Expression of CD44 variant proteins in human colorectal cancer is related to tumor progression.
Specific CD44 variant glycoproteins are overexpressed at particular stages of colorectal tumor progression. Some variants of the CD44 glycoprotein without exon v6 sequences appear at the earliest stage of tumorigenesis, i.e., in early adenomas. Expression of variants containing exon v6 sequences is largely restricted to the advanced stages of tumor development and in addition is more prevalent and intense in metastatic (Dukes C/D) than in nonmetastatic (Dukes A/B) carcinomas. The observation that CD44 variants containing a protein domain of CD44 that confers full metastatic potential to rat carcinoma and sarcoma cell lines is increasingly expressed during colorectal tumor progression indicates that this domain may have an important role in tumor progression and metastasis in humans. Information on v6 expression, which can be obtained by routine immunohistochemistry, may prove of important prognostic value, particularly in carcinomas (Dukes A and B) that have not yet given rise to detectable metastases.


Blood Transfusion and 30-Day Mortality in Patients With Coronary Artery Disease and Anemia Following Noncardiac Surgery.
Although liberal blood transfusion thresholds have not been beneficial following noncardiac surgery, it is unclear whether higher thresholds are appropriate for patients who develop postoperative myocardial infarction (MI). To evaluate the association between postoperative blood transfusion and mortality in patients with coronary artery disease and postoperative MI following noncardiac surgery. Retrospective cohort study involving Veterans Affairs facilities from January 1, 2000, to December 31, 2012. A total of 7361 patients with coronary artery disease who underwent inpatient noncardiac surgery and had a nadir postoperative hematocrit between 20% and 30%. Patients with significant bleeding, including any preoperative blood transfusion or transfusion of greater than 4 units during the intraoperative or postoperative setting, were excluded. Mortality rates were compared using both logistic regression and propensity score matching. Patients were stratified by postoperative nadir hematocrit and the presence of postoperative MI. Initial postoperative blood transfusion. The 30-day postoperative mortality rate. Of the 7361 patients, 2027 patients (27.5%) received at least 1 postoperative blood transfusion. Postoperative mortality occurred in 267 (3.6%), and MI occurred in 271 (3.7%). Among the 5334 patients without postoperative blood transfusion, lower nadir hematocrit was associated with an increased risk for mortality (hematocrit of 20% to <24%: 7.3%; 24% to <27%: 3.7%; and 27% to 30%: 1.6%; P < .01). In patients with postoperative MI, blood transfusion was associated with lower mortality, for those with hematocrit of 20% to 24% (odds ratio, 0.28; 95% CI, 0.13-0.64). In patients without postoperative MI, transfusion was associated with significantly higher mortality for those with hematocrit of 27% to 30% (odds ratio, 3.21; 95% CI, 1.85-5.60). These findings support a restrictive postoperative transfusion strategy in patients with stable coronary artery disease following noncardiac surgery. However, interventional studies are needed to evaluate the use of a more liberal transfusion strategy in patients who develop postoperative MI.


The Ensembl gene annotation system.
The Ensembl gene annotation system has been used to annotate over 70 different vertebrate species across a wide range of genome projects. Furthermore, it generates the automatic alignment-based annotation for the human and mouse GENCODE gene sets. The system is based on the alignment of biological sequences, including cDNAs, proteins and RNA-seq reads, to the target genome in order to construct candidate transcript models. Careful assessment and filtering of these candidate transcripts ultimately leads to the final gene set, which is made available on the Ensembl website. Here, we describe the annotation process in detail.Database URL: http://www.ensembl.org/index.html.


Retinoblastoma/p107/p130 pocket proteins: protein dynamics and interactions with target gene promoters.
The retinoblastoma (RB) tumor suppressor and its family members, p107 and p130, function by repressing E2F transcription factor activity to limit the expression of genes required for cell cycle progression. Traditionally, it is thought that the RB family proteins repress E2F target gene expression through complexing with E2F at gene promoters. However, whereas chromatin immunoprecipitation experiments have demonstrated p107 and p130 at E2F-responsive promoters, RB chromatin association has not been reliably observed. Here we used green fluorescent protein-tagged proteins to rigorously explore the mechanism of RB-mediated transcriptional repression relative to its p107 and p130 family members. The use of live cell fluorescent imaging demonstrated that RB, p107, and p130 exhibit similar nuclear dynamics. Although these findings suggest a similar engagement with nuclear structures, chromatin immunoprecipitation approaches with multiple independent antibodies failed to detect the association of RB with target gene promoters. However, by employing antibodies directed against green fluorescent protein, we could utilize the same antibody to assess RB, p107, and p130 engagement. This approach demonstrated RB association with target gene promoters in a fashion analogous to p107 and p130. Extension of this technology demonstrated that direct RB phosphorylation disrupts promoter association to regulate transcription. Thus, RB is associated with promoters in a manner similar to p107/p130 and that association is modulated by phosphorylation during cell cycle progression.


Contribution of solid fuel, gas combustion, or tobacco smoke to indoor air pollutant concentrations in Irish and Scottish homes.
There are limited data describing pollutant levels inside homes that burn solid fuel within developed country settings with most studies describing test conditions or the effect of interventions. This study recruited homes in Ireland and Scotland where open combustion processes take place. Open combustion was classified as coal, peat, or wood fuel burning, use of a gas cooker or stove, or where there is at least one resident smoker. Twenty-four-hour data on airborne concentrations of particulate matter<2.5 μm in size (PM2.5), carbon monoxide (CO), endotoxin in inhalable dust and carbon dioxide (CO2), together with 2-3 week averaged concentrations of nitrogen dioxide (NO2) were collected in 100 houses during the winter and spring of 2009-2010. The geometric mean of the 24-h time-weighted-average (TWA) PM2.5 concentration was highest in homes with resident smokers (99 μg/m3--much higher than the WHO 24-h guidance value of 25 μg/m3). Lower geometric mean 24-h TWA levels were found in homes that burned coal (7 μg/m3) or wood (6 μg/m3) and in homes with gas cookers (7 μg/m3). In peat-burning homes, the average 24-h PM2.5 level recorded was 11 μg/m3. Airborne endotoxin, CO, CO2, and NO2 concentrations were generally within indoor air quality guidance levels. Little is known about indoor air quality (IAQ) in homes that burn solid or fossil-derived fuels in economically developed countries. Recent legislative changes have moved to improve IAQ at work and in enclosed public places, but there remains a real need to begin the process of quantifying the health burden that arises from indoor air pollution within domestic environments. This study demonstrates that homes in Scotland and Ireland that burn solid fuels or gas for heating and cooking have concentrations of air pollutants generally within guideline levels. Homes where combustion of cigarettes takes place have much poorer air quality.


Dynamical hologram generation for high speed optical trapping of smart droplet microtools.
This paper demonstrates spatially selective sampling of the plasma membrane by the implementation of time-multiplexed holographic optical tweezers for Smart Droplet Microtools (SDMs). High speed (>1000fps) dynamical hologram generation was computed on the graphics processing unit of a standard display card and controlled by a user friendly LabView interface. Time multiplexed binary holograms were displayed in real time and mirrored to a ferroelectric Spatial Light Modulator. SDMs were manufactured with both liquid cores (as previously described) and solid cores, which confer significant advantages in terms of stability, polydispersity and ease of use. These were coated with a number of detergents, the most successful based upon lipids doped with transfection reagents. In order to validate these, trapped SDMs were maneuvered up to the plasma membrane of giant vesicles containing Nile Red and human biliary epithelial (BE) colon cancer cells with green fluorescent labeled protein (GFP)-labeled CAAX (a motif belonging to the Ras protein). Bright field and fluorescence images showed that successful trapping and manipulation of multiple SDMs in x, y, z was achieved with success rates of 30-50% and that subsequent membrane-SDM interactions led to the uptake of Nile Red or GFP-CAAX into the SDM.


Perceived Value of a Skills Laboratory With Virtual Reality Simulator Training in Arthroscopy: A Survey of Orthopedic Surgery Residents.
Arthroscopy is one of the most common procedures performed by orthopedic surgeons. Virtual reality (VR) simulation in general surgery residency training has been increasing over the past decade, but it has seen little use in the field of orthopedic surgery. To determine osteopathic orthopedic surgery residents' perceived value of having access to a VR simulator before performing an arthroscopic procedure on a live patient. A survey was developed and sent to all US osteopathic orthopedic surgery residency programs to be disseminated to all of their current residents. The survey consisted of 12 questions, which included Likert-type scale responses and yes or no responses. Fifty-eight residents out of approximately 507 responded. Forty-one of 57 respondents (72%) were in year 1 of residency when they performed their first arthroscopy, and 53 of 57 (93%) were not very comfortable when they performed their first arthroscopy. With respect to VR simulator exposure, approximately 31of 51 (61%) reported no exposure to a VR simulator, and 40 of 50 (80%) reported that their program did not provide a skills laboratory where they could practice arthroscopy. Of 50 respondents, 37 (74%) believed that a skills laboratory was important, 28 (56%) believed that a resident should perform 1 to 10 arthroscopies in a skills laboratory before performing one in the operating room, 34 (60%) believed that skills acquired in a skills laboratory would transfer to the operating room, and 33 (66%) agreed that every residency program should provide a skills laboratory. However, 29 (58%) believed that a skills laboratory would not improve patient safety. Osteopathic orthopedic surgery residents indicated that they would benefit from the addition of an arthroscopic skills laboratory with a VR simulator. Furthermore, they believed that the skills learned in the skills laboratory would transfer to the operating room and would increase their comfort level with the procedure.


Crystal structure of a mammalian voltage-dependent Shaker family K+ channel.
Voltage-dependent potassium ion (K+) channels (Kv channels) conduct K+ ions across the cell membrane in response to changes in the membrane voltage, thereby regulating neuronal excitability by modulating the shape and frequency of action potentials. Here we report the crystal structure, at a resolution of 2.9 angstroms, of a mammalian Kv channel, Kv1.2, which is a member of the Shaker K+ channel family. This structure is in complex with an oxido-reductase beta subunit of the kind that can regulate mammalian Kv channels in their native cell environment. The activation gate of the pore is open. Large side portals communicate between the pore and the cytoplasm. Electrostatic properties of the side portals and positions of the T1 domain and beta subunit are consistent with electrophysiological studies of inactivation gating and with the possibility of K+ channel regulation by the beta subunit.


Selected health behaviors moderate the progression of functional limitations in persons with multiple sclerosis: Eleven years of annual follow-up.
Multiple sclerosis (MS), a chronic neurological disease typically diagnosed in young adulthood, presents with a wide variety of symptoms, impairments and functional limitations. Given the chronic, unpredictable and long-term nature of this disease, preserving function is essential. The purpose of this study was to identify psychosocial and behavioral factors that might influence the trajectory of functional limitation through eleven years of longitudinal follow-up of a sample of persons with MS. Participants (N = 606) completed measures of health behaviors, related constructs and functional limitations annually over eleven years. Longitudinal measures of functional limitations were analyzed using random-effects regression that allows for study of individual differences in the trajectories of a measure. Using the best fitting quadratic growth model, we tested the within and between-person effects of Nutrition, Interpersonal Relationships, Exercise, Stress Management, Health Responsibilities, Spiritual Growth, Self-rated Health and Barriers, controlling for Age, Year since Diagnosis and Year of Dropout, on Functional Limitations in the 11th year. After adjusting for covariates, higher mean scores for Exercise and Self-rated Health were related to lower levels of Functional Limitations in Year 11. Higher mean scores for Stress Management, Health Responsibilities and Barriers were related to higher levels of Functional Limitations in Year 11. Higher mean Exercise scores and lower mean Health Responsibilities scores were related to slower rates of progression of functional limitations in Year 11. Findings suggest that the highly variable trajectory of functional limitations in MS may be extended and shaped through health behavior strategies.


Why do the lonely stay lonely? Chronically lonely adolescents' attributions and emotions in situations of social inclusion and exclusion.
The goal of this study was to identify mechanisms associated with chronic loneliness by examining the effect of adolescents' accumulated history of loneliness on responses to new social situations. Specifically, this study investigated whether attributions and emotions in situations of social inclusion and exclusion differ between chronically lonely adolescents and adolescents with a different loneliness history. A total of 730 adolescents (Mage at Wave 1 = 15.43 years) participated in a 4-wave longitudinal study with annual loneliness assessments. A chronic loneliness trajectory was identified, in addition to low-stable, moderate-stable, moderate-increasing, and high-decreasing loneliness trajectories. At Wave 4, vignettes depicting social inclusion and exclusion were presented, and participants rated a set of attributions and emotions following each vignette. Compared with individuals following other trajectories, chronically lonely adolescents were characterized by hypersensitivity to social exclusion (i.e., higher levels of negative emotions) and hyposensitivity to social inclusion (i.e., lower levels of enthusiasm). Further, chronically lonely adolescents had a stronger tendency to attribute social inclusion to circumstantial factors and social exclusion to internal and stable characteristics. This maladaptive attribution style partially mediated their emotional experiences. Together, results indicate that chronically lonely individuals respond to social situations in ways that may perpetuate rather than reduce their loneliness.


Metal-free radical oxidative alkoxycarbonylation and imidation of alkanes.
A metal-free radical oxidative carbonylation of alkanes is demonstrated, yielding esters and imides by means of di-tert-butylperoxide as an oxidant. Various alkanes, alcohols and amides were compatible in this system generating the desired carbonyl products in up to 86% yields. We proposed a plausible radical cross-coupling process based on the preliminary mechanistic studies.


Antisymmetric magnetoresistance in magnetic multilayers with perpendicular anisotropy.
While magnetoresistance (MR) has generally been found to be symmetric in applied field in nonmagnetic or magnetic metals, we have observed antisymmetric MR in Co/Pt multilayers. Simultaneous domain imaging and transport measurements show that the antisymmetric MR is due to the appearance of domain walls that run perpendicular to both the magnetization and the current, a geometry existing only in materials with perpendicular magnetic anisotropy. As a result, the extraordinary Hall effect gives rise to circulating currents in the vicinity of the domain walls that contributes to the MR. The antisymmetric MR and extraordinary Hall effect have been quantitatively accounted for by a theoretical model.


Strategies to improve medication adherence in patients with schizophrenia: the role of support services.
The purpose of this review is to describe research over the past 10 years on the role of support services in promoting medication adherence in mental health consumers diagnosed with schizophrenia. A literature search was conducted using the terms "medication adherence," "schizophrenia," and "support services," using Medline, PubMed, and CINAHL. Reference lists from published studies were also reviewed to identify additional research studies. Twenty-two articles focused on support-service intervention studies, and these were selected for review. Available support-service interventions include adherence therapy, electronic reminders via text messages and telephones, cognitive-behavioral and motivational strategies, and financial incentives. Support-service intervention strategies need to be tailored to the specific needs of mental health consumers with schizophrenia. More research is needed to investigate effective support services to enhance long-term adherence and adherence to medications for medical illnesses in this population.


Photonic crystals: emerging biosensors and their promise for point-of-care applications.
Biosensors are extensively employed for diagnosing a broad array of diseases and disorders in clinical settings worldwide. The implementation of biosensors at the point-of-care (POC), such as at primary clinics or the bedside, faces impediments because they may require highly trained personnel, have long assay times, large sizes, and high instrumental cost. Thus, there exists a need to develop inexpensive, reliable, user-friendly, and compact biosensing systems at the POC. Biosensors incorporated with photonic crystal (PC) structures hold promise to address many of the aforementioned challenges facing the development of new POC diagnostics. Currently, PC-based biosensors have been employed for detecting a variety of biotargets, such as cells, pathogens, proteins, antibodies, and nucleic acids, with high efficiency and selectivity. In this review, we provide a broad overview of PCs by explaining their structures, fabrication techniques, and sensing principles. Furthermore, we discuss recent applications of PC-based biosensors incorporated with emerging technologies, including telemedicine, flexible and wearable sensing, smart materials and metamaterials. Finally, we discuss current challenges associated with existing biosensors, and provide an outlook for PC-based biosensors and their promise at the POC.


CryoEM Structure of an Influenza Virus Receptor-Binding Site Antibody-Antigen Interface.
Structure-based vaccine design depends on extensive structural analyses of antigen-antibody complexes.Single-particle electron cryomicroscopy (cryoEM) can circumvent some of the problems of x-ray crystallography as a pipeline for obtaining the required structures. We have examined the potential of single-particle cryoEM for determining the structure of influenza-virus hemagglutinin (HA):single-chain variable-domain fragment complexes, by studying a complex we failed to crystallize in pursuing an extended project on the human immune response to influenza vaccines.The result shows that a combination of cryoEM and molecular modeling can yield details of the antigen-antibody interface, although small variation in the twist of the rod-likeHA trimer limited the overall resolution to about 4.5Å.Comparison of principal 3D classes suggests ways to modify the HA trimer to overcome this limitation. A closely related antibody from the same donor did yield crystals when bound with the same HA, giving us an independent validation of the cryoEM results.The two structures also augment our understanding of receptor-binding site recognition by antibodies that neutralize a wide range of influenza-virus variants.


The suitability of corneas stored by organ culture for penetrating keratoplasty and influence of donor and recipient factors on 5-year graft survival.
To determine the impact of donor factors on the suitability of corneas stored by organ culture for penetrating keratoplasty (PK) and the influence of donor and recipient factors on 5-year survival of first PK. Logistic regression analyses were carried out to determine the influence of donor factors on, respectively, the risk of microbial contamination during organ culture, the suitability of corneas for PK (endothelial cell density ≥ 2200 cells/mm(2)), and the quality of corneas (endothelial cell density ≥ 2500 cells/mm(2)). Only one cornea, randomly selected, from each donor was included in these analyses. A Cox regression analysis was used to determine the influence of donor and recipient factors on 5-year PK survival. Risk of contamination (n = 8317): Causes of donor death including infection, respiratory disease, and cancer all increased the risk of contamination during organ culture (P < 0.0001). Suitability for PK and endothelial quality (n = 7107): Donor age (P < 0.0001) and storage time in organ culture (P < 0.0001) were the principal factors affecting suitability and quality. Death to enucleation and enucleation to processing times had little influence. Corneas from organ donors were more likely to be suitable for PK (P = 0.0003). Five-year graft survival (n = 3014): Graft survival was dominated by the indication for PK (P < 0.0001). Allograft rejection was also a major risk factor for failure (P < 0.0001). The only donor factor affecting survival was sex (P = 0.008). Donor age and storage time but not postmortem times influenced the suitability of corneas for PK. The indication for PK and other recipient factors were the main predictors of graft failure.


Self-navigation with compressed sensing for 2D translational motion correction in free-breathing coronary MRI: a feasibility study.
Respiratory motion correction remains a challenge in coronary magnetic resonance imaging (MRI) and current techniques, such as navigator gating, suffer from sub-optimal scan efficiency and ease-of-use. To overcome these limitations, an image-based self-navigation technique is proposed that uses "sub-images" and compressed sensing (CS) to obtain translational motion correction in 2D. The method was preliminarily implemented as a 2D technique and tested for feasibility for targeted coronary imaging. During a 2D segmented radial k-space data acquisition, heavily undersampled sub-images were reconstructed from the readouts collected during each cardiac cycle. These sub-images may then be used for respiratory self-navigation. Alternatively, a CS reconstruction may be used to create these sub-images, so as to partially compensate for the heavy undersampling. Both approaches were quantitatively assessed using simulations and in vivo studies, and the resulting self-navigation strategies were then compared to conventional navigator gating. Sub-images reconstructed using CS showed a lower artifact level than sub-images reconstructed without CS. As a result, the final image quality was significantly better when using CS-assisted self-navigation as opposed to the non-CS approach. Moreover, while both self-navigation techniques led to a 69% scan time reduction (as compared to navigator gating), there was no significant difference in image quality between the CS-assisted self-navigation technique and conventional navigator gating, despite the significant decrease in scan time. CS-assisted self-navigation using 2D translational motion correction demonstrated feasibility of producing coronary MRA data with image quality comparable to that obtained with conventional navigator gating, and does so without the use of additional acquisitions or motion modeling, while still allowing for 100% scan efficiency and an improved ease-of-use. In conclusion, compressed sensing may become a critical adjunct for 2D translational motion correction in free-breathing cardiac imaging with high spatial resolution. An expansion to modern 3D approaches is now warranted.


Heritable arrhythmias associated with abnormal function of cardiac potassium channels.
Cardiomyocytes express a surprisingly large number of potassium channel types. The primary physiological functions of the currents conducted by these channels are to maintain the resting membrane potential and mediate action potential repolarization under basal conditions and in response to changes in the concentrations of intracellular sodium, calcium, and ATP/ADP. Here, we review the diversity and functional roles of cardiac potassium channels under normal conditions and how heritable mutations in the genes encoding these channels can lead to distinct arrhythmias. We briefly review atrial fibrillation and J-wave syndromes. For long and short QT syndromes, we describe their genetic basis, clinical manifestation, risk stratification, traditional and novel therapeutic approaches, as well as insights into disease mechanisms provided by animal and cellular models.


One-step hyperentanglement purification and hyperdistillation with linear optics.
We investigate a new approach for achieving hyperdistillation and hyperentanglement purification operations simultaneously on two-photon systems, whose state is described by nonlocal hyperentangled Bell states on both the spatial mode and polarization degree of freedoms. Exploiting linear optics and local entanglement resource, the quantum nondemolition (QND) parity-checking measurement and the heralded two-qubit amplification could are key steps in our scheme. With the QND parity-checking measurement and heralded qubit amplification operations, both the bit-flip (phase-flip) errors caused by decoherence in noisy channels and the vacuum errors caused by the transmission losses can be corrected. We show that the proposed scheme provides a new solution to overcome the problem of photon losses and decoherence simultaneously, which could be achieved with current technologies.


Clinical experience in the management of neovascular glaucoma.
Neovascular glaucoma (NVG) is a devastating ocular disease with poor prognosis. The ideal surgical procedure has yet to be determined. In this study, the clinical course and visual outcome of NVG and their fellow eyes were investigated and the most appropriate management was also evaluated. The study was conducted retrospectively consisting of NVG in-patients of Taipei Veterans General Hospital who were under the care of the same glaucoma specialist between January, 1998 and September, 2000. All patients had a minimal follow-up period of 6 months. The total number of patients enrolled was 35 (number of eyes enrolled was 35) with mean age of 66.4 +/- 12.3 years. The underlying cause was diabetes mellitus in 29 patients and central retinal vein occlusion in 6 patients. Twelve (34.3%) eyes had initial intraocular pressure (IOP) of over 60 mmHg. Only 1 (2.9%) eye had initial visual acuity better than 6/60. Four lesion eyes were able to receive panretinal photocoagulation whereas 31 eyes received panretinal cryotherapy. For IOP reducing procedures, 15 eyes received trabeculectomy, and 16 received Diode trans-scleral cyclophotocoagulation (TSCP). At the final visit, 20 eyes (trabeculectomy group: 11 and Diode TSCP group: 9) were able to maintain an IOP < or = 21 mmHg. Of these eyes, 15 (trabeculectomy group: 8 and Diode TSCP group: 7) were able to maintain or improve their vision. Of the remaining 4 eyes, 2 had cyclocryotherapy and 2 had trabeculectomy followed by Diode TSCP. IOP were controlled in these 4 eyes but none were able to maintain stable vision. Among the 34 fellow eyes with stable IOP, 32 were able to maintain stable vision. Trabeculectomy and Diode TSCP provided no statistically significant difference in IOP control (p = 0.32) and visual outcome (p = 0.59) in our patient group. More randomized, prospective trials are needed to define the most effective treatment for NVG.


Enhanced Photogenerated Electron Transfer in a Semiartificial Photosynthesis System Based on Highly Dispersed Titanium Oxide Nanoparticles.
In this study, a hybrid semiartificial photosynthesis system based on chloroplast (CLP) and titanium oxide nanoparticles (TiO2 NPs) was constructed. 2,6-Dichlorophenolindophenol (DCPIP) reduction by TiO2/CLP complex and methylene blue (MB) reduction by TiO2 were used to determine enhanced photogenerated electron transfer in this hybrid system. The DCPIP reduction by the TiO2/CLP complex showed the same trend as MB reduction by TiO2 as a function of concentration of TiO2 NPs, indicating interception of photogenerated electrons in TiO2 by CLP that leads to enhanced photosynthesis efficiency. Decreased photoluminescence intensity and shortened excited-state lifetime of the TiO2/CLP complex compared to that of pure TiO2 also support electron transfer from TiO2 to CLP. Longer visible light absorption wavelength and increasing valence band edges reveal the narrower band gap of TiO2/CLP, which finally results in the enhanced electron transfer from TiO2 to CLP. Higher ferricyanide reduction and enhanced ATP formation with the TiO2/CLP complex demonstrate the accelerated electron-transfer rate of the electron-transfer chain. This study reveals the mechanism of how TiO2 interacts with CLP to enhance the photosynthesis via constructing a semiartificial photosynthesis system.


Plasmonic gold-poly(N-isopropylacrylamide) core-shell colloids with homogeneous density profiles: a small angle scattering study.
Coating metal nanocrystals with responsive polymers provides a model case of smart, functional materials, where the optical properties can be modulated by external stimuli. However the optical response is highly sensitive to the polymer shell morphology, thickness and dielectric contrast. In this paper we study the nature of cross-linked, thermoresponsive polymer shells for the first time using four different scattering approaches to elucidate the density profile of the shells. Each scattering method provides unique information about the temperature-induced changes of shell thickness in terms of hydrodynamic radius and radius of gyration, the pair-distance distribution functions of the shells as well as the dynamic network fluctuations. Only a combination of these different scattering techniques allows to develop a morphological model of the core-shell particles. We further demonstrate control of the cross-linker distribution in core-shell synthesis by semi-batch precipitation copolymerization. Conducting the polymerization in three steps, we show for the first time that the polymer shell thickness can be successively increased without affecting the shell morphology and response behavior.


Review of the evidence regarding the use of antenatal multiple micronutrient supplementation in low- and middle-income countries.
Inadequate micronutrient intakes are relatively common in low- and middle-income countries (LMICs), especially among pregnant women, who have increased micronutrient requirements. This can lead to an increase in adverse pregnancy and birth outcomes. This review presents the conclusions of a task force that set out to assess the prevalence of inadequate micronutrient intakes and adverse birth outcomes in LMICs; the data from trials comparing multiple micronutrient supplements (MMS) that contain iron and folic acid (IFA) with IFA supplements alone; the risks of reaching the upper intake levels with MMS; and the cost-effectiveness of MMS compared with IFA. Recent meta-analyses demonstrate that MMS can reduce the risks of preterm birth, low birth weight, and small for gestational age in comparison with IFA alone. An individual-participant data meta-analysis also revealed even greater benefits for anemic and underweight women and female infants. Importantly, there was no increased risk of harm for the pregnant women or their infants with MMS. These data suggest that countries with inadequate micronutrient intakes should consider supplementing pregnant women with MMS as a cost-effective method to reduce the risk of adverse birth outcomes.


Beneficial use of spectral broadening resulting from the nonlinearity of the fiber-optic channel.
We discuss the possibility of exploiting spectral broadening resulting from fiber nonlinearity for the transmission of information. The spectral broadening induced by nonlinearity combined with the appropriate waveform can turn quadrature amplitude modulation-like constellations into frequency-shift-keying constellations over a much larger dimension. Thus, the Kerr effect can be thought of as a large dimensional mapper/modulator. A simple single-span fiber-optic link implemented over dispersion shifted fiber is assumed for the demonstration of the principle. It is shown that for a particular constellation the achievable data rates in the presence of nonlinearity can be significantly higher than the capacity characterizing a linear channel with the same input bandwidth.


Cognitive behaviour therapy for generalized anxiety disorder: Is CBT equally efficacious in adults of working age and older adults?
The current meta-analysis compared the efficacy of CBT for GAD between adults of working age and older people. In addition, we conducted a qualitative content analysis of treatment protocols used in studies with older clients to explore potential factors that may enhance treatment outcomes with this particular client group. Applying the inclusion criteria resulted in the identification of 15 studies with 22 comparisons between CBT and control groups (770 patients). When examining overall effect sizes for CBT for GAD between older people and adults of working age there were no statistically significant differences in outcome. However, overall effect size of CBT for GAD was moderate for older people (g=0.55, 95% CI 0.22-0.88) and large for adults of working age (g=0.94, 95% CI 0.52-1.36), suggesting that there is still room for improvement in CBT with older people. The main difference in outcome between CBT for GAD between the two age groups was related to methodological quality in that no older people studies used an intention-to-treat design. The content analysis demonstrated that studies with older clients were conducted according to robust CBT protocols but did not take account of gerontological evidence to make them more age-appropriate.


[Multidimensional Strategy Regarding the Reduction of Central-Line Associated Infection in Pediatric Intensive Care].
To determine the central-line associated bloodstream infection rate after implementation of central venous catheter-care practice bundles and guidelines and to compare it with the previous central-line associated bloodstream infection rate. A prospective, longitudinal, observational descriptive study with an exploratory component was performed in a Pediatric Intensive Care Unit during five months. The universe was composed of every child admitted to Pediatric Intensive Care Unit who inserted a central venous catheter. A comparative study with historical controls was performed to evaluate the result of the intervention (group 1 versus group 2). Seventy five children were included, with a median age of 23 months: 22 (29.3%) newborns; 28 (37.3%) with recent surgery and 32 (43.8%) with underlying illness. A total of 105 central venous catheter were inserted, the majority a single central venous catheter (69.3%), with a mean duration of 6.8 ± 6.7 days. The most common type of central venous catheter was the short-term, non-tunneled central venous catheter (45.7%), while the subclavian and brachial flexure veins were the most frequent insertion sites (both 25.7%). There were no cases of central-line associated bloodstream infection reported during this study. Comparing with historical controls (group 1), both groups were similar regarding age, gender, department of origin and place of central venous catheter insertion. In the current study (group 2), the median length of stay was higher, while the mean duration of central venous catheter (excluding peripherally inserted central line) was similar in both groups. There were no statistical differences regarding central venous catheter caliber and number of lumens. Fewer children admitted to Pediatric Intensive Care Unit had central venous catheter inserted in group 2, with no significant difference between single or multiple central venous catheter. After multidimensional strategy implementation there was no reported central-line associated bloodstream infection Conclusions: Efforts must be made to preserve the same degree of multidimensional prevention, in order to confirm the effective reduction of the central-line associated bloodstream infection rate and to allow its maintenance.


Comparative analysis of the mosaic genomes of tailed archaeal viruses and proviruses suggests common themes for virion architecture and assembly with tailed viruses of bacteria.
Tailed double-stranded DNA viruses (order Caudovirales) represent the dominant morphotype among viruses infecting bacteria. Analysis and comparison of complete genome sequences of tailed bacterial viruses provided insights into their origin and evolution. Structural and genomic studies have unexpectedly revealed that tailed bacterial viruses are evolutionarily related to eukaryotic herpesviruses. Organisms from the third domain of life, Archaea, are also infected by viruses that, in their overall morphology, resemble tailed viruses of bacteria. However, high-resolution structural information is currently unavailable for any of these viruses, and only a few complete genomes have been sequenced so far. Here we identified nine proviruses that are clearly related to tailed bacterial viruses and integrated into chromosomes of species belonging to four different taxonomic orders of the Archaea. This more than doubled the number of genome sequences available for comparative studies. Our analyses indicate that highly mosaic tailed archaeal virus genomes evolve by homologous and illegitimate recombination with genomes of other viruses, by diversification, and by acquisition of cellular genes. Comparative genomics of these viruses and related proviruses revealed a set of conserved genes encoding putative proteins similar to virion assembly and maturation, as well as genome packaging proteins of tailed bacterial viruses and herpesviruses. Furthermore, fold prediction and structural modeling experiments suggest that the major capsid proteins of tailed archaeal viruses adopt the same topology as the corresponding proteins of tailed bacterial viruses and eukaryotic herpesviruses. Data presented in this study strongly support the hypothesis that tailed viruses infecting archaea share a common ancestry with tailed bacterial viruses and herpesviruses.


Induction of apoptosis in human prostatic cancer cells with beta-glucan (Maitake mushroom polysaccharide).
To explore more effective treatment for hormone-refractory prostate cancer, we investigated the potential antitumor effect of beta-glucan, a polysaccharide of the Maitake mushroom, on prostatic cancer cells in vitro. Human prostate cancer PC-3 cells were treated with various concentrations of the highly purified beta-glucan preparation Grifron-D(R) (GD), and viability was determined at 24 h. Lipid peroxidation (LPO) assay and in situ hybridization (ISH) were performed to unravel the antitumor mechanism of GD. A dose-response study showed that almost complete (>95%) cell death was attained in 24 h with GD > or = 480 microg/mL. Combinations of GD in a concentration as low as 30 to 60 microg/mL with 200 microM vitamin C were as effective as GD alone at 480 microg/mL, inducing >90% cytotoxic cell death. Simultaneous use with various anticancer drugs showed little potentiation of their efficacy except for the carmustine/GD combination (approximately 90% reduction in cell viability). The significantly (twofold) elevated LPO level and positive ISH staining of GD-treated cells indicated oxidative membrane damage resulting in apoptotic cell death. A bioactive beta-glucan from the Maitake mushroom has a cytotoxic effect, presumably through oxidative stress, on prostatic cancer cells in vitro, leading to apoptosis. Potentiation of GD action by vitamin C and the chemosensitizing effect of GD on carmustine may also have clinical implications. Therefore, this unique mushroom polysaccharide may have great a potential as an alternative therapeutic modality for prostate cancer.


A New High-Temperature Superconductor: Bi2Sr3-x Cax Cu2O8+y.
A new superconductor that displays onset behavior near 120 K has been identified as Bi(2)Sr(3-x)Ca(x)Cu(2)O(8+y), with x ranging from about 0.4 to 0.9. Single crystal x-ray diffraction data were used to determine a pseudo-tetragonal structure based on an A-centered orthorhombic subcell with a = 5.399 A, b= 5.414A, and c = 30.904 A. The structure contains copper-oxygen sheets as in La(2)CuO(4) and YBa(2)Cu(3)O(7), but the copper-oxygen chains present in YBa(2)Cu(3)O(7) do not occur in Bi(2)Sr(3-x)Ca(x)Cu(2)O(8+y). The structure is made up of alternating double copper-oxygen sheets and double bismuth-oxygen sheets. There are Ca(2+) and Sr(2+) cations between the adjacent Cu-O sheets; Sr(2+) cations are also found between the Cu-O and Bi-O sheets. Electron microscopy studies show an incommensurate superstructure along the a axis that can be approximated by an increase of a factor of 5 over the subcell dimension. This superstructure is also observed by x-ray diffraction on single crystals, but twinning can make it appear that the superstructure is along both a and b axes. Flux exclusion begins in our samples at about 116 K and is very strong by 95 K. Electrical measurements on a single crystal of Bi(2)Sr(3-x)Ca(x)Cu(2)O(8+y) show a resistivity drop at about 116 K and apparent zero resistivity at 91 K.


Feasibility of a simple and scalable cognitive-behavioral intervention to treat problem substance use.
Our proof-of-concept study tested a simple cognitive-behavioral strategy based on experimental psychology research that draws on the concept of self-distancing and is consistent with mindfulness principles - using non-first person self-talk when facing substance use cues or cravings -- to help people achieve substance use goals. We evaluated participants' understanding, use, and utility of the intervention at follow-up. We recruited 17 New York City residents who used drugs. At baseline, we collected demographic and substance use data and conducted the intervention. At one-week follow-up, participants were asked about their understanding, use, and perceived utility of the intervention, and asked to complete an anonymous five-item assessment of the intervention. Sixteen participants completed follow-up. Understanding was judged "acceptable" or better for 15; 11 used their scripts during follow-up; four described their scripts as very useful, one as moderately, five as a little, and one as not useful. Nine returned assessments; ratings were strongly favorable. Results from our pilot are encouraging and point to further research on this intervention. The intervention is suitable for integration into longer-term therapy and we envision non-first person self-talk as one strategy alongside others individuals can employ to moderate their substance use.


Parallelism maps for optically contacted etalons.
A measurement technique is described that is capable of producing accurate numerical maps of the parallelism defect of optically contacted Fabry-Perot etalons. A photoelectric raster scan of the etalon transmission intensity distribution is performed at each of three closely spaced etalon tunings, one at maximum on-axis and two at the half-maxima on-axis positions. Simple data manipulation gives numerical or contour maps of the parallelism defect. Results demonstrating the effect of mechanical constraints on etalon parallelism are presented.


Bioassay of p-Chloroaniline for Possible Carcinogenicity (CAS No. 106-47-8).
p-Chloroaniline, a dye and chemical intermediate, was selected for bioassay by the National Cancer Institute because of the high incidence of bladder cancer observed among dye manufacturing industry workers. A bioassay for the possible carcinogenicity of p-chloroaniline was conducted using Fisher 344 rats and B6C3F1 mice. p-Chloroaniline was administered in the feed, at either of two concentrations, to groups of 50 male and 50 female animals of each species. Twenty animals of each sex and species were placed on test as controls. The high and low dietary concentrations of p-chloroaniline were, respectively, 500 and 250 ppm for rats and 5000 and 2500 ppm for mice. The compound was administered in the diet for 78 weeks, followed by an observation period of 24 weeks for rats and 13 weeks for mice. There were no significant positive associations between the dietary concentrations of p-chloroaniline administered and mortality in female rats or in mice of either sex; however, there was a significantly positive association between concentration and mortality in male rats. Adequate numbers of animals in all groups survived sufficiently long to be at risk from late-developing tumors. Mean body weight depression, in relation to controls, was observed in high dose female rats and dosed mice of both sexes, indicating that the concentration of p-chloroaniline administered to these animals may have approximated the maximum tolerated concentrations. Although splenic lesions were observed in male rats, no mean body weight depression relative to controls was associated with administration of p-chloroaniline to these animals. Therefore, it is possible that these animals may have been able to tolerate a higher dietary concentration of the compound. The only neoplastic lesions found that might be related to administration of the compound were mesenchymal tumors in the spleens of male rats and hemangiomatous tumors in mice. In male rats, there was a significant positive association between compound administration and the incidences of fibroma or fibrosarcoma of the spleen. Theincidences of these tumors were not significantly elevated when compared to those in control rats, but the rarity of these tumors in male Fisher 344 rats (0/360 in historical male control rats in this laboratory) strongly suggests a chemically related effect. In addition, three sarcomas of other types were found in high dose male rats. In mice of both sexes, hemangiomas and hemangiosarcomas were found at elevated incidences, when compared to control mice, in the spleen, liver, kidney, and multiple body sites. The increased incidences in dosed mice were statistically related to dose but were not statistically significant when compared directly to matched control animals. In comparison to historical control data, the incidences of hemangiomatous tumors in the dosed mice were elevated, but not greatly. The evidence was considered insufficient to conclusively relate the hemangiomatous tumors in mice to compound administration. Nonneoplastic proliferative and chronic inflammatory lesions were also found in the spleens of dosed rats and mice. The findings of small numbers of fibromas and sarcomas in the spleens of male rats was considered strongly suggestive of carcinogenicity because of the rarity of these tumors in the spleens of control rats. Hemangiomatous tumors in dosed mice may also have been associated with administration of p-chloroaniline. However, it is concluded that, under the conditions of this bioassay, sufficient evidence was not found to establish the carcinogenicity of p-chloroaniline for Fisher 344 rats or B6C3F1 mice. Levels of Evidence of Carcinogenicity: Male Rats: Equivocal Female Rats: Negative Male Mice: Equivocal Female Mice: Equivocal Synonyms: 4-chlorobenzeneamine; 4-chlorophenylamine; 4-chloroaniline; 4-CA; 1-amino-4-chlorobenzene


From grey to green: Efficacy of eco-engineering solutions for nature-based coastal defence.
Climate change is increasing the threat of erosion and flooding along coastlines globally. Engineering solutions (e.g. seawalls and breakwaters) in response to protecting coastal communities and associated infrastructure are increasingly becoming economically and ecologically unsustainable. This has led to recommendations to create or restore natural habitats, such as sand dunes, saltmarsh, mangroves, seagrass and kelp beds, and coral and shellfish reefs, to provide coastal protection in place of (or to complement) artificial structures. Coastal managers are frequently faced with the problem of an eroding coastline, which requires a decision on what mitigation options are most appropriate to implement. A barrier to uptake of nature-based coastal defence is stringent evaluation of the effectiveness in comparison to artificial protection structures. Here, we assess the current evidence for the efficacy of nature-based vs. artificial coastal protection and discuss future research needs. Future projects should evaluate habitats created or restored for coastal defence for cost-effectiveness in comparison to an artificial structure under the same environmental conditions. Cost-benefit analyses should take into consideration all ecosystem services provided by nature-based or artificial structures in addition to coastal protection. Interdisciplinary research among scientists, coastal managers and engineers is required to facilitate the experimental trials needed to test the value of these shoreline protection schemes, in order to support their use as alternatives to artificial structures. This research needs to happen now as our rapidly changing climate requires new and innovative solutions to reduce the vulnerability of coastal communities to an increasingly uncertain future.


"Wish bias" in antidepressant drug trials?
The present study investigated whether the outcome of randomized clinical trials studying fluoxetine favored fluoxetine, where this was the experimental agent, and favored comparator antidepressants in trials where fluoxetine was the reference agent. A systematic review of all double-blind, randomized clinical trials comparing fluoxetine with any other antidepressant drug in patients suffering from depression was carried out. Thirty-seven studies meeting the inclusion criteria were analyzed. A metaregression analysis indicated that, after adjusting for possible confounders, studies where fluoxetine was the experimental agent were positively associated with treatment effect, indicating a significant advantage for fluoxetine. The evidence that the outcome of fluoxetine trials varied according to whether this drug was used as a new compound or a reference one suggests the presence of bias.


Chinese herbal therapy and Western drug use, belief and adherence for hypertension management in the rural areas of Heilongjiang province, China.
Traditional Chinese medicine (TCM) including Chinese herbal therapy has been widely practiced in China. However, little is known about Chinese herbal therapy use for hypertension management, which is one of the most prevalent chronic conditions in China. Thus we described Chinese herbal therapy and western drug users, beliefs, hypertension knowledge, and Chinese herbal and western drug adherence and determinants of Chinese herbal therapy use among patients with hypertension in rural areas of Heilongjiang Province, China. This face-to-face cross sectional survey included 665 hypertensive respondents aged 30 years or older in rural areas of Heilongjiang Province, China. Of 665 respondents, 39.7% were male, 27.4% were aged 65 years or older. At the survey, 14.0% reported using Chinese herbal therapy and 71.3% reported using western drug for hypertension management. A majority of patients had low level of treatment adherence (80.6% for the Chinese herbal therapy users and 81.2% for the western drug users). When respondents felt that their blood pressure was under control, 72.0% of the Chinese herbal therapy users and 69.2% of the western drug users sometimes stopped taking their medicine. Hypertensive patients with high education level or better quality of life are more likely use Chinese herbal therapy. Majority of patients diagnosed with hypertension use western drugs to control blood pressure. Chinese herbal therapy use was associated with education level and quality of life.


Fast, automated, N-dimensional phase-unwrapping algorithm.
This work investigates the general problem of phase unwrapping for arbitrary N-dimensional phase maps. A cost function-based approach is outlined that leads to an integer programming problem. To solve this problem, a best-pair-first region merging approach is adopted as the optimization method. The algorithm was implemented and tested with 3D MRI medical data for venogram studies, as well as for fMRI applications in EPI unwarping and rapid, automated shimming.


Total hip arthroplasty in patients with underlying fibrous dysplasia.
Fibrous dysplasia is a developmental anomaly of bone formation that accounts for approximately 7% of benign bone tumors. It exists in a monostotic or polyostotic form, commonly occurs in the proximal femur, and may require total hip arthroplasty (THA) for its management in a select group of patients. The results of THA in patients with this disorder is not known. Of the 27,543 primary THAs performed at our institution between 1969 and 2001, 10 were in patients with fibrous dysplasia (prevalence of 0.04%). Two other patients (2 hips) with the same diagnoses were referred after a failed primary THA. The study group comprised 7 men and 4 women (1 bilateral) with an average age at primary THA of 44 years (range, 23-66 years). Four patients had the monostotic form and 7 patients had the polyostotic form. A cemented stem was used in 7 hips and cementless stem in the rest (N=12). Average follow-up was 15.7 years (range, 2-30 years). Seven hips in 6 patients were revised for loosening of components at an average of 12.5 years, and 2 of these were re-revised for the same reason. Loosening of a cementless femoral component led to early revision in 3 hips. The surgical outcomes for patients with monostotic was better than those with polyostotic disease. Long-term fixation of the femoral component is of concern in patients with fibrous dysplasia. Total hip arthroplasty provided these patients with long-lasting pain relief and function despite the higher rate of complications at the time of surgery.


Mechanical and Biocompatibility Properties of Calcium Phosphate Bioceramics Derived from Salmon Fish Bone Wastes.
Natural calcium phosphates derived from fish wastes are a promising material for biomedical application. However, their sintered ceramics are not fully characterized in terms of mechanical and biological properties. In this study, natural calcium phosphate was synthesized through a thermal calcination process from salmon fish bone wastes. The salmon-derived calcium phosphates (sCaP) were sintered at different temperatures to obtain natural calcium phosphate bioceramics and then were investigated in terms of their microstructure, mechanical properties and biocompatibility. In particular, this work is concerned with the effects of grain size on the relative density and microhardness of the sCaP bioceramics. Ca/P ratio of the sintered sCaP ranged from 1.73 to 1.52 when the sintering temperature was raised from 1000 to 1300 °C. The crystal phase of all the sCaP bioceramics obtained was biphasic and composed of hydroxyapatite (HA) and tricalcium phosphate (TCP). The density and microhardness of the sCaP bioceramics increased in the temperature interval 1000-1100 °C, while at temperatures higher than 1100 °C, these properties were not significantly altered. The highest compressive strength of 116 MPa was recorded for the samples sintered at 1100 °C. In vitro biocompatibility was also examined in the behavior of osteosarcoma (Saos-2) cells, indicating that the sCaP bioceramics had no cytotoxicity effect. Salmon-derived biphasic calcium phosphates (BCP) have the potential to contribute to the development of bone substituted materials.


Distinct cytokine profiles associated with COVID-19 severity and mortality.
Markedly elevated levels of proinflammatory cytokines and defective type-I interferon responses were reported in patients with coronavirus disease 2019 (COVID-19). We sought to determine whether particular cytokine profiles are associated with COVID-19 severity and mortality. Cytokine concentrations and severe acute respiratory syndrome coronavirus 2 antigen were measured at hospital admission in serum of symptomatic patients with COVID-19 (N = 115), classified at hospitalization into 3 respiratory severity groups: no need for mechanical ventilatory support (No-MVS), intermediate severity requiring mechanical ventilatory support (MVS), and critical severity requiring extracorporeal membrane oxygenation (ECMO). Principal-component analysis was used to characterize cytokine profiles associated with severity and mortality. The results were thereafter confirmed in an independent validation cohort (N = 86). At time of hospitalization, ECMO patients presented a dominant proinflammatory response with elevated levels of TNF-α, IL-6, IL-8, and IL-10. In contrast, an elevated type-I interferon response involving IFN-α and IFN-β was characteristic of No-MVS patients, whereas MVS patients exhibited both profiles. Mortality at 1 month was associated with higher levels of proinflammatory cytokines in ECMO patients, higher levels of type-I interferons in No-MVS patients, and their combination in MVS patients, resulting in a combined mortality prediction accuracy of 88.5% (risk ratio, 24.3; P < .0001). Severe acute respiratory syndrome coronavirus 2 antigen levels correlated with type-I interferon levels and were associated with mortality, but not with proinflammatory response or severity. Distinct cytokine profiles are observed in association with COVID-19 severity and are differentially predictive of mortality according to oxygen support modalities. These results warrant personalized treatment of COVID-19 patients based on cytokine profiling.


How COVID-19 has fundamentally changed clinical research in global health.
COVID-19 has had negative repercussions on the entire global population. Despite there being a common goal that should have unified resources and efforts, there have been an overwhelmingly large number of clinical trials that have been registered that are of questionable methodological quality. As the final paper of this Series, we discuss how the medical research community has responded to COVID-19. We recognise the incredible pressure that this pandemic has put on researchers, regulators, and policy makers, all of whom were doing their best to move quickly but safely in a time of tremendous uncertainty. However, the research community's response to the COVID-19 pandemic has prominently highlighted many fundamental issues that exist in clinical trial research under the current system and its incentive structures. The COVID-19 pandemic has not only re-emphasised the importance of well designed randomised clinical trials but also highlighted the need for large-scale clinical trials structured according to a master protocol in a coordinated and collaborative manner. There is also a need for structures and incentives to enable faster data sharing of anonymised datasets, and a need to provide similar opportunities to those in high-income countries for clinical trial research in low-resource regions where clinical trial research receives considerably less research funding.


Viable but nonculturable stage of Campylobacter jejuni and its role in survival in the natural aquatic environment.
Conditions influencing the survival of Campylobacter jejuni in the natural aquatic environment have been determined. Release of Campylobacter spp. into natural waters by animal hosts is postulated to play a key role in the maintenance of viability and transmission of the organism in the environment. Laboratory flask microcosms containing filter-sterilized stream water were used to test C. jejuni for the ability to remain viable in simulated natural systems. The microcosms were compared with the biphasic and shaking broth procedures used routinely for growth of Campylobacter spp. in the research laboratory. The stream-water microcosms were analyzed to determine effects of temperature and aeration on the survival of a well-characterized C. jejuni strain isolated originally from a human campylobacteriosis patient. Morphological characteristics were evaluated by phase-contrast microscopy and scanning or transmission electron microscopy. Survival curves were quantified on the basis of plate counts, epifluorescent microscopy, optical density measurements, and direct viable counts associated with protein synthesis in the absence of DNA replication. A significant difference was observed between results of direct enumeration, i.e., direct viable counts or acridine orange direct counts, and those from spread plate cultures. In all cases, increasing temperature of cultivation resulted in decreased recoverability on laboratory media, due possibly to an increased metabolic rate, as analyzed by CO2 evolution in the presence of radiolabeled glutamate. Stream water held at low temperature (4 degrees C) sustained significant numbers of campylobacters for greater than 4 months. Microcosms, aerated with shaking, exhibited logarithmic decline in recoverable C. jejuni, while stationary systems underwent a more moderate rate of decrease to the nonculturable state.(ABSTRACT TRUNCATED AT 250 WORDS)


Can physique and gluteal size predict penile length in adult Nigerian men?
In Nigeria, especially among the Igbo tribe, there is a well-held belief that a man's penile size can be predicted from his physique and the size of his buttocks, with people of small physique and flat buttocks likely to have long penile lengths. A prospective study to test the scientific veracity of this traditional and apparently mythical belief. Stretched penile length was measured in 115 men between the ages of 30-65 years and its correlation with the body-mass index and the circumference of the hip as measured around the most prominent points on their buttocks, was statistically determined. The mean age of the subjects was 42.30 years (SD = 9.67), with a median of 40 years and a range of 30-65 years. The mean penile length was 13.37 cm with a median of 13 cm and a range of 7.5-19.5 cm. The mean circumference of the body around the buttocks was 96.46 cm (SD = 10.91), median 98 cm, and range 73-122 cm. The body-mass index ranged 17.34-44.44, with the mean at 26.87 (SD = 5.86), and the median 25.53. Linear regression statistics showed no statistically significant correlation between stretched penile length and body-mass index, thus physique. There was a significant direct correlation between penile length and gluteal size. The supposed relationship between penile length and gluteal size may have a scientific basis, but contrary to belief, large buttocks is more predictive of longer penile length than small buttocks. Penile length has no relationship to physique.


Barriers to the identification of children with attention deficit/hyperactivity disorder.
In most countries, the majority of children with attention deficit/hyperactivity disorder (ADHD) are undiagnosed. In the United Kingdom, a major barrier to accessing specialist services is the limited recognition of disorders by general practitioners. However, it is unclear whether there are also barriers at other stages of the help-seeking process. For children with ADHD, this study aims to examine the correlates of the different stages of help-seeking. Children with ADHD (n = 232) were identified from the 1999 British Child and Adolescent Mental Health Survey. Rates and correlates of parental recognition of child mental health problems and contact with services for these problems were examined. Children who had used particular types of services were compared with those who had not. Most (80%) parents of children with ADHD recognise that their child has a problem although few (35%) construe this in terms of hyperactivity. The impact of the symptoms on key adults, rather than child factors, best predicted parental recognition of problems. Most parents had been in contact with education-based professionals but few had consulted primary care for these problems or had sought help from relevant specialist health services. Parental recognition of problems and perceived burden, rather than child factors, were the main correlates of contact with services. Parental views that their child has hyperactivity were associated with greater severity of symptoms. The main barrier to care for ADHD is the limited presentation of these problems to primary care. The majority of parents discuss their concerns with professionals based in education services. There is a need for parental education about ADHD and for health service input to support education professionals in their contact with concerned parents.


Genomic organization and complete nucleotide sequence of the TMEM1 gene on human chromosome 21q22.3.
TMEM1 (EHOC-1) gene encodes a putative transmembrane protein and is located on human chromosome band 21q22.3. Analysis of a 122,638-bp genomic sequence revealed that TMEM1 gene consists of 23 exons spanning approximately 94 kb and is transcribed in the direction of centromere to telomere. The 5' region of the TMEM1 gene was associated with a CpG island and the 3' end of the TMEM1 gene was mapped just proximal to the 5' end of the neighboring gene PWP2. We determined that the TMEM1 gene encodes a protein of 1,259 amino acids, which is 69-amino acids longer than the previously reported sequence. Since TMEM1 gene is considered to be a candidate for genetic disorders mapped in the 21q22.3 region, the information including complete nucleotide sequence and genomic organization of the TMEM1 gene should be invaluable for the mutation analysis of the corresponding genetic disorders.


Size of the ligand complex between the N-terminal domain of the gene III coat protein and the non-infectious phage strongly influences the usefulness of in vitro selective infective phage technology.
The selective infective phage (SIP) technology allows a rapid positive selection of interacting pairs of biological molecules that restore to non-infectious phages their ability to infect the bacterial host. After a successful infection, the phage is amplified and the DNA encoding the interacting ligand is isolated from the phage genome and sequenced. In our studies we have evaluated the usefulness of SIP for the identification and cloning of proteins interacting with a biotinylated target binding to a newly designed adapter molecule consisting of streptavidin fused to the C-terminus of the extracellular domain of the phage minor coat protein III. The new adapter was expressed in Escherichia coli and refolded from inclusion bodies. The two different domains joined within the chimaera were found to be biologically functional. We also demonstrated that non-covalent interactions between a non-infectious phage displaying a short peptide, which specifically binds the streptavidin, and the adapter molecule restore phage infectivity. To evaluate the potential of SIP as a general and generic tool for the screening of cDNA libraries that encode the ligands displayed at the surface of the phage and binding to biotinylated targets, we have increased both the size of the displayed ligand on the phage and the size of the biotinylated target bound to the streptavidin domain of the adapter molecule. In our model systems we show that the size of either the ligand or the target is a limiting factor for the technology.


Molecular dynamics study of the LCST transition in aqueous poly(N-n-propylacrylamide).
The breadth of technological applications of smart polymers relies on the possibility of tuning their molecular structure to respond to external stimuli. In this context, N-substituted acrylamide-based polymers are widely studied thermoresponsive polymers. Poly(N-n-propylacrylamide) (PNnPAm), which is a structural isomer of the poly(N-isopropylacrylamide) (PNIPAm) exhibits however, a lower phase transition in aqueous solution. In this work, we use all-atom molecular dynamics simulations of PNnPAm in aqueous solutions to study, from a microscopic point-of-view, the influence of chain size and concentration on the LCST of PNnPAm. Our analysis shows that the collapse of a single oligomer of PNnPAm upon heating is dependent on the chain length and corresponds to a complex interplay between hydration and intermolecular interactions. Analysis of systems with multiple chains shows an aggregation of PNnPAm chains above the LCST.


Autoantibodies to proteinase 3 and myeloperoxidase in systemic sclerosis.
We evaluated the prevalence and clinical significance of proteinase 3 (PR3-) and myeloperoxidase (MPO-) antineutrophil cytoplasmic antibodies (ANCA) in 115 patients with systemic sclerosis (SSc, scleroderma). Sera were assayed by 2 independent centers, which used indirect immunofluorescence (IIF) and direct ELISA as screening tests. Inhibition-ELISA for PR3- and MPO-ANCA and PR3 capture-ELISA experiments were also performed. The clinical features of the ANCA positive were compared with those of the ANCA negative scleroderma patients. The IIF test revealed 5 P-ANCA positive sera (4.34%). Surprisingly, by ELISA 2 of these were PR3-ANCA positive, one was MPO-ANCA positive, and 2 were both PR3- and MPO-ANCA positive. In addition, 3 IIF negative sera were ELISA positive, 2 for PR3- and one for MPO-ANCA. ELISA results were confirmed by fluid phase inhibition experiments. Only 2 out of the 6 PR3-direct ELISA positive sera were positive by PR3-capture ELISA at low titers. Neither PR3- nor MPO-ANCA were significantly associated to any clinical feature of patients with SSc. As well as the previously described MPO-ANCA, even PR3-ANCA may be detected in some sera from patients with SSc. The IIF pattern and the negative results obtained with PR3-capture ELISA suggest that different epitopes from those recognized by vasculitis sera might be involved with PR3-ANCA in SSc, and show the importance of combining IIF and ELISA tests for ANCA detection.


Attitudes and beliefs of adolescents and parents regarding adolescent suicide.
The goal was to understand the attitudes, beliefs, and perceptions of adolescents and parents of adolescents, from a variety of backgrounds, regarding adolescent suicide. This qualitative study used focus groups to elicit the thoughts of distinct sociodemographic groups. A professional moderator guided the sessions by using a semistructured script. All groups were audiotaped. The transcripts and transcript summaries were analyzed for recurrent themes. The study was performed in community centers and schools in Chicago, Illinois (urban), and the Kansas City, Kansas, area (suburban and rural). A total of 66 adolescents (13-18 years of age) and 30 parents of adolescents participated in 13 focus groups. Both adolescents and parents recognized adolescent suicide as a major problem, but not for their own communities. All parent and adolescent groups identified many risk factors for suicide. Most adolescents reported drug and alcohol use as risk factors for suicide. However, parents often viewed drug and alcohol use as normal adolescent behavior. Both adolescent and parent groups suggested securing or removing guns if an adolescent was known to be suicidal. All participants requested information about adolescent suicide. Adolescents and parents need help understanding that suicide is an underidentified problem in their own communities. Both adolescents and parents are interested in learning more about how to identify and to intervene with a suicidal adolescent. Pediatricians are well positioned to provide this information in the office and in the community.


Characterizing a Middle Bronze palatial wine cellar from Tel Kabri, Israel.
Scholars have for generations recognized the importance of wine production, distribution, and consumption in relation to second millennium BC palatial complexes in the Mediterranean and Near East. However, direct archaeological evidence has rarely been offered, despite the prominence of ancient viticulture in administrative clay tablets, visual media, and various forms of documentation. Tartaric and syringic acids, along with evidence for resination, have been identified in ancient ceramics, but until now the archaeological contexts behind these sporadic discoveries had been uneven and vague, precluding definitive conclusions about the nature of ancient viticulture. The situation has now changed. During the 2013 excavation season of the Kabri Archaeological Project, a rare opportunity materialized when forty large storage vessels were found in situ in an enclosed room located to the west of the central courtyard within the Middle Bronze Age Canaanite palace. A comprehensive program of organic residue analysis has now revealed that all of the relatively uniform jars contain evidence for wine. Furthermore, the enclosed context inherent to a singular intact wine cellar presented an unprecedented opportunity for a scientifically intensive study, allowing for the detection of subtle differences in the ingredients or additives within similar wine jars of apparently the same vintage. Additives seem to have included honey, storax resin, terebinth resin, cedar oil, cyperus, juniper, and perhaps even mint, myrtle, or cinnamon, all or most of which are attested in the 18th century BC Mari texts from Mesopotamia and the 15th century BC Ebers Papyrus from Egypt. These additives suggest a sophisticated understanding of the botanical landscape and the pharmacopeic skills necessary to produce a complex beverage that balanced preservation, palatability, and psychoactivity. This new study has resulted in insights unachievable in the past, which contribute to a greater understanding not only of ancient viticulture but also of Canaanite palatial economy.


The use of electro-acupuncture in conjunction with exercise for the treatment of chronic low-back pain.
To determine the effect of a series of electro-acupuncture (EA) treatment in conjunction with exercise on the pain, disability, and functional improvement scores of patients with chronic low-back pain (LBP). A blinded prospective randomized controlled study. A total of 52 patients were randomly allocated to an exercise group (n = 26) or an exercise plus EA group (n = 26) and treated for 12 sessions. Numerical Rating Scale (NRS), Aberdeen LBP scale, lumbar spinal active range of movement (AROM), and the isokinetic strength were assessed by a blinded observer. Repeated measures analysis of variance (R-ANOVA) with factors of group and time was used to compare the outcomes between the two groups at baseline (before treatment), immediately after treatment, 1-month follow-up, and 3-month follow-up. The level of significance was set at p = 0.05. Significantly better scores in the NRS and Aberdeen LBP scale were found in the exercise plus EA group immediately after treatment and at 1-month follow-up. Higher scores were also seen at 3-month follow-up. No significant differences were observed in spinal AROM and isokinetic trunk concentric strength between the two groups at any stage of follow-up. This study provides additional data on the potential role of EA in the treatment of LBP, and indicates that the combination of EA and back exercise might be an effective option in the treatment of pain and disability associated with chronic LBP.


Role of surgery in patients with recurrent, metastatic, or unresectable locally advanced gastrointestinal stromal tumors sensitive to imatinib: a retrospective analysis of the Spanish Group for Research on Sarcoma (GEIS).
Recurrent, metastatic, and locally advanced gastrointestinal stromal tumors (GISTs) can be treated successfully with imatinib mesylate. Surgery for residual disease has been suggested for nonrefractory metastatic GISTs to reduce the probability of resistant recurrent clones, although no randomized Phase III trial has been performed to answer the question about its benefit. We carried out an analysis of the outcome of patients with recurrent unresectable locally advanced or metastatic imatinib-sensitive priamary GIST in 14 institutions in Spain. We compared two cohorts: treated or not treated with surgery after partial response or stabilization by imatinib. Data were obtained from the online GIST registry of the Spanish Group for Research in Sarcomas. Selected patients were then divided into two groups: group A, treated initially only with imatinib, and group B, treated additionally with metastasectomy. Baseline characteristics between groups were compared, and univariate and multivariate analysis for progression-free survival and overall survival (OS) were performed. Analysis was undertaken in 171 patients considered nonrefractory to imatinib. The median follow-up time was 56.6 months. Focusing on OS, the Eastern Cooperative Oncology Group performance status different than 0, extent of disease limited to one metastatic organ, and comparison between groups A or B achieved statistical difference in the multivariate analysis. Median survival was 59.9 months in group A and 87.6 months in group B. Based in its benefit in OS, our study supports surgery of metastatic disease in GIST patients who respond to imatinib therapy.


Reduced capacity to sustain positive emotion in major depression reflects diminished maintenance of fronto-striatal brain activation.
Anhedonia, the loss of pleasure or interest in previously rewarding stimuli, is a core feature of major depression. While theorists have argued that anhedonia reflects a reduced capacity to experience pleasure, evidence is mixed as to whether anhedonia is caused by a reduction in hedonic capacity. An alternative explanation is that anhedonia is due to the inability to sustain positive affect across time. Using positive images, we used an emotion regulation task to test whether individuals with depression are unable to sustain activation in neural circuits underlying positive affect and reward. While up-regulating positive affect, depressed individuals failed to sustain nucleus accumbens activity over time compared with controls. This decreased capacity was related to individual differences in self-reported positive affect. Connectivity analyses further implicated the fronto-striatal network in anhedonia. These findings support the hypothesis that anhedonia in depressed patients reflects the inability to sustain engagement of structures involved in positive affect and reward.


The Importance and Utility of Hemoglobin A1c Levels in the Assessment of Donor Pancreas Allografts.
Hemoglobin A1C (HbA1c) levels are often obtained in potential pancreas graft donors to assess the overall long-term functional glycemic control or the possibility of unrecognized diabetes. Although routinely measured, the impact of donor HbA1c levels on pancreas graft outcomes has not been reported. Here, we researched the relationship between donor HbA1c levels and postoperative pancreas graft survival. Data from 266 pancreas transplant patients including 182 simultaneous kidney-pancreas and 84 pancreas alone transplants were reviewed for the study. The patients were separated into groups according to their HbA1c levels (5 groups: HbA1c < 5.0, 5.0-5.4, 5.5-5.9, ≥6.0 % and not available, or 2 groups: HbA1c <5.7, ≥5.7%). Overall, death-censored and technically successful pancreas graft survival and rejection rates of each group were compared. In the case of technically successful graft survival, graft losses due to technical problems in the first 60 days were excluded. All groups were similar with regard to donor variables including age, sex, ABO blood type, ethnicity, donor type and recipient variables including recipient age, sex, induction agents and maintenance treatment. Mean follow-up time was 4.2 ± 1.97 years. The overall graft survivals and death censored graft survivals among groups were not statistically different from one other (P > 0.05). Additionally, excluding early technical losses in 18 patients did not reveal any differences in graft survivals. Patient survival and biopsy-proven acute rejections were statistically similar among HbA1c strata. This univariate retrospective analysis of a single center/organ procurement organization use of HbA1c shows that donor HbA1c levels between 3.5 and 6.2 in otherwise transplantable pancreata are not associated with different short-term outcomes.


Clinical features of acute gastroenteritis associated with rotavirus, enteric adenoviruses, and bacteria.
In a prospective one year study, comprising children with acute gastroenteritis admitted to hospital or treated as outpatients, the clinical and laboratory features of rotavirus diarrhoea (168 cases) were compared with those of enteric adenovirus (32 cases), bacterial (42), mixed (16), and non-specific (135) infections. The rotavirus disease was remarkably consistent, with a sudden onset of vomiting, a high frequency of fever and dehydration, and a mean duration of diarrhoea of 5.9 days. Outpatients excreting rotavirus had a similar but milder illness, mainly on account of less pronounced vomiting. The predominant symptom of enteric adenoviruses was long lasting diarrhoea (mean 10.8 days). Abdominal pain, bloody stools, prolonged diarrhoea (mean 14.1 days), leucocytosis, and a raised erythrocyte sedimentation rate strongly suggested a bacterial aetiology. Mixed infections caused longer lasting diarrhoea (mean 8.0 days) than rotavirus alone, but the severity of the illness was not increased. The clinical features of infection with unidentified pathogens most resembled those of bacterial infections. Respiratory symptoms were not significantly associated with any particular pathogen. Hypernatraemia and complications were uncommon. This study showed that the clinical features of gastroenteritis with rotavirus, enteric adenoviruses, and bacteria each exhibited patterns that could guide the experienced clinician to a presumptive diagnosis.


Molecular chess? Hallmarks of anti-cancer drug resistance.
The development of resistance is a problem shared by both classical chemotherapy and targeted therapy. Patients may respond well at first, but relapse is inevitable for many cancer patients, despite many improvements in drugs and their use over the last 40 years. Resistance to anti-cancer drugs can be acquired by several mechanisms within neoplastic cells, defined as (1) alteration of drug targets, (2) expression of drug pumps, (3) expression of detoxification mechanisms, (4) reduced susceptibility to apoptosis, (5) increased ability to repair DNA damage, and (6) altered proliferation. It is clear, however, that changes in stroma and tumour microenvironment, and local immunity can also contribute to the development of resistance. Cancer cells can and do use several of these mechanisms at one time, and there is considerable heterogeneity between tumours, necessitating an individualised approach to cancer treatment. As tumours are heterogeneous, positive selection of a drug-resistant population could help drive resistance, although acquired resistance cannot simply be viewed as overgrowth of a resistant cancer cell population. The development of such resistance mechanisms can be predicted from pre-existing genomic and proteomic profiles, and there are increasingly sophisticated methods to measure and then tackle these mechanisms in patients. The oncologist is now required to be at least one step ahead of the cancer, a process that can be likened to 'molecular chess'. Thus, as well as an increasing role for predictive biomarkers to clinically stratify patients, it is becoming clear that personalised strategies are required to obtain best results.


Exclusion of NFAT5 from mitotic chromatin resets its nucleo-cytoplasmic distribution in interphase.
The transcription factor NFAT5 is a major inducer of osmoprotective genes and is required to maintain the proliferative capacity of cells exposed to hypertonic stress. In response to hypertonicity, NFAT5 translocates to the nucleus, binds to regulatory regions of osmoprotective genes and activates their transcription. Besides stimulus-specific regulatory mechanisms, the activity of transcription factors in cycling cells is also regulated by the passage through mitosis, when most transcriptional processes are downregulated. It was not known whether mitosis could be a point of control for NFAT5. Using confocal microscopy we observed that NFAT5 was excluded from chromatin during mitosis in both isotonic and hypertonic conditions. Analysis of NFAT5 deletions showed that exclusion was mediated by the carboxy-terminal domain (CTD). NFAT5 mutants lacking this domain showed constitutive binding to mitotic chromatin independent of tonicity, which caused them to localize in the nucleus and remain bound to chromatin in the subsequent interphase without hypertonic stimulation. We analyzed the contribution of the CTD, DNA binding, and nuclear import and export signals to the subcellular localization of this factor. Our results indicated that cytoplasmic localization of NFAT5 in isotonic conditions required both the exclusion from mitotic DNA and active nuclear export in interphase. Finally, we identified several regions within the CTD of NFAT5, some of them overlapping with transactivation domains, which were separately capable of causing its exclusion from mitotic chromatin. Our results reveal a multipart mechanism regulating the subcellular localization of NFAT5. The transactivating module of NFAT5 switches its function from an stimulus-specific activator of transcription in interphase to an stimulus-independent repressor of binding to DNA in mitosis. This mechanism, together with export signals acting in interphase, resets the cytoplasmic localization of NFAT5 and prevents its nuclear accumulation and association with DNA in the absence of hypertonic stress.


Bioavailable copper modulates oxidative phosphorylation and growth of tumors.
Copper is an essential trace element, the imbalances of which are associated with various pathological conditions, including cancer, albeit via largely undefined molecular and cellular mechanisms. Here we provide evidence that levels of bioavailable copper modulate tumor growth. Chronic exposure to elevated levels of copper in drinking water, corresponding to the maximum allowed in public water supplies, stimulated proliferation of cancer cells and de novo pancreatic tumor growth in mice. Conversely, reducing systemic copper levels with a chelating drug, clinically used to treat copper disorders, impaired both. Under such copper limitation, tumors displayed decreased activity of the copper-binding mitochondrial enzyme cytochrome c oxidase and reduced ATP levels, despite enhanced glycolysis, which was not accompanied by increased invasiveness of tumors. The antiproliferative effect of copper chelation was enhanced when combined with inhibitors of glycolysis. Interestingly, larger tumors contained less copper than smaller tumors and exhibited comparatively lower activity of cytochrome c oxidase and increased glucose uptake. These results establish copper as a tumor promoter and reveal that varying levels of copper serves to regulate oxidative phosphorylation in rapidly proliferating cancer cells inside solid tumors. Thus, activation of glycolysis in tumors may in part reflect insufficient copper bioavailability in the tumor microenvironment.


Posterior lumbar fusion: choice of approach and adjunct techniques.
The choice among the many options of approach and adjunct techniques in planning a posterior lumbar fusion can be problematic. Debates remain as to whether solid fusion has an advantage over pseudarthrosis regarding long-term symptom deterioration and whether an instrumented or a noninstrumented approach will best serve clinically and/or cost effectively, particularly in elderly patients. Increased motion resulting in higher rates of nonunion and the use of nonsteroidal anti-inflammatory drugs have been studied in animal models and are presumed risk factors, despite the lack of clinical investigation. Smoking is a proven risk factor for pseudarthrosis in both animal models and level III clinical studies. Recent long-term studies and image/clinical assessment of lumbar fusions and pseudarthrosis show that, although imaging remains a key area of difficulty in assessment, including an instrumented approach and a well-selected biologic adjunct, as well as achieving a solid fusion, all carry important long-term clinical advantages in avoiding revision surgery for nonunion.


Realist-informed review of motivational interviewing for adolescent health behaviors.
Clinical research investigating effective intervention strategies for adolescents to improve health behaviors has shifted to the application of motivational interviewing (MI). Evidence indicates that MI is an effective intervention for improving health behaviors as related to diet, exercise, and diabetes among adolescents. However, there is a lack of understanding about the mechanisms through which MI works and the contextual factors impacting MI effectiveness. The purpose of this review was to understand how, for whom, and under what circumstances MI works for adolescent health behavior change, which will inform future implementation of this intervention. To provide this in-depth understanding, a realist-informed systematic review was conducted in order to synthesize the evidence on the use of MI for health behaviors. Self-determination theory (SDT) was chosen as the candidate theory for testing in the present review. Databases including PsycINFO, Healthstar, Cochrane, and PubMed were searched for articles published until March 2017. The search strategy included studies that examined or reviewed the effectiveness or efficacy of MI to change health behaviors among adolescent populations. The search identified 185 abstracts, of which 28 were included in the review. The literature was synthesized qualitatively (immersion/crystallization) and tested SDT as the candidate theory. Based on SDT, three mechanisms were found within reviewed studies, including competence, relatedness, and autonomy. The following contexts were found to impact mechanisms: school setting, clinician MI proficiency, parental involvement, and peer involvement. This realist-informed systematic review provides advances in understanding the mechanisms involved in MI for adolescent health behavior change. Additionally, it provides important practical information as to which contexts create the conditions for these mechanisms to occur, leading to health behavior change. The results can inform future MI interventions for adolescent health behavior change. Future research should continue to test this realist theory and also examine mechanism variables not extensively documented in order to improve our understanding of MI in this population.


The feasibility of collecting information from people with Multiple Sclerosis for the UK MS Register via a web portal: characterising a cohort of people with MS.
A UK Register of people with Multiple Sclerosis has been developed to address the need for an increased knowledge-base about MS. The Register is being populated via: a web-based portal; NHS neurology clinical systems; and administrative data sources. The data are de-identified and linked at the individual level. At the outset, it was not known whether people with MS would wish to participate in the UK MS Register by personally contributing their data to the Register via a web-based system. Therefore, the research aim of this work was to build an internet-mounted recruitment and consenting technology for people with Multiple Sclerosis, and to assess its feasibility as a questionnaire delivery platform to contribute data to the UK MS Register, by determining whether the information provided could be used to describe a cohort of people with MS. The web portal was developed using VB.net and JQuery with a Microsoft SQL 2008 database. UK adults with MS can self-register and enter data about themselves by completing validated questionnaires. Descriptive statistics were used to characterise the respondents. The web portal was launched in May 2011, and in first three months 7,279 individuals registered on the portal. The ratio of men to women was 1:2.4 (n = 5,899), the mean self-reported age at first symptoms was 33.8 (SD 10.5) years, and at diagnosis 39.6 (SD 10.3) years (n = 4,401). The reported types of MS were: 15% primary progressive, 63% relapsing-remitting, 8% secondary progressive, and 14% unknown (n = 5,400). These characteristics are similar to those of the prevalent MS population. Employment rates, sickness/disability rates, ethnicity and educational qualifications were compared with the general UK population. Information about the respondents' experience of early symptoms and the process of diagnosis, plus living arrangements are also reported. These initial findings from the MS Register portal demonstrate the feasibility of collecting data about people with MS via a web platform, and show that sufficient information can be gathered to characterise a cohort of people with MS. The innovative design of the UK MS register, bringing together three disparate sources of data, is creating a rich resource for research into this condition.


How long do particles spend in vortical regions in turbulent flows?
We obtain the probability distribution functions (PDFs) of the time that a Lagrangian tracer or a heavy inertial particle spends in vortical or strain-dominated regions of a turbulent flow, by carrying out direct numerical simulations of such particles advected by statistically steady, homogeneous, and isotropic turbulence in the forced, three-dimensional, incompressible Navier-Stokes equation. We use the two invariants, Q and R, of the velocity-gradient tensor to distinguish between vortical and strain-dominated regions of the flow and partition the Q-R plane into four different regions depending on the topology of the flow; out of these four regions two correspond to vorticity-dominated regions of the flow and two correspond to strain-dominated ones. We obtain Q and R along the trajectories of tracers and heavy inertial particles and find out the time t_{pers} for which they remain in one of the four regions of the Q-R plane. We find that the PDFs of t_{pers} display exponentially decaying tails for all four regions for tracers and heavy inertial particles. From these PDFs we extract characteristic time scales, which help us to quantify the time that such particles spend in vortical or strain-dominated regions of the flow.


Comparison of plant hormone signalling systems.
Plant growth and development are controlled by nine structurally distinct small molecules termed phytohormones. Over the last 20 years, the molecular basis of their signal transduction, from receptors to transcription factors, has been dissected using mainly Arabidopsis thaliana and rice as model systems. Phytohormones can be broadly classified into two distinct groups on the basis of whether the subcellular localization of their receptors is in the cytoplasm or nucleus, and hence soluble, or membrane-bound, and hence insoluble. Soluble receptors, which control the responses to auxin, jasmonates, gibberellins, strigolactones and salicylic acid, signal either directly or indirectly via the destruction of regulatory proteins. Responses to abscisic acid are primarily mediated by soluble receptors that indirectly regulate the phosphorylation of targeted proteins. Insoluble receptors, which control the responses to cytokinins, brassinosteroids and ethylene, transduce their signal through protein phosphorylation. This chapter provides a comparison of the different components of these signalling systems, and discusses the similarities and differences between them.


A behavioral and neural evaluation of prospective decision-making under risk.
Making the best choice when faced with a chain of decisions requires a person to judge both anticipated outcomes and future actions. Although economic decision-making models account for both risk and reward in single-choice contexts, there is a dearth of similar knowledge about sequential choice. Classical utility-based models assume that decision-makers select and follow an optimal predetermined strategy, regardless of the particular order in which options are presented. An alternative model involves continuously reevaluating decision utilities, without prescribing a specific future set of choices. Here, using behavioral and functional magnetic resonance imaging (fMRI) data, we studied human subjects in a sequential choice task and use these data to compare alternative decision models of valuation and strategy selection. We provide evidence that subjects adopt a model of reevaluating decision utilities, in which available strategies are continuously updated and combined in assessing action values. We validate this model by using simultaneously acquired fMRI data to show that sequential choice evokes a pattern of neural response consistent with a tracking of anticipated distribution of future reward, as expected in such a model. Thus, brain activity evoked at each decision point reflects the expected mean, variance, and skewness of possible payoffs, consistent with the idea that sequential choice evokes a prospective evaluation of both available strategies and possible outcomes.