Reduction in hospital readmission stay of elderly patients by a community based hospital discharge scheme: a randomised controlled trial.
To compare a community support scheme using care attendants with standard aftercare for their effects on independence and morale of elderly patients discharged from hospital and on their use of health and social services. Randomised controlled study of cohort of patients over 75 discharged to their own homes. District general hospital and community. Total of 903 patients (mean age 82, 25% over 85). Total of 464 patients received support from care attendants on first day at home and for up to 12 hours a week for two weeks. Support comprised practical care, help with rehabilitation, and organising social help. The remaining 439 patients received standard aftercare. Difference between two groups of 7% in hospital readmission rates or one point on activities of daily living scale (power 80%, significance level 5%). Three months after the initial discharge 763 patients were interviewed (84%). There were no significant differences between the two groups in physical independence (activities of daily living scale), in measures of morale (Philadelphia scale), or in death rates. Hospital readmission rates within 18 months of discharge, however, were significantly higher in the control group and they spent more days in hospital (mean; control group 30.6 days, support group 17.1 days; p = 0.014). Of the patients living alone who were followed up for 18 months 21 (15%) receiving standard aftercare were readmitted more than twice compared with 6 (5%) supported by care attendants (p less than 0.01). If the findings are confirmed, and the policy extended to all patients over the age of 75 living alone, an average health district might expect either to save about 23 hospital beds at a net annual saving of about pounds 220,000 in the short term or to increase available beds by this number.


Developing a Wireless, High Precision and Processing Speed Pulse Monitoring Headset Using Photoplethysmography.
In this paper, thorough improvement of pulse monitoring and analysis equipment with a headset structure is presented. In order to study the most suitable infrared wavelength for the acquisition of the pulse wave at the earlobe, Monte Carlo simulation was adapted. Both high frequency noise and baseline drift, generated in the signal acquisition process, are considered. To further optimize the system design and improve accuracy, for the sensor's dimensional drift, the corresponding compensation was carried on in the software. This paper introduced nonlinear quantization, especially in terms of very weak pulse signal, in the time domain analysis process. A quick extraction method named table look-up combing with interpolation was utilized to obtain frequency domain information whose processing speed can be increased by about 30 times compared with fast Fourier transformation setting the sampling point as 300. The results demonstrated the sensor's excellent performance in pulse signal acquisition whose maximum residual is less than 0.004 mV. The test on a random sample of 300 people indicates that the system had high correlation with reference, validating the system accuracy is extremely high. Overall, this paper provides a practical pulse monitoring and analysis system with high precision and processing speed that can be widely applied in the field of health management or medical measurement.


Overcrowding is associated with delays in percutaneous coronary intervention for acute myocardial infarction.
Recently developed crowding measures, such as the Emergency Department (ED) Work Index (EDWIN) score, provide a quantifiable measurement of overcrowding in the ED. We sought to determine the association between overcrowding, measured with the EDWIN score, and the time required to initiate percutaneous coronary intervention (PCI) for patients presenting to the ED with acute myocardial infarction (AMI). We retrospectively reviewed the performance improvement (PI) data on all patients presenting to the ED over a 2-month period with chest pain and whose subsequent ECG showed AMI requiring PCI. We recorded the time from patient presentation to the (1) time to first ECG, (2) time to patient arrival in the catheterization laboratory, and (3) time to catheter balloon inflation. We calculated EDWIN scores using data archived from our electronic tracking board and compared the proportion of patients who achieved our established ED goal times between patients presenting during low crowding (EDWIN < 1.5) and high crowding (EDWIN > or = 1.5) conditions. Seventeen patients underwent emergent PCI in the study period. Patients presenting to the ED during periods of low crowding had shorter times to balloon inflation (median of 84 min, IQR 80 to 93 min) than patients presenting to the ED during periods of high crowding (median of 107 min, IQR 94 to 122 min), P = 0.008. Times to first ECG and to arrival in the catheterization laboratory were not significantly different between patients presenting during low and high crowding conditions. Overcrowding appears to be associated with a decreased likelihood of timely treatment for acute AMI in our ED.


Cloud-point extraction and delipidation of porcine brain proteins in combination with bottom-up mass spectrometry approaches for proteome analysis.
In this study, temperature-induced phase fractionation also known as cloud-point extraction (CPE) with the nonionic surfactant Triton X-114 was used to simultaneously extract hydrophobic and hydrophilic proteins from porcine brain tissue. Various protein precipitation/delipidation procedures were investigated to efficiently remove lipids and detergents while retaining maximum protein recoveries. The best performing delipidation method was then used in combination with CPE to compare three different mass spectrometry (MS) based "bottom-up" proteomic approaches for protein analysis of the porcine brain. In the first approach, the intact proteins were initially separated by one-dimensional (1D) gel electrophoresis. The excised protein bands were digested with trypsin, and the peptides were separated by reversed phase nanoliquid chromatography (RP-nanoLC) followed by electrospray ionization (ESI) tandem mass spectrometry (MS/MS) analysis. The other bottom-up proteomic approaches were based on first enzymatical digestion of the proteins followed by RP-nanoLC separation in combination with matrix assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS) or on the combination of in-solution isoelectric focusing (IEF) with ESI-nanoLC-MS/MS of the IEF separated peptides. In total, we found and unambiguously identified 331 unique proteins. The overlap between different techniques was about 10%, showing that the use of multiple proteomic approaches is beneficial to yield a better coverage of the proteome. Furthermore, the overlap between the CPE extracted hydrophilic and hydrophobic proteins was rather small (9-16%), indicating an efficient sample preparation technique to extract and separate hydrophilic and hydrophobic proteins from brain tissue. The percentage of identified membrane proteins was 27%, which is in accordance to the fact that about one-third of all genes in various organisms encode for this class of proteins. The results indicate that cloud point extraction is a promising sample preparation tool, which allows simultaneous in depth studies of brain derived membrane proteins as well as hydrophilic proteins. This technique can be very useful when studying human central nervous system (CNS) tissue or animal models of neurological diseases.


A general and rapid room-temperature synthesis approach for metal sulphide nanocrystals with tunable properties.
Colloidal metal sulphide (MS) nanocrystals (NCs) have recently attracted considerable attention because of their tunable properties that can be exploited in various physical, chemical and biological applications. In this work, we present a novel and general method for synthesis of monodispersed binary (CuS, Ag2S, CdS, PbS, and SnS), ternary (Ag-In-S, Cu-In-S and Cu-Sn-S) and quaternary (Cu-Zn-Sn-S) MS NCs. The synthesis is conducted at room temperature, with an immediate crystallization process and up to 60 seconds of growth time, enabling rapid synthesis without external heating. For some of the ternary and quaternary NCs produced with relatively low crystallinity, we then carried out a "colloidal annealing" process to improve their crystallinity without changing their composition. Moreover, we show that the morphology and optical properties of the NCs can be tuned by varying the concentration of precursors and reaction time. The shape evolution and photoluminescence of particular MS NCs were also studied. These results not only provide insights into the growth mechanisms of MS NCs, but also yield a generalized, low cost, and potentially scalable method to fabricate them.


Uncoupling heart cell specification and migration in the simple chordate Ciona intestinalis.
The bHLH transcription factor Mesp has an essential but ambiguous role in early chordate heart development. Here, we employ the genetic and morphological simplicity of the basal chordate Ciona intestinalis to elucidate Mesp regulation and function. Characterization of a minimal cardiac enhancer for the Ciona Mesp gene demonstrated direct activation by the T-box transcription factor Tbx6c. The Mesp enhancer was fused to GFP, permitting high-resolution visualization of heart cells as they migrate and divide. The enhancer was also used to drive targeted expression of an activator form of Mesp, which induces heart formation without migration. We discuss the implications of Tbx6-Mesp interactions for the evolution of cardiac mesoderm in invertebrates and vertebrates.


A robust diffusion-based gradient generator for dynamic cell assays.
This manuscript describes a new method to generate purely diffusive chemical gradients that can be modified in time. The device is simple in its design and easy to use, which makes it amenable to study biological processes that involve static or dynamic chemical gradients such as chemotaxis. We describe the theory underlying the convection-free gradient generator, illustrate the design to implement the theory, and present a protocol to align multiple layers of double sided tape and laminates to fabricate the device. Using this device, a population of mammalian cells was exposed to different concentrations of a toxin within a concentration gradient in a 48 h experiment. Cells were probed dynamically by cycling the gradient on and off, and cell response was monitored using time-lapse fluorescence microscopy. The experiment and results illustrate the type of applications involving dynamic cell behavior that can be targeted with this type of gradient generator.


The neural mechanisms of learning from competitors.
Learning from competitors poses a challenge for existing theories of reward-based learning, which assume that rewarded actions are more likely to be executed in the future. Such a learning mechanism would disadvantage a player in a competitive situation because, since the competitor's loss is the player's gain, reward might become associated with an action the player should themselves avoid. Using fMRI, we investigated the neural activity of humans competing with a computer in a foraging task. We observed neural activity that represented the variables required for learning from competitors: the actions of the competitor (in the player's motor and premotor cortex) and the reward prediction error arising from the competitor's feedback. In particular, regions positively correlated with the unexpected loss of the competitor (which was beneficial to the player) included the striatum and those regions previously implicated in response inhibition. Our results suggest that learning in such contexts may involve the competitor's unexpected losses activating regions of the player's brain that subserve response inhibition, as the player learns to avoid the actions that produced them.


Factors likely to influence the adoption of targeted selective treatment strategies by sheep farmers in Western Australia.
The investigation aimed to assess factors affecting the uptake of novel targeted selective treatment (TST) strategies by sheep farmers in Western Australia where the most common nematode species present were Teladosagia circumcincta, Trichostrongylus spp. and Nematodirus spp. ("scour worms"). The study used a questionnaire format with questions concentrated on current worm control practices and farmers' current understanding and adoption of putative TST strategies. Participants represented a range of environments (derived from four farming regions) and sheep management situations, and it is therefore likely that the results of this investigation will apply in other locations where scour worms predominate. Sixty-five percent of participants were aware of the TST concept and 25% had implemented it in some form. The awareness of the TST approach was greatest where sheep farmers were concerned about anthelmintic resistance, where tools such as worm egg counts and faecal worm egg count resistance tests were employed, and where professional advisers were consulted regarding worm control. Respondents that sought advice chiefly from rural merchandise retailers were considerably less (0.1-0.6 times) likely to be aware of these management tools or to be aware of TST approaches. The findings indicated that the adoption of TST strategies will require greater use of professional advisers for worm control advice by sheep farmers, and that advisers are conversant with TST concepts.


Suppression of NLRP3 inflammasome by γ-tocotrienol ameliorates type 2 diabetes.
The Nod-like receptor 3 (NLRP3) inflammasome is an intracellular sensor that sets off the innate immune system in response to microbial-derived and endogenous metabolic danger signals. We previously reported that γ-tocotrienol (γT3) attenuated adipose tissue inflammation and insulin resistance in diet-induced obesity, but the underlying mechanism remained elusive. Here, we investigated the effects of γT3 on NLRP3 inflammasome activation and attendant consequences on type 2 diabetes. γT3 repressed inflammasome activation, caspase-1 cleavage, and interleukin (IL) 1β secretion in murine macrophages, implicating the inhibition of NLRP3 inflammasome in the anti-inflammatory and antipyroptotic properties of γT3. Furthermore, supplementation of leptin-receptor KO mice with γT3 attenuated immune cell infiltration into adipose tissue, decreased circulating IL-18 levels, preserved pancreatic β-cells, and improved insulin sensitivity. Mechanistically, γT3 regulated the NLRP3 inflammasome via a two-pronged mechanism: 1) the induction of A20/TNF-α interacting protein 3 leading to the inhibition of the TNF receptor-associated factor 6/nuclear factor κB pathway and 2) the activation of AMP-activated protein kinase/autophagy axis leading to the attenuation of caspase-1 cleavage. Collectively, we demonstrated, for the first time, that γT3 inhibits the NLRP3 inflammasome thereby delaying the progression of type 2 diabetes. This study also provides an insight into the novel therapeutic values of γT3 for treating NLRP3 inflammasome-associated chronic diseases.


How Transitions in Dementia Care Trajectories Affect Health Problems in Partners: A Longitudinal Analysis With Linked Health and Administrative Data.
To evaluate whether the prevalence of health problems in cohabiting partners of people with dementia differs between the year before and the year after 3 transitions: the diagnosis of dementia, institutionalization, and the death of the person with dementia. Individuals with dementia and their partners were identified on the basis of data in the electronic health records (EHRs) of 451 Dutch general practices. EHRs were also the data source on their health problems, which were linked to the Dutch population registry and health administration data with demographic characteristics, date of institutionalization, and date of death. Differences in the prevalence of 16 groups of health problems and of specific health problems in partners during the year before and the year after the 3 transitions were examined using a generalized estimating equation. About 1,110 partners of persons with dementia were identified. Problems related to the illness and/or loss of the person with dementia were significantly more prevalent in the year after the dementia diagnosis (32% vs. 17%) and in the year after the death of the person with dementia (59% vs. 41%) than in the years before. Unspecified health problems were more prevalent in the year after the diagnosis than in the year before (30% vs. 22%). After institutionalization, an increase was found in digestive problems and urological problems (30% vs. 18% and 24% vs. 17%). Transitions during the dementia care trajectory, namely, the diagnosis, institutionalization, and death of the person with dementia, significantly affect the cohabiting partner's health.


Dosimetric validation of a commercial Monte Carlo based IMRT planning system.
Recently a commercial Monte Carlo based IMRT planning system (Monaco version 1.0.0) was released. In this study the dosimetric accuracy of this new planning system was validated. Absolute dose profiles, depth dose curves, and output factors calculated by Monaco were compared with measurements in a water phantom. Different static on-axis and off-axis fields were tested at various source-skin distances for 6, 10, and 18 MV photon beams. Four clinical IMRT plans were evaluated in a water phantom using a linear diode detector array and another six IMRT plans for different tumor sites in solid water using a 2D detector array. In order to evaluate the accuracy of the dose engine near tissue inhomogeneities absolute dose distributions were measured with Gafchromic EBT film in an inhomogeneous slab phantom. For an end-to-end test a four-field IMRT plan was applied to an anthropomorphic lung phantom with a simulated tumor peripherally located in the right lung. Gafchromic EBT film, placed in and around the tumor area, was used to evaluate the dose distribution. Generally, the measured and the calculated dose distributions agreed within 2% dose difference or 2 mm distance-to-agreement. But mainly at interfaces with bone, some larger dose differences could be observed. Based on the results of this study, the authors concluded that the dosimetric accuracy of Monaco is adequate for clinical introduction.


A Higher Mediterranean Diet Score, Including Unprocessed Red Meat, Is Associated with Reduced Risk of Central Nervous System Demyelination in a Case-Control Study of Australian Adults.
The evidence associating diet and risk of multiple sclerosis (MS) is inconclusive. The aim of this study was to investigate associations between a Mediterranean diet and risk of a first clinical diagnosis of central nervous system demyelination (FCD), a common precursor to MS. We used data from the 2003-2006 Ausimmune Study, an Australian multicenter, case-control study examining environmental risk factors for FCD, with participants matched on age, sex, and study region (282 cases, 558 controls; 18-59 y old; 78% female). The alternate Mediterranean diet score (aMED) was calculated based on data from a food-frequency questionnaire. We created a modified version of the aMED (aMED-Red) where ∼1 daily serving (65 g) of unprocessed red meat received 1 point. All other components remained the same as aMED. Conditional logistic regression (254 cases, 451 controls) was used to test associations between aMED and aMED-Red scores and categories and risk of FCD, adjusting for history of infectious mononucleosis, serum 25-hydroxyvitamin D concentrations, smoking, education, total energy intake, and dietary underreporting. There was no statistically significant association between aMED and risk of FCD [per 1-SD increase in aMED score: adjusted odds ratio (aOR): 0.89; 95% CI: 0.75, 1.06; P = 0.181]. There was evidence of a nonlinear relation between aMED-Red and risk of FCD when a quadratic term was used (P = 0.016). Compared with the lowest category of aMED-Red, higher categories were significantly associated with reduced risk of FCD, corresponding to a 37% (aOR: 0.63; 95% CI: 0.41, 0.98; P = 0.039), 52% (aOR: 0.48; 95% CI: 0.28, 0.83; P = 0.009), and 42% (aOR: 0.58; 95% CI: 0.35, 0.96; P = 0.034) reduced risk of FCD in categories 2, 3, and 4, respectively. A Mediterranean diet, including unprocessed red meat, was associated with reduced risk of FCD in this Australian adult population. The addition of unprocessed red meat to a Mediterranean diet may be beneficial for those at high risk of MS.


Functional study of the E276Q mutant hepatocyte nuclear factor-4alpha found in type 1 maturity-onset diabetes of the young: impaired synergy with chicken ovalbumin upstream promoter transcription factor II on the hepatocyte nuclear factor-1 promoter.
Seven mutations in the hepatocyte nuclear factor (HNF)-4alpha gene have been shown to correlate with type 1 maturity-onset diabetes of the young (MODY 1), a monogenic form of type 2 diabetes. Up to now, only the functional properties of two MODY 1 HNF-4alpha mutants, Q268X and V393I, have been investigated to address how the mutations in the HNF-4alpha gene, found by genetic studies, can give rise to impaired activities of mutated HNF-4alpha proteins and can cause this disease. The E276Q mutation results in a nonconservative substitution occurring in the HNF-4alpha E domain, which is involved in dimerization and transactivation activities as well as in protein-protein interactions with other transcription factors or coactivators. Using the mutated human HNF-4alpha2, we have found that, in the absence of chicken ovalbumin upstream promoter transcription factor II (COUP TFII), the E276Q substitution does not significantly affect the dimerization and transactivating activities of HNF-4alpha, at least on the promoters studied herein. On the other hand, in the presence of COUP TFII, the substitution impairs the enhancement of HNF-4-mediated activation of HNF-1 promoter. The impaired synergy between COUP TFII and HNF-4 on the HNF-1 promoter results from an alteration of their interaction. HNF-1 expression plays a crucial role in transactivation of insulin promoter and of numerous genes coding for enzymes involved in glucose homeostasis. Therefore, its downregulation resulting from the E276Q mutation in HNF-4alpha gene most probably impairs the function of pancreatic beta-cells.


A formative evaluation of a family-based walking intervention-Furness Families Walk4Life.
The family unit may be an important mechanism for increasing physical activity levels, yet little is known about what types of family-based interventions are effective. This study involved a formative evaluation of a 12 week intervention to encourage walking as a family based activity. The intervention consisted of several key elements including led walks and tailored resources, as well as remote support provided via the telephone. The project aimed to explore factors associated with successful delivery of the programme and to identify areas of improvement for future implementation. A total of nine interviews were undertaken with programme staff who were involved in either the set up or delivery of the intervention. In addition, four interviews and two focus groups were undertaken with participants to explore their experiences of the programme. The analysis involved both deductive and inductive reasoning. In total, 114 people participated in the programme, which included 36 adults, 10 adolescents and 68 children (≤ 10 years of age). Adult participants reported several barriers to walking including concerns over their children's behaviour and their ability to maintain 'control' of their children. Walking in a group with other families gave parents confidence to go out walking with their children and provided a valuable opportunity for social interaction for parents and children alike. The most successful walks incorporated specific destinations and an activity to undertake upon reaching the destination. Incorporating other activities along the way also helped to keep the children engaged. The results of this study have highlighted the important contribution that formative research can make in informing and refining a programme to increase appropriateness and effectiveness. The study has helped to highlight the key characteristics associated with delivering a successful walking intervention to young families. It is recommended that practitioners undertake formative research when developing novel health promotion initiatives to help refine the programme protocols.


Bacterial PAMPs and Allergens Trigger Increase in [Ca(2+)]i-induced Cytokine Expression in Human PDL Fibroblasts.
An oral environment is constantly exposed to environmental factors and microorganisms. The periodontal ligament (PDL) fibroblasts within this environment are subject to bacterial infection and allergic reaction. However, how these condition affect PDL fibroblasts has yet to be elucidated. PDL fibroblasts were isolated from healthy donors. We examined using reverse transcription-polymerase chain reaction and measuring the intracellular Ca(2+) concentration ([Ca(2+)]i). This study investigated the receptors activated by exogenous bacterial pathogens (Lipopolysaccharide and peptidoglycan) and allergens (German cockroach extract and house dust mite) as well as these pathogenic mediators-induced effects on the intracellular Ca(2+) signaling in human PDL fibroblasts. Moreover, we evaluated the expression of pro-inflammatory cytokines (interleukin (IL)-1β, IL-6, and IL-8) and bone remodeling mediators (receptor activator of NF-κB ligand and osteoprotegerin) and intracellular Ca(2+)-involved effect. Bacterial pathogens and allergic mediators induced increased expression of pro-inflammatory cytokines, and these results are dependent on intracellular Ca(2+). However, bacterial pathogens and allergic mediators did not lead to increased expression of bone remodeling mediators, except lipopolysaccharide-induced effect on receptor activator of NF-κB ligand expression. These experiments provide evidence that a pathogens and allergens-induced increase in [Ca(2+)]i affects the inflammatory response in human PDL fibroblasts.


Widespread ocular use of topical chloramphenicol: is there justifiable concern regarding idiosyncratic aplastic anaemia?
A theoretical but as yet not conclusively proved risk of chloramphenicol induced idiosyncratic aplastic anaemia exists with topical ophthalmic therapy, with the absolute, but highly improbable, maximum risk of death (equalling that of systemic therapy) being 1 in 50,000 to 90,000. To put this in realistic perspective, one must note that the comparable risk of fatal anaphylaxis resulting from penicillin therapy, from any route, is similar at 1 in 100,000. Indeed, it has been noted recently that with more than 200 million ocular chloramphenicol products dispensed in the UK in the past 10 years, only 11 reports (all non-fatal) of suspected topical chloramphenicol induced blood dyscrasia have been reported to the Committee on the Safety of Medicines since 1966. One also has to consider that inadvertent exposure to minute quantities of chloramphenicol (ng/ml) may occur through consumption of livestock that have been treated with chloramphenicol. Broad statements condemning topical chloramphenicol need to be tempered with its proved safety, tolerance, cost, and efficacy while acknowledging an extremely remote risk of the very serious adverse effect of drug induced aplastic anaemia. Risk-benefit assessment is the duty of all prescribing physicians and a decision to prescribe or not prescribe must be made on the basis of personal judgment and an awareness of the statistics in perspective. The only known factor to be associated with vulnerability in the case of topical chloramphenicol is family history. There is no evidence to date that suggests children are any more susceptible than adults.


Ensemble coding of faces occurs in children and develops dissociably from coding of individual faces.
Ensemble coding allows adults to access useful information about average properties of groups, sometimes even in the absence of detailed representations of individual group members. This form of coding may emerge early in development with initial reports of ensemble coding for simple properties (size, numerosity) in young children and even infants. Here we demonstrate that ensemble coding of faces, which provides information about average properties of social groups, is already present in 6-8-year-old children. This access to average information increases with age from 6 to 18 years and its development is dissociable from age-related improvements in the coding of individual face identities. This dissociation provides the first direct evidence that distinct processes underlie ensemble and individual coding of face identity, evidence that has been lacking from adult studies. More generally, our results add to the emerging evidence for impressively mature sensitivity to statistical properties of the visual environment in children. They indicate that children have access to gist information about social groups that may facilitate adaptive social behaviour.


Transferability of the Specific Reaction Parameter Density Functional for H2 + Pt(111) to H2 + Pt(211).
The accurate description of heterogeneously catalyzed reactions may require chemically accurate evaluation of barriers for reactions of molecules at the edges of metal nanoparticles. It was recently shown that a semiempirical density functional describing the interaction of a molecule dissociating on a flat metal surface (CHD3 + Pt(111)) is transferable to the same molecule reacting on a stepped surface of the same metal (Pt(211)). However, validation of the method for additional systems is desirable. To address the question whether the specific reaction parameter (SRP) functional that describes H2 + Pt(111) with chemical accuracy is also capable of accurately describing H2 + Pt(211), we have performed molecular beam simulations with the quasi-classical trajectory (QCT) method, using the SRP functional developed for H2 + Pt(111). Our calculations used the Born-Oppenheimer static surface model. The accuracy of the QCT method was assessed by comparison with quantum dynamics results for reaction of the ro-vibrational ground state of H2. The theoretical results for sticking of H2 and D2 on Pt(211) are in quite good agreement with the experiment, but uncertainties remain because of a lack of accuracy of the QCT simulations at low incidence energies and possible inaccuracies in the reported experimental incidence energies at high energies. We also investigated the nonadiabatic effect of electron-hole pair excitation on the reactivity using the molecular dynamics with the electron friction (MDEF) method, employing the local density friction approximation (LDFA). Only small effects of electron-hole pair excitation on sticking are found.


Acceptance and Continuation of Contraceptive Methods Immediate Postabortion.
Providing preabortion contraceptive counseling for the method of contraception may reduce the incidence of repeat abortions. This study aimed to compare the acceptance and continuation rates of intrauterine devices (IUDs), combined oral contraceptives (COCs), and condom use after abortion in women who received preabortion contraceptive counseling. Women seeking a first-trimester abortion prospectively received preabortion contraceptive counseling and the choice of method of contraception was based on the counseling and not related to prior methods of birth control. Outcomes included continuation of postabortion contraceptive use and repeat abortions over a 6-month follow-up period. Four hundred and fifty-five women (IUD group: n = 161; COC group: n = 149; condom group: n = 135) completed 6-month follow-up after the abortions. At the sixth month follow-up, patients continued using the IUD, COC, and condoms for contraception were 64.2, 10, and 51.5%, respectively. Higher age, being married, parity ≥1, and previous abortion were factors that were associated with more frequent selection of an IUD, while a higher education level was associated with a more frequent selection of COC and condoms. The continued use of COCs after abortion is low even with preabortion contraceptive counseling. The IUD offers reliable birth control with a lower discontinuation rate than COCs or condoms.


Recent developments in numerical modelling of subsurface flow constructed wetlands.
Numerical modelling of subsurface flow constructed wetlands (CWs) gained increasing interest during the last years. The main objective of the modelling work is, on the one hand, to increase the insight in dynamics and functioning of the complex CW system by using mechanistic or process based models that describe transformation and degradation processes in detail. As these mechanistic models are complex and therefore rather difficult to use there is, on the other hand, a need for simplified models for CW design. The design models should be premium to the currently used design guidelines that are mainly based on rules of thumb or simple first-order decay models. This paper presents an overview of the current developments on modelling of subsurface flow CWs based on the modelling work and model developments presented at the WETPOL 2007 symposium. Three kinds of models have been presented: simple transport and first-order decay models, complex mechanistic models, and a simplified model that has been developed for design of CWs. The models are presented and selected results are shown and discussed in relation to the available literature.


Proceedings of a roundtable event 'Workplace Diet and Health - priorities for researchers and practitioners'.
Understanding how the work environment impacts health behaviours is essential to a life course approach in public health nutrition. A roundtable event 'Workplace Diet and Health - priorities for researchers and practitioners' was held by the Nutrition Society in October 2022. The overarching aims of the roundtable event were to consider (i) the relevance of nutritional wellbeing for employers and organisations, (ii) the research priorities for workplace diet and health and (iii) how researchers and practitioners can work with stakeholders in the development and testing of workplace diet and health interventions and nutritional education. Participants represented a range of stakeholders including dietetic and nutrition professionals working in workplace health, academics and science communication with an interest in workplace diet and health, non-governmental organisations and providers of workplace nutritional health and wellbeing programmes. All roundtable participants agreed that good nutrition and access to healthy food at work was part of corporate responsibility comparable to that of health and safety provision. It was recognised that nutritional wellbeing was not seen as a priority by many companies due to the complexity and wide range of employee health and wellbeing options available and the perceived lack of clear financial benefit. Three priority areas were identified and agreed upon by roundtable participants: (1) strengthening the evidence base to demonstrate the tangible benefit of nutritional wellbeing interventions in the workplace, (2) creating a knowledge exchange hub to share best practices and experiences of working across sectors and (3) expand stakeholder engagement in workplace nutritional wellbeing.


Amino-terminal Pro-B-Type Natriuretic Peptide Among Patients Living With Both Human Immunodeficiency Virus and Heart Failure.
Among persons living with human immunodeficiency virus (PHIV), incident heart failure (HF) rates are increased and outcomes are worse; however, the role of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations among PHIV with HF has not been characterized. Patients were derived from a registry of those hospitalized with HF at an academic center in a calender year. We compared the NT-proBNP concentrations and the changes in NT-proBNP levels between PHIV with HF and uninfected controls with HF. Among 2578 patients with HF, there were 434 PHIV; 90% were prescribed antiretroviral therapy and 62% were virally suppressed. As compared to controls, PHIV had higher admission (3822 [IQR, 2413-7784] pg/ml vs 5546 [IQR, 3257-8792] pg/ml, respectively; P < .001), higher discharge (1922 [IQR, 1045-4652] pg/ml vs 3372 [IQR, 1553-5452] pg/ml, respectively; P < .001), and lower admission-to-discharge changes in NT-proBNP levels (32 vs 48%, respectively; P = .007). Similar findings were noted after stratifying based on left ventricular ejection fraction (LVEF). In a multivariate analysis, cocaine use, a lower LVEF, a higher NYHA class, a higher viral load (VL), and a lower CD4 count were associated with higher NT-proBNP concentrations. In follow-up, among PHIV, a higher admission NT-proBNP concentration was associated with increased cardiovascular mortality (first tertile, 11.5; second tertile, 20; third tertile, 44%; P < .001). Among PHIV, each doubling of NT-proBNP was associated with a 19% increased risk of death. However, among patients living without HIV, each doubling was associated with a 27% increased risk; this difference was attenuated among PHIV with lower VLs and higher CD4 counts. PHIV with HF had higher admission and discharge NT-proBNP levels, and less change in NT-proBNP concentrations. Among PHIV, VLs and CD4 counts were associated with NT-proBNP concentrations; in follow-up, higher NT-proBNP levels among PHIV were associated with cardiovascular mortality.


ETS transcription factor Erm controls subsynaptic gene expression in skeletal muscles.
Accumulation of specific proteins at synaptic structures is essential for synapse assembly and function, but mechanisms regulating local protein enrichment remain poorly understood. At the neuromuscular junction (NMJ), subsynaptic nuclei underlie motor axon terminals within extrafusal muscle fibers and are transcriptionally distinct from neighboring nuclei. In this study, we show that expression of the ETS transcription factor Erm is highly concentrated at subsynaptic nuclei, and its mutation in mice leads to severe downregulation of many genes with normally enriched subsynaptic expression. Erm mutant mice display an expansion of the muscle central domain in which acetylcholine receptor (AChR) clusters accumulate, show gradual fragmentation of AChR clusters, and exhibit symptoms of muscle weakness mimicking congenital myasthenic syndrome (CMS). Together, our findings define Erm as an upstream regulator of a transcriptional program selective to subsynaptic nuclei at the NMJ and underscore the importance of transcriptional control of local synaptic protein accumulation.


Antithymocyte globulin induction in living donor renal transplant recipients: final report of the TAILOR registry.
The Thymoglobulin Antibody Immunosuppression in Living Donor Recipients registry was established to assess clinical experience with rabbit antithymocyte globulin (rATG; Thymoglobulin) in living donor renal transplant recipients. From 2003 to 2008, US transplant centers prospectively entered information on patients who received rATG induction. In addition to standard United Network for Organ Sharing registry data elements, information was collected regarding immunosuppression, viral prophylaxis, acute rejection, and adverse events. Data on 2322 patients from 49 transplant centers were enrolled and met inclusion criteria for analysis. Patient and graft survival were 99.3% and 99.0% at 6 months and 98.4% and 98.2% at 12 months as recorded in Thymoglobulin Antibody Immunosuppression in Living Donor Recipients registry and were 91.5% and 83.2% at 5 years by Kaplan-Meier estimates based on linked United Network for Organ Sharing registry records. Freedom from rejection was 93.6% through 5 years. Mean rATG cumulative dose was 5.29 mg/kg. More than one-third of patients (37.6%) were steroid-free at discharge, and nearly half of patients (48%) were steroid-free at 12 months. Before discharge, 3.2% experienced serious adverse events, with 11 events (0.005%) reported as possibly or probably related to rATG. Incidence of cytomegalovirus infection was 4.2% at 12 months, and 99.1% of patients were posttransplant lymphoproliferative disorder-free through 5 years. rATG induction in living donor renal transplantation is safe and associated with a low incidence of acute rejection and posttransplantation complications.


Calcium metabolism and vitamin D in the extreme longevity.
Skeletal remodelling is a continuous process during life and is still active also in extreme senescence. In the elderly, bone resorption often prevails over bone formation, causing bone loss and fragility. Elderly subjects are exposed to the risk of fractures, and loss of self-sufficiency, if considering that the proximal femur is the most frequently involved site. Bone remodelling can maintain circulating calcium within physiological ranges, at the expense of a substantial loss of this ion from the skeleton, particularly during senescence. Calcium metabolism is regulated at cellular/molecular level by a network of cytokines, growth factors, systemic hormones that act on bone in paracrine/autocrine/systemic fashion. Among the molecules involved in bone metabolism, parathyroid hormone (PTH) and vitamin D present some peculiar aspects during senescence. The osteometabolic features in a consistent group of centenarians have been evaluated. It results that a severe hypovitaminosis D was present in 99 out of 104 centenarians (25-OH vitamin D below 5 nmol/L), and that it plays an important role as a factor inducing a vicious circle involving hypocalcemia, secondary hyperparathyroidism, together with biochemical features indicating a consistent bone loss. Serum C-terminal cross-linking telopeptide, a specific marker of bone resorption was elevated in 92% of these subjects. Moreover, it has been found that several femoral fractures had occurred after 90 years of age. These data offer a rational for the possible prevention of elevated bone turnover, bone loss and consequently the reduction of osteoporotic fractures and fractures-induced disability, in the oldest olds, through the simple supplementation with calcium and vitamin D.


Prevalence of congenital amusia.
Congenital amusia (commonly known as tone deafness) is a lifelong musical disorder that affects 4% of the population according to a single estimate based on a single test from 1980. Here we present the first large-based measure of prevalence with a sample of 20 000 participants, which does not rely on self-referral. On the basis of three objective tests and a questionnaire, we show that (a) the prevalence of congenital amusia is only 1.5%, with slightly more females than males, unlike other developmental disorders where males often predominate; (b) self-disclosure is a reliable index of congenital amusia, which suggests that congenital amusia is hereditary, with 46% first-degree relatives similarly affected; (c) the deficit is not attenuated by musical training and (d) it emerges in relative isolation from other cognitive disorder, except for spatial orientation problems. Hence, we suggest that congenital amusia is likely to result from genetic variations that affect musical abilities specifically.


Population-based study of capsular warning syndrome and prognosis after early recurrent TIA.
Many guidelines recommend emergency assessment for patients with ≥2 TIAs within 7 days, perhaps in recognition of the capsular warning syndrome. However, it is unclear whether all patients with multiple TIAs are at high early risk of stroke and whether treatable underlying pathologies are more prevalent in this group. We studied clinical characteristics, Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, and risk of stroke in 1,000 consecutive patients with incident and recurrent TIAs in a prospective, population-based study (Oxford Vascular Study). Of 1,000 patients with TIAs, 170 had a further TIA within 7 days (105 within 24 hours). Multiple TIAs were not associated with carotid stenosis or atrial fibrillation, and much of the 10.6 (95% confidence interval [CI] 6.5-15.9) risk of stroke during the 7 days after the first TIA was due to patients with small-vessel disease (SVD) etiology (10 of 24 vs 8 of 146, odds ratio [OR] = 12.3, 95% CI 3.7-41.9, p < 0.0001), particularly those with motor weakness (i.e., capsular warning syndrome) compared with hemisensory events (9 of 15 [60%], 95% CI 35.3-84.7 vs 1 of 9 [11.1%], 95% CI 0-31.7, p = 0.03). The 7-day risk of stroke after a recurrent TIA was similar to the risk after a single TIA in patients with non-SVD TIA (8 of 146 [5.5%] vs 76 of 830 [9.2%], OR = 0.58, 95% CI 0.25-1.3, p = 0.20). Of the 9 patients with stroke after a capsular warning syndrome, all had the recurrent TIA within 24 hours after the first TIA, and the subsequent stroke occurred within 72 hours of the second TIA in 8. The ABCD2 scores of all preceding TIAs were ≥4 in all 9 patients with capsular warning syndrome before stroke. Capsular warning syndrome is rare (1.5% of TIA presentations) but has a poor prognosis (7-day stroke risk of 60%). Otherwise, recurrent TIA within 7 days is not associated with a greater stroke risk than that after a single TIA.


Effects of low concentrations of zinc on the growth and dimorphism of Candida albicans: evidence for zinc-resistant and -sensitive pathways for mycelium formation.
In this analysis we have examined in detail the effects of low concentrations of zinc on the growth and dimorphism of Candida albicans. Evidence is presented that micromolar concentrations of zinc added to growth cultures grown at 25 degrees C (i) cause a twofold increase in the final concentration of spheres at sationary phase, (ii) result in an asynchronous block in the budding cycle at stationary phase, (iii) completely suppress mycelium formation in two independently isolated human strains which produce low but significant levels of mycelia at stationary phase, and (iv) completely suppress mycelium formation in cultures of mutant M10, in which over 60% of the cells form mycelia at stationary phase. In contrast, micromolar concentrations of zinc do not inhibit mycelium formation induced by releasing cells from stationary-phase cultures into fresh medium at 37 degrees C. In addition, if zinc is present in the growth medium of the initial culture at 25 degrees C, the average time of subsequent mycelium formation after release into fresh medium at 37 degrees C is halved. It is demonstrated that the above effects are specific to zinc. The possibility of alterante pathways for mycelium formation is suggested, and the medical implications of this possibility are discussed.


Mesenchymal glucocorticoid receptor regulates the development of multiple cell layers of the mouse lung.
Endogenous glucocorticoid (GC) hormones, signaling via the GC receptor (GR), are essential for normal lung development, and synthetic GCs are routinely used to treat respiratory disorders of very preterm babies. Germline GR knockout (GR(-/-)) mice show immature lung morphology and severe lung cellular hyperplasia during embryogenesis and die at birth due to respiratory failure. Two recent studies have reported contradictory results regarding the necessity for GR expression in specific lung germ layers during respiratory maturation. We further investigate in detail the lung phenotype in mice with a conditional deletion of GR in the endothelium, mesenchyme, and lung epithelium. We show that loss of GR in the mesenchyme alone produces a retarded lung phenotype almost identical to that of germline GR(-/-) mice, including severe postnatal lethality and lung cell hyperplasia. Loss of GR in lung epithelial cells and the endothelium had no gross effect on survival or lung morphology, but loss of epithelial GR caused increased cell proliferation in multiple compartments. Mesenchymal GR loss also produced increased epithelial cell proliferation, implying the existence of GC-regulated germ layer cross-talk. Protein levels of GR-mediated cell cycle regulators, including the cyclin-dependent kinase inhibitor p21(CIP1) and the growth factor midkine, were unaffected by mesenchymal GR deletion, yet expression of the extracellular matrix proteoglycan versican was up-regulated in the distal lung on loss of mesenchymal GR. These results show that GR-mediated signaling from the mesenchyme regulates respiratory maturation and ultimately survival at birth and that a key GR-repressed transcriptional target in lung mesenchymal cells is versican.


Albumin prevents reactive oxygen species-induced mitochondrial damage, autophagy, and apoptosis during serum starvation.
Aberrant levels of reactive oxygen species (ROS) rapidly generated from NADPH oxidase (NOX) activation can be cytotoxic due to activating pro-apoptotic signals. However, ROS also induce pro-survival autophagy through the engulfment of damaged mitochondria. This study is aimed at investigating the cytoprotective role of albumin against NOX/ROS-induced autophagy and apoptosis under serum starvation. Serum starvation induced apoptosis following a myeloid cell leukemia sequence 1 (Mcl-1)/Bax imbalance, loss of the mitochondrial transmembrane potential, and caspase activation accompanied by pro-survival autophagy following canonical inhibition of mammalian target of rapamycin complex 1 (mTORC1). Aberrant ROS generation, initially occurring through NOX, facilitated mitochondrial damage, autophagy, and apoptosis. Autophagy additionally regulated the accumulation of ROS-generating mitochondria. NOX/ROS permitted p38 mitogen-activated protein kinase (p38 MAPK)-regulated mitochondrial apoptosis, accompanied by non-canonical induction of autophagy. In addition, activation of glycogen synthase kinase (GSK)-3β by NOX/ROS-inactivated Akt facilitated a decrease in Mcl-1, followed by mitochondrial apoptosis as well as autophagy. Restoring albumin conferred an anti-oxidative effect against serum starvation-deregulated NOX, p38 MAPK, and Akt/GSK-3β/Mcl-1/caspase-3 signaling. Albumin also prevented autophagy by sustaining mTORC1. These results indicate an anti-oxidative role for albumin via preventing NOX/ROS-mediated mitochondrial signaling to stimulate apoptosis as well as autophagy. Autophagy, initially induced by canonical inhibition of mTORC1 and enhanced by non-canonical mitochondrial damage, acts physically as a pro-survival mechanism.


H5N1 and 1918 pandemic influenza virus infection results in early and excessive infiltration of macrophages and neutrophils in the lungs of mice.
Fatal human respiratory disease associated with the 1918 pandemic influenza virus and potentially pandemic H5N1 viruses is characterized by severe lung pathology, including pulmonary edema and extensive inflammatory infiltrate. Here, we quantified the cellular immune response to infection in the mouse lung by flow cytometry and demonstrate that mice infected with highly pathogenic (HP) H1N1 and H5N1 influenza viruses exhibit significantly high numbers of macrophages and neutrophils in the lungs compared to mice infected with low pathogenic (LP) viruses. Mice infected with the 1918 pandemic virus and a recent H5N1 human isolate show considerable similarities in overall lung cellularity, lung immune cell sub-population composition, and cellular immune temporal dynamics. Interestingly, while these similarities were observed, the HP H5N1 virus consistently elicited significantly higher levels of pro-inflammatory cytokines in whole lungs and primary human macrophages, revealing a potentially critical difference in the pathogenesis of H5N1 infections. Primary mouse and human macrophages and dendritic cells were also susceptible to 1918 and H5N1 influenza virus infection in vitro. These results together indicate that infection with HP influenza viruses such as H5N1 and the 1918 pandemic virus leads to a rapid cell recruitment of macrophages and neutrophils into the lungs, suggesting that these cells play a role in acute lung inflammation associated with HP influenza virus infection.


Short course radiation therapy for rectal cancer in the elderly: can radical surgery be avoided?
Rectal cancer in elderly patients can be difficult to manage. Short course radiation therapy (SCRT) has shown to be effective when given immediately prior to surgery. Here we report outcomes of elderly patients who underwent SCRT either alone or prior to resection. Between 2010 and 2015, elderly patients with rectal cancer and no distant metastatic disease were identified. Symptoms at diagnosis, therapies, toxicities, and pathologic and clinical response were recorded from patient charts. The SCRT prescription dose was 5 Gy ×5 to the rectal tumor and 4 Gy ×5 to the mesorectum, omitting the iliac nodes. Twenty patients were identified with median age of 85 years (range, 71-93 years). No patient received systemic therapy. Sixty percent of patients were cT3 at diagnosis. Half underwent resection post SCRT and half received SCRT as definitive therapy. The 1- and 2-year overall survival was 75% and 54%. Overall survival did not differ between patients treated with SCRT and surgery compared to SCRT alone (P=0.8). Of the 10 surgical patients, 3 had a complete pathologic response at time of resection and 3 patients died within 2 weeks due to perioperative complications. Of patients treated with SCRT alone, 8 were symptomatic at presentation and 5 had a clinician defined symptomatic response. No patient treated with SCRT monotherapy required additional palliative measures for outflow obstruction, but 2 progressed locally and died. SCRT is well tolerated, results in pathologic complete responses in a small percentage of patients, and achieves 63% symptom improvement rate as monotherapy. A high peri-operative complication rate was observed in this small series. In elderly patients, SCRT as initial treatment with a watch and wait approach for surgery is feasible and should be evaluated prospectively.


Physical health indicators in major mental illness: data from the Quality and Outcome Framework in the UK.
In the UK, the Quality and Outcome Framework (QOF) has specific targets for general practictioners to record body-mass index (BMI) and blood pressure (BP) in major mental illness, diabetes, and chronic kidney disease. Although incentives are given for aspects of major mental illness (schizophrenia, bipolar disorder, and related psychoses), barriers to care can occur. Our aim was to compare recording of specific targets for BP and BMI in individuals with major mental illness relative to diabetes and chronic kidney disease across the UK. Using 2012 and 2013 QOF data from 9731 general practices across all four countries in the UK, we calculated median payment, population achievement, and exception rates for BP indicators in major mental illness and chronic kidney disease and BMI indicators in major mental illness and diabetes. Differences in unweighted rates between practices in the same UK country were tested with a sign test. Differences in population achievement rate between practices in different countries were compared with those in England by use of a quantile regression analysis. UK payment and population achievement rates for BMI recording in major mental illness were significantly lower than were those in diabetes (payment 92·7% vs 95·5% and population achievement 84·0% vs 92·5%, p<0·0001) and exception rates were higher (8·1% vs 2·0%, p<0·0001). For BP recording, UK payment and population achievement rates were significantly lower for major mental illness than for chronic kidney disease (94·1% vs 97·8% and 87·0% vs 97·1%, p<0·0001), whereas exception rate was higher (6·5% vs 0·0%, p<0·0001). This difference was observed for all UK countries. Median population achievement rates for BMI and BP recording in major mental illness were significantly lower in Scotland than in England (for BMI -1·5%, 99% CI -2·7 to -0·3, and for BP -1·8%, -2·7 to -0·9; p<0·0001 for both). There were no cross-jurisdiction differences for chronic kidney disease and diabetes. We found lower payment rates, higher exception rates, and lower population achievement rates for BMI and BP recording in major mental illness than in diabetes and chronic kidney disease throughout the UK. We also found variation in these rates between countries. This finding is probably multifactorial, reflecting a combination of patient, clinician, and wider organisational factors; however, it might also suggest inequality in access to certain aspects of health care for people with major mental illness. None.


Oscillatory correlates of autobiographical memory.
Recollection of events from one's own life is referred to as autobiographical memory. Autobiographical memory is an important part of our self. Neuroimaging findings link self-referential processes with the default mode network (DMN). Much evidence coming primarily from functional magnetic resonance imaging studies shows that autobiographical memory and DMN have a common neural base. In this study, electroencephalographic data collected in 47 participants during recollection of autobiographical episodes were analyzed using temporal and spatial independent component analyses in combination with source localization. Autobiographical remembering was associated with an increase of spectral power in alpha and beta and a decrease in delta band. The increase of alpha power, as estimated by sLORETA, was most prominent in the posterior DMN, but was also observed in visual and motor cortices, prompting an assumption that it is associated with activation of DMN and inhibition of irrelevant sensory and motor areas. In line with data linking delta oscillations with aversive states, decrease of delta power was more pronounced in episodes associated with positive emotions, whereas episodes associated with negative emotions were accompanied by an increase of delta power. Vividness of recollection correlated positively with theta oscillations. These results highlight the leading role of alpha oscillations and the DMN in the processes accompanying autobiographical remembering.


Impact of synovial fluid flow on temperature regulation in knee cartilage.
Several studies have reported an increase of temperature in cartilage submitted to cyclic sinusoidal loading. The temperature increase is in part due to the viscous behavior of this tissue, which partially dissipates the input mechanical energy into heat. While the synovial fluid flow within the intra-articular gap and inside the porous cartilage is supposed to play an important role in the regulation of the cartilage temperature, no specific study has evaluated this aspect. In the present numerical study, a poroelastic model of the knee cartilage is developed to evaluate first the temperature increase in the cartilage due to dissipation and second the impact of the synovial fluid flow in the cartilage heat transfer phenomenon. Our results showed that, the local temperature is effectively increased in knee cartilage due to its viscous behavior. The synovial fluid flow cannot significantly preventing this phenomenon. We explain this result by the low permeability of cartilage and the moderate fluid exchange at the surface of cartilage under deformation.


On the trail of EHEC/EAEC--unraveling the gene regulatory networks of human pathogenic Escherichia coli bacteria.
Pathogenic Escherichia coli, such as Enterohemorrhagic E. coli (EHEC) and Enteroaggregative E. coli (EAEC), are globally widespread bacteria. Some may cause the hemolytic uremic syndrome (HUS). Varying strains cause epidemics all over the world. Recently, we observed an epidemic outbreak of a multi-resistant EHEC strain in Western Europe, mainly in Germany. The Robert Koch Institute reports >4300 infections and >50 deaths (July, 2011). Farmers lost several million EUR since the origin of infection was unclear. Here, we contribute to the currently ongoing research with a computer-aided study of EHEC transcriptional regulatory interactions, a network of genetic switches that control, for instance, pathogenicity, survival and reproduction of bacterial cells. Our strategy is to utilize knowledge of gene regulatory networks from the evolutionary relative E. coli K-12, a harmless strain mainly used for wet lab studies. In order to provide high-potential candidates for human pathogenic E. coli bacteria, such as EHEC, we developed the integrated online database and an analysis platform EhecRegNet. We utilize 3489 known regulations from E. coli K-12 for predictions of yet unknown gene regulatory interactions in 16 human pathogens. For these strains we predict 40,913 regulatory interactions. EhecRegNet is based on the identification of evolutionarily conserved regulatory sites within the DNA of the harmless E. coli K-12 and the pathogens. Identifying and characterizing EHEC's genetic control mechanism network on a large scale will allow for a better understanding of its survival and infection strategies. This will support the development of urgently needed new treatments. EhecRegNet is online via http://www.ehecregnet.de.


Direct recording and molecular identification of the calcium channel of primary cilia.
A primary cilium is a solitary, slender, non-motile protuberance of structured microtubules (9+0) enclosed by plasma membrane. Housing components of the cell division apparatus between cell divisions, primary cilia also serve as specialized compartments for calcium signalling and hedgehog signalling pathways. Specialized sensory cilia such as retinal photoreceptors and olfactory cilia use diverse ion channels. An ion current has been measured from primary cilia of kidney cells, but the responsible genes have not been identified. The polycystin proteins (PC and PKD), identified in linkage studies of polycystic kidney disease, are candidate channels divided into two structural classes: 11-transmembrane proteins (PKD1, PKD1L1 and PKD1L2) remarkable for a large extracellular amino terminus of putative cell adhesion domains and a G-protein-coupled receptor proteolytic site, and the 6-transmembrane channel proteins (PKD2, PKD2L1 and PKD2L2; TRPPs). Evidence indicates that the PKD1 proteins associate with the PKD2 proteins via coiled-coil domains. Here we use a transgenic mouse in which only cilia express a fluorophore and use it to record directly from primary cilia, and demonstrate that PKD1L1 and PKD2L1 form ion channels at high densities in several cell types. In conjunction with an accompanying manuscript, we show that the PKD1L1-PKD2L1 heteromeric channel establishes the cilia as a unique calcium compartment within cells that modulates established hedgehog pathways.


Does hand proficiency determine hand preference?
There is debate in the handedness literature over proficiency and preference measures are indicators of common underlying factors, or separate dimensions of behavior with different causes. It has been argued that hand preference has different origins from hand proficiency on the grounds that (i) the two types of measure are imperfectly correlated and (ii) distributions of relative hand proficiency are normal or nearly so, whereas distributions of hand preference are J-shaped. A model is described in which the probability that one hand will be preferred for a given activity is directly proportional to the relative proficiency of the two sides, the latter being normally distributed. It is shown that imperfect correlations between proficiency and preference measures, and J-shaped distributions of preference, can be predicted by such a model. These facts about hand preference and proficiency do not, therefore, go against the view that preference is determined by proficiency.


The plasmodesmal protein PDLP1 localises to haustoria-associated membranes during downy mildew infection and regulates callose deposition.
The downy mildew pathogen Hyaloperonospora arabidopsidis (Hpa) is a filamentous oomycete that invades plant cells via sophisticated but poorly understood structures called haustoria. Haustoria are separated from the host cell cytoplasm and surrounded by an extrahaustorial membrane (EHM) of unknown origin. In some interactions, including Hpa-Arabidopsis, haustoria are progressively encased by host-derived, callose-rich materials but the molecular mechanisms by which callose accumulates around haustoria remain unclear. Here, we report that PLASMODESMATA-LOCATED PROTEIN 1 (PDLP1) is expressed at high levels in Hpa infected cells. Unlike other plasma membrane proteins, which are often excluded from the EHM, PDLP1 is located at the EHM in Hpa-infected cells prior to encasement. The transmembrane domain and cytoplasmic tail of PDLP1 are sufficient to convey this localization. PDLP1 also associates with the developing encasement but this association is lost when encasements are fully mature. We found that the pdlp1,2,3 triple mutant is more susceptible to Hpa while overexpression of PDLP1 enhances plant resistance, suggesting that PDLPs enhance basal immunity against Hpa. Haustorial encasements are depleted in callose in pdlp1,2,3 mutant plants whereas PDLP1 over-expression elevates callose deposition around haustoria and across the cell surface. These data indicate that PDLPs contribute to callose encasement of Hpa haustoria and suggests that the deposition of callose at haustoria may involve similar mechanisms to callose deposition at plasmodesmata.


Fast homozygosity mapping and identification of a zebrafish ENU-induced mutation by whole-genome sequencing.
Forward genetics using zebrafish is a powerful tool for studying vertebrate development through large-scale mutagenesis. Nonetheless, the identification of the molecular lesion is still laborious and involves time-consuming genetic mapping. Here, we show that high-throughput sequencing of the whole zebrafish genome can directly locate the interval carrying the causative mutation and at the same time pinpoint the molecular lesion. The feasibility of this approach was validated by sequencing the m1045 mutant line that displays a severe hypoplasia of the exocrine pancreas. We generated 13 Gb of sequence, equivalent to an eightfold genomic coverage, from a pool of 50 mutant embryos obtained from a map-cross between the AB mutant carrier and the WIK polymorphic strain. The chromosomal region carrying the causal mutation was localized based on its unique property to display high levels of homozygosity among sequence reads as it derives exclusively from the initial AB mutated allele. We developed an algorithm identifying such a region by calculating a homozygosity score along all chromosomes. This highlighted an 8-Mb window on chromosome 5 with a score close to 1 in the m1045 mutants. The sequence analysis of all genes within this interval revealed a nonsense mutation in the snapc4 gene. Knockdown experiments confirmed the assertion that snapc4 is the gene whose mutation leads to exocrine pancreas hypoplasia. In conclusion, this study constitutes a proof-of-concept that whole-genome sequencing is a fast and effective alternative to the classical positional cloning strategies in zebrafish.


Production of bioactive substances by intestinal bacteria as a basis for explaining probiotic mechanisms: bacteriocins and conjugated linoleic acid.
The mechanisms by which intestinal bacteria achieve their associated health benefits can be complex and multifaceted. In this respect, the diverse microbial composition of the human gastrointestinal tract (GIT) provides an almost unlimited potential source of bioactive substances (pharmabiotics) which can directly or indirectly affect human health. Bacteriocins and fatty acids are just two examples of pharmabiotic substances which may contribute to probiotic functionality within the mammalian GIT. Bacteriocin production is believed to confer producing strains with a competitive advantage within complex microbial environments as a consequence of their associated antimicrobial activity. This has the potential to enable the establishment and prevalence of producing strains as well as directly inhibiting pathogens within the GIT. Consequently, these antimicrobial peptides and the associated intestinal producing strains may be exploited to beneficially influence microbial populations. Intestinal bacteria are also known to produce a diverse array of health-promoting fatty acids. Indeed, certain strains of intestinal bifidobacteria have been shown to produce conjugated linoleic acid (CLA), a fatty acid which has been associated with a variety of systemic health-promoting effects. Recently, the ability to modulate the fatty acid composition of the liver and adipose tissue of the host upon oral administration of CLA-producing bifidobacteria and lactobacilli was demonstrated in a murine model. Importantly, this implies a potential therapeutic role for probiotics in the treatment of certain metabolic and immunoinflammatory disorders. Such examples serve to highlight the potential contribution of pharmabiotic production to probiotic functionality in relation to human health maintenance.


Recurrent Connections in the Primate Ventral Visual Stream Mediate a Trade-Off Between Task Performance and Network Size During Core Object Recognition.
The computational role of the abundant feedback connections in the ventral visual stream is unclear, enabling humans and nonhuman primates to effortlessly recognize objects across a multitude of viewing conditions. Prior studies have augmented feedforward convolutional neural networks (CNNs) with recurrent connections to study their role in visual processing; however, often these recurrent networks are optimized directly on neural data or the comparative metrics used are undefined for standard feedforward networks that lack these connections. In this work, we develop task-optimized convolutional recurrent (ConvRNN) network models that more correctly mimic the timing and gross neuroanatomy of the ventral pathway. Properly chosen intermediate-depth ConvRNN circuit architectures, which incorporate mechanisms of feedforward bypassing and recurrent gating, can achieve high performance on a core recognition task, comparable to that of much deeper feedforward networks. We then develop methods that allow us to compare both CNNs and ConvRNNs to finely grained measurements of primate categorization behavior and neural response trajectories across thousands of stimuli. We find that high-performing ConvRNNs provide a better match to these data than feedforward networks of any depth, predicting the precise timings at which each stimulus is behaviorally decoded from neural activation patterns. Moreover, these ConvRNN circuits consistently produce quantitatively accurate predictions of neural dynamics from V4 and IT across the entire stimulus presentation. In fact, we find that the highest-performing ConvRNNs, which best match neural and behavioral data, also achieve a strong Pareto trade-off between task performance and overall network size. Taken together, our results suggest the functional purpose of recurrence in the ventral pathway is to fit a high-performing network in cortex, attaining computational power through temporal rather than spatial complexity.


The Italian multiple sclerosis register.
The past decade has seen extraordinary increase in worldwide availability of and access to several large multiple sclerosis (MS) databases and registries. MS registries represent powerful tools to provide meaningful information on the burden, natural history, and long-term safety and effectiveness of treatments. Moreover, patients, physicians, industry, and policy makers have an active interest in real-world observational studies based on register data, as they have the potential to answer the questions that are most relevant to daily treatment decision-making. In 2014, the Italian MS Foundation, in collaboration with the Italian MS clinical centers, promoted and funded the creation of the Italian MS Register, a project in continuity with the existing Italian MS Database Network set up from 2001. Main objective of the Italian MS Register is to create an organized multicenter structure to collect data of all MS patients for better defining the disease epidemiology, improving quality of care, and promoting research projects in high-priority areas. The aim of this article is to present the current framework and network of the Italian MS register, including the methodology used to improve the quality of data collection and to facilitate the exchange of data and the collaboration among national and international groups.


Virulence in Oat Crown Rust (Puccinia coronata f. sp. avenae) in the United States from 2006 through 2009.
The use of race-specific seedling genes for resistance is the primary means of controlling crown rust of oat (Puccinia coronata f. sp. avenae) in the United States. To better utilize those resistance genes, knowledge of the occurrence and frequency of corresponding virulence in the population of P. coronata f. sp. avenae in the United States is essential. In total, 571 single-pustule isolates of oat crown rust were collected from cultivated and wild oat (Avena sativa and A. fatua, respectively) in the major oat production areas of the United States from 2006 through 2009. They were tested for virulence on seedlings of 31 differential oat lines in the greenhouse. In all, 201 races were found among the 357 isolates from the spring oat region of the north-central United States, and 140 races were found among 214 isolates from the southern winter oat region. The crown rust populations from the winter and spring oat regions were clearly differentiated from one another, differing in the frequency of virulence for 24 of the 31 differentials. Some virulence associations previously reported in the U.S. oat crown rust population were also found in both regions in this survey, even when the dataset was clone corrected. Associations between virulence to the Pc genes were predominately positive in both regions but both positive and negative associations occurred more frequently in the winter oat region, where sexual reproduction does not occur. Some of the virulence diversity in the oat crown rust population in the United States can be related to the deployment of resistance genes in commercial oat cultivars and virulence associations existing in the oat crown rust population. When data from a previous report covering 2001 through 2005 is combined with data reported in this article, the mean virulence of the U.S. populations of crown rust continued to increase from 2001 to 2009. Virulence to Pc38, Pc39, Pc45, Pc48, Pc52, Pc55, Pc56, Pc57, Pc59, Pc62, Pc63, Pc64, Pc68, and Pc96 significantly increased in one or both regions during this time period. No significant declines in virulence frequency were found in either region. Genes for crown rust resistance derived from A. sterilis appear to be as rapidly defeated as has happened to Pc genes from A. sativa. There is an urgent need to find additional sources of effective resistance to P. coronata f. sp. avenae and introgress it into adapted oat cultivars.


Single nucleotide polymorphisms associated with sporadic brain arteriovenous malformations: where do we stand?
Brain arteriovenous malformations are characterized by a tangle of abnormal vessels directly shunting blood from the arterial to venous circulation. They are known to occur either sporadically or in the context of well-defined genetic disorders. Haemorrhage represents the most severe clinical manifestation, whereas other common symptoms include headache, seizures and neurological deficits. Although sporadic forms do not recognize a specific genetic cause, in recent years, it has been hypothesized that genes involved in angiogenesis and inflammation or coding for proteins, such as fibronectins, laminins and integrins, may play a role in the pathophysiology of brain arteriovenous malformations. More recently, a new trend of genetic studies has investigated the association between sporadic arteriovenous malformations and single nucleotide polymorphisms, single base variations between genomes within members of a biological species or between paired chromosomes in an individual, which may determine the susceptibility to develop complex diseases and influence their natural history. Several polymorphisms in two different families of genes have been associated with disease susceptibly and increased haemorrhagic risk. These genes are mainly involved in the inflammatory cascade and in the regulation of angiogenesis. However, most of the investigated polymorphisms have been selected on the basis of candidate genes because of their potential functional role in the pathogenesis of brain arteriovenous malformations or in other cerebrovascular diseases. Only one hypothesis-free genome-wide association study in a small number of patients has been performed so far, but it was unable to identify significant associations between brain arteriovenous malformations and specific genetic loci. In this article, we review and analyse the polymorphisms investigated to date in association with sporadic brain arteriovenous malformations in the medical literature. We discuss the biological, pathophysiological and clinical implications of these studies, with particular attention to the prediction of haemorrhagic risk and the possibility of building genetic profiles capable of defining the architectural features of the malformations and predict their evolution and natural history. We also present a joint analysis of the risk estimates found by the studies in literature that have evaluated the association between single nucleotide polymorphisms and brain arteriovenous malformation susceptibility and risk of bleeding. This analysis shows a statistically significant association between the interleukin 6 -174G>C (odds ratio = 1.97; 95% confidence interval: 1.15-3.38) and the tumour necrosis factor α -238G>A (odds ratio = 2.19; 95% confidence interval: 1.25-3.83) gene polymorphisms and risk of intracranial haemorrhage and between the activin-like kinase 1 (also known as ACVRL1) intervening sequence 3 -35A>G (odds ratio = 2.42; 95% confidence interval: 1.54-3.8) gene polymorphism and disease susceptibility.


Looking ahead: the perceived direction of gaze shifts before the eyes move.
How do we know where we are looking? Our direction of gaze is commonly thought to be assigned to the location in the world that falls on our fovea, but this may not always hold, especially, as we report here, just before an eye movement. Observers shifted their gaze to a clock with a fast-moving hand and reported the time perceived to be on the clock when their eyes first landed. The reported time was 39 ms earlier than the actual time the eyes arrived. In a control condition, the clock moved to the eyes, mimicking the retinal motion but without the eye movement. Here the reported time lagged 27 ms behind the actual time on the clock when it arrived. The timing of perceived fixation in our experiment is similar to that for the predictive activation observed in visual cortex neurons at the time of eye movements.


Effects of Airway Localization Device Use During Surgical Cricothyrotomy on Procedural Times and Confidence Levels of Pre-Hospital Personnel.
This study evaluated the effect of an airway localization device (ALD) on surgical cricothyrotomy (SC) success rates and prehospital provider confidence. SC is indicated in 0.62% to 1.8% of all patients with military trauma, especially those presenting with traumatic airway obstruction. The effect of ALD was evaluated in an airway mannequin model during SC with the Committee on Tactical Combat Casualty Care (CoTCCC)-recommended Control-Cric Cricothyrotomy System. Outcomes included procedural time, Likert measures of operator confidence, and qualitative data/feedback for suggested future improvements in device design and training. The average procedural times of the hospital corpsmen (HM) including 20 men and 8 women were 67 seconds (without ALD) and 87 seconds (with ALD) respectively, which were statistically significant. Provider confidence for all SC procedural steps increased significantly after SC with and without ALD. The average procedural times of the Navy Special Operations Forces (SOF) group comprising 8 males were 56 seconds (without ALD) and 64 seconds (with ALD), which was not statistically significant. Provider confidence for two SC procedural steps (adequate hook retraction and first-attempt SC tube insertion) increased significantly after SC with and without ALD. First-attempt SC success rates were 90% in each group. Both groups provided feedback on the Control-Cric and ALD, with qualitative feedback analyzed for further SC training recommendations. Procedural times were increased with ALD when compared to those without ALD, although the increase may not be clinically significant in this classroom setting.


Electronic cigarette usage patterns: a case study combining survey and social media data.
To identify who were social media active e-cigarette users, to compare the use patterns from both survey and social media data for data triangulation, and to jointly use both datasets to conduct a comprehensive analysis on e-cigarette future use intentions. We jointly used an e-cigarette use online survey (n = 5132) and a social media dataset. We conducted analysis from 3 different perspectives. We analyzed online forum participation patterns using survey data. We compared e-cigarette use patterns, including brand and flavor types, ratings, and purchase approaches, between the 2 datasets. We used logistic regression to study intentions to use e-cigarettes using both datasets. Male and younger e-cigarette users were the most likely to participate in e-cigarette-related discussion forums. Forum active survey participants were hardcore vapers. The e-cigarette use patterns were similar in the online survey data and the social media data. Intention to use e-cigarettes was positively related to e-liquid ratings and flavor ratings. Social media provided a valuable source of information on users' ratings of e-cigarette refill liquids. For hardcore vapers, social media data were consistent with online survey data, which suggests that social media may be useful to study e-cigarette use behaviors and can serve as a useful complement to online survey research. We proposed an innovative framework for social media data triangulation in public health studies. We illustrated how social media data, combined with online survey data, can serve as a new and rich information source for public health research.


Patterns of multimorbidity in primary care patients at high risk of future hospitalization.
Care management is seen as a promising approach to address the complex care needs of patients with multimorbidity. Predictive modeling based on insurance claims data is an emerging concept to identify patients likely to benefit from care management interventions. We aimed to identify and explore patterns of multimorbidity in primary care patients with high predicted risk of future hospitalizations in order to develop a primary care-based care management intervention. We conducted a retrospective cohort study to assess insurance claims data of 6026 patients from 10 primary care practices in Germany. We stratified the population by the predicted likelihood of hospitalization (LOH) using a diagnostic cost group-based case-finding software. Co-occurrence of chronic conditions in multimorbid patients with an upper-quartile LOH score was explored by extraction of mutually exclusive patterns. Predictive modeling identified multimorbid elderly patients with a high number of co-occurring chronic conditions (mean number 7.8 [SD 3.1]). Assessing co-occurrence of highly prevalent chronic conditions in 1407 multimorbid patients with upper-quartile LOH revealed 471 mutually exclusive patterns with low single frequencies. The observed prevalence significantly exceeded expected prevalence for patterns with causal comorbidity. Additionally, chronic pain (related to osteoarthritis) or depression could be identified as discordant co-occurring conditions in 80% (12/15) of the most common multimorbidity patterns. High-risk primary care patients suffer from heterogeneous individual patterns of co-occurring chronic conditions. Care management interventions will have to account for discordant co-occurring conditions such as osteoarthritis and depression.


Overexpression of the immunoreceptor CD300f has a neuroprotective role in a model of acute brain injury.
It is well known that cell surface immune receptors play a critical role in regulating immune and inflammatory processes in the central nervous system (CNS). We have analyzed the function of cluster of differentiation (CD)300f immunoreceptor in a model of excitotoxic rat brain damage. First, to explore the presence of endogenous ligand(s) for this receptor we used a human CD300f-Ig soluble protein and confocal microscopy, showing specific staining mainly in CNS white matter and on the surface of oligodendrocytes and certain astrocytes. Next, we demonstrated in a model of in vivo rat brain excitotoxic damage that the overexpression of human CD300f induced a significant reduction in the lesion volume. To validate these results, we cloned the rat ortholog of CD300f protein (rCD300f). The overexpression of rCD300f receptor had a comparable neuroprotective effect after the acute brain injury and a similar CNS staining pattern when stained with the rCD300f-Ig soluble protein. Interestingly, when we analyzed the expression pattern of rCD300f in brain cells by quantitative polymerase chain reaction and immunohistochemistry, we detected the expression of CD300f as expected in microglial cells, but also in oligodendrocytes and neurons. These data suggest that the neuroprotective role of CD300f would be the result of a complex network of cell interactions.


The impact of hepatitis C infection on ischemic heart disease via ischemic electrocardiogram.
Hepatitis C virus (HCV) infection is a serious disease worldwide and it leads to several serious hepatic sequels. Some studies find possible correlation between HCV and ischemic heart disease in retrospective observations. Based on lacked community-based evidence, the study aims to assess correlation between ischemic heart disease and chronic HCV infection via electrocardiogram (ECG) because its abnormalities is strongly associating with cardiovascular disease mortality. The population was from one community health examination in December 2010 in a southern village of Taiwan. A total of 9856 participants were evaluated and finally 5015 eligible residents with age older than 40 years were included. The baseline characteristics and laboratory data in nonischemic ECG and ischemic ECG groups were compared, and multivariate-adjusted analysis was used to evaluate the risks to ischemic ECG. The higher prevalence of hypertension, metabolic syndrome and even HCV infection (25.3% versus 11.6%; P < 0.001) in ischemic ECG group than those in nonischemic ECG group. In the multivariate adjusted analysis, HCV infection would lead to a 1.759-fold risk to ischemic ECG when compared with non-HCV subjects. HCV was strongly associated with ischemic ECG findings in this community study, and it could be a nonconventional risk factor for coronary artery disease.


Framework for interpreting sediment quality triad data.
Integration of multiple lines of evidence (MLOE) data in a sediment quality triad assessment can be accomplished by means of numerous approaches, with most relying on some form of expert best professional judgment. Best professional judgment (BPJ) can be problematic in application to large data sets or in a regulatory setting where the assessment protocol needs to be transparent and consistently reproducible. We present a quantitative, objective framework for integrating the results of triad-based assessments and test its efficacy by applying it to 25 California sites and comparing the resulting classifications with those of 6 experts who were provided the same data. The framework is based on integrating the answers to 2 questions: 1) is there biological degradation, and 2) is chemical exposure high enough to potentially result in a biological response? The framework produced results that matched the median classifications of the experts better than did 5 of the 6 experts. Moreover, the framework was unbiased, with samples that differed from the median expert response evenly divided between those classified as more or less impacted. The framework was also evaluated by application to a set of sites from known degraded and reference areas, which the framework distinguished well. Although any framework needs to be flexible to supplemental data when they are available, the framework presented provides an objective means for using a triad-based approach in large-scale assessments for which relying on expert input for every sample is impractical.


In vitro antioxidant properties and phenolic composition of Salvia virgata Jacq. from Turkey.
Antioxidant activities and phenolic compositions of the active fractions of Salvia virgata Jacq. (Lamiaceae) from Turkey were examined. The aerial part of S. virgata was extracted with different solvents in an order of increasing polarity such as hexane, ethyl acetate, methanol, and 50% aqueous methanol using a Soxhlet apparatus. Water extract was also prepared from S. virgata by reflux. All solvent fractions were investigated for their total phenolic contents, total flavonoids, flavonols, qualitative-quantitative compositions (by HPLC-PDA analysis), iron(III) reductive activities, free radical scavenging activities (using DPPH*), and effect upon linoleic acid peroxidation activities; also, the peroxidation level was determined by the TBA method. The results of activity tests given as IC50 values were estimated from nonlinear algorithm and compared with standards, viz., butylated hydroxytoluene, ascorbic acid, and gallic acid. Polar fractions were found to be more active for free radical activity whereas nonpolar fractions protected the peroxidation of linoleic acid. Rosmarinic acid was the most abundant component in the extracts, followed by caffeic acid and lutelin-7- O-glycoside.


Enhanced XUV pulse generation at 89 nm via nonlinear interaction of UV femtosecond filaments.
We demonstrated efficient generation of ultrafast extreme ultraviolet (XUV) pulses at 89 nm from an intense 267 nm UV femtosecond filamentation in argon gas. The XUV pulse generation efficiency was significantly enhanced through UV filament termination from the argon gas into the background vacuum that prevented backconversion of the generated third-harmonic XUV to the fundamental-wave UV pulses. This was further combined with noncollinear UV filament interaction that produced volume-plasma to pre-extract XUV pulses from the filament core, resulting in further XUV enhancement. The generated 89 nm XUV pulses reached what is so far, to our knowledge, the highest pulse energy of 190 nJ.


Pilot error and its relationship with higher organizational levels: HFACS analysis of 523 accidents.
Based on Reason's model of human error, the Human Factors Analysis and Classification System (HFACS) was developed as an analytical framework for the investigation of the role of human error in aviation accidents. However, there is little empirical work that formally describes numerically the relationship between the levels and components in the model (the organizational structures, psychological precursors of errors, and actual errors). This research analyzed 523 accidents in the Republic of China (ROC) Air Force between 1978 and 2002 through the application of the HFACS framework. The results revealed several key relationships between errors at the operational level and organizational inadequacies at both the immediately adjacent level (preconditions for unsafe acts) and higher levels in the organization (unsafe supervision and organizational influences). This research lends support to Reason's model that suggests that active failures are promoted by latent conditions in the organization. Fallible decisions in upper command levels were found to directly affect supervisory practices, thereby creating preconditions for unsafe acts, and hence indirectly impaired performance of pilots, leading to accidents. The HFACS framework was proven to be a useful tool for guiding accident investigations and developing accident prevention strategies.


Donor ABCB1 variant associates with increased risk for kidney allograft failure.
The impact of variation within genes responsible for the disposition and metabolism of calcineurin inhibitors (CNIs) on clinical outcomes in kidney transplantation is not well understood. Furthermore, the potential influence of donor, rather than recipient, genotypes on clinical endpoints is unknown. Here, we investigated the associations between donor and recipient gene variants with outcome among 4471 white, CNI-treated kidney transplant recipients. We tested for 52 single-nucleotide polymorphisms (SNPs) across five genes: CYP3A4, CYP3A5, ABCB1 (MDR1; encoding P-glycoprotein), NR1I2 (encoding the pregnane X receptor), and PPIA (encoding cyclophilin). In a discovery cohort of 811 patients from Birmingham, United Kingdom, kidney donor CC genotype at C3435T (rs1045642) within ABCB1, a variant known to alter protein expression, was associated with an increased risk for long-term graft failure compared with non-CC genotype (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.20-2.40; P=0.003). No other donor or recipient SNPs were associated with graft survival or mortality. We validated this association in 675 donors from Belfast, United Kingdom (HR, 1.68; 95% CI, 1.21-2.32; P=0.002), and in 2985 donors from the Collaborative Transplant Study (HR, 1.84; 95% CI, 1.08-3.13; P=0.006). In conclusion, these data suggest that an ABCB1 variant known to alter protein expression represents an attractive candidate for future study and risk stratification in kidney transplantation.


Microstructured superhydrorepellent surfaces: effect of drop pressure on fakir-state stability and apparent contact angles.
In this paper we present a generalized Cassie-Baxter equation to take into account the effect of drop pressure on the apparent contact angle θ(app). Also we determine the limiting pressure p(W) which causes the impalement transition to the Wenzel state and the pull-off pressure p(out) at which the drop detaches from the substrate. The calculations have been carried out for axial-symmetric pillars of three different shapes: conical, hemispherical-topped and flat-topped cylindrical pillars. Calculations show that, assuming the same pillar spacing, conical pillars may be more inclined to undergo an impalement transition to the Wenzel state, but, on the other hand, they are characterized by a vanishing pull-off pressure which causes the drop not to adhere to the substrate and therefore to detach very easily. We infer that this property should strongly reduce the contact angle hysteresis as experimentally observed in Martines et al (2005 Nano Lett. 5 2097-103). It is possible to combine large resistance to impalement transition (i.e. large value of p(W)) and small (or even vanishing) detaching pressure p(out) by employing cylindrical pillars with conical tips. We also show that, depending on the particular pillar geometry, the effect of drop pressure on the apparent contact angle θ(app) may be more or less significant. In particular we show that in the case of conical pillars increasing the drop pressure causes a significant decrease of θ(app) in agreement with some experimental investigations (Lafuma and Quéré 2003 Nat. Mater. 2 457), whereas θ(app) slightly increases for hemispherical or flat-topped cylindrical pillars.


Accuracy of four commercial systems for identification of Burkholderia cepacia and other gram-negative nonfermenting bacilli recovered from patients with cystic fibrosis.
Burkholderia cepacia has recently been recognized as an important pathogen in chronic lung disease in patients with cystic fibrosis (CF). Because of the social, psychological, and medical implications of the isolation of B. cepacia from CF patients, accurate identification of this organism is essential. We compared the accuracies of four commercial systems developed for the identification of nonfermenting, gram-negative bacilli with that of conventional biochemical testing for 150 nonfermenters including 58 isolates of B. cepacia recovered from respiratory secretions from CF patients. The accuracies of the four systems for identifying all nonfermenters ranged from 57 to 80%, with the RapID NF Plus system being most accurate. The accuracies of these systems for identifying B. cepacia ranged from 43 to 86%, with the Remel system being most accurate. Depending on the commercial system, from two to seven isolates were misidentified as B. cepacia. The relatively poor performance of the commercial systems requires that identification of certain nonfermenters be confirmed by conventional biochemical testing. These organisms include B. cepacia, Burkholderia sp. other than B. cepacia, and infrequently encountered environmental species (Pseudomonas and Flavobacterium species). In addition, conventional biochemical testing should be done if a commercial system fails to assign an identification to an organism. Confirmatory testing should preferably be performed by a reference laboratory with experience in working organisms isolated from CF patients.