Miracle-dz/UniFAR-FTUs huggingface dataset:
The Future of Information Science E ducatio n in Canada: Issues and D iscussion

This poster visually presents issues in the future of information science education in Canada. Theposter incorporates research completed for development of the new Bachelor of Information Technology–Information Resource Management program at Carleton University, launched in Fall 2016. http://bitdegree.ca/ In conclusion, key strategies for the future will be identified.
Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results.

PURPOSE Docetaxel and capecitabine, a tumor-activated oral fluoropyrimidine, show high single-agent efficacy in metastatic breast cancer (MBC) and synergy in preclinical studies. This international phase III trial compared efficacy and tolerability of capecitabine/docetaxel therapy with single-agent docetaxel in anthracycline-pretreated patients with MBC. PATIENTS AND METHODS Patients were randomized to 21-day cycles of oral capecitabine 1,250 mg/m(2) twice daily on days 1 to 14 plus docetaxel 75 mg/m(2) on day 1 (n = 255) or to docetaxel 100 mg/m(2) on day 1 (n = 256). RESULTS Capecitabine/docetaxel resulted in significantly superior efficacy in time to disease progression (TTP) (hazard ratio, 0.652; 95% confidence interval [CI], 0.545 to 0.780; P =.0001; median, 6.1 v 4.2 months), overall survival (hazard ratio, 0.775; 95% CI, 0.634 to 0.947; P =.0126; median, 14.5 v 11.5 months), and objective tumor response rate (42% v 30%, P =.006) compared with docetaxel. Gastrointestinal side effects and hand-foot syndrome were more common with combination therapy, whereas myalgia, arthralgia, and neutropenic fever/sepsis were more common with single-agent docetaxel. More grade 3 adverse events occurred with combination therapy (71% v 49%, respectively), whereas grade 4 events were slightly more common with docetaxel (31% v 25% with combination). CONCLUSION The significantly superior TTP and survival achieved with the addition of capecitabine to docetaxel 75 mg/m(2), with the manageable toxicity profile, indicate that this combination provides clear benefits over single-agent docetaxel 100 mg/m(2). Docetaxel/capecitabine therapy is an important treatment option for women with anthracycline-pretreated MBC.
A Non-Mouse-Adapted Enterovirus 71 (EV71) Strain Exhibits Neurotropism, Causing Neurological Manifestations in a Novel Mouse Model of EV71 Infection

ABSTRACT Enterovirus 71 (EV71) is a neurotropic pathogen that has been consistently associated with the severe neurological forms of hand, foot, and mouth disease. The lack of a relevant animal model has hampered our understanding of EV71 pathogenesis, in particular the route and mode of viral dissemination. It has also hindered the development of effective prophylactic and therapeutic approaches, making EV71 one of the most pressing public health concerns in Southeast Asia. Here we report a novel mouse model of EV71 infection. We demonstrate that 2-week-old and younger immunodeficient AG129 mice, which lack type I and II interferon receptors, are susceptible to infection with a non-mouse-adapted EV71 strain via both the intraperitoneal (i.p.) and oral routes of inoculation. The infected mice displayed progressive limb paralysis prior to death. The dissemination of the virus was dependent on the route of inoculation but eventually resulted in virus accumulation in the central nervous systems of both animal groups, indicating a clear neurotropism of the virus. Histopathological examination revealed massive damage in the limb muscles, brainstem, and anterior horn areas. However, the minute amount of infectious viral particles in the limbs from orally infected animals argues against a direct viral cytopathic effect in this tissue and suggests that limb paralysis is a consequence of EV71 neuroinvasion. Together, our observations support that young AG129 mice display polio-like neuropathogenesis upon infection with a non-mouse-adapted EV71 strain, making this mouse model relevant for EV71 pathogenesis studies and an attractive platform for EV71 vaccine and drug testing.
Virulence control in group A Streptococcus by a two-component gene regulatory system: Global expression profiling and in vivo infection modeling

Two-component gene regulatory systems composed of a membrane-bound sensor and cytoplasmic response regulator are important mechanisms used by bacteria to sense and respond to environmental stimuli. Group A Streptococcus, the causative agent of mild infections and life-threatening invasive diseases, produces many virulence factors that promote survival in humans. A two-component regulatory system, designated covRS (cov, control of virulence; csrRS), negatively controls expression of five proven or putative virulence factors (capsule, cysteine protease, streptokinase, streptolysin S, and streptodornase). Inactivation of covRS results in enhanced virulence in mouse models of invasive disease. Using DNA microarrays and quantitative RT-PCR, we found that CovR influences transcription of 15% (n = 271) of all chromosomal genes, including many that encode surface and secreted proteins mediating host–pathogen interactions. CovR also plays a central role in gene regulatory networks by influencing expression of genes encoding transcriptional regulators, including other two-component systems. Differential transcription of genes influenced by covR also was identified in mouse soft-tissue infection. This analysis provides a genome-scale overview of a virulence gene network in an important human pathogen and adds insight into the molecular mechanisms used by group A Streptococcus to interact with the host, promote survival, and cause disease.
Efferent desensitization of auditory nerve fibre responses in the cochlea of the turtle Pseudemys scripta elegans.

Extracellular recordings were made from single auditory afferents in the isolated half‐head of the turtle, and changes in their acoustic sensitivity were examined following electrical stimulation of the efferent fibres to the basilar papilla. Short trains of efferent shocks caused a prolonged elevation of the pure tone thresholds of the auditory afferents and an abolition of their spontaneous activity. These changes could be demonstrated in a majority of recordings and without antidromic firing of the afferent. The amount of desensitization increased steeply with shock number and a train of ten closely spaced shocks could elevate the threshold at the most sensitive or characteristic frequency by four orders of magnitude. Desensitization also occurred with single efferent shocks at repetition frequencies exceeding 25/s. Discharge rate versus sound pressure functions were constructed for a number of afferents. The maximum slope of the functions, and the saturated firing rates were both reduced by efferent stimulation; there was also an over‐all shift of the rate‐intensity function to higher stimulus levels. Such effects would enable the afferent to signal a wider range of sound pressures. Efferent stimulation caused a broadening of the afferent frequency‐threshold curves by removal of the narrowly‐tuned region around the characteristic frequency. We suggest that the loss in tuning and concomitant improvement in temporal resolution may be a functionally important consequence of efferent action.
Labor Room Setting Compared With the Operating Room for Simulated Perimortem Cesarean Delivery: A Randomized Controlled Trial

OBJECTIVE: To compare the labor room and operating room for perimortem cesarean delivery during simulated maternal arrests occurring outside the operating room. We hypothesized transport to the operating room for perimortem cesarean delivery would delay incision and other important resuscitation milestones. METHODS: We randomized 15 teams composed of obstetricians, nurses, anesthesiologists, and neonatal staff to perform perimortem cesarean delivery in the labor room or operating room. A manikin with an abdominal model overlay was used for simulated cesarean delivery. The scenario began in the labor room with maternal cardiopulmonary arrest and fetal bradycardia. The primary outcome was time to incision. Secondary outcomes included times to important milestones, percentage of tasks completed, and type of incision. RESULTS: The median (interquartile range) times from time zero to incision were 4:25 (3:59–4:50) and 7:53 (7:18–8:57) minutes in the labor room and operating room groups, respectively (P=.004). Fifty-seven percent of labor room teams and 14% of operating room teams achieved delivery within 5 minutes. Contacting the neonatal team, placing the defibrillator, resuming compressions after analysis, and endotracheal intubation all occurred more rapidly in the labor room group. CONCLUSION: Perimortem cesarean delivery performed in the labor room was significantly faster than perimortem cesarean delivery performed after moving to the operating room. Delivery within 5 minutes was challenging in either location despite optimal study conditions (eg, the manikin was light and easily moved; teams knew the scenario mandated perimortem cesarean delivery and were aware of being timed). Our findings imply that perimortem cesarean delivery during actual arrest would require more than 5 minutes and should be performed in the labor room rather than relocating to the operating room. LEVEL OF EVIDENCE: I
Methodology for GPS Synchronization Evaluation with High Accuracy

Clock synchronization in the order of nanoseconds is one of the critical factors for time-based localization. Currently used time synchronization methods are developed for the more relaxed needs of network operation. Their usability for positioning should be carefully evaluated. In this paper, we are particularly interested in GPS-based time synchronization. To judge its usability for localization we need a method that can evaluate the achieved time synchronization with nanosecond accuracy. Our method to evaluate the synchronization accuracy is inspired by signal processing algorithms and relies on fine-grain time information. The method is able to calculate the clock offset and skew between devices with nanosecond accuracy in real time. It was implemented using software defined radio technology. We demonstrate that GPS-based synchronization suffers from remaining clock offset in the range of a few hundred of nanoseconds but the clock skew is negligible. Finally, we determine a corresponding lower bound on the expected positioning error.
The ShiA protein encoded by the Shigella flexneri SHI‐2 pathogenicity island attenuates inflammation

Shigella spp. are the aetiologic agents of dysentery, a severe diarrhoeal syndrome characterized by acute inflammation in the colon. The inflammatory response, which includes recruitment of polymorphonuclear leukocytes (PMN), damages the colonic mucosa and exacerbates the infection. Shigella encodes a pathogenicity island (PAI), SHI‐2, which is localized in a region of the chromosome linked to the induction of inflammation. Surprisingly, SHI‐2 deletion mutants induce a stronger inflammatory response than wild‐type Shigella as measured by increased villus blunting, increased PMN infiltration and induction of apoptosis in a rabbit ileal loop model of shigellosis. Mutational analysis mapped the hyper‐inflammatory phenotype to a single gene, shiA. Similar to SHI‐2 deletion mutants, infection with a shiA mutant strain induces dramatically elevated levels of inflammation when compared to the wild‐type strain. Furthermore, infection with a wild‐type strain containing multiple copies of shiA results in fewer infiltrating PMN and apoptotic cells, as well as preservation of a normal villus architecture at the site of infection, thus acting in a dominant fashion over the pro‐inflammatory mechanisms of Shigella. The molecular mechanism of action of ShiA is independent of any in vitro phenotype associated with Shigella virulence. Our data suggest that ShiA allows Shigella to attenuate the host inflammatory response in a novel manner.
Exendin‐4, a Glucagon‐Like Peptide‐1 Receptor Agonist, Prevents Osteopenia by Promoting Bone Formation and Suppressing Bone Resorption in Aged Ovariectomized Rats

Osteoporosis mainly affects postmenopausal women and older men. Gastrointestinal hormones released after meal ingestion, such as glucose‐dependent insulinotropic peptide (GIP) and glucagon‐like peptide (GLP)‐2, have been shown to regulate bone turnover. However, whether GLP‐1, another important gastrointestinal hormone, and its analogues also have antiosteoporotic effects, especially in aged postmenopausal situation, has not been confirmed. In the present study, we evaluated the effects of the GLP‐1 receptor agonist exendin‐4 on ovariectomy (OVX)‐induced osteoporosis in old rats. Twelve‐month‐old female Sprague‐Dawley rats were subjected to OVX, and exendin‐4 was administrated 4 weeks after the surgery and lasted for 16 weeks. Bone characters and related serum and gene biomarkers were analyzed. Sixteen weeks of treatment with exendin‐4 slowed down body weight gain by decreasing fat mass and prevented the loss of bone mass in old OVX rats. Exendin‐4 also enhanced bone strength and prevented the deterioration of trabecular microarchitecture. Moreover, exendin‐4 decreased the urinary deoxypyridinoline (DPD)/creatinine ratio and serum C‐terminal cross‐linked telopeptides of type I collagen (CTX‐I) and increased serum alkaline phosphatase (ALP), osteocalcin (OC), and N‐terminal propeptide of type 1 procollagen (P1NP) levels, key biochemical markers of bone turnover. Interestingly, gene expression results further showed that exendin‐4 not only inhibited bone resorption by increasing the osteoprotegerin (OPG)/receptor activator of NF‐κB ligand (RANKL) ratio, but also promoted bone formation by increasing the expression of OC, Col1, Runx2, and ALP, which exhibited dual regulatory effects on bone turnover as compared with previous antiosteoporotic agents. In conclusion, these findings demonstrated for the first time the antiosteoporotic effects of exendin‐4 in old OVX rats and that it might be a potential candidate for treatment of aged postmenopausal osteoporosis.
Comparison of gefitinib versus erlotinib in patients with nonsmall cell lung cancer who failed previous chemotherapy

Gefitinib and erlotinib are commonly used for salvage therapy in patients with nonsmall cell lung cancer (NSCLC) who have progressed on prior therapies. Although both agents have similar structure and have demonstrated efficacy in NSCLC, gefitinib and erlotinib have not been directly compared in terms of efficacy and other clinical outcomes in patients with NSCLC who have failed prior chemotherapy. This prompted us to analyze the clinical outcomes between gefitinib‐treated and erlotinib‐treated patients with metastatic or recurrent NSCLC.
The role of cost-effectiveness analysis in health and medicine. Panel on Cost-Effectiveness in Health and Medicine.

OBJECTIVE To develop consensus-based recommendations guiding the conduct of cost-effectiveness analysis (CEA) to improve the comparability and quality of studies. The recommendations apply to analyses intended to inform the allocation of health care resources across a broad range of conditions and interventions. This article, first in a 3-part series, discusses how this goal affects the conduct and use of analyses. The remaining articles will outline methodological and reporting recommendations, respectively. PARTICIPANTS The Panel on Cost-Effectiveness in Health and Medicine, a nonfederal panel with expertise in CEA, clinical medicine, ethics, and health outcomes measurement, was convened by the US Public Health Service (PHS). EVIDENCE The panel reviewed the theoretical foundations of CEA, current practices, and alternative procedures for measuring and assigning values to resource use and health outcomes. CONSENSUS PROCESS The panel met 11 times during 2 1/2 years with PHS staff and methodologists from federal agencies. Working groups brought issues and preliminary recommendations to the full panel for discussion. Draft recommendations were circulated to outside experts and the federal agencies prior to finalization. CONCLUSIONS The panel's recommendations define a "reference case" cost-effectiveness analysis, a standard set of methods to serve as a point of comparison across studies. The reference case analysis is conducted from the societal perspective and accounts for benefits, harms, and costs to all parties. Although CEA does not reflect every element of importance in health care decisions, the information it provides is critical to informing decisions about the allocation of health care resources.
Essential Role of PDL1 Expression on Nonhematopoietic Donor Cells in Acquired Tolerance to Vascularized Cardiac Allografts

The PD1:PDL1 pathway is an essential negative costimulatory pathway that plays a key role in regulating the alloimune response. PDL1 is expressed not only on antigen‐presenting cells (APCs) but also cardiac endothelium. In this study, we investigated the importance of PDL1 expression on donor cardiac allograft in acquired transplantation tolerance in a fully MHC‐mismatched model. We generated PDL1 chimeric mice on B6 background that expressed PDL1 on either hematopoietic cells or nonhematopoietic cells of the heart. Sham animals were used as controls. These hearts were then transplanted into BALB/c recipients and treated with CTLA4‐Ig to induce tolerance. Cardiac endothelium showed significant expression of PDL1, which was upregulated upon transplantation. While the absence of PDL1 on hematopoietic cells of the heart resulted in delayed rejection and prevented long‐term tolerance in most but not all recipients, we observed an accelerated and early graft rejection of all donor allografts that lacked PDL1 on the endothelium. Moreover, PDL1‐deficient endothelium hearts had significant higher frequency of IFN‐γ‐producing alloreactive cells as well as higher frequency of CD8+ effector T cells. These findings demonstrate that PDL1 expression mainly on donor endothelium is functionally important in a fully allogeneic mismatched model for the induction of cardiac allograft tolerance.
The immunogenicity of soluble haptenated polymers is determined by molecular mass and hapten valence.

T cell-independent Ag are believed to stimulate antibody formation in the relative absence of Ag processing and T cell help. Previous studies on the type 2 T cell independent (TI-2) Ag DNP-polyacrylamide, have shown that when one systematically varies the molecular mass and hapten valence, the immunogenic potential of this type of molecule depends on definable molecular characteristics. It was found that to be immunogenic, these molecules had to exceed a threshold molecular mass of 100,000 Da and a threshold hapten valence of 20. The present study was undertaken to determine whether such findings could be generalized to other molecules belonging to the TI-2 class of Ag. The molecular characteristics of five chemically different fluoresceinated (FL)-polymers were systematically varied, and their ability to stimulate an IgM antihapten immune response was measured. The polymers used as carriers were carefully size-fractionated and consisted of one natural polymer (dextran), one modified natural polymer (carboxymethyl cellulose), and three synthetic polymers (Ficoll, polyvinyl alcohol, and polyacrylamide). The carriers varied in physical structure from the highly cross-linked Ficoll, to the somewhat branched dextran, to the linear polyacrylamide, carboxymethyl cellulose, and polyvinyl alcohol. Polymers were haptenated with FL and size-fractionated so as to yield a panel of molecules with varying molecular mass, hapten valence, and hapten density. Anti-FL IgM response to these haptenated polymers was measured in vivo after i.p. injection of the FL-polymer in saline, and measured in vitro after culture with unfractionated spleen cells from naive mice. In agreement with the previous studies on DNP-polyacrylamide, it was found that to be immunogenic, each of the FL-polymers had to exceed a comparable threshold value of molecular mass and of hapten valence. Optimal immunogenicity occurred when the FL-polymers had values of mass and hapten density lying within a predictable range. Immunogenicity decreased when these optimal parameters were substantially increased or decreased. We conclude that the immunogenicity of soluble haptenated polymers depends on predictable physical molecular characteristics, and is relatively independent of the chemical composition and conformation of the carrier polymer.
Clinical progression of moderate-to-severe Alzheimer's disease and caregiver burden: a 12-month multicenter prospective observational study

ABSTRACT Background: Prospective studies on the clinical progression of Alzheimer's disease (AD) and its relationship to caregiver burden are needed to improve illness management and use of resources. Methods: This national, multicenter, observational study evaluated 1235 moderate to severe AD patients under routine care in Spain. Baseline cross-sectional sociodemographic and clinical data, and changes from baseline to month 12 of various neuropsychological tests and clinical ratings, including Blessed Dementia Scale, Mini-mental State Examination (MMSE), Hughes Clinical Dementia Rating sum-of-boxes (CDR-SB), Clinical Global Impression of Change (CGIC) and Zarit Caregiver Burden scales, were recorded and comprehensively analyzed. Results: Baseline data were in accordance with characteristics consistently reported to influence AD risk regarding anthropometrics, sociocultural features and comorbidities. Significant progressive functional impairments (i.e. in routine activities and essential daily tasks) and cognitive (i.e. MMSE and CDR-SB) impairments were found at month 12. However, patients' behavior and caregivers' burden improved slightly, but significantly, corroborating the major influence of behavioral symptoms on caregivers' distress. Caregivers showed significantly lower burden with patients with higher levels of education and, to a lesser extent, when patients received AD-specific medication. Physicians accurately detected AD clinical evolution as their CGIC ratings significantly correlated with all tests. Conclusions: These findings reinforce previous AD knowledge and add data on the clinical course of advanced stages of AD. Caregiver burden depended more on patients' behavioral alterations than on their functional or cognitive declines; and it was diminished by their patients having higher levels of education and being treated with AD-specific medications. Research into unexplored factors that might reduce caregiver burden, ultimately benefiting both patients and caregivers, is encouraged.