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Glaucomatous optic neuropathy treatment options: The promise of novel therapeutics, techniques and tools to help preserve vision
No full textPeripheral vision loss followed by \u27tunnel vision\u27 and eventual irreversible blindness is the fate of patients afflicted by various forms of glaucoma including primary open-angle glaucoma (POAG) and normotensive glaucoma (NTG). These complex and heterogeneous diseases are characterized by extensive death of retinal ganglion cells (RGCs) accompanied by retraction and severance of their axonal connections to the brain and thus damage to and thinning of the optic nerve. Since patients suffering from this glaucomatous optic neuropathy (GON) first notice visual impairment when they have lost \u3e 40% of their RGCs, early diagnosis is the key to retard the progression of glaucoma. Elevated intraocular pressure (IOP), low cerebrospinal and/or low intracranial fluid pressure, advancing age, and ethnicity are major risk factors associated with POAG. However, retinal vascular abnormalities and a high sensitivity of RGCs and optic nerve head components to neurotoxic, inflammatory, oxidative and mechanical insults also contribute to vision loss in POAG/GON. Current treatment modalities for POAG and NTG involve lowering IOP using topical ocular drugs, combination drug products, and surgical interventions. Two recently approved multi-pharmacophoric drugs (e.g., rho kinase inhibitor, Netarsudil; a drug conjugate, Latanoprostene Bunod) and novel aqueous humor drainage devices (iStent and CyPass) are also gaining acceptance for treating POAG/NTG. Neuroprotective and regenerative agents, coupled with electroceutical, mechanical support systems, stem cell transplantation and gene therapy are emerging therapeutics on the horizon to help combat GON. The latter techniques and approaches hope to rejuvenate RGCs and repair the optic nerve structures, thereby providing a gain of function of the visual system for the glaucoma patients
Analysis of hsp27 and the autophagy marker LC3B \u3csup\u3eþ\u3c/sup\u3e puncta following preoperative chemotherapy identifies high-risk osteosarcoma patients
No full textChemotherapy-induced autophagy is a proposed mechanism of chemoresistance and potential therapeutic target in osteosarcoma. We evaluated heat shock protein 27 (HSP27) and autophagy-related proteins as predictors of pathologic treatment response and prognostic markers among osteosarcoma patients who received standard chemotherapy. We analyzed 394 tumor specimens (pre-treatment, post-treatment, and metastases) from 260 osteosarcoma patients by immunohistochemistry for cytoplasmic light chain 3B (LC3B)-positive puncta, sequestosome 1 (SQSTM1), high mobility group box 1 (HMGB1), and HSP27 expression. The staining percentage and intensity for each marker were scored and the extent to which marker expression was correlated with pathologic response, relapse-free survival (RFS), and overall survival (OS) was assessed. LCB3 þ puncta in post-treatment primary tumors (50%) and metastases (67%) was significantly higher than in pre-treatment biopsy specimens (30%; P ¼ 0.023 and \u3c0.001). Among 215 patients with localized osteosarcoma, both pretreatment [multivariate hazard ratio (HR), 26.7; 95% confidence interval (CI), 1.47–484; P ¼ 0.026] and post-treatment HSP27 expression (multivariate HR, 1.85; 95% CI, 1.03–3.33; P ¼ 0.039) were associated with worse OS. Lack of LC3B þ puncta at resection was an independent poor prognostic marker in both univariate (HR, 1.78; 95% CI, 1.05–3.03; P ¼ 0.034) and multivariate models (HR, 1.75; 95% CI, 1.01–3.04; P ¼ 0.045). Patients with LC3B þ / HSP27 tumors at resection had the best 10-year OS (75%) whereas patients with LC3B/HSP27 þ tumors had the worst 10-year survival (25%). Neither HSP27 expression nor the presence of LCB3 þ puncta was correlated with pathologic treatment response. Our findings establish HSP27 expression and LC3B þ puncta as independent prognostic markers in osteosarcoma patients receiving standard chemotherapy and support further investigation into strategies targeting HSP27 or modulating autophagy in osteosarcoma treatment
Kidnapping and the Challenges Confronting The Administration of Criminal Justice in Selected States of Nigeria
Get PDFThis paper examines the challenges confronting the administration of criminal justice in Nigeria with a view to underscore its implication with regards to the prevalence of kidnapping. In order to achieve the objective of the study, qualitative method – in-depth interviews and key informant interviews were utilized in generating data from 60 interviewees. The qualitative data generated from the study was analyzed using a manual content analysis. The study shows that corruption, inadequate court rooms and facilities, poor working condition, frequency in the transfer of police officers, uncooperative attitude of GSM operators, delay emanating from legal practitioners and Director of public prosecution, as well as lack of operating vehicles were some of the major challenges confronting the administration of criminal justice in the prosecution of kidnap cases. Based on the findings, it is recommended that government should stop paying lip service to the fight against corruption but instead take concrete steps to stem the rising tide. Besides a review of the conditions of service of the police, prison and judicial officers, there is the need to provide functional vehicles to the various prison authorities as well as renovating and refurbishing dilapidated buildings and furniture in the various courts
Perspectives on Sexual Abuse of School Children in Basic and Secondary Schools in Ghana
Get PDFObjective: To explore and document the extent of sexual abuse of school children in Ghana and initiate an informed dialogue with all stakeholders for solutions. Method: This is a descriptive and exploratory survey. Information was collected from 49 public schools (490 school children, 116 parents and 49 head-teachers) from 4 out of the 110 districts in the country. Three sets of interview schedules were used to solicit information from school children, parents and head-teachers. In addition four focus group discussion sessions were held separately for school boys, school girls, male adults and female adults in each study area. Furthermore, relevant existing documents were reviewed for background information. Results: There is evidence suggesting the occurrence of sexual abuse in Ghana public schools. About 11.2% of the children who responded had been victims of either rape or defilement which is ‘the natural or unnatural carnal knowledge of any child under sixteen years of age’. The occurrence and severity of abuse are strongly related to gender. 92% of victims were female students. Conclusions: The current system of protecting children from sexual abuse in and outside of schools is ineffective. The study suggests strengthening of the existing protection system with community/school-based child protection teams
Societal Derivations for the Illegal Gun Trafficking In Addis Ababa, Ethiopia
Get PDFCivilians are not allowed to buy or own a gun in Ethiopia. There are national laws, regulations and administrative procedures that allow production, export, import, and retransfer of small arms which are limited to state and federal security purposes; while any other, if any, is explained by the anti-terrorists act. The law requires a record of the acquisition, possession and transfer of each privately held firearm be retained in an official register. Nonetheless, both the anti-terrorist act and other firearm regulations, have not been successfully implemented to prevent illicit trafficking of guns and violent crimes associated with illegal gun possession. Church graveyards and jungles have been the busiest illegal gun exchange belts. This research assesses the societal apprehension to the illicit gun exchange. Residents in the village where illegal gun trafficking takes place have negative impressions to it. The illegal gun exchange create fear in city residents; limit the right of people to movement; and embarrass so many others. Trust in the police for security has diminished because, residents understood policemen themselves, as part of the illicit trafficking. The midnight time when people are most likely asleep is the peak time for gun trafficking and fire-testing. This compels citizens to prognosticate the impending terrorism
Recovery of the starting times of delayed signals
No full textWe present a new method to locate the starting points in time of an arbitrary number of (damped) delayed signals. For a finite data sequence, the method permits to first locate the starting point of the component with the longest delay, and then - by iteration - all the preceding ones. Numerical examples are given and noise sensitivity is tested
Optimal Service Rate in Cognitive Radio Networks with Different Queue Length Information
No full textCognitive radio (CR) technology effectively overcomes spectrum inefficiency by providing the capability that unlicensed users can share the radio frequency spectrum with licensed users. In this paper, we consider a CR system with heterogeneous users. A single primary user (PU) randomly generates service requests and a licensed band processes these requests. This PU band also can be flexibly accessed by secondary users (SUs) if available. The CR system is regarded as a preemptive priority queueing system. Under different information levels, we investigate the equilibrium strategic behaviors of PU and SUs. Based on users\u27 strategies, we study SU\u27s sojourn time (i.e., the period beginning from the time an SU request enters the system and ending from the time the SU request is completed), and obtain the analytical solutions of SU\u27s mean sojourn time. By theoretical and numerical analysis, the SU\u27s mean sojourn time is found not decreasing with the service rate of PU. This phenomenon is counterintuitive, and it implies the increase of the service rate of PU does not necessarily reduce the mean sojourn time of SU. In this sense, we investigate and find optimal service rates of PU in different information levels to meet the PU\u27s QoS requirement and simultaneously to maximize SU\u27s throughput from the viewpoint of the service providers
Hypoxia-targeted gold nanorods for cancer photothermal therapy
Get PDFTumor hypoxia is a well-recognized driver of resistance to traditional cancer therapies such as chemotherapy and radiation therapy. We describe development of a new nanoconstruct composed of gold nanorods (GNRs) conjugated to carbonic anhydrase IX (CAIX) antibody that specifically binds to CAIX, a biomarker of hypoxia, to facilitate targeting tumor hypoxic areas for focused photothermal ablation. Physicochemical characterization studies confirmed the size, shape, monodispersity, surface charge, and serum stability of the GNRs. Enzyme-linked immunosorbent assays and cellular binding and uptake studies confirmed successful conjugation of antibody to the GNRs and specificity for CAIX. Near-infrared irradiation of CAIX-overexpressing cells treated with GNR/anti-CAIX resulted in significantly higher cell death than cells treated with control GNRs. In vivo biodistribution studies using hyperspectral imaging and inductively coupled plasma mass spectrometry confirmed intravenous administration results not only in greater accumulation of GNR/anti-CAIX in tumors than control GNRs but also greater penetration into hypoxic areas of tumors. Nearinfrared ablation of these tumors showed no tumor regression in the sham-treated group, regression but recurrence in the non-targeted-GNR group, and complete tumor regression in the targeted-GNR group. GNR/anti-CAIX nanoconstructs show promise as hypoxia targeting and photothermal ablation agents for cancer treatment
Analysis of emission effects related to drivers’ compliance rates for cooperative vehicle-infrastructure system at signalized intersections
Get PDFUnknown remaining time of signal phase at a signalized intersection generally results in extra accelerations and decelerations that increase variations of operating conditions and thus emissions. A cooperative vehicle-infrastructure system can reduce unnecessary speed changes by establishing communications between vehicles and the signal infrastructure. However, the environmental benefits largely depend on drivers’ compliance behaviors. To quantify the effects of drivers’ compliance rates on emissions, this study applied VISSIM 5.20 (Planung Transport Verkehr AG, Karlsruhe, Germany) to develop a simulation model for a signalized intersection, in which light duty vehicles were equipped with a cooperative vehicle-infrastructure system. A vehicle-specific power (VSP)-based model was used to estimate emissions. Based on simulation data, the effects of different compliance rates on VSP distributions, emission factors, and total emissions were analyzed. The results show the higher compliance rate decreases the proportion of VSP bin = 0, which means that the frequencies of braking and idling were lower and light duty vehicles ran more smoothly at the intersection if more light duty vehicles complied with the cooperative vehicle-infrastructure system, and emission factors for light duty vehicles decreased significantly as the compliance rate increased. The case study shows higher total emission reductions were observed with higher compliance rate for all of CO2, NOx, HC, and CO emissions. CO2 was reduced most significantly, decreased by 16% and 22% with compliance rates of 0.3 and 0.7, respectively
Nanoparticles in daily life: Applications, toxicity and regulations
No full textAt nanoscale, man-made materials may show unique properties that differ from bulk and dissolved counterparts. The unique properties of engineered nanomaterials not only impart critical advantages but also confer toxicity because of their unwanted interactions with different biological compartments and cellular processes. In this review, we discuss various entry routes of nanomaterials in the human body, their applications in daily life, and the mechanisms underlying their toxicity. We further explore the passage of nanomaterials into air, water, and soil ecosystems, resulting in diverse environmental impacts. Briefly, we probe the available strategies for risk assessment and risk management to assist in reducing the occupational risks of potentially hazardous engineered nanomaterials including the control banding (CB) approach. Moreover, we substantiate the need for uniform guidelines for systematic analysis of nanomaterial toxicity, in silico toxicological investigations, and obligation to ensure the safe disposal of nanowaste to reduce or eliminate untoward environmental and health impacts. At the end, we scrutinize global regulatory trends, hurdles, and efforts to develop better regulatory sciences in the field of nanomedicines