Approximating Activation Edge-Cover and Facility Location Problems

What approximation ratio can we achieve for the Facility Location problem if whenever a client u connects to a facility v, the opening cost of v is at most theta times the service cost of u? We show that this and many other problems are a particular case of the Activation Edge-Cover problem. Here we are given a multigraph G=(V,E), a set R subseteq V of terminals, and thresholds {t^e_u,t^e_v} for each uv-edge e in E. The goal is to find an assignment a={a_v:v in V} to the nodes minimizing sum_{v in V} a_v, such that the edge set E_a={e=uv: a_u >= t^e_u, a_v >= t^e_v} activated by a covers R. We obtain ratio 1+max_{x>=1}(ln x)/(1+x/theta)~= ln theta - ln ln theta for the problem, where theta is a problem parameter. This result is based on a simple generic algorithm for the problem of minimizing a sum of a decreasing and a sub-additive set functions, which is of independent interest. As an application, we get the same ratio for the above variant of {Facility Location}. If for each facility all service costs are identical then we show a better ratio 1+max_{k in N}(H_k-1)/(1+k/theta), where H_k=sum_{i=1}^k 1/i. For the Min-Power Edge-Cover problem we improve the ratio 1.406 of [Calinescu et al, 2019] (achieved by iterative randomized rounding) to 1.2785. For unit thresholds we improve the ratio 73/60~=1.217 of [Calinescu et al, 2019] to 1555/1347~=1.155

Astrocytes in Pathogenesis of Multiple Sclerosis and Potential Translation into Clinic

Astrocytes are the most abundant glial cells in the central nervous system (CNS) and play a pivotal role in CNS homeostasis and functionality. Malfunction of astrocytes was implicated in multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), Alzheimer’s disease (AD), and multiple sclerosis (MS). The involvement of astrocytes in the pathology of neurodegenerative disorders supports the rationale of transplantation of healthy human astrocytes that can potentially compensate for diseased endogenous astrocytes. In this review, we will focus on the roles of astrocytes in the healthy CNS and under MS conditions. We will describe the cell sources and current cell-based therapies for MS with a focus on the potential of astrocyte transplantation. In addition, we will cover immerging early-stage clinical trials in MS that are currently being conducted using cell-based therapies

Astrocytes in Pathogenesis of ALS Disease and Potential Translation into Clinic

Astrocytes are the major cell population in the central nervous system (CNS) and play pivotal role in CNS homeostasis and functionality. Malfunction of astrocytes were implicated in multiple neurodegenerative diseases and disorders, including amyotrophic lateral sclerosis (ALS), spinal cord injury (SCI), brain stroke, Parkinson’s disease (PD), and Alzheimer disease (AD). These new insights led to the rationale that transplantation of healthy and functional human astrocytes could support survival of neurons and be of therapeutic value in treating neurodegenerative diseases. Here, we will mainly focus on the role of astrocytes in ALS disease, the major cell sources for generation of human astrocytes, or astrocyte like cells and show how multiple preclinical studies demonstrate the efficacy of these cells in animal models. In addition, we will cover immerging early stage clinical trials that are currently being conducted using human astrocytes or human astrocyte like cell population

Different factors are associated with sex hormones and Leydig cell function in Israelis and Palestinians in Jerusalem

Total testosterone (TT) is known to influence health and virility in men. Among men from United States and Europe, numerous sociodemographic and lifestyle factors were reported to be associated with TT. However, associations with TT and Leydig cell function in the Middle East are poorly described. A cross-sectional, population-based sample had a structured interview, physical examinations, and blood tests in two hospitals in Jerusalem, Israel. A subsample (25- to 44-year-old men, n = 286: 124 Israelis, 162 Palestinians) had sex hormone measurements. The primary outcomes were TT and free testosterone/luteinizing hormone (FT/LH) ratio, representing Leydig cell function. Associations with sociodemographic and lifestyle factors, body mass index (BMI), and physical activity (PA) were evaluated using multivariable linear regression. Compared with Palestinians, Israelis had similar TT (4.81 vs. 5.09 ng/mL, p =.405) and higher FT/LH (31.2 vs. 25.8 ng/IU, p =.002). In ln-transformed values, marital status had a stronger association in Palestinians (P for interaction = 0.03). Age, BMI, and PA had a stronger association with TT in Israelis with significant interactions with ethnicity. BMI <25 and a higher PA quartile were associated with a higher TT (p <.001). Among Israelis, age (p =.007), married marital status (p =.007), and BMI <25 were significantly associated with FT/LH. No associations of any factors were identified among Palestinians. Associations with several modifiable factors identified in Western samples were replicated in Israelis and to a lesser degree in Palestinians. Different relationships of several factors with TT and FT/LH could result from ethnically diverse genetic, sociodemographic, and behavioral characteristics that warrant further research

Upper Tract Imaging in Patients with Initial or Terminal Hematuria Suggestive of Bleeding from the Lower Urinary Tract: How Often is the Upper Urinary Tract Responsible for the Hematuria?

Objectives: Visible hematuria (VH) is a common urological complaint. A history of initial or terminal VH in men is indicative of a lower urinary tract (LUT) source. A careful clinical history could limit unnecessary extensive upper tract imaging in this group of patients with VH. We conducted a single-center prospective study to examine the usefulness of investigating the upper tract in patients with a history of VH likely from a LUT source (initial and/or terminal VH) with specific reference to the incidence of demonstrable significant upper tract abnormalities. Methods: We conducted a single-center prospective study of consecutive male patients presenting with VH over eight months. All patients underwent standard investigations including physical examination, flexible cystoscopy (FC), and radiological imaging (ultrasound scan (USS) and/or computed tomography urogram (CTU)). Those with a clear history of initial or terminal VH were identified for further scrutiny with regards to detectable upper tracts abnormalities. Results: In total, 57 patients (aged 23–95 years) with initial or terminal VH were identified. Of these, 56 had FC and nine patients were subsequently diagnosed with a LUT malignancy. With regards to upper urinary tract (UUT), 35 patients (61.4%) had an USS, 46 (80.7%) underwent a CTU, and 25 (43.9%) patients had both. In this group, no UUT malignancy was identified on upper tract imaging. Conclusions: Initial or terminal VH patients may not need extensive upper tract imaging. FC is recommended, but a non-invasive USS can be a safe initial investigation for the UUT, with a CTU subsequently considered in those with abnormalities on USS and those with ongoing bleeding. Further combined multicenter analysis will help corroborate these findings and could have several beneficial outcomes including a reduction in investigations cost, patient inconvenience, and ionizing radiation

SPICE: Simulation Package for Including Flavor in Collider Events

We describe SPICE: Simulation Package for Including Flavor in Collider Events. SPICE takes as input two ingredients: a standard flavor-conserving supersymmetric spectrum and a set of flavor-violating slepton mass parameters, both of which are specified at some high "mediation" scale. SPICE then combines these two ingredients to form a flavor-violating model, determines the resulting low-energy spectrum and branching ratios, and outputs HERWIG and SUSY LesHouches files, which may be used to generate collider events. The flavor-conserving model may be any of the standard supersymmetric models, including minimal supergravity, minimal gauge-mediated supersymmetry breaking, and anomaly-mediated supersymmetry breaking supplemented by a universal scalar mass. The flavor-violating contributions may be specified in a number of ways, from specifying charges of fields under horizontal symmetries to completely specifying all flavor-violating parameters. SPICE is fully documented and publicly available, and is intended to be a user-friendly aid in the study of flavor at the Large Hadron Collider and other future colliders.Comment: 31 pages, 3 figures, SPICE can be downloaded from http://hep.ps.uci.edu/~spice; v2: published versio

Biological treatment for psoriasis and the risk of herpes zoster: Results from the Psoriasis Longitudinal Assessment and Registry (PSOLAR).

PURPOSE: To describe the risk of herpes zoster (HZ) in patients with psoriasis and its relation to non-biologic systemic therapies or biologic treatment. MATERIALS AND METHODS: Psoriasis Longitudinal Assessment and Registry (PSOLAR) is an international, prospective, registry that follows adult patients with psoriasis eligible to receive non-biologic systemic therapies or biologic therapies. Mutually exclusive therapy cohorts were defined. HZ incident rates were calculated for each therapy cohort and rates between cohorts were compared using hazard ratios (HR) adjusted for potential confounders, in new users and prevalent-exposure patients. RESULTS: A total of 55 HZ events were identified in 10,469 patients in PSOLAR. The adjusted hazard ratio in the overall study population (new user and prevalent-exposed patients) was 2.22 (95% CI: 0.82-5.97; p = 0.116) for tumor necrosis factor-alpha (TNF) inhibitors, 2.73 (0.98-7.58; p = 0.054) for ustekinumab, and 1.04 (0.20-5.41; p = 0.966) for methotrexate vs. reference (combined phototherapy, systemic steroids, topical therapy, and immunomodulators other than methotrexate). CONCLUSIONS: Exposure to ustekinumab, TNF-alpha inhibitors, and methotrexate was not associated with a statistically significant increased risk of HZ. However, HRs were elevated for ustekinumab and TNF-alpha inhibitors; a larger number of herpes zoster events would be needed to assess the presence or absence of risk

NEK1 variants confer susceptibility to amyotrophic lateral sclerosis

To identify genetic factors contributing to amyotrophic lateral sclerosis (ALS), we conducted whole-exome analyses of 1,022 index familial ALS (FALS) cases and 7,315 controls. In a new screening strategy, we performed gene-burden analyses trained with established ALS genes and identified a significant association between loss-of-function (LOF) NEK1 variants and FALS risk. Independently, autozygosity mapping for an isolated community in the Netherlands identified a NEK1 p.Arg261His variant as a candidate risk factor. Replication analyses of sporadic ALS (SALS) cases and independent control cohorts confirmed significant disease association for both p.Arg261His (10,589 samples analyzed) and NEK1 LOF variants (3,362 samples analyzed). In total, we observed NEK1 risk variants in nearly 3% of ALS cases. NEK1 has been linked to several cellular functions, including cilia formation, DNA-damage response, microtubule stability, neuronal morphology and axonal polarity. Our results provide new and important insights into ALS etiopathogenesis and genetic etiology