Analysis of the visual spatiotemporal properties of American Sign Language.

Careful measurements of the temporal dynamics of speech have provided important insights into phonetic properties of spoken languages, which are important for understanding auditory perception. By contrast, analytic quantification of the visual properties of signed languages is still largely uncharted. Exposure to sign language is a unique experience that could shape and modify low-level visual processing for those who use it regularly (i.e., what we refer to as the Enhanced Exposure Hypothesis). The purpose of the current study was to characterize the visual spatiotemporal properties of American Sign Language (ASL) so that future studies can test the enhanced exposure hypothesis in signers, with the prediction that altered vision should be observed within, more so than outside, the range of properties found in ASL. Using an ultrasonic motion tracking system, we recorded the hand position in 3-dimensional space over time during sign language production of signs, sentences, and narratives. From these data, we calculated several metrics: hand position and eccentricity in space and hand motion speed. For individual signs, we also measured total distance travelled by the dominant hand and total duration of each sign. These metrics were found to fall within a selective range, suggesting that exposure to signs is a specific and unique visual experience, which might alter visual perceptual abilities in signers for visual information within the experienced range, even for non-language stimuli

Macroeconomic impacts of demographic change in Scotland : a computable general equilibrium analysis

This paper combines a multi-period economic Computable General Equilibrium (CGE) modelling framework with a demographic model to analyse the macroeconomic impact of the projected demographic trends in Scotland. Demographic trends are defined by the existing fertility-mortality rates and the level of annual net-migration. We employ a combination of a demographic and a CGE simulation to track the impact of changes in demographic structure upon macroeconomic variables under different scenarios for annual migration. We find that positive net migration can cancel the expected negative impact upon the labour market of other demographic changes. (Pressure on wages, falling employment). However, the required size of the annual net-migration is far higher than the current trends. The policy implication suggested by the results is that active policies are needed to attract migrants. We nevertheless report results when varying fertility and mortality assumptions. The impact of varying those assumptions is rather small

Kinetic models reveal the in vivo mechanisms of mutagenesis in microbes and man

This review summarizes the evidence indicating that mutagenic mechanisms in vivo are essentially the same in all living cells. Unique metabolic reactions to a particular environmental stress apparently target specific genes for increased rates of transcription and mutation, resulting in higher mutation rates for those genes most likely to solve the problem. Kinetic models which have demonstrated predictive value are described and are shown to simulate mutagenesis in vivo in Escherichia coli, the p53 tumor suppressor gene, and somatic hypermutation. In all three models, direct correlations are seen between mutation frequencies and transcription rates. G and C nucleosides in single-stranded DNA (ssDNA) are intrinsically mutable, and G and C silent mutations in p53 and in VH framework regions provide compelling evidence for intrinsic mechanisms of mutability, since mutation outcomes are neutral and are not selected. During transcription, the availability of unpaired bases in the ssDNA of secondary structures is rate-limiting for, and determines the frequency of mutations in vivo. In vitro analyses also verify the conclusion that intrinsically mutable bases are in fact located in ssDNA loops of predicted stem-loop structures (SLSs)

Effects of a physiotherapy and occupational therapy intervention on mobility and activity in care home residents: a cluster randomised controlled trial

Objective To compare the clinical effectiveness of a programme of physiotherapy and occupational therapy with standard care in care home residents who have mobility limitations and are dependent in performing activities of daily living

I. VH gene transcription creates stabilized secondary structures for coordinated mutagenesis during somatic hypermutation

During the adaptive immune response, antigen challenge triggers a million-fold increase in mutation rates in the variable-region antibody genes. The frequency of mutation is causally and directly linked to transcription, which provides ssDNA and drives supercoiling that stabilizes secondary structures containing unpaired, intrinsically mutable bases. Simulation analysis of transcription in VH5 reveals a dominant 65nt secondary structure in the non-transcribed strand containing six sites of mutable ssDNA that have also been identified independently in human B cell lines and in primary mouse B cells. This dominant structure inter-converts briefly with less stable structures and is formed repeatedly during transcription, due to periodic pauses and backtracking. In effect, this creates a stable yet dynamic mutability platform consisting of ever-changing patterns of unpaired bases that are simultaneously exposed and therefore able to coordinate mutagenesis. Such a complex of secondary structures may be the source of ssDNA for enzyme-based diversification, which ultimately results in high affinity antibodies

Geochemical Signatures as a Tool for Vermiculite Provenance Determination

Thirty-eight samples of known origin (China, Libby MT, South Africa, South Carolina) and 6 vermiculite product samples of unknown origin were analyzed for major and trace elements, including rare earth elements to determine the feasibility of distinguishing the provenance of the samples based upon a geochemical signature. Probability plots suggest that two of the four groups (Libby, South Carolina) were comprised of two subgroups. Results of hierarchical cluster analysis are highly sensitive to the linkage method chosen. Ward’s method is the most useful for this data and suggests that there are five groups within the data set (South African samples, two subsets of the Libby samples, a subset of the South Carolina samples, and a second subset of the South Carolina samples combined with the China samples). Similar results were obtained using k-cluster analysis. Neither clustering method was able to distinguish samples from China from the South Carolina samples. Discriminant analysis was used on a four-category model comprised of the original four groups and on a six-category model comprised of the five categories identified from the cluster analysis but with the China samples grouped into a sixth category. The discriminant/classification model was able to distinguish all of the groups including the China samples from one another for both the four- and six-category models with 100% of the samples properly classified. The 6 unknown product samples were classified with a probability of consistency of 99%. Both discriminant models were also run with a subset of our analyte set to be consistent with the smaller Gunter et al., (2005) analyte set. Twenty vermiculite samples (nine of known origin and eleven of unknown origin) from their study were classified based on our discriminant models with the reduced set of analytes. Of the twenty samples, Gunter et al. (2005) was able to classify 16 with cluster analysis while our 4-category discriminant analysis model allowed us to classify all twenty. Of the 16 samples Gunter et al. (2005) classified using cluster analysis, all but one sample was assigned the same classification by our 4-category model. Of the nine samples with known origin, all were correctly classified. Similar results were obtained for the six-category model. Comparison of the plots of the canonical roots, the Wilks’ L, and the square Mahalanobis distances suggest the full analyte set provides better discrimination of the groups than the reduced analyte set. The six-category model is more consistent with the results of the probability plots and the cluster analysis. Discriminant analysis of geochemical data from vermiculite ore is a powerful technique for determining the ore’s provenance

Fluidized Bed Asbestos Sampler Design and Testing

A large number of samples are required to characterize a site contaminated with asbestos from previous mine or other industrial operations. Current methods, such as EPA Region 10’s glovebox method, or the Berman Elutriator method are time consuming and costly primarily because the equipment is difficult to decontaminate between samples. EPA desires a shorter and less costly method for characterizing soil samples for asbestos. The objective of this was to design and test a qualitative asbestos sampler that operates as a fluidized bed. The proposed sampler employs a conical spouted bed to vigorously mix the soil and separate fine particulate including asbestos fibers on filters. The filters are then analyzed using transmission electron microscopy for presence of asbestos. During initial testing of a glass prototype using ASTM 20/30 sand and clay fines as asbestos surrogates, fine particulate adhered to the sides of the glass vessel and the tubing to the collection filter – presumably due to static charge on the fine particulate. This limited the fines recovery to ~5% of the amount added to the sand surrogate. A second prototype was constructed of stainless steel, which improved fines recovery to about 10%. Fines recovery was increased to 15% by either humidifying the inlet air or introducing a voltage probe in the air space above the sample. Since this was not a substantial improvement, testing using the steel prototype proceeded without using these techniques. Final testing of the second prototype using asbestos suggests that the fluidized bed is considerably more sensitive than the Berman elutriator method. Using a sand/tremolite mixture with 0.005% tremolite, the Berman elutriator did not segregate any asbestos structures while the fluidized bed segregated an average of 11.7. The fluidized bed was also able to segregate structures in samples containing asbestos at a 0.0001% concentration, while the Berman elutriator method did not detect any fibers at this concentration. Opportunities for improvement with the fluidized bed include improving reproducibility among replicates, increasing mass recovery, improving the lid gasket seal

Mechanisms of Genotoxin-Induced Transcription and Hypermutation in p53

It is widely assumed that genotoxin-induced damage (e.g., G-to-T transversions) to the tumor suppressor gene, p53, is a direct cause of cancer. However, genotoxins also induce the stress response, which upregulates p53 transcription and the formation of secondary structures from ssDNA. Since unpaired bases are thermodynamically unstable and intrinsically mutable, increased transcription could be the cause of hypermutation, and thus cancer. Support for this hypothesis has been obtained by analyzing 6662 mutations in all types of cancer compared to lung and colon cancers, using the p53 mutation database. The data suggest that genotoxins have two independent effects: first, they induce p53 transcription, which increases the number of mutable bases that determine the incidence of cancer. Second, genotoxins may alter the fate, or ultimate mutation of a mutable base, for example, by causing more of the available mutable Gs to mutate to T, leaving fewer to mutate to A. Such effects on the fate of mutable bases have no impact on the incidence of cancer, as both types of mutations lead to cancer

Population based time trends and socioeconomic variation in use of radiotherapy and radical surgery for prostate cancer in a UK region: continuous survey

Objective To examine variation in the management of prostate cancer in patients with different socioeconomic status

B-type natriuretic peptide-guided treatment for heart failure

Background Heart failure is a condition in which the heart does not pump enough blood to meet all the needs of the body. Symptoms of heart failure include breathlessness, fatigue and fluid retention. Outcomes for patients with heart failure are highly variable; however on average, these patients have a poor prognosis. Prognosis can be improved with early diagnosis and appropriate use of medical treatment, use of devices and transplantation. Patients with heart failure are high users of healthcare resources, not only due to drug and device treatments, but due to high costs of hospitalisation care. B‐type natriuretic peptide levels are already used as biomarkers for diagnosis and prognosis of heart failure, but could offer to clinicians a possible tool to guide drug treatment. This could optimise drug management in heart failure patients whilst allaying concerns over potential side effects due to drug intolerance. Objectives To assess whether treatment guided by serial BNP or NT‐proBNP (collectively referred to as NP) monitoring improves outcomes compared with treatment guided by clinical assessment alone. Search methods Searches were conducted up to 15 March 2016 in the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE (OVID), Embase (OVID), the Database of Abstracts of Reviews of Effects (DARE) and the NHS Economic Evaluation Database in the Cochrane Library. Searches were also conducted in the Science Citation Index Expanded, the Conference Proceedings Citation Index on Web of Science (Thomson Reuters), World Health Organization International Clinical Trials Registry and ClinicalTrials.gov. We applied no date or language restrictions. Selection criteria We included randomised controlled trials of NP‐guided treatment of heart failure versus treatment guided by clinical assessment alone with no restriction on follow‐up. Adults treated for heart failure, in both in‐hospital and out‐of‐hospital settings, and trials reporting a clinical outcome were included. Data collection and analysis Two review authors independently selected studies for inclusion, extracted data and evaluated risk of bias. Risk ratios (RR) were calculated for dichotomous data, and pooled mean differences (MD) (with 95% confidence intervals (CI)) were calculated for continuous data. We contacted trial authors to obtain missing data. Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, we assessed the quality of the evidence and GRADE profiler (GRADEPRO) was used to import data from Review Manager to create a 'Summary of findings' table. Main results We included 18 randomised controlled trials with 3660 participants (range of mean age: 57 to 80 years) comparing NP‐guided treatment with clinical assessment alone. The evidence for all‐cause mortality using NP‐guided treatment showed uncertainty (RR 0.87, 95% CI 0.76 to 1.01; patients = 3169; studies = 15; low quality of the evidence), and for heart failure mortality (RR 0.84, 95% CI 0.54 to 1.30; patients = 853; studies = 6; low quality of evidence). The evidence suggested heart failure admission was reduced by NP‐guided treatment (38% versus 26%, RR 0.70, 95% CI 0.61 to 0.80; patients = 1928; studies = 10; low quality of evidence), but the evidence showed uncertainty for all‐cause admission (57% versus 53%, RR 0.93, 95% CI 0.84 to 1.03; patients = 1142; studies = 6; low quality of evidence). Six studies reported on adverse events, however the results could not be pooled (patients = 1144; low quality of evidence). Only four studies provided cost of treatment results, three of these studies reported a lower cost for NP‐guided treatment, whilst one reported a higher cost (results were not pooled; patients = 931, low quality of evidence). The evidence showed uncertainty for quality of life data (MD ‐0.03, 95% CI ‐1.18 to 1.13; patients = 1812; studies = 8; very low quality of evidence). We completed a 'Risk of bias' assessment for all studies. The impact of risk of bias from lack of blinding of outcome assessment and high attrition levels was examined by restricting analyses to only low 'Risk of bias' studies. Authors' conclusions In patients with heart failure low‐quality evidence showed a reduction in heart failure admission with NP‐guided treatment while low‐quality evidence showed uncertainty in the effect of NP‐guided treatment for all‐cause mortality, heart failure mortality, and all‐cause admission. Uncertainty in the effect was further shown by very low‐quality evidence for patient's quality of life. The evidence for adverse events and cost of treatment was low quality and we were unable to pool results.</p