Protocol for Physiotherapy OR Tvt Randomised Efficacy Trial (PORTRET): a multicentre randomised controlled trial to assess the cost-effectiveness of the tension free vaginal tape versus pelvic floor muscle training in women with symptomatic moderate to severe stress urinary incontinence

<p>Abstract</p> <p>Background</p> <p>Stress urinary incontinence is a common condition affecting approximately 20% of adult women causing substantial individual (quality of life) and economic (119 million Euro/year spent on incontinence pads in the Netherlands) burden. Pelvic floor muscle training (PFMT) is regarded as first line treatment, but only 15-25% of women will be completely cured. Approximately 65% will report that their condition improved, but long term adherence to treatment is problematic. In addition, at longer term (2-15 years) follow-up 30-50% of patients will end up having surgery. From 1996 a minimal invasive surgical procedure, the Tension-free Vaginal Tape (TVT) has rapidly become the gold standard in surgical treatment of stress urinary incontinence. With TVT 65-95% of women are cured. However, approximately 3-6% of women will develop symptoms of an overactive bladder, resulting in reduced quality of life. Because of its efficacy the TVT appears to be preferable over PFMT but both treatments and their costs have not been compared head-to-head in a randomised clinical trial.</p> <p>Methods/Design</p> <p>A multi-centre randomised controlled trial will be performed for women between 35 - 80 years old with moderate to severe, predominantly stress, urinary incontinence, who have not received specialised PFMT or previous anti-incontinence surgery. Women will be assigned to either PFMT by a specialised physiotherapist for a standard of 9-18 session in a period of 6 months, or TVT(O) surgery. The main endpoint of the study is the subjective improvement of urinary incontinence. As secondary outcome the objective cure will be assessed from history and clinical parameters. Subjective improvement in quality of life will be measured by generic (EQ-5D) and disease-specific (Urinary Distress Inventory and Incontinence Impact Questionnaire) quality of life instruments. The economical endpoint is short term (1 year) incremental cost-effectiveness in terms of costs per additional year free of urinary incontinence and costs per Quality Adjusted Life Years (QALY) gained. Finally, treatment strategy and patient characteristics will be combined in a prediction model, to allow for individual treatment decisions in future patients. Four hundred female patients will be recruited from over 30 hospitals in the Netherlands</p> <p>Trial registration</p> <p>Nederlands trial register: NTR 1248</p

Ecological Modeling of Aedes aegypti (L.) Pupal Production in Rural Kamphaeng Phet, Thailand

Background - Aedes aegypti (L.) is the primary vector of dengue, the most important arboviral infection globally. Until an effective vaccine is licensed and rigorously administered, Ae. aegypti control remains the principal tool in preventing and curtailing dengue transmission. Accurate predictions of vector populations are required to assess control methods and develop effective population reduction strategies. Ae. aegypti develops primarily in artificial water holding containers. Release recapture studies indicate that most adult Ae. aegypti do not disperse over long distances. We expect, therefore, that containers in an area of high development site density are more likely to be oviposition sites and to be more frequently used as oviposition sites than containers that are relatively isolated from other development sites. After accounting for individual container characteristics, containers more frequently used as oviposition sites are likely to produce adult mosquitoes consistently and at a higher rate. To this point, most studies of Ae. aegypti populations ignore the spatial density of larval development sites. Methodology - Pupal surveys were carried out from 2004 to 2007 in rural Kamphaeng Phet, Thailand. In total, 84,840 samples of water holding containers were used to estimate model parameters. Regression modeling was used to assess the effect of larval development site density, access to piped water, and seasonal variation on container productivity. A varying-coefficients model was employed to account for the large differences in productivity between container types. A two-part modeling structure, called a hurdle model, accounts for the large number of zeroes and overdispersion present in pupal population counts. Findings - The number of suitable larval development sites and their density in the environment were the primary determinants of the distribution and abundance of Ae. aegypti pupae. The productivity of most container types increased significantly as habitat density increased. An ecological approach, accounting for development site density, is appropriate for predicting Ae. aegypti population levels and developing efficient vector control program

High Field Alloy, Thermoelectric, and mm Wave Studies of the Field Induced Superconducting State in λ-(BETS)

Alloy studies in the π -d organic conductor λ-(BETS) 2 Fe x Ga 1−x Cl 4 have given new insight into the nature of field induced superconductivity (FISC), since the mechanism of the FISC involves cancellation of the π − d exchange field by the external field. Alloying on the Fe x Ga 1−x site allows tuning of the exchange field, thereby influencing the FISC phase boundary. A brief review of the low temperature phases are given, and new high magnetic field thermoelectric and mm wave results that probe the low temperature ground state are presented. The discovery of magnetic field induced superconductivity in λ-(BETS) 2 FeCl 4 [1] (BETS= bis(ethylenedithio)tetraselenafulvalene) has drawn attention to the π−d electron spin exchange mechanisms At higher magnetic fields , field induced superconductivity (FISC) is stabilized in λ-(BETS) 2 FeCl 4 below 5 K between 18 and 45

Are mice good models for human neuromuscular disease? Comparing muscle excursions in walking between mice and humans

The mouse is one of the most widely used animal models to study neuromuscular diseases and test new therapeutic strategies. However, findings from successful pre-clinical studies using mouse models frequently fail to translate to humans due to various factors. Differences in muscle function between the two species could be crucial but often have been overlooked. The purpose of this study was to evaluate and compare muscle excursions in walking between mice and humans

Telomeric expression sites are highly conserved in trypanosoma brucei

Subtelomeric regions are often under-represented in genome sequences of eukaryotes. One of the best known examples of the use of telomere proximity for adaptive purposes are the bloodstream expression sites (BESs) of the African trypanosome Trypanosoma brucei. To enhance our understanding of BES structure and function in host adaptation and immune evasion, the BES repertoire from the Lister 427 strain of T. brucei were independently tagged and sequenced. BESs are polymorphic in size and structure but reveal a surprisingly conserved architecture in the context of extensive recombination. Very small BESs do exist and many functioning BESs do not contain the full complement of expression site associated genes (ESAGs). The consequences of duplicated or missing ESAGs, including ESAG9, a newly named ESAG12, and additional variant surface glycoprotein genes (VSGs) were evaluated by functional assays after BESs were tagged with a drug-resistance gene. Phylogenetic analysis of constituent ESAG families suggests that BESs are sequence mosaics and that extensive recombination has shaped the evolution of the BES repertoire. This work opens important perspectives in understanding the molecular mechanisms of antigenic variation, a widely used strategy for immune evasion in pathogens, and telomere biology

COSPAR Sample Safety Assessment Framework (SSAF).

The Committee on Space Research (COSPAR) Sample Safety Assessment Framework (SSAF) has been developed by a COSPAR appointed Working Group. The objective of the sample safety assessment would be to evaluate whether samples returned from Mars could be harmful for Earth's systems (e.g., environment, biosphere, geochemical cycles). During the Working Group's deliberations, it became clear that a comprehensive assessment to predict the effects of introducing life in new environments or ecologies is difficult and practically impossible, even for terrestrial life and certainly more so for unknown extraterrestrial life. To manage expectations, the scope of the SSAF was adjusted to evaluate only whether the presence of martian life can be excluded in samples returned from Mars. If the presence of martian life cannot be excluded, a Hold & Critical Review must be established to evaluate the risk management measures and decide on the next steps. The SSAF starts from a positive hypothesis (there is martian life in the samples), which is complementary to the null-hypothesis (there is no martian life in the samples) typically used for science. Testing the positive hypothesis includes four elements: (1) Bayesian statistics, (2) subsampling strategy, (3) test sequence, and (4) decision criteria. The test sequence capability covers self-replicating and non-self-replicating biology and biologically active molecules. Most of the investigations associated with the SSAF would need to be carried out within biological containment. The SSAF is described in sufficient detail to support planning activities for a Sample Receiving Facility (SRF) and for preparing science announcements, while at the same time acknowledging that further work is required before a detailed Sample Safety Assessment Protocol (SSAP) can be developed. The three major open issues to be addressed to optimize and implement the SSAF are (1) setting a value for the level of assurance to effectively exclude the presence of martian life in the samples, (2) carrying out an analogue test program, and (3) acquiring relevant contamination knowledge from all Mars Sample Return (MSR) flight and ground elements. Although the SSAF was developed specifically for assessing samples from Mars in the context of the currently planned NASA-ESA MSR Campaign, this framework and the basic safety approach are applicable to any other Mars sample return mission concept, with minor adjustments in the execution part related to the specific nature of the samples to be returned. The SSAF is also considered a sound basis for other COSPAR Planetary Protection Category V, restricted Earth return missions beyond Mars. It is anticipated that the SSAF will be subject to future review by the various MSR stakeholders

Motor neuronopathy with dropped hands and downbeat nystagmus: A distinctive disorder? A case report

BACKGROUND: Eye movements are clinically normal in most patients with motor neuron disorders until late in the disease course. Rare patients are reported to show slow vertical saccades, impaired smooth pursuit, and gaze-evoked nystagmus. We report clinical and oculomotor findings in three patients with motor neuronopathy and downbeat nystagmus, a classic sign of vestibulocerebellar disease. CASE PRESENTATION: All patients had clinical and electrodiagnostic features of anterior horn cell disease. Involvement of finger and wrist extensors predominated, causing finger and wrist drop. Bulbar or respiratory dysfunction did not occur. All three had clinically evident downbeat nystagmus worse on lateral and downgaze, confirmed on eye movement recordings using the magnetic search coil technique in two patients. Additional oculomotor findings included alternating skew deviation and intermittent horizontal saccadic oscillations, in one patient each. One patient had mild cerebellar atrophy, while the other two had no cerebellar or brainstem abnormality on neuroimaging. The disorder is slowly progressive, with survival up to 30 years from the time of onset. CONCLUSION: The combination of motor neuronopathy, characterized by early and prominent wrist and finger extensor weakness, and downbeat nystagmus with or without other cerebellar eye movement abnormalities may represent a novel motor neuron syndrome