Properties of Injectable Apatite-Forming Premixed Cements.
Previous studies reported premixed calcium phosphate cements (CPCs) that were stable in the package and form hydroxyapatite (HA) as the product after exposure to an aqueous environment. These cements had setting times of greater than 60 min, which are too long to be useful for some clinical applications. The present study investigated properties of fast-setting HA-forming premixed CPCs that initially consisted of two separate premixed pastes: (1) finely ground (1.0 μm in median size) dicalcium phosphate anhydrous (DCPA) mixed with an aqueous NaH(2)PO(4) solution, 1.5 mol/L or 3.0 mol/L in concentration, and (2) tetracalcium phosphate consisting of combinations of particles of two different size distributions, 5 μm (TTCP5) and 17 μm (TTCP17) in median size, mixed with glycerin. Equal volume of Pastes 1 and 2 were injected with the use of atwo-barrel syringe fitted with a static mixer into sample molds. The molar Ca/P ratio of combined paste was approximately 1.5. Cements were characterized in terms of setting time (Gilmore needle), diametral tensile strength (DTS), and phase composition (powder x-ray diffraction, XRD). Setting times were found to range from (4.3 ± 0.6 to 68 ± 3) min (mean ± sd; n = 3), and 1-d and 7-d DTS values were from (0.89 ± 0.08 to 2.44 ± 0.16) MPa (mean ± sd; n = 5). Both the NaH(2)PO(4) concentration and TTCP particle size distribution had significant (p < 0.01) effects on setting time and DTS. Powder XRD analysis showed that low crystallinity HA and unreacted DCPA were present in the 1-day specimens, and the extent of HA formation increased with increasing amount of TTCP5 in the TTCP paste. CONCLUSION: Injectable HA-forming premixed CPCs with setting times from 4 to 70 min can be prepared by using DCPA and TTCP as the ingredients. Compared to the conventional powder liquid cements, these premixed CPCs have the advantages of being easy to use and having a range of hardening times.


Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study.
Many women of childbearing potential take antiepileptic drugs, but the cognitive effects of fetal exposure are uncertain. We aimed to assess effects of commonly used antiepileptic drugs on cognitive outcomes in children up to 6 years of age. In this prospective, observational, assessor-masked, multicentre study, we enrolled pregnant women with epilepsy on antiepileptic drug monotherapy (carbamazepine, lamotrigine, phenytoin, or valproate) between October, 1999, and February, 2004, at 25 epilepsy centres in the UK and the USA. Our primary outcome was intelligence quotient (IQ) at 6 years of age (age-6 IQ) in all children, assessed with linear regression adjusted for maternal IQ, antiepileptic drug type, standardised dose, gestational birth age, and use of periconceptional folate. We also assessed multiple cognitive domains and compared findings with outcomes at younger ages. This study is registered with ClinicalTrials.gov, number NCT00021866. We included 305 mothers and 311 children (six twin pairs) in the primary analysis. 224 children completed 6 years of follow-up (6-year-completer sample). Multivariate analysis of all children showed that age-6 IQ was lower after exposure to valproate (mean 97, 95% CI 94-101) than to carbamazepine (105, 102-108; p=0·0015), lamotrigine (108, 105-110; p=0·0003), or phenytoin (108, 104-112; p=0·0006). Children exposed to valproate did poorly on measures of verbal and memory abilities compared with those exposed to the other antiepileptic drugs and on non-verbal and executive functions compared with lamotrigine (but not carbamazepine or phenytoin). High doses of valproate were negatively associated with IQ (r=-0·56, p<0·0001), verbal ability (r=-0·40, p=0·0045), non-verbal ability (r=-0·42, p=0·0028), memory (r=-0·30, p=0·0434), and executive function (r=-0·42, p=0·0004), but other antiepileptic drugs were not. Age-6 IQ correlated with IQs at younger ages, and IQ improved with age for infants exposed to any antiepileptic drug. Compared with a normative sample (173 [93%] of 187 children), right-handedness was less frequent in children in our study overall (185 [86%] of 215; p=0·0404) and in the lamotrigine (59 [83%] of 71; p=0·0287) and valproate (38 [79%] of 40; p=0·0089) groups. Verbal abilities were worse than non-verbal abilities in children in our study overall and in the lamotrigine and valproate groups. Mean IQs were higher in children exposed to periconceptional folate (108, 95% CI 106-111) than they were in unexposed children (101, 98-104; p=0·0009). Fetal valproate exposure has dose-dependent associations with reduced cognitive abilities across a range of domains at 6 years of age. Reduced right-handedness and verbal (vs non-verbal) abilities might be attributable to changes in cerebral lateralisation induced by exposure to antiepileptic drugs. The positive association of periconceptional folate with IQ is consistent with other recent studies.


An Ethical Comparison between In-Vitro Fertilization and NaProTechnology.
In vitro fertilization (IVF) is morally objectionable for a number of reasons: the destruction of human embryos, the danger to women and newborn infants, and the replacement of the marital act in procreation. Recent studies have shown a significant risk of maternal death and morbidity associated with ovarian hyper-stimulation syndrome and multiple pregnancies after IVF. Due to lack of uniform regulations for IVF clinics, there is under-reporting of the adverse effects. NaProTechonology is one ethical alternative to IVF for female infertility. One study has confirmed earlier findings that NaProTechonology results in a number of live births similar to that of assisted reproductive technology, without the danger to women and newborn infants. Adoption of born children is another ethical and praiseworthy alternative to IVF.


Comet assay with nuclear extract incubation.
Alkaline comet assay is a simple sensitive method for detecting DNA strand breaks. However, at the time of cell lysis, only a fraction of the entire DNA damage appears as DNA strand breaks, while some DNA strand breaks may have been rejoined and some DNA lesions may still remain unexcised. We showed that nuclear extract (NE) prepared from human cells could excise the DNA adducts induced by UVC, X-ray, and methyl methanesulfonate (MMS). Thus, the comet assay with NE incubation allows a closer estimation of total DNA damage. Among the human urothelial carcinoma cell lines we tested, the NE of NTUB1 cells showed higher activity in excising the DNA adducts induced by UVC, but with a lower activity in excising the DNA adducts induced by MMS than the NE of BFTC905 cells. Moreover, under the same dose of X-ray irradiation, a larger difference in total DNA damage between two cell lines was revealed in comet assay incubated with NE than without NE. Therefore, the comet assay with NE incubation may be useful in the research of cancer risk, drug resistance, and DNA repair proteins.


Holographic subtraction.
A holographic technique by which two dissimilar optical fields can be subtracted to yield only their difference is presented. The principle underlying this technique is that of optical interference between a holographically reconstructed field and a direct real-time one. Experimental verification is presented for the three cases of image-plane, fourier-transform, and Fresnel side-band holograms. Also considered is the application of this concept to change detection between photographic transparencies of some scene taken at different times.


Spectral radiance of a low current graphite arc.
The spectral radiance of the anode of a low current graphite arc has been determined throughout most of the 850-210 nm region by utilizing a recently developed high accuracy spectroradiometer. The estimated standard deviation uncertainty varies from about 1.5% at the longer wavelengths to about 5% at the shorter. Results are given at twenty wavelength points in the region and also as a continuous function of wavelength throughout most of the region, excluding some areas of high molecular band radiation originating in the arc stream.


Group Intervention for Young Adults With Mood and Anxiety Disorders Transitioning to College.
Young adults with chronic mood and anxiety disorders may receive a range of services in pediatric care (eg, psychiatry, therapy) and within the school system (eg, individualized education plans). Such services rely on the involvement of parents or guardians to support youth (eg, attending appointments, administering medications). However, in college, young adults are often on their own and need to assume responsibility for scheduling appointments, obtaining and taking medications, and seeking out additional services (eg, accommodations). Unfortunately, many young adults may not have developed the skills needed to navigate campus and health care systems effectively, which can often lead to dire consequences. Adding to these difficulties are the high rates of depression and suicidal ideation observed in today's college students. Many students need intermediate levels of care to stay in school successfully, although not all have the maturity and skills to navigate health care without a transition plan. To address the needs of young adults transitioning out of pediatric mental health care, we developed a brief group intervention delivered to young adults and their parents during the 6 months before college or transition to living independently in the community. The transition group program structured sessions focused on scaffolding knowledge about one's own skills (and deficits) related to independent living, successful transition to college or community, and ability to independently manage a chronic mental health disorder. All young adults and parents reported that they would recommend or strongly recommend the group to a friend, and the majority found the group to be acceptable with regard to length and frequency. For both young adults and parents, the future outlook also improved from pregroup to postgroup.


Major advances in genetic evaluation techniques.
The past quarter-century in genetic evaluation of dairy cattle has been marked by evolution in methodology and computer capacity, expansion in the array of evaluated traits, and globalization. Animal models replaced sire and sire-maternal grandsire models and, more recently, application of Bayesian theory has become standard. Individual test-day observations have been used more effectively in estimation of lactation yield or directly as input to evaluation models. Computer speed and storage are less limiting in choosing procedures. The increased capabilities have supported evaluation of additional traits that affect the net profitability of dairy cows. The importance of traits other than yield has increased, in a few cases due to an antagonistic relationship with yield. National evaluations combined internationally provide evaluations for bulls from all participating countries on each of the national scales, facilitating choices from among many more bulls. Selection within countries has increased inbreeding and the use of similar genetics across countries reduces the previously available outcross population. Concern about inbreeding has prompted changes in evaluation methodology and mating practices, and has promoted interest in crossbreeding. In just the past decade, distribution of genetic evaluations has gone from mailed paper or computer tapes for a limited audience to publicly accessible, request-driven distribution via the Internet. Among the distributed information is a choice of economic indices that combine an increasing array of traits into numbers reflecting breeding goals under different milk-pricing conditions. Considerable progress in genomics and the mapping of the bovine genome have identified markers for some deleterious recessive genes, but broader benefits of marker-assisted selection are still in the future. A possible exception is the proprietary use of DNA testing by semen producers to select among potential progeny test bulls. The collection and analysis of industry-wide data to evaluate genetic merit will continue to be the most important tool for genetic progress into the foreseeable future.


PDRMIP: A Precipitation Driver and Response Model Intercomparison Project, Protocol and preliminary results.
As the global temperature increases with changing climate, precipitation rates and patterns are affected through a wide range of physical mechanisms. The globally averaged intensity of extreme precipitation also changes more rapidly than the globally averaged precipitation rate. While some aspects of the regional variation in precipitation predicted by climate models appear robust, there is still a large degree of inter-model differences unaccounted for. Individual drivers of climate change initially alter the energy budget of the atmosphere leading to distinct rapid adjustments involving changes in precipitation. Differences in how these rapid adjustment processes manifest themselves within models are likely to explain a large fraction of the present model spread and needs better quantifications to improve precipitation predictions. Here, we introduce the Precipitation Driver and Response Model Intercomparison Project (PDRMIP), where a set of idealized experiments designed to understand the role of different climate forcing mechanisms were performed by a large set of climate models. PDRMIP focuses on understanding how precipitation changes relating to rapid adjustments and slower responses to climate forcings are represented across models. Initial results show that rapid adjustments account for large regional differences in hydrological sensitivity across multiple drivers. The PDRMIP results are expected to dramatically improve our understanding of the causes of the present diversity in future climate projections.


Extra-cardiac findings in cardiovascular magnetic resonance: what the imaging cardiologist needs to know.
Cardiovascular magnetic resonance (CMR) is an established non-invasive technique to comprehensively assess cardiovascular structure and function in a variety of acquired and inherited cardiac conditions. A significant amount of the neck, thorax and upper abdomen are imaged at the time of routine clinical CMR, particularly in the initial multi-slice axial and coronal images. The discovery of unsuspected disease at the time of imaging has ethical, financial and medico-legal implications. Extra-cardiac findings at the time of CMR are common, can be important and can change clinical management. Certain patient groups undergoing CMR are at particular risk of important extra-cardiac findings as several of the cardiovascular risk factors for atherosclerosis are also risk factors for malignancy. Furthermore, the presence of certain extra-cardiac findings may contribute to the interpretation of the primary cardiac pathology as some cardiac conditions have multi-systemic extra-cardiac involvement. The aim of this review is to give an overview of the type of extra-cardiac findings that may become apparent on CMR, subdivided by anatomical location. We focus on normal variant anatomy that may mimic disease, common incidental extra-cardiac findings and important imaging signs that help distinguish sinister pathology from benign disease. We also aim to provide a framework to the approach and potential further diagnostic work-up of incidental extra-cardiac findings discovered at the time of CMR. However, it is beyond the scope of this review to discuss and determine the clinical significance of extracardiac findings at CMR.


Phosphorylation of the Chloroplastic Metalloprotease FtsH in Arabidopsis Characterized by Phos-Tag SDS-PAGE.
FtsH is an essential ATP-dependent metalloprotease for protein quality control in the thylakoid membrane of Arabidopsis thaliana chloroplasts. It is required for chloroplast development during leaf growth, and particularly for the specific degradation of photo-damaged D1 protein in the photosystem II (PSII) complex to maintain photosynthesis activity. In the thylakoid membrane, the reversible phosphorylation of proteins is known to control the activity and remodeling of photosynthetic complexes, and previous studies implicate that FtsH is also phosphorylated. We therefore assessed the phosphorylation status of FtsH and its possible role in the regulatory mechanism in this study. The phosphorylation level of FtsHs that compose the FtsH heterohexameric complex was investigated by phosphate-affinity gel electrophoresis using a Phos-Tag molecule. Phos-tag SDS-PAGE of thylakoid proteins and subsequent immunoblot analysis showed that both type A (FtsH1/5) and type B (FtsH2/8) subunits were separable into phosphorylated and non-phosphorylated forms. Neither different light conditions nor the lack of two major thylakoid kinases, STN7 and STN8, resulted in any clear difference in FtsH phosphorylation, suggesting that this process is independent of the light-dependent regulation of photosynthesis-related proteins. Site-directed mutagenesis of putatively phosphorylated Ser or Thr residues into Ala demonstrated that Ser-212 may play a role in FtsH stability in the thylakoid membranes. Different phosphorylation status of FtsH oligomers analyzed by two-dimensional clear-native/Phos-tag SDS-PAGE implied that phosphorylation partially affects FtsH complex formation or its stability.


Precise timing of the last interglacial period from mass spectrometric determination of thorium-230 in corals.
The development of mass spectrometric techniques for determination of (230)Th abundance has made it possible to reduce analytical errors in (238)U-(234)U-(230)Th dating of corals even with very small samples. Samples of 6 x 10(8) atoms of (230)Th can be measured to an accuracy of +/-3 percent (2sigma) and 3 x 10(10) atoms of (230)Th can be measured to an accuracy of +/-0.2 percent. The time range over which useful age data on corals can be obtained now ranges from about 50 to about 500,000 years. For young corals, this approach may be preferable to (14)C dating. The precision with which the age of a coral can now be determined should make it possible to critically test the Milankovitch hypothesis concerning Pleistocene climate fluctuations. Analyses of a number of corals that grew during the last interglacial period yield ages of 122,000 to 130,000 years. The ages coincide with, or slightly postdate, the summer solar insolation high at 65 degrees N latitude which occurred 128,000 years ago. This supports the idea that changes in Pleistocene climate can be the result of variations in the distribution of solar insolation caused by changes in the geometry of the earth's orbit and rotation axis.


Adjuvant Vaccination with Allogenic Dendritic Cells Significantly Prolongs Overall Survival in High-Grade Gliomas: Results of a Phase II Trial.
Immunotherapy for cancer treatment has gained increased attention in recent years. Recently, our group reported the case of a patient with glioblastoma who underwent vaccination based on dendritic cells and experienced a strong Th1 immune response together with near-complete tumor remission. Here we report the results of a phase I/II prospective, non-controlled clinical trial with 37 patients harboring glioblastoma or grade 4 astrocytomas. At the time of first recurrence after surgery, patients began receiving monthly intradermal injections of allogenic DC-autologous tumor cell hybridomas. Overall survival, quality of life, and immunological profiles were assessed prospectively. Compared with patients in the Genomic Data Commons data bank, overall survival for vaccinated patients with glioblastoma was 27.6 ± 2.4 months (vs. 16.3 ± 0.7, log-rank p < 0.001, hazard ratio 0.53, 95%CI 0.36-0.78, p < 0.01), and it was 59.5 ± 15.9 for vaccinated astrocytoma grade 4 patients (vs. 19.8 ± 2.5, log-rank p < 0.05, hazard ratio 0.18, 95%CI 0.05-0.62, p < 0.01). Furthermore, seven vaccinated patients (two IDH-1-mutated and five wild type) remain alive at the time of this report (overall survival 47.9 months, SD 21.1, range: 25.4-78.6 months since diagnosis; and 34.2 months since recurrence, range: 17.8 to 40.7, SD 21.3). We believe that the data reported here can foster the improvement of treatment protocols for high-grade gliomas based on cellular immunotherapy.


The effects of cashew nut intake on lipid profile and blood pressure: A systematic review and meta-analysis of randomized controlled trials.
Dyslipidemia and hypertension are important risk factors for cardiovascular disease (CVD). Some studies have suggested that the consumption of nuts may reduce CVD risk. The present systematic review and meta-analysis was conducted to investigate the efficacy of cashew nut consumption on lipid profile and blood pressure. PubMed, Embase, Scopus, Web of Science and Cochrane Library were systematically searched to identify randomized control trials (RCTs) examining the effects of cashew nut intake on serum triglycerides (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), serum total cholesterol (TC), systolic blood pressure (SBP) or diastolic blood pressure (DBP) until 15 November 2019. A random-effects model was used to pool weighted mean difference (WMD) and 95 % confidence intervals (CI). Potential publication bias was assessed using Egger's test. Sensitivity analysis was performed to assess the impact of each individual study on the pooled results. A meta-analysis on 392 participants showed that cashew nut consumption had no significant effects on lipid profile and DBP. However, there was a significant reduction in SBP (WMD = -3.39, 95 % CI = [-6.13, -0.65], P = 0.01, I2 = 0.0 %) in the group receiving cashew nut compared to the controls. There was no significant publication bias in the meta-analysis. A sensitivity analysis showed that omitting each study did not change the significance of results. This meta-analysis demonstrated that cashew nut consumption might reduce SBP but has no effects on lipid profile and DBP.


Improving Luttinger-liquid plasmons in carbon nanotubes by chemical doping.
We realized the real-space imaging of Luttinger-liquid plasmons in semiconducting single-walled carbon nanotubes (s-SWCNTs) and studied the effects of chemical-doping-induced charge carrier density modulation on plasmons. Using scattering-type scanning near-field optical microscopy (s-SNOM), we compared the Luttinger-liquid plasmonic behavior in pre- and post-HNO3-doped SWCNTs. Raman measurements revealed that the physical mechanism is P-type doping. Through HNO3 doping, we effectively increased the charge carrier density in s-SWCNTs and achieved quantum plasmons simultaneously with strong confinement (λ0/λp ≈ 70) and high quality factor (Q ≈ 20). The combination of high quality factor and strong subwavelength confinement in Luttinger-liquid plasmons is critical to the future application of plasmonic devices.


Performance analysis of multiple Indoor Positioning Systems in a healthcare environment.
The combination of an aging population and nursing staff shortages implies the need for more advanced systems in the healthcare industry. Many key enablers for the optimization of healthcare systems require provisioning of location awareness for patients (e.g. with dementia), nurses, doctors, assets, etc. Therefore, many Indoor Positioning Systems (IPSs) will be indispensable in healthcare systems. However, although many IPSs have been proposed in literature, most of these have been evaluated in non-representative environments such as office buildings rather than in a hospital. To remedy this, the paper evaluates the performance of existing IPSs in an operational modern healthcare environment: the "Sint-Jozefs kliniek Izegem" hospital in Belgium. The evaluation (data-collecting and data-processing) is executed using a standardized methodology and evaluates the point accuracy, room accuracy and latency of multiple IPSs. To evaluate the solutions, the position of a stationary device was requested at 73 evaluation locations. By using the same evaluation locations for all IPSs the performance of all systems could objectively be compared. Several trends can be identified such as the fact that Wi-Fi based fingerprinting solutions have the best accuracy result (point accuracy of 1.21 m and room accuracy of 98%) however it requires calibration before use and needs 5.43 s to estimate the location. On the other hand, proximity based solutions (based on sensor nodes) are significantly cheaper to install, do not require calibration and still obtain acceptable room accuracy results. As a conclusion of this paper, Wi-Fi based solutions have the most potential for an indoor positioning service in case when accuracy is the most important metric. Applying the fingerprinting approach with an anchor installed in every two rooms is the preferred solution for a hospital environment.


Physical activity and head and neck cancer risk.
To investigate the relation of physical activity to head and neck cancer. We prospectively examined the association between physical activity and head and neck cancer in 487,732 men and women, who, at baseline in 1995-1996, were 50-71 years old and free of cancer and emphysema. Follow-up occurred through 31 December 2003. During follow-up, 1,249 participants developed head and neck cancer, of which 42.0%, 18.9%, and 32.5% were located in the oral cavity, pharynx, and larynx, respectively. In analyses adjusted for age and gender, the relative risks (RR) of head and neck cancer for increasing frequency of physical activity (0, < 1, 1-2, 3-4, and >or=5 times per week) were 1.0 (reference), 0.76, 0.66, 0.57, and 0.62 (95% CI = 0.52-0.74), respectively (p for trend < 0.001). After multivariate adjustment including smoking, the relation was attenuated and became statistically non-significant (RR comparing extreme physical activity categories = 0.89, 95% CI = 0.74-1.06; p for trend = 0.272). In analyses of head and neck cancer subtypes, the corresponding RRs for cancers of the oral cavity, pharynx, and larynx were 0.98 (95% CI = 0.75-1.29), 0.70 (95% CI = 0.45-1.08), and 0.82 (95% CI = 0.59-1.13), respectively. Our findings suggest that physical activity is unlikely to play an important role in the prevention of head and neck cancer.


Investigating the human spinal sensorimotor pathways through functional magnetic resonance imaging.
Most of our knowledge about the human spinal ascending (sensory) and descending (motor) pathways comes from non-invasive electrophysiological investigations. However, recent methodological advances in acquisition and analyses of functional magnetic resonance imaging (fMRI) data from the spinal cord, either alone or in combination with the brain, have allowed us to gain further insights into the organization of this structure. In the current review, we conducted a systematic search to produced somatotopic maps of the spinal fMRI activity observed through different somatosensory, motor and resting-state paradigms. By cross-referencing these human neuroimaging findings with knowledge acquired through neurophysiological recordings, our review demonstrates that spinal fMRI is a powerful tool for exploring, in vivo, the human spinal cord pathways. We report strong cross-validation between task-related and resting-state fMRI in accordance with well-known hemicord, postero-anterior and rostro-caudal organization of these pathways. We also highlight the specific advantages of using spinal fMRI in clinical settings to characterize better spinal-related impairments, predict disease progression, and guide the implementation of therapeutic interventions.


Ease of Caregiving for Children: Re-Validation of Psychometric Properties of the Measure for Children with Cerebral Palsy up to 11 Years of Age.
Purpose: To re-validate stability and hierarchal ordering of items, test-retest reliability, and construct validity of the Ease of Caregiving for Children measure for parents of children with cerebral palsy (CP) up to 11 years of age.Methods: Participants were 613 parents of children with CP between 1.5 and 11 years of age. Parents completed Ease of Caregiving for Children and both parents and therapists classified children's levels of gross motor, manual and communication functions.Results: Rasch analysis indicated acceptable fit of items, stable item calibration, and logical ordering of items by difficulty. Test-retest reliability was good: ICC = 0.69 (95% CI 0.52-0.81). For construct validity, ease of caregiving was higher for parents of children with higher functioning compared to parents of children with lower functioning, p < .001.Conclusions: Ease of Caregiving for Children is a unidimensional, reliable and valid measure of physical caregiving for parents of children with CP 1.5-11 years.


Phenotype reversion in fetal human liver epithelial cells identifies the role of an intermediate meso-endodermal stage before hepatic maturation.
Understanding the biological potential of fetal stem/progenitor cells will help define mechanisms in liver development and homeostasis. We isolated epithelial fetal human liver cells and established phenotype-specific changes in gene expression during continuous culture conditions. Fetal human liver epithelial cells displayed stem cell properties with multilineage gene expression, extensive proliferation and generation of mesenchymal lineage cells, although the initial epithelial phenotype was rapidly supplanted by meso-endodermal phenotype in culture. This meso-endodermal phenotype was genetically regulated through cytokine signaling, including transforming growth factor beta, bone morphogenetic protein, fibroblast growth factor and other signaling pathways. Reactivation of HNF3alpha (FOXA1) transcription factor, a driver of hepatic specification in the primitive endoderm, indicated that the meso-endodermal phenotype represented an earlier developmental stage of cells. We found that fetal liver epithelial cells formed mature hepatocytes in vivo, including after genetic manipulation using lentiviral vectors, offering convenient assays for analysis of further cell differentiation and fate. Taken together, these studies demonstrate plasticity in fetal liver epithelial stem cells, offer paradigms for defining mechanisms regulating lineage switching in stem cells, and provide potential avenues for regulating cell phenotypes for applications of stem cells, such as for cell therapy.


Position paper: sonic and ultrasonic scalers in periodontics. Research, Science and Therapy Committee of the American Academy of Periodontology.
Ultrasonic and sonic scalers appear to attain similar results as hand instruments for removing plaque, calculus, and endotoxin. Ultrasonic scalers used at medium power seem to produce less root surface damage than hand or sonic scalers. Due to instrument width, furcations may be more accessible using ultrasonic or sonic scalers than manual scalers. It is not clear whether root surface roughness is more or less pronounced following power-driven scalers or manual scalers. It is also unclear if root surface roughness affects long-term wound healing. Periodontal scaling and root planing includes thorough calculus removal, but complete cementum removal should not be a goal of periodontal therapy. Studies have established that endotoxin is weakly adsorbed to the root surface, and can be easily removed with light, overlapping strokes with an ultrasonic scaler. A significant disadvantage of power-driven scalers is the production of contaminated aerosols. Because ultrasonics and sonics produce aerosols, additional care is required to achieve and maintain good infection control when incorporating these instrumentation techniques into dental practice. Preliminary evidence suggests that the addition of certain antimicrobials to the lavage during ultrasonic instrumentation may be of minimal clinical benefit. However, more randomized controlled clinical trials need to be conducted over longer periods of time to better understand the long-term benefits of ultrasonic and sonic debridement.


The 2-deoxy-D-glucose-neutral red test and vagotomy: an experimental study.
The 2-deoxy-D-glucose - neutral red test proved to be successful in assessing completeness of vagotomy in the baboon both intra- and postoperatively. There were no deleterious side-effects and we found that both products could be sterilized adequately. So far we have used this test of 5 patients in the immediate postoperative phase; in 1 patients, on whom the surgeon thought he had done an incomplete parietal cell vagotomy, the test was found to be positive within a week of the operation.


Using a storyboarding technique in the classroom to address end of life experiences in practice and engage student nurses in deeper reflection.
This paper evaluates the use of storyboarding within a classroom setting as a means of addressing end of life issues and engaging second year student nurses in creative, critical thinking and deeper reflection on practice. Storyboarding is a process that was developed to encourage learners to use the creative right brain and the critical left brain to formulate ideas in front of a group and then to look at those ideas critically (Lottier, 1986). The session was evaluated using a questionnaire and group discussion to elicit perceived learning from students. The activity was to create the storyboards in small groups, then review the content generated by discussion with the whole group. Main themes identified by the students included breaking bad news, dealing with cardiac arrest situation, coping with families following bereavement and the dying patient. Evaluation of the teaching session suggested that students found storyboarding helped to identify cultural aspects and feelings related to the dying patient. Students valued sharing with each other and the opportunity to have their experiences heard. It was noted that although this method provided as valuable learning experience for the student it is staff and time intensive and attention is required to establish a climate of trust and safety. The risk of exposing unexpected emotions within individual students appears no greater than with other approaches to teaching about loss, death and dying.


High-power very large mode-area thulium-doped fiber laser.
Large-pitch photonic-crystal fibers have demonstrated their unique capability of combining very large mode areas, high output powers and robust single-mode operation at a wavelength of 1 μm. In this Letter, we present the experimental realization of thulium-doped very large mode-area fibers based on the large-pitch fibers with record mode-field diameters exceeding 60 μm and delivering more than 52 W of output power.


Glucose 6 Phosphate Dehydrogenase (G6PD) quantitation using biosensors at the point of first contact: a mixed method study in Cambodia.
Quantitative measurement of Glucose-6-Phosphate Dehydrogenase (G6PD) enzyme activity is critical to decide on appropriate treatment and provision of radical cure regimens for vivax malaria. Biosensors are point-of-care semi-quantitative analysers that measure G6PD enzyme activity. The main objective of this study was to evaluate the operational aspects of biosensor deployment in the hands of village malaria workers (VMWs) in Cambodia over a year. Following initial orientation and training at Kravanh Referral Hospital, each VMW (n = 28) and laboratory technician (n = 5) was provided a biosensor (STANDARD SD Biosensor, Republic of Korea) with supplies for routine use. Over the next 12 months VMWs convened every month for refresher training, to collect supplies, and to recalibrate and test their biosensors. A quantitative self-administered questionnaire was used to assess the skills necessary to use the biosensor after the initial training. Subsequently, VMWs were visited at their location of work for field observation and evaluation using an observer-administered questionnaire. All quantitative questionnaire-based data were analysed descriptively. Semi-structured interviews (SSIs) were conducted among all participants to explore their experience and practicalities of using the biosensor in the field. SSIs were transcribed and translated into English and underwent thematic analysis. A total of 33 participants completed the training and subsequently used the biosensor in the community. Quantitative assessments demonstrated progressive improvement in skills using the biosensor. VMWs expressed confidence and enthusiasm to use biosensors in their routine work. Providing G6PD testing at the point of first contact avoids a multitude of barriers patients have to overcome when travelling to health centres for G6PD testing and radical cure. Deploying biosensors in routine work of VMWs was also considered an opportunity to expand and strengthen the role of VMWs as health care providers in the community. VMWs reported practical concerns related to the use of biosensor such as difficulty in using two pipettes, difficulty in extracting the code chip from the machine, and the narrow base of buffer tube. VMWs considered the biosensor a practical and beneficial tool in their routine work. Providing VMWs with biosensors can be considered when followed by appropriate training and regular supervision. Providing community management of vivax malaria at the point of first contact could be key for elimination.


Determination of geometrical and viscoelastic properties of PLA/PHB samples made by additive manufacturing for urethral substitution.
Additive manufacturing has a great potential for creating hard tissue substitutes, such as bone and cartilage, or soft tissues, such as vascular and skin grafts. This study is a pilot study for 3D printing of a new material mixture potentially used as a tubular substitute for urethra replacement. This new mixture is a blend of polylactic acid (PLA) and polyhydroxybutyrate (PHB). The basic aspect that affects the 3D printing process is correct material preparation and setting of 3D printer parameters. Selection of material and printing parameters depend on printing technology. The printing technology affects material behavior during printing process. The goal of preprocessing and 3D printing process is to provide stabile conditions during manufacturing to obtain usable printed samples. The study deals with preparation of material before 3D printing - material drying. Moisture in material affects material degradation and viscosity during printing. According to this, it is necessary to verify recommended drying parameters. Verification was performed by printing strand samples from dried and non-dried material and also by calculating and comparing respective viscosities that change in time. Printed strand clearly show that non-dried material degrades in less than 10 min, what leads to inappropriate application in short-time printing. Dried material shows significant stability and degrades slightly during selected time span. For metrological verification of material stability two sample types were designed and manufactured - a cubic sample which represents basic scaffold structures and a tubular one that serves as urethra substitution. Obtained results showed appropriate usability of selected technology and printing parameters for PLA / PHB material blend.


Predictive Integration of Gene Ontology-Driven Similarity and Functional Interactions.
There is a need to develop methods to automatically incorporate prior knowledge to support the prediction and validation of novel functional associations. One such important source is represented by the Gene Ontology (GO)™ and the many model organism databases of gene products annotated to the GO. We investigated quantitative relationships between the GO-driven similarity of genes and their functional interactions by analyzing different types of associations in Saccharomyces cerevisiae and Caenorhabditis elegans. Interacting genes exhibited significantly higher levels of GO-driven similarity (GOS) in comparison to random pairs of genes used as a surrogate for negative interactions. The Biological Process hierarchy provides more reliable results for co-regulatory and protein-protein interactions. GOS represent a relevant resource to support prediction of functional networks in combination with other resources.


Evaluation of the Implementation of Family Life and HIV Education Programme in Nigeria.
Family Life and HIV Education (FLHE) programme was introduced nationwide in Nigeria in 2003. Since then little is known about the patterns of its implementation across the states in the six geo-political zones in Nigeria. This study represents an attempt to fill this lacuna in the FLHE literature in Nigeria. Quantitative data was collected from the Federal Ministry of Education and the State Ministries of Education on all salient aspects of FLHE implementation. The findings from data collected in 35 states and the Abuja Federal Capital Territory show large variations in the year of adoption of the programme, level of implementation of the programme, the proportion of implementing schools that are reporting to the coordinating government ministries/agencies, the level to which schools have been supplied with relevant curriculum, and promptness of distribution of materials across the zones. All these indices did not show significant level of interdependence. In general, there were higher levels of FLHE activities in the South than the North. Several problems affect implementation of FLHE in Nigeria, most of which will require increased financial and technical support from government and other organizations. The FLHE programme has had positive effects in the states and among schools where the implementation has been effective, underscoring the need for a more effective implementation of the programmes throughout the country.


Ethanol-induced oxidant stress modulates hepatic autophagy and proteasome activity.
In this review, we describe research findings on the effects of alcohol exposure on two major catabolic systems in liver cells: the ubiquitin-proteasome system (UPS) and autophagy. These hydrolytic systems are not unique to liver cells; they exist in all eukaryotic tissues and cells. However, because the liver is the principal site of ethanol metabolism, it sustains the greatest damage from heavy drinking. Thus, the focus of this review is to specifically describe how ethanol oxidation modulates the activities of the UPS and autophagy and the mechanisms by which these changes contribute to the pathogenesis of alcohol-induced liver injury. Here, we describe the history and the importance of cellular hydrolytic systems, followed by a description of each catabolic pathway and the differential modulation of each by ethanol exposure. Overall, the evidence for an involvement of these catabolic systems in the pathogenesis of alcoholic liver disease is quite strong. It underscores their importance, not only as effective means of cellular recycling and eventual energy generation, but also as essential components of cellular defense.


Elucidating the role of ferrous ion cocatalyst in enhancing dilute acid pretreatment of lignocellulosic biomass.
Recently developed iron cocatalyst enhancement of dilute acid pretreatment of biomass is a promising approach for enhancing sugar release from recalcitrant lignocellulosic biomass. However, very little is known about the underlying mechanisms of this enhancement. In the current study, our aim was to identify several essential factors that contribute to ferrous ion-enhanced efficiency during dilute acid pretreatment of biomass and to initiate the investigation of the mechanisms that result in this enhancement. During dilute acid and ferrous ion cocatalyst pretreatments, we observed concomitant increases in solubilized sugars in the hydrolysate and reducing sugars in the (insoluble) biomass residues. We also observed enhancements in sugar release during subsequent enzymatic saccharification of iron cocatalyst-pretreated biomass. Fourier transform Raman spectroscopy showed that major peaks representing the C-O-C and C-H bonds in cellulose are significantly attenuated by iron cocatalyst pretreatment. Imaging using Prussian blue staining indicated that Fe2+ ions associate with both cellulose/xylan and lignin in untreated as well as dilute acid/Fe2+ ion-pretreated corn stover samples. Analyses by scanning electron microscopy and transmission electron microscopy revealed structural details of biomass after dilute acid/Fe2+ ion pretreatment, in which delamination and fibrillation of the cell wall were observed. By using this multimodal approach, we have revealed that (1) acid-ferrous ion-assisted pretreatment increases solubilization and enzymatic digestion of both cellulose and xylan to monomers and (2) this pretreatment likely targets multiple chemistries in plant cell wall polymer networks, including those represented by the C-O-C and C-H bonds in cellulose.


Optimal (2)H rf Pulses and (2)H-(13)C Cross-Polarization Methods for Solid-State (2)H MAS NMR of Perdeuterated Proteins.
We present a novel concept for rf pulses and optimal control designed cross-polarization experiments for quadrupolar nuclei. The methods are demonstrated for (2)H CP-MAS and (2)H multiple-pulse NMR of perdeuterated proteins, for which sensitivity enhancements up to an order of magnitude are presented relative to commonly used approaches. The so-called RESPIRATION rf pulses combines the concept of short broad-band pulses with generation of pulses with large flip angles through distribution of the rf pulse over several rotor echoes. This lead to close-to-ideal rf pulses, facilitating implementation of experiments relying on the ability to realize high-performance 90 and 180° pulses, as, for example, in refocused INEPT and double-to-single quantum coherence experiments, or just pulses that provide a true representation of the quadrupolar powder pattern to extract information about the structure or dynamics. The optimal control (2)H → (13)C CP-MAS method demonstrates transfer efficiencies up to around 85% while being extremely robust toward rf inhomogeneity and resonance offsets.


Identifying Inhibitors of Inflammation: A Novel High-Throughput MALDI-TOF Screening Assay for Salt-Inducible Kinases (SIKs).
Matrix-assisted laser desorption/ionization time-of-flight (MALDI TOF) mass spectrometry has become a promising alternative for high-throughput drug discovery as new instruments offer high speed, flexibility and sensitivity, and the ability to measure physiological substrates label free. Here we developed and applied high-throughput MALDI TOF mass spectrometry to identify inhibitors of the salt-inducible kinase (SIK) family, which are interesting drug targets in the field of inflammatory disease as they control production of the anti-inflammatory cytokine interleukin-10 (IL-10) in macrophages. Using peptide substrates in in vitro kinase assays, we can show that hit identification of the MALDI TOF kinase assay correlates with indirect ADP-Hunter kinase assays. Moreover, we can show that both techniques generate comparable IC50 data for a number of hit compounds and known inhibitors of SIK kinases. We further take these inhibitors to a fluorescence-based cellular assay using the SIK activity-dependent translocation of CRTC3 into the nucleus, thereby providing a complete assay pipeline for the identification of SIK kinase inhibitors in vitro and in cells. Our data demonstrate that MALDI TOF mass spectrometry is fully applicable to high-throughput kinase screening, providing label-free data comparable to that of current high-throughput fluorescence assays.


Vascular endothelium-leukocyte interaction; sticking shear force in venules.
To determine the shear force acting on a white blood cell sticking to the endothelium of a blood vessel, the flow field about a single white blood cell in a venule was determined by hign-speed motion picture photomicrography. The force acting on the white blood cell was then calculated according to the principles of fluid mechanics. In this paper, the calculation was made using an experimentally determined dimensionless shear force coefficient obtained from a kinematically and dynamically similar model. The large physical model of the hemodynamic system could be easily instrumented, and the shear force acting on the model cell and the flow field around it were measured. The data were then used to calculate a shear force coefficient. On the basis of dynamic similarity, this shear force coefficient was applied to the white blood cell in the venule. The shear force coefficient was strongly influenced by the hematocrit, so in vivo hematocrits were measured from electron micrographs. It was found that in the venules of the rabbit omentum a white blood cell sticking to the endothelial wall was subjected to a shear force in the range of 4 times 10--5 dynes to 234 times 10--5 dynes; the exact value depended on the size and motion of the white blood cell, the size of the blood vessel, the velocity of the blood flow, and the local hematocrit, which varied between 20% and 40% in venules of about 40 mum in diameter. The contact area between the white blood cell and the endothelial cell was estimated, and the shear stress was found to range between 50 dynes/cm-2 and 1060 dynes/cm-2. The normal stress of interaction between the white blood cell and the endothelium had a maximum value that was of the same order of magnitude as the shear stress. The accumulated relative error of the experimental procedure was about 49%. The instantaneous shear force was a random function of time because of random fluctuations of the hematocrit.


Why are people without medical needs transported by ambulance? A study of indications for pre-hospital care.
The purpose of this report was to describe the characteristics of patients transported by ambulance, in spite of being evaluated by the ambulance staff at the scene as not requiring prehospital care. A second aim was to compare these patients with those judged as being in need of this care. Three ambulance service districts located in different rural and metropolitan geographical areas were included in the study and all three were covered by a single emergency dispatch centre. Following the dispatch of ambulances, the staff assessed and recorded the medical needs of the patients at the scene, according to a questionnaire developed for the study. In addition to the questionnaire, data were extracted from the ambulance medical records database for each patient. If the patients were just transported by ambulance without receiving any other prehospital intervention, they were assessed as not being in need of the emergency service. The evaluation included events at the scene and during transportation. The ambulance staff making the needs assessments were emergency medical technicians and registered nurses. In this report, 604 patients who did not require prehospital care are described and compared with the remaining group of patients who required this care (1373). For analysis, descriptive statistics were used to analyse the data. The ambulance staff assessed that, among patients reported by the emergency medical dispatch centre as having abdominal or urinary problems, 42% did not need the ambulance service. Even among intrahospital transports (patients for whom medical personnel made the request for an ambulance), 45% did not require ambulance transport, as judged by the ambulance staff. Among patients reported by the emergency medical dispatch centre as having chest pain or other heart symptoms or trauma/accidents, respectively, only small percentages (18%) and (17%) did not require the ambulance service, as assessed by the ambulance staff. Most of the patients without obvious medical needs had been allocated an ambulance response for nonurgent conditions, that is priority level 2 or 3, but patients without medical needs were even found at the highest priority level 1. Of the patients who did not require an ambulance, more than half (55%) would have been able to get to a hospital in their own car or by taxi, whereas the remainder of the patients needed a transport vehicle in which they could lie down, but which was not equipped and staffed like an ambulance. Among the patients transported by the emergency medical service system in the study areas, a significant percentage were judged by the ambulance staff as not being in need of prehospital interventions. The majority were transported by a fully equipped emergency medical ambulance to an emergency medical department at a hospital, without requiring any prehospital interventions either at the scene or during transportation. The emergency medical service organization has to develop clear criteria for the utilization of ambulance services that can be accepted and implemented by the dispatch centres and by healthcare personnel. These criteria need to include safety margins and at the same time enable the appropriate use of resources.


Effects of beta-blockade and exercise on cardiovascular and cognitive functioning.
Twenty-four men with mild essential hypertension were assigned randomly to receive propranolol (n = 9), atenolol (n = 7), or a placebo (n = 8). All subjects participated in a 12-week study and provided physiological and behavioral data four times during the study: after a medication-free baseline period (Session 1); after 2 weeks of medication, without exercise (Session 2); after 8 weeks of continued medication while participating in a program of aerobic exercise (Session 3); and after 2 weeks of maintenance exercise without medication (Session 4). Subjects' maximal oxygen uptake increased significantly between Sessions 2 and 3, and the magnitude of this increase did not vary across the drug groups. Subjects' resting heart rates varied as a function of the presence of beta-blocking medication, but there was in addition a reduction attributable to exercise training that did not vary across the drug groups. The decrease in blood pressure associated with beta-blockade (Session 2) was not decreased any further by exercise training (Session 3). Despite an increase in blood pressure following the withdrawal of active medication (Session 4), blood pressure remained significantly lower compared with the Session 1 baseline level. Performance in a reaction-time test of short-term memory functioning improved slightly for all three groups between Sessions 1 and 2 and remained constant thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)


A population genetics perspective of the Indus Valley through uniparentally-inherited markers.
Analysis of mtDNA and Y-chromosome variation in the Indo-Gangetic plains shows that it was a region where genetic components of different geographical origins (from west, east and south) met. The genetic architecture of the populations now living in the area comprise genetic components dating back to different time-periods during the Palaeolithic and the Neolithic. mtDNA data analysis has demonstrated a number of deep-rooting lineages of Pleistocene origin that may be witness to the arrival of the first settlers of South and Southwest Asia after humans left Africa around 60,000 YBP. In addition, comparisons of Y-chromosome and mtDNA data have indicated a number of recent and sexually asymmetrical demographic events, such as the migrations of the Parsis from Iran to India, and the maternal traces of the East African slave trade.


Inclusion of young people with disabilities in the future of work: forecasting workplace, labour market and community-based strategies through an online and accessible Delphi survey protocol.
The future of work is expected to transform the nature of work, create unique employment barriers for young people living with disabilities and disrupt pathways to better health. We present a Delphi survey protocol through which we aim to obtain future-oriented strategies that can improve the accessibility and inclusion of young people with disabilities in the future of work. The Delphi survey will be conducted primarily online, over two rounds and in a format that is accessible to people living with disabilities. A diverse sample of subject matter experts (eg, policy makers, employment service providers, labour market experts) and participants with lived experience of a disability will be recruited using a purposive sampling strategy. All participants will be asked to complete both rounds of the Delphi survey. In the first round, open-ended questions will be asked about workplace, community-based or policy supports that can foster the inclusion of young people with disabilities in the labour market and that can also address specific future of work trends which span sociopolitical, economic, environmental and technological domains. In the second round of the survey, we will aim to build consensus; participants will be provided with a summary of specific strategies that correspond to the different future of work trends emerging from round one and will be asked to rank-order strategies according to their importance. Following the completion of the second round, consensus-based and future-focused recommendations will be generated that can support young people with disabilities in the world of work over the coming decades. The study protocol has been cleared by the University of Toronto's research ethics board (#40727). The study will identify future-focused support strategies that will be shared with people living with disabilities, policy makers and disability employment service providers through an integrated knowledge transfer and exchange approach.


Intraspinal Pressure Monitoring in a Patient with Spinal Cord Injury Reveals Different Intradural Compartments: Injured Spinal Cord Pressure Evaluation (ISCoPE) Study.
We recently described a technique for monitoring intraspinal pressure (ISP) after traumatic spinal cord injury (TSCI). This is analogous to intracranial pressure monitoring after brain injury. We showed that, after severe TSCI, ISP at the injury site is elevated as the swollen cord is compressed against the dura. In a patient with complete thoracic TSCI, we sequentially monitored subdural ISP above the injury, at the injury site, and below the injury intraoperatively. Postoperatively, we simultaneously monitored subdural ISP and intraparenchymal ISP at the injury site and compared the two ISP signals as well as their Fast Fourier Transform spectra. Subdural ISP recorded from the injury site was higher than subdural ISP recorded from above or below the injury site by more than 10 mmHg. The subdural and intraparenchymal ISP signals recorded from the injury site had comparable amplitudes and Fast Fourier Transform spectra. Intraparenchymal pulse pressure was twofold larger than subdural pulse pressure. After severe TSCI, three intradural compartments form (space above injury, injury site, space below injury) with different ISPs. At the level of maximum spinal cord swelling (injury site), subdural ISP is comparable to intraparenchymal ISP.


Calcium/phosphate-induced immobilization of fluorescent phosphatidylserine in synthetic bilayer membranes: inhibition of lipid transfer between vesicles.
Resonance energy transfer between 4-nitro-2,1,3-benzoxadiazole (NBD) acyl chain labeled phospholipid analogues and (lissamine) rhodamine B labeled phosphatidylethanolamine was used to monitor the rate of NBD-labeled lipid transfer between a variety of small unilamellar donor vesicles and dioleoylphosphatidylcholine (DOPC) acceptor vesicles. In the presence of appropriate concentrations of Ca2+ and phosphate, the transfer rate of NBD-phosphatidylserine (NBD-PS) from vesicles composed of lipid extracts from human red blood cells was reduced by approximately 10-fold, while the transfer rates of NBD-phosphatidylcholine, -ethanolamine, -glycerol, -N-succinylethanolamine, and -phosphatidic acid were essentially unaffected. A systematic evaluation of the lipid composition needed to facilitate the Ca2+/phosphate-induced inhibition of NBD-PS transfer revealed that the process was dependent upon the inclusion of both cholesterol and phosphatidylethanolamine (PE) in the donor vesicle population. Inhibition of NBD-PS transfer required the sequential addition of phosphate and Ca2+ to the vesicles, indicating that the combined interaction of Ca2+ and phosphate at the membrane surface was a prerequisite for inhibition to occur. Parallel experiments designed to determine the possible mechanism of this phenomenon showed that inhibition of NBD-PS transfer was not due to Ca2+-mediated phase separations or vesicle-vesicle fusion. However, the addition of Ca2+ and phosphate to vesicles composed of total red blood cell lipids or cholesterol/PE did result in their aggregation. On the other hand, aggregation per se did not seem to be responsible for the inhibition of transfer since NBD-PS-containing vesicles composed of DOPC or DOPC/DOPE also aggregated, although NBD-PS transfer was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)


Monitoring N719 dye configurations on (1 x n)-reconstructed anatase (100) by means of STM: reversible configurational changes upon illumination.
We report experimental results concerning the STM imaging of cis-bis (isothiocyanate)-bis-(2,2'-bipyridyl-4,4'dicarboxylate)ruthenium(II)bis(tetrabutylammonium) dye (known as N719) adsorbed on a single crystal of anatase TiO(2)(100). The cleaning pretreatment, by sputtering and annealing, of TiO(2)(100) yields a reproducible (1 x n) surface reconstruction. Previous to dye deposition, TiO(2) was covered with one monolayer of 4-tert-butylpyridine (4-TBP) in ultrahigh vacuum (UHV) in order to protect the surface against air contamination. N719 was subsequently deposited by dipping the crystal into the dye solution. 4-TBP was removed partially in the solution and totally by heating the sample to around 285-300 degrees C in UHV. The images of the deposited 4-TBP on TiO(2)(100) revealed a complete surface coverage showing three modes of adsorption on TiO(2). The relatively uncomplicated desorption of 4-TBP enables the accommodation and chemisorption of most N719 molecules directly onto the TiO(2) surface. The STM imaging of N719 was affected, in a reversible way, by illumination, because the quality of the image changed after a few hours in the dark or under illumination conditions. The results presented herein are discussed in terms of changes in molecular configurations and in open circuit potentials.


Obesity prevention at the point of purchase.
The point of purchase is when people may make poor and impulsive decisions about what and how much to buy and consume. Because point of purchase strategies frequently work through non-cognitive processes, people are often unable to recognize and resist them. Because people lack insight into how marketing practices interfere with their ability to routinely eat healthy, balanced diets, public health entities should protect consumers from potentially harmful point of purchase strategies. We describe four point of purchase policy options including standardized portion sizes; standards for meals that are sold as a bundle, e.g. 'combo meals'; placement and marketing restrictions on highly processed low-nutrient foods; and explicit warning labels. Adoption of such policies could contribute significantly to the prevention of obesity and diet-related chronic diseases. We also discuss how the policies could be implemented, along with who might favour or oppose them. Many of the policies can be implemented locally, while preserving consumer choice.


Single locus typing of MHC class I and class II B loci in a population of red jungle fowl.
In species with duplicated major histocompatibility complex (MHC) genes, estimates of genetic variation often rely on multilocus measures of diversity. It is possible that such measures might not always detect more detailed patterns of selection at individual loci. Here, we describe a method that allows us to investigate classical MHC diversity in red jungle fowl (Gallus gallus), the wild ancestor of the domestic chicken, using a single locus approach. This is possible due to the well-characterised gene organisation of the 'minimal essential' MHC (BF/BL region) of the domestic chicken, which comprises two differentially expressed duplicated class I (BF) and two class II B (BLB) genes. Using a combination of reference strand-mediated conformation analysis, cloning and sequencing, we identify nine BF and ten BLB alleles in a captive population of jungle fowl. We show that six BF and five BLB alleles are from the more highly expressed locus of each gene, BF2 and BLB2, respectively. An excess of non-synonymous substitutions across the jungle fowl BF/BL region suggests that diversifying selection has acted on this population. Importantly, single locus screening reveals that the strength of selection is greatest on the highly expressed BF2 locus. This is the first time that a population of red jungle fowl has been typed at the MHC region, laying the basis for further research into the underlying processes acting to maintain MHC diversity in this and other species.


Non-Hodgkin's lymphomas with primary localization in large bowel and rectum.
From 1989, at the Department of Medical Oncology of the Institute for Oncology and Radiology in Belgrade, seven patients with primary NHL of large bowel and rectum have been observed and treated, 3 males and 4 females. In 3 patients an urgent laparotomy without previous diagnostic procedures was performed, while 4 patients had laparotomy only after radiographic and endoscopic diagnosis of a tumor. Six patients had radical surgery and 1 palliative only. Five patients had lymphoma localized in cecoascedental part of colon (2 centroblastic, 1 lymphoplasmocytic, 1 Burkitt and 1 Burkitt's like), 1 patient had it in the transversal part of colon (centroblastic), and one in the rectum (diffuse centrocytic). By further investigation, in 2 cases with localization within transversal part of colon and rectum no other sites of NHL were found. They are under regular controls with 45+ and 45+ months disease free survival. Out of 5 patients with localization within cecum or ascendent part of colon, in 2 cases with Burkitt/Burkitt-like histology retroperitoneal lymphadenopathy were found, one female had NHL central propagation, and the other one lymphoma generalization. Both patients had early death from lymphoma. The remaining three patients following chemotherapy with the ProMACE regimen (as they too had a post laparotomy stage II disease) achieved a complete response lasting for 36+, 41+ and 66+ months. Since the median survival in our group of patients is at the moment 41+ months and the median has not yet been reached, our experience does not confirm literature data claiming bad prognosis of primary NHL of the colon and rectum. A long disease free survival can be obtained in these patients either with surgery only or surgery + chemotherapy, depending on disease stage and possibly initial topographic localization.


Cross-Over Study Comparing Postprandial Glycemic Increase After Addition of a Fixed-Dose Mitiglinide/Voglibose Combination or a Dipeptidyl Peptidase-4 Inhibitor to Basal Insulin Therapy in Patients with Type 2 Diabetes Mellitus.
BACKGROUND Although the efficacy of combination therapy consisting of basal insulin and oral hypoglycemic agents (OHAs) has been shown, which OHAs are the most efficient remains unclear. MATERIAL AND METHODS Five patients with type 2 diabetes were enrolled and treated with insulin degludec and metformin as a basal therapy. The patients were randomized in a cross-over fashion to receive a combination of mitiglinide (10 mg) and voglibose (0.2 mg) (M+V) 3 times daily or linagliptin (5 mg) (L) once daily for 8 weeks. After 8 weeks, 2 kinds of meal tolerance tests were performed as breakfast on 2 consecutive days. The first breakfast contained 460 kcal (carbohydrates, 49.1%; protein, 15.7%; fat, 35.2%), while the second contained 462 kcal (carbohydrates, 37.2%; protein, 19.6%; fat, 43.2%). Self-monitoring blood glucose levels were measured at 0, 30, 60, and 120 min after the meal tests, and the increase in the postprandial area under the curve (AUC)0-120 min was determined. The HbA1c, glycated albumin, and 1,5-anhydroglucitol (AG) levels were measured, and continuous glucose monitoring was performed. RESULTS The increase in the postprandial AUC0-120 min was significantly smaller in the M+V group than in the L group after both meals. The 24-h average, 24-h standard deviations, 24-h AUC, and mean amplitude of glycemic excursion (MAGE) were similar for both groups and after both meals. The change in 1,5-AG was higher in the M+V group than in the L group. CONCLUSIONS The combination of M+V with basal therapy improved postprandial glucose excursion more effectively than L in T2DM patients.


Extended- Versus Narrower-Spectrum Antibiotics for Appendicitis.
Appendicitis guidelines recommend either narrower- or extended-spectrum antibiotics for treatment of complicated appendicitis. The goal of this study was to compare the effectiveness of extended-spectrum versus narrower-spectrum antibiotics for children with appendicitis. We performed a retrospective cohort study of children aged 3 to 18 years discharged between 2011 and 2013 from 23 freestanding children's hospitals with an appendicitis diagnosis and appendectomy performed. Subjects were classified as having complicated appendicitis if they had a postoperative length of stay ≥3 days, a central venous catheter placed, major or severe illness classification, or ICU admission. The exposure of interest was receipt of systemic extended-spectrum antibiotics (piperacillin ± tazobactam, ticarcillin ± clavulanate, ceftazidime, cefepime, or a carbapenem) on the day of appendectomy or the day after. The primary outcome was 30-day readmission for wound infection or repeat abdominal surgery. Multivariable logistic regression, propensity score weighting, and subgroup analyses were used to control for confounding by indication. Of 24 984 patients, 17 654 (70.7%) had uncomplicated appendicitis and 7330 (29.3%) had complicated appendicitis. Overall, 664 (2.7%) patients experienced the primary outcome, 1.1% among uncomplicated cases and 6.4% among complicated cases (P < .001). Extended-spectrum antibiotic exposure was significantly associated with the primary outcome in complicated (adjusted odds ratio, 1.43 [95% confidence interval, 1.06 to 1.93]), but not uncomplicated, (adjusted odds ratio, 1.32 [95% confidence interval, 0.88 to 1.98]) appendicitis. These odds ratios remained consistent across additional analyses. Extended-spectrum antibiotics seem to offer no advantage over narrower-spectrum agents for children with surgically managed acute uncomplicated or complicated appendicitis.


Migraines and meditation: does spirituality matter?
Migraine headaches are associated with symptoms of depression and anxiety (Waldie and Poulton Journal of Neurology, Neurosurgery, and Psychiatry 72: 86-92, 2002) and feelings of low self-efficacy (French et al. Headache, 40: 647-656, 2000). Previous research suggests that spiritual meditation may ameliorate some of the negative traits associated with migraine headaches (Wachholtz and Pargament Journal of behavioral Medicine, 30: 311-318, 2005). This study examined two primary questions: (1) Is spiritual meditation more effective in enhancing pain tolerance and reducing migraine headache related symptoms than secular meditation and relaxation? and, (2) Does spiritual meditation create better mental, physical, and spiritual health outcomes than secular meditation and relaxation techniques? Eighty-three meditation naïve, frequent migraineurs were taught Spiritual Meditation, Internally Focused Secular Meditation, Externally Focused Secular Meditation, or Muscle Relaxation which participants practiced for 20 min a day for one month. Pre-post tests measured pain tolerance (with a cold pressor task), headache frequency, and mental and spiritual health variables. Compared to the other three groups, those who practiced spiritual meditation had greater decreases in the frequency of migraine headaches, anxiety, and negative affect, as well as greater increases in pain tolerance, headache-related self-efficacy, daily spiritual experiences, and existential well being.


Increased expression of transcription factor EB (TFEB) is associated with autophagy, migratory phenotype and poor prognosis in non-small cell lung cancer.
We investigated the role of lysosomal biogenesis and hydrolase activity in the clinical behavior and postoperative outcome of lung cancer. Using immunohistochemistry we investigated the expression of the transcription factor EB (TFEB) which orchestrates lysosomal biogenesis, the lysosome membrane protein LAMP2a and of the lysosomal hydrolase cathepsin D in a series of 98 non-small cell lung carcinomas (NSCLC) treated with surgery alone. In vitro experiments with the A549 and H1299 lung cancer cell lines were also performed. Overexpression of TFEB, LAMP2a and Cathepsin D was noted in 47/98 (47.9%), 43/98 (43.9%) and 39/98 (39.8%) cases, respectively, and were significantly correlated with each other and with adenocarcinomas. High LAMP2a was related to high histology grade. Linear regression analysis confirmed significant association of TFEB with BNIP3 (p=0.0003, r=0.35) and LC3A with LAMP2a expression (p=0.0002, r=0.37). An inverse association of Cathepsin D expression with stone-like structures (SLS) was recorded (p=0.02, r=0.22). On univariate analysis all three lyososomal variables were associated with poor prognosis (p=0.05, 0.04 and 0.01, for TFEB, Cathepsin D and LAMP2a, respectively). Multivariate analysis showed that the SLS number (p=0.0001, HR5.37), Cathepsin D expression (p=0.01, HR=2.2) and stage (p=0.01, HR=1.5) were independent prognostic variables. Silencing of TFEB with siRNAs in the A549 and H1299 lung cancer cell lines did not affect proliferation but resulted in reduced migration ability. Lysosomal biogenesis is linked to autophagosomal protein expression in NSCLC and characterizes subgroups of high risk patients after complete surgical lung tumor resection.


A genome-wide association and admixture mapping study of bronchodilator drug response in African Americans with asthma.
Short-acting β2-adrenergic receptor agonists (SABAs) are the most commonly prescribed asthma medications worldwide. Response to SABAs is measured as bronchodilator drug response (BDR), which varies among racial/ethnic groups in the United States. However, the genetic variation that contributes to BDR is largely undefined in African Americans with asthma. To identify genetic variants that may contribute to differences in BDR in African Americans with asthma, we performed a genome-wide association study (GWAS) of BDR in 949 African-American children with asthma, genotyped with the Axiom World Array 4 (Affymetrix, Santa Clara, CA) followed by imputation using 1000 Genomes phase III genotypes. We used linear regression models adjusting for age, sex, body mass index (BMI) and genetic ancestry to test for an association between BDR and genotype at single-nucleotide polymorphisms (SNPs). To increase power and distinguish between shared vs. population-specific associations with BDR in children with asthma, we performed a meta-analysis across 949 African Americans and 1830 Latinos (total = 2779). Finally, we performed genome-wide admixture mapping to identify regions whereby local African or European ancestry is associated with BDR in African Americans. We identified a population-specific association with an intergenic SNP on chromosome 9q21 that was significantly associated with BDR (rs73650726, p = 7.69 × 10-9). A trans-ethnic meta-analysis across African Americans and Latinos identified three additional SNPs within the intron of PRKG1 that were significantly associated with BDR (rs7903366, rs7070958 and rs7081864, p ≤ 5 × 10-8). Our results failed to replicate in three additional populations of 416 Latinos and 1615 African Americans. Our findings indicate that both population-specific and shared genetic variation contributes to differences in BDR in minority children with asthma, and that the genetic underpinnings of BDR may differ between racial/ethnic groups.


Pharmaceutical prices, quantities and innovation. Comparing Japan with the US.
Per capita expenditure on pharmaceuticals is higher in Japan than in the US, despite a series of drug price reductions instigated by the Japanese Ministry of Health and Welfare that began in 1981. For some individual products, these price reductions cumulatively totalled more than 50%. This article argues that although the price of individual drugs is lower in Japan than in the US, aggregate expenditure is higher because of the greater use of newly-introduced original drugs and lower use of generics. Providers and consumers also tend to use drugs in larger quantities in Japan, because of polypharmacy and greater use of vitamins and nutrients, antihypertensives, cerebral metabolic activators (e.g. idebenone) and milder-acting drugs (i.e. drugs with low toxicity but unproven clinical efficacy). The level of expenditure is unlikely to decline, despite changes to pricing policy and ongoing efforts to improve the pharmaceutical distribution system and to discourage physician dispensing activities.


Clinical Significance of Age at the Time of Diagnosis among Young Breast Cancer Patients.
The aims of this study were to investigate outcomes corresponding to age at diagnosis as categorized into 5-year intervals and to explore whether endocrine-responsive tumors display clinical benefits from endocrine therapy after chemotherapy among young breast cancer patients. A total of 1,171 patients who were under 40 years old at diagnosis between 1985 and 2007 were divided into 3 subgroups: ≤30 years (Group I, 13.3%), 31-35 years (Group II, 30.5%), and 36-40 years (Control group, 56.2%). Clinicopathological factors and outcomes were compared using a chi-square test, the Kaplan-Meier method, and Cox's hazards models. There were no significant differences in the characteristics and treatment patterns between the 3 groups, except for the grade, hormone receptors expression, and use of endocrine therap. Group I showed the worst survival and subsequently Group II presented worse outcomes than the Control group, mainly among hormone receptors-positive patients. Groups I and II showed increased risks of recurrence and death in multivariate analyses. Among 529 hormone receptors-positive patients who received chemotherapy, favorable outcomes for patients who were treated with endocrine agents were demonstrated, mainly in patients aged 35 years or less. However, interaction tests between the use of endocrine therapy and age at diagnosis were not significant. Age at diagnosis is an independent prognostic factor and the age of 35 years is a rational cut-off among young patients. Our subgroup analysis suggests that endocrine therapy may provide additional benefits even in young breast cancers. Therefore, further researches should be directed towards improving outcomes for this population.


Stimulant use disorders in people with psychosis: a meta-analysis of rate and factors affecting variation.
Stimulant abuse and dependence often complicate the care of people with psychotic disorders. This study systematically reviews the prevalence estimates reported for stimulant abuse and dependence in people with psychotic disorders, and examines personal, clinical, regional and methodological factors which explain variation in these rates. PsychINFO, EMBASE and MEDLINE (1946-2013) were searched systematically for studies reporting on stimulant drug use disorders in representative samples of people with psychotic disorders. Random effects models estimated the pooled rate of a stimulant use disorder, defined to include stimulant abuse and stimulant dependence. Study characteristics associated with heterogeneity in rates of stimulant use disorder were examined by subgroup analyses for categorical variables, by meta-regression for continuous independent variables and by multiple meta-regression. Sixty-four studies provided 68 estimates of lifetime or recent stimulant use disorders in 22,500 people with psychosis. The pooled rate of stimulant use disorder was 8.9% (95% CI 7.4%, 10.5%). Higher rates of stimulant use disorders were reported in studies of affective psychosis, studies from inpatient settings, studies from the USA and Australia, and studies with higher rates of cannabis disorder; in multiple meta-regression analysis these factors explained 68% of between-study variance. Rates of stimulant use disorder were stable over time, and unrelated to age, sex, stage of psychosis, type of stimulant drug or study methodology factors. Reported rates of stimulant use disorder in people with psychosis are much higher than in the general population but vary widely and are associated with regional, service setting and clinical differences between studies. It is likely that stimulants contribute to the overall burden of psychosis, and that social and environmental factors combine with drug and illness-related factors to influence stimulant use in psychosis.


Characterizing the Cellular Immune Response to Parainfluenza Virus 3.
Parainfluenza virus type 3 (PIV3) infections are a major cause of morbidity and mortality in immunocompromised individuals, with no approved therapies. Our group has demonstrated the safety and efficacy of adoptively transferred virus-specific T cells for the prevention and treatment of a broad range of viral infections including BK virus, cytomegalovirus, adenovirus, human herpesvirus 6, and Epstein-Barr virus. However, this approach is restricted to well-characterized viruses with known immunogenic/protective T-cell target antigens, precluding extension to PIV3. We now characterize the cellular immune response to all 7 PIV3-encoded antigens in 17 healthy donors and define a hierarchy of immunogenicity based on the frequency of responding donors and the magnitude of specific cells. We show that reactive populations of both CD4+ and CD8+ T cells are capable of producing Th1-polarized effector cytokines and killing PIV3-expressing targets. Furthermore, we confirm the clinical relevance of these cells by demonstrating a direct correlation between the presence of PIV3-specific T cells and viral control in allogeneic hematopoietic stem cell transplant recipients. Taken together, our findings support the clinical use of PIV3-specific T cells produced with our Good Manufacturing Practice-compliant manufacturing process, in immunocompromised patients with uncontrolled infections.


The University Hospital Zurich Offers a Medical Online Consultation Service for Men With Intimate Health Problems.
The University Hospital of Zurich offers a text-based, Medical Online Consultation Service to the public since 1999. Users asked health questions anonymously to tele-doctors. This study focused on the characteristics of male enquirers with intimate health problems, the content of their questions, the medical advice given by tele-doctors and the rating of the service to prove the benefit of an online service for medical laymen. This retrospective study included 5.1% of 3,305 enquiries from 2008 to 2010 using the International Classification of Diseases-10 and International Classification of Primary Care codes relevant for intimate and sexual health problems in men. A professional text analysis program (MAXQDA) supported the content analysis, which is based on the procedure of inductive category development described by Mayring. The average age was 40 years, 63.1% enquirers had no comorbidity, in 62.5% it was the first time they consulted a doctor, and 70.2% asked for a specific, single, intimate health issue. In 64.3%, the most important organ of concern was the penis. Overall, 30.4% asked about sexually transmitted diseases. In 74.4% a doctor visit was recommended to clarify the health issue. The rating of the problem solving was very good. The service was mainly used by younger men without comorbidity and no previous contact with a doctor with regard to an intimate health problem. The anonymous setting of the teleconsultation provided men individual, professional medical advice and decision support. Teleconsultation is suggested to empower patients by developing more health literacy.


Multiple Testing under Dependence via Semiparametric Graphical Models.
It has been shown that graphical models can be used to leverage the dependence in large-scale multiple testing problems with significantly improved performance (Sun & Cai, 2009; Liu et al., 2012). These graphical models are fully parametric and require that we know the parameterization of f1 - the density function of the test statistic under the alternative hypothesis. However in practice, f1 is often heterogeneous, and cannot be estimated with a simple parametric distribution. We propose a novel semiparametric approach for multiple testing under dependence, which estimates f1 adaptively. This semiparametric approach exactly generalizes the local FDR procedure (Efron et al., 2001) and connects with the BH procedure (Benjamini & Hochberg, 1995). A variety of simulations show that our semiparametric approach outperforms classical procedures which assume independence and the parametric approaches which capture dependence.


Pastoral care use among post-9/11 veterans who screen positive for mental health problems.
As a result of their military experience, veterans with mental health problems may have unique motivations for seeking help from clergy. Patterns and correlates of seeking pastoral care were examined using a nationwide representative survey that was conducted among veterans of post-9/11 conflicts (adjusted N = 1,068; 56% response rate). Separate multivariate logistic regression models were used to examine veteran characteristics associated with seeking pastoral care and seeking mental health services. Among post-9/11 veterans with a probable mental disorder (n = 461)-defined as a positive screen for posttraumatic stress disorder, major depressive disorder, or alcohol misuse-20.2% reported talking to a "pastoral counselor" in the preceding year, 44.7% reported talking to a mental health professional, and 46.6% reported talking to neither. In a multivariate analysis for veterans with a probable mental disorder, seeing a pastoral counselor was associated with an increased likelihood of seeing a mental health professional in the past year (OR: 2.16; 95% CI: [1.28, 3.65]). In a separate bivariate analysis, pastoral counselors were more likely to be seen by veterans who indicated concerns about stigma or distrust of mental health care. These results suggest that pastoral and mental health care services may complement one another and underscore the importance of enhancing understanding and collaboration between these disciplines so as to meet the needs of the veterans they serve.


Expression of the prostate-specific antigen gene by a primary ovarian carcinoma.
We describe a patient with primary ovarian carcinoma that developed after liver transplantation whose tumor was highly positive for prostate-specific antigen (PSA). PSA in tumor tissue was characterized by two immunoassays, HPLC, immunohistochemistry, reverse transcription-PCR, Southern blotting, and DNA sequencing. PSA in the ovarian tumor was present as free, M(r) 33,000 protein (> 90%) and as PSA bound to alpha 1-antichymotrypsin (M(r) 100,000; < 10%). Immunohistochemistry localized PSA in the cytoplasm of epithelial cells of the tumor. Two separate reverse transcription-PCRs for PSA amplified the expected products which hybridized specifically to a PSA cDNA probe on Southern blots. Sequencing of the PCR products, representing the whole coding sequence of the PSA gene, revealed identity with the sequence of PSA cDNA from prostate tissue. These data suggest that the PSA produced by the ovarian tumor was identical in molecular weight and sequence to prostatic PSA. Based on data of tissue culture experiments with breast carcinoma cell lines, we speculate that the PSA gene in the tumor of this patient was up-regulated by the therapeutically administered glucocorticoids after liver transplantation.


1Alpha,25-(OH)2D3 acts in the early phase of osteoblast differentiation to enhance mineralization via accelerated production of mature matrix vesicles.
1Alpha,25-dihydroxyitamin D(3) (1,25D3) deficiency leads to impaired bone mineralization. We used the human pre-osteoblastic cell line SV-HFO, which forms within 19 days of culture an extracellular matrix that starts to mineralize around day 12, to examine the mechanism by which 1,25D3 regulates osteoblasts and directly stimulates mineralization. Time phase studies showed that 1,25D3 treatment prior to the onset of mineralization, rather than during mineralization led to accelerated and enhanced mineralization. This is supported by the observation of unaltered stimulation by 1,25D3 even when osteoblasts were devitalized just prior to onset of mineralization and after 1,25D3 treatment. Gene Chip expression profiling identified the pre-mineralization and mineralization phase as two strongly distinctive transcriptional periods with only 0.6% overlap of genes regulated by 1,25D3. In neither phase 1,25D3 significantly altered expression of extracellular matrix genes. 1,25D3 significantly accelerated the production of mature matrix vesicles (MVs) in the pre-mineralization. Duration rather than timing determined the extent of the 1,25D3 effect. We propose the concept that besides indirect effects via intestinal calcium uptake 1,25D3 directly accelerates osteoblast-mediated mineralization via increased production of mature MVs in the period prior to mineralization. The accelerated deposition of mature MVs leads to an earlier onset and higher rate of mineralization. These effects are independent of changes in extracellular matrix protein composition. These data on 1,25D3, mineralization, and MV biology add new insights into the role of 1,25D3 in bone metabolism and emphasize the importance of MVs in bone and maintaining bone health and strength by optimal mineralization status.


[Criteria for efficacy of anticoagulant therapy in patients with thromboses of deep veins of lower limbs].
The authors analysed the results of a prospective study of dynamics of laboratory indices of plasma haemostasis on the background of anticoagulant therapy in a total of 60 patients (23 women and 37 men) presenting with idiopathic thromboses of deep veins of lower limbs in order to work out criteria for its efficacy and safety. Anticoagulant therapy was carried out using nonfractionated heparin according to the standard regimens. The patients' mean age amounted to 57.4±13.6 years. Studying the system of haemostasis along with generally known standard laboratory indices (activated partial prothrombin time, D-dimer, fibrinogen, prothrombin level, INR, PTI) included one of the global coagulogical tests - a method of thrombodynamics whose main parameter was Vs (stationary clot growth rate). The results of anticoagulant therapy were assessed by dynamics of clinical symptomatology, the findings of ultrasonographic angioscanning, and by the dynamics of laboratory parameters of plasma haemostasis. The obtained findings demonstrated that anticoagulant therapy with nonfractionated heparin followed by switching to warfarin is an effective method of conservative treatment of patients with idiopathic thromboses, making it possible to attain laboratory confirmed hypocoagulation accompanied by both clinical and US-controlled improvements. The results of the thrombodynamics assay by the dynamics of a decrease in the D-dimer level made it possible to statistically significantly single out a group with no effect of heparin (no effect of hypocoagulation) and high sensitivity in singling out groups of ineffective therapy with warfarin, which on the background of normo- or hypercoagulation is a marker of increased fibrinogenesis and, consequently, of high risk for the development of recurrent thrombosis in such patients.


Determination of the feasibility of using a portable X-ray fluorescence (XRF) analyzer in the field for measurement of lead content of sieved soil.
Soil samples collected in housing areas with potential lead contamination generally are analyzed with flame atomic absorption spectrometry (FAAS) or other laboratory methods. Previous work indicates that field-portable X-ray fluorescence (XRF) analysis is capable of detecting soil lead levels comparable to those detected by FAAS in samples sieved to less than 125 microm in a laboratory. A considerable savings, both economical and in laboratory reporting time, would occur if a practical field method could be developed that does not require laboratory digestion and analysis. The XRF method also would provide immediate results that would facilitate the provision of information to residents and other interested parties more quickly than is possible with conventional laboratory methods. The goal of the study reported here was to determine the practicality of using the field-portable XRF analyzer for analysis of lead in soil samples that were sieved in the field. The practicality of using the XRF was determined by the amount of time it took to prepare and analyze the samples in the field and by the ease with which the procedure could be accomplished on site. Another objective of the study was to determine the effects of moisture on the process of sieving the soil. Seventy-eight samples were collected from 30 locations near 10 houses and were prepared and analyzed at the locations where they were collected. Mean soil lead concentrations by XRF were 816 ppm before drying and 817 ppm after drying, and by laboratory FAAS were 1,042 ppm. Correlation of field-portable XRF and FAAS results was excellent for samples sieved to less than 125 microm, with R2 values of .9902 and .992 before and after drying, respectively. The saturation ranged from 10 percent to 90 percent. At 65 percent saturation or higher, it was not feasible to sieve the soil in the field without a thorough drying step, since the soil would not pass through the sieve. Therefore the field method with sieving was not practical when the soil was 65 percent or more saturated unless a time-consuming drying process was included.


Exchange-Correlation Functionals via Local Interpolation along the Adiabatic Connection.
The construction of density-functional approximations is explored by modeling the adiabatic connection locally, using energy densities defined in terms of the electrostatic potential of the exchange-correlation hole. These local models are more amenable to the construction of size-consistent approximations than their global counterparts. In this work we use accurate input local ingredients to assess the accuracy of a range of local interpolation models against accurate exchange-correlation energy densities. The importance of the strictly correlated electrons (SCE) functional describing the strong coupling limit is emphasized, enabling the corresponding interpolated functionals to treat strong correlation effects. In addition to exploring the performance of such models numerically for the helium and beryllium isoelectronic series and the dissociation of the hydrogen molecule, an approximate analytic model is presented for the initial slope of the local adiabatic connection. Comparisons are made with approaches based on global models, and prospects for future approximations based on the local adiabatic connection are discussed.


Comparison of the coaxial circle circuit with the conventional circle circuit.
The coaxial circle system helps prevent heat loss during surgery, and it also acts as a humidifier. This study aimed to compare the coaxial breathing system and the conventional system in their ability to warm and moisturize inhaled gases, and we also analyzed lung function protection and saccharin clearance time in patients who underwent tympanomastoidectomy (TMT) with the aid of these two systems. Forty adult patients of ASA physical status I-II were scheduled for elective TMT. A standard volume-dependent ventilator setting was used to establish normocapnia. The coaxial circle system was used in the treated group (n=20), whereas the conventional circuit system was used in the control group (n=20). Saccharin clearance, VC (vital capacity), FRC (functional residual capacity), FEV1 (forced expiratory volume in 1 second), airway pressure, relative humidity and temperature of inspired gas, body temperature and adverse and hemodynamic effects were measured at different perioperative periods. The relative humidity (mg H2O Lt -1) of inspired gas in the treated group was higher than in the control group at 5, 15, 30, 45, 60 and 90 minutes after anesthesia induction. The temperature of inspired gas (Centigrade) in the treated group was higher than in the control group (p<0.05) after 5, 10, 15, 30, 45, and 90 minutes of anesthesia. Postoperative saccharin clearance time was lower than before the operation in the treated group (p<0.05). Postoperative FRC was lower than preoperative FRC in the study and control groups (p<0.05). The coaxial circle system decreased postoperative saccharin clearance time and increased postoperative FRC, relative humidity and the temperature of inspired fresh gas, without any adverse perioperative effects in patients who underwent TMT.


Oestrogen treatment for tall stature in girls: estimating the effect on height and the error in height prediction.
To determine the effect of oestrogen treatment on attenuating the growth of tall girls after adjusting for error in height prediction. Retrospective cohort study. Tall girls assessed by Australian paediatric endocrinologists between 1959 and 1993. A total of 279 girls received oestrogen treatment (diethylstilboestrol or ethinyl oestradiol) and 367 girls were assessed but not treated. Estimated mature height (EMH) was calculated using radiographic assessment of bone age in adolescence. Final adult height was self-reported at follow-up. To control for error in the EMH predictions and their different distributions by treatment status, pairs of treated and untreated girls, matched on EMH within 1 cm, were selected for analysis. Covariate adjusted estimates of treatment effect (final height - EMH) were calculated. RESULTS In the sample of 108 matched pairs, the mean difference between the final height and EMH was -1.4 cm (SE 0.29) in the treated group and 1.1 cm (SE 0.23) in the untreated group, giving an unadjusted treatment effect of -2.5 cm (95% CI -3.2 to 1.8). A regression model based on 107 pairs of treated and untreated girls contained a significant interaction between bone age at treatment initiation and treatment, which estimated an approximately 1 cm per year decrease in treatment effect. The treatment effect was greatest in those commencing treatment at an early bone age and was significant if initiated before a bone age of 15 years. On average, oestrogen treatment resulted in an adult height that was less than predicted. Although treatment was more effective in the least mature girls, the mean height difference was relatively modest for most treated girls.