Automatic target validation based on neuroscientific literature mining for tractography.

Target identification for tractography studies requires solid anatomical knowledge validated by an extensive literature review across species for each seed structure to be studied. Manual literature review to identify targets for a given seed region is tedious and potentially subjective. Therefore, complementary approaches would be useful. We propose to use text-mining models to automatically suggest potential targets from the neuroscientific literature, full-text articles and abstracts, so that they can be used for anatomical connection studies and more specifically for tractography. We applied text-mining models to three structures: two well-studied structures, since validated deep brain stimulation targets, the internal globus pallidus and the subthalamic nucleus and, the nucleus accumbens, an exploratory target for treating psychiatric disorders. We performed a systematic review of the literature to document the projections of the three selected structures and compared it with the targets proposed by text-mining models, both in rat and primate (including human). We ran probabilistic tractography on the nucleus accumbens and compared the output with the results of the text-mining models and literature review. Overall, text-mining the literature could find three times as many targets as two man-weeks of curation could. The overall efficiency of the text-mining against literature review in our study was 98% recall (at 36% precision), meaning that over all the targets for the three selected seeds, only one target has been missed by text-mining. We demonstrate that connectivity for a structure of interest can be extracted from a very large amount of publications and abstracts. We believe this tool will be useful in helping the neuroscience community to facilitate connectivity studies of particular brain regions. The text mining tools used for the study are part of the HBP Neuroinformatics Platform, publicly available at http://connectivity-brainer.rhcloud.com/.

Involuntary outpatient treatment for mental health problems in Switzerland: a literature review.

BACKGROUND: In 2008, the Swiss Civil Code was amended. From 1 January 2013, each Swiss canton may propose specific provisions for involuntary outpatient treatment (community treatment orders (CTOs)) for individuals with mental disorders. AIM: This review catalogues the legal provisions of the various Swiss cantons for CTOs and outlines the differences between them. It sets this in the context of variations in clinical provisions between the cantons. METHODS: Databases were searched to obtain relevant publications about CTOs in Switzerland. The Swiss Medical Association, Swiss Federal Statistical Office, Swiss Health Observatory and all the 26 Cantonal medical officers were contacted to complete the information. Conférence des cantons en matière de protection des mineurs et des adultes (COPMA), the authority which monitors guardianship legislation, and Pro Mente Sana, a patients' right association, were also approached. RESULTS: Three articles about CTOs in Switzerland were identified. Psychiatric provisions vary considerably between cantons and only a few could provide complete or even partial figures for rates of compulsion in previous years. Prior to 2013, only 6 of the 20 cantons, for which information was returned, had any provision for CTOs. Now, every canton has some form of legal basis but the level of detail is often limited. In eight cantons, the powers of the measure are not specified (for example, use of medication). In 12 cantons, the maximum duration of the CTO is not specified. German speaking cantons and rural cantons are more likely to specify the details of CTOs. CONCLUSION: Highly variable Swiss provision for CTOs is being introduced despite the absence of convincing international evidence for their effectiveness or good quality data on current coercive practice. Careful monitoring and assessment of these new cantonal provisions are essential.

Is high dose rate brachytherapy reliable and effective treatment for prostate cancer patients? A review of the literature.

The intrinsic physical and radiobiological characteristics of High Dose Rate Brachytherapy (HDR-BT) are well suited to the treatment of prostate cancer. HDR-BT was initially used as a boost to external beam brachytherapy, but has subsequently been employed as the sole treatment, which is termed HDR monotherapy. This review summarizes the clinical outcomes and toxicity results of the principal studies and discusses the radiobiological basis supporting its use.

Spectrum of digoxin-induced ocular toxicity: a case report and literature review.

BACKGROUND: Digoxin intoxication results in predominantly digestive, cardiac and neurological symptoms. This case is outstanding in that the intoxication occurred in a nonagenarian and induced severe, extensively documented visual symptoms as well as dysphagia and proprioceptive illusions. Moreover, it went undiagnosed for a whole month despite close medical follow-up, illustrating the difficulty in recognizing drug-induced effects in a polymorbid patient. CASE PRESENTATION: Digoxin 0.25 mg qd for atrial fibrillation was prescribed to a 91-year-old woman with an estimated creatinine clearance of 18 ml/min. Over the following 2-3 weeks she developed nausea, vomiting and dysphagia, snowy and blurry vision, photopsia, dyschromatopsia, aggravated pre-existing formed visual hallucinations and proprioceptive illusions. She saw her family doctor twice and visited the eye clinic once until, 1 month after starting digoxin, she was admitted to the emergency room. Intoxication was confirmed by a serum digoxin level of 5.7 ng/ml (reference range 0.8-2 ng/ml). After stopping digoxin, general symptoms resolved in a few days, but visual complaints persisted. Examination by the ophthalmologist revealed decreased visual acuity in both eyes, 4/10 in the right eye (OD) and 5/10 in the left eye (OS), decreased color vision as demonstrated by a score of 1/13 in both eyes (OU) on Ishihara pseudoisochromatic plates, OS cataract, and dry age-related macular degeneration (ARMD). Computerized static perimetry showed non-specific diffuse alterations suggestive of either bilateral retinopathy or optic neuropathy. Full-field electroretinography (ERG) disclosed moderate diffuse rod and cone dysfunction and multifocal ERG revealed central loss of function OU. Visual symptoms progressively improved over the next 2 months, but multifocal ERG did not. The patient was finally discharged home after a 5 week hospital stay. CONCLUSION: This case is a reminder of a complication of digoxin treatment to be considered by any treating physician. If digoxin is prescribed in a vulnerable patient, close monitoring is mandatory. In general, when facing a new health problem in a polymorbid patient, it is crucial to elicit a complete history, with all recent drug changes and detailed complaints, and to include a drug adverse reaction in the differential diagnosis.

Ocular adnexal (orbital) solitary fibrous tumor: nuclear STAT6 expression and literature review.

PURPOSE: To report the clinico-pathological features of solitary fibrous tumor occurring in the ocular adnexa (OA) in a single center. To assess the presence of NAB2-STAT6 genes fusion in OA solitary fibrous tumor detected by nuclear overexpression of STAT6. METHODS: Retrospective study including orbital and OA solitary fibrous tumors treated between 2006 and 2014 in our center. The clinical, radiological, and histopathological findings were evaluated. STAT6 expression was assessed by immunohistochemistry. RESULTS: Five patients were identified and presented with a chronic OA mass. The tumors were radiologically well delimited, highly vascularized and without bone erosion. All the patients underwent complete surgical excision. Pathological examination confirmed solitary fibrous tumor in all cases. All tumors demonstrated a nuclear expression of STAT6. There were no recurrences, with a mean follow-up of 5 years after surgery. Our review demonstrated that proptosis was the most common presentation occurring in 60 % of the cases. In the ocular adnexa, adverse histological criteria were found in 19.7 % of the tumors, and recurrences were observed in 48 % of these cases. Thirty-six percent of patients presented at least one local recurrence, and metastastic spread was found in 2.4 % of the cases. Tumor-related death was described in two cases. CONCLUSION: Ocular adnexal SFT are rare and usually present as a chronic orbital mass with proptosis. In the OA, solitary fibrous tumor demonstrates STAT6 nuclear expression, as documented in other locations. Recurrences are unusual and metastasis exceptional. Initial surgical resection should be complete in order to avoid recurrence.

Management of severe blunt hepatic injury in the era of computed tomography and transarterial embolization: A systematic review and critical appraisal of the literature.

BACKGROUND: During the last decade, the management of blunt hepatic injury has considerably changed. Three options are available as follows: nonoperative management (NOM), transarterial embolization (TAE), and surgery. We aimed to evaluate in a systematic review the current practice and outcomes in the management of Grade III to V blunt hepatic injury. METHOD: The MEDLINE database was searched using PubMed to identify English-language citations published after 2000 using the key words blunt, hepatic injury, severe, and grade III to V in different combinations. Liver injury was graded according to the American Association for the Surgery of Trauma classification on computed tomography (CT). Primary outcome analyzed was success rate in intention to treat. Critical appraisal of the literature was performed using the validated National Institute for Health and Care Excellence "Quality Assessment for Case Series" system. RESULTS: Twelve articles were selected for critical appraisal (n = 4,946 patients). The median quality score of articles was 4 of 8 (range, 2-6). Overall, the median Injury Severity Score (ISS) at admission was 26 (range, 0.6-75). A median of 66% (range, 0-100%) of patients was managed with NOM, with a success rate of 94% (range, 86-100%). TAE was used in only 3% of cases (range, 0-72%) owing to contrast extravasation on CT with a success rate of 93% (range, 81-100%); however, 9% to 30% of patients required a laparotomy. Thirty-one percent (range, 17-100%) of patients were managed with surgery owing to hemodynamic instability in most cases, with 12% to 28% requiring secondary TAE to control recurrent hepatic bleeding. Mortality was 5% (range, 0-8%) after NOM and 51% (range, 30-68%) after surgery. CONCLUSION: NOM of Grade III to V blunt hepatic injury is the first treatment option to manage hemodynamically stable patients. TAE and surgery are considered in a highly selective group of patients with contrast extravasation on CT or shock at admission, respectively. Additional standardization of the reports is necessary to allow accurate comparisons of the various management strategies. LEVEL OF EVIDENCE: Systematic review, level IV.

Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria: a literature review and meta-analysis of individual patient data.

BACKGROUND: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). METHODS: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. RESULTS: In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P <0.001); fever (>37.5 °C) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). CONCLUSIONS: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility.

Aesthetic Breast Augmentation Mastopexy Followed by Post-surgical Pyoderma Gangrenosum (PSPG): Clinic, Treatment, and Review of the Literature.

INTRODUCTION: Pyoderma gangrenosum (PG) is a rare autoinflammatory neutrophilic ulcerative skin disease, often developing after a trauma or surgical wounds. In the literature there are several reports of post-surgical PG (PSPG) of the breast. The authors of this article experienced an impressive case of PSPG after an aesthetic breast augmentation mastopexy. PSPG is a rare but severe complication in this elective aesthetic surgical procedure. METHOD: A systematic review of the literature was performed, focusing on PSPG after aesthetic breast surgery (augmentation mammoplasty/mastopexy). The online databases Pubmed, Medline, and Cochrane were used and additionally a Google© search was conducted. We compared the data obtained from a systematic literature review to an index case of PSPG after esthetic augmentation mammoplasty. RESULTS: The literature search identified seven articles describing eight cases of PSPG after aesthetic breast surgery. In four of these cases augmentation mammoplasty had been carried out, in two cases mastopexy and in two cases augmentation mammoplasty and mastopexy (augmentation mastopexy). The patient we treated and describe in this paper underwent an augmentation mastopexy outside our clinic. Eight patients suffered from local disease, at the site of surgical wounds, one patient had disseminated disease. Leukocytosis was present in five cases (out of nine). Eight patients had received corticosteroid treatment, one patient refused such treatment. The duration of corticosteroid treatment was on average for 41 days (range 21-60 days). In all cases, the areola had been spared. Complete healing of PSPG was observed on average after 5 months (range 1.5 months-1 year). DISCUSSION: PSPG of the breast after aesthetic breast surgery is rare, but every plastic surgeon should consider this possibility, especially if skin disease develops post-surgery, mimicking wound infection that does not respond to broad-spectrum antibiotic treatment. CONCLUSION: Although the literature does not recommend this step, implant removal is recommended by the authors because bacterial wound infection normally cannot be ruled out definitely in the early stages of disease. Additional surgical intervention should be limited to the absolute necessary and performed only under adequate systemic immunosuppressive therapy. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

AA amyloidosis treated with tocilizumab: case series and updated literature review.

BACKGROUND: In published case reports, tocilizumab (TCZ) has shown good efficacy for AA amyloidosis in almost all patients. We investigated the efficacy and safety of TCZ in AA amyloidosis in a multicentre study of unselected cases. METHODS: We e-mailed rheumatology and internal medicine departments in France, Switzerland and North Africa by using the Club Rhumatismes Inflammation (CRI) network and the French TCZ registry, Registry RoAcTEmra (REGATE), to gather data on consecutive patients with histologically proven AA amyloidosis who had received at least one TCZ infusion. Efficacy was defined as a sustained decrease in proteinuria level and/or stable or improved glomerular filtration rate (GFR) and by TCZ maintenance. RESULTS: We collected 12 cases of AA amyloidosis treated with TCZ as monotherapy (mean age of patients 63 ± 16.2 years, amyloidosis duration 20.6 ± 31.3 months): eight patients had rheumatoid arthritis (RA), six with previous failure of anti-tumor necrosis factor α (anti-TNF-α) therapy. In total, 11 patients had renal involvement, with two already on hemodialysis (not included in the renal efficacy assessment). For the nine other patients, baseline GFR and proteinuria level were 53.6 ± 32.8 mL/min and 5 ± 3.3 g/24 h, respectively. The mean follow-up was 13.1 ± 11 months. TCZ was effective for six of the eight RA patients (87.5%) according to European League Against Rheumatism response criteria (four good and two moderate responders). As expected, C-reactive protein (CRP) level decreased with treatment for 11 patients. Renal amyloidosis (n = 9) progressed in three patients and was stabilized in three. Overall, three patients showed improvement, with sustained decrease in proteinuria level (42%, 82% and 96%). Baseline CRP level was higher in subsequent responders to TCZ than other patients (p = 0.02). Among the six RA patients with previous anti-TNF-α therapy, amyloidosis was ameliorated in one and stabilized in three. Three serious adverse events occurred (two diverticulitis and one major calciphylaxia due to renal failure). Finally, 7 of 12 (58%) patients continued TCZ. CONCLUSIONS: The efficacy of TCZ for AA amyloidosis varies depending on the inflammatory status at treatment onset. Discrepancies between our study of unselected consecutive patients and reported cases may be due to publication bias. These results support further prospective trials of TCZ for AA amyloidosis.

Literature report : a review of policy learning in five strands of political science research

This paper reviews the policy learning literature in political science. In recent years, the number of publications on learning in the political realm increased dramatically. Researchers have focused on how policymakers and administrators adapt policies based on learning processes or experiences. Thereby, learning has been discussed in very different ways. Authors have referred to learning in the context of ideas, understood as deeply held beliefs, and, as change and adaptation of policy instruments. Two other strands of literature have taken into consideration learning, namely the diffusion literature and research on transfer, which put forward learning to understand who learns from whom and what. Opposed to these views, political learning emphasizes the adaptation of new strategies by policymakers over the transfer of knowledge or broad ideas. In this approach, learning occurs due to the failure of existing policies, increasing problem pressure, scientific innovations, or a combination of these elements.