Cost-effectiveness of transcatheter versus surgical aortic valve replacement in patients at lower surgical risk: results from the NOTION trial.
The aim of this study was to estimate the cost-effectiveness of transcatheter aortic valve implantation (TAVI) versus surgical aortic valve replacement (SAVR) in patients at lower surgical risk. Discounted costs from a societal perspective and effectiveness as quality-adjusted life years (QALYs) were projected to lifetime via a decision-analytic model calibrated to 60-month data from the NOTION trial. The base case assumed a scenario in which any mortality benefit would gradually fade out over time, with other scenarios explored in sensitivity analyses. The incremental cost-effectiveness ratio (ICER) was compared to the country-specific willingness-to-pay (WTP) threshold of 1.13 million Danish kroner (DKK). The base case ICER was DKK 696,264/QALY (around €72,100/QALY via purchasing parity adjustment). Variation in long-term mortality beyond five years led to limited variation of incremental costs (DKK 64,200 to 64,600), but a more pronounced variation in incremental QALYs (0.07 to 0.19 QALYs for most conservative and optimistic assumptions, compared to base case of 0.09 QALYs). All resulting ICERs (range DKK 334,200 to DKK 904,100 per QALY gained) were below the WTP threshold. TAVI in a cohort of primarily low surgical risk patients was found to be a cost-effective treatment strategy in the Danish healthcare system. Cost-effectiveness analyses in other settings are warranted as are registries given the sensitivity of the model to long-term mortality.


Family-based factors associated with overweight and obesity among Pakistani primary school children.
Childhood obesity epidemic is now penetrating the developing countries including Pakistan, especially in the affluent urban population. There is no data on association of family-based factors with overweight and obesity among school-aged children in Pakistan. The study aimed to explore the family-based factors associated with overweight and obesity among Pakistani primary school children. A population-based cross-sectional study was conducted with a representative multistage cluster sample of 1860 children aged five to twelve years in Lahore, Pakistan. Overweight (> +1SD BMI-for-age z-score) and obesity (> +2SD BMI-for-age z-score) were defined using the World Health Organization reference 2007. Chi-square test was used as the test of trend. Linear regression was used to examine the predictive power of independent variables in relation to BMI. Logistic regression was used to quantify the independent predictors of overweight and adjusted odds ratios (aOR) with 95% confidence intervals (CI) were obtained. All regression analyses were controlled for age and gender and statistical significance was considered at P < 0.05. Significant family-based correlates of overweight and obesity included higher parental education (P < 0.001), both parents working (P = 0.002), fewer siblings (P < 0.001), fewer persons in child's living room (P < 0.001) and residence in high-income neighborhoods (P < 0.001). Smoking in living place was not associated with overweight and obesity. Higher parental education (P < 0.001) and living in high-income neighborhoods (P < 0.001) showed a significant independent positive association with BMI while greater number of siblings (P = 0.001) and persons in child's living room (P = 0.022) showed a significant independent inverse association. College-level or higher parental education as compared to high school-level or lower parental education (aOR 2.54, 95% CI 1.76-3.67), living in high-income neighborhoods as compared to low-income neighborhoods (aOR 2.13, 95% CI 1.31-3.46) and three or less siblings as compared to more than three siblings (aOR 1.75, 95% CI 1.26-2.42) were significant independent predictors of overweight. Family-based factors were significantly associated with overweight and obesity among school-aged children in Pakistan. Higher parental education, living in high-income neighborhoods and fewer siblings were independent predictors of overweight. These findings support the need to design evidence-based child health policy and implement targeted interventions, considering the impact of family-based factors and involving communities.


Updating Animal Welfare Thinking: Moving beyond the "Five Freedoms" towards "A Life Worth Living".
The Five Freedoms have had major impact on animal welfare thinking internationally. However, despite clear initial statements that the words 'freedom from' should indicate 'as free as possible from', the Freedoms have come to be represented as absolute or fundamental freedoms, even rights, by some animal advocate and other groups. Moreover, a marked increase in scientific understanding over the last two decades shows that the Freedoms do not capture the more nuanced knowledge of the biological processes that is germane to understanding animal welfare and which is now available to guide its management. For example, the named negative experiences of thirst, hunger, discomfort and pain, and others identified subsequently, including breathlessness, nausea, dizziness, debility, weakness and sickness, can never be eliminated, merely temporarily neutralised. Each one is a genetically embedded element that motivates animals to behave in particular ways to obtain specific life-sustaining resources, avoid or reduce physical harm or facilitate recovery from infection or injury. Their undoubted negativity creates a necessary sense of urgency to respond, without which animals would not survive. Also, the temporary neutralisation of these survival-critical affects does not in and of itself generate positive experience. This questions the commonly held assumption that good animal welfare will result when these internally generated negative affects are minimised. Animals may also experience other negative affects that include anxiety, fear, panic, frustration, anger, helplessness, loneliness, boredom and depression. These situation-related affects reflect animals' perceptions of their external circumstances. Although they are elicited by threatening, cramped, barren and/or isolated conditions, they can often be replaced by positive affects when animals are kept with congenial others in spacious, stimulus-rich and safe environments which provide opportunities for them to engage in behaviours they find rewarding. These behaviours may include environment-focused exploration and food acquisition activities as well as animal-to-animal interactive activities, all of which can generate various forms of comfort, pleasure, interest, confidence and a sense of control. Animal welfare management should aim to reduce the intensity of survival-critical negative affects to tolerable levels that nevertheless still elicit the required behaviours, and should also provide opportunities for animals to behave in ways they find rewarding, noting that poor management of survival-critical affects reduces animals' motivation to utilize such rewarding opportunities. This biologically more accurate understanding provides support for reviewing the adequacy of provisions in current codes of welfare or practice in order to ensure that animals are given greater opportunities to experience positive welfare states. The purpose is to help animals to have lives worth living, which is not possible when the predominant focus of such codes is on survival-critical measures. Finally, an updated characterisation of animal welfare that incorporates this more accurate understanding is presented.


Elisa comparison of three whole-cell antigens of Borrelia burgdorferi sensu lato in serological study of dogs from area of Kosice, eastern Slovakia.
Three antigens of Borrelia burgdorferi sensu lato (B. burgdorferi sensu stricto--Slovak strain Ir 105, B. garini - Slovak strain K 24 and B. burgdorferi sensu stricto--American strain B 31) were compared by ELISA on a group of dogs from urban agglomeration of Kosice, eastern Slovakia. Of 256 serum samples from dogs examined for the presence of anti-Borrelia IgG antibodies, 128 (50%) were positive with Ir 105 antigen, 107 (41.7%) with K 24 and 74 (28.9%) with B 31. The seroprevalence between strains B 31 and K 24 and B 31 and Ir 105 differed statistically significantly (test chi2, p < 0.05), however, the difference between strains K 24 and Ir 105 was insignificant. A significantly higher seroprevalence of all the strains examined was detected in hunting dogs (test chi2, p < 0.05) when compared with service and pet dogs. The seroprevalence correlated with the frequency of outing the dogs in woody areas with the occurrence of borreliae in ticks (R = 0.5 or 0.7) as well as with the frequency of finding engorged ticks (R = 0.5). An epizootiological anamnesis showed a fair specificity in all the strains examined. The Slovak strains showed the higher consistency of positive and negative findings (70%) but statistically lower specificity than the American strain.


A new quantitative method for gunshot residue analysis by ion beam analysis.
Imaging and analyzing gunshot residue (GSR) particles using the scanning electron microscope equipped with an energy dispersive X-ray spectrometer (SEM-EDS) is a standard technique that can provide important forensic evidence, but the discrimination power of this technique is limited due to low sensitivity to trace elements and difficulties in obtaining quantitative results from small particles. A new, faster method using a scanning proton microbeam and Particle Induced X-ray Emission (μ-PIXE), together with Elastic Backscattering Spectrometry (EBS) is presented for the non-destructive, quantitative analysis of the elemental composition of single GSR particles. In this study, the GSR particles were all Pb, Ba, Sb. The precision of the method is assessed. The grouping behaviour of different makes of ammunition is determined using multivariate analysis. The protocol correctly groups the cartridges studied here, with a confidence >99%, irrespective of the firearm or population of particles selected.


Benzodiazepines have high-affinity binding sites and induce melanogenesis in B16/C3 melanoma cells.
We found that two markers of differentiation, tyrosinase (monophenol, dihydroxyphenylalanine:oxygen oxidoreductase, EC 126.96.36.199) activity and melanin synthesis, are induced by diazepam in B16/C3 mouse melanoma cells. We also demonstrated high-affinity binding sites for [3H]diazepam in these cells by radioreceptor assay, and we visualized binding to the cell surface by fluorescence microscopy with a benzodiazepine analog conjugated to a fluorescein-labeled protein. Our studies also showed that there are differences between the binding characteristics in intact cells and in membrane fractions prepared from these cells. Scatchard analysis of the binding data from membrane fractions gave a linear plot (Kd = 9.1 X 10(-8) M). With intact cells, a curvilinear Scatchard plot was obtained. This was resolved into two components defining binding sites with affinity constants of 1.7 X 10(-9) M and 4.6 X 10(-7) M. Thus, it appears that [3H]diazepam binding in intact cells is more complex than in isolated membranes. Several related benzodiazepines, including flunitrazepam, Ro-5-4864, nitrazepam, oxazepam, lorazepam, Ro-5-3072, chlordiazepoxide, and clonazepam also induced melanogenesis. When these compounds were tested for their ability to inhibit [3H]diazepam binding, flunitrazepam, diazepam, and Ro-5-4864 were found to be the most effective inhibitors. These three compounds were also the most potent in inducing melanogenesis. Our results suggest that the benzodiazepines modulate cell differentiation. The presence of high-affinity binding sites in this homogeneous, easily grown cell line may provide a useful model for studies on the mechanism of action of these compounds.


Using a Personal Health Library-Enabled mHealth Recommender System for Self-Management of Diabetes Among Underserved Populations: Use Case for Knowledge Graphs and Linked Data.
Traditionally, digital health data management has been based on electronic health record (EHR) systems and has been handled primarily by centralized health providers. New mechanisms are needed to give patients more control over their digital health data. Personal health libraries (PHLs) provide a single point of secure access to patients' digital health data and enable the integration of knowledge stored in their digital health profiles with other sources of global knowledge. PHLs can help empower caregivers and health care providers to make informed decisions about patients' health by understanding medical events in the context of their lives. This paper reports the implementation of a mobile health digital intervention that incorporates both digital health data stored in patients' PHLs and other sources of contextual knowledge to deliver tailored recommendations for improving self-care behaviors in diabetic adults. We conducted a thematic assessment of patient functional and nonfunctional requirements that are missing from current EHRs based on evidence from the literature. We used the results to identify the technologies needed to address those requirements. We describe the technological infrastructures used to construct, manage, and integrate the types of knowledge stored in the PHL. We leverage the Social Linked Data (Solid) platform to design a fully decentralized and privacy-aware platform that supports interoperability and care integration. We provided an initial prototype design of a PHL and drafted a use case scenario that involves four actors to demonstrate how the proposed prototype can be used to address user requirements, including the construction and management of the PHL and its utilization for developing a mobile app that queries the knowledge stored and integrated into the PHL in a private and fully decentralized manner to provide better recommendations. To showcase the main features of the mobile health app and the PHL, we mapped those features onto a framework comprising the user requirements identified in a use case scenario that features a preventive intervention from the diabetes self-management domain. Ongoing development of the app requires a formative evaluation study and a clinical trial to assess the impact of the digital intervention on patient-users. We provide synopses of both study protocols. The proposed PHL helps patients and their caregivers take a central role in making decisions regarding their health and equips their health care providers with informatics tools that support the collection and interpretation of the collected knowledge. By exposing the PHL functionality as an open service, we foster the development of third-party applications or services and provide motivational technological support in several projects crossing different domains of interest.


Chronic kidney disease and postoperative morbidity after elective orthopedic surgery.
Reduced estimated glomerular filtration rate (eGFR) is strongly associated with increased cardiovascular risk and all-cause mortality. Associations with morbidity in elective, moderate-risk noncardiac surgery have not been explored. We hypothesized that chronic kidney disease (CKD) would be associated with excess morbidity after elective, moderate-risk orthopedic surgery. Patients undergoing elective orthopedic joint replacement procedures were studied, representing a large proportion of global surgical procedures and characterized by highly homogeneous anesthetic and surgical practice. eGFR was calculated from routine creatinine measurements using the Modification of Diet in Renal Disease equation. CKD was defined as eGFR < 60 mL/min/1.73 m². Cardiac risk (Revised Cardiac Risk Index) and evidence-based, perioperative factors associated with perioperative morbidity (operative time, blood loss, perioperative temperature) were also recorded prospectively. The primary end point was postoperative morbidity, recorded prospectively using the postoperative morbidity survey. Morbidity differences were analyzed between patients with CKD and normal preoperative renal function (χ² test for trend) and presented as hazard ratio (HR) or odds ratio (OR) with 95% confidence intervals (95% CIs). The secondary end points were time to hospital discharge and time to become morbidity free (analyzed by log-rank test), both between and within CKD compared with normal renal function patients. Multiple regression analysis was performed to assess the association of CKD, perioperative factors with morbidity, and length of hospital stay. Postoperative morbidity survey was recorded in 526 patients undergoing elective orthopedic surgery. CKD patients (n = 142; 27%) sustained excess morbidity on postoperative day 5 (OR 2.1 [95% CI: 1.2-3.7]; P < 0.0001). CKD patients took longer (HR 1.6 [95% CI: 1.2-1.9]) to become morbidity free (log-rank test, P < 0.0001). Time to hospital discharge was delayed by 4 days in CKD patients (HR 1.4 [95% CI: 1.2-1.7]; P = 0.0001; log-rank test). CKD patients sustained more pulmonary (OR 2.2 [95% CI:1.3-3.6]; P = 0.002), infectious (OR 1.7 [95% CI:1.1-2.7]; P = 0.01), cardiovascular (OR 2.4 [95% CI: 1.2-4.8]; P = 0.01), renal (OR 2.3 [95% CI:1.5-3.5]; P < 0.00,001), neurological (OR 4.3 [95% CI:1.3-17.7]; P = 0.005), and pain (OR 1.8 [95% CI:1.03-3.1]; P = 0.04) morbidities. Further stratification of CKD revealed preoperative eGFR ≤ 50 mL/min/1.73 m(2) to be associated with more frequent morbidity and longer hospital stay, independent of age. Multiple regression analysis identified CKD (P = 0.006) and congestive cardiac failure (P = 0.002) as preoperative factors associated with prolonged hospital stay. A substantial minority of patients with CKD undergoing elective orthopedic procedures are at increased risk of prolonged morbidity and hospital stay. Preoperative eGFR may enhance perioperative risk stratification beyond traditional risk factors.


Development of a Resonant Microwave Sensor for Sediment Density Characterization.
In this study, a sensor based on the development of a planar antenna immersed in sediments dedicated to water content monitoring in this type of material is proposed and experimentally validated. It is produced by a conventional Printed Circuit Board (PCB) manufacturing process on a double-sided metalized FR4 substrate. The sensitivity of the sensor is ensured by the variation of the real part of the complex dielectric permittivity of sediments with water content at around 1 GHz. As shown, in this frequency range, electrode polarization and Maxwell-Wagner polarization effects become negligible, leading to only a bulk water polarization sensitivity. The sensor operates in the reflection mode by monitoring the variation of the resonant frequency as a function of the sediment density through the S11 reflection measurements. An experimental sensitivity of 820   MHz . g - 1 . cm 3 was achieved. Despite the simplification of data interpretation at the considered frequency, the influence of ionic species such as NaCl in sediments on the real part of the relative complex dielectric permittivity is highlighted. This demonstrates the importance of considering a second parameter such as the S11 level at low frequency or the electrical conductivity to extract the density from the frequency measurements.


Sensorimotor changes following lesion of mid-dorsal caudate nucleus in rats.
Effects of mid-dorsal caudate nucleus on sensorimotor changes were studied in rats. After electrolytic lesion of this area of brain there was impairment in sensory functions and decline in motor component was observed to be statistically significant.


Mathematical modeling in necrotizing enterocolitis--a new look at an ongoing problem.
Necrotizing enterocolitis (NEC) is the most common and lethal disease that affects the gastrointestinal (GI) tract of the premature infant. The etiology of NEC remains undefined. The only consistent epidemiological precursors for NEC are prematurity and enteral alimentation. Various inflammatory mediators, including tumor necrosis factor (TNF)-a, interleukin (IL)-1, IL-6, IL-8, IL-10, IL-18, platelet-activating factor (PAF), and nitric oxide (NO) have been implicated in the pathogenesis of NEC, but the kinetics and role of these agents are ill-defined. Currently, there are no biomarker predictors of NEC risk and severity. Sera or tissue from early time points in the development of the disease may help delineate early inflammatory events that predispose an individual to NEC, thus providing an interventional opportunity. We suggest that the lack of diagnostic and therapeutic modalities for NEC are due to the absence of a systems view of the disease, which in turn is hindered by a lack of sensitive physiological measurements that predict perturbations in the intestinal tissue compartment and an inability to reliably test serial samples for the presence of inflammatory mediators in small volumes and in a high-throughput manner. Computational modeling is a useful tool in the study of complex systems such as the inflammatory process. Computation models provide an "existence proof" for a given mechanism, uncover subtle inconsistencies between the underlying hypotheses and quantitative data, and force one to ask how much is known. We suggest that a properly validated and calibrated mathematical model of inflammation and its pathologic consequences in NEC will be useful for predicting the physiologic and biologic response in infants suffering from the disease.


Logistical aspects of large telemedicine networks. 1: Site directories.
We carried out a survey of the site coordinators in a mature telemedicine network of about 200 sites. The site directory contained information about 221 videoconference facilities. There were 191 site coordinators in all (i.e. some coordinators were responsible for more than one site). Of the 221 sites, we were able to contact 87 on first attempt and 155 by the fourth attempt. Thus there were 66 sites (30%) which were not contactable. We asked each site coordinator to describe any videoconference activity that had taken place over the previous five working days. Of the contacted 155 sites, 78 reported some videoconference activity during the period in question. The total reported videoconference activity was 12,800 min during the one-week monitoring period, that is, an estimated 924 h per month. The most common categories of work were education or training (511 h) and management or administration (225 h), which between them accounted for 80% of all reported videoconference activity. Fifty of the 155 sites (32%) reported that the equipment was not located in an area suitable for patient consultations. In addition, 20 sites (13%) volunteered that their videoconferencing facilities were not in working order at the time of the survey. We did not ask this question in the survey, so that this result represents a lower bound for the true number of inoperable systems.


Nickel-Catalyzed Annulations of ortho-Haloarylimines.
We report the discovery, development, and mechanism of a nickel-catalyzed annulation reaction between o-haloarylimines and electron-poor olefins. The reaction produces two adjacent anti stereocenters and a free secondary amine. Spirocycles are formed from cyclic imines. We characterized the key oxidative addition intermediate and identified a major path leading to competing homocoupling products. The activation energy of oxidative addition and the rate of oxidative addition complex isomerization were determined. The sensitivity of the reaction to reaction conditions was established in a quantitative manner and both the scope and limitations of the method are presented.


Hodgkin Lymphoma Presenting With Spinal Cord Compression: Challenges for Diagnosis and Initial Management.
Hodgkin lymphoma (HL) can present with extra-nodal disease, but spinal cord compression is exceptionally rare. We describe a 15-year-old presenting with hip/back pain with normal initial examination. Persistent pain and raised inflammatory markers prompted further investigation with MRI, which revealed an epidural mass causing spinal cord compression. On examination, there was no palpable lymphadenopathy or cauda equina syndrome, but absent lower limb reflexes were noted. Following multidisciplinary discussion, it was determined that cauda equina syndrome was imminent and therefore surgical debulking was undertaken, both to prevent this complication and establish a diagnosis. At surgery, the tumor was highly vascular. Frozen section confirmed lesional material. Following surgery, and given the frozen section findings, a short course of steroids was commenced to reduce any peri-surgical edema. Unfortunately, histopathology was ultimately non-diagnostic, due to failure of immunohistochemistry on technically challenging material. Consequently, ultrasound-guided excision biopsy of a (non-palpable) cervical lymph node was performed five days later; histopathology showed typical effacement of the normal architecture and a conspicuous population of CD15/CD30-positive larger pale cells present, confirming nodular sclerosis classic HL, despite recent steroids. We review the available literature for HL presenting with spinal cord compression and describe the challenges for diagnosis and initial management in such cases.


Animal Models for the Study of Keratoconus.
Keratoconus (KC) is characterized by localized, central thinning and cone-like protrusion of the cornea. Its precise etiology remains undetermined, although both genetic and environmental factors are known to contribute to disease susceptibility. Due to KC's complex nature, there is currently no ideal animal model to represent both the corneal phenotype and underlying pathophysiology. Attempts to establish a KC model have involved mice, rats, and rabbits, with some additional novel animals suggested. Genetic animal models have only been attempted in mice. Similarly, spontaneously occurring animal models for KC have only been discovered in mice. Models generated using chemical or environmental treatments have been attempted in mice, rats, and rabbits. Among several methods used to induce KC in animals, ultraviolet radiation exposure and treatment with collagenase are some of the most prevalent. There is a clear need for an experimental model animal to elucidate the underlying mechanisms behind the development and progression of keratoconus. An appropriate animal model could also aid in the development of treatments to slow or arrest the disorder.


Analysis and Classification of Event-Related Potentials During Image Observation.
In the field of cognitive neuroscience, researchers have conducted extensive studies on object categorization using Event-Related Potential (ERP) analysis, specifically by analyzing electroencephalographic (EEG) response signals triggered by visual stimuli. The most common approach for visual ERP analysis is to use a low presentation rate of images and an active task where participants actively discriminate between target and non-target images. However, researchers are also interested in understanding how the human brain processes visual information in real-world scenarios. To simulate real-life object recognition, this study proposes an analysis pipeline of visual ERPs evoked by images presented in a Rapid Serial Visual Presentation (RSVP) paradigm. Such an approach allows for the investigation of recurrent patterns of visual ERP signals across specific categories and subjects. The pipeline includes segmentation of the EEGs in epochs, and the use of the resulting features as inputs for Support Vector Machine (SVM) classification. Results demonstrate common ERP patterns across the selected categories and the ability to obtain discriminant information from single visual stimuli presented in the RSVP paradigm.


Is the measurement of cerebral microembolic signals a good surrogate marker for evaluating the efficacy of antiplatelet agents in the prevention of stroke?
Stroke is difficult to treat with few treatment options. Until such time as appropriate therapeutic regimens are established, prevention, both in the primary and in the secondary setting, is of paramount importance. Evaluation of pharmacological agents for the prevention of stroke in conventional clinical studies has the advantage that the outcome parameter is a direct measure of efficacy, and the disadvantage that many patients must be recruited and many evaluations performed over an extended period to provide adequate statistical power, making such studies lengthy and costly. Measurement of cerebral microembolic signals (MES) using transcranial Doppler ultrasonography has been proposed as a useful surrogate end point to investigate new antiplatelet agents and to evaluate further the benefits of existing antiplatelet therapies. MES measurements may provide a means of more directly evaluating the pharmacological activity of an antiplatelet agent. However, does measurement of MES accurately predict efficacy in stroke prevention? This review evaluates recent studies where the relationship between MES and cerebral ischaemic events has been explored and studies where the effects of antiplatelet agents on MES rates have been investigated. Overall, there is a growing body of evidence to suggest that MES may be used as a surrogate marker for cerebral infarction and clinical events, thus allowing quick appraisal of the efficacy of antiplatelet agents. Studies currently in progress should provide further insight into the value of the measurement of MES in clinical studies in stroke prevention.


Alteration of the Intra- and Inter-Lobe Connectivity of the Brain Structural Network in Normal Aging.
The morphological changes in cortical parcellated regions during aging and whether these atrophies may cause brain structural network intra- and inter-lobe connectivity alterations are subjects that have been minimally explored. In this study, a novel fractal dimension-based structural network was proposed to measure atrophy of 68 parcellated cortical regions. Alterations of structural network parameters, including intra- and inter-lobe connectivity, were detected in a middle-aged group (30-45 years old) and an elderly group (50-65 years old). The elderly group exhibited significant lateralized atrophy in the left hemisphere, and most of these fractal dimension atrophied regions were included in the regions of the "last-in, first-out" model. Globally, the elderly group had lower modularity values, smaller component size modules, and fewer bilateral association fibers. They had lower intra-lobe connectivity in the frontal and parietal lobes, but higher intra-lobe connectivity in the temporal and occipital lobes. Both groups exhibited similar inter-lobe connecting pattern. The elderly group revealed separations, sparser long association fibers, commissural fibers, and lateral inter-lobe connectivity lost effect, mainly in the right hemisphere. New wiring and reconfiguring modules may have occurred within the brain structural network to compensate for connectivity, decreasing and preventing functional loss in cerebral intra- and inter-lobe connectivity.


Outcome of repeat trabeculectomies: long-term follow-up.
To assess medium-term to long-term outcomes of a cohort of repeat trabeculectomy augmented with mitomycin C (MMC). A prospective evaluation of consecutive separate site repeat MMC-augmented trabeculectomies undertaken at a single institution between October 2000 and December 2012. Information regarding visual acuity (VA), intraocular pressure (IOP), visual field progression, postoperative interventions, surgery complications and success of surgery are presented.Complete and qualified (ie, with or without glaucoma medication) success rates were presented on the basis of three levels of IOP control: ≤21, ≤17 and ≤14 mm Hg without hypotony or reoperation. Fifty-six eyes of 56 patients were evaluated. Thirty-seven per cent of the cohort had a previously augmented trabeculectomy. Mean follow-up was 6.3±3.4 years. At 60-month follow-up, 56.1% of patients achieved complete success and 75.6% achieved qualified success at the ≤21 mm Hg target. Complete and qualified success rates were 53.7% and 73.2%, respectively at the ≤17 mm Hg target and 51.2% and 61.0%, respectively at the ≤14 mm Hg target. Mean preoperative IOP was 29.1±6.0 mm Hg. At the 60-month follow-up visit the mean IOP was 12.6±4.7 mm Hg. Requirement for topical medications dropped from a mean of 2.9 to 0.5 per patient. No medications were required in 68.3%. Safe repeat trabeculectomy technique with antimetabolite titrated against the individual patients risk profile can result in improved results in the medium-term to long-term.


Effects of transcranial magnetic stimulation over the left posterior superior temporal gyrus on picture-word interference.
Word-production theories argue that during language production, a concept activates multiple lexical candidates in left temporal cortex, and the intended word is selected from this set. Evidence for theories on spoken-word production comes, for example, from the picture-word interference task, where participants name pictures superimposed by congruent (e.g., picture: rabbit, distractor "rabbit"), categorically related (e.g., distractor "sheep"), or unrelated (e.g., distractor "fork") words. Typically, whereas congruent distractors facilitate naming, related distractors slow down picture naming relative to unrelated distractors, resulting in semantic interference. However, the neural correlates of semantic interference are debated. Previous neuroimaging studies have shown that the left mid-to-posterior STG (pSTG) is involved in the interference associated with semantically related distractors. To probe the functional relevance of this area, we targeted the left pSTG with focal repetitive transcranial magnetic stimulation (rTMS) while subjects performed a picture-word interference task. Unexpectedly, pSTG stimulation did not affect the semantic interference effect but selectively increased the congruency effect (i.e., faster naming with congruent distractors). The facilitatory TMS effect selectively occurred in the more difficult list with an overall lower name agreement. Our study adds new evidence to the causal role of the left pSTG in the interaction between picture and distractor representations or processing streams, only partly supporting previous neuroimaging studies. Moreover, the observed unexpected condition-specific facilitatory rTMS effect argues for an interaction of the task- or stimulus-induced brain state with the modulatory TMS effect. These issues should be systematically addressed in future rTMS studies on language production.


Activation of human CD4 T lymphocytes. Interaction of fibronectin with VLA-5 receptor on CD4 cells induces the AP-1 transcription factor.
Fibronectin synergized with anti-CD3 antibody to promote CD4 cell proliferation in a serum-free culture system whereas no proliferation was observed when CD4 cells were cultured with anti-CD3 alone or fibronectin alone. In addition, anti-CD29 (integrin beta 1) as well as anti-VLA-5 (human fibronectin receptor) antibodies blocked this CD4 cell activation in this system. Although anti-CD3 alone or fibronectin alone cannot induce IL-2 message by CD4 cells, the combination of anti-CD3 plus fibronectin induced IL-2 message by CD4 cells. In an analysis of the molecular mechanism by which IL-2 message was generated, we showed that a fibronectin-VLA-5 fibronectin receptor interaction may contribute an independent signal distinct from the CD3 pathway of activation by the induction of an AP-1 transcriptional factor. Thus the VLA-5 fibronectin receptor on CD4 cells can play a complementary role in CD3-TCR-mediated signal transduction through its interaction with fibronectin.


[The 1755 Lisbon earthquake: collections of eighteenth-century texts].
This study describes three collections of texts published in the years following the 1755 earthquake in Lisbon. Housed at archives and libraries in Portugal, the texts represent a variety of literary genres and strategies of argumentation. Here they have been analyzed according to pre-established categories. They were written during a time of transition characterized by ideological hesitations and by an eclecticism of conservative bent, a time when the latest experimentalist currents coexisted alongside attempts to reconcile scholastic Aristotelianism and experimentalism. The study focuses on a narrower set of texts, of special interest to the history of science; these can be classified into one of two topics: (i) physical explanations for the earth tremors and (ii) hygienist concerns about this type of natural disaster.


Severe acute malnutrition in Asia.
Severe acute malnutrition (SAM) is a common condition that kills children and intellectually maims those who survive. Close to 20 million children under the age of 5 years suffer from SAM globally, and about 1 million of them die each year. Much of this burden takes place in Asia. Six countries in Asia together have more than 12 million children suffering from SAM: 0.6 million in Afghanistan, 0.6 million in Bangladesh, 8.0 million in India, 1.2 million in Indonesia, 1.4 million in Pakistan, and 0.6 million in Yemen. This article is based on a review of SAM burden and intervention programs in Asian countries where, despite the huge numbers of children suffering from the condition, the coverage of interventions is either absent on a national scale or poor. Countries in Asia have to recognize SAM as a major problem and mobilize internal resources for its management. Screening of children in the community for SAM and appropriate referral and back referral require good health systems. Improving grassroots services will not only contribute to improving management of SAM, it will also improve infant and young child feeding and nutrition in general. Ready-to-use therapeutic food (RUTF), the key to home management of SAM without complications, is still not endorsed by many countries because of its unavailability in the countries and its cost. It should preferably be produced locally from locally available food ingredients. Countries in Asia that do not have the capacity to produce RUTF from locally available food ingredients can benefit from other countries in the region that can produce it. Health facilities in all high-burden countries should be staffed and equipped to treat children with SAM. A continuous cascade of training of health staff on management of SAM can offset the damage that results from staff attrition or transfers. The basic nutrition interventions, which include breastfeeding, appropriate complementary feeding, micronutrient supplementation, and management of acute malnutrition, should be scaled up in Asian countries that are plagued with the burden of malnutrition.


Nurses' perception about Human Resource Management system and prosocial organisational behaviour: Mediating role of job efficacy.
To examine the relationship between nurses' perception about human resource management system and prosocial organisational behaviour through job efficacy. Literature suggests that non-profit organisations are often confronted with financial constraints on one side and the expectation of delivering high-quality services on the other. Employees voluntarily engaging in service-oriented behaviours help to bridge this gap to some extent, and human resource management system plays a significant role in eliciting the requisite behaviours. In this article, the case of nurses from non-profit hospitals has been undertaken to examine the aspects of human resource management system that needs focus while promoting prosocial organisational behaviours among the nurses for ensuring better service delivery. Cross-sectional design was employed. Data were collected from 387 nurses working in non-profit hospitals in India through questionnaires and were analysed with the help of structural equation modelling. In the absence of sophisticated human resource system in non-profit hospitals, the study found that nurses' perception about human resource management system is positively related to prosocial organisational behaviours, and job efficacy partially mediates the relationship. Positive perceptions such as involvement with the job and communication as well as supervisors' support are essential human resource practices for fostering self-efficacy and, thus, improving prosocial organisational behaviour of nurses working in non-profit hospitals. Non-profit hospitals should focus on nurses' participation and supervisory support, which would provide a better human touch approach to patient care and also improve service quality. The findings shed light on the nursing management of non-profit hospitals in terms of human resource management that has to be given much attention for institutionalizing prosocial organisational behaviour.


Quorum sensing disruption regulates hydrolytic enzyme and biofilm production in estuarine bacteria.
Biofilms of heterotrophic bacteria cover organic matter aggregates and constitute hotspots of mineralization, primarily acting through extracellular hydrolytic enzyme production. Nevertheless, regulation of both biofilm and hydrolytic enzyme synthesis remains poorly investigated, especially in estuarine ecosystems. In this study, various bioassays, mass spectrometry and genomics approaches were combined to test the possible involvement of quorum sensing (QS) in these mechanisms. QS is a bacterial cell-cell communication system that relies notably on the emission of N-acylhomoserine lactones (AHLs). In our estuarine bacterial collection, we found that 28 strains (9%), mainly Vibrio, Pseudomonas and Acinetobacter isolates, produced at least 14 different types of AHLs encoded by various luxI genes. We then inhibited the AHL QS circuits of those 28 strains using a broad-spectrum lactonase preparation and tested whether biofilm production as well as β-glucosidase and leucine-aminopeptidase activities were impacted. Interestingly, we recorded contrasted responses, as biofilm production, dissolved and cell-bound β-glucosidase and leucine-aminopeptidase activities significantly increased in 4%-68% of strains but decreased in 0%-21% of strains. These findings highlight the key role of AHL-based QS in estuarine bacterial physiology and ultimately on biogeochemical cycles. They also point out the complexity of QS regulations within natural microbial assemblages.


Determinants of Sickness Absence and Return to Work Among Employees with Common Mental Disorders: A Scoping Review.
Purpose To present an overview of the existing evidence on prognostic factors of (recurrent) sickness absence (SA) and return to work (RTW) among workers with a common mental disorder (CMD). This scoping review provides information about determinants for SA and RTW, which could be used to develop better interventions aimed at the prevention of SA and promotion of RTW among workers with a CMD. Methods Relevant articles were identified in PubMed, Embase, PsycINFO, PSYNDEX, and SINGLE up to October 2016. In order to be included, studies should provide insight into prognostic factors of SA or RTW of workers with a CMD. We classified all factors according to the domains of the International Classification of Functioning, Disability and Health. Results Our searches identified 2447 possible relevant articles, of which 71 were included for data extraction. There is consistent evidence in ≥3 studies that previous episodes of CMD, higher symptom severity, previous absenteeism, co-morbidity, high job demands, low job control, high job strain, female gender, lower educational level, smoking behavior, and low perceived general health are predictors of SA in people with CMDs. Earlier RTW is consistently predicted by lower symptom severity, having no previous absenteeism, younger age, and positive expectations concerning sick-leave duration or RTW. Conclusions The amount of research on determinants for SA and RTW in workers with CMD has increased dramatically in recent years, although most studies are from the Netherlands and Scandinavia. There are some research gaps identified in this scoping review that need further attention in primary and secondary studies. Based on the summary of the evidence, we provide guidance for policy, practice and research.


Dorsoventral transposition of the heart chambers in sturgeon Acipenser naccarii alevins.
This is the first description of a dorsoventral transposition of the heart chambers in sturgeons Acipenser naccarii. The affected individuals were 2 farmed alevins aged 9 and 10 d posthatching, respectively. One was examined by light microscopy and the other by scanning electron microscopy. In both cases, the atrium and sinus venosus occupied a left ventrolateral position, the ventricle, conus arteriosus and bulbus arteriosus were located dorsally, and the transverse septum was incomplete. The anomalous heart examined by light microscopy did not differ histologically from normal hearts of similar developmental stages. The abnormal dorsoventral arrangement of the heart chambers was presumably due to a distortion of the morphogenetic movements that bring the ventricle to the ventral and the atrium to the dorsal position. The present findings, together with genetic data reported in the literature, suggest that the defective cardiac phenotype detected in the present specimens might result from a mutation affecting the sturgeon ortholog of the zebrafish overlooped (olp) gene.


Reducing Glucokinase Activity to Enhance Insulin Secretion: A Counterintuitive Theory to Preserve Cellular Function and Glucose Homeostasis.
Pancreatic beta-cells are the only cells in the body that can synthesize and secrete insulin. Through the process of glucose-stimulated insulin secretion, beta-cells release insulin into circulation, stimulating GLUT4-dependent glucose uptake into peripheral tissue. Insulin is normally secreted in pulses that promote signaling at the liver. Long before type 2 diabetes is diagnosed, beta-cells become oversensitive to glucose, causing impaired pulsatility and overstimulation in fasting levels of glucose. The resulting hypersecretion of insulin can cause poor insulin signaling and clearance at the liver, leading to hyperinsulinemia and insulin resistance. Continued overactivity can eventually lead to beta-cell exhaustion and failure at which point type 2 diabetes begins. To prevent or reverse the negative effects of overstimulation, beta-cell activity can be reduced. Clinical studies have revealed the potential of beta-cell rest to reverse new cases of diabetes, but treatments lack durable benefits. In this perspective, we propose an intervention that reduces overactive glucokinase activity in the beta-cell. Glucokinase is known as the glucose sensor of the beta-cell due to its high control over insulin secretion. Therefore, glycolytic overactivity may be responsible for hyperinsulinemia early in the disease and can be reduced to restore normal stimulus-secretion coupling. We have previously reported that reducing glucokinase activity in prediabetic mouse islets can restore pulsatility and enhance insulin secretion. Building on this counterintuitive finding, we review the importance of pulsatile insulin secretion and highlight how normalizing glucose sensing in the beta cell during prediabetic hyperinsulinemia may restore pulsatility and improve glucose homeostasis.


Reevaluation of the Protein Requirement in Chinese Elderly Adults without Sarcopenia with the Indicator Amino Acid Oxidation Technique.
It is now generally believed that elderly may have slightly higher dietary protein requirements than those of the young-middle-aged adults. We have previously conducted related studies by the indicator amino acid oxidation (IAAO) technique, but more research data are needed to revise the protein requirements of the elderly. The main objective was to reevaluate the dietary protein requirements of healthy Chinese adults (65-80y) without sarcopenia by using the IAAO technique. Nine healthy adult men and seven healthy adult women participated in the study, with protein intakes ranging from 0.1 to 1.8 g/(kg·d). Diets that delivered energy at a 1.5 resting energy expenditure (REE) were isocaloric. The amounts of phenylalanine and tyrosine needed to remain constant for each protein dosage. By applying a nonlinear mixed-effects model analysis on the F13CO2 data, which revealed a breakpoint in F13CO2 in response to graded protein intakes, the mean protein requirement was calculated. The mean estimated average requirement (EAR) for healthy elderly Chinese adults without sarcopenia was determined to be 0.94 g/(kg·d). The protein recommended nutrient intake (RNI) determined using various derivation approaches ranged from 1.13 to 1.36 g/(kg·d). The EAR for Chinese adults without sarcopenia aged 65-80 years in this study is 6.8% higher than the current recommended EAR [0.88 g/(kg·d)]. The RNI derived using various derivation approaches are all greater than the current RNI [0.98 g/(kg·d)]. This trial was registered with the Chinese clinical trial registry as ChiCTR2200061382.


Permeameter data verify new turbulence process for MODFLOW.
Abstract A sample of Key Largo Limestone from southern Florida exhibited turbulent flow behavior along three orthogonal axes as reported in recently published permeameter experiments. The limestone sample was a cube measuring 0.2 m on edge. The published nonlinear relation between hydraulic gradient and discharge was simulated using the turbulent flow approximation applied in the Conduit Flow Process (CFP) for MODFLOW-2005 mode 2, CFPM2. The good agreement between the experimental data and the simulated results verifies the utility of the approach used to simulate the effects of turbulent flow on head distributions and flux in the CFPM2 module of MODFLOW-2005.


Routine hospital use of a new commercial whole blood interferon-gamma assay for the diagnosis of tuberculosis infection.
Interferon (IFN)-gamma blood tests may improve the current level of diagnostic accuracy for tuberculosis infection. The QuantiFERON-TB Gold (QFT-Gold) has been used in selected populations and shows higher specificity than the tuberculin skin test (TST). To evaluate the QFT-Gold test in unselected patients and assess the level of agreement with the TST. The test has been routinely performed on whole blood samples in our microbiology laboratory for 8 months. Demographic, clinical, and microbiological data have been collected and correlated to the QFT-Gold results. Of 318 patients tested, 68 (21.4%) gave an indeterminate (low positive mitogen control) QFT-Gold result. Indeterminate results were significantly overrepresented in patients with a negative TST (28.9% vs. 6.6% in TST-positive patients; p < 0.0001, chi2 test) and were more frequent in patients receiving immunosuppressive therapies than in those who were not receiving such treatments (odds ratio, 3.35; 95% confidence interval, 1.84-6.08; p < 0.0001). After excluding indeterminate results, the concordance between QFT-Gold and TST was significantly lower in Bacille Calmette-Guérin-vaccinated individuals (41.5%) than in nonvaccinated individuals (80.3%) (p < 0.0001). In 11 patients with active tuberculosis (5 culture-confirmed), QFT-Gold provided more positive results than the TST (66.7% vs. 33.3%; p = 0.165). The QFT-Gold test is feasible in routine hospital use for the diagnosis of tuberculosis infection. As with the TST, immunosuppression may negatively affect the test's performance, with a significant rate of indeterminate results in the most vulnerable population.


Anti-proliferative and anti-secretory effects of everolimus on human pancreatic neuroendocrine tumors primary cultures: is there any benefit from combination with somatostatin analogs?
Therapeutic management of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is challenging. The mammalian target of rapamycin (mTOR) inhibitor everolimus recently obtained approval from the Food and Drug Administration for the treatment of patients with advanced pancreatic neuroendocrine tumors (pNETs). Despite its promising antitumor efficacy observed in cell lines, clinical benefit for patients is unsatisfactory. The limited therapeutic potential of everolimus in cancer cells has been attributed to Akt activation due to feedback loops relief following mTOR inhibition. Combined inhibition of Akt might then improve everolimus antitumoral effect. In this regard, the somatostatin analog (SSA) octreotide has been shown to repress the PI3K/Akt pathway in some tumor cell lines. Moreover, SSAs are well tolerated and routinely used to reduce symptoms caused by peptide release in patients carrying functional GEP-NETs. We have recently established and characterized primary cultures of human pNETs and demonstrated the anti-proliferative effects of both octreotide and pasireotide. In this study, we aim at determining the antitumor efficacy of everolimus alone or in combination with the SSAs octreotide and pasireotide in primary cultures of pNETs. Everolimus reduced both Chromogranin A secretion and cell viability and upregulated Akt activity in single treatment. Its anti-proliferative and anti-secretory efficacy was not improved combined with the SSAs. Both SSAs did not overcome everolimus-induced Akt upregulation. Furthermore, caspase-dependent apoptosis induced by SSAs was lost in combined treatments. These molecular events provide the first evidence supporting the lack of marked benefit in patients co-treated with everolimus and SSA.


Lithium-induced reduction in intracellular inositol supply in cholinergically stimulated parotid gland.
The effects of lithium and cholinergic stimulation on inositol phospholipid metabolism have been assessed using rat parotid gland slices and isolated acinar cells labelled with 32Pi. Cholinergic stimulation using carbachol caused substantial breakdown of phosphatidylinositol 4,5-bisphosphate (PtdInsP2) and enhanced labelling of phosphatidate (PA) and phosphatidylinositol (PtdIns). Lithium alone had little effect upon 32Pi incorporation, but in combination with carbachol it greatly reduced the PtdIns labelling response to the agonist. Instead the label accumulated in a lipid identified as cytidine monophosphorylphosphatidate. There was also an enhancement of the PA labelling response to carbachol. These lithium-induced alterations in agonist-stimulated phospholipid metabolism were reversed if 10-30 mM-inositol was included in the incubation medium. Despite reduced PtdIns synthesis, lithium had relatively little effect on polyphosphoinositide labelling in stimulated cells. Resynthesis of polyphosphoinositides was monitored in acinar cells that had been stimulated with carbachol and then treated with atropine to block muscarinic receptors. Treatment with lithium during the carbachol-stimulation phase reduced the rate of phosphatidylinositol 4-phosphate synthesis, but had no significant effect upon PtdInsP2. The results suggest that an active inositol phosphatase pathway is essential to maintain intracellular inositol levels, but that PtdInsP2 synthesis is not markedly reduced by a substantial fall in intracellular inositol. This implies a close control over the rates of PtdInsP2 breakdown and resynthesis during agonist stimulation.


Chronic daily headache: correlation between the 2004 and the 1988 International Headache Society diagnostic criteria.
In a previous study, we compared the 1988 International Headache Society (IHS) criteria and the Silberstein-Lipton criteria (S-L) in a subspeciality clinic sample of 638 patients with chronic daily headache (CDH) assessed both clinically and with headache diaries. Both systems allowed for the classification of most patients with CDH. The 1988 IHS classification required multiple diagnoses and was more complex to apply. The aim of this study was to revisit the same database, now comparing the prior classification systems with the new 2004 IHS classification. In contrast with the 1st edition, the 2nd edition includes criteria for chronic migraine (CM), new daily persistent headache (NDPH), and hemicrania continua (HC). We reviewed the clinical records and the headache diaries of 638 patients seen between 1980 and 2001 at a headache center. All patients had primary CDH according to the S-L criteria. Using the S-L criteria as a reference, of the 158 patients with transformed migraine (TM) without medication overuse, just 9 (5.6%) met 2004 IHS criteria for CM. Most of the subjects were classified using combinations of migraine and CTTH diagnoses, much like the 1988 IHS classification. Similarly, using the new IHS system, just 41/399 (10.2%) subjects with TM with medication overuse were classified as probable CM with probable medication overuse. Most patients with NDPH without overuse were easily classified using the 2004 criteria (95.8%). Regarding NDPH with medication overuse, the diagnostic groups were much like results for the 1st edition. All patients with chronic tension-type headache (CTTH) and hemicrania continua (HC) according to the S-L system were easily classified using the 2004 IHS criteria. We conclude that the 2004 IHS criteria facilitate the classification of NDPH without medication overuse and HC. For subjects with TM according to the S-L system, the new IHS criteria are complex to use and require multiple diagnoses. Very few patients with TM in the S-L system could be classified with a single diagnosis in the 2004 IHS classification. In fact, CM was so rare that it would be virtually impossible to conduct clinical trials of this entity using the 2004 IHS criteria. Clinical trials of this entity should therefore be conducted using the S-L criteria. Finally, we propose that in the 3rd edition of the IHS classification, the diagnosis of NDPH be revised so as not to exclude migraine features.


Mapping Hidden Residual Structure within the Myc bHLH-LZ Domain Using Chemical Denaturant Titration.
Intrinsically disordered proteins (IDPs) underpin biological regulation and hence are highly desirable drug-development targets. NMR is normally the tool of choice for studying the conformational preferences of IDPs, but the association of regions with residual structure into partially collapsed states can lead to poor spectral quality. The bHLH-LZ domain of the oncoprotein Myc is an archetypal example of such behavior. To circumvent spectral limitations, we apply chemical denaturant titration (CDT)-NMR, which exploits the predictable manner in which chemical denaturants disrupt residual structure and the rapid exchange between conformers in IDP ensembles. The secondary structure propensities and tertiary interactions of Myc are determined for all bHLH-LZ residues, including those with poor NMR properties under native conditions. This reveals conformations that are not predictable using existing crystal structures. The CDT-NMR method also maps sites perturbed by the prototype Myc inhibitor, 10058-F4, to areas of residual structure.


The Triage of Older Adults with Physiologic Markers of Serious Injury Using a State-Wide Prehospital Plan.
In January of 2010, North Carolina (NC) USA implemented state-wide Trauma Triage Destination Plans (TTDPs) to provide standardized guidelines for Emergency Medical Services (EMS) decision making. No study exists to evaluate whether triage behavior has changed for geriatric trauma patients. The impact of the NC TTDPs was investigated on EMS triage of geriatric trauma patients meeting physiologic criteria of serious injury, primarily based on whether these patients were transported to a trauma center. This is a retrospective cohort study of geriatric trauma patients transported by EMS from March 1, 2009 through September 30, 2009 (pre-TTDP) and March 1, 2010 through September 30, 2010 (post-TTDP) meeting the following inclusion criteria: (1) age 50 years or older; (2) transported to a hospital by NC EMS; (3) experienced an injury; and (4) meeting one or more of the NC TTDP's physiologic criteria for trauma (n = 5,345). Data were obtained from the Prehospital Medical Information System (PreMIS). Data collected included proportions of patients transported to a trauma center categorized by specific physiologic criteria, age category, and distance from a trauma center. The proportion of patients transported to a trauma center pre-TTDP (24.4% [95% CI 22.7%-26.1%]; n = 604) was similar to the proportion post-TTDP (24.4% [95% CI 22.9%-26.0%]; n = 700). For patients meeting specific physiologic triage criteria, the proportions of patients transported to a trauma center were also similar pre- and post-TTDP: systolic blood pressure <90 mmHg (22.5% versus 23.5%); respiratory rate <10 or >29 (23.2% versus 22.6%); and Glascow Coma Scale (GCS) score <13 (26.0% versus 26.4%). Patients aged 80 years or older were less likely to be transported to a trauma center than younger patients in both the pre- and post-TTDP periods. State-wide implementation of a TTDP had no discernible effect on the proportion of patients 50 years and older transported to a trauma center. Under-triage remained common and became increasingly prevalent among the oldest adults. Research to understand the uptake of guidelines and protocols into EMS practice is critical to improving care for older adults in the prehospital environment.


Induction of leukemia-associated inhibitory activity and bone marrow granulocyte-macrophage progenitor cell alterations during infection with Abelson virus.
Neonatal and adult BALB/c mice were investigated in a longitudinal study for the acquisition of leukemia-associated inhibitory activity (LIA) interactions after inoculation with Abelson virus in vivo. Within 2 to 4 days after virus infection, the granulocyte-macrophage colony-forming cells from the bone marrow and spleen of the infected mice became insensitive to inhibition by LIA, even though colony morphology appeared normal. Shortly after, or simultaneously with, the detection of the colony-forming cell resistance phenomenon, LIA was found in bone marrow, spleen, and thymus cells. The abnormal interactions appeared to be related to induction of lymphoma in BALB/c neonates and to a lymphoproliferative disease in adult BALB/c mice. In contrast, normal cellular interactions were noted in adult C57BL/6 mice which were not susceptible to the Abelson disease after virus inoculation and in untreated neonatal and adult BALB/c and adult C57BL/6 mice. Their colony-forming cells were sensitive to inhibition by LIA, and no LIA was detected in their bone marrow, spleen, and thymus cells. The abnormal cellular interactions are similar to those noted in human leukemia, lymphoma, and "preleukemia." This suggests that Abelson virus-infected mice can serve as a model for the study of LIA interactions.


Restoring Finger-Specific Sensory Feedback for Transradial Amputees via Non-Invasive Evoked Tactile Sensation.
Objective: This study assessed the feasibility to restore finger-specific sensory feedback in transradial amputees with electrical stimulation of evoked tactile sensation (ETS). Methods: Here we investigated primary somatosensory cortical (SI) responses of ETS using Magnetoencephalography. Results: SI activations revealed a causal correlation with peripheral stimulation of projected finger regions on the stump skin. Peak latency was accountable to neural transmission from periphery to SI. Peak intensity of SI response was proportional to the strength of peripheral stimulation, manifesting a direct neural pathway from skin receptors to SI neurons. Active regions in SI at the amputated side were consistent to the finger/hand map of homunculus, forming a mirror imaging to that of the contralateral hand. With sensory feedback, amputees can recognize a pressure at prosthetic fingers as that at the homonymous lost fingers. Conclusions: Results confirmed that the direct neural pathway from periphery to SI allows effective communication of finger-specific sensory information to these amputees.


The Medstone STS: a technical review.
The Medstone STS does not require the urologist to compromise his lithotripsy success because of insufficient power, inadequate imaging, or restrictions caused by patient positioning. The attention to the details required for success in treatment in the investigators opinion make the Medstone STS a very attractive device for the performance of lithotripsy.


Perceptions among occupational and physical therapy students of a nontraditional methodology for teaching laboratory gross anatomy.
This pilot study was designed to assess the perceptions of physical therapy (PT) and occupational therapy (OT) students regarding the use of computer-assisted pedagogy and prosection-oriented communications in the laboratory component of a human anatomy course at a comprehensive health sciences university in the southeastern United States. The goal was to determine whether student perceptions changed over the course of a summer session regarding verbal, visual, tactile, and web-based teaching methodologies. Pretest and post-test surveys were distributed online to students who volunteered to participate in the pilot study. Despite the relatively small sample size, statistically significant results indicated that PT and OT students who participated in this study perceived an improved ability to name major anatomical structures from memory, to draw major anatomical structures from memory, and to explain major anatomical relationships from memory. Students differed in their preferred learning styles. This study demonstrates that the combination of small group learning and digital web-based learning seems to increase PT and OT students' confidence in their anatomical knowledge. Further research is needed to determine which forms of integrated instruction lead to improved student performance in the human gross anatomy laboratory.


Blood lead concentrations of Swedish preschool children in a community with high lead levels from mine waste in soil and dust.
The lead concentration in capillary blood was investigated in 49 preschool children (0.7-7.4 years of age) visiting a day-care center in a Swedish community with high lead contamination from mining and milling in soil and dust in populated areas [up to 1400 and 14,000 micrograms.g-1 (6.76 and 67.63 mumol.g-1) of dry weight, respectively]. The blood lead levels were examined twice (in April and in September) in 33 of the children. The lead levels were low on both sampling occasions [arithmetic mean 31 (SD 13, median 30, range 13-79) micrograms.l-1, ie, arithmetic mean 0.15, (SD 0.06, median 0.14, range 0.06-0.38) mumol.l-1]. Whereas children up to four years of age showed significantly increased levels from April to September, a significant decrease was seen in older children. The level of lead in soil at home, gender, smoking habits at home, and estimated level of hand-to-mouth activity did not appear as strong determinants of lead in blood. The results indicate that lead from mine waste in soil and dust fallout does not constitute a significant health hazard for preschool children in Falun.


Ficolins and the lectin pathway of complement in patients with systemic lupus erythematosus.
The complement system plays a pathophysiological role in systemic lupus erythematosus (SLE). This study aims to investigate whether an association exists between the ficolins that are part of the lectin complement pathway and SLE. EDTA plasma samples from 68 Danish SLE patients and 29 healthy donors were included in the study. Plasma concentrations of Ficolin-1, -2, and -3 were determined in specific sandwich ELISAs. Lectin pathway activity via Ficolin-3 was measured in ELISA on acetylated bovine serum albumin (acBSA) and measured as Ficolin-3 binding and deposition of C4, C3 and the terminal complement complex (TCC). SLE patients had increased levels of Ficolin-3, 21.6μg/ml as compared to 17.0μg/ml in healthy controls (P=0.0098). The Ficolin-1 plasma concentration was negatively correlated with SLE Disease Activity Index (SLEDAI) (Rho=-0.29, P=0.015) and positively correlated to the [Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index] (SDI) (Rho=0.27, P=0.026). The Ficolin-1 concentration was also associated with the occurrence of arterial (P=0.0053) but not venous thrombosis (P=0.42). Finally, deposition of C4, C3 and TCC in the Ficolin-3 pathway were all correlated to SLEDAI, respectively (P<0.0076). The Ficolin-1 association to SLEDAI and SDI as well as arterial thrombosis shown in this study suggests that Ficolin-1 may be a potential new biomarker for patients with SLE. Furthermore, Ficolin-3 mediated complement activation may be valuable in monitoring disease activity in SLE patients due to the high sensitivity for complement consumption in the assay independent of the Ficolin-3 concentration.


Induction of mammary tumors in virgin female BALB/c mice by single low doses of 7,12-dimethylbenz[a]anthracene.
The induction of mammary tumors in virgin female inbred BALB/c mice after administration of 7,12-dimethylbenz[a]anthracene (DMBA) over a wide range of doses was studied. Mice were exposed at 12 weeks of age to single or multiple doses of DMBA ranging from 0.0025 to 12.0 mg by gastric intubation and were checked regularly for mammary tumors. The experiment was terminated when the mice were 800 days of age. In the dose range of 0.0025--0.125 mg DMBA, the incidence of mammary tumors was dose-dependent. At higher doses, the mammary tumor incidence became less dose-dependent and was nearly independent of doses above the 0.25-mg level. Analysis of the data for the rate of appearance of mammary tumors with age of the animals and for the age at death of non-mammary tumor-bearing animals indicated that in the low dose range induction of mammary tumors was the predominant effect of DMBA exposure, whereas at moderate to high doses the toxic and carcinogenic effects of DMBA on other tissues significantly influenced the final incidence of mammary tumors. Greater than 90% of the tumors that resulted from administration of low doses of DMBA were adenocarcinomas. In contrast, adenocarcinomas and adenoacanthomas were found in approximately equal proportions following administration of high doses of DMBA.


Waiting lists and prioritization of children for services: Speech-language pathologists' perspectives.
Waiting lists occur when the availability of speech-language pathology services does not meet the demand. Speech-language pathologists (SLPs) commonly manage waiting lists and their consequences using prioritization. The aims of this study were to: (1) describe speech-language pathology waiting lists for children and factors associated with their presence in workplaces throughout the world, and (2) describe factors considered in and influencing SLPs' prioritization of children for services. A questionnaire about pediatric waiting lists and prioritization was completed by 267 SLPs from 10 countries working in health, disability, education, and private sectors. Valid responses to closed questions from 264 SLPs were analyzed quantitatively. Most (73.6 %) SLPs reported having a waiting list in their workplace. Waiting lists were most common in community health centres (97.4 %). Waiting times ranged from 0 to 42 months (M = 8.09, SD = 5.84). High priority was assigned to infants (77.4 %), toddlers (65.3 %), children with feeding difficulties (88.5 %), and children who stutter (47.4 %). Prioritization parameters ranked as most important were: severity (M = 4.34), availability of resources (M = 4.11), diagnosis (M = 4.04), and age (M = 3.91). Many workplaces have long waiting lists for speech-language pathology services. Young children, feeding, and stuttering were most often considered high priority; however, prioritization can be complex, implicit, and influenced by external factors. Collaborative development of explicit, transparent waiting list and prioritization guidelines within workplaces, and the development and evaluation of active waiting strategies for children and families are recommended.


Enhancement of radiation therapy by the novel vascular targeting agent ZD6126.
The aim of this study was to evaluate the antitumor efficacy of the novel vascular targeting agent ZD6126 (N-acetylcochinol-O-phosphate) in the rodent KHT sarcoma model, either alone or in combination with single- or fractionated-dose radiation therapy. C3H/HeJ mice bearing i.m. KHT tumors were injected i.p. with ZD6126 doses ranging from 10 to 150 mg/kg. Tumors were irradiated locally in unanesthetized mice using a linear accelerator. Tumor response to ZD6126 administered alone or in combination with radiation was assessed by clonogenic cell survival assay or tumor growth delay. Treatment with ZD6126 led to a rapid tumor vascular shutdown as determined by Hoechst 33342 diffusion. Histologic evaluation showed morphologic damage of tumor cells within a few hours after drug exposure, followed by extensive central tumor necrosis and neoplastic cell death as a result of prolonged ischemia. When combined with radiation, a 150 mg/kg dose of ZD6126 reduced tumor cell survival 10-500-fold compared with radiation alone. These enhancements in tumor cell killing could be achieved for ZD6126 given both before and after radiation exposure. Further, the shape of the cell survival curve observed after the combination therapy suggested that including ZD6126 in the treatment had a major effect on the radiation-resistant hypoxic cell subpopulation associated with this tumor. Finally, when given on a once-weekly basis in conjunction with fractionated radiotherapy, ZD6126 treatment was found to significantly increase the tumor response to daily 2.5 Gy fractions. The present results demonstrated that in the KHT sarcoma, ZD6126 caused rapid tumor vascular shutdown, induction of central tumor necrosis, tumor cell death secondary to ischemia, and enhancement of the antitumor effects of radiation therapy.


Correction of ventricular cerebrospinal fluid (CSF) samples for blood content does not increase sensitivity and specificity for the detection of CSF infection.
Blood contamination is commonly observed in ventricular cerebrospinal fluid (CSF) samples from patients with extraventricular drainage systems. Because the introduction of blood may interfere with the white blood cell count as a useful marker for the diagnosis of an infection, correction for blood content would be desirable. In a retrospective study, we analysed the use of correction formulas in 724 blood-contaminated ventricular CSF samples. Using a standard correction method the white blood cell count was not normalised in most CSF samples, with pleocytosis indicating an inflammatory stimulus set by the blood itself or by the foreign body. When correcting white blood cell counts in the CSF of culture-positive patients, some samples were normalised or overcorrected. In addition, correction of the CSF white blood cell count did not increase sensitivity and specificity for the detection of culture-positive CSF samples. Correction is not necessary when using the white blood cell count as a parameter to predict CSF infection in ventricular CSF samples.


[Effectiveness and tolerability of zoledronic acid in the treatment of metastatic prostate cancer].
To assess the effectiveness and tolerability of zoledronic acid in prostate cancer patients with bone metastases at the hormone-sensitive (HS) and hormone-independent (HI) stages. A nationwide, observational, prospective, open and multi-centre trial was devised, with a total of 218 male patients diagnosed with prostate cancer at the HS stage (36%) or HI stage (64%) who were administered zoledronic acid (4 mg/IV/month for 6 months) in addition to their specific oncological treatment. Effectiveness was assessed by the following means: 1) Assessment of the improvement in pain and mobility; 2) Incidence and time to onset of skeletal-related events (SREs) and 3) Analysis of bone markers. Tolerability was assessed by means of registering the number and type of adverse effects. A satisfaction survey was carried out amongst the patients after the end of the trial. Out of the 218 patients, 170 (78%) were evaluable for effectiveness. A decrease in pain ratings at rest and during movement was observed in all patients, whether in the HS or HI groups (p < 0.0001). Improved mobility was observed likewise (p = 0.005), as was quality of life. The global incidence of skeletal events was 11.2%, with a time to onset of SREs of 10.7 months. There were no significant differences observed between HS vs. HI patients. Osteolysis markers (N-telopeptide) decreased significantly with the treatment across both the HS and HI groups. For safety reasons. 212 patients were evaluable (97.2%). The incidence of adverse drug reactions was 16% (34/212) and was found to be significantly higher in HS patients (22.4%) compared with HI patients (11.9%). Overall, the tolerability of zoledronic acid was good, with no significant morbidity in either group (HS and HI). 66% of the patients reported feeling satisfied or very satisfied. Zoledronic acid proved effective in the relief of pain, improving mobility and quality of life as well as reducing or delaying the occurrence of skeletal-related events in prostate cancer patients presenting metastatic bone disease, regardless of the phase, whether HS or HI, they found themselves in. Tolerability and patient satisfaction were rates as good.


Temperature-dependent dissociation of Lucké renal adenocarcinoma cells.
Fragments of Lucké renal adenocarcinoma were subjected to dissociation by rapid shaking after exposure to a divalent cation-free electrolyte solution, with or without 5 X 10(-4) M ethylenediaminetetraacetate (EDTA), at 7 degrees C and 28 degrees C. More cells detached at 28 degrees C than at 7 degrees C. Dissociation of cells from normal mesonephros fragments was minimal at both temperatures. It has been shown else-where that this frog tumor elaborates collagenase in a temperature-dependent manner. More collagenase is detected at 30 degrees C than at 7 degrees C. Normal kidney elaborates low levels of collagenase at both temperatures. Because our results suggested the possibility that some dissociation of the tumor cells may have been attributable to tumor-elaborated collagenase, we studied the effect of two collagenase inhibitors on dissociation. Both EDTA at high concentration and cysteine inhibit collagenase and both diminished tumor-cell dissociation.


Probing Transferrin Receptor Overexpression in Gastric Cancer Mice Models.
Exposure to carcinogenic chemicals, Helicobacter pylori infection, and high dietary salt are the risk factors associated with gastric cancer. Mice models of gastric cancer are key to understanding the cancer mechanism, to discerning the role played by different factors, and to determining therapeutic effects of different treatments. The goal has been to find targets which are only expressed with cancer so that they can be targeted specifically without harming normal cells. One such target could be the transferrin receptor, a glycoprotein receptor that is expressed many-folds on rapidly growing cells due to the greater demand of iron. In this study, gastric cancer was developed in mice (BALB/c) with human cancer-associated risk factors by feeding them with tumor-inducing concentration of methyl nitrosourea, dietary salt, and H. pylori along with normal feed and water. Three strategies were adopted to induce gastric cancer; (1) use of N-methyl-N-nitrosourea (MNU) with high dietary salt (NaCl), (2) infection with H. pylori (isolated from human gastric tissue), and (3) use of MNU along with high concentration of NaCl after H. pylori infection. Mice were dissected after induction, and histological study of gastric tissue was done with Hematoxylin and Eosin staining. A diagnostic probe comprising transferrin conjugated with cadmium sulfide quantum dots was prepared and characterized. It was used to study the transferrin receptor overexpression in gastric tissue of cancer-induced mice relative to the normal mice. Mice of group 3 showed the highest rate of the cancer incidence ratio (96%) along with a high expression of transferrin receptors among the three groups. Histochemical studies showed that different types of gastric cancer depend upon the cancer-induction conditions. The mouse model of group 3 has the potential to be used in the future to study the therapeutic effects of cancer medicines, and overexpression of transferrin receptors could be identified through the designed probe to be used as diagnostics.


[Current clinical immunology: a genetic and molecular perspective].
During the last few decades, basic scientists and clinicians have gained a deeper insight of the cellular and molecular physiology of the immune system. The widespread application of molecular biology and genetic techniques has advanced our understanding of states of health and disease, bringing forth renewed hopes concerning the advent of a more "specific" therapeutic era of clinical immunology. The precise structural and genetic characterization of molecular complexes such as B and T-cell receptors, the Major Histocompatibility Complex (MHC), cytokines, chemokines, cellular receptors and co-receptors has produced a wealth of information open to both diagnostic and therapeutic purposes. We herein review several recent advances in the molecular and genetic characterization of immune deficiency states, autoimmunity and the induction of antigen specific immune unresponsiveness or tolerance, together with the therapeutic implications of these findings.


Wanna know about vaping? Patterns of message exposure, seeking and sharing information about e-cigarettes across media platforms.
Awareness and use of electronic cigarettes has rapidly grown in the USA recently, in step with increased product marketing. Using responses to a population survey of US adults, we analysed demographic patterns of exposure to, searching for and sharing of e-cigarette-related information across media platforms. An online survey of 17,522 US adults was conducted in 2013. The nationally representative sample was drawn from GfK Group's KnowledgePanel plus off-panel recruitment. Fixed effects logit models were applied to analyse relationships between exposure to, searching for and sharing of e-cigarette-related information and demographic characteristics, e-cigarette and tobacco use, and media behaviours. High levels of awareness about e-cigarettes were indicated (86% aware; 47% heard through media channels). Exposure to e-cigarette-related information was associated with tobacco use, age, gender, more education, social media use and time spent online. Although relatively small proportions of the sample had searched for (∼5%) or shared (∼2%) e-cigarette information, our analyses indicated demographic patterns to those behaviours. Gender, high income and using social media were associated with searching for e-cigarette information; lesbian, gay and bisexual and less education were associated with sharing. Current tobacco use, age, being Hispanic and time spent online were associated with both searching and sharing. US adults are widely exposed to e-cigarette marketing through the media; such marketing may differentially target specific demographic groups. Further research should longitudinally examine how exposure to, searching for and sharing of e-cigarette information relate to subsequent use of e-cigarettes and/or combustible tobacco.


Is consumer behaviour towards footwear predisposing for lower extremity injuries in runners and walkers? A prospective study.
Runners and walkers often suffer from lower extremity injuries. Little is known about the relationship between their consumer behaviour towards footwear and the development of those injuries. Therefore, the aim of this study was to investigate if consumer behaviour towards footwear is a risk factor for lower extremity injuries. A prospective cohort study was set-up in leisure-time walkers and runners. Potential risk factors in consumer behaviour were obtained by means of a baseline questionnaire related to the acquisition of current walking or running shoes. Information on injuries sustained during a 24 week period after the baseline questionnaire was obtained in 104 runners and 104 walkers using a 2-weekly questionnaire. Binary logistic regression analysis was used to identify risk factors for lower extremity injuries in the consumer behaviour. Forty- nine (24%) subjects suffered a self-reported lower extremity injury. 35 injuries occurred in runners and 14 among walkers.Undergoing a gait analysis before buying shoes was associated with an increased occurrence of lower extremity injuries (odds ratio (OR) 4.76). A protective factor was caring a lot about the right fitting of the shoes (OR 0.11). Runners and walkers should pay attention to the correct size when buying footwear to diminish the risk of lower extremity injury. Buying footwear after a gait analysis increased the risk of a lower extremity injury in runners and walkers, however, this might be associated with the increased risk that was already present because of previous injury. This trial was not registered since this was an observational study and no intervention took place.


The influence of trace NO(2) on the kinetics of ammonia oxidation and the characteristics of nitrogen removal from wastewater.
Ammonia oxidizing bacteria-enriched sludge was obtained in a sequencing batch reactor with synthetic wastewater. Batch tests of ammonia oxidation were carried out with the sludge, in the presence of only trace NO(2) and in the presence of O(2) and trace NO(2), respectively. The Andrews model is used to describe NO(2)-dependent ammonia oxidation. The maximum ammonia oxidation rate of 139.11 mg N.(g sludge COD h)(-1), occurred in the presence of 21% O(2) and 100 ppm NO(2), which was 3 times higher than the aerobic ammonia oxidation rate without NO(2). The kinetic model of ammonia oxidation in the presence of O(2) and trace NO(2) is developed, and the function of NO(2) apparently enhancing ammonia oxidation is suggested. The maximal nitrogen removel of 34.19% occurred at the 21% O(2) and 100 ppm NO(2) in the mixed gases. Nitrogen removal principally depended on the denitrification activity and NO(2)-dependent ammonia oxidation activity of ammonia-oxidizing bacteria (AOB).


Similarity of bone ingrowth in rats and goats: a bone chamber study.
Bone ingrowth has been studied extensively in rats by use of bone chambers. However, it is not known whether results in small animals, with respect to bone ingrowth processes, are similar in large animals, in which more realistic models are often used. Since the metabolic rate in small animals is, in general, higher than that in larger species, we hypothesized that bone ingrowth in chambers develops more rapidly in small animals. Therefore, identical bone chambers were placed in the tibias of rats and goats. After 6 and 12 weeks, histologic and histomorphometric examinations were carried out to measure bone and tissue ingrowth distances. Bone ingrowth was higher in both species at 12, compared with 6 weeks (P < 0.01). Tissue ingrowth in general (including soft tissue) was less in rats than in goats at both time periods (P < 0.001). However, bone ingrowth did not differ between species. Thus, when differences in size of an osseous defect are corrected for, there seems to be only little influence of differences in body size.


Molecular characterization of a prophenoloxidase cDNA from the malaria mosquito Anopheles stephensi.
Some refractory anopheline mosquitoes are capable of killing Plasmodium, the causative agent of malaria, by melanotic encapsulation of invading ookinetes. Phenoloxidase (PO) appears to be involved in the formation of melanin and toxic metabolites in the surrounding capsule. A cDNA encoding Anopheles stephensi prophenoloxidase (Ans-proPO) was isolated from a cDNA library screened with an amplimer produced by reverse transcriptase polymerase chain reaction (RT-PCR) with degenerate primers designed against conserved proPO sequences. The 2.4-kb-long cDNA has a 2058 bp open reading frame encoding Ans-proPO of 686 amino acids. The deduced amino acid sequence shows significant homology to other insect proPO sequences especially at the two putative copper-binding domains. In A. stephensi, Ans-proPO expression was detected in larval, pupal and adult stages. The Ans-proPO mRNA was detected by RT-PCR and in situ hybridization in haemocytes, fat body and epidermis of adult female mosquitoes. A low level of expression was detected in the ovaries, whereas no expression was detected in the midguts. Semi-quantitative RT-PCR analysis of Ans-proPO mRNA showed that its expression was similar in adult female heads, thoraxes and abdomens. No change in the level of Ans-proPO expression was found in adult females after blood feeding, bacterial challenge or Plasmodium berghei infection. However, elevated PO activity was detected in P. berghei-infected mosquitoes, suggesting that in non-selected permissive mosquitoes PO may be involved in limiting parasite infection. Genomic Southern blot and immunoblots suggest the presence of more than one proPO gene in the A. stephensi genome, which is consistent with the findings in other Diptera and Lepidoptera species. The greatest similarity in sequence and expression profile between Ans-proPO and A. gambiae proPO6 suggests that they might be homologues. Our results demonstrate that Ans-proPO is constitutively expressed through different developmental stages and under different physiological conditions, implying that other factors in the proPO activation cascade regulate melanotic encapsulation.


Densitometric study of developing femur.
The purpose of this work was to extend to long bones the study on the ossification of human fetal skeleton in relation to conceptual age by a quantitative methodological approach. Postero-anterior scans were performed on 29 dried fetal femora (from 11.5 weeks of conceptual age to term) by a Hologic QDR 1000 X-ray densitometer with Ultra-Hi-Resolution software. The results were expressed as bone mineral content (BMC, g) and bone mineral density (BMD, g/cm2). BMD was calculated on a rectangular area corresponding to the total length and minimum width of the shaft. This area was divided into five equal sections along its longitudinal axis in order to estimate the rate of ossification from a spatio-temporal point of view. Our data show that BMC has a high correlation with conceptual age during the whole prenatal life, increasing in the third trimester (r >/= 0. 96). During development, BMD is progressively less correlated with conceptual age (r = 0.95 in the first half of development, r = 0.68 in the second half), particularly according to a bidirectional gradient from the middle to the proximal and distal ends of the shaft. Our findings confirm the data obtained in our previous studies on the ossification of fetal human spines, and suggest an individual variability in bone density at term of development and particularly at the level of spongiosa, viz. in the areas mostly involved in architectural changes during the morphogenesis of the long bones.


Donor-derived Cell-free DNA Identifies Antibody-mediated Rejection in Donor Specific Antibody Positive Kidney Transplant Recipients.
Elevated levels of donor-derived cell-free DNA (dd-cfDNA) in the plasma of renal allograft recipients indicates organ injury and an increased probability of active rejection. Donor-specific antibodies (DSA) to HLA antigens are associated with risk of antibody-mediated rejection (ABMR). This study assessed the combined use of dd-cfDNA and DSA testing to diagnose active ABMR. Donor-derived cell-free DNA was assayed in 90 blood samples with paired DSA and clinically indicated biopsies from 87 kidney transplant patients. Sixteen cases met criteria for active ABMR. Performance characteristics of dd-cfDNA for diagnosis of active ABMR were determined for samples with prior or current positive DSA (DSA+, n = 33). The median level of dd-cfDNA (2.9%) in DSA+ patients with active ABMR was significantly higher than the median level (0.34%) in DSA+ patients without ABMR (P < 0.001). The median level of dd-cfDNA in DSA- patients was 0.29%. The positive predictive value of dd-cfDNA (at 1%) to detect active ABMR in DSA+ patients was 81%, whereas the negative predictive value was 83%. The positive predictive value for DSA+ alone was 48%. The combined use of dd-cfDNA and DSA testing may improve the noninvasive diagnosis of active ABMR in kidney transplant patients. Patients with dd-cfDNA+/ DSA+ results have a high probability of active ABMR.


Effect of salt stress on seed germination and seedling growth of three salinity plants.
Seeds of three halophyte species included Limonium sinense Kuntze, Glycine soja sieb. and Sorghum sudanense Stapf. were used to investigate the effects of different salinity concentrations on their germination percentage, germination energy, germination index, relative germination rate, relative salt-injury rate, radicle length and hypocotyl length. Results showed that seeds of G. soja can germinate well and rapidly at lower level of salt (< 200 mmol L(-1)), 50 mmol L(-1) salt concentrations is better to S. sudanense, suitable salt concentrations was beneficial to germinate of S. sudanense seeds. Seeds of L. sinense and S. sudanense can germinate at higher level of salt (400 mmol L(-1)). Three plant seeds had different physiological mechanism for germination under salt stress, radicle hypocotyl ratio of L. sinense and S. sudanense increased with increasing salt suggested that they had the higher tolerance in shoot growth under NaCl stress, which is perhaps the reason for their wide utilisation for saline soil rehabilitation.


Thoracoscopic lobectomy is associated with acceptable morbidity and mortality in patients with predicted postoperative forced expiratory volume in 1 second or diffusing capacity for carbon monoxide less than 40% of normal.
A predicted postoperative (ppo) forced expiratory volume in 1 second (FEV1%) or diffusing capacity of the lung for carbon monoxide (DLCO%) of <40% has traditionally been considered to convey a high risk of lobectomy owing to elevated postoperative morbidity and mortality. These recommendations, however, were largely derived from the pre-video-assisted thoracoscopic surgical (VATS) era. We hypothesized that VATS lobectomy would be associated with acceptable morbidity and mortality at ppoFEV1% and ppoDLCO% values < 40%. PpoFEV1% and ppoDLCO% were calculated for patients undergoing open or VATS lobectomy for lung cancer in the Society of Thoracic Surgeons General Thoracic database from 2009 to 2011. Univariate comparisons, multivariate analyses, and 1:1 propensity matching were performed. A total of 13,376 patients underwent lobectomy (50.9% open, 49.1% VATS). A decreased ppoFEV1% and ppoDLCO% were each independent predictors for both cardiopulmonary complications and mortality in the open group (all P ≤ .008). In the VATS group, ppoFEV1% was an independent predictor of complications (P = .001) but not mortality (P = .77), and ppoDLCO% was an independent predictor of complications (P = .046) and mortality (P = .008). With decreasing ppoFEV1% or ppoDLCO%, complications and mortality increased at a greater rate in the open lobectomy than in a propensity-matched VATS group (n = 4215 each). For patients with ppoFEV1% < 40%, mortality was greater in the open (4.8%) than in the matched VATS group (0.7%, P = .003). Similar results were seen for ppoDLCO% < 40% (5.2% open, 2.0% VATS, P = .003). The rate of complications was significantly greater at ppoFEV1% < 40% in the open (21.9%) than in the matched VATS (12.8%, P = .005) group and similar results were seen with ppoDLCO% < 40% (14.9% open, 10.4% VATS, P = .016). VATS lobectomy can be performed with acceptable rates of morbidity and mortality in patients with reduced ppoFEV1% or ppoDLCO%.


Engineering a catabolic pathway in plants for the degradation of 1,2-dichloroethane.
Plants are increasingly being employed to clean up environmental pollutants such as heavy metals; however, a major limitation of phytoremediation is the inability of plants to mineralize most organic pollutants. A key component of organic pollutants is halogenated aliphatic compounds that include 1,2-dichloroethane (1,2-DCA). Although plants lack the enzymatic activity required to metabolize this compound, two bacterial enzymes, haloalkane dehalogenase (DhlA) and haloacid dehalogenase (DhlB) from the bacterium Xanthobacter autotrophicus GJ10, have the ability to dehalogenate a range of halogenated aliphatics, including 1,2-DCA. We have engineered the dhlA and dhlB genes into tobacco (Nicotiana tabacum 'Xanthi') plants and used 1,2-DCA as a model substrate to demonstrate the ability of the transgenic tobacco to remediate a range of halogenated, aliphatic hydrocarbons. DhlA converts 1,2-DCA to 2-chloroethanol, which is then metabolized to the phytotoxic 2-chloroacetaldehyde, then chloroacetic acid, by endogenous plant alcohol dehydrogenase and aldehyde dehydrogenase activities, respectively. Chloroacetic acid is dehalogenated by DhlB to produce the glyoxylate cycle intermediate glycolate. Plants expressing only DhlA produced phytotoxic levels of chlorinated intermediates and died, while plants expressing DhlA together with DhlB thrived at levels of 1,2-DCA that were toxic to DhlA-expressing plants. This represents a significant advance in the development of a low-cost phytoremediation approach toward the clean-up of halogenated organic pollutants from contaminated soil and groundwater.