Geometric invariance of determining and resonating centers: Odd- and any-number limitations of Pyragas control.

In the spirit of the well-known odd-number limitation, we study the failure of Pyragas control of periodic orbits and equilibria. Addressing the periodic orbits first, we derive a fundamental observation on the invariance of the geometric multiplicity of the trivial Floquet multiplier. This observation leads to a clear and unifying understanding of the odd-number limitation, both in the autonomous and the non-autonomous setting. Since the presence of the trivial Floquet multiplier governs the possibility of successful stabilization, we refer to this multiplier as the determining center. The geometric invariance of the determining center also leads to a necessary condition on the gain matrix for the control to be successful. In particular, we exclude scalar gains. The application of Pyragas control on equilibria does not only imply a geometric invariance of the determining center but surprisingly also on centers that resonate with the time delay. Consequently, we formulate odd- and any-number limitations both for real eigenvalues together with an arbitrary time delay as well as for complex conjugated eigenvalue pairs together with a resonating time delay. The very general nature of our results allows for various applications.

A Randomized Clinical Trial of Standard versus Expanded Cultures to Diagnose Urinary Tract Infections in Women.

PURPOSE: We compared urinary tract infection (UTI) symptom resolution rates at 7-10 days in symptomatic women randomized to treatment based on standard urine culture (SUC) versus expanded quantitative urine culture (EQUC) results. MATERIALS AND METHODS: Women ≥18 years old who responded "yes" to "do you feel you have a UTI?" agreed to urethral catheterization and followup. Symptoms were assessed using the validated UTI Symptom Assessment (UTISA) questionnaire. Culture method was randomized 2:1 (SUC:EQUC); antibiotics were prescribed to women with positive cultures. The primary outcome, UTI symptom resolution, was determined 7-10 days following enrollment on all participants regardless of treatment. RESULTS: Demographic data were similar between groups. Of the SUC and EQUC groups 63% and 74% had positive cultures (p=0.10), respectively. Of participants with positive cultures 97% received antibiotics. Primary outcome data were provided by 215 of 225 participants (SUC 143 [95%], EQUC 72 [97%]). At the primary outcome assessment, 64% and 69% in the SUC and EQUC groups, respectively, reported UTI symptom resolution (p=0.46); UTISA scores improved from baseline in the EQUC arm compared to the SUC arm (p=0.04). In the subset of women predominated by non-Escherichia coli (76), there was a trend toward more symptom resolution in the EQUC arm (21%, p=0.08). CONCLUSIONS: Symptom resolution was similar for the overall population (E. coli and non-E. coli) of women treated for UTI symptoms based on SUC or EQUC. Although the sample size limits conclusions regarding the utility of EQUC in women with non-E. coli uropathogens, the detected trend indicates that this understudied clinical subset warrants further study.

Patient experience of anti-vegf intravitreal injection.

Intravitreal anti-vascular epithelial growth factor (anti-VEGF) injections have revolutionised the treatment of macular diseases, but can be stressful for the patient. We surveyed 904 patients receiving injections at 5 centres in France regarding their feelings toward anti-VEGF injections. The mean age was 77.4 years, and the injections were performed mostly for age related macular degeneration (72%). Half of the patients had previously received>10 injections, 35.6% had received 3-10 injections, and 14.2% had received<3 injections. The mean (SD) stress score was 4.2 [on a scale from 1-10 (0=least stressful, 10=extremely stressful)]. Most patients (70%) reported low to moderate stress (score ≤5). The number of previous injections did not influence stress scores. Paradoxically, 61.2% of patients reported finding injections to be less stressful over time. Most patients found injections to be less traumatic than expected (64%) or just as they had anticipated (25%). Most patients (88%) were not bothered by the presence of other patients in the waiting room. Most patients (78.8%) preferred to be injected quickly before they had time to feel stressed about the procedure. Injections were generally well accepted; most patients would prefer to maintain their current schedule of injections and their current vision (55.7%), or would be willing to have more frequent injections for better vision (39.5%). Our results suggest that stress appears to be more related to the patient's psychological make-up than to the treatment experience or the number of injections received.

[Update from France Macula Federation: Diagnosis of wet AMD]. / Actualisations de la Fédération France Macula : diagnostic de la DMLA exsudative.

PURPOSE: To update the recommendations of the France Macula Federation for the diagnosis of wet age-related macular degeneration (AMD). METHODS: Analysis of literature and expert opinion. RESULTS: The FMF recommends diagnosing wet AMD by combining the results of fundus examination (or color or monochromatic fundus photographs), optical coherence tomography (OCT) showing exudative signs, and morphological visualization of the neovascular membrane, which may be obtained non-invasively (OCT-angiography) or invasively (fluorescein and/or indocyanine green angiography). Under optimal conditions in which all these tools are available, the FMF recommends using non-invasive methods as first-line tools and resorting to dye angiography if diagnostic doubt remains. CONCLUSION: As observed in other fields of medical imaging, non-invasive methods are preferred to invasive methods for the diagnosis of wet AMD, while the latter are reserved for more difficult cases.

[Management of wet AMD in France in 2015]. / Prise en charge de la DMLA exsudative en France en 2015.

PURPOSE AND CONTEXT: Intravitreal administration of anti-VEGF agents, available in France since 2007, allows stabilization and improvement in visual acuity in wet age-related macular degeneration (AMD). In the past few years, the management of this disease has evolved in terms of both diagnostic methods and treatment schedules, which have been adapted to the pathophysiology of AMD. The goal of this survey, performed in a representative sample of French ophthalmologists, was to describe the evolution of medical practices one year after a similar survey (Massé et al., J Fr Ophtalmol 2016; 39: 40-7). METHOD: The survey was performed from December, 2014 to March, 2015 in 191 ophthalmologists (53 general ophthalmologists and 98 retina specialists) with an on-line questionnaire. This questionnaire was designed by a committee of ophthalmologists to describe practices concerning screening, diagnosis, treatment and follow-up of wet AMD. RESULTS: An initial intravitreal injection of an anti-VEGF agent was usually performed within 10 days after the diagnosis of wet AMD by 98% of ophthalmologists and within 5 days by 63%. The treatment protocols favored by retina specialists were pro re nata (PRN) for 58%, Observe and Plan for 25% and Treat and Extend for 17%. Bilateral intravitreal injections were performed on the same day by 46% of retina specialists, mostly for the convenience of the patient and because of the low infectious risk. The initial protocol was maintained by one third of retina specialists throughout the course of treatment, while two thirds of them reported that they reassessed the protocol on average after 5 months. CONCLUSION: This survey on the practices of the ophthalmologists in wet AMD highlights an improvement in the time course of patient management and an evolution of treatment schedules toward individualized protocols.

How we can make ecotoxicology more valuable to environmental protection.

There is increasing awareness that the value of peer-reviewed scientific literature is not consistent, resulting in a growing desire to improve the practice and reporting of studies. This is especially important in the field of ecotoxicology, where regulatory decisions can be partly based on data from the peer-reviewed literature, with wide-reaching implications for environmental protection. Our objective is to improve the reporting of ecotoxicology studies so that they can be appropriately utilized in a fair and transparent fashion, based on their reliability and relevance. We propose a series of nine reporting requirements, followed by a set of recommendations for adoption by the ecotoxicology community. These reporting requirements will provide clarity on the the test chemical, experimental design and conditions, chemical identification, test organisms, exposure confirmation, measurable endpoints, how data are presented, data availability and statistical analysis. Providing these specific details will allow for a fuller assessment of the reliability and relevance of the studies, including limitations. Recommendations for the implementation of these reporting requirements are provided herein for practitioners, journals, reviewers, regulators, stakeholders, funders, and professional societies. If applied, our recommendations will improve the quality of ecotoxicology studies and their value to environmental protection.

[Overview of medical practices in wet AMD in France]. / Vue d'ensemble des pratiques médicales dans la DMLA exsudative en France.

BACKGROUND AND OBJECTIVES: Wet AMD is characterized by the formation of choroidal neovascularization, mediated by vascular endothelial growth factor (VEGF) and responsible for a decrease in visual acuity and metamorphopsia of sudden onset. Intravitreal anti-VEGF can stabilize or even improve visual acuity. Although there is a consensus among ophthalmologists about the induction phase injection of anti-VEGF, there appear to be differences in practice regarding therapeutic treatment modalities. The goal of this work was to explore this hypothesis and to better understand real life practices. METHOD: The Ipsos institute conducted a qualitative survey of 16 retinal specialists and 9 general ophthalmologists in September and October 2013, using a questionnaire developed by a scientific committee of experts. Fifteen telephone interviews and 4 face-to-face meetings with a retina specialist and an ophthalmologist were conducted. This qualitative study allowed the development of a quantitative survey of 200 retina specialists and general ophthalmologists, conducted between November 2013 and January 2014, to describe practices in diagnosis, treatment and follow-up of wet AMD. RESULTS: A distribution of roles between the ophthalmologist making the initial diagnosis and the retinal specialists responsible for treatment and follow-up was noted. Treatment was initiated within 10 days of diagnosis as recommended by the HAS in only one third of patients. After the induction phase of treatment, i.e. three monthly injections of anti-VEGF, treatment and monitoring practices were heterogeneous with 74% of physicians using a PRN treatment protocol, 22% a bimonthly protocol (with monthly monitoring in 19.4% of cases) and 4% a "treat and extend" protocol. There was little change in the protocol chosen in the case of recurrence. CONCLUSION: Three quarters of ophthalmologists report using a PRN protocol, and over 90% report seeing their patients monthly, either for injection or for a check-up. This apparent uniformity is in reality more complex: for the large majority, they prefer to closely follow the patient so as to treat the slightest recurrence, but with great variability in practices with regard to individualization of treatment.

[Functional outcomes obtained after vesicoureteral reimplantation surgery in adults: A review]. / Étiologies et résultats fonctionnels après réimplantation urétéro-vésicale chez l'adulte : revue de la littérature.

OBJECTIVES: Vesico-ureteral reimplantations (VUR) for adults are complex procedures, often practicing for distal ureteral lesions. Our goal was to synthesis the main indications for VUR, different techniques and their functional outcomes. MATERIAL AND METHODS: A literature review in English by Medline, Embase and Google scholar was performed using the following keywords: ureter; laparoscopy; robotics, reimplantation; surgery; obstruction; morbidity; complications; psoas hitch; Boari flap; ureteroneocystostomy. RESULTS: In more than half of the cases, aetiology was a iatrogenic ureteral lesion. When the ureteral defect was less than 2 cm, direct or non-refluxing VUR was the technique of choice. If defect was superior than 2 cm the Boari flap or vesicopsoas hitch were preferred. Several surgical approaches were feasible: open, laparoscopic only, robot assisted laparoscopic. Estimated blood loss, pain and mean hospital stay seemed better with conventional or robotic coelioscopy. Nevertheless, complications, pre-/post-operative renal function and mean operative time seemed similar. The most frequent major complication was the anastomotic urine leakage. CONCLUSIONS: The VUR techniques are well codified now even if it's a rare procedure. Functional outcomes are satisfied according to literature and morbidity is more and more decreasing but the level of evidence of the studies is low.

[Management of macular edema secondary to retinal vein occlusion]. / Prise en charge de l'œdème maculaire secondaire à une occlusion veineuse rétinienne.

BACKGROUND: In recent years, intravitreal injections have added to the treatment modalities available for macular edema (ME) secondary to retinal vein occlusion (RVO). This article aims to provide an update regarding the management of ME secondary to RVO. METHODS: A work group met in order to analyze the literature available on Embase/PubMed, regarding treatments for venous occlusion that have received market approval and are reimbursed in France. In total, 33 articles were selected. Consensus within the group for recommendations was based on this data from the literature review and clinical experience and was reported in this article. RESULTS: The management of ME secondary to branch retinal vein occlusion (BRVO) or central vein occlusion of the retina (CRVO) differs on a number of points. Methods of best practice were discussed separately for BRVO and CRVO, taking into account various ocular and associated parameters. DISCUSSION: Ranibizumab and dexamethasone implant are the first-line treatments for visual impairment due to ME secondary to RVO. The choice of either of these drugs may take into account various ocular and extraocular parameters. A change of treatment to one or the other or to laser may also be considered during follow-up.

Color vision and neuroretinal function in diabetes.

PURPOSE: We investigate how type 2 diabetes (T2DM) and diabetic retinopathy (DR) affect color vision (CV) and mfERG implicit time (IT), whether CV and IT are correlated, and whether CV and IT abnormality classifications agree. METHODS: Adams desaturated D-15 color test, mfERG, and fundus photographs were examined in 37 controls, 22 T2DM patients without DR (NoRet group), and 25 T2DM patients with DR (Ret group). Color confusion score (CCS) was calculated. ITs were averaged within the central 7 hexagons (central IT; ≤4.5°) and outside this area (peripheral IT; ≥4.5°). DR was within (DRIN) or outside (DROUT) of the central 7 hexagons. Group differences, percentages of abnormalities, correlations, and agreement were determined. RESULTS: CCS was greater in the NoRet (P = 0.002) and Ret (P < 0.0001) groups than in control group. CCS was abnormal in 3, 41, and 48 % of eyes in the control, NoRet, and Ret groups, respectively. Ret group CV abnormalities were more frequent in DRIN than in DROUT subgroups (71 vs. 18 %, respectively; P < 0.0001). CCS and IT were correlated only in the Ret group, in both retinal zones (P ≤ 0.028). Only in the Ret group did CCS and peripheral IT abnormality classifications agree (72 %; P < 0.05). CONCLUSION: CV is affected in patients with T2DM, even without DR. Central DR increases the likelihood of a CV deficit compared with non-central DR. mfERG IT averaged across central or peripheral retinal locations is less frequently abnormal than CV in the absence of DR, and these two measures are correlated only when DR is present.

Outcomes after implementation of a multimodal standard care pathway for laparoscopic colorectal surgery.

BACKGROUND: The aim of the study was to assess which aspects of an enhanced recovery programme are associated with better outcomes following laparoscopic colorectal surgery. METHODS: A database of laparoscopic colorectal procedures performed in 2011 was reviewed. Elements of the enhanced recovery programme and compliance were evaluated for short-term (30-day) outcomes. Individual elements included gabapentin, celecoxib, intrathecal analgesia, diet, postoperative fluids, and paracetamol/non-steroidal anti-inflammatory drug pain management. RESULTS: Five hundred and forty-one consecutive procedures were included. Compliance with the enhanced recovery programme elements ranged from 82.4 to 99.3 per cent. Median length of hospital stay was 3 (i.q.r. 2-5) days, with 25.9 per cent of patients discharged within 48 h. Patients without complications had a median length of stay of 3 (i.q.r. 2-4) days if compliant and 3 (3-5) days if not (P < 0.001). Low oral opiate intake (oral morphine equivalent of less than 30 mg) (odds ratio (OR) 1.97, 95 per cent confidence interval 1.29 to 3.03; P = 0.002), full compliance (OR 2.36, 1.42 to 3.90; P < 0.001) and high surgeon volume (more than 100 cases per year) (OR 1.50, 1.19 to 1.89; P < 0.001) were associated with discharge within 48 h. Compliance with the elements of oral intake and fluid management in the first 48 h was associated with a reduced rate of complications (8.1 versus 19.6 per cent; P = 0.001). Median oral opiate intake was 37.5 (i.q.r. 0-105) mg in 48 h, with 26.2 per cent of patients receiving no opiates. CONCLUSION: Compliance with an enhanced recovery pathway was associated with less opiate use, fewer complications and a shorter hospital stay.

Human endothelial lecitin-like oxLDL receptor-1 (LOX-1) expression is not associated with impairment of endothelium-dependent vasoreactivity in conduit vessels.

UNLABELLED: The cellular uptake of oxidized low density lipoprotein (LDL) is mediated through the oxidized LDL receptor-1, LOX-1. We investigated whether circulating factors link LOX-1 expression in endothelial cells and impaired endothelium-dependent vasoreactivity (EDVR) as functional indicator of atherogenesis. EDVR was measured as flow-mediated dilation (FMD) of the brachial artery in 27 patients with a known history of cardiovascular disease. Human umbilical vein endothelial cells (HUVEC) were incubated with bradykinin or prostacyclin in the presence of tumour necrosis factor-alpha (TNF-α) or with serum of each patient for four hours. Total mRNA and protein extracts were analysed for LOX-1 and eNOS expression relative to the expression in medium-treated cells and corrected for GAPDH expression. RESULTS: Prostacyclin and bradykinin did not modulate LOX-1 basal expression but were able to prevent significantly the up-regulation of LOX-1 expression by TNF-α, in HUVEC in vitro. Impaired EDVR was associated significantly with reduced endothelial nitric oxide synthase (eNOS) protein expression in HUVEC (r=0.788, P<0.001), diabetes (P=0.024), and smoking status (yes/no, P=0.047). In contrast, no such association was established with LOX-1 mRNA (r=0.292, P=0.138) or with LOX-1 protein expression in HUVEC (r=0.201, P=0.312). CONCLUSIONS: Using a combination of in vitro experiments with in vivo measurements, we found no evidence that endothelial LOX-1 expression and EDVR mediated through circulating factors were associated.

Caring for people with dementia in general hospitals: an education curriculum from the Alzheimer's Society of Lower Saxony, Germany.

Since 2006, the Alzheimer's Society of Lower Saxony, Germany, has been working to improve care and medical treatment for people with cognitive impairment or dementia in general hospitals. An interdisciplinary team systematically worked on the topic for several years and presented results at various symposia. In 2011, a two-stage curriculum was completed and sent in combination with additional training documents to all hospitals and nursing training colleges in Lower Saxony, Germany. The manual comprised a two-step approach with a 14-h training for hospital staff and a 160-h training for qualification of trainers and dementia appointees/chaperones. In addition, the manual included a list of 13 essential points for "dealing with demented people in a general hospital," the information sheet of the German Alzheimer's Society on aspects requiring special attention when a demented person is admitted to a hospital, short descriptions of best practice models, a list of established speakers in the field, and a 30-min film. In 2012, the project won the "Preis für Engagement und Selbsthilfe" of the Hertie Foundation and the "Niedersächsischen Gesundheitspreis" awarded by the Lower Saxon Ministry for Social, Women, Family, and Health Affairs.

Stool DNA testing for the detection of colorectal neoplasia in patients with inflammatory bowel disease.

BACKGROUND: Current approaches to the detection of colorectal neoplasia associated with inflammatory bowel disease (IBD-CRN) are suboptimal. AIM: To test the feasibility of using stool assay of exfoliated DNA markers to detect IBD-CRN. METHODS: This investigation comprised tissue and stool studies. In the tissue study, gene sequencing and methylation assays were performed on candidate genes using tissue DNA from 25 IBD-CRNs and from 25 IBD mucosae without CRN. Mutations on p53, APC, KRAS, BRAF or PIK3CA genes were insufficiently informative, but several aberrantly methylated genes were highly discriminant. In the stool study, we evaluated candidate methylated genes (vimentin, EYA4, BMP3, NDRG4) in a prospective blinded study on buffered stools from 19 cases with known IBD-CRN and 35 age- and sex-matched IBD controls without CRN. From stool-extracted DNA, target genes were assayed using quantitative allele-specific real-time target and signal amplification method. RESULTS: IBD-CRN cases included 17 with ulcerative colitis (UC) and two with Crohn's disease (CD); nine had cancer and 10 had dysplasia. Controls included 25 with UC and 10 with CD. Individually, BMP3, vimentin, EYA4 and NDRG4 markers showed high discrimination in stools with respective areas under the ROC curve of 0.91, 0.91, 0.85 and 0.84 for total IBD-CRN and of 0.97, 0.97, 0.95 and 0.85 for cancer. At 89% specificity, the combination of BMP3 and mNDRG4 detected 9/9 (100%) of CRC and 80% of dysplasia, 4/4 (100%) of high grade and 4/6 (67%) of low grade. CONCLUSION: These findings demonstrate the feasibility of stool DNA testing for non-invasive detection of colorectal neoplasia associated with inflammatory bowel disease.

[Intravitreal ranibizumab for management of choroidal neovascularization secondary to angioid streaks: a case report]. / Traitement par injection intravitréenne de ranibizumab de néovaisseaux choroïdiens compliquant des stries angioïdes : à propos d'un cas.

Angioid streaks are biomicroscopically observable manifestations that frequently lead to choroidal neovascularization. Traditional treatments used to include laser photocoagulation or photodynamic therapy. Over the past few years, anti-VEGF therapies have been used as an alternative treatment. The case of a 54-year-old patient who received anti-VEGF therapy (ranibizumab) for the treatment of choroidal neovascularization secondary to angioid streaks is reported. The patient received two injections that led to complete resolution of intraretinal fluid and reduction in lesion size. After 1 year of follow-up, the patient has presented no recurrence. This case illustrates the efficacy of intravitreal anti-VEGF therapy for choroidal neovascularization in angioid streaks. Further prospective studies on a larger number of patients should help establish the best treatment and follow-up strategies.