Neuromodulation and the role of electrodiagnostic techniques

Electrodiagnostic techniques have been utilized in surgery since the early 1960s. These techniques have been primarily used in neurosurgery; however, with the introduction of neuromodulation for voiding dysfunction, these techniques have now found their way into the field of female pelvic medicine. This article will review techniques applicable to evaluate pelvic floor function as it relates to neuromodulation. It will also review the literature describing how these techniques are used to help determine appropriate candidates as well as improve surgical outcomes. A PubMed search was conducted using the terms neuromodulation, Interstim, electrodiagnosis, electrodiagnostic techniques, electromyography with limits to the pelvic floor, and voiding dysfunction. Eight articles and three abstracts were found that directly related to the use of electrodiagnostic techniques as they apply to neuromodulation. Electrodiagnostic techniques may play a role in helping predict appropriate candidates for neuromodulation as well as improve surgical outcomes

Survival gains needed to offset persistent adverse treatment effects in localised prostate cancer

BACKGROUND: Men diagnosed with localised prostate cancer (LPC) face difficult choices between treatment options that can cause persistent problems with sexual, urinary and bowel function. Controlled trial evidence about the survival benefits of the full range of treatment alternatives is limited, and patients' views on the survival gains that might justify these problems have not been quantified. METHODS: A discrete choice experiment (DCE) was administered in a random subsample (n=357, stratified by treatment) of a population-based sample (n=1381) of men, recurrence-free 3 years after diagnosis of LPC, and 65 age-matched controls (without prostate cancer). Survival gains needed to justify persistent problems were estimated by substituting side effect and survival parameters from the DCE into an equation for compensating variation (adapted from welfare economics). RESULTS: Median (2.5, 97.5 centiles) survival benefits needed to justify severe erectile dysfunction and severe loss of libido were 4.0 (3.4, 4.6) and 5.0 (4.9, 5.2) months. These problems were common, particularly after androgen deprivation therapy (ADT): 40 and 41% overall (n=1381) and 88 and 78% in the ADT group (n=33). Urinary leakage (most prevalent after radical prostatectomy (n=839, mild 41%, severe 18%)) needed 4.2 (4.1, 4.3) and 27.7 (26.9, 28.5) months survival benefit, respectively. Mild bowel problems (most prevalent (30%) after external beam radiotherapy (n=106)) needed 6.2 (6.1, 6.4) months survival benefit. CONCLUSION: Emerging evidence about survival benefits can be assessed against these patient-based benchmarks. Considerable variation in trade-offs among individuals underlines the need to inform patients of long-term consequences and incorporate patient preferences into treatment decisions. © 2012 Cancer Research UK. All rights reserved

Single donor ionization energies in a nanoscale CMOS channel

One consequence of the continued downwards scaling of transistors is the reliance on only a few discrete atoms to dope the channel, and random fluctuations of the number of these dopants is already a major issue in the microelectonics industry. While single-dopant signatures have been observed at low temperature, studying the impact of only one dopant up to room temperature requires extremely small lengths. Here, we show that a single arsenic dopant dramatically affects the off-state behavior of an advanced microelectronics field effect transistor (FET) at room temperature. Furthermore, the ionization energy of this dopant should be profoundly modified by the close proximity of materials with a different dielectric constant than the host semiconductor. We measure a strong enhancement, from 54meV to 108meV, of the ionization energy of an arsenic atom located near the buried oxide. This enhancement is responsible for the large current below threshold at room temperature and therefore explains the large variability in these ultra-scaled transistors. The results also suggest a path to incorporating quantum functionalities into silicon CMOS devices through manipulation of single donor orbitals

Climate change adaptation in European river basins

This paper contains an assessment and standardized comparative analysis of the current water management regimes in four case-studies in three European river basins: the Hungarian part of the Upper Tisza, the Ukrainian part of the Upper Tisza (also called Zacarpathian Tisza), Alentejo Region (including the Alqueva Reservoir) in the Lower Guadiana in Portugal, and Rivierenland in the Netherlands. The analysis comprises several regime elements considered to be important in adaptive and integrated water management: agency, awareness raising and education, type of governance and cooperation structures, information management and—exchange, policy development and—implementation, risk management, and finances and cost recovery. This comparative analysis has an explorative character intended to identify general patterns in adaptive and integrated water management and to determine its role in coping with the impacts of climate change on floods and droughts. The results show that there is a strong interdependence of the elements within a water management regime, and as such this interdependence is a stabilizing factor in current management regimes. For example, this research provides evidence that a lack of joint/participative knowledge is an important obstacle for cooperation, or vice versa. We argue that there is a two-way relationship between information management and collaboration. Moreover, this research suggests that bottom-up governance is not a straightforward solution to water management problems in large-scale, complex, multiple-use systems, such as river basins. Instead, all the regimes being analyzed are in a process of finding a balance between bottom-up and top–down governance. Finally, this research shows that in a basin where one type of extreme is dominant—like droughts in the Alentejo (Portugal) and floods in Rivierenland (Netherlands)—the potential impacts of other extremes are somehow ignored or not perceived with the urgency they might deserv

Merging cloned alloy models with colorful refactorings

Likewise to code, clone-and-own is a common way to create variants of a model, to explore the impact of different features while exploring the design of a software system. Previously, we have introduced Colorful Alloy, an extension of the popular Alloy language and toolkit to support feature-oriented design, where model elements can be annotated with feature expressions and further highlighted with different colors to ease understanding. In this paper we propose a catalog of refactorings for Colorful Alloy models, and show how they can be used to iteratively merge cloned Alloy models into a single feature-annotated colorful model, where the commonalities and differences between the different clones are easily perceived, and more efficient aggregated analyses can be performed.This work is financed by the ERDF — European Regional Development Fund through the Operational Programme for Competitiveness and Internationalisation – COMPETE 2020 Programme and by National Funds through the Portuguese funding agency, FCT – Fundação para a Ciência e a Tecnologia within project PTDC/CCI-INF/29583/2017 – POCI-01-0145-FEDER-029583

Prediction of peptide and protein propensity for amyloid formation

Understanding which peptides and proteins have the potential to undergo amyloid formation and what driving forces are responsible for amyloid-like fiber formation and stabilization remains limited. This is mainly because proteins that can undergo structural changes, which lead to amyloid formation, are quite diverse and share no obvious sequence or structural homology, despite the structural similarity found in the fibrils. To address these issues, a novel approach based on recursive feature selection and feed-forward neural networks was undertaken to identify key features highly correlated with the self-assembly problem. This approach allowed the identification of seven physicochemical and biochemical properties of the amino acids highly associated with the self-assembly of peptides and proteins into amyloid-like fibrils (normalized frequency of β-sheet, normalized frequency of β-sheet from LG, weights for β-sheet at the window position of 1, isoelectric point, atom-based hydrophobic moment, helix termination parameter at position j+1 and ΔGº values for peptides extrapolated in 0 M urea). Moreover, these features enabled the development of a new predictor (available at http://cran.r-project.org/web/packages/appnn/index.html) capable of accurately and reliably predicting the amyloidogenic propensity from the polypeptide sequence alone with a prediction accuracy of 84.9 % against an external validation dataset of sequences with experimental in vitro, evidence of amyloid formation

Potential Associations between Severity of Infection and the Presence of Virulence-Associated Genes in Clinical Strains of Staphylococcus aureus

BACKGROUND: The clinical spectrum of Staphylococcus aureus infection ranges from asymptomatic nasal carriage to osteomyelitis, infective endocarditis (IE) and death. In this study, we evaluate potential association between the presence of specific genes in a collection of prospectively characterized S. aureus clinical isolates and clinical outcome. METHODOLOGY/PRINCIPAL FINDINGS: Two hundred thirty-nine S. aureus isolates (121 methicillin-resistant S. aureus [MRSA] and 118 methicillin-susceptible S. aureus [MSSA]) were screened by array comparative genomic hybridization (aCGH) to identify genes implicated in complicated infections. After adjustment for multiple tests, 226 genes were significantly associated with severity of infection. Of these 226 genes, 185 were not in the SCCmec element. Within the 185 non-SCCmec genes, 171 were less common and 14 more common in the complicated infection group. Among the 41 genes in the SCCmec element, 37 were more common and 4 were less common in the complicated group. A total of 51 of the 2014 sequences evaluated, 14 non-SCCmec and 37 SCCmec, were identified as genes of interest. CONCLUSIONS/SIGNIFICANCE: Of the 171 genes less common in complicated infections, 152 are of unknown function and may contribute to attenuation of virulence. The 14 non-SCCmec genes more common in complicated infections include bacteriophage-encoded genes such as regulatory factors and autolysins with potential roles in tissue adhesion or biofilm formation

Quantifying the natural history of post-radical prostatectomy incontinence using objective pad test data

BACKGROUND: Urinary incontinence (UI) following radical prostatectomy is a well-recognized risk of the surgery. In most patients post-operative UI improves over time. To date, there is limited objective, quantitative data on the natural history of the resolution of post-prostatectomy UI. The purpose of this study was to define the natural history of post radical prostatectomy incontinence using an objective quantitative tool, the 1-hour standard pad test. METHODS: 203 consecutive patients underwent radical prostatectomy by a single surgeon between 03/98 & 08/03. A standardized 1-hour pad test was administered at subsequent postoperative clinic visits. The gram weight of urine loss was recorded and subdivided into four groups defined according to the grams of urine loss: minimal (<1 g), mild (>1, <10 g), moderate (10–50 g) and severe (>50 g). Patients were evaluated: at 2 weeks (catheter removal), 6 weeks, 18 weeks, 30 weeks, 42 weeks and 54 weeks. The data set was analyzed for average urine loss as well as grams of urine loss at each time point, the percentage of patients and the distribution of patients in each category. RESULTS: Mean follow up was 118 weeks. The majority of patients experienced incontinence immediately after catheter removal at 2 weeks that gradually improved with time. While continued improvement was noted to 1 year, most patients who achieved continence did so by 18 weeks post-op. CONCLUSION: While the majority of patients experience mild to severe UI immediately following catheter removal, there is a rapid decrease in leaked weight during the first 18 weeks following RRP. Patients continue to improve out to 1 year with greater than 90% having minimal leakage by International Continence Society criteria

Toxic risk of stereotactic body radiotherapy and concurrent helical tomotherapy followed by erlotinib for non-small-cell lung cancer treatment - case report

<p>Abstract</p> <p>Background</p> <p>Stereotactic body radiation therapy (SBRT) applied by helical tomotherapy (HT) is feasible for lung cancer in clinical. Using SBRT concurrently with erlotinib for non-small cell lung cancer (NSCLC) is not reported previously.</p> <p>Case Presentation</p> <p>A 77-year-old man with stage III NSCLC, received erlotinib 150 mg/day, combined with image-guided SBRT via HT. A total tumor dose of 54 Gy/9 fractions was delivered to the tumor bed. The tumor responded dramatically and the combined regimen was well tolerated. After concurrent erlotinib-SBRT, erlotinib was continued as maintenance therapy. The patient developed dyspnea three months after the combined therapy and radiation pneumonitis with interstitial lung disease was suspected.</p> <p>Conclusions</p> <p>Combination SBRT, HT, and erlotinib therapy provided effective anti-tumor results. Nonetheless, the potential risks of enhanced adverse effects between radiation and erlotinib should be monitored closely, especially when SBRT is part of the regimen.</p