Formal Verification of Neural Network Controlled Autonomous Systems

In this paper, we consider the problem of formally verifying the safety of an autonomous robot equipped with a Neural Network (NN) controller that processes LiDAR images to produce control actions. Given a workspace that is characterized by a set of polytopic obstacles, our objective is to compute the set of safe initial conditions such that a robot trajectory starting from these initial conditions is guaranteed to avoid the obstacles. Our approach is to construct a finite state abstraction of the system and use standard reachability analysis over the finite state abstraction to compute the set of the safe initial states. The first technical problem in computing the finite state abstraction is to mathematically model the imaging function that maps the robot position to the LiDAR image. To that end, we introduce the notion of imaging-adapted sets as partitions of the workspace in which the imaging function is guaranteed to be affine. We develop a polynomial-time algorithm to partition the workspace into imaging-adapted sets along with computing the corresponding affine imaging functions. Given this workspace partitioning, a discrete-time linear dynamics of the robot, and a pre-trained NN controller with Rectified Linear Unit (ReLU) nonlinearity, the second technical challenge is to analyze the behavior of the neural network. To that end, we utilize a Satisfiability Modulo Convex (SMC) encoding to enumerate all the possible segments of different ReLUs. SMC solvers then use a Boolean satisfiability solver and a convex programming solver and decompose the problem into smaller subproblems. To accelerate this process, we develop a pre-processing algorithm that could rapidly prune the space feasible ReLU segments. Finally, we demonstrate the efficiency of the proposed algorithms using numerical simulations with increasing complexity of the neural network controller

A systematic review of the evidence for single stage and two stage revision of infected knee replacement

BACKGROUND: Periprosthetic infection about the knee is a devastating complication that may affect between 1% and 5% of knee replacement. With over 79 000 knee replacements being implanted each year in the UK, periprosthetic infection (PJI) is set to become an important burden of disease and cost to the healthcare economy. One of the important controversies in treatment of PJI is whether a single stage revision operation is superior to a two-stage procedure. This study sought to systematically evaluate the published evidence to determine which technique had lowest reinfection rates. METHODS: A systematic review of the literature was undertaken using the MEDLINE and EMBASE databases with the aim to identify existing studies that present the outcomes of each surgical technique. Reinfection rate was the primary outcome measure. Studies of specific subsets of patients such as resistant organisms were excluded. RESULTS: 63 studies were identified that met the inclusion criteria. The majority of which (58) were reports of two-stage revision. Reinfection rated varied between 0% and 41% in two-stage studies, and 0% and 11% in single stage studies. No clinical trials were identified and the majority of studies were observational studies. CONCLUSIONS: Evidence for both one-stage and two-stage revision is largely of low quality. The evidence basis for two-stage revision is significantly larger, and further work into direct comparison between the two techniques should be undertaken as a priority

Early Experience With Uniplanar Versus Biplanar Expandable Interbody Fusion Devices in Single-Level Minimally Invasive Transforaminal Lumbar Interbody Fusion

ObjectiveTo compare the early radiographic and clinical outcomes of expandable uniplanar versus biplanar interbody cages used for single-level minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). MethodA retrospective review of 1-level MIS-TLIFs performed with uniplanar and biplanar polyetheretherketone cages was performed. Radiographic measurements were performed on radiographs taken preoperatively, at 6-week follow-up, and 1-year follow-up. Oswestry Disability Index (ODI) and visual analogue scale (VAS) for back and leg at 3-month and 1-year follow-up. ResultsA total of 93 patients (41 uniplanar, 52 biplanar) were included. Both cage types provided significant postoperative improvements in anterior disc height, posterior disc height, and segmental lordosis at 1 year. No significant differences in cage subsidence rates were found between uniplanar (21.9%) and biplanar devices (32.7%) at 6 weeks (odds ratio, 2.015; 95% confidence interval, 0.651–6.235; p = 0.249) with no additional instances of subsidence at 1 year. No significant differences in the magnitude of improvements based on ODI, VAS back, or VAS leg at 3-month or 1-year follow-up between groups and the proportion of patients achieving the minimal clinically important difference in ODI, VAS back, or VAS leg at 1 year were not statistically significantly different (p \u3e 0.05). Finally, there were no significant differences in complication rates (p = 0.283), 90-day readmission rates (p = 1.00), revision surgical procedures (p = 0.423), or fusion rates at 1 year (p = 0.457) between groups. ConclusionsBiplanar and uniplanar expandable cages offer a safe and effective means of improving anterior disc height, posterior disc height, segmental lordosis, and patient-reported outcome measures at 1 year postoperatively. No significant differences in radiographic outcomes, subsidence rates, mean subsidence distance, 1-year patient-reported outcomes, and postoperative complications were noted between groups

Association analysis identifies ZNF750 regulatory variants in psoriasis

<p>Abstract</p> <p>Background</p> <p>Mutations in the <it>ZNF750 </it>promoter and coding regions have been previously associated with Mendelian forms of psoriasis and psoriasiform dermatitis. <it>ZNF750 </it>encodes a putative zinc finger transcription factor that is highly expressed in keratinocytes and represents a candidate psoriasis gene.</p> <p>Methods</p> <p>We examined whether <it>ZNF750 </it>variants were associated with psoriasis in a large case-control population. We sequenced the promoter and exon regions of <it>ZNF750 </it>in 716 Caucasian psoriasis cases and 397 Caucasian controls.</p> <p>Results</p> <p>We identified a total of 47 variants, including 38 rare variants of which 35 were novel. Association testing identified two <it>ZNF750 </it>haplotypes associated with psoriasis (p < 0.05). We also identified an excess of rare promoter and 5'untranslated region (UTR) variants in psoriasis cases compared to controls (p = 0.041), whereas there was no significant difference in the number of rare coding and rare 3' UTR variants. Using a promoter functional assay in stimulated human primary keratinocytes, we showed that four <it>ZNF750 </it>promoter and 5' UTR variants displayed a 35-55% reduction of <it>ZNF750 </it>promoter activity, consistent with the promoter activity reduction seen in a Mendelian psoriasis family with a <it>ZNF750 </it>promoter variant. However, the rare promoter and 5' UTR variants identified in this study did not strictly segregate with the psoriasis phenotype within families.</p> <p>Conclusions</p> <p>Two haplotypes of <it>ZNF750 </it>and rare 5' regulatory variants of <it>ZNF750 </it>were found to be associated with psoriasis. These rare 5' regulatory variants, though not causal, might serve as a genetic modifier of psoriasis.</p

International Influences and Drag: Just a Case of Tucking or Binding?

Recently there has been an  internationalisation in the training of UK drag performers. Whilst papers exist focused on drag kings and queens related to their community, few explore how kings/queens train – and fewer still explore international aspects. There are formal courses for drag, but historically this training was informal, present within specific performance communities built around LGBTQ cultures. Tracing dominant figures in such training – the drag mother/father – in order to historicise and contextualise the current explosion in drag performance,the paper argues that the potential globalisation of drag is largely down to the diversification of sources of knowledge available via the internet. Traditionally, performers trained with an established practitioner, where regional variances of drag were passed on. However, current new performers often learn ‘tricks of the trade’ through internet videos posted by people on other continents. In these videos, practitioners pass on their knowledge from the perspective of their locality, as if universal. New kings/queens are not passive in this training and locally infuse their acts, yet historical and local erasures persist. The paper argues that to engage with drag as performance one must be aware of locality and the deep connects drag has with its communities

Distribution pattern of psoriasis, anxiety and depression as possible causes of sexual dysfunction in patients with moderate to severe psoriasis

BACKGROUND: Psoriasis may significantly impair sexual function. Depression and organic factors appear to play a key role in this relation. However, beyond genital psoriasis, the importance of the disease's distribution patterns has not been considered. OBJECTIVES: To research sexual function in psoriasis patients and investigate the roles of anxiety, depression and psoriasis' distribution patterns in sexual dysfunction. METHODS: A comparative study matched for sex and age was performed. Eighty patients with moderate to severe psoriasis and 80 healthy controls were included. The participants completed the Massachusetts General Hospital-Sexual Functioning Questionnaire, the Hospital Anxiety and Depression Scale, and the Self-Administered Psoriasis Area and Severity Index. RESULTS: Psoriasis was associated with sexual dysfunction, odds ratio=5.5 (CI 95% 2.6-11.3; p<0.001). Certain distribution patterns of psoriasis, involving specific body regions, were associated with an increase in sexual dysfunction in the group presenting the disease, odds ratio 7.9 (CI 95% 2.3-33.4; p<0.001). Multivariate logistic regression analysis identified anxiety and depression, and the involvement of these specific areas, as possible independent risk factors for sexual dysfunction in patients with moderate to severe psoriasis. CONCLUSION: This study identifies body areas potentially related to sexual dysfunction, independently of anxiety and depression, in psoriasis patients. The results suggest that the assessment of sexual dysfunction and the involvement of these body areas should be considered as disease severity criteria when choosing the treatment for psoriasis patients

Targeting of human interleukin-12B by small hairpin RNAs in xenografted psoriatic skin

<p>Abstract</p> <p>Background</p> <p>Psoriasis is a chronic inflammatory skin disorder that shows as erythematous and scaly lesions. The pathogenesis of psoriasis is driven by a dysregulation of the immune system which leads to an altered cytokine production. Proinflammatory cytokines that are up-regulated in psoriasis include tumor necrosis factor alpha (TNFα), interleukin-12 (IL-12), and IL-23 for which monoclonal antibodies have already been approved for clinical use. We have previously documented the therapeutic applicability of targeting TNFα mRNA for RNA interference-mediated down-regulation by anti-TNFα small hairpin RNAs (shRNAs) delivered by lentiviral vectors to xenografted psoriatic skin. The present report aims at targeting mRNA encoding the shared p40 subunit (IL-12B) of IL-12 and IL-23 by cellular transduction with lentiviral vectors encoding anti-IL12B shRNAs.</p> <p>Methods</p> <p>Effective anti-IL12B shRNAs are identified among a panel of shRNAs by potency measurements in cultured cells. The efficiency and persistency of lentiviral gene delivery to xenografted human skin are investigated by bioluminescence analysis of skin treated with lentiviral vectors encoding the luciferase gene. shRNA-expressing lentiviral vectors are intradermally injected in xenografted psoriatic skin and the effects of the treatment evaluated by clinical psoriasis scoring, by measurements of epidermal thickness, and IL-12B mRNA levels.</p> <p>Results</p> <p>Potent and persistent transgene expression following a single intradermal injection of lentiviral vectors in xenografted human skin is reported. Stable IL-12B mRNA knockdown and reduced epidermal thickness are achieved three weeks after treatment of xenografted psoriatic skin with lentivirus-encoded anti-IL12B shRNAs. These findings mimick the results obtained with anti-TNFα shRNAs but, in contrast to anti-TNFα treatment, anti-IL12B shRNAs do not ameliorate the psoriatic phenotype as evaluated by semi-quantitative clinical scoring and by immunohistological examination.</p> <p>Conclusions</p> <p>Our studies consolidate the properties of lentiviral vectors as a tool for potent gene delivery and for evaluation of mRNA targets for anti-inflammatory therapy. However, in contrast to local anti-TNFα treatment, the therapeutic potential of targeting IL-12B at the RNA level in psoriasis is questioned.</p

Does Smoking Status Influence Health-Related Quality of Life Outcome Measures in Patients Undergoing ACDF?

STUDY DESIGN: Retrospective comparative study. OBJECTIVE: Whereas smoking has been shown to affect the fusion rates for patients undergoing an anterior cervical discectomy and fusion (ACDF), the relationship between smoking and health-related quality of life outcome measurements after an ACDF is less clear. The purpose of this study was to evaluate whether smoking negatively affects patient outcomes after an ACDF for cervical degenerative pathology. METHODS: Patients with tumor, trauma, infection, and previous cervical spine surgery and those with less than a year of follow-up were excluded. Smoking status was assessed by self-reported smoking history. Patient outcomes, including Neck Disability Index, Short Form 12 Mental Component Score, Short Form 12 Physical Component Score (PCS-12), Visual Analogue Scale (VAS) arm pain, VAS neck pain, and pseudarthrosis rates were evaluated. Outcomes were compared between smoking groups using multiple linear and logistic regression, controlling for age, sex, and body mass index (BMI), among other factors. A P value \u3c.05 was considered significant. RESULTS: A total of 264 patients were included, with a mean follow-up of 19.8 months, age of 53.1 years, and BMI of 29.6 kg/m2. There were 43 current, 69 former, and 152 nonsmokers in the cohort. At baseline, nonsmokers had higher PCS-12 scores than current smokers (P = .010), lower VAS neck pain than current (P = .035) and former (P = .014) smokers, as well as lower VAS arm pain than former smokers (P = .006). Postoperatively, nonsmokers had higher PCS-12 scores than both current (P = .030) and former smokers (P = .035). Smoking status was not a significant predictor of change in patient outcome in multivariate analysis. CONCLUSIONS: Whereas nonsmokers had higher function and lower pain than former or current smokers preoperatively, smoking status overall was not found to be an independent predictor of outcome scores after ACDF. This supports the notion that smoking status alone should not deter patients from undergoing ACDF for cervical degenerative pathology