Examining the Agreement of Structural Loss Measured With Heidelberg Retinal Tomograhy and Functional Loss With Standard Automated Perimetry (SAP; Octopus), Pulsar Perimetry (PP), and Moorfields Motion Displacement Test (MDT) Perimetry

Purpose: To examine the relationship of functional measurements with structural measures. Methods: 146 eyes of 83 test subjects underwent Heidelberg Retinal Tomography (HRTIII) (disc area<2.43, mphsd<40), and perimetry testing with Octopus (SAP; Dynamic), Pulsar (PP; TOP) and Moorfields MDT (ESTA). Glaucoma was defined as progressive structural or functional loss (20 eyes). Perimetry test points were grouped into 6 sectors based on the estimated optic nerve head angle into which the associated nerve fiber bundle enters (Garway-Heath map). Perimetry summary measures (PSM) (MD SAP/ MD PP/ PTD MDT) were calculated from the average total deviation of each measured threshold from the normal for each sector. We calculated the 95% significance level of the sectorial PSM from the respective normative data. We calculated the percentage agreement with group1 (G1), healthy on HRT and within normal perimetric limits, and group 2 (G2), abnormal on HRT and outside normal perimetric limits. We also examined the relationship of PSM and rim area (RA) in those sectors classified as abnormal by MRA (Moorfields Regression Analysis) of HRT. Results: The mean age was 65 (range= [37, 89]). The global sensitivity versus specificity of each instrument in detecting glaucomatous eyes was: MDT 80% vs. 88%, SAP 80% vs. 80%, PP 70% vs. 89% and HRT 80% vs. 79%. Highest percentage agreement of HRT (respectively G1, G2, sector) with PSM were MDT (89%, 57%, nasal superior), SAP (83%, 74%, temporal superior), PP (74%, 63%, nasal superior). Globally percentage agreement (respectively G1, G2) was MDT (92%, 28%), SAP (87%, 40%) and PP (77%, 49%). Linear regression showed there was no significant trend globally associating RA and PSM. However, sectorally the supero-nasal sector had a statistically significant (p<0.001) trend with each instrument, the associated r2 coefficients are (MDT 0.38 SAP 0.56 and PP 0.39). Conclusions: There were no significant differences in global sensitivity or specificity between instruments. Structure-function relationships varied significantly between instruments and were consistently strongest supero-nasally. Further studies are required to investigate these relationships in detail.

Self-Care, Sense Of Coherence And Depression In Patients Hospitalized For Decompensated Heart Failure

OBJECTIVE To analyze the self-care behaviors according to gender, the symptoms of depression and sense of coherence and compare the measurements of depression and sense of coherence according to gender. METHOD A correlational, cross-sectional study that investigated 132 patients with decompensated heart failure (HF). Data were collected through interviews and consultation to medical records, and analyzed using the chi-square and the Student's t tests with significance level of 0.05. Participants were 75 men and 57 women, aged 63.2 years on average (SD = 13.8). RESULTS No differences in self-care behavior by gender were found, except for rest after physical activity (p = 0.017). Patients who practiced physical activity showed fewer symptoms of depression (p<0.001). There were no differences in sense of coherence according to self-care behavior and gender. Women had more symptoms of depression than men (p = 0.002). CONCLUSION Special attention should be given to women with HF considering self-care and depressive symptoms.

Making sense of AMPA receptor trafficking by modeling molecular mechanisms of synaptic plasticity.

Synaptic plasticity involves a complex molecular machinery with various protein interactions but it is not yet clear how its components give rise to the different aspects of synaptic plasticity. Here we ask whether it is possible to mathematically model synaptic plasticity by making use of known substances only. We present a model of a multistable biochemical reaction system and use it to simulate the plasticity of synaptic transmission in long-term potentiation (LTP) or long-term depression (LTD) after repeated excitation of the synapse. According to our model, we can distinguish between two phases: first, a "viscosity" phase after the first excitation, the effects of which like the activation of NMDA receptors and CaMKII fade out in the absence of further excitations. Second, a "plasticity" phase actuated by an identical subsequent excitation that follows after a short time interval and causes the temporarily altered concentrations of AMPA subunits in the postsynaptic membrane to be stabilized. We show that positive feedback is the crucial element in the core chemical reaction, i.e. the activation of the short-tail AMPA subunit by NEM-sensitive factor, which allows generating multiple stable equilibria. Three stable equilibria are related to LTP, LTD and a third unfixed state called ACTIVE. Our mathematical approach shows that modeling synaptic multistability is possible by making use of known substances like NMDA and AMPA receptors, NEM-sensitive factor, glutamate, CaMKII and brain-derived neurotrophic factor. Furthermore, we could show that the heteromeric combination of short- and long-tail AMPA receptor subunits fulfills the function of a memory tag.

Clients of sex workers in Switzerland: it makes sense to counsel and propose rapid test for HIV on the street, a preliminary report.

BACKGROUND: Clients of street sex workers may be at higher risk for HIV infection than the general population. Furthermore, there is a lack of knowledge regarding HIV testing of clients of sex workers in developed countries. METHOD: This pilot study assessed the feasibility and acceptance of rapid HIV testing by the clients of street-based sex workers in Lausanne, Switzerland. For 5 evenings, clients in cars were stopped by trained field staff for face-to-face interviews focusing on sex-related HIV risk behaviors and HIV testing history. The clients were then offered a free anonymous rapid HIV test in a bus parked nearby. Rapid HIV testing and counselling were performed by experienced nurse practitioners. Clients with reactive tests were offered confirmatory testing, medical evaluation, and care in our HIV clinic. RESULT: We intercepted 144 men, 112 (77.8%) agreed to be interviewed. Among them, 50 (46.6%) had never been tested for HIV. A total of 31 (27.7%) rapid HIV tests were performed, 16 (51.6%) in clients who had not previously been tested. None were reactive. Initially, 19 (16.9%) additional clients agreed to HIV testing but later declined due to the 40-minute queue for testing. CONCLUSION: This pilot study showed that rapid HIV testing in the red light district of Lausanne was feasible, and that the clients of sex workers accepted testing at an unexpectedly high rate. This setting seems particularly appropriate for targeted HIV screening, since more than 40% of the clients had not previously been tested for HIV even though they engaged in sex-related HIV risk behaviour.

Estudi i implementació d’un mètode de reconstrucció 3D basat en SfM i registre de vistes 3D parcials

Aquest projecte es basarà en reconstruir una imatge 3D gran a partir d’una seqüència d’imatges 2D capturades per una càmera. Ens centrem en l’estudi de les bases matemàtiques de la visió per computador així com en diferents mètodes emprats en la reconstrucció 3D d’imatges. Per portar a terme aquest estudi s’utilitza la plataforma de desenvolupament MatLab ja que permet tractar operacions matemàtiques, imatges i matrius de gran tamany amb molta senzillesa, rapidesa i eficiència, per aquesta raó s’usa en moltes recerques sobre aquest tema. El projecte aprofundeix en el tema descrit anteriorment estudiant i implementant un mètode que consisteix en aplicar Structure From Motion (SFM) a pocs frames seguits obtinguts d’una seqüència d’imatges 2D per crear una reconstrucció 3D. Quan s’han creat dues reconstruccions 3D consecutives i fent servir un frame com a mínim en comú entre elles, s’aplica un mètode de registre d’estructures 3D, l’Iterative Closest Point (ICP), per crear una reconstrucció 3D més gran a través d’unir les diferents reconstruccions obtingudes a partir de SfM. El mètode consisteix en anar repetint aquestes operacions fins al final dels frames per poder aconseguir una reconstrucció 3D més gran que les petites imatges que s’aconsegueixen a través de SfM. A la Figura 1 es pot veure un esquema del procés que es segueix. Per avaluar el comportament del mètode, utilitzem un conjunt de seqüències sintètiques i un conjunt de seqüències reals obtingudes a partir d’una càmera. L’objectiu final d’aquest projecte és construir una nova toolbox de MatLab amb tots els mètodes per crear reconstruccions 3D grans per tal que sigui possible tractar amb facilitat aquest problema i seguir-lo desenvolupant en un futur

Audit report on the Iowa Water Pollution Control Works Financing Program (Clean Water Program) and the Iowa Drinking Water Facilities Financing Program (Drinking Water Program), joint programs of the Iowa Finance Authority and the Iowa Department of Natural Resources, for the year ended June 30, 2006

Audit report on the Iowa Water Pollution Control Works Financing Program (Clean Water Program) and the Iowa Drinking Water Facilities Financing Program (Drinking Water Program), joint programs of the Iowa Finance Authority and the Iowa Department of Natural Resources, for the year ended June 30, 2006

Microcrystals As Damps And Their Role In Joint Inflammation

The concept of danger signals as important triggers of inflammation and immune activation has passed from fanciful hypothesis to a widely accepted biological process with receptors, signalling cascades and mediators. Products of cell death or cell stress are prime examples of DAMPs. They interact with receptors on the cell surface such as TLRs as well as cytoplasmic proteins such as the NLRs to modulate cellular metabolism and activation. Recently, the identification of the inflammasomes and their role in processing IL-1b and IL18 provided further insights into how DAMPs provoke inflammation. A class of substances that are potent activators of the inflammasome is microcrystals. All three microcrystals associated with joint disease in man : urate, CPP and hydroxyapatite require the NLRP3 inflammasome to process and release IL-1b from leucocytes. This mechanism most probably explain the inflammatory phase of acute crystal arthritis. However, microcrystals can also induce apoptosis, cell death as well as cell activation, depending on the cell type they are in contact with. These different cellular effects could well explain the role crystals can play in degenerative joint diseases, where inflammation is not as prominent. Our understanding of the intracellular pathways linking microcrystals to inflammation and cell activation is currently still very sketchy, and we hope that the detailed analysis of these pathways may lead to better comprehension and treatment of microcrystal induced joint diseases.Disclosures : The author has declared no conflicts of interest.

Stepwise multiple testing as formalized data snooping

It is common in econometric applications that several hypothesis tests arecarried out at the same time. The problem then becomes how to decide whichhypotheses to reject, accounting for the multitude of tests. In this paper,we suggest a stepwise multiple testing procedure which asymptoticallycontrols the familywise error rate at a desired level. Compared to relatedsingle-step methods, our procedure is more powerful in the sense that itoften will reject more false hypotheses. In addition, we advocate the useof studentization when it is feasible. Unlike some stepwise methods, ourmethod implicitly captures the joint dependence structure of the teststatistics, which results in increased ability to detect alternativehypotheses. We prove our method asymptotically controls the familywise errorrate under minimal assumptions. We present our methodology in the context ofcomparing several strategies to a common benchmark and deciding whichstrategies actually beat the benchmark. However, our ideas can easily beextended and/or modied to other contexts, such as making inference for theindividual regression coecients in a multiple regression framework. Somesimulation studies show the improvements of our methods over previous proposals. We also provide an application to a set of real data.

Recurrent dominant mutations affecting two adjacent residues in the motor domain of the monomeric kinesin KIF22 result in skeletal dysplasia and joint laxity.

Spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type (lepto-SEMDJL, aka SEMDJL, Hall type), is an autosomal dominant skeletal disorder that, in spite of being relatively common among skeletal dysplasias, has eluded molecular elucidation so far. We used whole-exome sequencing of five unrelated individuals with lepto-SEMDJL to identify mutations in KIF22 as the cause of this skeletal condition. Missense mutations affecting one of two adjacent amino acids in the motor domain of KIF22 were present in 20 familial cases from eight families and in 12 other sporadic cases. The skeletal and connective tissue phenotype produced by these specific mutations point to functions of KIF22 beyond those previously ascribed functions involving chromosome segregation. Although we have found Kif22 to be strongly upregulated at the growth plate, the precise pathogenetic mechanisms remain to be elucidated.

Research joint ventures in an international economy

D'Aspremont and Jacquemin's (1988) model is extended to studyalternative configurations of research agreements in a two--country integratedworld economy. Under unambiguous conditions on spillovers we show that:1) Allowing national firms to cooperate in R\&D confers them an advantageover foreign rivals, an effect similar to R\&D subsidies. 2) In a policygame, each government would allow national cooperative agreements. 3) Contraryto other trade policies which lead to a ``prisoners' dilemma'' result,welfare in both countries increases when they both allow R\&D cooperation.4) Welfare is even higher if a generalized (international) coalition isformed.

Clinical and ultrasonographic predictors of joint replacement for knee osteoarthritis: results from a large, 3-year, prospective EULAR study.

OBJECTIVES: To determine clinical and ultrasonographic predictors of joint replacement surgery across Europe in primary osteoarthritis (OA) of the knee. METHODS: This was a 3-year prospective study of a painful OA knee cohort (from a EULAR-sponsored, multicentre study). All subjects had clinical evaluation, radiographs and ultrasonography (US) at study entry. The rate of knee replacement surgery over the 3-year follow-up period was determined using Kaplan-Meier survival data analyses. Predictive factors for joint replacement were identified by univariate log-rank test then multivariate analysis using a Cox proportional-hazards regression model. Potential baseline predictors included demographic, clinical, radiographic and US features. RESULTS: Of the 600 original patients, 531 (88.5%), mean age 67+/-10 years, mean disease duration 6.1+/-6.9 years, had follow-up data and were analysed. During follow-up (median 3 years; range 0-4 years), knee replacement was done or required for 94 patients (estimated event rate of 17.7%). In the multivariate analysis, predictors of joint replacement were as follows: Kellgren and Lawrence radiographic grade (grade &gt; or =III vs &lt;III, hazards ratio (HR) = 4.08 (95% CI 2.34 to 7.12), p&lt;0.0001); ultrasonographic knee effusion (&gt; or =4 mm vs &lt;4 mm) (HR = 2.63 (95% CI 1.70 to 4.06), p&lt;0.0001); knee pain intensity on a 0-100 mm visual analogue scale (&gt; or =60 vs &lt;60) (HR = 1.81 (95% CI 1.15 to 2.83), p=0.01) and disease duration (&gt; or =5 years vs &lt;5 years) (HR=1.63 (95% CI 1.08 to 2.47), p=0.02). Clinically detected effusion and US synovitis were not associated with joint replacement in the univariate analysis. CONCLUSION: Longitudinal evaluation of this OA cohort demonstrated significant progression to joint replacement. In addition to severity of radiographic damage and pain, US-detected effusion was a predictor of subsequent joint replacement.

Organisational values as "attractors of chaos": An emerging cultural change to manage organisational complexity

Business organisations are excellent representations of what in physics and mathematics are designated "chaotic" systems. Because a culture of innovation will be vital for organisational survival in the 21st century, the present paper proposes that viewing organisations in terms of "complexity theory" may assist leaders in fine-tuning managerial philosophies that provide orderly management emphasizing stability within a culture of organised chaos, for it is on the "boundary of chaos" that the greatest creativity occurs. It is argued that 21st century companies, as chaotic social systems, will no longer be effectively managed by rigid objectives (MBO) nor by instructions (MBI). Their capacity for self-organisation will be derived essentially from how their members accept a shared set of values or principles for action (MBV). Complexity theory deals with systems that show complex structures in time or space, often hiding simple deterministic rules. This theory holds that once these rules are found, it is possible to make effective predictions and even to control the apparent complexity. The state of chaos that self-organises, thanks to the appearance of the "strange attractor", is the ideal basis for creativity and innovation in the company. In this self-organised state of chaos, members are not confined to narrow roles, and gradually develop their capacity for differentiation and relationships, growing continuously toward their maximum potential contribution to the efficiency of the organisation. In this way, values act as organisers or "attractors" of disorder, which in the theory of chaos are equations represented by unusually regular geometric configurations that predict the long-term behaviour of complex systems. In business organisations (as in all kinds of social systems) the starting principles end up as the final principles in the long term. An attractor is a model representation of the behavioral results of a system. The attractor is not a force of attraction or a goal-oriented presence in the system; it simply depicts where the system is headed based on its rules of motion. Thus, in a culture that cultivates or shares values of autonomy, responsibility, independence, innovation, creativity, and proaction, the risk of short-term chaos is mitigated by an overall long-term sense of direction. A more suitable approach to manage the internal and external complexities that organisations are currently confronting is to alter their dominant culture under the principles of MBV.

Sense and antisense transcripts in the histone H1 (HIS-1) locus of Leishmania major.

Histone H1 in the parasitic protozoan Leishmania is a developmentally regulated protein encoded by two genes, HIS-1.1 and HIS-1.2. These genes are separated by approximately 20 kb of sequence and are located on the same DNA strand of chromosome 27. When Northern blots of parasite RNA were probed with HIS-1 strand-specific riboprobes, we detected sense and antisense transcripts that were polyadenylated and developmentally regulated. When the HIS-1.2 coding region was replaced with the coding region of the neomycin phosphotransferase gene, antisense transcription of this gene was unaffected, indicating that the regulatory elements controlling antisense transcription were located outside of the HIS-1.2 gene, and that transcription in Leishmania can occur from both DNA strands even in the presence of transcription of a selectable marker in the complementary strand. A search for other antisense transcripts within the HIS-1 locus identified an additional transcript (SC-1) within the intervening HIS-1 sequence, downstream of adenine and thymine-rich sequences. These results show that gene expression in Leishmania is not only regulated polycistronically from the sense strand of genomic DNA, but that the complementary strand of DNA also contains sequences that could drive expression of open reading frames from the antisense strand of DNA. These findings suggest that the parasite has evolved in such a way as to maximise the transcription of its genome, a mechanism that might be important for it to maintain virulence.

Audit report on the Iowa Water Pollution Control Works Financing Program and the Iowa Drinking Water Facilities Financing Program, joint programs of the Iowa Finance Authority and the Iowa Department of Natural Resources for the year ended June 30, 2007

Audit report on the Iowa Water Pollution Control Works Financing Program and the Iowa Drinking Water Facilities Financing Program, joint programs of the Iowa Finance Authority and the Iowa Department of Natural Resources for the year ended June 30, 2007