Reservoir Computing Approach to Robust Computation using Unreliable Nanoscale Networks

As we approach the physical limits of CMOS technology, advances in materials science and nanotechnology are making available a variety of unconventional computing substrates that can potentially replace top-down-designed silicon-based computing devices. Inherent stochasticity in the fabrication process and nanometer scale of these substrates inevitably lead to design variations, defects, faults, and noise in the resulting devices. A key challenge is how to harness such devices to perform robust computation. We propose reservoir computing as a solution. In reservoir computing, computation takes place by translating the dynamics of an excited medium, called a reservoir, into a desired output. This approach eliminates the need for external control and redundancy, and the programming is done using a closed-form regression problem on the output, which also allows concurrent programming using a single device. Using a theoretical model, we show that both regular and irregular reservoirs are intrinsically robust to structural noise as they perform computation

Phase I/II study of resection and intraoperative cesium-131 radioisotope brachytherapy in patients with newly diagnosed brain metastases.

OBJECT: Resected brain metastases have a high rate of local recurrence without adjuvant therapy. Adjuvant whole-brain radiotherapy (WBRT) remains the standard of care with a local control rate \u3e 90%. However, WBRT is delivered over 10-15 days, which can delay other therapy and is associated with acute and long-term toxicities. Permanent cesium-131 ((131)Cs) implants can be used at the time of metastatic resection, thereby avoiding the need for any additional therapy. The authors evaluated the safety, feasibility, and efficacy of a novel therapeutic approach with permanent (131)Cs brachytherapy at the resection for brain metastases. METHODS: After institutional review board approval was obtained, 24 patients with a newly diagnosed metastasis to the brain were accrued to a prospective protocol between 2010 and 2012. There were 10 frontal, 7 parietal, 4 cerebellar, 2 occipital, and 1 temporal metastases. Histology included lung cancer (16), breast cancer (2), kidney cancer (2), melanoma (2), colon cancer (1), and cervical cancer (1). Stranded (131)Cs seeds were placed as permanent volume implants. The prescription dose was 80 Gy at a 5-mm depth from the resection cavity surface. Distant metastases were treated with stereotactic radiosurgery (SRS) or WBRT, depending on the number of lesions. The primary end point was local (resection cavity) freedom from progression (FFP). Secondary end points included regional FFP, distant FFP, median survival, overall survival (OS), and toxicity. RESULTS: The median follow-up was 19.3 months (range 12.89-29.57 months). The median age was 65 years (range 45-84 years). The median size of resected tumor was 2.7 cm (range 1.5-5.5 cm), and the median volume of resected tumor was 10.31 cm(3) (range 1.77-87.11 cm(3)). The median number of seeds used was 12 (range 4-35), with a median activity of 3.82 mCi per seed (range 3.31-4.83 mCi) and total activity of 46.91 mCi (range 15.31-130.70 mCi). Local FFP was 100%. There was 1 adjacent leptomeningeal recurrence, resulting in a 1-year regional FFP of 93.8% (95% CI 63.2%-99.1%). One-year distant FFP was 48.4% (95% CI 26.3%-67.4%). Median OS was 9.9 months (95% CI 4.8 months, upper limit not estimated) and 1-year OS was 50.0% (95% CI 29.1%-67.8%). Complications included CSF leak (1), seizure (1), and infection (1). There was no radiation necrosis. CONCLUSIONS: The use of postresection permanent (131)Cs brachytherapy implants resulted in no local recurrences and no radiation necrosis. This treatment was safe, well tolerated, and convenient for patients, resulting in a short radiation treatment course, high response rate, and minimal toxicity. These findings merit further study with a multicenter trial

Circadian Clocks as Modulators of Metabolic Comorbidity in Psychiatric Disorders

Psychiatric disorders such as schizophrenia, bipolar disorder, and major depressive disorder are often accompanied by metabolic dysfunction symptoms, including obesity and diabetes. Since the circadian system controls important brain systems that regulate affective, cognitive, and metabolic functions, and neuropsychiatric and metabolic diseases are often correlated with disturbances of circadian rhythms, we hypothesize that dysregulation of circadian clocks plays a central role in metabolic comorbidity in psychiatric disorders. In this review paper, we highlight the role of circadian clocks in glucocorticoid, dopamine, and orexin/melanin-concentrating hormone systems and describe how a dysfunction of these clocks may contribute to the simultaneous development of psychiatric and metabolic symptoms

Open access at the Medical University of Graz - therapeutic decisions caught between research and clinical practice

Open access at a medical university very often just happens by chance. However, sustained success can be achieved by targeted measures and institutional support. Many authors - caught between teaching, research and clinical tasks - are hardly able to fully know and take advantage of the various options of open access and the requirements stipulated by research funders. Authors hence need to rely on the framework provided by their institutions. Therefore, this framework must cover professionally and efficiently the possibilities offered by open access and become part of authors' daily routine. If this is accomplished to a sufficient extent, such as with transformative agreements, Plan S and publication funds, the number of open access publications goes up without knowing which measure has been crucial and open access publishing just seems to happen.Open Access an einer Medizinischen Universität passiert oftmals einfach. Dennoch lassen sich mit gezielten Maßnahmen und institutioneller Unterstützung Erfolge erzielen. Viele AutorInnen sind aber oftmals zwischen Forschung, Lehre und klinischem Alltag kaum in der Lage, die zusätzlichen Variationen und Förderbedingungen von Open Access zu durchschauen und für sich zu nutzen. So müssen diese sich auf Strukturen verlassen können, welche ihnen die Institutionen bereitstellen. Diese Strukturen müssen daher professionell und effizient die Möglichkeiten die Open Access bietet erfassen und versuchen diese in die tägliche Struktur der AutorInnen einzubauen. Gelingt dies in ausreichenden Maßen wie bei Transformationsabkommen, Plan S und Publikationsfonds, dann erhöht sich die Rate der Open-Access-Publikationen, ohne diese einer spezifischen Maßnahme zuordnen zu können, sie passieren dann augenscheinlich einfach

Investigating the role of cortisol and growth hormone in fatty liver development: fatty liver index in patients with pituitary adenomas

Non-alcoholic fatty liver disease (NAFLD) is a hallmark of the metabolic syndrome and has been shown to be an independent predictor of cardiovascular mortality. Although glucocorticoids and growth hormone are known to be implicated in its pathophysiology, it has only rarely been investigated in the context of patients with pituitary insufficiency or former cortisol excess. Case-control study in patients with biochemically controlled Cushing's disease (CD; N = 33) and non-functioning pituitary adenomas (NFPA; N = 79). NAFLD was estimated by calculating the fatty liver index (FLI) including BMI, waist circumference, GGT and triglyceride levels. Although there was no difference in FLI between patients with NFPA and CD, we identified average daily hydrocortisone (HC) intake in those with adrenal insufficiency to be an independent predictor of FLI (beta = 1.124; p = 0.017), even after adjusting for BMI and waist circumference. In line, those with a FLI > 60 were also taking in average significantly more HC per day than those with a score < 60 (21.05 mg +/- 5.9 vs. 17.9 mg +/- 4.4; p = 0.01). FLI was also the best independent predictor for HbA1c and fasting glucose levels (both p = 0.001). Growth hormone deficiency and replacement therapy were not associated with FLI in either group. While HC dosage affects FLI as an estimate of NFLD in patients with CD and NFPA, the benefit of GH replacement still needs to be determined. In contrast to reports in CD patients with active disease, NAFLD in those with biochemical control was not different from NFPA patients

Is insulin-like growth factor-I a good marker for treatment adherence in growth hormone deficiency in adulthood?

ObjectiveThere is a paucity of studies on adherence to growth hormone treatment in growth hormone deficient (GHD) adults. Therefore, this study reports on adherence to GH-replacement therapy in adults with GHD, with a special focus on the course and potential predictors of nonadherence. DesignRetrospective single-centre cohort study. PatientsFrom the local patient database, 179 suitable patients with GHD were identified. MeasurementsThe primary outcome was adherence assessed by calculating the percentage of available prescription data in comparison with recommended GH dosages over a mean follow-up period of 924 months. Patients were categorized into five adherence categories ranging from 80%. ResultsMean overall adherence was 740%, with 529% of patients falling into the adherence group of >80% and 88% of <20%. There was a significant drop in adherence (98%) between the first and second years of treatment (P < 0001). Patients with childhood-onset GHD were significantly less adherent to GH treatment than patients with adult-onset GHD (620% vs 770%, P = 0012); however, this finding was no longer significant after including age as a covariate. Frequency of IGF-1 levels lying outside the age- and sex-specific reference range was not a good indicator for adherence. ConclusionAlthough overall adherence was relatively high in our study sample, there is a significant amount of patients who should be regarded as nonadherent. This applies in particular to younger patients. Treating physicians should be aware of the fact that IGF-1 levels do not seem to be a good indicator for adherence

Leptin: A hormone linking activation of neuroendocrine axes with neuropathology

Leptin, a peptide hormone secreted by adipocytes, plays a central role in controlling appetite and weight in both rodents and humans. Basic science and clinical research suggest that this hormone not only affects the regulation of the neuroendocrine axes, but also exerts effects on the central nervous system with subsequent alterations in psychological functions. For instance, leptin suppresses cortisol secretion during stress-related activation of the adrenal axis. As psychiatric disorders like depression are associated with hypercortisolism, leptin is proposed to exert anti-depressant-like effects due to its inhibition of chronically overactive hypothalamo-pituitary-adrenal axis function. Moreover, leptin status of depressed patients could serve as a prognostic marker for therapy response. Besides its influence on neuroendocrine pathways leptin seems to have direct central effects on brain development and neuroplasticity. Low leptin levels have been shown to be associated with increased risk of developing dementia, supporting the idea of a pro-cognitive effect of leptin. These areas may have direct clinical implications and deserve to be studied further in the future. (C) 2014 Elsevier Ltd. All rights reserved

Primary Empty Sella Syndrome and the Prevalence of Hormonal Dysregulation : A Systematic Review

Background: Empty sella is the neuroradiological or pathological finding of an apparently empty sella turcica containing no pituitary tissue. The prevalence of primary empty sella, i.e., empty sella without any discernible cause, is not precisely known; estimates range from 2% to 20%. Technical advances in neuroradiology have made empty sella an increasingly common incidental finding. It remains unclear whether, and to what extent, asymptomatic adult patients with an incidentally discovered empty sella should undergo diagnostic testing for hormonal disturbances. Methods: To answer this question, the authors carried out a systematic search in the PubMed and Web of Science databases for publications that appeared in the period 1995-2016 and that contained the search term "empty sella" (registration: PROS-dPERO 2015: CRD42015024550). Results: The search yielded 1282 hits. After the exclusion of duplicates, pediatric reports, case reports, and veterinary studies, 120 publications on primary empty sella syndrome (PES) were identified. 4 of these dealt with the prevalence of pituitary insufficiency in patients with PES as an incidental finding. Among patients with PES, the relative frequency of pituitary insufficiency in the pooled analysis was 52% (95% confidence interval [38; 65]). Conclusion: The data on PES as an incidental finding are too sparse to enable any evidence-based recommendation on the potential indications for hormone testing or its nature and extent. We advise basic neuroendocrinological testing (fasting cortisol, free thyroxine [fT4], estradiol or testosterone, insulin-like growth factor 1 [IGF-1], and prolactin). There is an unexplained discrepancy between the reported high prevalence of pituitary insufficiency among persons with PES and its low prevalence in epidemiologic studies. We suspect that the former may be high because of selection bias in the publications that we reviewed, or else the latter may be erroneously low