In this essay, I analyse two episodes from the recent television series, Philip K. Dick’s Electric Dreams. I contend that, by adapting Philip K. Dick’s short stories from the 1950s for the screen, ...the creators of “Impossible Planet” and “The Commuter” offer an important new perspective from which to appreciate the value of his early fiction, which is too often dismissed by critics as juvenilia. Moreover, by re-visioning Dick’s work as posthuman Gothic narratives, the episodes refract long-standing Gothic anxieties about alterity and (post)human existence through a lens that is more often associated with science fiction. This hybridization is instrumental to Philip K. Dick’s Electric Dreams’ interrogation of the paradigmatic binaries between life/death, interiority/exteriority and reality/virtuality. In my analysis, I use Rosi Braidotti’s theory of posthuman death, as well as Roger Luckhurst’s concept of Weird zones, to illuminate how Electric Dreams explores some of the existential issues that arise from human-technological imbrication.
Purpose To summarize the epidemiology of pathologic myopia and myopic choroidal neovascularization (CNV) and their impact on vision. Design Systematic literature review of all English-language ...studies evaluating the epidemiology and visual burden of pathologic myopia or myopic CNV. Methods PubMed and EMBASE were searched with no time limits using predefined search strings for English-language studies evaluating the epidemiology and visual burden of pathologic myopia and myopic CNV. Results In total, 39 relevant publications were identified. Population-based studies reported pathologic myopia to be the first to third most frequent cause of blindness. The prevalence of pathologic myopia was reported to be 0.9%-3.1%, and the prevalence of visual impairment attributable to pathologic myopia ranged from 0.1%-0.5% (European studies) and from 0.2%-1.4% (Asian studies). The prevalence of CNV in individuals with pathologic myopia was reported to be 5.2%-11.3%, and was bilateral in approximately 15% of patients. All studies of visual outcome in patients with myopic CNV (duration ranging from less than 3 months to 21.5 years) reported deterioration in best-corrected visual acuity over time. Older age, subfoveal CNV location, and larger baseline lesion size were predictors of worse visual outcomes. Conclusions Pathologic myopia is an important cause of vision loss worldwide, affecting up to 3% of the population. Of these, a substantial proportion of patients develop myopic CNV, which mostly causes a significant progressive decrease in visual acuity. This condition should therefore be a target for new treatment strategies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Summary Diabetic retinopathy is a common and specific microvascular complication of diabetes, and remains the leading cause of preventable blindness in working-aged people. It is identified in a ...third of people with diabetes and associated with increased risk of life-threatening systemic vascular complications, including stroke, coronary heart disease, and heart failure. Optimum control of blood glucose, blood pressure, and possibly blood lipids remains the foundation for reduction of risk of retinopathy development and progression. Timely laser therapy is effective for preservation of sight in proliferative retinopathy and macular oedema, but its ability to reverse visual loss is poor. Vitrectomy surgery might occasionally be needed for advanced retinopathy. New therapies, such as intraocular injection of steroids and antivascular endothelial growth-factor agents, are less destructive to the retina than are older therapies, and could be useful in patients who respond poorly to conventional therapy. The outlook for future treatment modalities, such as inhibition of other angiogenic factors, regenerative therapy, and topical therapy, is promising.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
ABSTRACT
Background:
The revised ESPGHAN/NASPGHAN 2016 guideline on the diagnosis and management of Helicobacter pylori (H pylori) infection discourages a “test and treat” strategy. Instead, upper ...endoscopy (EGD) is recommended when a valid clinical indication is present. Likewise, new treatment recommendations for first‐line therapies strongly encourage obtaining antimicrobial susceptibility before treatment. We conducted this study to assess the effect of revised guidelines on clinical practice at our center.
Methods:
Retrospective chart review of patients with H pylori infection diagnosis either by serology, stool antigen test, urea breath test, or EGD at Boston Children's Hospital between January 2013 and July 2019. We compared demographic and clinical data between initial guideline and 2016 revision (January 2013 to November 2016) and period after revised guideline (December 2016 to July 2019).
Results:
Two hundred and fifty‐six patients were included. EGD was the initial diagnostic test in 49% (50/103, prerevised guideline) and in 52% (79/153, postrevised guideline). Biopsy culture was sent in 3% of patients for both periods (3/103 and 4/153, respectively). PPI‐clarithromycin‐amoxicillin triple therapy was the most common regimen in both periods. Clarithromycin use was lower in postrevised guideline period (P = 0.003) whereas the opposite was noted for metronidazole and tetracycline (P = 0.009 and P = 0.02, respectively). There was no significant difference in eradication rate between periods (86% vs 81%).
Conclusions:
Low adherence to the updated H pylori guideline recommendations was observed among pediatric gastroenterologists at our center with low use of gastric biopsy culture. The guideline revision was associated with avoidance of clarithromycin use as a second‐line therapy, but no change in eradication rates. Future interventions should address the importance of obtaining gastric biopsy culture for antibiotic susceptibilities to guide therapy.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Recently, nanometer sized vesicles (termed exosomes) have been described as a component of urine. Such vesicles may be a useful non-invasive source of markers in renal disease. Their utility as a ...source of markers in urological cancer remains unstudied. Our aim in this study was to investigate the feasibility and value of analysing urinary exosomes in prostate cancer patients undergoing standard therapy.
Ten patients (with locally advanced PCa) provided spot urine specimens at three time points during standard therapy. Patients received 3-6 months neoadjuvant androgen deprivation therapy prior to radical radiotherapy, comprising a single phase delivering 55 Gy in 20 fractions to the prostate and 44 Gy in 20 fractions to the pelvic nodes. Patients were continued on adjuvant ADT according to clinical need. Exosomes were purified, and the phenotype compared to exosomes isolated from the prostate cancer cell line LNcaP. A control group of 10 healthy donors was included. Serum PSA was used as a surrogate treatment response marker. Exosomes present in urine were quantified, and expression of prostate markers (PSA and PSMA) and tumour-associated marker 5T4 was examined.
The quantity and quality of exosomes present in urine was highly variable, even though we handled all materials freshly and used methods optimized for obtaining highly pure exosomes. There was approx 2-fold decrease in urinary exosome content following 12 weeks ADT, but this was not sustained during radiotherapy. Nevertheless, PSA and PSMA were present in 20 of 24 PCa specimens, and not detected in healthy donor specimens. There was a clear treatment-related decrease in exosomal prostate markers in 1 (of 8) patient.
Evaluating urinary-exosomes remains difficult, given the variability of exosomes in urine specimens. Nevertheless, this approach holds promise as a non-invasive source of multiple markers of malignancy that could provide clinically useful information.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Landmark Cases in the Law of Tort contains thirteen original essays on leading tort cases, ranging from the early nineteenth century to the present day. It is the third volume in a series of ...collected essays on landmark cases (the previous two volumes having dealt with restitution and contract). The cases examined raise a broad range of important issues across the law of tort, including such diverse areas as acts of state and public nuisance, as well as central questions relating to the tort of negligence. Several of the essays place cases in their historical context in ways that change our understanding of the case's significance. Sometimes the focus is on drawing out previously neglected aspects of cases which have been – undeservedly – assigned minor importance. Other essays explore the judicial methodologies and techniques that worked to shape leading principles of tort law.
Osimertinib, a third-generation EGFR tyrosine kinase inhibitor has demonstrated efficacy in tumors harboring the EGFR T790M resistance mutation. Inevitably, resistance to third-generation inhibitors ...results in disease progression, with the EGFR C797S mutation being one of several resistance pathways identified to date. On the basis of preclinical data, we report what is the first known case of a patient harboring the T790M and C797S mutations in trans treated with combination gefitinib and osimertinib.
On development of progressive disease after multiple therapies, the patient’s plasma was sequenced using the Oncomine Lung cfDNA Assay (Thermo Fisher Scientific, Waltham, MA). Subsequent monitoring of circulating tumor DNA in plasma was performed by droplet digital polymerase chain reaction.
Sequencing showed that the T790M and C797S mutations were in trans. Within 2 weeks of commencement of combination therapy, rapid clinical improvement occurred. Accompanying this, a rapid decline in the C797S mutation subclone in plasma was detected. However, the levels of the EGFR exon 19 deletion driver mutation and the T790M resistance mutation in the circulating tumor DNA continued to rise and the patient died from progressive disease 6 weeks after commencement of combination therapy. There were no adverse events seen with the combination therapy.
This is, to the best of our knowledge, the first reported case of combination EGFR tyrosine kinase inhibitor therapy tailored to the allelic conformation of T790M and C797S mutation that resulted in brief clinical improvement without toxicity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This article investigates the application of underwater acoustic sensor networks (UASNs) for large scale monitoring of the ocean environment. The low propagation speed of acoustic waves presents a ...fundamental challenge for medium access control (MAC)-coordinating the access of multiple nodes to the shared acoustic communication medium. In this article, we propose sequential dual-hop transmit delay allocation MAC (SDH-TDA-MAC)-a centralized MAC and routing protocol that facilitates efficient dual-hop scheduling in UASNs without the need for clock synchronization among the sensor nodes. BELLHOP-based simulations of a 100 node network reveal that SDH-TDA-MAC can achieve full network connectivity with 16-dB lower transmit power, compared with the single-hop TDA-MAC protocol. This provides considerable energy savings, while still providing network goodput in excess of 50% of the channel capacity. We also present a method of incorporating routing redundancy into the SDH-TDA-MAC protocol that achieves a good tradeoff between the network throughput and reliability. For example, in a channel with 10% probability of link outage, incorporating double routing redundancy into SDH-TDA-MAC increases the packet delivery ratio from 81% to 95%, a significant improvement in network reliability, while still achieving the network goodput of 22% of the channel capacity, considerably higher than typical MAC protocols designed for UASNs. In summary, the high network goodput, low transmit power compared with the single-hop approach, no requirement for clock synchronization, and robust packet delivery via route diversity make SDH-TDA-MAC an efficient, reliable, and practical approach to data gathering in UASNs.
Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) that leads to progressive and irreversible loss of visual function. Geographic atrophy is defined by the presence ...of sharply demarcated atrophic lesions of the outer retina, resulting from loss of photoreceptors, retinal pigment epithelium (RPE), and underlying choriocapillaris. These lesions typically appear first in the perifoveal macula, initially sparing the foveal center, and over time often expand and coalesce to include the fovea. Although the kinetics of GA progression are highly variable among individual patients, a growing body of evidence suggests that specific characteristics may be important in predicting disease progression and outcomes. This review synthesizes current understanding of GA progression in AMD and the factors known or postulated to be relevant to GA lesion enlargement, including both affected and fellow eye characteristics. In addition, the roles of genetic, environmental, and demographic factors in GA lesion enlargement are discussed. Overall, GA progression rates reported in the literature for total study populations range from 0.53 to 2.6 mm2/year (median, ∼1.78 mm2/year), assessed primarily by color fundus photography or fundus autofluorescence (FAF) imaging. Several factors that could inform an individual's disease prognosis have been replicated in multiple cohorts: baseline lesion size, lesion location, multifocality, FAF patterns, and fellow eye status. Because best-corrected visual acuity does not correspond directly to GA lesion enlargement due to possible foveal sparing, alternative assessments are being explored to capture the relationship between anatomic progression and visual function decline, including microperimetry, low-luminance visual acuity, reading speed assessments, and patient-reported outcomes. Understanding GA progression and its individual variability is critical in the design of clinical studies, in the interpretation and application of clinical trial results, and for counseling patients on how disease progression may affect their individual prognosis.
The discovery of nearly 180-year-old cranial measurements in the archives of 19th century American physician and naturalist Samuel George Morton can address a lingering debate, begun in the late 20th ...century by paleontologist and historian of science Stephen Jay Gould, about the unconscious bias alleged in Morton's comparative data of brain size in human racial groups. Analysis of Morton's lost data and the records of his studies does not support Gould's arguments about Morton's biased data collection. However, historical contextualization of Morton with his scientific peers, especially German anatomist Friedrich Tiedemann, suggests that, while Morton's data may have been unbiased, his cranial race science was not. Tiedemann and Morton independently produced similar data about human brain size in different racial groups but analyzed and interpreted their nearly equivalent results in dramatically different ways: Tiedemann using them to argue for equality and the abolition of slavery, and Morton using them to entrench racial divisions and hierarchy. These differences draw attention to the epistemic limitations of data and the pervasive role of bias within the broader historical, social, and cultural context of science.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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