SafeWeb: A Middleware for Securing Ruby-Based Web Applications

Web applications in many domains such as healthcare and finance must process sensitive data, while complying with legal policies regarding the release of different classes of data to different parties. Currently, software bugs may lead to irreversible disclosure of confidential data in multi-tier web applications. An open challenge is how developers can guarantee these web applications only ever release sensitive data to authorised users without costly, recurring security audits. Our solution is to provide a trusted middleware that acts as a “safety net” to event-based enterprise web applications by preventing harmful data disclosure before it happens. We describe the design and implementation of SafeWeb, a Ruby-based middleware that associates data with security labels and transparently tracks their propagation at different granularities across a multi-tier web architecture with storage and complex event processing. For efficiency, maintainability and ease-of-use, SafeWeb exploits the dynamic features of the Ruby programming language to achieve label propagation and data flow enforcement. We evaluate SafeWeb by reporting our experience of implementing a web-based cancer treatment application and deploying it as part of the UK National Health Service (NHS)

Transcatheter aortic valve implantation for severe aortic stenosis. 30-day outcomes of singlecenter experience

Wprowadzenie. Przezskórne wszczepienie zastawki aortalnej (TAVI) jest alternatywą dla chirurgicznej wymiany zastawki aortalnej. Cel. Ocena ryzyka okołoproceduralnego TAVI, skuteczności implantacji oraz wyników leczenia bezpośredniego i 30-dniowej obserwacji pacjentów z Kliniki Kardiologii Inwazyjnej Centralnego Szpitala Klinicznego MSWiA. Materiały i metody. Analizą objęto 45 chorych zakwalifikowanych do przezskórnego wszczepienia zastawki aortalnej. Średni wiek leczonej populacji wynosił 82 lata. Kobiety stanowiły 55% chorych poddanych zabiegowi. Średni wynik EuroScore II wyniósł 4,78%. W badanej populacji dokonano analizy parametrów klinicznych (klasyfikacja NYHA, CCS), biochemicznych (między innymi kreatynina, hemoglobina, NT-proBNP) oraz echokardiograficznych (LVEF, AVA). Badani chorzy przed zabiegiem TAVI mieli wykonaną również 64-rzędową tomografię komputerową (ocena pierścienia zastawki oraz dostępu naczyniowego) oraz angiografię tętnic wieńcowych. Zastawki CoreValve użyto u 39 pacjentów, Edwards-Sapien u 4, Symetis u 2. Wyniki. Całkowita śmiertelność do 30 dni od zabiegu wyniosła 4,5 % (n = 2). Nie odnotowano żadnego zgonu w okresie okołozabiegowym. Implantację stymulatora po zabiegu TAVI wykonano u sześciu chorych ze względu na występowanie bloku lewej odnogi pęczka Hisa (n = 3) lub wysokiego stopnia bloku przedsionkowo-komorowego (n = 3). Częstość udaru mózgu wynosiła 4,5% (n = 2). U 4,5% (n = 2) pacjentów wystąpiła tamponada serca niezakończona zgonem. Odnotowano istotne zwiększenie pola powierzchni ujścia aortalnego, jak również redukcję gradientu przezzastawkowego i stopnia niedomykalności zastawki aortalnej, zarówno centralnej, jak i okołozastawkowej. Wnioski. Pacjenci z ciężkim objawowym zwężeniem aorty, którzy nie zostali zakwalifikowani do chirurgicznej wymiany zastawki aortalnej ze względu na zaawansowany wiek, dysfunkcję lewej komory lub współwystępowanie wielu czynników ryzyka, odnoszą korzyści z TAVI. Również dla pacjentów bez najwyższego ryzyka chirurgicznego, TAVI może być korzystną alternatywą.  Introduction. Transcatheter aortic valve implantation (TAVI) is an alternative therapeutic method for surgery aortic valve replacement (AVR). Aim. To assess periprocedural risk of TAVI and in-hospital and 30-day follow-up result in patients treated in the Department of Invasive Cardiology in Central Clinical Hospital of the Ministry of Interior in Warsaw, Poland. Material and methods. Forty-five aortic stenosis patients (mean age 82 years, 55% females ) not suitable for surgery underwent TAVI. Average EuroScore II was 4.78%. We examined clinical parameters (NYHA and CCS class), biochemical markers (including creatinine, haemoglobin, NT-proBNP) as well echocardiographic (LVEF, AVA) and CT-derived findings. CoreValve was implanted in 39 patients, Edwards Sapien in 4, Symetis in 2. Results. After 30 days the all-cause mortality rate was 4.5% (n = 2). At 30 days, 6 patients needed permanent stimulation, symptomatic stroke was found in 4.5% (n = 2) of the patients, and cardiac tamponade in 4.5% (n = 2). The aortic valve area and mean pressure gradient were significantly improved. We observed reduction of aortic regurgitation. Conclusion. The patients with severe symptomatic aortic stenosis do not undergo surgery for replacement of the aortic valve, owing to advanced age, left ventricular dysfunction, or the presence of multiple coexisting conditions were taking benefits from TAVI back. For patients, who are at not a highest surgical risk, TAVI may be a worthwhile alternative

Automatic rule extraction from access rules using Genetic Programming

International audienceThe security policy rules in companies are generally proposed by the Chief Security Officer (CSO), who must, for instance, select by hand which access events are allowed and which ones should be forbidden. In this work we propose a way to automatically obtain rules that gen-eralise these single-event based rules using Genetic Programming (GP), which, besides, should be able to present them in an understandable way. Our GP-based system obtains good dataset coverage and small ratios of false positives and negatives in the simulation results over real data, after testing different fitness functions and configurations in the way of coding the individuals

The interaction of vasoactive substances during exercise modulates platelet aggregation in hypertension and coronary artery disease

<p>Abstract</p> <p>Background</p> <p>Acute vigorous exercise, associated with increased release of plasma catecholamines, transiently increases the risk of primary cardiac arrest. We tested the effect of acute submaximal exercise on vasoactive substances and their combined result on platelet function.</p> <p>Methods</p> <p>Healthy volunteers, hypertensive patients and patients with coronary artery disease (CAD) performed a modified treadmill exercise test. We determined plasma catecholamines, thromboxane A₂, prostacyclin, endothelin-1 and platelet aggregation induced by adenosine diphosphate (ADP) and collagen at rest and during exercise.</p> <p>Results</p> <p>Our results during exercise showed a) platelet activation (increased thromboxane B₂, TXB₂), b) increased prostacyclin release from endothelium and c) decreased platelet aggregation in all groups, significantly more in healthy volunteers than in patients with CAD (with hypertensives lying in between these two groups).</p> <p>Conclusion</p> <p>Despite the pronounced activation of Sympathetic Nervous System (SNS) and increased TXB₂levels during acute exercise platelet aggregation decreases, possibly to counterbalance the prothrombotic state. Since this effect seems to be mediated by the normal endothelium (through prostacyclin and nitric oxide), in conditions characterized by endothelial dysfunction (hypertension, CAD) reduced platelet aggregation is attenuated, thus posing such patients in increased risk for thrombotic complications.</p

Effect of Adjunct Metformin Treatment in Patients with Type-1 Diabetes and Persistent Inadequate Glycaemic Control. A Randomized Study

Despite intensive insulin treatment, many patients with type-1 diabetes (T1DM) have longstanding inadequate glycaemic control. Metformin is an oral hypoglycaemic agent that improves insulin action in patients with type-2 diabetes. We investigated the effect of a one-year treatment with metformin versus placebo in patients with T1DM and persistent poor glycaemic control.One hundred patients with T1DM, preserved hypoglycaemic awareness and HaemoglobinA(1c) (HbA(1c)) > or = 8.5% during the year before enrolment entered a one-month run-in on placebo treatment. Thereafter, patients were randomized (baseline) to treatment with either metformin (1 g twice daily) or placebo for 12 months (double-masked). Patients continued ongoing insulin therapy and their usual outpatient clinical care. The primary outcome measure was change in HbA(1c) after one year of treatment. At enrolment, mean (standard deviation) HbA(1c) was 9.48% (0.99) for the metformin group (n = 49) and 9.60% (0.86) for the placebo group (n = 51). Mean (95% confidence interval) baseline-adjusted differences after 12 months with metformin (n = 48) versus placebo (n = 50) were: HbA(1c), 0.13% (-0.19; 0.44), p = 0.422; Total daily insulin dose, -5.7 U/day (-8.6; -2.9), p<0.001; body weight, -1.74 kg (-3.32; -0.17), p = 0.030. Minor and overall major hypoglycaemia was not significantly different between treatments. Treatments were well tolerated.In patients with poorly controlled T1DM, adjunct metformin therapy did not provide any improvement of glycaemic control after one year. Nevertheless, adjunct metformin treatment was associated with sustained reductions of insulin dose and body weight. Further investigations into the potential cardiovascular-protective effects of metformin therapy in patients with T1DM are warranted.ClinicalTrials.gov NCT00118937

Lesion of the Cerebellar Noradrenergic Innervation Enhances the Harmaline-Induced Tremor in Rats

Abnormal synchronous activation of the glutamatergic olivo-cerebellar pathway has been suggested to be crucial for the harmaline-induced tremor. The cerebellum receives two catecholaminergic pathways: the dopaminergic pathway arising from the ventral tegmental area/substantia nigra pars compacta, and the noradrenergic one from the locus coeruleus. The aim of the present study was to examine a contribution of the cerebellar catecholaminergic innervations to the harmaline-induced tremor in rats. Rats were injected bilaterally into the cerebellar vermis with 6-hydroxydopamine (6-OHDA; 8 μg/0.5 μl) either alone or this treatment was preceded (30 min earlier) by desipramine (15 mg/kg ip). Harmaline was administered to animals in doses of 7.5 or 15 mg/kg ip. Tremor of forelimbs was measured as a number of episodes during a 90-min observation. Rats were killed by decapitation 30 or 120 min after harmaline treatment. The levels of dopamine, noradrenaline, serotonin, and their metabolites were measured by HPLC in the cerebellum, substantia nigra, caudate–putamen, and frontal cortex. 6-OHDA injected alone enhanced the harmaline-induced tremor. Furthermore, it decreased the noradrenaline level by ca. 40–80% in the cerebellum and increased the levels of serotonin and 5-HIAA in the caudate–putamen and frontal cortex in untreated and/or harmaline-treated animals. When 6-OHDA treatment was preceded by desipramine, it decreased dopaminergic transmission in some regions of the cerebellum while inducing its compensatory activation in others. The latter lesion did not markedly influence the tremor induced by harmaline. The present study indicates that noradrenergic innervation of the cerebellum interacts with cerebral serotonergic systems and plays an inhibitory role in the harmaline-induced tremor

Interactive effects of mGlu5 and 5-HT2A receptors on locomotor activity in mice

RationaleMetabotropic glutamate (mGlu) receptors have been suggested to play a role in neuropsychiatric disorders including schizophrenia, drug abuse, and depression. Because serotonergic hallucinogens increase glutamate release and mGlu receptors modulate the response to serotonin (5-HT)(2A) activation, the interactions between serotonin 5-HT(2A) receptors and mGlu receptors may prove to be important for our understanding of these diseases.ObjectiveWe tested the effects of the serotonergic hallucinogen and 5-HT(2A) agonist, 2,5-dimethoxy-4-methylamphetamine (DOM), and the selective 5-HT(2A) antagonist, M100907, on locomotor activity in the mouse behavioral pattern monitor (BPM) in mGlu5 wild-type (WT) and knockout (KO) mice on a C57 background.ResultsBoth male and female mGlu5 KO mice showed locomotor hyperactivity and diminished locomotor habituation compared with their WT counterparts. Similarly, the mGlu5-negative allosteric modulator 2-methyl-6-(phenylethynyl)pyridine (MPEP) also increased locomotor hyperactivity, which was absent in mGlu5 KO mice. The locomotor hyperactivity in mGlu5 receptor KO mice was potentiated by DOM (0.5 mg/kg, subcutaneously (SC)) and attenuated by M100907 (1.0 mg/kg, SC). M100907 (0.1 mg/kg, SC) also blocked the hyperactivity induced by MPEP.ConclusionsThese studies demonstrated that loss of mGlu5 receptor activity either pharmacologically or through gene deletion leads to locomotor hyperactivity in mice. Additionally, the gene deletion of mGlu5 receptors increased the behavioral response to the 5-HT(2A) agonist DOM, suggesting that mGlu5 receptors either mitigate the behavioral effects of 5-HT(2A) hallucinogens or that mGlu5 KO mice show an increased sensitivity to 5-HT(2A) agonists. Taken together, these studies indicate a functional interaction between mGlu5 and 5-HT(2A) receptors

Selective mGluR1 Antagonist EMQMCM Inhibits the Kainate-Induced Excitotoxicity in Primary Neuronal Cultures and in the Rat Hippocampus

Abundant evidence suggests that indirect inhibitory modulation of glutamatergic transmission, via metabotropic glutamatergic receptors (mGluR), may induce neuroprotection. The present study was designed to determine whether the selective antagonist of mGluR1 (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate (EMQMCM), showed neuroprotection against the kainate (KA)-induced excitotoxicity in vitro and in vivo. In in vitro studies on mouse primary cortical and hippocampal neuronal cultures, incubation with KA (150 μM) induced strong degeneration [measured as lactate dehydrogenase (LDH) efflux] and apoptosis (measured as caspase-3 activity). EMQMCM (0.1–100 μM) added 30 min to 6 h after KA, significantly attenuated the KA-induced LDH release and prevented the increase in caspase-3 activity in the cultures. Those effects were dose- and time-dependent. In in vivo studies KA (2.5 nmol/1 μl) was unilaterally injected into the rat dorsal CA1 hippocampal region. Degeneration was calculated by counting surviving neurons in the CA pyramidal layer using stereological methods. It was found that EMQMCM (5–10 nmol/1 μl) injected into the dorsal hippocampus 30 min, 1 h, or 3 h (the higher dose only) after KA significantly prevented the KA-induced neuronal degeneration. In vivo microdialysis studies in rat hippocampus showed that EMQMCM (100 μM) significantly increased γ-aminobutyric acid (GABA) and decreased glutamate release. When perfused simultaneously with KA, EMQMCM substantially increased GABA release and prevented the KA-induced glutamate release. The obtained results indicate that the mGluR1 antagonist, EMQMCM, may exert neuroprotection against excitotoxicity after delayed treatment (30 min to 6 h). The role of enhanced GABAergic transmission in the neuroprotection is postulated