Phylogenetic and Biological Characterization of Fusarium oxysporum Isolates Associated with Onion in South Africa.
Fusarium oxysporum f. sp. cepae causes Fusarium basal rot of onion, a disease of worldwide importance. Limited information is available on the phylogenetic diversity, vegetative compatibility groups (VCGs), mating type idiomorphs, and virulence of F. oxysporum isolates associated with onion. Therefore, these characteristics were investigated in 19 F. oxysporum f. sp. cepae isolates from Colorado, 27 F. oxysporum f. sp. cepae and 33 F. oxysporum isolates nonpathogenic to onion from South Africa. Six F. oxysporum f. sp. cepae VCGs (0421 to 0426) were identified, of which three were new. The dominant VCGs in Colorado and South Africa were VCG 0421 (47% of isolates) and VCG 0425 (74%), respectively. VCG 0423 was the only VCG that was shared between the two regions. Molecular phylogenies (intergenic spacer region of the rDNA, elongation factor 1α, and mitochondrial small-subunit) confirmed the polyphyletic nature of F. oxysporum f. sp. cepae and showed that some F. oxysporum f. sp. cepae and nonpathogenic F. oxysporum isolates were genetically related. Most F. oxysporum f. sp. cepae isolates clustered into two distinct, well-supported clades. The largest clade only contained highly virulent isolates, including the two main VCGs (0421 and 0425), whereas the basal clade mostly contained moderately virulent isolates. These groupings along with the VCG data provide an important basis for selection of isolates for use in breeding programs, and for the development of molecular makers to identify VCGs. Mating type genotyping revealed the distribution of both mating type (MAT1-1 and MAT1-2) idiomorphs across phylogenetic clades, and the fact that several isolates contained both idiomorphs.


[Peritoneal dialysis in the Lazio region: results from 2017 regional audit].
In 2011, a first peritoneal dialysis audit was held in the Lazio region to analyze the problems hindering the spread of this method and to improve the quality of care through the sharing of best practices across Centers. A scientific board was therefore set up, representing all the Centers offering PD, in order to assess clinical effectiveness using KPIs (Key Performance Indicators) and to quantify the objectives to be achieved. The analysis made it possible to identify the main problems and take action, all the while monitoring progress through KPIs. A second audit was carried out in 2017 and the collected data was analyzed and compared with the findings of the previous study. Overall, data showed an increase in prevalence, although the incidence showed a slight decrease. Indicators on the change of dialysis treatment, the dropout from domiciliary treatment and the incidence of late referral appeared stable over time. A slight improvement was observed in clinical data on peritonitis and on the length of hospitalization. All participants in the audit declared that sharing and discussing clinical practices had been really useful. In addition, through the drafting of practical documents (guides for patients, guidance on informed consent, protocols of clinical follow-up), a number of tools have been provided to ensure a uniformly high level of care across the different regional Centers.


Evolutionary development of the neurocranium in Dissorophoidea (Tetrapoda: Temnospondyli), an integrative approach.
Ontogenetic data can play a prominent role in addressing questions in tetrapod evolution, but such evidence from the fossil record is often incompletely considered because it is limited to initiation of ossification, or allometric changes with increasing size. In the present study, specimens of a new species of an archaic amphibian (280 Myr old), Acheloma n. sp., a member of the temnospondyl superfamily Dissorophoidea and the sister group to Amphibamidae, which is thought to include at least two of our modern amphibian clades, anurans and caudatans (Batrachia), provides us with new developmental data. We identify five ontogenetic events, enabling us to construct a partial ontogenetic trajectory (integration of developmental and transformation sequence data) related to the relative timing of completion of neurocranial structures. Comparison of the adult amphibamid morphology with this partial ontogeny identifies a heterochronic event that occurred within the neurocranium at some point in time between the two taxa, which is consistent with the predictions of miniaturization in amphibamids, providing the first insights into the influence of miniaturization on the neurocranium in a fossil tetrapod group. This study refines hypotheses of large-scale evolutionary trends within Dissorophoidea that may have facilitated the radiation of amphibamids and, projected forward, the origin of the generalized batrachian skull. Most importantly, this study highlights the importance of integrating developmental and transformation sequence data, instead of onset of ossification alone, into investigations of major events in tetrapod evolution using evidence provided by the fossil record, and highlights the value of even highly incomplete growth series comprised of relatively late-stage individuals.


Implementation of Crew Resource Management: A Qualitative Study in 3 Intensive Care Units.
Classroom-based crew resource management (CRM) training has been increasingly applied in health care to improve safe patient care. Crew resource management aims to increase participants' understanding of how certain threats can develop as well as provides tools and skills to respond to such threats. Existing literature shows promising but inconclusive results that might be explained by the quality of the implementation. The present research systematically describes the implementation from the perspective of 3 trained intensive care units (ICUs). The design of the study was built around 3 stages of implementation: (1) the preparation, (2) the actions after the CRM training, and (3) the plans for the future. To assess all stages in 3 Dutch ICUs, 12 semistructured interviews with implementation leaders were conducted, the End-of-Course Critique questionnaire was administered, and objective measurements consisting of the number and types of plans of action were reported. The results categorize initiatives that all 3 ICUs successfully launched, including the development of checklists, each using a different implementation strategy. All ICUs have taken several steps to sustain their approach for the foreseeable future. Three similarities between the units were seen at the start of the implementation: (1) acknowledgment of a performance gap in communication, (2) structural time allocated for CRM, and (3) a clear vision on how to implement CRM. This study shows that CRM requires preparation and implementation, both of which require time and dedication. It is promising to note that all 3 ICUs have developed multiple quality improvement initiatives and aim to continue doing so.


Efficacy of rasburicase (recombinant urate oxidase) in the prevention and treatment of malignancy-associated hyperuricemia: an Indian experience.
Patients with hematological malignancies that are highly proliferative and have high tumor burden are at high risk of developing hyperuricemia and tumor lysis syndrome (TLS), spontaneously and while undergoing chemotherapy. To assess the safety and efficacy of a new generic formulation of recombinant rasburicase in prevention and treatment of malignancy-associated hyperuricemia. An open-label, multicenter, phase-III study was conducted on 100 eligible patients with high risk for TLS. Rasburicase was administered 0.2 mg/kg intravenously over 30 min, daily, for 4 days. The outcome measures were percentage of reduction in plasma uric acid at 4 h after rasburicase, plasma uric acid area under the curve (AUC)(0-96 h) and incidence of adverse events. Eighty eight patients completed the study period of 10 days. After rasburicase administration, there was a 75.3 ± 28.5% of reduction in plasma uric acid at 4 h as compared to baseline. The plasma uric acid AUC(0-96 h) was 259.9 ± 215.5 mg/dL h. Safety of rasburicase was assessed on the basis of changes in vitals, hematological, and biochemical parameters from baseline to termination. Except for the plasma uric acid level, there was no significant difference in any of the parameters. Mild to moderate adverse events were reported in 29 patients. Three patients had serious adverse events (SAEs) unrelated to rasburicase. These results demonstrated that recombinant rasburicase that is indigenously developed is effective for prevention and management of hyperuricemia in patients who are at high risk of developing TLS.


Travelers with sickle cell disease.
Sickle cell disease (SCD) is the most common genetic disease among persons with African ancestry. This article provides a background to SCD and reviews many important aspects of travel preparation in this population. The medical literature was searched for studies on travel-associated preparedness and complications in individuals with SCD. Topics researched included malaria, bacterial infections, vaccinations, dehydration, altitude, air travel, and travel preparedness. There is very little published literature that specifically addresses the risks faced by travelers with SCD. Rates of medical complications during travel appear to be high. There is a body of literature that describes complications of SCD in indigenous populations, particularly within Africa. The generalizability of these data to a traveler is uncertain. Combining these sources of data and the broader medical literature, we address major travel-related questions that may face a provider preparing an individual with SCD for safe travel. Travelers with SCD face considerable medical risks when traveling to developing tropical countries, including malaria, bacterial infections, hypovolemia, and sickle cell-associated vaso-occlusive crises. For individuals with SCD, frank counseling about the risks, vigilant preventative measures, and contingency planning for illness while abroad are necessary aspects of the pre-travel visit.


Epigenetics and epilepsy.
Seizures can give rise to enduring changes that reflect alterations in gene-expression patterns, intracellular and intercellular signaling, and ultimately network alterations that are a hallmark of epilepsy. A growing body of literature suggests that long-term changes in gene transcription associated with epilepsy are mediated via modulation of chromatin structure. One transcription factor in particular, repressor element 1-silencing transcription factor (REST), has received a lot of attention due to the possibility that it may control fundamental transcription patterns that drive circuit excitability, seizures, and epilepsy. REST represses a suite of genes in the nervous system by utilizing nuclear protein complexes that were originally identified as mediators of epigenetic inheritance. Epigenetics has traditionally referred to mechanisms that allow a heritable change in gene expression in the absence of DNA mutation. However a more contemporaneous definition acknowledges that many of the mechanisms used to perpetuate epigenetic traits in dividing cells are utilized by neurons to control activity-dependent gene expression. This review surveys what is currently understood about the role of epigenetic mechanisms in epilepsy. We discuss how REST controls gene expression to affect circuit excitability and neurogenesis in epilepsy. We also discuss how the repressor methyl-CpG-binding protein 2 (MeCP2) and activator cyclic AMP response element binding protein (CREB) regulate neuronal activity and are themselves controlled by activity. Finally we highlight possible future directions in the field of epigenetics and epilepsy.


Edge Computing to Secure IoT Data Ownership and Trade with the Ethereum Blockchain.
With an increasing penetration of ubiquitous connectivity, the amount of data describing the actions of end-users has been increasing dramatically, both within the domain of the Internet of Things (IoT) and other smart devices. This has led to more awareness of users in terms of protecting personal data. Within the IoT, there is a growing number of peer-to-peer (P2P) transactions, increasing the exposure to security vulnerabilities, and the risk of cyberattacks. Blockchain technology has been explored as middleware in P2P transactions, but existing solutions have mainly focused on providing a safe environment for data trade without considering potential changes in interaction topologies. we present EdgeBoT, a proof-of-concept smart contracts based platform for the IoT built on top of the ethereum blockchain. With the Blockchain of Things (BoT) at the edge of the network, EdgeBoT enables a wider variety of interaction topologies between nodes in the network and external services while guaranteeing ownership of data and end users' privacy. in EdgeBoT, edge devices trade their data directly with third parties and without the need of intermediaries. This opens the door to new interaction modalities, in which data producers at the edge grant access to batches of their data to different third parties. Leveraging the immutability properties of blockchains, together with the distributed nature of smart contracts, data owners can audit and are aware of all transactions that have occurred with their data. we report initial results demonstrating the potential of EdgeBoT within the IoT. we show that integrating our solutions on top of existing IoT systems has a relatively small footprint in terms of computational resource usage, but a significant impact on the protection of data ownership and management of data trade.


In vivo catabolism of alpha 1-antichymotrypsin is mediated by the Serpin receptor which binds alpha 1-proteinase inhibitor, antithrombin III and heparin cofactor II.
The in vivo catabolism of 125I-labeled alpha 1-antichymotrypsin was studied in our previously described mouse model. Native alpha 1-antichymotrypsin cleared with an apparent t1/2 of 85 min, but alpha 1-antichymotrypsin in complex with chymotrypsin or cathepsin G cleared with a t1/2 of 12 min. Clearance of the complex was blocked by a large molar excess of unlabeled complexes of proteinases with either alpha 1-antichymotrypsin or alpha 1-proteinase inhibitor. These studies indicate that the clearance of alpha 1-antichymotrypsin-proteinase complexes utilizes the same pathway as complexes with the homologous inhibitor alpha 1-proteinase inhibitor. Previous studies have demonstrated that this pathway is also responsible for the catabolism of two other serine proteinase inhibitors, antithrombin III and heparin cofactor II. This pathway is thus responsible for removing several proteinases involved in coagulation and inflammation from the circulation, thereby decreasing the likelihood of adventitious proteolysis.


Response diversity in Mediterranean coralligenous assemblages facing climate change: Insights from a multispecific thermotolerance experiment.
Climate change threatens coastal benthic communities on a global scale. However, the potential effects of ongoing warming on mesophotic temperate reefs at the community level remain poorly understood. Investigating how different members of these communities will respond to the future expected environmental conditions is, therefore, key to anticipating their future trajectories and developing specific management and conservation strategies. Here, we examined the responses of some of the main components of the highly diverse Mediterranean coralligenous assemblages to thermal stress. We performed thermotolerance experiments with different temperature treatments (from 26 to 29°C) with 10 species from different phyla (three anthozoans, six sponges and one ascidian) and different structural roles. Overall, we observed species-specific contrasting responses to warming regardless of phyla or growth form. Moreover, the responses ranged from highly resistant species to sensitive species and were mostly in agreement with previous field observations from mass mortality events (MMEs) linked to Mediterranean marine heat waves. Our results unravel the diversity of responses to warming in coralligenous outcrops and suggest the presence of potential winners and losers in the face of climate change. Finally, this study highlights the importance of accounting for species-specific vulnerabilities and response diversity when forecasting the future trajectories of temperate benthic communities in a warming ocean.


The influence of social norms on the dynamics of vaccinating behaviour for paediatric infectious diseases.
Mathematical models that couple disease dynamics and vaccinating behaviour often assume that the incentive to vaccinate disappears if disease prevalence is zero. Hence, they predict that vaccine refusal should be the rule, and elimination should be difficult or impossible. In reality, countries with non-mandatory vaccination policies have usually been able to maintain elimination or very low incidence of paediatric infectious diseases for long periods of time. Here, we show that including injunctive social norms can reconcile such behaviour-incidence models to observations. Adding social norms to a coupled behaviour-incidence model enables the model to better explain pertussis vaccine uptake and disease dynamics in the UK from 1967 to 2010, in both the vaccine-scare years and the years of high vaccine coverage. The model also illustrates how a vaccine scare can perpetuate suboptimal vaccine coverage long after perceived risk has returned to baseline, pre-vaccine-scare levels. However, at other model parameter values, social norms can perpetuate depressed vaccine coverage during a vaccine scare well beyond the time when the population's baseline vaccine risk perception returns to pre-scare levels. Social norms can strongly suppress vaccine uptake despite frequent outbreaks, as observed in some small communities. Significant portions of the parameter space also exhibit bistability, meaning long-term outcomes depend on the initial conditions. Depending on the context, social norms can either support or hinder immunization goals.


Assessment of independent predictors for long-term mortality between women and men after coronary artery bypass grafting: are women different from men?
The long-term mortality of coronary artery bypass grafting in women in not certain. The purpose of this study was to determine and compare risk factors for long-term mortality in women and men undergoing coronary artery bypass grafting. Between 1992 and 2002, 3760 consecutive patients (2598 men and 1162 women) underwent isolated coronary artery bypass grafting. Long-term survival data were obtained from the National Death Index (mean follow-up, 5.1 +/- 3.2 years). Multivariable Cox regression analysis was performed, including 64 preoperative, intraoperative, and postoperative factors separately in women and men. There were no differences in in-hospital mortality (2.7% in men vs 2.9% in women, P = .639) and 5-year survival (82.0% +/- 0.8% in men vs 81.1% +/- 1.3% in women, P = .293). After adjustment for all independent predictors of long-term mortality, female sex was an independent predictor of improved 5-year survival (hazard ratio, 0.82; 95% confidence interval, 0.71-0.96; P = .014). Twenty-one independent predictors for long-term mortality were determined in men, whereas only 12 were determined in women. There were 9 common risk factors (age, ejection fraction, diabetes mellitus, > or =2 arterial grafts, postoperative myocardial infarction, deep sternal wound infection, sepsis and/or endocarditis, gastrointestinal complications, and respiratory failure); however, their weights were different between women and men. Malignant ventricular arrhythmias, calcified aorta, and preoperative renal failure were independent predictors only in women. Emergency operation, previous cardiac operation, peripheral vascular disease, left ventricular hypertrophy, current and past congestive heart failure, chronic obstructive pulmonary disease, body mass index of greater than 29, preoperative dialysis, thrombolysis within 7 days before coronary artery bypass grafting, intraoperative stroke, and postoperative renal failure were independent predictors only in men. Despite equality between sexes in early outcome and superiority of female sex in long-term survival, there were 3 independent predictors for long-term mortality after coronary artery bypass grafting unique for women compared with 12 for men. Clinical decision making and follow-up should not be influenced by stereotypes but by specific findings.


Natural radioactivity of Australian building materials, industrial wastes and by-products.
The natural radioactivity due to the presence of 226Ra, 232Th and 40K in conventional raw materials and some solid industrial wastes and by-products which are being used or have a potential for use in the building and ceramic industries in Australia has been measured by gamma-ray spectrometry. The majority of materials examined in this work showed fairly low levels of radioactivity. Some samples of red mud, phosphogypsum, zircon products and fly ash did show higher levels of radioactivity than would be acceptable on the basis of a criterion formula for gamma-ray activity suggested for use in some OECD countries. But this higher level of radioactivity should not pose an environmental health problem when these materials constitute a relatively small portion of the materials used in a normal building. The present work has also shown that the radioactivity levels of some of the materials can be reduced through the removal of fines by sieving, as the fines seem to contain a higher concentration of radioactive nuclides.


X-ray microanalysis of airway surface liquid collected in cystic fibrosis mice.
The airway surface liquid (ASL) that lines the airway surface epithelium plays a major role in airway antibacterial defense and mucociliary transport efficiency, two key factors in cystic fibrosis (CF) disease. A major difficulty is to collect ASL in native conditions without stimulation or alteration of the underlying airway epithelium. Using a cryoprobe specifically adapted to collect native ASL from the tracheal mouse surface, we analyzed by X-ray microanalysis the complete ASL and plasma ion content in Cftr(tm1Hgu)/Cftr(tm1Hgu) mice compared with that in control littermates. ASL ion content from eight Cftr(tm1Hgu)/Cftr(tm1Hgu) mice and eight control littermates did not appear significantly different. The mean (+/-SE) concentrations were 2,352 +/- 367 and 2,058 +/- 401 mmol/kg dry weight for Na, 1,659 +/- 272 and 1,448 +/- 281 mmol/kg dry weight for Cl, 357 +/- 57 and 337 +/- 38 mmol/kg dry weight for S, 1,066 +/- 220 and 787 +/- 182 mmol/kg dry weight for K, 400 +/- 82 and 301 +/- 58 mmol/kg dry weight for Ca, 105 +/- 31 and 105 +/- 20 mmol/kg dry weight for Mg, 33 +/- 15 and 29 +/- 9 mmol/kg dry weight for P in non-CF and CF mice, respectively. This cryotechnique appears to be a promising technique for analyzing the complete elemental composition of native ASL in CF and non-CF tissues.


Managing aquatic ecosystems and water resources under multiple stress--an introduction to the MARS project.
Water resources globally are affected by a complex mixture of stressors resulting from a range of drivers, including urban and agricultural land use, hydropower generation and climate change. Understanding how stressors interfere and impact upon ecological status and ecosystem services is essential for developing effective River Basin Management Plans and shaping future environmental policy. This paper details the nature of these problems for Europe's water resources and the need to find solutions at a range of spatial scales. In terms of the latter, we describe the aims and approaches of the EU-funded project MARS (Managing Aquatic ecosystems and water Resources under multiple Stress) and the conceptual and analytical framework that it is adopting to provide this knowledge, understanding and tools needed to address multiple stressors. MARS is operating at three scales: At the water body scale, the mechanistic understanding of stressor interactions and their impact upon water resources, ecological status and ecosystem services will be examined through multi-factorial experiments and the analysis of long time-series. At the river basin scale, modelling and empirical approaches will be adopted to characterise relationships between multiple stressors and ecological responses, functions, services and water resources. The effects of future land use and mitigation scenarios in 16 European river basins will be assessed. At the European scale, large-scale spatial analysis will be carried out to identify the relationships amongst stress intensity, ecological status and service provision, with a special focus on large transboundary rivers, lakes and fish. The project will support managers and policy makers in the practical implementation of the Water Framework Directive (WFD), of related legislation and of the Blueprint to Safeguard Europe's Water Resources by advising the 3rd River Basin Management Planning cycle, the revision of the WFD and by developing new tools for diagnosing and predicting multiple stressors.


Hematologic abnormalities and flow cytometric immunophenotyping results in dogs with hematopoietic neoplasia: 210 cases (2002-2006).
Growing interest in veterinary oncohematology has facilitated the recent development and advancement of new techniques, such as flow cytometry, for immunophenotyping hematopoietic neoplasia in animals. The aim of this retrospective study was to characterize hematologic abnormalities and flow cytometric immunophenotyping (FCI) results in cases of hematopoietic neoplasia in dogs. Signalment, CBC data, and FCI results were obtained for 210 dogs with blood samples submitted to our laboratory. Immunophenotyping was carried out using an Epics XL-MCL flow cytometer and a panel of 10 antibodies (CD45, CD3, CD4, CD8, CD79, CD21, CD14, CD34, CD41/61, CD61). The prevalence and severity of hematologic abnormalities was determined for the different types of hematopoietic neoplasms. Based on cell morphology and phenotype, cases were classified as: acute lymphoblastic leukemia (ALL, n=51), acute myeloid leukemia (AML, n=33), chronic lymphocytic leukemia (CLL, n=61), and leukemic high-grade lymphoma (L-HGL, n=65). Most cases of ALL (47/51) and L-HGL (41/65) had a B-cell phenotype, while most cases of CLL (54/61) had a T-cell phenotype, with a high prevalence of the large granular lymphocyte subtype (49/61). Anemia was found in 85% of all cases and was significantly more severe in ALL and AML compared with CLL and L-HGL. Neutropenia was seen in 64-78% of acute leukemias (AML and ALL) in contrast to no cases of CLL and 11% of L-HGL. Thrombocytopenia was seen in 88-90% of acute leukemias in contrast to 15% of CLL and 40% of L-HGL. Thrombocytopenia was more prevalent (71% vs 22%) and significantly more severe in T-cell vs B-cell L-HGL. A standard CBC is useful in suggesting the type of hemoproliferative disorder and may also help to predict the phenotype, especially in cases of L-HGL.


Rational functionalization of reduced graphene oxide with an imidazole group for the electrochemical sensing of bisphenol A - an endocrine disruptor.
Reduced graphene oxide has been rationally functionalized with histamine for the highly sensitive and selective electrochemical determination of bisphenol A (BPA). Histamine is covalently attached to graphene oxide by amide coupling and the oxygen functionalities of graphene oxide are partially reduced electrochemically. The facilitated electrochemical oxidation of BPA was achieved in neutral pH with functionalized reduced graphene oxide. The pH of the reaction controls the oxidation of BPA. Electrochemical oxidation is not favourable at pH less than the pKa of histamine due to the protonation of the imidazole nitrogen. The electrode is highly sensitive (1727.29 ± 12.48 nA μM-1 cm-2) towards BPA and shows a linear response up to 30 μM of BPA. It could detect as low as 0.03 nM of BPA (S/N = 5). The other coexisting analytes do not interfere with the voltammetric measurement of BPA.


Noninvasive measurement of plasma glucose from exhaled breath in healthy and type 1 diabetic subjects.
Effective management of diabetes mellitus, affecting tens of millions of patients, requires frequent assessment of plasma glucose. Patient compliance for sufficient testing is often reduced by the unpleasantness of current methodologies, which require blood samples and often cause pain and skin callusing. We propose that the analysis of volatile organic compounds (VOCs) in exhaled breath can be used as a novel, alternative, noninvasive means to monitor glycemia in these patients. Seventeen healthy (9 females and 8 males, 28.0 ± 1.0 yr) and eight type 1 diabetic (T1DM) volunteers (5 females and 3 males, 25.8 ± 1.7 yr) were enrolled in a 240-min triphasic intravenous dextrose infusion protocol (baseline, hyperglycemia, euglycemia-hyperinsulinemia). In T1DM patients, insulin was also administered (using differing protocols on 2 repeated visits to separate the effects of insulinemia on breath composition). Exhaled breath and room air samples were collected at 12 time points, and concentrations of ~100 VOCs were determined by gas chromatography and matched with direct plasma glucose measurements. Standard least squares regression was used on several subsets of exhaled gases to generate multilinear models to predict plasma glucose for each subject. Plasma glucose estimates based on two groups of four gases each (cluster A: acetone, methyl nitrate, ethanol, and ethyl benzene; cluster B: 2-pentyl nitrate, propane, methanol, and acetone) displayed very strong correlations with glucose concentrations (0.883 and 0.869 for clusters A and B, respectively) across nearly 300 measurements. Our study demonstrates the feasibility to accurately predict glycemia through exhaled breath analysis over a broad range of clinically relevant concentrations in both healthy and T1DM subjects.


Evolution of faculty affairs and faculty development offices in U.S. medical schools: a 10-year follow-up survey.
To determine how U.S. MD-granting medical schools manage, fund, and evaluate faculty affairs/development functions and to determine the evolution of these offices between 2000 and 2010. In December 2010, the authors invited faculty affairs designees at 131 U.S. MD-granting medical schools to complete a questionnaire developed by the Association of American Medical Colleges Group on Faculty Affairs, based on a 2000 survey. Schools were asked about core functions, budget, staffing, and performance metrics. The authors analyzed the data using descriptive statistics. A total of 111 schools (84.7%) responded. Fifty percent of the offices were established since 2000. Seventy-eight percent reported their top core function as administrative support for appointments, promotions, and tenure, as in 2000. Faculty policies, appointments, databases, governance support, grievance proceedings, management issues, and annual trend analyses continued as major functions. All 11 core functions identified in 2000 remain predominantly provided by central offices of faculty affairs, except support of major leadership searches. Web site communication emerged as a new core function. Similar to 2000, several other offices were responsible for some faculty development functions. Office size and budget correlated positively with size of the faculty and age of the office (P < .05 for all). Thirty-five schools (31.5%) reported formally evaluating their faculty affairs office. The number of faculty affairs offices and their responsibilities have substantially increased since 2000. Most major core functions have not changed. These offices are now an established part of the central administration of most medical schools.


Earlier HIV diagnosis--are mobile services the answer?
To assess the age and gender differences of clients accessing mobile HIV counselling and testing (HCT) compared with clients accessing facility-based testing, and to determine the difference in HIV prevalence and baseline CD4 counts. This was a prospective observational cross-sectional study of 3 different HIV testing services in Cape Town. We compared data on age, sex, HIV status and CD4 counts collected between August and December 2008 from a mobile testing service (known as the Tutu Tester), a primary health care clinic, and a district hospital. A total of 3 820 individuals were tested: 2 499 at the mobile, 657 at the clinic, and 664 at the hospital. Age and sex distribution differed across services, with the mobile testing more men and older individuals. HIV prevalence was lowest at the mobile (5.9%) compared with the clinic (18.0%) and hospital (23.3%). Of the HIV-infected individuals from the mobile service, 75% had a CD4 count higher than 350 cells/µl compared with 48% and 32% respectively at the clinic and hospital. Age- and sex-adjusted risk for HIV positivity was 3.5 and 4.9 times higher in the clinic-based and hospital-based services compared with the mobile service. Mobile services are accessed by a different population compared with facility-based services. Mobile service clients were more likely to be male and less likely to be HIV-positive, and those infected presented with earlier disease.


Direct quantification of cannabinoids and cannabinoid glucuronides in whole blood by liquid chromatography-tandem mass spectrometry.
The first method for quantifying cannabinoids and cannabinoid glucuronides in whole blood by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and validated. Solid-phase extraction followed protein precipitation with acetonitrile. High-performance liquid chromatography separation was achieved in 16 min via gradient elution. Electrospray ionization was utilized for cannabinoid detection; both positive (Δ(9)-tetrahydrocannabinol [THC] and cannabinol [CBN]) and negative (11-hydroxy-THC [11-OH-THC], 11-nor-9-carboxy-THC [THCCOOH], cannabidiol [CBD], THC-glucuronide, and THCCOOH-glucuronide) polarity were employed with multiple reaction monitoring. Calibration by linear regression analysis utilized deuterium-labeled internal standards and a 1/x(2) weighting factor, yielding R(2) values >0.997 for all analytes. Linearity ranged from 0.5 to 50 μg/L (THC-glucuronide), 1.0-100 μg/L (THC, 11-OH-THC, THCCOOH, CBD, and CBN), and 5.0-250 μg/L (THCCOOH-glucuronide). Imprecision was <10.5% CV, recovery was >50.5%, and bias within ±13.1% of target for all analytes at three concentrations across the linear range. No carryover and endogenous or exogenous interferences were observed. This new analytical method should be useful for quantifying cannabinoids in whole blood and further investigating cannabinoid glucuronides as markers of recent cannabis intake.


Reducing falls in older adults recently discharged from hospital: a systematic review and meta-analysis.
older adults are known to have increased falls rates and functional decline following hospital discharge, with substantial economic healthcare costs. This systematic review aimed to synthesise the evidence for effective falls prevention interventions in older adults recently discharged from hospital. literature searches of six databases of quantitative studies conducted from 1990 to June 2017, reporting falls outcomes of falls prevention interventions for community-dwelling older adults discharged from hospital were included. Study quality was assessed using a standardised JBI critical appraisal tool (MAStARI) and data pooled using Rev-Man Review Manager®. sixteen studies (total sample size N = 3,290, from eight countries, mean age 77) comprising 12 interventions met inclusion criteria. We found home hazard modification interventions delivered to those with a previous falls history (1 study), was effective in reducing the number of falls (RR 0.63, 95%CI 0.43, 0.93, Low GRADE evidence). Home exercise interventions (3 studies) significantly increased the proportion of fallers (OR 1.74, 95%CI 1.17, 2.60, Moderate GRADE evidence), and did not significantly reduce falls rate (RR 1.27, 95%CI 0.99, 1.62, Very Low GRADE evidence) or falls injury rate (RR 1.16, 95%CI, 0.83,1.63, Low GRADE evidence). Nutritional supplementation for malnourished older adults (1 study) significantly reduced the proportion of fallers (HR 0.41, 95% CI 0.19, 0.86, Low GRADE evidence). the recommended falls prevention interventions for older adults recently discharged from hospital are to provide home hazard minimisation particularly if they have a recent previous falls history and consider nutritional supplementation if they are malnourished.


Glucagon-Like Peptide 1 and Its Cleavage Products Are Renoprotective in Murine Diabetic Nephropathy.
Incretin-based therapies, including glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors, are potent glucose-lowering drugs. Still, only GLP-1 receptor agonists with close peptide homology to GLP-1 (liraglutide and semaglutide) but neither exenatide-based GLP-1 receptor agonists nor DPP-4 inhibitors were found to reduce cardiovascular events. This different response might relate to GLP-1 receptor-independent actions of GLP-1 caused by cleavage products only liberated by GLP-1 receptor agonists with close peptide structure to GLP-1. To test this hypothesis, we directly compared metabolic, renal, and cardiac effects of GLP-1 and its cleavage products in diabetic db/db mice. Using an adeno-associated viral vector system, we overexpressed DPP-4-resistant GLP-1 (7-37 Mut8) and the two GLP-1 cleavage products, GLP-1 (9-37) and GLP-1 (28-37), in diabetic db/db mice. Only GLP-1 (7-37 Mut8), but none of the cleavage products, significantly improved glucose metabolism. Still, all GLP-1 constructs significantly reduced tubulointerstitial renal damage, lowered expression of the tubular injury markers, and attenuated renal accumulation of macrophages and T cells. This was associated with a systemic immunomodulatory effect, which was similarly found in an acute renal ischemia/reperfusion injury model. In conclusion, GLP-1 cleavage products proved sufficient to mediate organ-protective effects, which might help to explain differences between GLP-1 receptor agonists.


Perceptions of a Good Death in Children with Life-Shortening Conditions: An Integrative Review.
Background: For children with life-shortening illness, achieving a "good death" can be a tacit goal. There is little understanding of how different stakeholders perceive what a "good death" might be. Objective: To review empirical literature to construct an understanding of a "good death" for children with life-shortening conditions. Design: An integrative review approach was followed. This involved searching across Embase, Web of Science, Medline, CINAHL, and PsycINFO (no date limits set), as well as identifying eligible studies tracking reference lists. Appraisal of shortlisted articles in full text was performed, followed by data extraction, synthesis, and interpretation. Results: Analysis of articles (n = 24) yielded a dynamic and layered narrative about a good death that revolved around three themes. (1) Level of needs: includes both practical support and aspirational goals such as "do everything." (2) The composite experience: whether positive or negative adds to produce a sense of suffering. (3) Control (preservation and letting go): moving from maintaining status quo to acceptance of the child's death, the experience of which also contributes to suffering. Framed using a health care system perspective, a concept map that interprets a good death in children with life-shortening conditions is represented. Conclusions: A single yet holistic understanding of a good death experienced in the "real world" is suggested. Pediatric health and social care providers, and even policy makers, can use this new understanding to conceive alternative approaches to enhance support to dying children and their families.


Community level predictors of physical activity among women in the preconception period.
Although physical activity is a key behavior targeted during the preconception period given its significant impact on pregnancy/birth outcomes and psychological well-being, few women meet national guidelines. While intrapersonal factors influencing physical activity among this population have been studied, community factors remain unexplored. The objective of this study was to examine community level predictors of physical activity among preconception women. Data from Add Health were limited to women (Wave III; age 18-28; n = 7,596) and excluded respondents who were pregnant, physically disabled, and missing data. The outcome variable was ≥5 instances of moderate-vigorous physical activity (MVPA) in 1 week. Community predictor variables included neighborhood-level structural and social determinants (e.g., socio-demographic composition; landscape diversity; urbanization; access to resources; crime; vehicle availability). Multilevel logistic regression modeling was used to estimate the odds of engaging in ≥5 instances of MVPA. Few women (26 %) reported ≥5 instances of MVPA in 1 week. Adjusted multilevel analysis revealed women in the preconception period were more likely to report high MVPA when living in communities with larger population densities (OR 1.34, 95 % CI 1.02-1.77) and median household income greater than $50,000 (OR 1.33, 95 % CI 1.06-1.66). Additionally, a significant inverse trend was found between high MVPA and proportion of the community without a high school diploma. Findings suggest that neighborhood composition may have an impact on preconception physical activity status. Implications include increased efforts targeting community conditions for facilitating physical activity; ultimately, improving health among women and subsequent offspring.


Hits and misses: leveraging tDCS to advance cognitive research.
The popularity of non-invasive brain stimulation techniques in basic, commercial, and applied settings grew tremendously over the last decade. Here, we focus on one popular neurostimulation method: transcranial direct current stimulation (tDCS). Many assumptions regarding the outcomes of tDCS are based on the results of stimulating motor cortex. For instance, the primary motor cortex is predictably suppressed by cathodal tDCS or made more excitable by anodal tDCS. However, wide-ranging studies testing cognition provide more complex and sometimes paradoxical results that challenge this heuristic. Here, we first summarize successful efforts in applying tDCS to cognitive questions, with a focus on working memory (WM). These recent findings indicate that tDCS can result in cognitive task improvement or impairment regardless of stimulation site or direction of current flow. We then report WM and response inhibition studies that failed to replicate and/or extend previously reported effects. From these opposing outcomes, we present a series of factors to consider that are intended to facilitate future use of tDCS when applied to cognitive questions. In short, common pitfalls include testing too few participants, using insufficiently challenging tasks, using heterogeneous participant populations, and including poorly motivated participants. Furthermore, the poorly understood underlying mechanism for long-lasting tDCS effects make it likely that other important factors predict responses. In conclusion, we argue that although tDCS can be used experimentally to understand brain function its greatest potential may be in applied or translational research.


Surface and vertical dimensional changes of mineral trioxide aggregate and biodentine in different environmental conditions.
Surface changes in biological environments are critical for the evaluation of physical and biological activity of biomaterials. Objective: This study investigated surface alterations of calcium silicate-based cements after exposure to different environments. Material and Methods: Forty-eight cylindrical cavities were prepared on root surfaces. The cavities were filled using ProRoot MTA or Biodentine and assigned to four subgroups (n=6): dry, wet, acidic, and blood. Surface topographies were evaluated using an optical profilometer for 28 days, and the roughness of the material surfaces was quantified. Vertical dimensional change was measured by determining the height difference between the material surface and the flat tooth surface. Data were compared with a two-way repeated measures ANOVA and Bonferroni tests. Results: In dry condition, the surface roughness of MTA or Biodentine was constant up to 3 days (p>0.05) but decreased after 28 days (p<0.05). In dry condition, ProRoot MTA presented constant surface level through time, while Biodentine showed decreased surface level after 28 days. In wet condition, the roughness and the surface levels of both materials increased after 1 day (p<0.05). Neither the surface roughness nor the levels of the materials showed significant changes in acidic conditions (p>0.05). Both materials showed the highest roughness in blood conditions on the 1st day (p<0.05), while the surface roughness in blood decreased dramatically after 28 days. The roughness of Biodentine was higher in wet conditions up to 3 days compared with ProRoot MTA (p<0.05). Likewise, in blood condition, Biodentine showed higher roughness on the 28th day than ProRoot MTA (p<0.05). Conclusions: Dry, wet, and blood conditions had a time-dependent effect on the surface roughness and vertical dimensional changes of the materials. However, acidic conditions did not affect the roughness and the surface level of the materials.


Comparison of immunocytology to tissue culture for diagnosis of presumed herpesvirus dendritic epithelial keratitis.
The objective of this study is to prospectively compare the sensitivity and specificity of immunodetection of herpes simplex virus (HSV) in impression cytology specimens obtained directly from presumed herpesvirus dendritic epithelial keratitis with virus isolation by tissue culture of cells scraped from the same lesion. Corneal impression cytology and tissue culture were performed on 29 consecutive patients presenting with presumed herpesvirus dendritic epithelial keratitis during a 6-month period. Impression cytology of dendritic epithelial keratitis lesions with Millipore Biopore membranes were evaluated for the presence of antigens specific to HSV type I (HSV-1), HSV-2, and varicella-zoster virus (VZV) using monoclonal antibodies specific to these herpesviruses and immunofluorescent staining techniques. Tissue culture was positive for HSV-1 in 52% (13 of 25) of dendritic epithelial keratitis patients without skin lesions, and was negative for VZV in 4 patients with dendritic epithelial keratitis and skin lesions in the distribution of the first division of the trigeminal nerve. The remaining 12 tissue cultures showed no cytopathic effect. Compared with tissue culture, impression cytology was 100% sensitive (13 of 13) and 92% specific (11 of 12) for the diagnosis of HSV-1 dendritic epithelial keratitis (Kappa coefficient of agreement 0.92). Although our sample size for VZV dendritic epithelial keratitis was small, the impression cytology findings correlated with our clinical diagnosis more often than tissue culture (2 of 4 versus 0 of 4). Impression cytology allows simultaneous debridement of dendritic epithelial keratitis and, when combined with immunocytologic staining procedures, provides a simpler, more rapid, and less expensive alternative to tissue culture for the diagnosis of dendritic epithelial keratitis caused by HSV or VZV.


Selective targeting of p53 gene mutational hotspots in human cancers by etiologically defined carcinogens.
In lung and liver cancers, p53 mutations are mostly G:C to T:A transversions. This type of mutation is known to be induced by benzo(a)pyrene and aflatoxin B1 which are associated with the etiology of lung and liver cancers, respectively. Using a novel assay based on DNA polymerase fingerprint analysis, we identified p53 nucleotides targeted by these carcinogens. Thirteen of 14 nucleotide residues of the p53 gene which underwent G:C to T:A mutations in lung cancers were targeted by benzo(a)pyrene. Similarly, aflatoxin B1 formed adducts at a mutational hotspot specific for liver cancer. The same nucleotide (third base of codon 249), which mutates rarely in lung cancers, was not a target for benzo(a)pyrene. These in vitro observations indicate that p53 mutational hotspots identified in different tumors are selected targets specifically for the etiologically defined environmental carcinogens.


Attendance at Narcotics Anonymous and Alcoholics Anonymous meetings, frequency of attendance and substance use outcomes after residential treatment for drug dependence: a 5-year follow-up study.
This study investigates the relationship between frequency of attendance at Narcotics Anonymous and Alcoholics Anonymous (NA/AA) meetings and substance use outcomes after residential treatment of drug dependence. It was predicted that post-treatment NA/AA attendance would be related to improved substance use outcomes. Using a longitudinal, prospective cohort design, interviews were conducted with drug-dependent clients (n = 142) at intake to residential treatment, and at 1 year, 2 years and 4-5 years follow-up. Data were collected by structured interviews. All follow-up interviews were carried out by independent professional interviewers. Abstinence from opiates was increased throughout the 5-year follow-up period compared to pre-treatment levels. Clients who attended NA/AA after treatment were more likely to be abstinent from opiates at follow-up. Abstinence from stimulants increased at follow-up but (except at 1-year follow-up) no additional benefit was found for NA/AA attendance. There was no overall change in alcohol abstinence after treatment but clients who attended NA/AA were more likely to be abstinent from alcohol at all follow-up points. More frequent NA/AA attenders were more likely to be abstinent from opiates and alcohol when compared both to non-attenders and to infrequent (less than weekly) attenders. NA/AA can support and supplement residential addiction treatment as an aftercare resource. In view of the generally poor alcohol use outcomes achieved by drug-dependent patients after treatment, the improved alcohol outcomes of NA/AA attenders suggests that the effectiveness of existing treatment services may be improved by initiatives that lead to increased involvement and engagement with such groups.


Fluorogenic aptamers resolve the flexibility of RNA junctions using orientation-dependent FRET.
To further understand the transcriptome, new tools capable of measuring folding, interactions, and localization of RNA are needed. Although Förster resonance energy transfer (FRET) is an angle- and distance-dependent phenomenon, the majority of FRET measurements have been used to report distances, by assuming rotationally averaged donor-acceptor pairs. Angle-dependent FRET measurements have proven challenging for nucleic acids due to the difficulties in incorporating fluorophores rigidly into local substructures in a biocompatible manner. Fluorescence turn-on RNA aptamers are genetically encodable tags that appear to rigidly confine their cognate fluorophores, and thus have the potential to report angular-resolved FRET. Here, we use the fluorescent aptamers Broccoli and Mango-III as donor and acceptor, respectively, to measure the angular dependence of FRET. Joining the two fluorescent aptamers by a helix of variable length allowed systematic rotation of the acceptor fluorophore relative to the donor. FRET oscillated in a sinusoidal manner as a function of helix length, consistent with simulated data generated from models of oriented fluorophores separated by an inflexible helix. Analysis of the orientation dependence of FRET allowed us to demonstrate structural rigidification of the NiCo riboswitch upon transition metal-ion binding. This application of fluorescence turn-on aptamers opens the way to improved structural interpretation of ensemble and single-molecule FRET measurements of RNA.


Mechanism of K+-induced actin assembly.
The assembly of highly purified actin from Dictyostelium discoideum amoebae and rabbit skeletal muscle by physiological concentrations of KCI proceeds through successive stages of (a) rapid formation of a distinct monomeric species referred to as KCI-monomer, (b) incorporation of KCI-monomers into an ATP-containing filament, and (c) ATP hydrolysis that occurs significantly after the incorporation event. KCI-monomer has a conformation which is distinct from that of either conventional G- or F-actin, as judged by UV spectroscopy at 210-220 nm and by changes in ATP affinity. ATP is not hydrolyzed during conversion of G-actin to KCI-monomer. KCI-monomer formation precedes filament formation and may be necessary for the assembly event. Although incorporation of KCI-monomers into filaments demonstrates lagphase kinetics by viscometry, both continuous absorbance monitoring at 232 nm and rapid sedimentation of filaments demonstrate hyperbolic assembly curves. ATP hydrolysis significantly lags the formation of actin filaments. When half of the actin has assembled, only 0.1 to 0.2 mole of ATP are hydrolyzed per mole of actin present as filaments.


Genetic analysis of von Hippel-Lindau disease.
Mutations in the von Hippel-Lindau (VHL) gene are responsible for VHL disease, congenital polycythemia, and are found in many sporadic tumor types as well. Reports of VHL mutations are dispersed throughout original articles and databases that have not been recently updated. We compiled a comprehensive mutation table of 1,548 germline and somatic VHL mutations, derived from this protein of only 213 amino acids. We describe detailed phenotype and gene mutation information for 945 VHL families, including 30 previously unpublished kindreds from The Netherlands (six novel mutations). These data represent the most extensive catalog of germline VHL mutations to date. We also review VHL disease, known and theorized pathogenesis of common VHL manifestations, and genotype-phenotype correlations. Analysis of all VHL families, excluding germline mutations resulting in congenital polycythemias, describes the spectrum of mutation types: 52% missense, 13% frameshift, 11% nonsense, 6% in-frame deletions/insertions, 11% large/complete deletions, and 7% splice mutations. This easy-to-use compilation of VHL mutations is intended to facilitate research and function as a necessary adjunct for physicians when providing patient information.


Antibacterial effects of Iranian fennel essential oil on isolates of Acinetobacter baumannii.
The aim of the present study was the evaluation of the antibacterial activity of Fennel essential oil on isolates of Acinetobacter baumannii. Forty eight isolates were collected from clinical specimens from burn wards of hospitals in Tehran, Iran between April and September, 2006. The susceptibility of isolates was determined using a broth microdilution method. Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of isolates to Fennel essential oil were determined. The susceptibilities of isolates to different antibiotics were tested using agar disk diffusion method. The rates of resistance were determined to antibiotics as follows: cefazolin 100%, ciprofloxacin 100%, ofloxacin 95.8%, kanamycin 95.8%, carbenicillin 93.7%, ticarcillin 93.7%, piperacillin 88.9%, co-trimoxazole 79.1%, ceftizoxime 75%, gentamicin 70.8%, cefalotin 60.4%, amikacin 52% and imipenem 14.6%. Fennel essential oil possessed antibacterial effect against all isolates of A. baumannii. These results suggest the potential use of the Fennel essential oil for the control of multi-drug resistant A. baumannii infections. However, more adequate studies must be carried out to verify the possibility of using it for fighting bacterial infections in human.


Lateral integration of vertical-cavity surface-emitting laser and slow light Bragg reflector waveguide devices.
We present the modeling and the experiment on the lateral integration of a vertical-cavity surface-emitting laser (VCSEL) and slow light Bragg reflector waveguide devices. The modeling shows an efficient direct-lateral coupling from a VCSEL to an integrated slow light waveguide. The calculated result shows a possibility of 13 dB chip gain and an extinction ratio over 5 dB for a compact slow light semiconductor optical amplifier (SOA) and electroabsorption modulator integrated with a VCSEL, respectively. We demonstrate an SOA-integrated VCSEL, exhibiting the maximum output power over 6 mW. Also, we fabricate a sub-50-μm long electroabsorption modulator laterally integrated with a VCSEL. An extinction ratio of over 15 dB for a voltage swing of 2.0 V is obtained without noticeable change of threshold. In addition, we demonstrate an on-chip electrothermal beam deflector integrated with a VCSEL.


Controllable pulse parameter transcranial magnetic stimulator with enhanced circuit topology and pulse shaping.
This work aims at flexible and practical pulse parameter control in transcranial magnetic stimulation (TMS), which is currently very limited in commercial devices. We present a third generation controllable pulse parameter device (cTMS3) that uses a novel circuit topology with two energy-storage capacitors. It incorporates several implementation and functionality advantages over conventional TMS devices and other devices with advanced pulse shape control. cTMS3 generates lower internal voltage differences and is implemented with transistors with a lower voltage rating than prior cTMS devices. cTMS3 provides more flexible pulse shaping since the circuit topology allows four coil-voltage levels during a pulse, including approximately zero voltage. The near-zero coil voltage enables snubbing of the ringing at the end of the pulse without the need for a separate active snubber circuit. cTMS3 can generate powerful rapid pulse sequences (< 10 ms inter pulse interval) by increasing the width of each subsequent pulse and utilizing the large capacitor energy storage, allowing the implementation of paradigms such as paired-pulse and quadripulse TMS with a single pulse generation circuit. cTMS3 can also generate theta (50 Hz) burst stimulation with predominantly unidirectional electric field pulses. The cTMS3 device functionality and output strength are illustrated with electrical output measurements as well as a study of the effect of pulse width and polarity on the active motor threshold in ten healthy volunteers. The cTMS3 features could extend the utility of TMS as a research, diagnostic, and therapeutic tool.


South Africans with recent pregnancy rarely know partner's HIV serostatus: implications for serodiscordant couples interventions.
Implementation of safer conception strategies requires knowledge of partner HIV-serostatus. We recruited women and men in a high HIV-prevalence setting for a study to assess periconception risk behavior among individuals reporting HIV-serodiscordant partnerships. We report screening data from that study with the objective of estimating the proportion of individuals who are aware that they are in an HIV-serodiscordant relationship at the time of conception. We screened women and men attending antenatal and antiretroviral clinics in Durban, South Africa for enrollment in a study of periconception risk behavior among individuals with serodiscordant partners. Screening questionnaires assessed for study eligibility including age 18-45 years (for women) or at least 18 years of age (for men), pregnancy in past year (women) or partner pregnancy in the past 3 years (men), HIV status of partner for recent pregnancy, participant's HIV status, and infected partner's HIV status having been known before the referent pregnancy. Among 2620 women screened, 2344 (90%) met age and pregnancy criteria and knew who fathered the referent pregnancy. Among those women, 963 (41%) did not know the pregnancy partner's HIV serostatus at time of screening. Only 92 (4%) reported knowing of a serodiscordant partnership prior to pregnancy. Among 1166 men screened, 225 (19%) met age and pregnancy criteria. Among those men, 71 (32%) did not know the pregnancy partner's HIV status and only 30 (13%) reported knowing of a serodiscordant partnership prior to pregnancy. In an HIV-endemic setting, awareness of partner HIV serostatus is rare. Innovative strategies to increase HIV testing and disclosure are required to facilitate HIV prevention interventions for serodiscordant couples.


Studies on the rumen flagellate Neocallimastix frontalis.
The vast increase in the population density of the rumen flagellate Neocallimastix frontalis shortly after the host animal has commenced eating is caused by stimulation of a reproductive body on a vegetative phase of the organism to differentiate and liberate the flagellates. The stimulant is a component of the host's diet. The vegetative stage of N. frontalis bears a strong morphological resemblance to that of certain species of aquatic phycomycete fungi, and consists of a reproductive body borne on a single, much branched rhizoid. The flagellates liberated in vivo within 15 to 45 min of feeding lose their motility within I h and develop into the vegetative phase, thus producing a rapid decrease in population density of the flagellates. Conditions for maximum flagellate production are similar to those occurring in the rumen: pH 6-5, 39 degrees C, absence of O2, presence of CO2. Differentiation of the reproductive body is inhibited by compounds affecting membrane structure and function, but not by inhibitors of protein synthesis. The organism was cultured in vitro in an undefined medium in the absence of bacteria or other flagellates.


Tunable interactions between paramagnetic colloidal particles driven in a modulated ratchet potential.
We study experimentally and theoretically the interactions between paramagnetic particles dispersed in water and driven above the surface of a stripe patterned magnetic garnet film. An external rotating magnetic field modulates the stray field of the garnet film and generates a translating potential landscape which induces directed particle motion. By varying the ellipticity of the rotating field, we tune the inter-particle interactions from net repulsive to net attractive. For attractive interactions, we show that pairs of particles can approach each other and form stable doublets which afterwards travel along the modulated landscape at a constant mean speed. We measure the strength of the attractive force between the moving particles and propose an analytically tractable model that explains the observations and is in quantitative agreement with experiment.


Clinicopathologic analysis of IgG4-related skin disease.
IgG4-related disease is a recently recognized systemic syndrome characterized by mass-forming lesions with lymphoplasmacytic infiltration, increase in the number of IgG4(+) cells in affected tissues and elevation of serum IgG4 levels. In 2009, we were the first to report skin lesions in patients with IgG4-related disease, but no large case series has been reported and clinicopathological findings remain unclear. To clarify these features, we herein report 10 patients (9 men and 1 woman; median age, 64 years; age range, 46-81 years) with IgG4-related skin disease. All patients had erythematous and itchy plaques or subcutaneous nodules on the skin of the head and neck, particularly in the periauricular, cheek, and mandible regions, except for one patient, whose forearm and waist skin were affected. In addition, eight patients had extracutaneous lesions: these were found on the lymph nodes in six patients, the lacrimal glands in three patients, the parotid glands in three patients, and the kidney in one patient. Histologically examined extracutaneous lesions were consistent with IgG4-related disease; five of six lymph node lesions showed progressively transformed germinal centers-type IgG4-related lymphadenopathy. Cases of IgG4-related skin disease were classified into two histological patterns: those exhibiting a nodular dermatitis pattern and those with a subcutaneous nodule pattern. The infiltrate was rich in plasma cells, small lymphocytes, and eosinophils; the majority of the plasma cells were IgG4(+). The IgG4(+) cell count was 49-396 per high-power field (mean±s.d., 172±129), with an IgG4(+)/IgG(+) cell ratio ranging from 62 to 92%. Serum IgG4 levels were elevated in all examined patients. In conclusion, patients with IgG4-related skin disease had uniform clinicopathology. Lesions were frequently present on the skin of the periauricular, cheek, and mandible regions, and were frequently accompanied by IgG4-related lymphadenopathy.


3D palmprint and hand imaging system based on full-field composite color sinusoidal fringe projection technique.
Palmprint and hand shape, as two kinds of important biometric characteristics, have been widely studied and applied to human identity recognition. The existing research is based mainly on 2D images, which lose the third-dimensional information. The biological features extracted from 2D images are distorted by pressure and rolling, so the subsequent feature matching and recognition are inaccurate. This paper presents a method to acquire accurate 3D shapes of palmprint and hand by projecting full-field composite color sinusoidal fringe patterns and the corresponding color texture information. A 3D imaging system is designed to capture and process the full-field composite color fringe patterns on hand surface. Composite color fringe patterns having the optimum three fringe numbers are generated by software and projected onto the surface of human hand by a digital light processing projector. From another viewpoint, a color CCD camera captures the deformed fringe patterns and saves them for postprocessing. After compensating for the cross talk and chromatic aberration between color channels, three fringe patterns are extracted from three color channels of a captured composite color image. Wrapped phase information can be calculated from the sinusoidal fringe patterns with high precision. At the same time, the absolute phase of each pixel is determined by the optimum three-fringe selection method. After building up the relationship between absolute phase map and 3D shape data, the 3D palmprint and hand are obtained. Color texture information can be directly captured or demodulated from the captured composite fringe pattern images. Experimental results show that the proposed method and system can yield accurate 3D shape and color texture information of the palmprint and hand shape.


Minimal tethered cord syndrome: what's necessary to justify a new surgical indication?
Traditionally, surgical division of the terminal filum (filum terminale) has been reserved for patients with imaging-apparent spinal cord tethering. The occurrence of medically refractory voiding dysfunction of neurogenic origin, without magnetic resonance (MR) imaging documentation of abnormality in the spine, has been termed "minimal" tethered cord syndrome (TCS). The rationale for and utility of using surgical division of the terminal filum in the treatment of minimal TCS are unproven. Six studies that involved surgical division of the terminal filum for minimal TCS were identified and reviewed. A seventh study conducted prior to the MR imaging era, in which authors used myelography, was also included. In addition, two investigations of the clinicopathological findings in such cases were analyzed. A tripartite criterion for justifying the introduction of a new surgical indication is proposed and analyzed in light of this evidence. In children with minimal TCS there are definite pathological changes in the terminal filum that are not visible on routine spinal MR imaging. These changes suggest that the pathophysiology of minimal TCS, like TCS that is demonstrated on neuroimaging, may involve abnormal traction on the distal spinal cord. Additional data are needed regarding the sensitivity and specificity of various clinical studies intended to identify children with minimal TCS. All existing data supporting the efficacy of surgery for minimal TCS have been generated by Class III studies. Clinical equipoise exists for this surgical indication, and, therefore, a prospective randomized trial should be completed.


Simple sequence repeats together with mismatch repair deficiency can bias mutagenic pathways in Pseudomonas aeruginosa during chronic lung infection.
Pseudomonas aeruginosa is an opportunistic pathogen that chronically infects the airways of cystic fibrosis (CF) patients and undergoes a process of genetic adaptation based on mutagenesis. We evaluated the role of mononucleotide G:C and A:T simple sequence repeats (SSRs) in this adaptive process. An in silico survey of the genome sequences of 7 P. aeruginosa strains showed that mononucleotide G:C SSRs but not A:T SSRs were greatly under-represented in coding regions, suggesting a strong counterselection process for G:C SSRs with lengths >5 bp but not for A:T SSRs. A meta-analysis of published whole genome sequence data for a P. aeruginosa strain from a CF patient with chronic airway infection showed that G:C SSRs but not A:T SSRs were frequently mutated during the infection process through the insertion or deletion of one or more SSR subunits. The mutation tendency of G:C SSRs was length-dependent and increased exponentially as a function of SSR length. When this strain naturally became a stable Mismatch Repair System (MRS)-deficient mutator, the degree of increase of G:C SSRs mutations (5-fold) was much higher than that of other types of mutation (2.2-fold or less). Sequence analysis of several mutated genes reported for two different collections, both containing mutator and non-mutator strains of P. aeruginosa from CF chronic infections, showed that the proportion of G:C SSR mutations was significantly higher in mutators than in non-mutators, whereas no such difference was observed for A:T SSR mutations. Our findings, taken together, provide genome-scale evidences that under a MRS-deficient background, long G:C SSRs are able to stochastically bias mutagenic pathways by making the genes in which they are harbored more prone to mutation. The combination of MRS deficiency and virulence-related genes that contain long G:C SSRs is therefore a matter of concern in P. aeruginosa CF chronic infection.


Preventing Delirium Takes a Village: Systematic Review and Meta-analysis of Delirium Preventive Models of Care.
Each hospital day of delirium incurs greater healthcare costs, higher levels of care, greater staff burden, and higher complication rates. Accordingly, administrators are incentivized to identify models of care that reduce delirium rates and associated costs. We present a systematic review and meta-analysis of delirium prevention models of care. Ovid MEDLINE, CINAHL, Cochrane Database of Systematic Reviews, EMBASE, and PsycINFO. Eligible models of care were defined as provider-oriented interventions involving revision of professional roles, multidisciplinary teams, and service integration. Included studies implemented multidomain, multicomponent interventions, used a validated delirium instrument, and enrolled a control group to evaluate efficacy or effectiveness. We extracted data on study design; Population, model of care, outcomes, and results. A total of 15 studies were included. All but two studies reported reduction in delirium or its duration, and 11 studies reported statistically significant improvements. Using random effects models, the pooled odds ratios of delirium incidence were 0.56 (95% CI: 0.37-0.85) from three randomized controlled trials, 0.63 (95% CI 0.37-1.07) from four pre-post intervention studies, and 0.79 (95% CI: 0.46-1.37) from three additional nonrandomized studies. Several models of care can prevent delirium. In general, higher quality studies were more likely to demonstrate statistical significance of an effect. The diverse models of care included here explored interventions adapted to specific care settings, especially by addressing setting-specific delirium risk factors. These care models illustrate a range of promising strategies that deserve growing recognition, refinement, and implementation.


Optimizing Blood Transfusion Practices Through Bundled Intervention Implementation in Patients With Gynecologic Cancer Undergoing Laparotomy.
To examine blood transfusion practices and develop a standardized bundle of interventions to address the high rate of perioperative red blood cell transfusion among patients with ovarian and endometrial cancer. This was a retrospective cohort study. Our primary aim was to determine whether an implemented bundled intervention was associated with a reduction in perioperative red blood cell transfusions among cases of laparotomy for cancer. Secondary aims included comparing perioperative demographic, surgical, complication, and cost data. Interventions included blood transfusion practice standardization using American Society of Anesthesiologists guidelines, an intraoperative hemostasis checklist, standardized intraoperative fluid status communication, and evidence-based use of tranexamic acid. Prospective data from women undergoing laparotomy for ovarian or endometrial cancer from September 28, 2015, to May 31, 2016, defined the study cohort and were compared with historical controls (September 1, 2014, to September 25, 2015). Outcomes were compared in the full unadjusted cohorts and in propensity-matched cohorts. In the intervention and historical cohorts, respectively, 89 and 184 women underwent laparotomy for ovarian cancer (n=74 and 152) or advanced endometrial cancer (n=15 and 32). Tranexamic acid was administered in 54 (60.7%) patients. The perioperative transfusion rate was lower for the intervention group compared with historical controls (18.0% [16/89] vs 41.3% [76/184], P<.001), a 56.4% reduction. This improvement in the intervention group remained significant after propensity matching (16.2% [13/80] vs 36.2% [29/80], P=.004). The hospital readmission rate was also lower for the intervention group compared with historical controls (1.1% [1/89] vs 12.5% [23/184], P=.002); however, this improvement did not attain statistical significance after propensity matching (1.2% [1/80] vs 7.5% [6/80], P=.12). Cost analysis demonstrated that this intervention was cost-neutral during index hospitalization plus 30-day follow-up. Application of a standardized bundle of evidence-based interventions was associated with reduced blood use in our gynecologic oncology practice.


Comparison of four membrane filter methods for fecal coliform enumeration in tropical waters.
Four membrane filter methods for the enumeration of fecal coliforms were compared for accuracy, specificity, and recovery. Water samples were taken several times from 13 marine, 1 estuarine, and 4 freshwater sites around Puerto Rico, from pristine waters and waters receiving treated and untreated sewage and effluent from a tuna cannery and a rum distillery. Differences of 1 to 3 orders of magnitude in the levels of fecal coliforms were observed in some samples by different recovery techniques. Marine water samples gave poorer results, in terms of specificity, selectivity, and comparability, than freshwater samples for all four fecal coliform methods used. The method using Difco m-FC agar with a resuscitation step gave the best overall results; however, even this method gave higher false-positive error, higher undetected-target error, lower selectivity, and higher recovery of nontarget organisms than the method using MacConkey membrane broth, the worst method for temperate waters. All methods tested were unacceptable for the enumeration of fecal coliforms in tropical fresh and marine waters. Thus, considering the high densities of fecal coliforms observed at most sites in Puerto Rico by all these methods, it would seem that these density estimates are, in many cases, grossly overestimating the degree of recent fecal contamination. Since Escherichia coli appears to be a normal inhabitant of tropical waters, fecal contamination may be indicated when none is present. Using fecal coliforms as an indicator is grossly inadequate for the detection of recent human fecal contamination and associated pathogens in both marine and fresh tropical waters.


Differential network analysis reveals genetic effects on catalepsy modules.
We performed short-term bi-directional selective breeding for haloperidol-induced catalepsy, starting from three mouse populations of increasingly complex genetic structure: an F2 intercross, a heterogeneous stock (HS) formed by crossing four inbred strains (HS4) and a heterogeneous stock (HS-CC) formed from the inbred strain founders of the Collaborative Cross (CC). All three selections were successful, with large differences in haloperidol response emerging within three generations. Using a custom differential network analysis procedure, we found that gene coexpression patterns changed significantly; importantly, a number of these changes were concordant across genetic backgrounds. In contrast, absolute gene-expression changes were modest and not concordant across genetic backgrounds, in spite of the large and similar phenotypic differences. By inferring strain contributions from the parental lines, we are able to identify significant differences in allelic content between the selected lines concurrent with large changes in transcript connectivity. Importantly, this observation implies that genetic polymorphisms can affect transcript and module connectivity without large changes in absolute expression levels. We conclude that, in this case, selective breeding acts at the subnetwork level, with the same modules but not the same transcripts affected across the three selections.


Linkage mapping of a large Colombian family segregating for X linked retinoschisis: refinement of the chromosomal location.
Juvenile X linked retinoschisis (RS) is a bilateral vitreoretinal dystrophy that develops early in life. Previous linkage studies have localised the RS gene to Xp22.1-p22.3 between DXS207 and AFM 291Wf5, which represents a genetic distance of approximately 3.7 cM. In an effort to facilitate the eventual cloning of the RS gene, we have analysed a large Colombian family, using 10 microsatellite markers that have been mapped to the region Xp22.1-p22.3. A total of 93 members, including 19 affected and eight unaffected males, two affected females, and six obligate carrier females were analysed. Close linkage was observed between the disease locus and DXS999 (Zmax = 2.27, theta max = 0.05), DXS987 (Zmax = 2.61, theta max = 0.1), DXS443 (Zmax = 4.23, theta max = 0.1), and DXS274 (Zmax = 3.49, theta max = 0.05) markers. Recombination with the RS locus was found for all marker loci except DXS197, DXS43, and DXS1195. These results place the RS locus within an interval of approximately 2 cM between the flanking markers DXS1053 and DXS999, approximately 1.7 cM closer than the previously reported boundary. The results also further confirm the lack of genetic heterogeneity of RS.


Beyond Body Mass Index: Advantages of Abdominal Measurements for Recognizing Cardiometabolic Disorders.
The clinical recognition of cardiometabolic disorders might be enhanced by anthropometry based on the sagittal abdominal diameter (SAD; also called "abdominal height") or waist circumference rather than on weight. Direct comparisons of body mass index (BMI, weight/height(2)) with SAD/height ratio (SADHtR) or waist circumference/height ratio (WHtR) have not previously been tested in nationally representative populations. Nonpregnant adults without diagnosed diabetes (ages 20-64 years; n = 3071) provided conventional anthropometry and supine SAD (by sliding-beam caliper) in the 2011-2012 US National Health and Nutrition Examination Survey. Population-weighted, logistic models estimated how strongly each anthropometric indicator was associated with 5 cardiometabolic disorders: Dysglycemia (glycated hemoglobin ≥5.7%), HyperNonHDLc (non-high-density-lipoprotein [HDL] cholesterol ≥4.14 mmol/L, or taking anticholesteremic medications), Hypertension (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg, or taking antihypertensive medications), HyperALT (alanine transaminase ≥p75 [75th percentile, sex-specific]), and HyperGGT (gamma-glutamyltransferase ≥p75 [sex-specific]). After scaling each indicator, adjusted odds ratios (aORs) tended to be highest for SADHtR and lowest for BMI when identifying each disorder except dysglycemia. When SADHtR entered models simultaneously with BMI, the aORs for BMI no longer directly identified any condition, whereas SADHtR identified persons with HyperNonHDLc by aOR 2.78 (95% confidence interval [CI], 1.71-4.51), Hypertension by aOR 2.51 (95% CI, 1.22-5.15), HyperALT by aOR 2.89 (95% CI, 1.56-5.37), and HyperGGT by aOR 5.43 (95% CI, 3.01-9.79). WHtR competed successfully against BMI with regard to Dysglycemia, HyperNonHDLc, and HyperGGT. c-Statistics of SADHtR and WHtR were higher than those of BMI (P <.001) for identifying HyperNonHDLc and HyperGGT. Among nonelderly adults, SADHtR or WHtR recognized cardiometabolic disorders better than did the BMI.


Treating individuals 2. Subgroup analysis in randomised controlled trials: importance, indications, and interpretation.
Large pragmatic trials provide the most reliable data about the effects of treatments, but should be designed, analysed, and reported to enable the most effective use of treatments in routine practice. Subgroup analyses are important if there are potentially large differences between groups in the risk of a poor outcome with or without treatment, if there is potential heterogeneity of treatment effect in relation to pathophysiology, if there are practical questions about when to treat, or if there are doubts about benefit in specific groups, such as elderly people, which are leading to potentially inappropriate undertreatment. Analyses must be predefined, carefully justified, and limited to a few clinically important questions, and post-hoc observations should be treated with scepticism irrespective of their statistical significance. If important subgroup effects are anticipated, trials should either be powered to detect them reliably or pooled analyses of several trials should be undertaken. Formal rules for the planning, analysis, and reporting of subgroup analyses are proposed.


Routine primary care management of acute low back pain: adherence to clinical guidelines.
One of the major challenges for general practitioners is to manage individuals with acute low back pain appropriately to reduce the risk of chronicity. A prospective study was designed to assess the actual management of acute low back pain in one primary care setting and to determine whether existing practice patterns conform to published guidelines. Twenty-four family physicians from public primary care centers of the Basque Health Service in Bizkaia, Basque Country (Spain), participated in the study. A total of 105 patients aged 18-65 years presenting with acute low back pain over a 6-month period were included. Immediately after consultation, a research assistant performed a structured clinical interview. The patients' care provided by the general practitioner was compared with the Agency for Health Care Policy and Research (AHCPR) guidelines and guidelines issued by the Royal College of General Practitioners. The diagnostic process showed a low rate of appropriate use of history (27%), physical examination (32%), lumbar radiographs (31%), and referral to specialized care (33%). Although the therapeutic process showed a relatively high rate of appropriateness in earlier mobilization (77%) and educational advice (65%), only 23% of patients were taught about the benign course of back pain. The study revealed that management of acute low back pain in the primary care setting is far from being in conformance with published clinical guidelines.


Placental extracellular vesicles express active dipeptidyl peptidase IV; levels are increased in gestational diabetes mellitus.
Gestational diabetes mellitus (GDM) is the most common metabolic disorder in pregnancy and is characterized by insulin resistance and decreased circulating glucagon-like peptide-1 (GLP-1). GDM resolves rapidly after delivery implicating the placenta in the disease. This study examines the biological functions that cause this pathology. The placenta releases syncytiotrophoblast-derived extracellular vesicles (STB-EVs) into the maternal circulation, which is enhanced in GDM. Dipeptidyl peptidase IV (DPPIV) is known to play a role in type 2 diabetes by breaking down GLP-1, which in turn regulates glucose-dependent insulin secretion. STB-EVs from control and GDM women were analysed. We show that normal human placenta releases DPPIV-positive STB-EVs and that they are higher in uterine than paired peripheral blood, confirming placental origin. DPPIV-bound STB-EVs from normal perfused placentae are dose dependently inhibited with vildagliptin. DPPIV-bound STB-EVs from perfused placentae are able to breakdown GLP-1 in vitro. STB-EVs from GDM perfused placentae show greater DPPIV activity. Importantly, DPPIV-bound STB-EVs increase eightfold in the circulation of women with GDM. This is the first report of STB-EVs carrying a biologically active molecule that has the potential to regulate maternal insulin secretion.


Characterization of K+ channel-dependent as well as -independent components of pinacidil-induced vasodilation.
The mechanisms of pinacidil-induced direct vasodilation were studied in vitro in RMA and RAO. In RMA, pinacidil produced dose-dependent relaxations of norepinephrine (5 microM)-induced contractions with an IC50 of 0.2 microM. This component of pinacidil relaxation appeared to be dependent on K+ conductance because pretreatment with tetraethylammonium (10 mM), Ba++ (0.5 mM), glyburide (1 microM) and 20 mM K+ all caused a rightward shift of the pinacidil dose-response curve (DRC) and a corresponding increase in the pinacidil IC50. However, additional relaxation effects of pinacidil were still evident in the presence of various K+ channel blockers. Pinacidil also showed a relaxation DRC under the condition of 80 mM K+ contraction in both RMA and RAO with IC50 values of 27 and 50 microM, respectively. Pinacidil could also produce maximal relaxation in RMA and RAO remained unaffected in 145 mM K+ (zero Na+) depolarizing solution suggesting a lack of dependence on Na(+)-Ca++ exchange mechanism for this action of pinacidil. Studies using 1 or 3 min pulse labeling with 45Ca showed an absence of an inhibitory effect of pinacidil (at 50 and 100 microM) on unidirectional 45Ca influx stimulated by high-K+. Net 45Ca uptake studies showed that pinacidil inhibited high-K+ stimulated 45Ca uptake at 100 but not at 50 microM. Ryanodine (10-100 microM) was used as a tool to investigate the role of sarcoplasmic reticulum (SR) in this action of pinacidil. Under the condition in which ryanodine (10-100 microM) treatment was found to cause the SR to be nonfunctional, pinacidil relaxation DRC remained unaltered, suggesting a lack of a stimulatory effect of pinacidil on SR Ca++ accumulation. These data thus show that the K+ channel-independent effect of pinacidil does not involve to any significant degree an effect of pinacidil on plasmalemmal voltage-sensitive Ca++ channels, SR Ca++ stores, Na(+)-Ca++ exchange or membrane hyperpolarization.(ABSTRACT TRUNCATED AT 250 WORDS)


Proceedings of the 2019 Santa Fe Bone Symposium: New Concepts in the Care of Osteoporosis and Rare Bone Diseases.
The 20th annual Santa Fe Bone Symposium was held August 9-10, 2019, in Santa Fe, New Mexico, USA. This is an annual meeting devoted to clinical applications of recent advances in skeletal research that impact the care of patients with osteoporosis, metabolic bone diseases, and inherited bone diseases. Participants included practicing and academic physicians, fellows, advanced practice providers, fracture liaison service (FLS) coordinators, clinical researchers, and bone density technologists. The symposium consisted of lectures, case presentations, and panel discussions, with an emphasis on learning through interaction of all attendees. Topics included new approaches in the use of anabolic agents for the treatment osteoporosis, a review of important events in skeletal health over the past year, new and emerging treatments for rare bone diseases, the use of genetic testing for bone diseases in clinical practice, medication-associated causes of osteoporosis, new concepts in the use of estrogen therapy for osteoporosis, new Official Positions of the International Society for Clinical Densitometry, skeletal consequences of bariatric surgery, and update on the progress and potential of Bone Health TeleECHO, a virtual community of practice using videoconferencing technology to link healthcare professionals for advancing the care of osteoporosis worldwide. Sessions on rare bone diseases were developed in collaboration with the Rare Bone Disease Alliance. Symposium premeetings included an FLS workshop by the National Osteoporosis Foundation and others devoted to the use of new therapeutic agents for the care of osteoporosis and related disorders.


Coupled high Q-factor surface nanoscale axial photonics (SNAP) microresonators.
We experimentally demonstrate series of identical two, three, and five coupled high Q-factor surface nanoscale axial photonics (SNAP) microresonators formed by periodic nanoscale variation of the optical fiber radius. These microresonators are fabricated with a 100 μm period along an 18 μm radius optical fiber. The axial FWHM of these microresonators is 80 μm and their Q-factor exceeds 10(7). In addition, we demonstrate a SNAP microresonator with the axial FWHM as small as 30 μm and the axial FWHM of the fundamental mode as small as 10 μm. These results may potentially enable the dense integration of record low loss coupled photonic microdevices on the optical fiber platform.


Returning to work after long term sickness absence due to low back pain - the struggle within: a qualitative study of the patient's experience.
Low back pain (LBP) is a major cause of work absence. Assisting individuals back into work is an important part of rehabilitation. To explore the experiences of individuals returning to work after an episode of sickness absence due to LBP. Five women employed by a UK University who had returned to work. In this qualitative study, participants underwent semi-structured interviews about their experiences. The transcripts were analysed using interpretative phenomenological analysis. Two primary themes emerged 1) perceived pressure to return to work and 2) strategies employed to relieve the pressure to return. Pressure to return to work arose from a number of sources including guilt and a personal work ethic, internally, and from colleagues and management, externally. This pressure led to the individual employing a number of strategies to reduce it. These ranged from a simple denial of health concerns and decision to return to work regardless of their condition, to placing the responsibility of the decision not to return to work onto a significant other, such as a family member or health care professional. Individuals returning to work with LBP experience considerable pressure to return and use a range of strategies to mediate that pressure.


Hormone-induced intercellular signal transfer dissociates cyclic AMP-dependent protein kinase.
We used co-cultures of porcine ovarian granulosa cells and mouse adrenocortical tumor cells (Y-1) to examine the kinetics of contact-dependent intercellular signal transfer and to assess the molecular mechanisms employed by this process. Exposure to follicle-stimulating hormone (FSH) caused cAMP-dependent protein kinase dissociation in granulosa cells and, with time, in Y-1 cells if, and only if, they contacted a responding granulosa cell. Y-1 cells close to a granulosa cell but not touching it failed to respond similarly. In reciprocal experiments, co-cultures were stimulated with adrenocorticotropic hormone (ACTH). Y-1 cells dissociated protein kinase as did granulosa cells in contact with Y-1 cells; however, granulosa cells that were not in contact with Y-1 cells failed to respond to the hormone. Fluorogenic steroids were secreted by Y-1 cells cultured alone and stimulated with ACTH, but were not secreted by cultures exposed to FSH. Neither hormone caused fluorogenic steroid production by granulosa cells. On the other hand these steroids were secreted in co-cultures stimulated with ACTH and to a lesser degree in co-cultures exposed to FSH. Autoradiography revealed that I125-FSH bound only to granulosa cells, never to Y-1 cells, even if they were in contact with an ovarian cell. The possibility of cell fusion was tested by experiments in which Y-1 cell membranes were labeled with cationized ferritin. These cells were then placed in co-culture with ovarian granulosa cells that had previously been allowed to ingest latex spheres. At regions of gap junctions between Y-1 and granulosa cells ferritin remained attached to the adrenal cell membrane and was never observed to migrate to the granulosa cell membrane. From these data, we conclude that hormone specific stimulation of one cell type leads to protein kinase dissociation in heterotypic partners only if they contact a hormone responsive cell. This signal transfer is bidirectional, exhibits temporal kinetics and occurs in the absence of apparent cell fusion. The only structural feature connecting Y-1 and granulosa cells were gap junctions implying they provided the communication channels; however, alternative mechanisms cannot be excluded. We have not established the identity of the signal being transferred although cAMP is a logical candidate.


Design optimization of integrated BiDi triplexer optical filter based on planar lightwave circuit.
Design optimization of a novel integrated bi-directional (BiDi) triplexer filter based on planar lightwave circuit (PLC) for fiber-to-the premise (FTTP) applications is described. A multi-mode interference (MMI) device is used to filter the up-stream 1310nm signal from the down-stream 1490nm and 1555nm signals. An array waveguide grating (AWG) device performs the dense WDM function by further separating the two down-stream signals. The MMI and AWG are built on the same substrate with monolithic integration. The design is validated by simulation, which shows excellent performance in terms of filter spectral characteristics (e.g., bandwidth, cross-talk, etc.) as well as insertion loss.


Reducing GBA2 Activity Ameliorates Neuropathology in Niemann-Pick Type C Mice.
The enzyme glucocerebrosidase (GBA) hydrolyses glucosylceramide (GlcCer) in lysosomes. Markedly reduced GBA activity is associated with severe manifestations of Gaucher disease including neurological involvement. Mutations in the GBA gene have recently also been identified as major genetic risk factor for Parkinsonism. Disturbed metabolism of GlcCer may therefore play a role in neuropathology. Besides lysosomal GBA, cells also contain a non-lysosomal glucosylceramidase (GBA2). Given that the two β-glucosidases share substrates, we speculated that over-activity of GBA2 during severe GBA impairment might influence neuropathology. This hypothesis was studied in Niemann-Pick type C (Npc1-/-) mice showing secondary deficiency in GBA in various tissues. Here we report that GBA2 activity is indeed increased in the brain of Npc1-/- mice. We found that GBA2 is particularly abundant in Purkinje cells (PCs), one of the most affected neuronal populations in NPC disease. Inhibiting GBA2 in Npc1-/- mice with a brain-permeable low nanomolar inhibitor significantly improved motor coordination and extended lifespan in the absence of correction in cholesterol and ganglioside abnormalities. This trend was recapitulated, although not to full extent, by introducing a genetic loss of GBA2 in Npc1-/- mice. Our findings point to GBA2 activity as therapeutic target in NPC.


A time series evaluation of the FAST National Stroke Awareness Campaign in England.
In February 2009, the Department of Health in England launched the Face, Arm, Speech, and Time (FAST) mass media campaign, to raise public awareness of stroke symptoms and the need for an emergency response. We aimed to evaluate the impact of three consecutive phases of FAST using population-level measures of behaviour in England. Interrupted time series (May 2007 to February 2011) assessed the impact of the campaign on: access to a national stroke charity's information resources (Stroke Association [SA]); emergency hospital admissions with a primary diagnosis of stroke (Hospital Episode Statistics for England); and thrombolysis activity from centres in England contributing data to the Safe Implementation of Thrombolysis in Stroke UK database. Before the campaign, emergency admissions (and patients admitted via accident and emergency [A&E]) and thrombolysis activity was increasing significantly over time, whereas emergency admissions via general practitioners (GPs) were decreasing significantly. SA webpage views, calls to their helpline and information materials dispatched increased significantly after phase one. Website hits/views, and information materials dispatched decreased after phase one; these outcomes increased significantly during phases two and three. After phase one there were significant increases in overall emergency admissions (505, 95% CI = 75 to 935) and patients admitted via A&E (451, 95% CI = 26 to 875). Significantly fewer monthly emergency admissions via GPs were reported after phase three (-19, 95% CI = -29 to -9). Thrombolysis activity per month significantly increased after phases one (3, 95% CI = 1 to 6), and three (3, 95% CI = 1 to 4). Phase one had a statistically significant impact on information seeking behaviour and emergency admissions, with additional impact that may be attributable to subsequent phases on information seeking behaviour, emergency admissions via GPs, and thrombolysis activity. Future campaigns should be accompanied by evaluation of impact on clinical outcomes such as reduced stroke-related morbidity and mortality.