Against Motivational Efficacy of Beliefs

Bromwich (2010) argues that a belief is motivationally efficacious in that, other things being equal, it disposes an agent to answer a question in accordance with that belief. I reply that what we are disposed to do is largely determined by our genes, whereas what we believe is largely determined by stimuli from the environment. We have a standing and default disposition to answer questions honestly, ceteris paribus, even before we are exposed to environmental stimuli. Since this standing and default disposition is innate, and our beliefs have their source in environmental stimuli, our beliefs cannot be the source of the disposition. Moreover, a recent finding in neuroscience suggests that motivation is extrinsic to belief

KCRS: A Blockchain-Based Key Compromise Resilient Signature System

Digital signatures are widely used to assure authenticity and integrity of messages (including blockchain transactions). This assurance is based on assumption that the private signing key is kept secret, which may be exposed or compromised without being detected in the real world. Many schemes have been proposed to mitigate this problem, but most schemes are not compatible with widely used digital signature standards and do not help detect private key exposures. In this paper, we propose a Key Compromise Resilient Signature (KCRS) system, which leverages blockchain to detect key compromises and mitigate the consequences. Our solution keeps a log of valid certificates and digital signatures that have been issued on the blockchain, which can deter the abuse of compromised private keys. Since the blockchain is an open system, KCRS also provides a privacy protection mechanism to prevent the public from learning the relationship between signatures. We present a theoretical framework for the security of the system and a provably-secure construction. We also implement a prototype of KCRS and conduct experiments to demonstrate its practicability

Development of a local antibiogram for a teaching hospital in Ghana

Background: Antimicrobial resistance threatens adequate healthcare provision against infectious diseases. Antibiograms, combined with patient clinical history, enable clinicians and pharmacists to select the best empirical treatments prior to culture results. Objectives: To develop a local antibiogram for the Ho Teaching Hospital. Methods: This was a retrospective cross-sectional study, using data collected on bacterial isolates from January-December 2021. Samples from urine, stool, sputum, blood, and cerebrospinal fluid (CSF) were considered as well as, aspirates and swabs from wound, ears and vagina of patients. Bacteria were cultured on both enrichment and selective media including blood agar supplemented with 5% sheep blood and MacConkey agar, and identified by both the VITEK 2 system and routine biochemical tests. Data on routine culture and sensitivity tests performed on bacterial isolates from patient samples were retrieved from the hospital's health information system. Data were then entered into and analysed using WHONET. Results: In all, 891 pathogenic microorganisms were isolated from 835 patients who had positive culture tests. Gram-negative isolates accounted for about 77% of the total bacterial species. Escherichia coli (246), Pseudomonas spp. (180), Klebsiella spp. (168), Citrobacter spp. (101) and Staphylococcus spp. (78) were the five most isolated pathogens. Most of the bacterial isolates showed high resistance (>70%) to ampicillin, piperacillin, ceftazidime, ceftriaxone, cefotaxime, penicillin G, amoxicillin, amoxicillin/clavulanic acid, ticarcillin/clavulanic acid and trimethoprim/sulfamethoxazole. Conclusions: The isolates from the various samples were not susceptible to most of the antibiotics used in the study. The study reveals the resistance patterns of E. coli and Klebsiella spp.To some antibiotics on the WHO 'Watch' and 'Reserve' lists. Using antibiograms as part of antimicrobial stewardship programmes would optimize antibiotic use and preserve their efficacy

Adjuvant TACE inhibitor treatment improves the outcome of TLR2(-/- )mice with experimental pneumococcal meningitis

BACKGROUND: Streptococcus (S.) pneumoniae meningitis has a high lethality despite antibiotic treatment. Inflammation is a major pathogenetic factor, which is unresponsive to antibiotics. Therefore adjunctive therapies with antiinflammatory compounds have been developed. TNF484 is a TNF-alpha converting enzyme (TACE) inhibitor and has been found efficacious in experimental meningitis. Toll-like receptor 2 (TLR2) contributes to host response in pneumococcal meningitis by enhancing bacterial clearing and downmodulating inflammation. In this study, TNF484 was applied in mice, which lacked TLR2 and exhibited a strong meningeal inflammation. METHODS: 10(3 )CFU S. pneumoniae serotype 3 was inoculated subarachnoidally into C57BL/6 wild type (wt) mice or TLR2(-/-), CD14(-/- )and CD14(-/-)/TLR2(-/- )mice. Severity of disease and survival was followed over 9 days. Response to antibiotics (80 mg/kg ceftriaxone i.p. for 5 days) and/or TACE inhibitor treatment (1 mg/kg s.c. twice daily for 4 days) was evaluated. Animals were sacrificed after 12, 24, and 48 h for analysis of bacterial load in cerebrospinal fluid (CSF) and brain and for TNF and leukocyte measurements in CSF. RESULTS: TLR2(-/- )mice were significantly sicker than the other mouse strains 24 h after infection. All knockout mice showed higher disease severity after 48 h and died earlier than wt mice. TNF release into CSF was significantly more elevated in TLR2(-/- )than in the other strains after 24 h. Brain bacterial numbers were significantly higher in all knockout than wt mice after 24 h. Modulation of outcome by antibiotic and TACE inhibitor treatment was evaluated. With antibiotic therapy all wt, CD14(-/- )and TLR2(-/-)/CD14(-/- )mice, but only 79% of TLR2(-/- )mice, were rescued. TACE inhibitor treatment alone did not rescue, but prolonged survival in wt mice, and in TLR2(-/- )and CD14(-/- )mice to the values observed in untreated wt mice. By combined antibiotic and TACE inhibitor treatment 95% of TLR2(-/- )mice were rescued. CONCLUSION: During pneumococcal meningitis strong inflammation in TLR2-deficiency was associated with incomplete responsiveness to antibiotics and complete response to combined antibiotic and TACE inhibitor treatment. TACE inhibitor treatment offers a promising adjuvant therapeutic strategy in pneumococcal meningitis

Towards improved cover glasses for photovoltaic devices

For the solar energy industry to increase its competitiveness there is a global drive to lower the cost of solar generated electricity. Photovoltaic (PV) module assembly is material-demanding and the cover glass constitutes a significant proportion of the cost. Currently, 3 mm thick glass is the predominant cover material for PV modules, accounting for 10-25% of the total cost. Here we review the state-of-the-art of cover glasses for PV modules and present our recent results for improvement of the glass. These improvements were demonstrated in terms of mechanical, chemical and optical properties by optimizing the glass composition, including addition of novel dopants, to produce cover glasses that can provide: (i) enhanced UV protection of polymeric PV module components, potentially increasing module service lifetimes; (ii) re-emission of a proportion of the absorbed UV photon energy as visible photons capable of being absorbed by the solar cells, thereby increasing PV module efficiencies; (iii) Successful laboratory-scale demonstration of proof-of-concept, with increases of 1-6% in Isc and 1-8% Ipm. Improvements in both chemical and crack resistance of the cover glass were also achieved through modest chemical reformulation, highlighting what may be achievable within existing manufacturing technology constraints

Sex differences in money pathology in the general population

This study examined sex differences in money beliefs and behaviours. Over 100,000 British participants completed two measures online, one of which assessed “money pathology” (Forman in Mind over money, Doubleday, Toronto, 1987), and the other four “money types”, based on the emotional associations of money (Furnham et al. in Personal Individ Differ, 52:707–711, 2012). Nearly all measures showed significant sex differences with medium to large effect sizes, and with females exhibiting more “money pathology” than males. The biggest difference on the money types was on money being associated with generosity (money representing love) where men scored much lower than females, and autonomy (money representing freedom) where men scored higher than women. For men, more than women, money represented Power and Security. Men were more likely to be Hoarders while women did more emotional regulatory purchasing. Implications and limitations of this study are discussed

Myosin Light Chain Kinase Mediates Intestinal Barrier Disruption following Burn Injury

Background: Severe burn injury results in the loss of intestinal barrier function, however, the underlying mechanism remains unclear. Myosin light chain (MLC) phosphorylation mediated by MLC kinase (MLCK) is critical to the pathophysiological regulation of intestinal barrier function. We hypothesized that the MLCK-dependent MLC phosphorylation mediates the regulation of intestinal barrier function following burn injury, and that MLCK inhibition attenuates the burn-induced intestinal barrier disfunction. Methodology/Principal Findings: Male balb/c mice were assigned randomly to either sham burn (control) or 30 % total body surface area (TBSA) full thickness burn without or with intraperitoneal injection of ML-9 (2 mg/kg), an MLCK inhibitor. In vivo intestinal permeability to fluorescein isothiocyanate (FITC)-dextran was measured. Intestinal mucosa injury was assessed histologically. Tight junction proteins ZO-1, occludin and claudin-1 was analyzed by immunofluorescent assay. Expression of MLCK and phosphorylated MLC in ileal mucosa was assessed by Western blot. Intestinal permeability was increased significantly after burn injury, which was accompanied by mucosa injury, tight junction protein alterations, and increase of both MLCK and MLC phosphorylation. Treatment with ML-9 attenuated the burn-caused increase of intestinal permeability, mucosa injury, tight junction protein alterations, and decreased MLC phosphorylation, but not MLCK expression

ERG Deregulation Induces PIM1 Over-Expression and Aneuploidy in Prostate Epithelial Cells

The ERG gene belongs to the ETS family of transcription factors and has been found to be involved in atypical chromosomal rearrangements in several cancers. To gain insight into the oncogenic activity of ERG, we compared the gene expression profile of NIH-3T3 cells stably expressing the coding regions of the three main ERG oncogenic fusions: TMPRSS2/ERG (tERG), EWS/ERG and FUS/ERG. We found that all three ERG fusions significantly up-regulate PIM1 expression in the NIH-3T3 cell line. PIM1 is a serine/threonine kinase frequently over-expressed in cancers of haematological and epithelial origin. We show here that tERG expression induces PIM1 in the non-malignant prostate cell line RWPE-1, strengthening the relation between tERG and PIM1 up-regulation in the initial stages of prostate carcinogenesis. Silencing of tERG reversed PIM1 induction. A significant association between ERG and PIM1 expression in clinical prostate carcinoma specimens was found, suggesting that such a mechanism may be relevant in vivo. Chromatin Immunoprecipitation experiments showed that tERG directly binds to PIM1 promoter in the RWPE-1 prostate cell line, suggesting that tERG could be a direct regulator of PIM1 expression. The up-regulation of PIM1 induced by tERG over-expression significantly modified Cyclin B1 levels and increased the percentage of aneuploid cells in the RWPE-1 cell line after taxane-based treatment. Here we provide the first evidence for an ERG-mediated PIM1 up-regulation in prostate cells in vitro and in vivo, suggesting a direct effect of ERG transcriptional activity in the alteration of genetic stability

Fecal Microbiota Transplantation Is Safe and Effective in Patients With Clostridioides difficile Infection and Cirrhosis

Background & Aims Clostridioides difficile infection (CDI) harms a large proportion of patients with cirrhosis. Fecal microbiota transplantation (FMT) is recommended for recurrent CDI, but its effects in patients with cirrhosis have not been established. We performed a multicenter observational study to evaluate the efficacy and safety of FMT for CDI in patients with cirrhosis. Methods We performed a retrospective study of 63 adults with cirrhosis (median model for end-stage liver disease score, 14.5; 24 patients with decompensated cirrhosis) who underwent FMT for CDI from January 2012 through November 2018 at 8 academic centers in the United States, Canada, and Italy. We collected data on patient demographics and characteristics of cirrhosis, CDI, and FMT from medical records and compared differences among patients with different severities of cirrhosis, and FMT successes vs failures at the 8-week follow-up evaluation. We also obtained data on adverse events (AEs) and severe AEs within 12 weeks of FMT. Results Patients underwent FMT for recurrent CDI (55 of 63; 87.3%), severe CDI (6 of 63; 9.5%), or fulminant CDI (2 of 63; 3.2%) primarily via colonoscopy (59 of 63; 93.7%) as outpatients (47 of 63; 76.8%). FMT success was achieved for 54 patients (85.7%). Among FMT failures, a higher proportion used non-CDI antibiotics at the time of FMT (44.4% vs 5.6%; P < .001), had Child–Pugh scores of B or C (100% vs 37.7%; P < .001), used probiotics (77.8% vs 24.1%; P = .003), had pseudomembranes (22.2% vs 0; P = .018), and underwent FMT as inpatients (45.5% vs 19%; P = .039), compared with FMT successes. In multivariable analysis, use of non-CDI antibiotics at the time of FMT (odds ratio, 17.43; 95% CI, 2.00–152.03; P = .01) and use of probiotics (odds ratio, 11.9; 95% CI, 1.81–78.3; P = .01) were associated with a greater risk of FMT failure. FMT-related AEs occurred in 33.3% of patients (21 of 63)—most were self-limited abdominal cramps or diarrhea. There were only 5 severe AEs that possibly were related to FMT; none involved infection or death. Conclusions In a retrospective study, we found FMT to be safe and effective for the treatment of CDI in patients with cirrhosis