a waste water treatment plant loaded with volatile organic compounds. The options considered are biofiltration, active carbon adsorption and catalytic and thermal oxidation. The amount of resources and utilities to construct and operate each system have been investigated from the point of view of the Second Law of thermodynamics. The unit in which all resources are treated is Joules of exergy. It was concluded that biofiltration was the most exergetically efficient system. The cumulative exergy consumption of the resources and utilities for construction and operation have been quantified in exergy terms. Further on, the requirements for the abatement of emissions generated by operating the waste gas treatment systems and the amount of renewables have been taken into account in the assessment of the sustainability of the waste gas treatment technologies. Finally, a comparison between exergy analysis and life cycle analysis in assessing the sustainability of the waste gas treatment options, is presented.


Cytotoxic T lymphocytes recognize structurally diverse, clade-specific and cross-reactive peptides in human immunodeficiency virus type-1 gag through HLA-B53.
Human immunodeficiency virus type-1 (HIV-1) cytotoxic T lymphocyte (CTL) epitopes have largely been defined in Caucasian populations infected with clade B virus. Identification of potentially protective CTL epitopes in non-B clade-infected African subjects is important for vaccine development. In a study of CTL responses in clade A-infected Gambians, using cytotoxicity, interferon-gamma (IFN-gamma) enzyme-linked immunospot (ELISpot) and HLA-B53-peptide tetramer assays, we identified three HLA-B53-restricted epitopes in HIV-1 gag p24. CTL specific for an epitope in a highly immunogenic region of the p24 protein showed no cross-reactivity to other HIV-1 clades. Two of the epitopes would not have been predicted from the peptide-binding motif due to the absence of a proline anchor at position 2. Structural analysis of HLA-B53 and its relative, HLA B35, enabled us to re-define the peptide-binding motif to include other P2 anchors. These results demonstrate the value of combined immunological and structural analyses in defining novel CTL epitopes and have implications for HIV-1 vaccine design.


Telomerase redux: ready for prime time?
By maintaining genome integrity, controlling cell proliferation, and regulating tissue homeostasis, telomerase plays a critical role in the pathology of aging and cancer. Telomerase is composed of telomerase RNA, or telomerase RNA component (TERC), which serves as a template for telomeric DNA synthesis, and a catalytic subunit, telomerase reverse transcriptase (TERT). The canonical function of TERT is the synthesis of telomeric DNA repeats and the maintenance of telomere length. Recent studies suggest that adeno-associated virus (AAV)-expressed TERT in adult mice can increase life span and health span. Because TERT physically interacts with proteins that regulate gene expression, and because TERT's expression at high levels is associated with oncogenic transformation, its synthesis needs to be carefully regulated. Due to safety concerns, transient expression of TERT mRNA may be preferred for tissue engineering and adoptive stem cell therapy.


The National Environmental Public Health Tracking Network Access to Parks Indicator: A National County-Level Measure of Park Proximity.
Parks and recreation departments and public health organizations both work to improve the well-being of their communities. Measuring residential proximity to parks could be a specific area of shared interest, given that proximity to parks is needed for walking access, and the use of parks is, in turn, associated with many physical, social, and mental health benefits. The CDC's publicly available National Environmental Public Health Tracking Network (NEPHTN) Access to Parks Indicator (API) focuses on one major component of access, residential proximity to parks. The API uses a commercial parks database and U.S. Census data to estimate the number and percentage of individuals in the U.S. that live within a half-mile of a park boundary, a measure commonly used to represent park proximity. The API is calculated at the state and county levels and is available for all states and counties in the U.S. Using estimates from the API, we examined the distribution of residential proximity to parks by geography and race/ethnicity. Additionally, we evaluated differences in park proximity by rural/urban status of counties. In 2010, 39% of the total U.S. population lived within a half-mile of a park. This percentage varied widely between states, ranging from 9% in West Virginia to 67% in Hawaii and 88% in the District of Columbia (DC). Park proximity was lowest among non-Hispanic whites (34.2%) and highest among individuals belonging to the non-Hispanic other race category (52.0%). Metropolitan counties had the highest percentage of residents living within a half-mile of a park (43.3%); the percentage was lower in non-metropolitan counties adjacent to a metropolitan county (15.0%) and non-metropolitan counties not adjacent to a metropolitan county (18.5%). Park proximity was higher in metropolitan counties with a larger population size and in non-metropolitan counties with a higher degree of urbanization. The NEPHTN Access to Parks Indicator provides an opportunity to understand park proximity in counties and states throughout the U.S., including identifying disparities that may exist between population subgroups and comparing geographic areas. Parks and recreational professionals can use this information to compare their county or state to other geographic areas and, in combination with local data on parks within their jurisdiction, inform decisions to improve the distribution of parks and the well-being of their communities.


Longitudinal changes in muscle strength and mass after acute stroke.
Reduced mobility after stroke may cause a loss of muscle mass which may, in theory, contribute to disability. We investigated longitudinal changes in muscle strength, lean cross-sectional area and muscle mass in all limbs after acute stroke. We recruited 17 patients within 72 h of hospital admission and measured (a) hand grip strength, (b) knee extensor strength and (c) arm and leg lean cross-sectional area on 6 occasions over 6 months. Appendicular and total muscle mass (dual-energy X-ray absorptiometry) were measured at 3 weeks and 6 months. There was no significant change over time in the strength, lean cross-sectional area and muscle mass of the arms or legs. We noted that muscle strength was substantially lower in all limbs compared with population norms. We found no evidence of a decline in muscle strength or mass in any limb after the stroke, which could have been attributed to reduced mobility. The observed muscle weakness in the ipsilateral side may have pre-dated the stroke.


A rodent model of protein turnover used to design an experiment for measuring the rates of channeling, recycling and protein synthesis.
We described previously a mechanistic model of whole-body protein turnover in rodents. Channeling was defined as the flow of amino acids from the extracellular compartment to aminoacyl tRNA and protein synthesis. Recycling was defined as the flow of amino acids from protein degradation to aminoacyl tRNA (protein synthesis) without mixing with the intracellular pool of amino acids. In this paper, the model is applied to tissues and whole body and is used to develop an experimental protocol for estimating protein fractional synthesis rate, recycling and channeling. Channeling, recycling and protein synthesis must be estimated simultaneously because changes in specific radioactivities over time are highly dependent on the rate of protein synthesis. Injection-specific radioactivities, body weights and experimental variation were used with the model to generate data at different rates of recycling and channeling. The data generated were then used to determine the best time points and experimental method to estimate percentages of recycling, channeling and protein synthesis rate by the iterative Method of Maximum Likelihood. Specific radioactivity at each time point was based on simulated data from three rodents at each of six time points. Predicted protein synthesis rates were within 5%/d of observed rates for all methods. Predicted rates of recycling and channeling were generally within 15% of observed rates except recycling in muscle at high channeling and high recycling. Standard deviations of the predictions of percentages of channeling and recycling were between 0.148 and 44.5% for the pulse dose method, 0.0655 and 197% for the continuous infusion method and 0.351 and 962% for the flooding dose method. The experimental design that yields the best estimates of channeling, recycling and protein synthesis is the pulse dose. Changes in amino acid specific radioactivities in the extracellular, aminoacyl tRNA and protein pools were greatest and should be measured at 2, 6, 10, 40, 70 and 100 min in the pulse method.


Association Between Gun Law Reforms and Intentional Firearm Deaths in Australia, 1979-2013.
Rapid-fire weapons are often used by perpetrators in mass shooting incidents. In 1996 Australia introduced major gun law reforms that included a ban on semiautomatic rifles and pump-action shotguns and rifles and also initiated a program for buyback of firearms. To determine whether enactment of the 1996 gun laws and buyback program were followed by changes in the incidence of mass firearm homicides and total firearm deaths. Observational study using Australian government statistics on deaths caused by firearms (1979-2013) and news reports of mass shootings in Australia (1979-May 2016). Changes in intentional firearm death rates were analyzed with negative binomial regression, and data on firearm-related mass killings were compared. Implementation of major national gun law reforms. Changes in mass fatal shooting incidents (defined as ≥5 victims, not including the perpetrator) and in trends of rates of total firearm deaths, firearm homicides and suicides, and total homicides and suicides per 100,000 population. From 1979-1996 (before gun law reforms), 13 fatal mass shootings occurred in Australia, whereas from 1997 through May 2016 (after gun law reforms), no fatal mass shootings occurred. There was also significant change in the preexisting downward trends for rates of total firearm deaths prior to vs after gun law reform. From 1979-1996, the mean rate of total firearm deaths was 3.6 (95% CI, 3.3-3.9) per 100,000 population (average decline of 3% per year; annual trend, 0.970; 95% CI, 0.963-0.976), whereas from 1997-2013 (after gun law reforms), the mean rate of total firearm deaths was 1.2 (95% CI, 1.0-1.4) per 100,000 population (average decline of 4.9% per year; annual trend, 0.951; 95% CI, 0.940-0.962), with a ratio of trends in annual death rates of 0.981 (95% CI, 0.968-0.993). There was a statistically significant acceleration in the preexisting downward trend for firearm suicide (ratio of trends, 0.981; 95% CI, 0.970-0.993), but this was not statistically significant for firearm homicide (ratio of trends, 0.975; 95% CI, 0.949-1.001). From 1979-1996, the mean annual rate of total nonfirearm suicide and homicide deaths was 10.6 (95% CI, 10.0-11.2) per 100,000 population (average increase of 2.1% per year; annual trend, 1.021; 95% CI, 1.016-1.026), whereas from 1997-2013, the mean annual rate was 11.8 (95% CI, 11.3-12.3) per 100,000 (average decline of 1.4% per year; annual trend, 0.986; 95% CI, 0.980-0.993), with a ratio of trends of 0.966 (95% CI, 0.958-0.973). There was no evidence of substitution of other lethal methods for suicides or homicides. Following enactment of gun law reforms in Australia in 1996, there were no mass firearm killings through May 2016. There was a more rapid decline in firearm deaths between 1997 and 2013 compared with before 1997 but also a decline in total nonfirearm suicide and homicide deaths of a greater magnitude. Because of this, it is not possible to determine whether the change in firearm deaths can be attributed to the gun law reforms.


Evaluation of Whole-Brain Resting-State Functional Connectivity in Spinal Cord Injury: A Large-Scale Network Analysis Using Network-Based Statistic.
Large-scale network analysis characterizes the brain as a complex network of nodes and edges to evaluate functional connectivity patterns. The utility of graph-based techniques has been demonstrated in an increasing number of resting-state functional MRI (rs-fMRI) studies in the normal and diseased brain. However, to our knowledge, graph theory has not been used to study the reorganization pattern of resting-state brain networks in patients with traumatic complete spinal cord injury (SCI). In the present analysis, we applied a graph-theoretical approach to explore changes to global brain network architecture as a result of SCI. Fifteen subjects with chronic (> 2 years) complete (American Spinal Injury Association [ASIA] A) cervical SCI and 15 neurologically intact controls were scanned using rs-fMRI. The data were preprocessed followed by parcellation of the brain into 116 regions of interest (ROI) or nodes. The average time series was extracted at each node, and correlation analysis was performed between every pair of nodes. A functional connectivity matrix for each subject was then generated. Subsequently, the matrices were averaged across groups, and network changes were evaluated between groups using the network-based statistic (NBS) method. Our results showed decreased connectivity in a subnetwork of the whole brain in SCI compared with control subjects. Upon further examination, increased connectivity was observed in a subnetwork of the sensorimotor cortex and cerebellum network in SCI. In conclusion, our findings emphasize the applicability of NBS to study functional connectivity architecture in diseased brain states. Further, we show reorganization of large-scale resting-state brain networks in traumatic SCI, with potential prognostic and therapeutic implications.


An investigation of shoulder forces in active shoulder tackles in rugby union football.
In rugby union football the tackle is the most frequently executed skill and one most associated with injury, including shoulder injury to the tackler. Despite the importance of the tackle, little is known about the magnitude of shoulder forces in the tackle and influencing factors. The objectives of the study were to measure the shoulder force in the tackle, as well as the effects of shoulder padding, skill level, side of body, player size, and experimental setting on shoulder force. Experiments were conducted in laboratory and field settings using a repeated measures design. Thirty-five participants were recruited to the laboratory and 98 to the field setting. All were male aged over 18 years with rugby experience. The maximum force applied to the shoulder in an active shoulder tackle was measured with a custom built forceplate incorporated into a 45 kg tackle bag. The overall average maximum shoulder force was 1660 N in the laboratory and 1997 N in the field. This difference was significant. The shoulder force for tackling without shoulder pads was 1684 N compared to 1635 N with shoulder pads. There was no difference between the shoulder forces on the dominant and non-dominant sides. Shoulder force reduced with tackle repetition. No relationship was observed between player skill level and size. A substantial force can be applied to the shoulder and to an opponent in the tackle. This force is within the shoulder's injury tolerance range and is unaffected by shoulder pads.


Carbon dioxide protects the perinatal brain from hypoxic-ischemic damage: an experimental study in the immature rat.
Clinical investigations suggest that premature infants who require mechanical ventilation from respiratory distress syndrome are at increased risk for periventricular leukomalacia if hypocapnia occurs during respiratory management. The question remains as to the contribution of hypocapnia to hypoxic-ischemic brain damage and whether or not hypercapnia is neuroprotective. Seven-day postnatal rats underwent unilateral common carotid artery ligation followed thereafter by exposure to systemic hypoxia with 8% oxygen (O2) combined with either 0, 3, 6, or 9% carbon dioxide (CO2) for 2.5 hours at 37 degrees C. Survivors underwent neuropathologic examination at 30 days of postnatal age, and their brains were categorized as follows: 0 = normal; 1 = mild atrophy; 2 = moderate atrophy; 3 = atrophy with cystic cavitation < 3 mm; 4 = cystic cavitation > 3 mm of the cerebral hemisphere ipsilateral to the carotid artery ligation. The width of the ipsilateral hemisphere also was determined on a posterior coronal section and compared with that of the contralateral hemisphere to ascertain the severity of cerebral atrophy/cavitation. Data were analyzed by linear models. CO2 tensions averaged 26, 42, 54, and 71 mm Hg in the 0, 3, 6, and 9% CO2 exposed animals, respectively, during systemic hypoxia. Blood O2 tensions during hypoxia were not different among the four groups and averaged 34.7 mm Hg. Neuropathologic results showed that 30/38 (79%) rats exposed to 3% CO2 showed either no or mild brain damage compared with 13/33 (39%) controls (0% CO2). Cystic cavitation occurred in only four CO2 exposed rat pups compared with 14 controls (P = .001). At 6% CO2 exposure, all of 20 rat pups showed either no damage or mild atrophy compared with controls (P < .001); and at 9% CO2 exposure, 19/23 (83%) rat pups showed no or mild damage compared with controls (P < .001). The data also showed that the greatest reduction in brain damage occurred in immature rats exposed to 6% CO2 with slightly less protection at 9% CO2 (P = .012), the latter comparable with the severity of brain damage sustained by animals inhaling 3% CO2. Analyses of coronal width ratios at each CO2 exposure provided results comparable with those of the gross neuropathology scores. The results indicate that in an immature rat model normocapnic cerebral hypoxia-ischemia is associated with less severe brain damage than in hypocapnic hypoxia-ischemia and that mild hypercapnia is more protective than normocapnia. The findings in an experimental model merit further animal investigations as well as a clinical reappraisal of the ventilatory management of sick newborn human infants.


Evaluation of the clinical efficacy and safety of an eye counter pad containing caffeine and vitamin K in emulsified Emu oil base.
People strive to maintain the best look and have a youthful appearance. The skin around the eye is an area without many oil glands and collagen in comparison to the body rest, so it is more prone to fine lines and dehydration, which makes it look dull. The aim of this research is to develop and evaluate in vivo efficacy of an anti-wrinkle and dark circle eye pad consisting of 3% w/w caffeine and 1% vitamin K in a convenient, healthy, and cosmeceutical base. Pre-emulsions containing selected ingredients in a specified effective concentration were prepared. The selected formulation, based upon pharmaceutical parameters, was coated on a nonwoven fabric in an eye counter shape, and stored in a jar. Then in vivo trial was carried out for investigation of its anti-wrinkling efficacy on 11 healthy women. In a single blind trial, the sample pad was applied under the right eye and the placebo pad, consisting of water, was placed under the left eye simultaneously. The efficacy and safety of the formulation was evaluated visually and with a multi skin test MC 900 instrument. After four weeks, the skin around the right eye of all the subjects experienced a reduction in the depth of wrinkles and dark circles, and from a subjective point of view, the appearance and elasticity of the skin were improved. The caffeine pad containing vitamin K in an Emu oil base shows an improvement in eye counter appearance with anti-dark circle capacity and as an emollient.


Congenital cutis laxa syndrome: type II autosomal recessive inheritance.
Cutis laxa is a term that refers to markedly loose skin that is not hyperelastic. It is regarded as a genetically heterogeneous group of diseases and is presently divided into five types. We report a male patient with type II autosomal recessive disease. The patient was the third child of first-cousin consanguineous, healthy parents. His two siblings died a few hours after birth. One of the siblings also had similar features and wrinkled skin. Our case had markedly loose and wrinkled skin especially over the dorsum of the hands and feet, and on the face and abdomen, dolichocephaly, hypertelorism, blepharochalasis, long filtrum, pectus excavatus, large fontanelles, prominent low-set ears and umbilical hernia. These findings and skin biopsy were consistent with cutis laxa syndrome. In addition to these findings, consanguinity, atypical facies, large fontanelles and umbilical hernia were typical manifestations of type II autosomal recessive cutis laxa.


Cortical activity regulates corticothalamic synapses in dorsal lateral geniculate nucleus of rats.
In the visual system, the afferent axons from the dorsal lateral geniculate nucleus (dLGN) to the primary visual cortex (V1) show significant activity-dependent plasticity in early postnatal life. To determine whether activity-dependent plasticity operates also in feedback projections from V1 to dLGN, we inactivated cortical inputs pharmacologically and examined possible changes in the density of synaptic proteins, vesicular glutamate transporter 1 (VGluT1) and type 1 metabotropic glutamate receptor alpha (mGluR1alpha), which locate pre- and postsynaptically at feedback projections, respectively in dLGN of rats. The intensity of the immunohistochemical signal of mGluR1alpha in dLGN significantly decreased following the cortical inactivation for at least 2 days, and the decrease was maintained under cortical inactivation until 28 days. On the other hand, the signal intensity of VGluT1 showed a significant increase following 14 or 28 days of cortical inactivation. In adult rats, however, we found no significant change in VGluT1 signal intensity and only a small and transient downregulation of mGluR1alpha following 7-day inactivation. Thus, the decrease in presynaptic activity induces a rapid downregulation of postsynaptic mGluR1alpha followed by a delayed upregulation of presynaptic VGluT1 in young rats. These results suggest that feedback synapses are regulated by neural activity during development.


Comparison of darbepoetin alfa and epoetin alfa in the management of anemia of critical illness.
To compare the effectiveness of darbepoetin alfa with epoetin alfa (recombinant human erythropoietin [rHuEPO]) for achieving transfusion independence and increasing hemoglobin concentrations in critically ill patients. Retrospective, descriptive study. Level I trauma center intensive care units. Seventy-two patients who spent at least 3 days in the cardio-thoracic, medical, or surgery-trauma intensive care units and received at least one weekly dose of rHuEPO 40,000 units (33 patients) or darbepoetin alfa 100 microg (39 patients). Number of rHuEPO and darbepoetin alfa doses, hemoglobin concentrations, and cumulative number of transfusions were recorded for up to 28 days after the first dose was given, and the data were statistically analyzed. Beginning a median of 10 days after the patients were admitted to the intensive care unit, they received a median of 3.5 doses of darbepoetin alfa or 4 doses of rHuEPO. Mean hemoglobin concentrations at which treatment with darbepoetin alfa and rHuEPO were started were 8 and 8.2 g/dl, respectively (p=0.41). Transfusion independence was achieved in 44% of patients in the darbepoetin alfa group compared with 36% of patients in the rHuEPO group (p=0.63). Patients in both groups received a mean of 2.7 units of packed red blood cells during the 28-day study period. The mean change in hemoglobin levels from baseline over time did not significantly differ between groups (p=0.75). Patients receiving darbepoetin alfa 100 microg/week and those receiving rHuEPO 40,000 units/week for anemia of critical illness achieved similar rates of transfusion independence and increases in hemoglobin concentrations from baseline at 28 days. Compared with previously published studies, erythropoietic agents were administered late in the course of critical illness in response to low hemoglobin concentrations.


Rcount: simple and flexible RNA-Seq read counting.
Analysis of differential gene expression by RNA sequencing (RNA-Seq) is frequently done using feature counts, i.e. the number of reads mapping to a gene. However, commonly used count algorithms (e.g. HTSeq) do not address the problem of reads aligning with multiple locations in the genome (multireads) or reads aligning with positions where two or more genes overlap (ambiguous reads). Rcount specifically addresses these issues. Furthermore, Rcount allows the user to assign priorities to certain feature types (e.g. higher priority for protein-coding genes compared to rRNA-coding genes) or to add flanking regions. Rcount provides a fast and easy-to-use graphical user interface requiring no command line or programming skills. It is implemented in C++ using the SeqAn (www.seqan.de) and the Qt libraries (qt-project.org). Source code and 64 bit binaries for (Ubuntu) Linux, Windows (7) and MacOSX are released under the GPLv3 license and are freely available on github.com/MWSchmid/Rcount. email@example.com Test data, genome annotation files, useful Python and R scripts and a step-by-step user guide (including run-time and memory usage tests) are available on github.com/MWSchmid/Rcount.


Interferon-gamma inducible protein-10 as a potential biomarker in localized scleroderma.
The purpose of this study was to evaluate the presence and levels of interferon-gamma inducible protein-10 (IP-10) in the plasma and skin of pediatric localized scleroderma (LS) patients compared to those of healthy pediatric controls and to determine if IP-10 levels correlate to clinical disease activity measures. The presence of IP-10 in the plasma was analyzed using a Luminex panel in 69 pediatric patients with LS and compared to 71 healthy pediatric controls. Of these patients, five had available skin biopsy specimens with concurrent clinical and serological data during the active disease phase, which were used to analyze the presence and location of IP-10 in the skin by immunohistochemistry (IHC). IP-10 levels were significantly elevated in the plasma of LS patients compared to that of healthy controls and correlated to clinical disease activity measures in LS. Immunohistochemistry staining of IP-10 was present in the dermal infiltrate of LS patients and was similar to that found in psoriasis skin specimens, the positive disease control. Elevation of IP-10 levels in the plasma compared to those of healthy controls and the presence of IP-10 staining in the affected skin of LS patients indicates that IP-10 is a potential biomarker in LS. Furthermore, significant elevation of IP-10 in LS patients with active versus inactive disease and correlations between IP-10 levels and standardized disease outcome measures of activity in LS strongly suggest that IP-10 may be a biomarker for disease activity in LS.


Safety and Immunogenicity of an Anti-Zika Virus DNA Vaccine.
Although Zika virus (ZIKV) infection is typically self-limiting, other associated complications such as congenital birth defects and the Guillain-Barré syndrome are well described. There are no approved vaccines against ZIKV infection. In this phase 1, open-label clinical trial, we evaluated the safety and immunogenicity of a synthetic, consensus DNA vaccine (GLS-5700) encoding the ZIKV premembrane and envelope proteins in two groups of 20 participants each. The participants received either 1 mg or 2 mg of vaccine intradermally, with each injection followed by electroporation (the use of a pulsed electric field to introduce the DNA sequence into cells) at baseline, 4 weeks, and 12 weeks. The median age of the participants was 38 years, and 60% were women; 78% were White and 22% Black; in addition, 30% were Hispanic. At the interim analysis at 14 weeks (i.e., after the third dose of vaccine), no serious adverse events were reported. Local reactions at the vaccination site (e.g., injection-site pain, redness, swelling, and itching) occurred in approximately 50% of the participants. After the third dose of vaccine, binding antibodies (as measured on enzyme-linked immunosorbent assay) were detected in all the participants, with geometric mean titers of 1642 and 2871 in recipients of 1 mg and 2 mg of vaccine, respectively. Neutralizing antibodies developed in 62% of the samples on Vero-cell assay. On neuronal-cell assay, there was 90% inhibition of ZIKV infection in 70% of the serum samples and 50% inhibition in 95% of the samples. The intraperitoneal injection of postvaccination serum protected 103 of 112 IFNAR knockout mice (bred with deletion of genes encoding interferon-α and interferon-β receptors) (92%) that were challenged with a lethal dose of ZIKV-PR209 strain; none of the mice receiving baseline serum survived the challenge. Survival was independent of the neutralization titer. In this phase 1, open-label clinical trial, a DNA vaccine elicited anti-ZIKV immune responses. Further studies are needed to better evaluate the safety and efficacy of the vaccine. (Funded by GeneOne Life Science and others; ZIKA-001 ClinicalTrials.gov number, NCT02809443.).


Enhanced luminescence efficiency by surface plasmon coupling of Ag nanoparticles in a polymer light-emitting diode.
This study achieved a substantial enhancement in electroluminescence by coupling localized surface plasmons in a single layer of Ag nanoparticles. Thermal evaporation was used to fabricate 20-nm Ag particles sandwiched between a gallium-doped zinc oxide film and a glass substrate to form novel window materials for use in polymer light-emitting diodes (PLEDs). The PLEDs discussed herein are single-layer devices based on a poly(9,9-di-n-octyl-2,7-fluorene) (PFO) emissive layer. In addition to low cost, this novel fabrication method can effectively prevent interruption or degradation of the charge transport properties of the active layer to meet the high performance requirements of PLEDs. Due to the surface-plasmon-enhanced emission, the electroluminescence intensity was increased by nearly 1-fold, compared to that of the same PLED without the interlayer of Ag nanoparticles.


Objective Evaluation of a Didactic Curriculum for the Radiation Oncology Medical Student Clerkship.
A structured didactic radiation oncology clerkship curriculum for medical students is in use at multiple academic medical centers. Objective evidence supporting this educational approach over the traditional clerkship model is lacking. This study evaluated the curriculum efficacy using an objective knowledge assessment. Medical students received the Radiation Oncology Education Collaborative Study Group (ROECSG) curriculum consisting of 3 lectures (Overview of Radiation Oncology, Radiation Biology/Physics, and Practical Aspects of Simulation/Radiation Emergencies) and a radiation oncology treatment-planning workshop. A standardized 20-item multiple choice question (MCQ) knowledge assessment was completed pre- and post-curriculum and approximately 6 months after receiving the curriculum. One hundred forty-six students at 22 academic medical centers completed the ROECSG curriculum from July to November 2016. One hundred nine students completed pre- and post-clerkship MCQ knowledge assessments (response rate 74.7%). Twenty-four students reported a prior rotation at a ROECSG institution and were excluded from analysis. Mean assessment scores increased from pre- to post-curriculum (63.9% vs 80.2%, P < .01). Mean MCQ knowledge subdomain assessment scores all improved post-curriculum (t test, P values < .01). Post-scores for students rotating de novo at ROECSG institutions (n = 30) were higher compared with pre-scores for students with ≥1 prior rotations at non-ROECSG institutions (n = 55) (77.3% vs 68.8%, P = .01), with an effect size of 0.8. Students who completed rotations at ROECSG institutions continued to demonstrate a trend toward improved performance on the objective knowledge assessment at approximately 6 months after curriculum exposure (70.5% vs 65.6%, P = .11). Objective evaluation of a structured didactic curriculum for the radiation oncology clerkship at early and late time points demonstrated significant improvement in radiation oncology knowledge. Students who completed clerkships at ROECSG institutions performed objectively better than students who completed clerkships at non-ROECSG institutions. These results support including a structured didactic curriculum as a standard component of the radiation oncology clerkship.


Study of the new ellipsometric measurement method using integrated analyzer in parallel mode.
A new type of ellipsometer using an integrated analyzer composed of 12 sub-analyzers with different azimuth angles was constructed and studied. By using a two-dimensional CCD array camera to measure the light intensity emerging in parallel from each sub-analyzer with the azimuth angles uniformly distributed in the range of about 180 degrees , the ellipsometric parameters were extracted within the data acquisition time less than 1 second. The ellipsometric parameters for the polished bulk Si sample were measured to show good agreement with the results measured by using another two ellipsometric methods. The new method having the merits of high speed and reliability in the optical data measurement can be potentially used in the fields where the in situ data acquisition with high precision is the key issue as required.


Herbal (Phyllanthus niruri) protein isolate protects liver from nimesulide induced oxidative stress.
Present study was conducted to evaluate the role of a protein fraction (PI, protein isolate) of the herb, Phyllanthus niruri (P. niruri) against nimesulide-induced oxidative stress in vivo using a murine model. Mice were intraperitoneally treated with that at a dose of 5mg/kg body weight for 7 days before and separately 1-5 days after nimesulide (at a dose of 10mg/kg body weight for 7 days) administration to evaluate its preventive and curative role. Levels of reduced glutathione (GSH), antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT), as well as thiobarbituric acid reactive substances (TBARS) were measured in the liver homogenates of all study groups. Pretreatment with isolated P. niruri protein fraction significantly enhanced nimesulide-induced reduced levels of antioxidant enzymes and GSH as well as reduced the enhanced level of lipid peroxidation. Post-treatment studies showed that the recovery after nimesulide induced oxidative stress was more rapid if PI was administered compared to the spontaneous recovery of liver. Histological studies also suggest that this protein fraction could prevent as well as cure liver from nimesulide induced oxidative stress. DPPH radical scavenging assay showed that it could scavenge free radicals. Its antioxidant property was compared with that of a known potent antioxidant, Vitamin E. Besides, the effect of a non-relevant protein, BSA, was also included in the study. Heat treatment and trypsin digestion destroyed the biological activity of this protein fraction. In conclusion, data obtained suggest that the P. niruri protein fraction may protect liver from nimesulide-induced oxidative stress probably via promotion of antioxidant defense.


Noninvasive brain stimulation with high-frequency and low-intensity repetitive transcranial magnetic stimulation treatment for posttraumatic stress disorder.
We aimed to investigate the efficacy of 20 Hz repetitive transcranial magnetic stimulation (rTMS) of either right or left dorsolateral prefrontal cortex (DLPFC) as compared to sham rTMS for the relief of posttraumatic stress disorder (PTSD)-associated symptoms. In this double-blind, placebo-controlled phase II trial conducted between October 2005 and July 2008, 30 patients with DSM-IV-diagnosed PTSD were randomly assigned to receive 1 of the following treatments: active 20 Hz rTMS of the right DLPFC, active 20 Hz rTMS of the left DLPFC, or sham rTMS. Treatments were administered in 10 daily sessions over 2 weeks. A blinded rater assessed severity of core PTSD symptoms, depression, and anxiety before, during, and after completion of the treatment protocol. In addition, a battery of neuropsychological tests was measured before and after treatment. Results show that both active conditions-20 Hz rTMS of left and right DLPFC-induced a significant decrease in PTSD symptoms as indexed by the PTSD Checklist and Treatment Outcome PTSD Scale; however, right rTMS induced a larger effect as compared to left rTMS. In addition, there was a significant improvement of mood after left rTMS and a significant reduction of anxiety following right rTMS. Improvements in PTSD symptoms were long lasting; effects were still significant at the 3-month follow-up. Finally, neuropsychological evaluation showed that active 20 Hz rTMS is not associated with cognitive worsening and is safe for use in patients with PTSD. These results support the notion that modulation of prefrontal cortex can alleviate the core symptoms of PTSD and suggest that high-frequency rTMS of right DLPFC might be the optimal treatment strategy.


Effects of neural progenitor cell transplantation in children with severe cerebral palsy.
Cerebral palsy (CP) is a chronic nervous system disease that severely damages the physical and developmental health of children. Traditional treatment brings about only improvement of mild to moderate CP, but severe CP still lacks effective interventions. To explore safety and efficacy of using neural progenitor cells (NPCs) to treat CP in children, we performed NPC transplantation in 45 patients with severe CP by injecting NPCs derived from aborted fetal tissue into the lateral ventricle. Gross motor function measures (GMFM), the Peabody Developmental Motor Scale-Fine Motor (PDMS-FM) test, and a unified survey questionnaire designed specifically for children with CP were used to evaluate neurological function of the patients. Motor development was significantly accelerated within the first month after cell transplantation, but the rate of improvement gradually slowed to preoperative levels. However, after 1 year, the developmental level in each functional sphere (gross motor, fine motor, and cognition) of the treatment group was significantly higher compared to the control group. No delayed complications of this therapy were noted. These results suggest that NPC transplantation is a safe and effective therapeutic method for treating children with severe CP.


Prophylactic oral ganciclovir compared with deferred therapy for control of cytomegalovirus in renal transplant recipients.
Treatment with prophylactic oral acyclovir, intravenous ganciclovir, or immunoglobulins to prevent cytomegalovirus (CMV) infection and disease in renal transplantation is associated with variable efficacy and significant expense. We studied control of CMV in renal transplant recipients using either prophylactic oral ganciclovir or deferred therapy with intensive monitoring with polymerase chain reaction (PCR) analysis. Forty-two recipients were followed for 6 months after transplantation. Ganciclovir (1000 mg p.o. t.i.d.; n=19) or acyclovir (200 mg p.o. b.i.d.; n=23) was begun at transplantation and continued for 12 weeks. PCR for CMV was performed on buffy-coat specimens every week for 15 weeks and at months 5 and 6. No patients in the ganciclovir group, compared with 14 of 23 patients (61%) in the deferred-therapy group (P<0.0001), developed CMV disease during the first 12 weeks. In the ganciclovir group, 4 of 19 patients (21%) subsequently experienced 5 episodes, whereas 14 patients in the deferred-therapy group experienced 18 episodes (P=0.013 for subjects and P=0.026 for episodes). The time to disease was also delayed in the ganciclovir group compared with the deferred-therapy group (133+/-17 days vs. 51+/-7 days; P<0.0001). Oral ganciclovir also prevented CMV viremia during prophylaxis (2/19 patients [11%] vs. 23/23 patients [100%]). Time to CMV viremia was delayed in the ganciclovir group; however, 13/19 patients (68%) ultimately showed PCR evidence for CMV viremia (P=0.005). An initial 12-week course of oral ganciclovir prevents CMV disease and infection in renal transplant recipients during prophylaxis, and the benefits persist after discontinuation.


Short report: secondary transmission in porcine cysticercosis: description and their potential implications for control sustainability.
Taenia solium taeniasis/cysticercosis is one of few potentially eradicable infectious diseases and is the target of control programs in several countries. The larval stage of this zoonotic cestode invades the human brain and is responsible for most cases of adult-onset epilepsy in the world. The pig is the natural intermediate host, harboring the larvae or cysticerci. Our current understanding of the life cycle implicates humans as the only definitive host and tapeworm carrier (developing taeniasis) and thus the sole source of infective eggs that are responsible for cysticercosis in both human and pigs through oral-fecal transmission. Here we show evidence of an alternative pig-to-pig route of transmission, previously not suspected to exist. In a series of four experiments, naive sentinel pigs were exposed to pigs that had been infected orally with tapeworm segments (containing infective eggs) and moved to a clean environment. Consistently in all four experiments, at least one of the sentinel pigs became seropositive or infected with parasite cysts with much lower cyst burdens than did primarily infected animals. Second-hand transmission of Taenia solium eggs could explain the overdispersed pattern of porcine cysticercosis, with few pigs harboring heavy parasite burdens and many more harboring small numbers of parasites. This route of transmission opens new avenues for consideration with respect to control strategies.


Transcriptionally active HERV-H retrotransposons demarcate topologically associating domains in human pluripotent stem cells.
Chromatin architecture has been implicated in cell type-specific gene regulatory programs, yet how chromatin remodels during development remains to be fully elucidated. Here, by interrogating chromatin reorganization during human pluripotent stem cell (hPSC) differentiation, we discover a role for the primate-specific endogenous retrotransposon human endogenous retrovirus subfamily H (HERV-H) in creating topologically associating domains (TADs) in hPSCs. Deleting these HERV-H elements eliminates their corresponding TAD boundaries and reduces the transcription of upstream genes, while de novo insertion of HERV-H elements can introduce new TAD boundaries. The ability of HERV-H to create TAD boundaries depends on high transcription, as transcriptional repression of HERV-H elements prevents the formation of boundaries. This ability is not limited to hPSCs, as these actively transcribed HERV-H elements and their corresponding TAD boundaries also appear in pluripotent stem cells from other hominids but not in more distantly related species lacking HERV-H elements. Overall, our results provide direct evidence for retrotransposons in actively shaping cell type- and species-specific chromatin architecture.


Ecosystem Evapotranspiration as a Response to Climate and Vegetation Coverage Changes in Northwest Yunnan, China.
Climate and human-driven changes play an important role in regional droughts. Northwest Yunnan Province is a key region for biodiversity conservation in China, and it has experienced severe droughts since the beginning of this century; however, the extent of the contributions from climate and human-driven changes remains unclear. We calculated the ecosystem evapotranspiration (ET) and water yield (WY) of northwest Yunnan Province, China from 2001 to 2013 using meteorological and remote sensing observation data and a Surface Energy Balance System (SEBS) model. Multivariate regression analyses were used to differentiate the contribution of climate and vegetation coverage to ET. The results showed that the annual average vegetation coverage significantly increased over time with a mean of 0.69 in spite of the precipitation fluctuation. Afforestation/reforestation and other management efforts attributed to vegetation coverage increase in NW Yunnan. Both ET and WY considerably fluctuated with the climate factors, which ranged from 623.29 mm to 893.8 mm and -51.88 mm to 384.40 mm over the time period. Spatially, ET in the southeast of NW Yunnan (mainly in Lijiang) increased significantly, which was in line with the spatial trend of vegetation coverage. Multivariate linear regression analysis indicated that climatic factors accounted for 85.18% of the ET variation, while vegetation coverage explained 14.82%. On the other hand, precipitation accounted for 67.5% of the WY. We conclude that the continuous droughts in northwest Yunnan were primarily climatically driven; however, man-made land cover and vegetation changes also increased the vulnerability of local populations to drought. Because of the high proportion of the water yield consumed for subsistence and poor infrastructure for water management, local populations have been highly vulnerable to climate drought conditions. We suggest that conservation of native vegetation and development of water-conserving agricultural practices should be implemented as adaptive strategies to mitigate climate change.


Tight binding of proteins to membranes from older human cells.
The lens is an ideal model system for the study of macromolecular aging and its consequences for cellular function, since there is no turnover of lens fibre cells. To examine biochemical processes that take place in the lens and that may also occur in other long-lived cells, membranes were isolated from defined regions of human lenses that are synthesised at different times during life, and assayed for the presence of tightly bound cytosolic proteins using quantitative iTRAQ proteomics technology. A majority of lens beta crystallins and all gamma crystallins became increasingly membrane bound with age, however, the chaperone proteins alpha A and alpha B crystallin, as well as the thermally-stable protein, βB2 crystallin, did not. Other proteins such as brain-associated signal protein 1 and paralemmin 1 became less tightly bound in the older regions of the lens. It is evident that protein-membrane interactions change significantly with age. Selected proteins that were formerly cytosolic become increasingly tightly bound to cell membranes with age and are not removed even by treatment with 7 M urea. It is likely that such processes reflect polypeptide denaturation over time and the untoward binding of proteins to membranes may alter membrane properties and contribute to impairment of communication between older cells.


Integrated evidence reveals a new species in the ancient blue coral genus Heliopora (Octocorallia).
Maintaining the accretion potential and three dimensional structure of coral reefs is a priority but reef-building scleractinian corals are highly threatened and retreating. Hence future reefs are predicted to be dominated by non-constructional taxa. Since the Late Triassic however, other non-scleractinian anthozoans such as Heliopora have contributed to tropical and subtropical reef-building. Heliopora is an ancient and highly conserved reef building octocoral genus within the monospecific Family Helioporidae, represented by a single extant species - H. coerulea, Pallas, 1766. Here we show integrated morphological, genomic and reproductive evidence to substantiate the existence of a second species within the genus Heliopora. Importantly, some individuals of the new species herein described as Heliopora hiberniana sp. nov. feature a white skeleton indicating that the most diagnostic and conserved Heliopora character (the blue skeleton) can be displaced. The new species is currently known only from offshore areas in north Western Australia, which is a part of the world where coral bleaching events have severely impacted the scleractinian community over the last two decades. Field observations indicate individuals of both H. coerulea and H. hiberniana sp. nov. were intact after the 2016 Scott Reef thermal stress event, and we discuss the possibility that bleaching resistant non-scleractinian reef builders such as Heliopora could provide new ecological opportunities for the reconfiguration of future reefs by filling empty niches and functional roles left open by the regression of scleractinian corals.


The Devon Active Villages Evaluation (DAVE) trial: study protocol of a stepped wedge cluster randomised trial of a community-level physical activity intervention in rural southwest England.
Although physical inactivity has been linked with numerous chronic health conditions and overall mortality, the majority of English adults report doing insufficient physical activity. To increase population physical activity levels, researchers have called for more community-level interventions. To evaluate these complex public health interventions, innovative study designs are required. This study protocol describes Devon Active Villages, a community-level intervention providing physical activity opportunities to 128 rural villages in southwest England, and the methods used to evaluate its effectiveness in increasing physical activity levels. A stepped wedge cluster randomised trial will be used to evaluate whether Devon Active Villages leads to increased physical activity levels in rural communities. Community engagement will help tailor activity programmes for each village; communities will then be supported for a further twelve months. The intervention will be delivered over four periods, each lasting twelve weeks. Data collection consists of a postal survey of a random sample of adults aged 18 years and over, at baseline and after each of the four intervention periods. The questionnaire includes questions on participant demographics, physical activity behaviour, local environment characteristics, awareness of local activity programmes, and psychosocial factors. Based on detecting an increase in the proportion of people who meet physical activity guidelines (from 25% to 30%), at least ten respondents are needed from each of the 128 villages at each stage (80% power at the 5% level of significance). Anticipating a 20% response rate, 6,400 questionnaires will be sent out at each stage (i.e., 50 surveys to each village). Using data from all five periods, a comparison of study outcomes between intervention and control arms will be performed, allowing for time period (as a fixed effect) and the random effect induced by correlation of outcomes (clustering) within villages. This paper describes the use of a stepped wedge cluster randomised trial to evaluate a complex, community-level physical activity intervention in an under-studied population of adults in rural communities in southwest England. The study addresses gaps in the current literature by providing new insights into physical activity levels in this population. Current Controlled Trials ISRCTN37321160.


Spatio-temporal patterns in a mechanical model for mesenchymal morphogenesis.
We present an in-depth study of spatio-temporal patterns in a simplified version of a mechanical model for pattern formation in mesenchymal morphogenesis. We briefly motivate the derivation of the model and show how to choose realistic boundary conditions to make the system well-posed. We firstly consider one-dimensional patterns and carry out a nonlinear perturbation analysis for the case where the uniform steady state is linearly unstable to a single mode. In two-dimensions, we show that if the displacement field in the model is represented as a sum of orthogonal parts, then the model can be decomposed into two sub-models, only one of which is capable of generating pattern. We thus focus on this particular sub-model. We present a nonlinear analysis of spatio-temporal patterns exhibited by the sub-model on a square domain and discuss mode interaction. Our analysis show that when a two-dimensional mode number admits two or more degenerate mode pairs, the solution of the full nonlinear system of partial differential equations is a mixed mode solution in which all the degenerate mode pairs are represented in a frequency locked oscillation.


Guide to the vascular flora of the savannas and flatwoods of Shaken Creek Preserve and vicinity (Pender & Onslow counties, North Carolina, U.S.A.).
Shaken Creek Preserve ("SCP") is a 2,448 ha (6,050 ac) natural area in Pender and Onslow Counties, North Carolina (U.S.A). Best known for its high-quality longleaf pine savanna habitat, the site contains seven savanna or savanna-like plant community types (i.e., flatwoods or sandhills), three of which are globally critically imperiled (G1): Sandy Pine Savanna (Rush Featherling subtype), Wet Loamy Pine Savanna, and Very Wet Loamy Pine Savanna. SCP hosts three Federally Endangered plant species and six Federal Species of Concern. Formerly a private hunting club, the site was virtually unknown to scientists until the 1990s; consequently, few biological inventories of SCP have been conducted. In particular, no systematic floristic inventories of the species-rich savannas have been undertaken, despite the fact that floristic data is critical to the effective management of any natural area. The goals of this study were to (1) inventory the vascular flora of the savannas, flatwoods, and sandhill community types on site through the collection of voucher specimens; (2) provide a comprehensive checklist of the flora based on collections and reports made from the site and from the same or similar habitats in the vicinity (i.e., within 2 miles of SCP); and (3) create an illustrated guide based on the checklist. In order to increase the usefulness of the guide, taxa not currently known from SCP but collected or reported from the same or similar habitats within two miles of SCP, are included in the guide. Eighty-three families containing 450 taxa, including thirty-two Significantly Rare and thirty-eight Watch List taxa, were collected or reported from SCP; an additional seven families containing a total of 102 taxa, including eighteen Significantly Rare and seven Watch List taxa, were collected or reported from the vicinity. In total, ninety families containing 552 taxa, including fifty Significantly Rare and forty-five Watch List taxa, are treated in the guide. Dichotomous keys are provided to all vouchered or reported families, genera, and species. The following features are provided for all species and infraspecific taxa: flowering and fruiting phenology; synonymy with Manual of the Vascular Flora of the Carolinas, the Flora of North America, and Flora of the Southern and Mid-Atlantic States; relevant voucher information; and, for most taxa, line drawings and/or photographs. For taxa collected from SCP, community types in which the taxa occur and estimates of abundance on site are also provided.


Attentional Control and Suppressing Negative Thought Intrusions in Pathological Worry.
Adaptive behavior relies on the ability to effectively and efficiently ignore irrelevant information, an important component of attentional control. The current research found that fundamental difficulties in ignoring irrelevant material are related to dispositional differences in trait propensity to worry, suggesting a core deficit in attentional control in high worriers. The degree of deficit in attentional control correlated with the degree of difficulty in suppressing negative thought intrusions in a worry assessment task. A cognitive training procedure utilizing a flanker task was used in an attempt to improve attentional control. Although the cognitive training was largely ineffective, improvements in attentional control were associated with improvements in the ability to suppress worry-related thought intrusions. Across two studies, the findings indicate that the inability to control worry-related negative thought intrusions is associated with a general deficiency in attentional control.


Metabarcoding is powerful yet still blind: a comparative analysis of morphological and molecular surveys of seagrass communities.
In the context of the sixth wave of extinction, reliable surveys of biodiversity are increasingly needed to infer the cause and consequences of species and community declines, identify early warning indicators of tipping points, and provide reliable impact assessments before engaging in activities with potential environmental hazards. DNA metabarcoding has emerged as having potential to provide speedy assessment of community structure from environmental samples. Here we tested the reliability of metabarcoding by comparing morphological and molecular inventories of invertebrate communities associated with seagrasses through estimates of alpha and beta diversity, as well as the identification of the most abundant taxa. Sediment samples were collected from six Zostera marina seagrass meadows across Brittany, France. Metabarcoding surveys were performed using both mitochondrial (Cytochrome Oxidase I) and nuclear (small subunit 18S ribosomal RNA) markers, and compared to morphological inventories compiled by a long-term benthic monitoring network. A sampling strategy was defined to enhance performance and accuracy of results by preventing the dominance of larger animals, boosting statistical support through replicates, and using two genes to compensate for taxonomic biases. Molecular barcodes proved powerful by revealing a remarkable level of diversity that vastly exceeded the morphological survey, while both surveys identified congruent differentiation of the meadows. However, despite the addition of individual barcodes of common species into taxonomic reference databases, the retrieval of only 36% of these species suggest that the remaining were either not present in the molecular samples or not detected by the molecular screening. This finding exemplifies the necessity of comprehensive and well-curated taxonomic reference libraries and multi-gene surveys. Overall, results offer methodological guidelines and support for metabarcoding as a powerful and repeatable method of characterizing communities, while also presenting suggestions for improvement, including implementation of pilot studies prior to performing full "blind" metabarcoding assessments to optimize sampling and amplification protocols.


The RD-Connect Registry & Biobank Finder: a tool for sharing aggregated data and metadata among rare disease researchers.
In rare disease (RD) research, there is a huge need to systematically collect biomaterials, phenotypic, and genomic data in a standardized way and to make them findable, accessible, interoperable and reusable (FAIR). RD-Connect is a 6 years global infrastructure project initiated in November 2012 that links genomic data with patient registries, biobanks, and clinical bioinformatics tools to create a central research resource for RDs. Here, we present RD-Connect Registry & Biobank Finder, a tool that helps RD researchers to find RD biobanks and registries and provide information on the availability and accessibility of content in each database. The finder concentrates information that is currently sparse on different repositories (inventories, websites, scientific journals, technical reports, etc.), including aggregated data and metadata from participating databases. Aggregated data provided by the finder, if appropriately checked, can be used by researchers who are trying to estimate the prevalence of a RD, to organize a clinical trial on a RD, or to estimate the volume of patients seen by different clinical centers. The finder is also a portal to other RD-Connect tools, providing a link to the RD-Connect Sample Catalogue, a large inventory of RD biological samples available in participating biobanks for RD research. There are several kinds of users and potential uses for the RD-Connect Registry & Biobank Finder, including researchers collaborating with academia and the industry, dealing with the questions of basic, translational, and/or clinical research. As of November 2017, the finder is populated with aggregated data for 222 registries and 21 biobanks.


Exploiting the dispersion of the double-negative-index fishnet metamaterial to create a broadband low-profile metallic lens.
Metamaterial lenses with close values of permittivity and permeability usually display low reflection losses at the expense of narrow single frequency operation. Here, a broadband low-profile lens is designed by exploiting the dispersion of a fishnet metamaterial together with the zoning technique. The lens operates in a broadband regime from 54 GHz to 58 GHz, representing a fractional bandwidth ~7%, and outperforms Silicon lenses between 54 and 55.5 GHz. This broadband operation is demonstrated by a systematic analysis comprising Huygens-Fresnel analytical method, full-wave numerical simulations and experimental measurements at millimeter waves. For demonstrative purposes, a detailed study of the lens operation at two frequencies is done for the most important lens parameters (focal length, depth of focus, resolution, radiation diagram). Experimental results demonstrate diffraction-limited ~0.5λ transverse resolution, in agreement with analytical and numerical calculations. In a lens antenna configuration, a directivity as high as 16.6 dBi is achieved. The different focal lengths implemented into a single lens could be potentially used for realizing the front end of a non-mechanical zoom millimeter-wave imaging system.


Solvent-dependent aromatic versus antiaromatic conformational switching in meso-(heptakis)pentafluorophenyl [32]heptaphyrin.
We have investigated conformational switching dynamics of meso-heptakis(pentafluorophenyl) [32]heptaphyrin(220.127.116.11.1.1.1) in various solvents using steady-state, time-resolved, and temperature-dependent spectroscopy. Absorption and fluorescence spectra of [32]heptaphyrin are quite sensitive to solvent environments. In nonpolar toluene, the antiaromatic figure-of-eight conformation is dominant, as seen in the X-ray crystallography, based on broad and weak absorption bands without any fluorescence and moderate paratropic ring current. On the other hand, a well-resolved sharp absorption spectrum, strong fluorescence, and diatropic ring current in the 1H NMR spectrum in slightly polar THF indicate that most of [32]heptaphyrin molecules take significantly distorted Möbius conformation with aromatic character. By using transient absorption (TA) spectroscopy, the lowest singlet excited-state lifetimes have been revealed to decay biexponentially with the time constants of 5 and 65 ps for figure-of-eight and Möbius conformations, respectively. Based on these results along with vertical excitation energy calculations, we are able to assign two conformers as Hückel antiaromatic and Möbius aromatic species, respectively; it shoulf be noted that the aromaticity/antiaromaticity does not change with temperature variation. Interestingly, in moderately polar solvent, ethyl ether, we find out that these two conformational isomers coexist with a dynamic equilibrium, as revealed by excitation-wavelength-dependent TA, temperature-dependent absorption and 1H NMR spectra. Through our findings, we have demonstrated that the conformational switching dynamics between Hckel antiaromatic and Möbius aromatic conformers in [32]heptaphyrin(184.108.40.206.1.1.1) are strongly affected by solvent medium as well as temperature.


Effect of genotype on slaughtering performance and meat physical and sensory characteristics of organic laying hens.
Slaughtering yields and some meat physical and sensorial parameters of laying hens reared under organic system production were studied. The hens belonged to both Italian dual-purpose breeds [Ermellinata di Rovigo (ER; brown eggshell) and Robusta Maculata (RM; brown eggshell)] as well as hybrid genotypes [Hy Line White 36 (white eggshell) and Hy Line Brown (brown eggshell)]. The birds were reared under organic farming system production from 24 to 44 wk of age, when they were slaughtered. They were reared throughout summer and autumn, and the temperature ranged from about 28 to 3 degrees C. Local breeds presented higher (P < 0.01) live BW and dressing percentage compared with hybrids. The RM and ER carcasses had (P < 0.01) the highest breast and leg (thigh and drumstick) percentage, respectively. The muscle-bone ratio of the Hy Line White 36 drumstick was lower (P < 0.05) than the RM ratio, whereas the other groups were intermediate. The ER breast presented the highest (P < 0.01) lightness value and the lowest (P < 0.01) final pH value compared with the other 3 groups. The breast meat significantly differed according to genotype for almost all the studied sensorial parameters (adhesivity, fibrousness, chewiness, solubility, juiciness, tenderness, shear resistance), with the exception of aroma and odor intensity. In the thigh, genotype significantly affected aroma, adhesivity, fibrousness, solubility, tenderness, and shear resistance.


Consistent patterns of distractor effects during decision making.
The value of a third potential option or distractor can alter the way in which decisions are made between two other options. Two hypotheses have received empirical support: that a high value distractor improves the accuracy with which decisions between two other options are made and that it impairs accuracy. Recently, however, it has been argued that neither observation is replicable. Inspired by neuroimaging data showing that high value distractors have different impacts on prefrontal and parietal regions, we designed a dual route decision-making model that mimics the neural signals of these regions. Here we show in the dual route model and empirical data that both enhancement and impairment effects are robust phenomena but predominate in different parts of the decision space defined by the options' and the distractor's values. However, beyond these constraints, both effects co-exist under similar conditions. Moreover, both effects are robust and observable in six experiments.


The long-term effects of phage concentration on the inhibition of planktonic bacterial cultures.
Since the early 1920s there has been an interest in using bacteriophages (phages) for the control of bacterial pathogens. While there are many factors that have limited the success of phage bio-control, one particular problem is the variability of outcomes between phages and bacteria. Specifically, there is a significant need for a better understanding of how initial phage concentrations affect long-term bacterial inhibition. In work reported herein three phages were isolated for Escherichia coli K12, Pseudomonas aeruginosa PAO1, as well as Bacillus cereus and bio-control experiments were performed with phage concentrations ranging from 10(5) to 10(8) plaque forming units per mL over the course of 72 h. For four of the nine phages isolated there was a linear relationship between inhibition and phage concentration, suggesting the effect of phage concentration is important at longer time scales. For three of the isolated phages, phage concentrations had no effect on bacterial inhibition suggesting that even at the lowest concentration the method of action was saturated and lower concentrations might still be effective. Additionally, a cocktail was created and was compared to the previously isolated phages. There was no statistical difference between the cocktail and the best performing phage highlighting the importance of selecting the appropriate phages for treatment. These results suggest that, for certain phages, there is a strong relationship between phage concentration and long-term bacterial growth inhibition and the initial phage concentration is an important indicator of the long-term outcome.


Toward link predictability of complex networks.
The organization of real networks usually embodies both regularities and irregularities, and, in principle, the former can be modeled. The extent to which the formation of a network can be explained coincides with our ability to predict missing links. To understand network organization, we should be able to estimate link predictability. We assume that the regularity of a network is reflected in the consistency of structural features before and after a random removal of a small set of links. Based on the perturbation of the adjacency matrix, we propose a universal structural consistency index that is free of prior knowledge of network organization. Extensive experiments on disparate real-world networks demonstrate that (i) structural consistency is a good estimation of link predictability and (ii) a derivative algorithm outperforms state-of-the-art link prediction methods in both accuracy and robustness. This analysis has further applications in evaluating link prediction algorithms and monitoring sudden changes in evolving network mechanisms. It will provide unique fundamental insights into the above-mentioned academic research fields, and will foster the development of advanced information filtering technologies of interest to information technology practitioners.


Bacterial Mg2+ homeostasis, transport, and virulence.
Organisms must maintain physiological levels of Mg(2+) because this divalent cation is critical for the stabilization of membranes and ribosomes, for the neutralization of nucleic acids, and as a cofactor in a variety of enzymatic reactions. In this review, we describe the mechanisms that bacteria utilize to sense the levels of Mg(2+) both outside and inside the cytoplasm. We examine how bacteria achieve Mg(2+) homeostasis by adjusting the expression and activity of Mg(2+) transporters and by changing the composition of their cell envelope. We discuss the connections that exist between Mg(2+) sensing, Mg(2+) transport, and bacterial virulence. Additionally, we explore the logic behind the fact that bacterial genomes encode multiple Mg(2+) transporters and distinct sensing systems for cytoplasmic and extracytoplasmic Mg(2+). These analyses may be applicable to the homeostatic control of other cations.


Coral-mucus-associated Vibrio integrons in the Great Barrier Reef: genomic hotspots for environmental adaptation.
Integron cassette arrays in a dozen cultivars of the most prevalent group of Vibrio isolates obtained from mucus expelled by a scleractinian coral (Pocillopora damicornis) colony living on the Great Barrier Reef were sequenced and compared. Although all cultivars showed >99% identity across recA, pyrH and rpoB genes, no two had more than 10% of their integron-associated gene cassettes in common, and some individuals shared cassettes exclusively with distantly-related members of the genus. Of cassettes shared within the population, a number appear to have been transferred between Vibrio isolates, as assessed by phylogenetic analysis. Prominent among the mucus Vibrio cassettes with potentially inferable functions are acetyltransferases, some with close similarity to known antibiotic-resistance determinants. A subset of these potential resistance cassettes were shared exclusively between the mucus Vibrio cultivars, Vibrio coral pathogens and human pathogens, thus illustrating a direct link between these microbial niches through exchange of integron-associated gene cassettes.


Supraglottic airway device versus tracheal intubation in the initial airway management of out-of-hospital cardiac arrest: the AIRWAYS-2 cluster RCT.
When a cardiac arrest occurs, cardiopulmonary resuscitation should be started immediately. However, there is limited evidence about the best approach to airway management during cardiac arrest. The objective was to determine whether or not the i-gel® (Intersurgical Ltd, Wokingham, UK) supraglottic airway is superior to tracheal intubation as the initial advanced airway management strategy in adults with non-traumatic out-of-hospital cardiac arrest. This was a pragmatic, open, parallel, two-group, multicentre, cluster randomised controlled trial. A cost-effectiveness analysis accompanied the trial. The setting was four ambulance services in England. Patients aged ≥ 18 years who had a non-traumatic out-of-hospital cardiac arrest and were attended by a participating paramedic were enrolled automatically under a waiver of consent between June 2015 and August 2017. Follow-up ended in February 2018. Paramedics were randomised 1 : 1 to use tracheal intubation (764 paramedics) or i-gel (759 paramedics) for their initial advanced airway management and were unblinded. The primary outcome was modified Rankin Scale score at hospital discharge or 30 days after out-of-hospital cardiac arrest, whichever occurred earlier, collected by assessors blinded to allocation. The modified Rankin Scale, a measure of neurological disability, was dichotomised: a score of 0-3 (good outcome) or 4-6 (poor outcome/death). The primary outcome for the economic evaluation was quality-adjusted life-years, estimated using the EuroQol-5 Dimensions, five-level version. A total of 9296 patients (supraglottic airway group, 4886; tracheal intubation group, 4410) were enrolled [median age 73 years; 3373 (36.3%) women]; modified Rankin Scale score was known for 9289 patients. Characteristics were similar between groups. A total of 6.4% (311/4882) of patients in the supraglottic airway group and 6.8% (300/4407) of patients in the tracheal intubation group had a good outcome (adjusted difference in proportions of patients experiencing a good outcome: -0.6%, 95% confidence interval -1.6% to 0.4%). The supraglottic airway group had a higher initial ventilation success rate than the tracheal intubation group [87.4% (4255/4868) vs. 79.0% (3473/4397), respectively; adjusted difference in proportions of patients: 8.3%, 95% confidence interval 6.3% to 10.2%]; however, patients in the tracheal intubation group were less likely to receive advanced airway management than patients in the supraglottic airway group [77.6% (3419/4404) vs. 85.2% (4161/4883), respectively]. Regurgitation rate was similar between the groups [supraglottic airway group, 26.1% (1268/4865); tracheal intubation group, 24.5% (1072/4372); adjusted difference in proportions of patients: 1.4%, 95% confidence interval -0.6% to 3.4%], as was aspiration rate [supraglottic airway group, 15.1% (729/4824); tracheal intubation group, 14.9% (647/4337); adjusted difference in proportions of patients: 0.1%, 95% confidence interval -1.5% to 1.8%]. The longer-term outcomes were also similar between the groups (modified Rankin Scale: at 3 months, odds ratio 0.89, 95% confidence interval 0.69 to 1.14; at 6 months, odds ratio 0.91, 95% confidence interval 0.71 to 1.16). Sensitivity analyses did not alter the overall findings. There were no unexpected serious adverse events. Mean quality-adjusted life-years to 6 months were 0.03 in both groups (supraglottic airway group minus tracheal intubation group difference -0.0015, 95% confidence interval -0.0059 to 0.0028), and total costs were £157 (95% confidence interval -£270 to £583) lower in the tracheal intubation group. Although the point estimate of the incremental cost-effectiveness ratio suggested that tracheal intubation may be cost-effective, the huge uncertainty around this result indicates no evidence of a difference between groups. Limitations included imbalance in the number of patients in each group, caused by unequal distribution of high-enrolling paramedics; crossover between groups; and the fact that participating paramedics, who were volunteers, might not be representative of all paramedics in the UK. Findings may not be applicable to other countries. Among patients with out-of-hospital cardiac arrest, randomisation to the supraglottic airway group compared with the tracheal intubation group did not result in a difference in outcome at 30 days. There were no notable differences in costs, outcomes and overall cost-effectiveness between the groups. Future work could compare alternative supraglottic airway types with tracheal intubation; include a randomised trial of bag mask ventilation versus supraglottic airways; and involve other patient populations, including children, people with trauma and people in hospital. This trial is registered as ISRCTN08256118. This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and supported by the NIHR Comprehensive Research Networks and will be published in full in Health Technology Assessment; Vol. 26, No. 21. See the NIHR Journals Library website for further project information.


Treatment with rosuvastatin for severe dyslipidemia in patients with schizophrenia and schizoaffective disorder.
Mortality rates in patients with schizophrenia are double compared to those in the general population, with cardiovascular disease causing 50% of the excess. Lowering low-density lipoprotein (LDL) cholesterol is recognized as a primary target for the prevention of cardiovascular mortality according to the National Cholesterol Education Program-Adult Treatment Panel III. Use of lipid-lowering drugs such as statins is recommended when lifestyle changes are not sufficient to reach the LDL goal. The efficacy and safety of rosuvastatin treatment were evaluated in schizophrenic patients. 100 schizophrenic patients with severe dyslipidemia were identified. All were treated with antipsychotics. Fifty-two patients were treated with rosuvastatin and compared with 48 who did not receive statin treatment. All patients were screened for cardiovascular risk factors and examined at baseline. The effects of lipid-lowering medication on lipid profile, glucose homeostasis, and components of metabolic syndrome were evaluated at 3-month follow-up. The study began in 2003, and all data available until December 2005 are reported. After 3 months of statin therapy, a significant decrease in triglycerides, total cholesterol, LDL cholesterol, and non-high-density lipoprotein (non-HDL) cholesterol and in associated ratios (LDL/HDL, total cholesterol/HDL) was observed. The difference was highly significant compared to patients not receiving statin treatment. No significant changes occurred in HDL cholesterol, body mass index and waist circumference, or glucose homeostasis. The only component of metabolic syndrome affected by statin therapy was the serum triglyceride level. Rosuvastatin proved effective in the management of dyslipidemia in patients with schizophrenia treated with antipsychotics. More complex treatment may be required for associated metabolic disturbances.


Measuring disease progression in early Parkinson disease: the National Institutes of Health Exploratory Trials in Parkinson Disease (NET-PD) experience.
Optimizing assessments of rate of progression in Parkinson disease (PD) is important in designing clinical trials, especially of potential disease-modifying agents. To examine the value of measures of impairment, disability, and quality of life in assessing progression in early PD. Inception cohort analysis of data from 413 patients with early, untreated PD who were enrolled in 2 multicenter, randomized, double-blind clinical trials. Participants were randomly assigned to 1 of 5 treatments (67 received creatine, 66 received minocycline, 71 received coenzyme Q10, 71 received GPI-1485, and 138 received placebo). We assessed the association between the rates of change in measures of impairment, disability, and quality of life and time to initiation of symptomatic treatment. Time between baseline assessment and need for the initiation of symptomatic pharmaceutical treatment for PD was the primary indicator of disease progression. After adjusting for baseline confounding variables with regard to the Unified Parkinson's Disease Rating Scale (UPDRS) Part II score, the UPDRS Part III score, the modified Rankin Scale score, level of education, and treatment group, we assessed the rate of change for the following measurements: the UPDRS Part II score; the UPDRS Part III score; the Schwab and England Independence Scale score (which measures activities of daily living); the Total Functional Capacity scale; the 39-item Parkinson's Disease Questionnaire, summary index, and activities of daily living subscale; and version 2 of the 12-item Short Form Health Survey Physical Summary and Mental Summary. Variables reaching the statistical threshold in univariate analysis were entered into a multivariable Cox proportional hazards model using time to symptomatic treatment as the dependent variable. More rapid change (ie, worsening) in the UPDRS Part II score (hazard ratio, 1.15 [95% CI, 1.08-1.22] for 1 scale unit change per 6 months), the UPDRS Part III score (hazard ratio, 1.09 [95% CI, 1.06-1.13] for 1 scale unit change per 6 months), and the Schwab and England Independence Scale score (hazard ratio, 1.29 [95% CI, 1.12-1.48] for 5 percentage point change per 6 months) was associated with earlier need for symptomatic therapy. AND RELEVANCE In early PD, the UPDRS Part II score and Part III score and the Schwab and England Independence Scale score can be used to measure disease progression, whereas the 39-item Parkinson's Disease Questionnaire and summary index, Total Functional Capacity scale, and the 12-item Short Form Health Survey Physical Summary and Mental Summary are not sensitive to change. clinicaltrials.gov Identifiers: NCT00063193 and NCT00076492.