Osteopathic Manipulative Treatment and Cardiovascular Autonomic Parameters in Rugby Players: A Randomized, Sham-Controlled Trial.
The purpose of this study was to investigate the effects of osteopathic manipulative treatment (OMT) on cardiovascular autonomic parameters after a rugby match. Resting and reactivity (ie, response to orthostasis) measures of mean arterial pressure, heart rate, and heart rate variability were assessed in 23 male players after a single session of OMT, both 18 to 20 hours after a rugby match and in a corresponding no-match condition, in a randomized, sham-controlled, crossover design. Signs of reduced heart rate variability and elevated mean arterial pressure and heart rate were found 18 to 20 hours after a rugby match compared with the no-match condition. A significant increase in heart rate variability and a significant reduction in mean arterial pressure were observed after OMT in both the after-match and no-match conditions. Heart rate and heart rate variability responses to orthostasis were not affected by previous match competition, but were significantly larger after OMT compared with sham treatment. This study suggests the presence of cardiovascular autonomic alterations in rugby players after a competitive match, which may be indicative of prolonged fatigue and incomplete recovery. In these players, favorable changes in cardiovascular autonomic parameters were observed following a single session of OMT.


Analysis of fibulin-3 after exposure to asbestos-like fibers.
A significantly increased incidence of malignant mesothelioma in Biancavilla (Sicily, Italy) has been ascribed to exposure to fluoro-edenite, a fibrous amphibole extracted from a local stone quarry. Fibulin-3 is a highly conserved glycoprotein proposed as a biomarker for malignant mesothelioma that belongs to the family of extracellular matrix proteins. Previous studies demonstrated high Fibulin-3 plasma levels in workers with pleural plaques exposed to fluoro-edenite. Therefore, in order to gain insight into the biomolecular mechanisms of fluoro-edenite toxicity, we performed the analysis of Fibulin-3 expression by immunohistochemistry in the lung samples derived from sheep belonging to the area of Biancavilla. Furthermore, an in vitro model of exposed fluoro-edenite fibroblasts was used to perform functional experiments to better understand the modulation of Fibulin-3 expression. The percentage of immunostained area by Fibulin-3 was very much higher in exposed lungs compared with non-exposed ones. The Fibulin-3 protein level was significantly expressed in primary human lung fibroblasts exposed to 50 and 100µg/ml of fluoro-edenite fibers for 72h, compared to the unexposed controls. The results from the present study further demonstrate the implication of Fibulin-3 during fluoro-edenite exposure. This would endorse our previous results regarding the use of Fibulin-3 as a possible screening biomarker for fluoro-edenite exposed individuals, thereby contributing to the monitoring of the population at risk. The present study also suggested that the Fibulin-3 overexpression may reflect a defensive response of the tissues after exogenous stimuli and may be implicated in cancer development, especially in the context of fluoro-edenite contamination. However, further studies are necessary in order to make Fibulin-3 a customized screening tool.


Driving Rate Dependence of Avalanche Statistics and Shapes at the Yielding Transition.
We study stress time series caused by plastic avalanches in athermally sheared disordered materials. Using particle-based simulations and a mesoscopic elastoplastic model, we analyze system size and shear-rate dependence of the stress-drop duration and size distributions together with their average temporal shape. We find critical exponents different from mean-field predictions, and a clear asymmetry for individual avalanches. We probe scaling relations for the rate dependency of the dynamics and we report a crossover towards mean-field results for strong driving.


Alcohol intake as a risk factor for fracture.
High intakes of alcohol have adverse effects on skeletal health, but evidence for the effects of moderate consumption are less secure. The aim of this study was to quantify this risk on an international basis and explore the relationship of this risk with age, sex, and bone mineral density (BMD). We studied 5,939 men and 11,032 women from three prospectively studied cohorts comprising CaMos, DOES, and the Rotterdam Study. Cohorts were followed for a total of 75,433 person-years. The effect of reported alcohol intake on the risk of any fracture, any osteoporotic fracture, and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined included age and BMD. The results of the different studies were merged using weighted beta-coefficients. Alcohol intake was associated with a significant increase in osteoporotic and hip fracture risk, but the effect was nonlinear. No significant increase in risk was observed at intakes of 2 units or less daily. Above this threshold, alcohol intake was associated with an increased risk of any fracture (risk ratio [RR] = 1.23; 95% CI, 1.06-1.43), any osteoporotic fracture (RR = 1.38; 95% CI, 1.16-1.65), or hip fracture (RR = 1.68; 95% CI, 1.19-2.36). There was no significant interaction with age, BMD, or time since baseline assessment. Risk ratios were moderately but not significantly higher in men than in women, and there was no evidence for a different threshold for effect by gender. We conclude that reported intake of alcohol confers a risk of some importance beyond that explained by BMD. The validation of this risk factor on an international basis permits its use in case-finding strategies.


A plant plasma membrane proton-ATPase gene is regulated by development and environment and shows signs of a translational regulation.
A proton-pumping ATPase is present in the plasma membrane of plant cells where it sustains transport-related functions. This enzyme is encoded by a family of genes that shows signs of both transcriptional and post-transcriptional regulation. The regulation of pma1, one of the Nicotiana plumbaginifolia H+-ATPase genes, was characterized with the help of the beta-glucuronidase (gusA) receptor gene in transgenic plants. pma1 is active in the root epidermis, the stem cortex, and guard cells. This activity depends on developmental and growth conditions. For instance, pma1 activity in guard cells was strongly enhanced when the plant material (young seedlings or mature leaves) was incubated in liquid growth medium. pma1 is also expressed in several tissues of the reproductive organs where active transport is thought to occur but where scarcely any ATPase activity has been identified, namely in the tapetum, the pollen, the transmitting tissue, and the ovules. Several pma genes have a long 5'untranslated region (leader sequence) containing an upstream open reading frame (URF). Analysis of translational and transcriptional fusions with gusA in transgenic plants suggests that the pma1 leader sequence might activate translation of the main open reading frame, even though the URF is translated by a large majority of the scanning ribosomes. As confirmation, transient expression experiments showed that the pma1 leader causes a fourfold post-transcriptional increase of main open reading frame expression. Deletion of the URF by site-directed mutagenesis stimulated the main open reading frame translation 2.7-fold in an in vitro translational assay. These results are consistent with a regulatory mechanism involving translation reinitiation. Altogether, they suggest a fine, multilevel regulation of H+-ATPase activity in the plant.


How health care reform can transform the health of criminal justice-involved individuals.
Provisions of the Affordable Care Act offer new opportunities to apply a public health and medical perspective to the complex relationship between involvement in the criminal justice system and the existence of fundamental health disparities. Incarceration can cause harm to individual and community health, but prisons and jails also hold enormous potential to play an active and beneficial role in the health care system and, ultimately, to improving health. Traditionally, incarcerated populations have been incorrectly viewed as isolated and self-contained communities with only peripheral importance to the public health at large. This misconception has resulted in missed opportunities to positively affect the health of both the individuals and the imprisoned community as a whole and potentially to mitigate risk behaviors that may contribute to incarceration. Both community and correctional health care professionals can capitalize on these opportunities by working together to advocate for the health of the criminal justice-involved population and their communities. We present a set of recommendations for the improvement of both correctional health care, such as improving systems of external oversight and quality management, and access to community-based care, including establishing strategies for postrelease care and medical record transfers.


Chemoprevention for Barrett's esophagus trial. Design and outcome measures.
Barrett's esophagus is a premalignant condition in which normal squamous epithelium of the esophagus is replaced by metaplastic columnar epithelium. It is a known risk factor for the development of esophageal adenocarcinoma. With the incidence of esophageal adenocarcinoma rising, it is reasonable to study Barrett's esophagus as a potential target for therapy that may prevent, delay and/or reverse ongoing tumorigenic processes. Epidemiologic and animal studies support the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in the chemoprevention of several cancers, including esophageal cancer. Cyclo-oxygenase-2 (COX-2) inhibitors are a new class of NSAIDs that inhibit prostaglandin synthesis by selectively blocking the COX-2 enzyme. The COX-2 enzyme has been reported to be over-expressed in premalignant and malignant states, including in Barrett's esophagus and esophageal adenocarcinoma. The Chemoprevention for Barrett's Esophagus Trial (CBET) is a phase IIb, multicenter, randomized, double-masked, placebo-controlled study of the selective COX-2 inhibitor, celecoxib, in patients with Barrett's dysplasia. The sample size is 200 patients with high or low grade Barrett's dysplasia. Celecoxib is administered orally, 200 mg twice per day; the dosing schedule for placebo is the same. Randomization is stratified by dysplasia grade and by clinic. Endoscopy with biopsies is performed at specified time intervals according to the highest grade of dysplasia determined at randomization. The primary outcome measure is the change from baseline to 1 year in the proportion of biopsies exhibiting dysplasia. Secondary outcomes include change from baseline in the maximal grade, extent and surface area of dysplasia. Tertiary outcomes will include measurements of various relevant biomarkers.


Xenopus oocytes as a heterologous expression system for studying ion channels with the patch-clamp technique.
Oocytes from the Xenopus laevis represent one of the most widely used expression systems for functional characterization of ion channels. Their large size facilitates both injection of heterologous cRNA and subsequent electrophysiological recordings of ion channel currents. Furthermore, Xenopus oocytes translate cRNA very efficiently, resulting in the generation of a large number of ion channels in the plasma membrane. In this chapter, we outline methods for oocyte preparation and maintenance and describe procedures for patch-clamping of oocytes, with a special focus on the macropatch technique. We discuss some common problems associated with patch-clamping of oocytes and their use as an expression system for ion channels.


Chitosan oligosaccharides inhibit adipogenesis in 3T3-L1 adipocytes.
The 3T3-L1 cell line is a well-established and commonly used in vitro model to assess adipocyte differentiation. Over the course of several days, confluent 3T3-L1 cells can be converted to adipocytes in the presence of an adipogenic cocktail. In this study, the effects of chitosan oligosaccharides (CO) on adipocyte differentiation of 3T3-L1 cells were studied. The CO significantly decreased lipid accumulation, a marker of adipogenesis, in a dose-dependent manner. The low molecular mass CO (1-3 kDa) were the most effective at inhibiting adipocyte differentiation. Moreover, mRNA expression levels of both CCAAT/enhancer-binding protein (C/EBP) alpha and peroxisome proliferator-activated receptor (PPAR) gamma, the key adipogenic transcription factors, were markedly decreased by CO treatments. CO also significantly downregulated adipogenic marker proteins such as leptin, adiponectin, and resistin. Our results suggest a role for CO as anti-obesity agents by inhibiting adipocyte differentiation mediated through the downregulated expression of adipogenic transcription factors and other specific genes.


A phase II study of imatinib mesylate and capecitabine in metastatic breast cancer: Southwest Oncology Group Study 0338.
Imatinib mesylate is a potent inhibitor of the Bcr-Abl, c-Kit, and platelet-derived growth factor receptor (PDGFR) tyrosine kinases. On the basis of variable expression of c-Kit and PDGFR in breast cancer and of in vitro data supporting synergy between imatinib and capecitabine, the Southwest Oncology Group conducted a phase II trial of the combination in metastatic breast cancer. Eligible patients had progressive, measurable metastatic breast cancer and received<or=2 previous chemotherapy regimens for metastatic disease. Previous 5-fluorouracil or capecitabine for metastatic disease was not allowed. Patients were accrued on a 2-stage design and received imatinib mesylate 400 mg by mouth daily and capecitabine at 1000 mg/m2 by mouth twice daily for 14 days of a 21-day cycle. The primary endpoint was the confirmed response rate (RR). Tumors were evaluated for c-Kit, PDGFR-beta, and hormone receptor expression. Nineteen fully evaluable patients were enrolled, with a confirmed RR of 11% (95% CI, 1%-33%). Eleven percent had unconfirmed partial responses, and 42% had stable disease. The trial did not accrue to the second stage. The estimated 6-month progression-free survival was 16% (95% CI, 0%-32%), and the median overall survival was 14 months (95% CI, 7-15 months). The combination was well tolerated. Of 8 available tumor samples, 2 stained for c-Kit, and all had stromal staining for PDGFR-beta. In unselected patients, the combination of imatinib mesylate and capecitabine was well tolerated but did not result in improved RRs compared to those reported with capecitabine alone.


Role of frameshift ubiquitin B protein in Alzheimer's disease.
Alzheimer's disease (AD) is the most common neurodegenerative disease and is characterized by accumulation of misfolded and aggregated proteins. Since the ubiquitin-proteasome system (UPS) is the major intracellular protein quality control (PQC) system in eukaryotic cells, it is likely involved in the etiology of AD. The frameshift form of ubiquitin (Ubb(+1) ) accumulates in the neuritic plaques and neurofibrillary tangles in patients with AD. Ubb(+1) accumulates in an age-dependent manner as a result of RNA-polymerase mediated molecular misreading during transcription, which allows the formation of mutant proteins in the absence of gene mutations. The accumulation of the Ubb(+1) protein may act as an endogenous reporter for proteasome dysfunction and a growing number of studies have shown that Ubb(+1) may play more important pathogenic roles in AD etiology than previously hypothesized. The yeast Saccharomyces cerevisiae shares many conserved biological processes with all eukaryotic cells, including human neurons. This organism has been regarded as a model system for investigating the fundamental intracellular mechanisms, including those underlying neurodegeneration. We propose here that yeast systems biology approaches, combined with cell and molecular biology approaches will increase the relevant knowledge needed for advancement and elucidation of mechanisms and complex traits, which could provide new targets for therapeutic intervention in AD. WIREs Syst Biol Med 2016, 8:300-313. doi: 10.1002/wsbm.1340 For further resources related to this article, please visit the WIREs website.


Pembrolizumab versus placebo as post-nephrectomy adjuvant therapy for clear cell renal cell carcinoma (KEYNOTE-564): 30-month follow-up analysis of a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.
The first interim analysis of the KEYNOTE-564 study showed improved disease-free survival with adjuvant pembrolizumab compared with placebo after surgery in patients with clear cell renal cell carcinoma at an increased risk of recurrence. The analysis reported here, with an additional 6 months of follow-up, was designed to assess longer-term efficacy and safety of pembrolizumab versus placebo, as well as additional secondary and exploratory endpoints. In the multicentre, randomised, double-blind, placebo-controlled, phase 3 KEYNOTE-564 trial, adults aged 18 years or older with clear cell renal cell carcinoma with an increased risk of recurrence were enrolled at 213 hospitals and cancer centres in North America, South America, Europe, Asia, and Australia. Eligible participants had an Eastern Cooperative Oncology Group performance status of 0 or 1, had undergone nephrectomy 12 weeks or less before randomisation, and had not received previous systemic therapy for advanced renal cell carcinoma. Participants were randomly assigned (1:1) via central permuted block randomisation (block size of four) to receive pembrolizumab 200 mg or placebo intravenously every 3 weeks for up to 17 cycles. Randomisation was stratified by metastatic disease status (M0 vs M1), and the M0 group was further stratified by ECOG performance status and geographical region. All participants and investigators involved in study treatment administration were masked to the treatment group assignment. The primary endpoint was disease-free survival by investigator assessment in the intention-to-treat population (all participants randomly assigned to a treatment). Safety was assessed in the safety population, comprising all participants who received at least one dose of pembrolizumab or placebo. As the primary endpoint was met at the first interim analysis, updated data are reported without p values. This study is ongoing, but no longer recruiting, and is registered with ClinicalTrials.gov, NCT03142334. Between June 30, 2017, and Sept 20, 2019, 994 participants were assigned to receive pembrolizumab (n=496) or placebo (n=498). Median follow-up, defined as the time from randomisation to data cutoff (June 14, 2021), was 30·1 months (IQR 25·7-36·7). Disease-free survival was better with pembrolizumab compared with placebo (HR 0·63 [95% CI 0·50-0·80]). Median disease-free survival was not reached in either group. The most common all-cause grade 3-4 adverse events were hypertension (in 14 [3%] of 496 participants) and increased alanine aminotransferase (in 11 [2%]) in the pembrolizumab group, and hypertension (in 13 [3%] of 498 participants) in the placebo group. Serious adverse events attributed to study treatment occurred in 59 (12%) participants in the pembrolizumab group and one (<1%) participant in the placebo group. No deaths were attributed to pembrolizumab. Updated results from KEYNOTE-564 support the use of adjuvant pembrolizumab monotherapy as a standard of care for participants with renal cell carcinoma with an increased risk of recurrence after nephrectomy. Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA.


Development and clinical evaluation of automatic fiducial detection for tumor tracking in cine megavoltage images during volumetric modulated arc therapy.
Real-time tracking of implanted fiducials in cine megavoltage (MV) imaging during volumetric modulated arc therapy (VMAT) delivery is complicated due to the inherent low contrast of MV images and potential blockage of dynamic leaves configurations. The purpose of this work is to develop a clinically practical autodetection algorithm for motion management during VMAT. The expected field-specific segments and the planned fiducial position from the Eclipse (Varian Medical Systems, Palo Alto, CA) treatment planning system were projected onto the MV images. The fiducials were enhanced by applying a Laplacian of Gaussian filter in the spatial domain for each image, with a blob-shaped object as the impulse response. The search of implanted fiducials was then performed on a region of interest centered on the projection of the fiducial when it was within an open field including the case when it was close to the field edge or partially occluded by the leaves. A universal template formula was proposed for template matching and normalized cross correlation was employed for its simplicity and computational efficiency. The search region for every image was adaptively updated through a prediction model that employed the 3D position of the fiducial estimated from the localized positions in previous images. This prediction model allowed the actual fiducial position to be tracked dynamically and was used to initialize the search region. The artifacts caused by electronic interference during the acquisition were effectively removed. A score map was computed by combining both morphological information and image intensity. The pixel location with the highest score was selected as the detected fiducial position. The sets of cine MV images taken during treatment were analyzed with in-house developed software written in MATLAB (The Mathworks, Inc., Natick, MA). Five prostate patients were analyzed to assess the algorithm performance by measuring their positioning accuracy during treatment. The algorithm was able to accurately localize the fiducial position on MV images with success rates of more than 90% per case. The percentage of images in which each fiducial was localized in the studied cases varied between 23% and 65%, with at least one fiducial having been localized between 40% and 95% of the images. This depended mainly on the modulation of the plan and fiducial blockage. The prostate movement in the presented cases varied between 0.8 and 3.5 mm (mean values). The maximum displacement detected among all patients was of 5.7 mm. An algorithm for automatic detection of fiducial markers in cine MV images has been developed and tested with five clinical cases. Despite the challenges posed by complex beam aperture shapes, fiducial localization close to the field edge, partial occlusion of fiducials, fast leaf and gantry movement, and inherently low MV image quality, good localization results were achieved in patient images. This work provides a technique for enabling real-time accurate fiducial detection and tumor tracking during VMAT treatments without the use of extra imaging dose.


Effect of grain size on uranium(VI) surface complexation kinetics and adsorption additivity.
The contribution of variable grain sizes to uranium adsorption/desorption was studied using a sediment from the US DOE Hanford site. The sediment was wet sieved into four size fractions: coarse sand (1-2 mm), medium sand (0.2-1 mm), fine sand (0.053-0.2 mm), and clay/silt fraction (<0.053 mm). For each size fraction and their composite (sediment), batch and flow-cell experiments were performed to determine uranium adsorption isotherms and kinetic uranium adsorption and subsequent desorption. The results showed that uranium adsorption isotherms and adsorption/desorption kinetics were size specific, reflecting the effects of size-specific adsorption site concentration and kinetic rate constants. The larger-size fraction had a larger mass percentage in the sediment but with a smaller adsorption site concentration and generally a slower uranium adsorption/desorption rate. The same equilibrium surface complexation reaction and reaction constant could describe uranium adsorption isotherms for all size fractions and the composite after accounting for the effect of adsorption site concentration. Mass-weighted, linear additivity was observed for both uranium adsorption isotherms and adsorption/desorption kinetics in the composite. One important implication of this study is that grain-size distribution may be used to estimate uranium adsorption site and adsorption/desorption kinetic rates in heterogeneous sediments from a common location.


Management of pain in TMD patients: Bio-oxidative ozone therapy versus occlusal splints.
To compare the effects of bio-oxidative ozone application with occlusal splints in temporomandibular disorder (TMD) patients with pain. Forty participants were selected after the diagnosis of TMD and randomly divided into two groups: ozone group (OG, n = 20) and occlusal splint group (OCSG, n = 20). Ozone was applied to patients three times per week, for a total of six sessions. Patients in the OCSG were instructed to use occlusal splints every night over a period of four weeks. Mandibular movements showed significant differences for the time factor in OG and OCSG. Pressure pain thresholds of the temporal and masseter muscles at follow-up were significantly higher in the OCSG group. Both treatments statistically decreased the visual analog scale (VAS) scores. However, no statistically significant difference was observed between groups after the application of treatments. Occlusal splint treatment is still the gold treatment modality for objective pain relief in patients with TMD pain.


Yoga as an ancillary treatment for neurological and psychiatric disorders: a review.
Yoga is gaining acceptance as an ancillary medical treatment, but there have been few studies evaluating its therapeutic benefits in neurological and major psychiatric conditions. The authors reviewed the literature in English on the efficacy of yoga for these disorders. Only randomized, controlled trials were included, with the exception of the only study of yoga for bipolar disorder, which was observational. Trials were excluded if yoga was not the central component of the intervention. Of seven randomized, controlled trials of yoga in patients with neurological disorders, six found significant, positive effects. Of 13 randomized, controlled trials of yoga in patients with psychiatric disorders, 10 found significant, positive effects. These results, although encouraging, indicate that additional randomized, controlled studies are needed to critically define the benefits of yoga for both neurological and psychiatric disorders.


Magnetization of SrCu2(BO3)2 in ultrahigh magnetic fields up to 118 T.
The magnetization process of the orthogonal-dimer antiferromagnet SrCu2(BO3)2 is investigated in high magnetic fields of up to 118 T. A 1/2 plateau is clearly observed in the field range 84 to 108 T in addition to 1/8, 1/4, and 1/3 plateaus at lower fields. Using a combination of state-of-the-art numerical simulations, the main features of the high-field magnetization, a 1/2 plateau of width 24 T, a 1/3 plateau of width 34 T, and no 2/5 plateau, are shown to agree quantitatively with the Shastry-Sutherland model if the ratio of inter- to intradimer exchange interactions J'/J=0.63. It is further predicted that the intermediate phase between the 1/3 and 1/2 plateaus is not uniform but consists of a 1/3 supersolid followed by a 2/5 supersolid and possibly a domain-wall phase, with a reentrance into the 1/3 supersolid above the 1/2 plateau.


Atomistic and continuum scale modeling of functionalized graphyne membranes for water desalination.
Recent theoretical and experimental studies reported ultra-high water permeability and salt rejection in nanoporous single-layer graphene. However, creating and controlling the size and distribution of nanometer-scale pores pose significant challenges to application of these membranes for water desalination. Graphyne and hydrogenated graphyne have tremendous potential as ultra-permeable membranes for desalination and wastewater reclamation due to their uniform pore-distribution, atomic thickness and mechano-chemical stability. Using molecular dynamics (MD) simulations and upscale continuum analysis, the desalination performance of bare and hydrogenated α-graphyne and γ-{2,3,4}-graphyne membranes is evaluated as a function of pore size, pore geometry, chemical functionalization and applied pressure. MD simulations show that pores ranging from 20 to 50 Å2 reject in excess of 90% of the ions for pressures up to 1 GPa. Water permeability is found to range up to 85 L cm-2 day-1 MPa-1, which is up to three orders of magnitude larger than commercial seawater reverse osmosis (RO) membranes and up to ten times that of nanoporous graphene. Pore chemistry, functionalization and geometry are shown to play a critical role in modulating the water flux, and these observations are explained by water velocity, density, and energy barriers in the pores. The atomistic scale investigations are complemented by upscale continuum analysis to examine the performance of these membranes in application to cross-flow RO systems. This upscale analysis, however, shows that the significant increase in permeability, observed from MD simulations, does not fully translate to current RO systems due to transport limitations. Nevertheless, upscale calculations predict that the higher permeability of graphyne membranes would allow up to six times higher permeate recovery or up to 6% less energy consumption as compared to thin-film composite membranes at currently accessible operating conditions. Significantly higher energy savings and permeate recovery can be achieved if higher feed-flow rates can be realized.


Efficacy of an Online Self-Help Treatment for Comorbid Alcohol Misuse and Emotional Problems in Young Adults: Protocol for a Randomized Controlled Trial.
Alcohol misuse and emotional problems (ie, depression and anxiety) are highly comorbid among Canadian young adults. However, there is a lack of integrated, accessible, and evidence-based treatment options for these young adults. The main goal of this study is to develop and test the efficacy of an integrated, online self-help program designed to target both alcohol misuse and emotional problems. A two-arm randomized controlled trial design will be used to compare the efficacy of the online integrated treatment to a psychoeducational control group. A target sample of 214 participants will be recruited and randomly assigned to either condition. The integrated treatment will last 8 weeks, and participants will work through 12 modules. Modules will incorporate content based on principles of cognitive behavioral therapy and motivational interviewing. Participants in the control group will receive links to psychoeducational resources and will have access to the full treatment after follow-up. The primary outcome will be the number of Canadian standard drinks consumed in the week leading up the assessment. Secondary outcomes of interest include symptoms of depression, anxiety, alcohol-related problems, quality of life, and use of other drugs. Assessments will be completed at 3 time-points: at baseline, at the end of treatment (ie, 8 weeks), and at follow-up (ie, 24 weeks). Upon completion, data will be analyzed using generalized linear mixed models. Data collection began in June 2018 and will continue until January 2020. Final study results will be submitted for publication by July 2020. Currently, there are no integrated treatments designed to target alcohol misuse and the range of emotional problems experienced by young adults. This research stands to provide an effective, accessible (ie, Web-based), and feasible option to treat the many struggling young adults in this country. ClinicalTrials.gov ID NCT03406039; https://clinicaltrials.gov/ct2/show/NCT03406039 (Archived by WebCite at http://www.webcitation.org/72fDefnrh). PRR1-10.2196/11298.


Computational Design of Non-natural Sugar Alcohols to Increase Thermal Storage Density: Beyond Existing Organic Phase Change Materials.
Thermal storage, a technology that enables us to control thermal energy, makes it possible to reuse a huge amount of waste heat, and materials with the ability to treat larger thermal energy are in high demand for energy-saving societies. Sugar alcohols are now one promising candidate for phase change materials (PCMs) because of their large thermal storage density. In this study, we computationally design experimentally unknown non-natural sugar alcohols and predict their thermal storage density as a basic step toward the development of new high performance PCMs. The non-natural sugar alcohol molecules are constructed in silico in accordance with the previously suggested molecular design guidelines: linear elongation of a carbon backbone, separated distribution of OH groups, and even numbers of carbon atoms. Their crystal structures are then predicted using the random search method and first-principles calculations. Our molecular simulation results clearly demonstrate that the non-natural sugar alcohols have potential ability to have thermal storage density up to ∼450-500 kJ/kg, which is significantly larger than the maximum thermal storage density of the present known organic PCMs (∼350 kJ/kg). This computational study suggests that, even in the case of H-bonded molecular crystals where the electrostatic energy contributes mainly to thermal storage density, the molecular distortion and van der Waals energies are also important factors to increase thermal storage density. In addition, the comparison between the three eight-carbon non-natural sugar alcohol isomers indicates that the selection of preferable isomers is also essential for large thermal storage density.


Exploring Coverage of the 2008 Irish Dioxin Crisis in the Irish and UK Newsprint Media.
The 2008 dioxin crisis occurred as a result of contamination of Irish pork. The event had significant implications for Ireland's economy and the reputation of its agricultural industry, as well as raising concerns for human health. This study describes the results of a content analysis of Irish and UK newspaper coverage of the 2008 Irish dioxin crisis, as this is likely to provide insight into how public perceptions of this issue were shaped. Articles from 16 print publications were systematically sampled for the period December 2008 to February 2009. The resulting data set of 141 articles was examined using a coding protocol developed based on previous research and refined during piloting. Results indicated that the dioxin crisis was primarily portrayed by the media as an industry/economic crisis, dominant in 26.9% of articles in the sample. Within this dominant portrayal, the agricultural industry was frequently cited as being in crisis (42.6%); however, the implications of the crisis on the wider economic environment also received attention (17.7%). Differences between Irish and UK-based media were also examined, revealing that while the Irish media most frequently described the crisis in terms of its impact on the industry and economy, the UK media were more likely to portray the crisis as a risk to health. These dominant media messages and message framings have implications for the public understanding of the issue in each country and potential consequences regarding perception of the adequacy of existing food policy and regulatory oversight.


Myeloma and marrow adiposity: Unanswered questions and future directions.
Multiple myeloma (MM) is a haematological malignancy characterised by the proliferation and accumulation of terminally differentiated abnormal plasma cells in the bone marrow. Patients suffer from bone pain, factures, anaemia, osteolytic lesions and renal failure. Despite recent advancement in therapy MM remains an incurable disease due to the emergences of drug resistance and frequent relapse. For many decades, research has been heavily focused on understanding the relationship between bone cells such as osteoblast, osteocytes and osteoclasts and the infiltrating tumour cells. However, it is now clear that the tumour-supportive bone microenvironment including cellular and non-cellular components play an important role in driving MM progression and bone disease. One of the most abundant cell types in the bone microenvironment is the bone marrow adipocyte (BMAd). Once thought of as inert space filling cells, they have now been recognised as having specialised functions, signalling in an autocrine, paracrine and endocrine manner to support normal systemic homeostasis. BMAds are both an energy store and a source of secreted adipokines and bioactive substances, MM cells are able to hijack this metabolic machinery to fuel migration, growth and survival. With global obesity on the rise, it has never been more important to further understand the contribution these cells have in both normal and disease settings. The aim of this review is to summarise the large body of emerging evidence supporting the interplay between BMAds and MM cells and to delineate how they fit into the vicious cycle of disease.


Luminescent Platinum(II) Complexes of N^N-^N Amido Ligands with Benzannulated N-Heterocyclic Donor Arms: Quinolines Offer Unexpectedly Deeper Red Phosphorescence than Phenanthridines.
A platform for investigating the impact of π-extension in benzannulated, anionic pincer-type N^N-^N-coordinating amido ligands and their Pt(II) complexes is presented. Based on bis(8-quinolinyl)amine, symmetric and asymmetric proligands bearing quinoline or π-extended phenanthridine (3,4-benzoquinoline) units are reported, along with their red-emitting, phosphorescent Pt(II) complexes of the form (N^N-^N)PtCl. Comparing the photophysical properties of complexes of (quinolinyl)amido ligands with those of π-extended (phenanthridinyl)amido analogues revealed a counterintuitive impact of site-selective benzannulation. Contrary to conventional assumptions regarding π-extension, and in contrast to isoenergetic lowest energy absorption bands and a red shift in fluorescence from the organic proligands, a blue shift of nearly 40 nm in the emission wavelength is observed for Pt(II) complexes with more extended bis(phenanthridinyl) ligand π-systems. Comparing the ground state and triplet excited state structures optimized from density functional theory (DFT) and time-dependent-DFT calculations, we trace this effect to a greater rigidity of the benzannulated complexes, resulting in a higher energy emissive triplet state, rather than to a significant perturbation of orbital energies caused by π-extension.


The link between personality dimensions and pain perception in patients with diabetes mellitus or cancer.
Diabetes mellitus and cancer are two diseases with a strong psychological impact. Personality traits modulate the perception of pain and the response to disease. The specificity of this study consists of the assessment of personality, pain and emotional impact in the two diseases. The study included 130 participants assigned to 3 groups: patients with diabetes mellitus, patients with cancer disease, and a control group. The personality traits of all the participants were analyzed using Cloninger's Temperament and Character Inventory (TCI). For the evaluation of pain, as well as associated anxiety and depression in the diabetes and cancer groups, the Brief Pain Inventory (BPI) and the Hospital Anxiety and Depression Scale (HADS) were used. Patients with diabetes mellitus and cancer disease had significantly higher total values on the Harm Avoidance scale (HA) (p<0.001) and lower total values on the Self-Directedness scale (SD), Reward Dependence scale (RD), Cooperativeness scale (CO) (p<0.001) compared to the control group. Major anxiety was predominant in patients with diabetes mellitus (34%), and major depression was prevalent in cancer patients (17.5%). Patients with diabetes mellitus obtained a significantly higher severity score at BPI scale than patients with cancer disease (p=0.03). The existence of a mutual personality profile featuring high levels of Harm Avoidance and low levels of Self-Directedness in patients with diabetes mellitus and cancer who experience pain has great implications for the therapeutic approach. A potential future avenue of management in these diseases may lie in targeting particular personality aspects of chronic pain patients.


Analyzing heat capacity profiles of peptide-containing membranes: cluster formation of gramicidin A.
The analysis of peptide and protein partitioning in lipid membranes is of high relevance for the understanding of biomembrane function. We used statistical thermodynamics analysis to demonstrate the effect of peptide mixing behavior on heat capacity profiles of lipid membranes with the aim to predict peptide aggregation from c(P)-profiles. This analysis was applied to interpret calorimetric data on the interaction of the antibiotic peptide gramicidin A with lipid membranes. The shape of the heat capacity profiles was found to be consistent with peptide clustering in both gel and fluid phase. Applying atomic force microscopy, we found gramicidin A aggregates and established a close link between thermodynamics data and microscopic imaging. On the basis of these findings we described the effect of proteins on local fluctuations. It is shown that the elastic properties of the membrane are influenced in the peptide environment.


Role of Bud3p in producing the axial budding pattern of yeast.
Yeast cells can select bud sites in either of two distinct spatial patterns. a cells and alpha cells typically bud in an axial pattern, in which both mother and daughter cells form new buds adjacent to the preceding division site. In contrast, a/alpha cells typically bud in a bipolar pattern, in which new buds can form at either pole of the cell. The BUD3 gene is specifically required for the axial pattern of budding: mutations of BUD3 (including a deletion) affect the axial pattern but not the bipolar pattern. The sequence of BUD3 predicts a product (Bud3p) of 1635 amino acids with no strong or instructive similarities to previously known proteins. However, immunofluorescence localization of Bud3p has revealed that it assembles in an apparent double ring encircling the mother-bud neck shortly after the mitotic spindle forms. The Bud3p structure at the neck persists until cytokinesis, when it splits to yield a single ring of Bud3p marking the division site on each of the two progeny cells. These single rings remain for much of the ensuing unbudded phase and then disassemble. The Bud3p rings are indistinguishable from those of the neck filament-associated proteins (Cdc3p, Cdc10p, Cdc11p, and Cdc12p), except that the latter proteins assemble before bud emergence and remain in place for the duration of the cell cycle. Upon shift of a temperature-sensitive cdc12 mutant to restrictive temperature, localization of both Bud3p and the neck filament-associated proteins is rapidly lost. In addition, a haploid cdc11 mutant loses its axial-budding pattern upon shift to restrictive temperature. Taken together, the data suggest that Bud3p and the neck filaments are linked in a cycle in which each controls the position of the other's assembly: Bud3p assembles onto the neck filaments in one cell cycle to mark the site for axial budding (including assembly of the new ring of neck filaments) in the next cell cycle. As the expression and localization of Bud3p are similar in a, alpha, and a/alpha cells, additional regulation must exist such that Bud3p restricts the position of bud formation in a and alpha cells but not in a/alpha cells.


Industry funding was associated with increased use of core outcome sets.
The objective of this study was to assess the uptake of the rheumatoid arthritis core outcome set (RA-COS) using data from multiple data providers, and to investigate factors that may influence this uptake. An observational review was carried out on all clinical trials of rheumatoid arthritis that were indexed on the World Health Organization-International Clinical Trials Registry Platform (WHO-ICTRP). Various measures of COS uptake were calculated from information presented in the trial registries and trial publications. Logistic regression was conducted to investigate factors thought to be associated with planned COS uptake. A total of 341 trials were eligible for the evaluation of RA-COS uptake. In the decade leading up to 2019, the assessment of uptake based on published results was maintained at just over 80%. Trials that were not commercially funded were much less likely to plan to measure the RA-COS than those with industry funding (60% vs. 80%; adjusted OR 0.18, 95% CI 0.11 to 0.32; P < 0.001). This study has demonstrated that the use of the WHO-ICTRP can identify a large and geographically diverse range of trials to include in the evaluation of COS uptake.


[NT-Pro-BNP levels performance before and after reversion to sinus rhythm in patients with preserved ventricular function].
Our objective was to evaluate changes of N-terminal pro-BNP (NT-Pro-BNP) levels at baseline and after restoration to sinus rhythm in hemodynamic stable patients with lone atrial fibrillation (LAF) with preserved left ventricular function. NT-Pro-BNP levels were obtained before and after cardioversion in thirty hemodynamic stable patients with LAF and preserved left ventricular function. At baseline levels of NT-Pro BNP levels were significatively higher than a normal control group. NT-Pro-BNP levels decreased significantly following cardioversion from 529 (157-1763) to 318 (98-870) pg/ml, p < 0.0001. Decreasing of N-terminal pro-BNP concentrations was observed after any mode of cardioversion: electrical or pharmacologic, 345 (153-1151) pg/ml to 169 (86-407) pg/ml, p: 0.02 and from 1624 (541-4010) pg/ml to 856 (532-1160) pg/ml, p < 0.001, respectively. N-terminal pro-BNP decreasing was observed mainly in patients with length of LAF longer than 8 hours: 1289 (338-2103) to 410 (169-905) pg/ml, p < 0.001 but no difference was detected when such length was less than 8 hours: 274 (137-2300) to 286 (82-1440), p = NS. Our study showed that baseline levels of NT-pro-BNP decreased shortly after reversion of patients with LAF to sinus rhythm. This performance occurs predominantly in patients with LAF length of at least eight hours.


Telemedical Care and Monitoring for Patients with Chronic Heart Failure Has a Positive Effect on Survival.
Telemedical care and monitoring programs for patients with chronic heart failure have shown beneficial effects on survival in several small studies. The utility in routine care remains unclear. We evaluated a large-sized telemedicine program in a routine care setting, enrolling in total 2,622 patients (54.7 percent male, mean age: 73.7 years) with chronic heart failure. We used reimbursement data from a large statutory health insurance and approached a matched control analysis. In a complex propensity score matching procedure, 3,719 suitable controls (54.2 percent male, mean age: 74.5 years) were matched to 1,943 intervention patients (54.1 percent male, mean age: 74.4 years). The primary endpoint of our analysis was survival after 1 year. Analyses revealed a higher survival probability among subjects of the intervention group compared to controls group after 1 year (adjusted OR: 1.47, CI 95 percent: 1.21-1.80, p < .001) and 2 years (adjusted OR: 1.51, CI 95 percent: 1.28-1.77, p < .001), respectively. The probabilities to survive after 1 and 2 years were significantly increased in the intervention group. Our findings confirm previous results of controlled trials and importantly indicate that patients with chronic heart failure may benefit from telemonitoring programs in routine care.


Is impulsivity a common trait in bipolar and unipolar disorders?
Impulsivity is increased in bipolar and unipolar disorders during episodes and is associated with substance abuse disorders and suicide risk. Impulsivity between episodes predisposes to relapses and poor therapeutic compliance. However, there is little information about impulsivity during euthymia in mood disorders. We sought to investigate trait impulsivity in euthymic bipolar and unipolar disorder patients, comparing them to healthy individuals and unaffected relatives of bipolar disorder patients. Impulsivity was evaluated by the Barratt Impulsiveness Scale (BIS-11A) in 54 bipolar disorder patients, 25 unipolar disorder patients, 136 healthy volunteers, and 14 unaffected relatives. The BIS-11A mean scores for all four groups were compared through the Games-Howell test for all possible pairwise combinations. Additionally, we compared impulsivity in bipolar and unipolar disorder patients with and without a history of suicide attempt and substance abuse disorder. Bipolar and unipolar disorder patients scored significantly higher than the healthy controls and unaffected relatives on all measures of the BIS-11A except for attentional impulsivity. On the attentional impulsivity measures there were no differences among the unaffected relatives and the bipolar and unipolar disorder groups, but all three of these groups scored higher than the healthy participant group. There was no difference in impulsivity between bipolar and unipolar disorder subjects with and without suicide attempt. However, impulsivity was higher among bipolar and unipolar disorder subjects with past substance use disorder compared to patients without such a history. Questionnaire-measured impulsivity appears to be relatively independent of mood state in bipolar and unipolar disorder patients; it remains elevated in euthymia and is higher in individuals with past substance abuse. Elevated attentional and lower non-planning impulsivity in unaffected relatives of bipolar disorder patients distinguished them from healthy participants, suggesting that increased attentional impulsivity may predispose to development of affective disorders, while reduced attentional impulsivity may be protective.


Assessing thermochemical properties of materials through ab initio quantum-mechanical methods: the case of α-Al2O3.
The thermochemical behavior of α-Al2O3 corundum in the whole temperature range 0-2317 K (melting point) and under pressures up to 12 GPa is predicted by applying ab initio methods based on the density functional theory (DFT), the use of a local basis set and periodic-boundary conditions. Thermodynamic properties are treated both within and beyond the harmonic approximation to the lattice potential. In particular, a recent implementation of the quasi-harmonic approximation, in the Crystal program, is here shown to provide a reliable description of the thermal expansion coefficient, entropy, constant-volume and constant-pressure specific heats, and temperature dependence of the bulk modulus, nearly up to the corundum melting temperature. This is a remarkable outcome suggesting α-Al2O3 to be an almost perfect quasi-harmonic crystal. The effect of using different computational parameters and DFT functionals belonging to different levels of approximations on the accuracy of the thermal properties is tested, providing a reference for further studies involving alumina polymorphs and, more generally, quasi-ionic minerals.


[Financial protection in health: Mexico, 1992 to 2004].
To document trends in financial protection in the health care system in Mexico between 1992 and 2004, applying a series of indicators that measure catastrophic and impoverishing health spending and the Index of Fairness in Financial Contributions. MATERIALS Y METHODS: This study uses the biannual time series of the Survey of Household Income and Expenditures (ENIGH) spanning the period 1992 to 2004. The methodologies seek to measure the level and distribution of the burden of health care finance on households, and the financial protection offered to them by the health care system. Four indicators are presented: 1) the Index of Fairness in Financial Contributions, 2) the proportion of households with catastrophic health expenditure, 3) the proportion of households with impoverishment due to health spending and 4) the sum of the proportion of households with catastrophic or impoverishing health spending, which is referred to as excessive health spending. The analysis presented in this document is descriptive, leaving for later studies a deeper analysis of causal aspects. The number of families that suffer impoverishment due to health spending increased from 5.2% in 1992, reached a high of 9.9% in 1996, and then gradually declined to 1.8% by 2004. The proportion of households with catastrophic expenses began at 2.8% in 1992, increased to 4.2% in 1998 and then fell to a level of 2.6% in 2004. The improvements from 2000 on are concentrated among the uninsured population, families affiliated to Popular Health Insurance, and households in the poorest two quintiles of the income distribution. The patterns over time in excessive health spending reflect a worsening during periods of economic crisis, post-crisis recovery, and a sustained improvement beginning in the year 2000. The data suggest that part of the reduction in the number of households with excessive health spending is due to the extension of financial protection for Mexican families through the Popular Health Insurance, while another part is associated with a decline in poverty. In addition,this paper documents an important relationship between economic trends and catastrophic and impoverishing health spending, suggesting the importance of financially protecting families through health insurance. Financial protection assists in guaranteeing that when economic crisis--of a country or of a family--coincides with illness, health care payments do not become the cause of a long or permanent period of impoverishment for households.


GABA-independent GABAA receptor openings maintain tonic currents.
Activation of GABA(A) receptors (GABA(A)Rs) produces two forms of inhibition: phasic inhibition generated by the rapid, transient activation of synaptic GABA(A)Rs by presynaptic GABA release, and tonic inhibition generated by the persistent activation of perisynaptic or extrasynaptic GABA(A)Rs, which can detect extracellular GABA. Such tonic GABA(A)R-mediated currents are particularly evident in dentate granule cells in which they play a major role in regulating cell excitability. Here we show that in rat dentate granule cells in ex vivo hippocampal slices, tonic currents are predominantly generated by GABA-independent GABA(A) receptor openings. This tonic GABA(A)R conductance is resistant to the competitive GABA(A)R antagonist SR95531 (gabazine), which at high concentrations acts as a partial agonist, but can be blocked by an open channel blocker, picrotoxin. When slices are perfused with 200 nm GABA, a concentration that is comparable to CSF concentrations but is twice that measured by us in the hippocampus in vivo using zero-net-flux microdialysis, negligible GABA is detected by dentate granule cells. Spontaneously opening GABA(A)Rs, therefore, maintain dentate granule cell tonic currents in the face of low extracellular GABA concentrations.


Nonequilibrium collective dynamics in photoexcited lipid multilayers by time resolved diffuse x-ray scattering.
We study the nonequilibrium shape fluctuations in fluorescence labeled phospholipid multibilayers composed of the model lipid DOPC and the well-known lipid dye Texas red, driven out of equilibrium by short laser pulses. The temporal evolution of the lipid bilayer undulations after excitation was recorded by time resolved x-ray diffraction. Already at moderate peak intensities (Pp≤10(5) W/cm2), pulsed laser illumination leads to significant changes of the undulation modes in a well-defined lateral wavelength band. The observed phenomena evolve on nano- to microsecond time scales after optical excitation, and can be described in terms of a modulation instability in the lipid multilamellar stack.


The human preprotachykinin-A gene promoter has been highly conserved and can drive human-like marker gene expression in the adult mouse CNS.
Toward an understanding of the mechanisms controlling Preprotachykinin-A (PPTA) transcription, we introduced a 380-kb human yeast artificial chromosome containing the PPTA gene tagged with the beta-galactosidase gene into transgenic mice. This resulted in a pattern of LacZ expression in the central nervous system (CNS) remarkably similar to that reported for PPTA mRNA in the rat. However, the human gene drove expression in areas of the mouse CNS not associated with strong PPTA expression in rodents but which have been shown to express PPTA in the human. This study clearly demonstrates the high degree of conservation of the mechanisms involved in PPTA transcription that has occurred throughout 100 million of divergent human and rodent evolution. This study also defines the maximum linear extent of the human PPT-A promoter. We believe these findings constitute the removal of a significant obstacle in studying the transcriptional regulation of the human PPTA gene in vivo.


Anonymous partnerships among MSM and transgender women (TW) recently diagnosed with HIV and other STIs in Lima, Peru: an individual-level and dyad-level analysis.
Partner notification (PN) following sexually transmitted disease (STI) diagnosis is a key strategy for controlling HIV/STI transmission. Anonymous partnerships are an important barrier to PN and often associated with high-risk sexual behaviour. Limited research has examined the profile of men who have sex with men (MSM) and transgender women (TW) who engage in anonymous sex. To better understand anonymous partnership practices in Lima, Peru, we assessed participant-level and partnership-level characteristics associated with anonymous sex among a sample of MSM and TW recently diagnosed with HIV/STI. MSM and TW diagnosed with HIV/STI within the past month completed a cross-sectional survey regarding anticipated PN practices. Participants reported sexual partnership types and characteristics of up to three of their most recent partners. Using a Poisson generalised estimating equation model, we assessed participant-level and partnership-level characteristics associated with anonymous partnerships. Among 395 MSM and TW with HIV/STI, 36.0% reported at least one anonymous sexual partner in the past 3 months (mean of 8.6 anonymous partners per participant; SD 17.0). Of the 971 partnerships reported, 118 (12.2%) were anonymous and the majority (84.8%) were with male partners, followed by 11.0% with female partners and 4.2% with transgender/travesti partners. Partner-level characteristics associated with increased likelihood of having an anonymous partner included female (adjusted prevalence ratio (aPR) 2.28, 95% CI 1.05 to 4.95, p=0.04) or transgender/travesti (aPR 4.03, 95% CI 1.51 to 10.78, p=0.006) partner gender. By assessing both individual-level and dyadic-level factors, these results represent an important step in understanding the complexity of partnership interactions and developing alternative PN strategies for Latin America.


Direct sequencing and expression analysis of a large number of miRNAs in Aedes aegypti and a multi-species survey of novel mosquito miRNAs.
MicroRNAs (miRNAs) are a novel class of gene regulators whose biogenesis involves hairpin structures called precursor miRNAs, or pre-miRNAs. A pre-miRNA is processed to make a miRNA:miRNA* duplex, which is then separated to generate a mature miRNA and a miRNA*. The mature miRNAs play key regulatory roles during embryonic development as well as other cellular processes. They are also implicated in control of viral infection as well as innate immunity. Direct experimental evidence for mosquito miRNAs has been recently reported in anopheline mosquitoes based on small-scale cloning efforts. We obtained approximately 130, 000 small RNA sequences from the yellow fever mosquito, Aedes aegypti, by 454 sequencing of samples that were isolated from mixed-age embryos and midguts from sugar-fed and blood-fed females, respectively. We also performed bioinformatics analysis on the Ae. aegypti genome assembly to identify evidence for additional miRNAs. The combination of these approaches uncovered 98 different pre-miRNAs in Ae. aegypti which could produce 86 distinct miRNAs. Thirteen miRNAs, including eight novel miRNAs identified in this study, are currently only found in mosquitoes. We also identified five potential revisions to previously annotated miRNAs at the miRNA termini, two cases of highly abundant miRNA* sequences, 14 miRNA clusters, and 17 cases where more than one pre-miRNA hairpin produces the same or highly similar mature miRNAs. A number of miRNAs showed higher levels in midgut from blood-fed female than that from sugar-fed female, which was confirmed by northern blots on two of these miRNAs. Northern blots also revealed several miRNAs that showed stage-specific expression. Detailed expression analysis of eight of the 13 mosquito-specific miRNAs in four divergent mosquito genera identified cases of clearly conserved expression patterns and obvious differences. Four of the 13 miRNAs are specific to certain lineage(s) within mosquitoes. This study provides the first systematic analysis of miRNAs in Ae. aegypti and offers a substantially expanded list of miRNAs for all mosquitoes. New insights were gained on the evolution of conserved and lineage-specific miRNAs in mosquitoes. The expression profiles of a few miRNAs suggest stage-specific functions and functions related to embryonic development or blood feeding. A better understanding of the functions of these miRNAs will offer new insights in mosquito biology and may lead to novel approaches to combat mosquito-borne infectious diseases.


Motoneuron fate specification revealed by patterned LIM homeobox gene expression in embryonic zebrafish.
In zebrafish, individual primary motoneurons can be uniquely identified by their characteristic cell body positions and axonal projection patterns. The fate of individual primary motoneurons remains plastic until just prior to axogenesis when they become committed to particular identities. We find that distinct primary motoneurons express particular combinations of LIM homeobox genes. Expression precedes axogenesis as well as commitment, suggesting that LIM homeobox genes may contribute to the specification of motoneuronal fates. By transplanting them to new spinal cord positions, we demonstrate that primary motoneurons can initiate a new program of LIM homeobox gene expression, as well as the morphological features appropriate for the new position. We conclude that the patterned distribution of different primary motoneuronal types within the zebrafish spinal cord follows the patterned expression of LIM homeobox genes, and that this reflects a highly resolved system of positional information controlling gene transcription.


Controversies between regulations of research ethics and protection of personal data: informed consent at a cross-road.
This paper explores some key discrepancies between two sets of normative requirements applicable to the research use of personal data and human biological materials: (a) the data protection regime which follows the application of the European Union General Data Protection Regulation (GDPR), and (b) the Declaration of Helsinki, CIOMS guidelines and other research ethics regulations. One source of this controversy is that the GDPR requires consent to process personal data to be clear, concise, specific and granular, freely given and revocable and therefore has challenged the concept of 'broad consent', which has been widely applied in the context of biobanking. Another source of controversy is the interplay between regulations of research ethics and protection of personal data related to the secondary use of personal data and biological materials. In this case, the GDPR 'research condition' provides an alternative to re-consent for the use of previously collected personal data and biological materials. Although the mentioned controversies have been raised in the legal literature, they have not been explicitly addressed from the research ethics perspective. Should consent be regarded as a priority legal basis for personal data processing in health data research? Can broad consent still be a suitable legal ground for biobanking? What should be the role of research ethics provisions that differ from the GDPR standards, and what should be the role and function of research ethics committees in the changing environment of health data research? These are the ongoing controversies to be explored in the paper.


Long-chain polyunsaturated fatty acid supplementation in preterm infants.
The n-3 and n-6 essential fatty acids alpha linolenic acid (ALA) and linoleic acid (LA) are the precursors of the n-3 and n-6 longchain polyunsaturated fatty acids (LCPUFA). Controversy exists over whether LCPUFA are essential nutrients for preterm infants, who may not be able to synthesise sufficient amounts of LCPUFA to satisfy the needs of the developing brain and retina. The aim of this review is to assess whether supplementation of formula with LCPUFA is safe and of benefit to preterm infants. Trials were identified by MEDLINE (February 2007), Oxford Database of Perinatal Trials, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2007) and by checking reference lists of relevant articles and conference proceedings. All randomised trials of formula supplemented with LCPUFA and with clinical endpoints were reviewed. Fifteen randomised trials assessing the clinical effects of feeding formula supplemented with LCPUFA were included in the review. Of the fifteen randomised trials included in the review, four of these were not classified as of high quality, due to low follow-up, uncertainty regarding concealment of patient allocation and randomisation, and problems with assessment methodology. VISUAL ACUITY: Visual acuity over the first year was measured by Teller or Lea acuity cards in eight studies, by VEP in six studies and by ERG in two studies. Most studies found no significant differences in any visual assessment between supplemented and control infants. Most of the trials have used Bayley Scales of Infant Development (BSID) at 12 to 24 months post-term with three out of seven studies reporting some benefit of LCPUFA in different populations of supplemented infants at different postnatal ages. Meta-analysis of BSID of four studies at 12 months (N = 364) and three studies at 18 months (N = 494) post-term showed no significant effect of supplementation on neurodevelopment. Carlson 1992 and Carlson 1996 demonstrated lower novelty preferences (possibly predictive of lower intelligence) in the supplemented compared with the control group. The investigators however concluded that supplemented infants may have more rapid visual information processing given that they had more looks and each look was of shorter duration. Four out of thirteen studies reported benefits of LCPUFA on growth of supplemented infants at different postnatal ages. Two trials (Carlson 1992; Carlson 1996) suggested that LCPUFA supplemented infants grow less well than controls, possibly due to a reduction in AA levels that occurs when n-3 supplements are used without n-6 supplements. Recent trials with addition of AA to the supplement have reported no significant negative effect on growth. Fewtrell 2002 reported mild reductions in length and weight z scores at 18 months. Contrary to these results, meta-analysis of five studies (Uauy 1990; Carlson 1996; Hansen 1997; Vanderhoof 1999; Innis 2002) showed increased weight and length at two months post-term in supplemented infants. Meta-analysis of four studies at 12 months (N = 271) and two studies at 18 months (N = 396) post-term showed no significant effect of supplementation on weight, length or head circumference. Uauy 1992 reported no significant effect of LCPUFA supplementation on bleeding time and red cell membrane fragility. Infants enrolled in the trials were relatively mature and healthy preterm infants. Assessment schedule and methodology, dose and source of supplementation and fatty acid composition of the control formula varied between trials. When the results of the RCT's are pooled, no clear long-term benefits were demonstrated for infants receiving formula supplemented with LCPUFA. There was no evidence that supplementation of formula with n-3 and n-6 LCPUFA impaired the growth of preterm infants.


Novel synthetic vertebrae provide realistic haptics for pedicle screw placement.
During vertebral surgery, misplaced pedicle screws can harm vital neural and vascular structures. Haptic distinction between cortical and cancellous bone structures is therefore essential for correct screw placement. This tactile experience during pedicle screw placement can be obtained by training on human or animal specimens even if expensive or ethically questionable. In this study, novel synthetic vertebrae were evaluated within a hybrid simulator to provide realistic haptics for the training of spine surgeries. Synthetic vertebrae were custommade of calcium powder-based composites imitating both, cancellous and cortical bone. The mechanical properties of synthetic surrogates were validated for pedicle screw placement and cement augmentation and were compared with those obtained from human vertebrae and insertion torques were analyzed. In human vertebrae pedicle screw torque measurements resulted in mean torque slopes of 82±33Nm/m. Calcium carbonate-based materials achieved lower torques than the human bone whereas calcium phosphate-based bone surrogates showed comparable results. A further differentiation of the calcium phosphate-based vertebrae revealed, that synthetic vertebrae with lower amounts of blowing agent, achieved suitable torques (83 ± 28Nm/m) in comparison to the human reference (p = 0.39). Cement application and subsequent fluoroscopy images confirmed, that the cancellous core of the synthetic vertebrae enabled cement augmentation. In conclusion, our findings suggest, that the artificial bone samples mimic the properties of human bone during pedicle screw placement and cement augmentation and are therefore suitable as synthetic vertebrae in a hybrid surgical simulator.


Developing the evidence base for peer-led services: changes among participants following Wellness Recovery Action Planning (WRAP) education in two statewide initiatives.
The purpose of this analysis was to evaluate the outcomes of two statewide initiatives in Vermont and Minnesota, in which self-management of mental illness was taught by peers to people in mental health recovery using Wellness Recovery Action Planning (WRAP). Pre-post comparisons were made of reports from 381 participants (147 in Vermont and 234 in Minnesota) on a survey instrument that assessed three dimensions of self-management: 1) attitudes, such as hope for recovery and responsibility for one's own wellness; 2) knowledge, regarding topics such as early warning signs of decompensation and symptom triggers; and 3) skills, such as identification of a social support network and use of wellness tools. Significant positive changes in self-management attitudes, skills and behaviors were observed on 76% of items completed by Vermont participants (13 of 17 survey items), and 85% of items completed by Minnesota participants (11 of 13 items). In both states, participants reported significant increases in: 1) their hopefulness for their own recovery; 2) awareness of their own early warning signs of decompensation; 3) use of wellness tools in their daily routine; 4) awareness of their own symptom triggers; 5) having a crisis plan in place; 6) having a plan for dealing with symptoms; 7) having a social support system; and 8) ability to take responsibility for their own wellness. Given the rapid growth of this intervention in the U.S. and internationally, these results contribute to the evidence base for peer-led services, and suggest that more rigorous investigations are warranted in the future.


Expression of a Plasmodium gene introduced into subtelomeric regions of Plasmodium berghei chromosomes.
Targeted integration of exogenous DNA into the genome of malaria parasites will allow their phenotype to be modulated by means of gene disruption or the stable expression of foreign and mutated genes. Described here is the site-specific integration through reciprocal exchange, and subsequent expression, of a selectable marker gene into the genome of the pathogenic, bloodstage forms of the rodent malaria parasite Plasmodium berghei. Stable integration of a single copy of the marker gene (retained for more than 70 generations in the absence of drug pressure) into a nontranscribed subtelomeric repeat array of different chromosomes was observed. Expression of the gene within the subtelomeres indicated that the previously recorded absence of transcription in these regions could be due to a corresponding absence of genes rather than active silencing mechanisms.


A novel manipulation method of human body ownership using an fMRI-compatible master-slave system.
Bodily self-consciousness has become an important topic in cognitive neuroscience aiming to understand how the brain creates a unified sensation of the self in a body. Specifically, full body illusion (FBI) in which changes in bodily self-consciousness are experimentally introduced by using visual-tactile stimulation has led to improve understanding of these mechanisms. This paper introduces a novel approach to the classic FBI paradigm using a robotic master-slave system which allows us to examine interactions between action and the sense of body ownership in behavioral and MRI experiments. In the proposed approach, the use of the robotic master-slave system enables unique stimulation in which experimental participants can administer tactile cues on their own back using active self-touch. This active self-touch has never been employed in FBI experiments and it allows to test the role of sensorimotor integration and agency (the feeling of control over our actions) in FBI paradigms. The objective of this study is to propose a robotic-haptic platform allowing a new FBI paradigm including the active self-touch in MRI environments. This paper, first, describes the design concept and the performance of the prototype device in the fMRI environment (for 3T and 7T MRI scanners). In addition, the prototype device is applied to a classic FBI experiment, and we verify that the use of the prototype device succeeded in inducing the FBI. These results indicate that the proposed approach has a potential to drive advances in our understanding of human body ownership and agency by allowing novel manipulation and paradigms.


The effect of education on the nursing care quality of patients who are under mechanical ventilation in ICU ward.
Nurses have the most important role among health care workers (HCWs) in each hospital (Aiken et al., 2008) [1]. Nurses education can lead to the improvement of nursing care If is implemented and designed based on nurses' needs and proper principles (Aiken et al., 2008) [1]. Nowadays, increased quality of the treatment and increase the chances of survival of patients with acute respiratory failure are very important (Teixeira et al., 2013) [2]. Nursing care plan in ICU patients is one of the important elements in nursing care, and one of the main strategies is promotion of education level. Nurses due to longtime relationship with nursing staff in 24 hours and use of multiple roles of education have excellent position in evaluating educational needs and performing clinical educator roles. The effect of education on the nursing care quality of patients who were under mechanical ventilation (UMV) in intensive care unit (ICU) ward of Razi hospital is evaluated during 2015. The present study is descriptive-analytical and semi experimental research. Research statistical population included 30 nurses. In this paper, the effects of communication with the patient, correct suctioning, compliance of aseptic techniques, the correct discharge of tube cuff, chest physiotherapy, the correct change positions, health food gavage, prevent of foot drop, oral hygiene, the eyes hygiene and protect the cornea have been studied. After completion of the questionnaires by patients, the obtained coded data were fed into EXCEL. Reliability was confirmed with coefficient Alfa 0.86 and the result of software and techniques were entered to SPSS for statistics and analysis.


Age-at-Death Estimation for Modern Populations in Mexico and Puerto Rico through the Use of 3D Laser Scans of the Pubic Symphysis.
Reliable age-at-death estimates from the adult skeleton are of fundamental importance in forensic anthropology, because it contributes to the identity parameters used in a medicolegal death investigation. However, reliable estimates are difficult because many traditional aging methods depend on a set of population-specific criteria derived from individuals of European and African descent. The absence of information on the potential differences in the aging patterns of underrepresented, especially Latinx, populations may hinder our efforts to produce useful age-at-death estimates. In response to these concerns, this study explores the utility of currently available aging techniques and whether population-specific aging methods among Latinx groups are needed. The authors obtained data from two skeletal collections representing modern individuals of Mexican and Puerto Rican origin. They examined five newly developed computational shape-based techniques using 3D laser scans of the pubic symphysis and one traditional bone-to-phase technique. A validation test of all computational and traditional methods was implemented, and new population-specific equations using the computational algorithms were generated and tested against a subsample. Results suggest that traditional and computational aging techniques applied to the pubic symphysis perform best with individuals within 35-45 years of age. Levels of bias and inaccuracy increase as chronological age increases, with overestimation of individuals younger than 35 years and underestimation of individuals older than 45 years. New regression models provided error rates comparable to, and in some occasions outperformed, the original computational models developed on white American males, but age estimates did not significantly improve. This study shows that population-specific models do not necessarily improve age estimates in Latinx samples. Results do suggest that computational methods can ultimately outperform the Suchey-Brooks method and provide improved objectivity when estimating age at death in Latinx samples.


A tuneable microfluidic system for long duration chemotaxis experiments in a 3D collagen matrix.
In many cell types, migration can be oriented towards a chemical stimulus. In mammals, for example, embryonic cells migrate to follow developmental cues, immune cells migrate toward sites of inflammation, and cancer cells migrate away from the primary tumour and toward blood vessels during metastasis. Understanding how cells migrate in 3D environments in response to chemical cues is thus crucial to understanding directed migration in normal and disease states. To date, chemotaxis in mammalian cells has been primarily studied using 2D migration models. However, it is becoming increasingly clear that the mechanisms by which cells migrate in 2D and 3D environments dramatically differ, and cells in their native environments are confronted with a complex chemical milieu. To address these issues, we developed a microfluidic device to monitor the behaviour of cells embedded in a 3D collagen matrix in the presence of complex concentration fields of chemoattractants. This tuneable microsystem enables the generation of (1) homogeneous, stationary gradients set by a purely diffusive mechanism, or (2) spatially evolving, stationary gradients, set by a convection-diffusion mechanism. The device allows for stable gradients over several days and is large enough to study the behaviour of large cell aggregates. We observe that primary mature dendritic cells respond uniformly to homogeneous diffusion gradients, while cell behaviour is highly position-dependent in spatially variable convection-diffusion gradients. In addition, we demonstrate a directed response of cancer cells migrating away from tumour-like aggregates in the presence of soluble chemokine gradients. Together, this microfluidic device is a powerful system to observe the response of different cells and aggregates to tuneable chemical gradients.


Survey of the incidence and aetiology of mastitis on dairy farms in England and Wales.
A survey of clinical and subclinical mastitis was carried out on 97 dairy farms in England and Wales, selected at random from members of a national milk recording scheme. The farmers were asked to collect aseptic milk samples from five consecutive cases of clinical mastitis and from five quarters with high somatic cell counts using a defined protocol, and they completed a questionnaire that included information on the cows sampled, the herd and the history of mastitis in the herd. The samples were collected throughout the year. The mean incidence of clinical mastitis was 47 cases per 100 cows per year (estimated from historic farm records) and 71 cases per 100 cows per year (estimated from the samples collected). Streptococcus uberis and Escherichia coli were isolated in pure culture from 23.5 per cent and 19.8 per cent, respectively, of the clinical samples; 26.5 per cent of the clinical samples produced no growth. The most common isolates from the samples with high cell counts were coagulase-negative staphylococci (15 per cent), S uberis (14 per cent) and Corynebacterium species (10 per cent). Staphylococcus aureus and coagulase-positive staphylococci together accounted for 10 per cent of the samples with high somatic cell counts; 39 per cent produced no bacterial growth.


Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis.
Little is known about the efficacy of golimumab, a fully human monoclonal antibody to tumor necrosis factor (TNF) -α, for treatment of ulcerative colitis (UC). We evaluated subcutaneous golimumab induction therapy in TNF-α antagonist-naïve patients with moderate-to-severe UC despite conventional treatment. We integrated double-blind phase 2 dose-finding and phase 3 dose-confirmation trials in a study of 1064 adults with UC (Mayo score: 6-12; endoscopic subscore ≥ 2; 774 patients in phase 3). Patients were randomly assigned to groups given golimumab doses of 100 mg and then 50 mg (phase 2 only), 200 mg and then 100 mg, or 400 mg and then 200 mg, 2 weeks apart. The phase 3 primary end point was week-6 clinical response. Secondary end points included week-6 clinical remission, mucosal healing, and Inflammatory Bowel Disease Questionnaire (IBDQ) score change. In phase 2, median changes from baseline in the Mayo score were -1.0, -3.0, -2.0, and -3.0, in the groups given placebo, 100 mg/50 mg, 200/100 mg, and 400/200 mg golimumab, respectively. In phase 3, rates of clinical response at week 6 were 51.0% and 54.9% among patients given 200 mg/100 mg and 400 mg/200 mg golimumab, respectively, vs 30.3% among those given placebo (both, P ≤ .0001). Rates of clinical remission and mucosal healing and mean changes in IBDQ scores were significantly greater in both golimumab groups vs the placebo group (P ≤ .0014, all comparisons). Rates of serious adverse events were 6.1% and 3.0%, and rates of serious infection were 1.8% and 0.5%, in the placebo and golimumab groups, respectively. One patient in the 400 mg/200 mg group died as a result of surgical complications of an ischiorectal abscess. Treatment with subcutaneous golimumab induces clinical response, remission, and mucosal healing, and increases quality of life in larger percentages of patients with active UC than placebo. ClinicalTrials.gov Number: NCT00487539.


Theory of planned behavior and adherence in chronic illness: a meta-analysis.
Social-cognitive models such as the theory of planned behavior have demonstrated efficacy in predicting behavior, but few studies have examined the theory as a predictor of treatment adherence in chronic illness. We tested the efficacy of the theory for predicting adherence to treatment in chronic illness across multiple studies. A database search identified 27 studies, meeting inclusion criteria. Averaged intercorrelations among theory variables were computed corrected for sampling error using random-effects meta-analysis. Path-analysis using the meta-analytically derived correlations was used to test theory hypotheses and effects of moderators. The theory explained 33 and 9 % of the variance in intention and adherence behavior respectively. Theoretically consistent patterns of effects among the attitude, subjective norm, perceived behavioral control, intention and behavior constructs were found with small-to-medium effect sizes. Effect sizes were invariant across behavior and measurement type. Although results support theory predictions, effect sizes were small, particularly for the intention-behavior relationship.


Generation of a novel allelic series of cryptochrome mutants via mutagenesis reveals residues involved in protein-protein interaction and CRY2-specific repression.
CRYPTOCHOME proteins are necessary for mammalian circadian rhythms and have many well-established biochemical roles within the molecular clock. While studies examining the effect of null Cry alleles have been informative, they have failed to dissect out the relative importance of, and the molecular mechanisms behind, the many roles of the CRY1 and CRY2 proteins. To address this, we created an allelic series of Cry mutants through random mutagenesis, followed by a cell-based screen to isolate mutants with aberrant repression of CLOCK-BMAL1. We identified 22 mutants with mutations resulting in single amino acid substitutions which cause a variety of deficiencies in different CRY functions. To illustrate the breadth and value of these new tools, we present an in-depth analysis of two of these mutants, CRY2G354D and CRY2G351D; the former shows deficiency in clock protein binding and is required for repression by both CRYs, while in contrast, the latter displays normal binding function but exhibits a CRY2-specific repression phenotype. Further, while overexpression of CRY2 in NIH 3T3 cells caused a dose-dependent decrease in rhythm amplitude, overexpression of CRY2G351D abolished rhythmicity. In summary, characterization of these unique alleles provides new opportunities for more-sophisticated insight into the multifaceted functions of the CRY proteins in circadian rhythms.


Early Visual Processing is Affected by Clinical Subtype in Patients with Unilateral Spatial Neglect: A Magnetoencephalography Study.
To determine whether visual evoked magnetic fields (VEFs) elicited by right and left hemifield stimulation differ in patients with unilateral spatial neglect (USN) that results from cerebrovascular accident. Pattern-reversal stimulation of the right and left hemifield was performed in three patients with left USN. Magnetoencephalography (MEG) was recorded using a 160-channel system, and VEFs were quantified in the 400 ms after each stimulus. The presence or absence of VEF components at around 100 ms (P100m component) and 145 ms (N145m component) after stimulus onset was determined. The source of the VEF was determined using a single equivalent current dipole model for spherical volume conduction. All patients were evaluated using the behavioral inattention test (BIT). In response to right hemifield stimulation, the P100m and N145m components of the VEF were evident in all three patients. In response to left hemifield stimulation, both components were evident in Patient 3, whereas only the P100m component was evident in Patient 1 and only the N145m component was evident in Patient 2. Patient 1 exhibited impairments on the line bisection and cancelation tasks of the BIT, Patient 2 exhibited impairments on the copying, drawing and cancelation tasks of the BIT, and Patient 3 exhibited impairments on the cancelation task of the BIT. These results demonstrate that early VEFs are disrupted in patients with USN and support the concept that deficits in visual processing differ according to the clinical subtype of USN and the lesion location. This study also demonstrates the feasibility of using MEG to explore subtypes of neglect.


Cortical binocularity in infants.
The primate visual cortex, including that of man, receives separate input from each eye and these interact in binocular cortical neurones. This organization is known to be vulnerable to disruption in early life. To understand the development of human visual cortex, and to detect and assess disorders of binocular function at the earliest possible age, a robust method is needed for detecting binocular interactions in the infant's visual system. We have done this by recording cortical visual evoked responses (VERs) to the onset and offset of binocular correlation in a large-screen dynamic random dot display. We report here that, in general, the human infant has a functional binocular visual cortex by 3 months of age, with some individuals showing cortical binocularity at an earlier age.


Non-steroidal anti-inflammatory drug-induced small intestinal damage is Toll-like receptor 4 dependent.
Enterobacteria and cytokines both play roles in the pathophysiology of NSAID-induced enteropathy. Toll-like receptor (TLR) 4 recognises lipopolysaccharide (LPS), resulting in activation of an inflammatory cascade via the accessory protein MyD88. To investigate role of TLR4 in inflammatory responses in indomethacin-induced enteropathy. Indomethacin was administered p.o. to non-fasting rats and mice to induce small intestinal damage. The extent of such damage was evaluated by measuring the injured area stained dark blue with Evans blue. Rats were given antibiotics (ampicillin, aztreonam or vancomycin) p.o., or intraperitoneal LPS (a TLR4 ligand) or neutralising antibodies against neutrophils, tumour necrosis factor (TNF)-alpha, or monocyte chemotactic protein (MCP)-1. Furthermore, the intestinal ulcerogenicity of indomethacin was examined in TLR4-mutant, TLR4(-/-), and MyD88(-/-) mice. Indomethacin induced small intestinal damage with an increase in expression of TNF-alpha and MCP-1 in both rats and mice. Antibodies against neutrophils, TNF-alpha and MCP-1 inhibited the damage by 83%, 67% and 63%, respectively, in rats. Ampicillin and aztreonam also inhibited this damage, and decreased the number of Gram-negative bacteria in the small intestinal contents of the rat. However, vancomycin, which exhibited no activity against Gram-negative bacteria, had no preventive effect against this damage. Administration of LPS 1 h after indomethacin aggravated the damage, whereas LPS pretreatment inhibited it with reduction of expression of TLR4 and cytokines. In TLR4-mutant mice, the damage and cytokine expression were markedly inhibited. TLR4(-/-) and MyD88(-/-) mice were also resistant to the damage. Indomethacin may injure the small intestine through a TLR4/MyD88-dependent pathway.


State Health Agency and Local Health Department Workforce: Identifying Top Development Needs.
To identify occupations with high-priority workforce development needs at public health departments in the United States. We surveyed 46 state health agencies (SHAs) and 112 local health departments (LHDs). We asked respondents to prioritize workforce needs for 29 occupations and identify whether more positions, more qualified candidates, more competitive salaries for recruitment or retention, or new or different staff skills were needed. Forty-one SHAs (89%) and 36 LHDs (32%) participated. The SHAs reported having high-priority workforce needs for epidemiologists and laboratory workers; LHDs for disease intervention specialists, nurses, and administrative support, management, and leadership positions. Overall, the most frequently reported SHA workforce needs were more qualified candidates and more competitive salaries. The LHDs most frequently reported a need for more positions across occupations and more competitive salaries. Workforce priorities for respondents included strengthening epidemiology workforce capacity, adding administrative positions, and improving compensation to recruit and retain qualified employees. Strategies for addressing workforce development concerns of health agencies include providing additional training and workforce development resources, and identifying best practices for recruitment and retention of qualified candidates.


Predictors of cognitive function and recovery 10 years after traumatic brain injury in young children.
Childhood traumatic brain injury (TBI) has implications for functional outcomes, but few studies have documented long-term outcomes. The purpose of this study was to plot recovery of cognitive and functional skills after early childhood TBI to 10 years postinjury and to identify the contribution of injury, environment, preinjury characteristics, and acute functional recovery. Subjects were recruited consecutively to this prospective, longitudinal study, which used a between-factor design, with injury severity as the independent variable. Forty children with TBI aged 2 and 7 years were recruited on admission to a tertiary pediatric hospital, divided according to injury severity, and compared with 16 healthy controls acutely and 12 and 30 months and 10 years postinjury. Cognition, adaptive ability, executive function, and social/behavioral skills were examined. Children with severe TBI had poorest outcomes, with deficits greatest for cognition. Recovery trajectories were similar across severity groups but with significant gains in verbal skills from 12 and 30 months to 12 months and 10 years. Predictors of outcome included preinjury ability (for adaptive function) and family function (social/behavioral skills). Results confirm a high risk of persisting deficits after severe TBI in early childhood. Children with less severe TBI appear to recover to function normally. Contrary to speculation about "growing into deficits," after protracted recovery to 30 months, young children make age-appropriate progress at least to 10 years postinsult. Environmental factors were found to contribute to adaptive and social/behavioral recovery.


Anatomical eponyms in Cardiology from to the 60s to the XXI century.
Eponym from the Greek [epi, "upon"] + [onuma, name], is a person, whether real or fictitious, after whom an item is named or thought to be named. Eponymous terms are used every day in Medicine, in our clinical years, and they have been part of the tradition of Medicine, culture, and history. Despite all the inconvenience, all those who are no against eponym has only one statement: "medical eponyms will continue to be used because there is a sense of history to their use. They are use in contemporary life, eponyms are here to stay". The following study aims at to show the presence of current anatomical eponyms on the best well-known Textbooks and Atlas of Human Anatomy, ranging from the oldest to the newest one, comprising a period from 1960 until 2011, regarding the cardiovascular system, particularly the heart. The three International Anatomical Terminologies have been critical as the basis of our study. Exclusion criteria were syndromes, diseases, signs, anomalies, surgical procedures, indexes, tests, grading, and the methods, which are used as eponyms in Cardiology, once they are not considered Anatomical Terms. It has been our intent to show that different eponyms characterize the same anatomical structure. A list with the 25 most common eponyms listed by the three International Anatomical Terminologies is listed in Table1. Should eponyms be abandoned? Of course not, once they remain a useful reflection of medical history. We could prove to our journey from 1960 to 2011, that the best well-known Atlas and Textbooks available do not use so many anatomical eponyms in Cardiology. They are only 25 (without including arteries, veins, and nerves of the cardiovascular system) and all the authors use no more than 9 or 12 of them. We just want to alert the Health and Allied Health Sciences Professional and students that we 'strongly recommend' not to use an eponym when it is made at the expense of an anatomical structure.


Monolithically integrated all-optical gate switch using intersubband transition in InGaAs/AlAsSb coupled double quantum wells.
We have developed a compact all-optical gate switch with a footprint less than 1 mm2, in which an optical nonlinear waveguide using cross-phase-modulation associated with intersubband transition in InGaAs/AlGaAs/AlAsSb coupled double quantum wells and a Michelson interferometer (MI) are monolithically integrated on an InP chip. The MI configuration allows a transverse magnetic pump light direct access to an MI arm for phase modulation while passive photonic integrated circuits serve a transverse electric signal light. Full switching of the π-rad nonlinear phase shift is achieved with a pump pulse energy of 8.6 pJ at a 10-GHz repetition rate. We also demonstrate all-optical demultiplexing of a 160-Gb/s signal to a 40-Gb/s signal.


Self-reported comorbidities, perceived needs, and sources for usual care for older and younger homeless adults.
While older individuals who are homeless tend to be in poorer health, it is less clear how they view their health care needs and whether their self-reported patterns for accessing health services differ from younger homeless counterparts. Cross-sectional, community-based survey of homeless adults in Pittsburgh and Philadelphia using face-to-face interviews from population proportionate sampling of sites and random sampling of subjects. Survey questions included physical and mental health comorbidities, self-reported health care, social services and personal needs, means of economic support, and sources for usual health care. For analysis purposes, respondents were grouped by age 18 to 49 years old and 50 years old or older. Overall, 531 adults were interviewed, with 74 respondents 50 years old or older (13.9%). Older homeless persons were 3.6 times more likely to report a chronic medical condition, 2.8 times more likely to have health insurance, and 2.4 times more likely to be dependent on heroin than homeless persons less than 50 years old. However, they also tended to use shelter-based clinics and street outreach teams more commonly as their source of usual care (20.9% vs 10.6%, P=.02) and were significantly less likely to report a need for substance abuse treatment despite high rates of abuse. Older homeless adults have a greater disease burden than their younger counterparts. However, it is unclear whether these needs are being appropriately identified and met. There is a need for specific and targeted outreach to connect them to appropriate services.