Enhancing Key Digital Literacy Skills: Information Privacy, Information Security, and Copyright/Intellectual Property

Key Messages Background Knowledge and skills in the areas of information security, information privacy, and copyright/intellectual property rights and protection are of key importance for organizational and individual success in an evolving society and labour market in which information is a core resource. Organizations require skilled and knowledgeable professionals who understand risks and responsibilities related to the management of information privacy, information security, and copyright/intellectual property. Professionals with this expertise can assist organizations to ensure that they and their employees meet requirements for the privacy and security of information in their care and control, and in order to ensure that neither the organization nor its employees contravene copyright provisions in their use of information. Failure to meet any of these responsibilities can expose the organization to reputational harm, legal action and/or financial loss. Context Inadequate or inappropriate information management practices of individual employees are at the root of organizational vulnerabilities with respect to information privacy, information security, and information ownership issues. Users demonstrate inadequate skills and knowledge coupled with inappropriate practices in these areas, and similar gaps at the organizational level are also widely documented. National and international regulatory frameworks governing information privacy, information security, and copyright/intellectual property are complex and in constant flux, placing additional burden on organizations to keep abreast of relevant regulatory and legal responsibilities. Governance and risk management related to information privacy, security, and ownership are critical to many job categories, including the emerging areas of information and knowledge management. There is an increasing need for skilled and knowledgeable individuals to fill organizational roles related to information management, with particular growth in these areas within the past 10 years. Our analysis of current job postings in Ontario supports the demand for skills and knowledge in these areas. Key Competencies We have developed a set of key competencies across a range of areas that responds to these needs by providing a blueprint for the training of information managers prepared for leadership and strategic positions. These competencies are identified in the full report. Competency areas include: conceptual foundations risk assessment tools and techniques for threat responses communications contract negotiation and compliance evaluation and assessment human resources management organizational knowledge management planning; policy awareness and compliance policy development project managemen

Impact of exposure to diesel exhaust during pregnancy on mammary gland development and milk composition in the rabbit

Exposure to fine-particulate air pollution is a major global health concern because it is associated with reduced birth weight and an increased risk of cardiovascular disease. Here we have investigated the potential for exposure to diesel exhaust during pregnancy to influence mammary gland development and milk composition. Female rabbits were therefore exposed by nose-only inhalation to either diluted diesel exhaust fumes (1 mg/m3) or clean air for 2h/day, 5 days/week, from the 3rd to the 27th days of pregnancy. On Day 28 of pregnancy, mammary glands were collected from twelve females (six controls and six diesel-exposed) and assessed for morphological and functional alterations. Milk samples were collected from eighteen dams (nine controls and nine diesel-exposed) during early (days 2 to 4) and established (days 13 to 16) lactation to verify the composition of fatty acids and major proteins and leptin levels. The mammary alveolar lumina contained numerous fat globules, and stearoyl CoA reductase expression was higher in mammary epithelia from diesel exhaust-exposed rabbits, which together suggested increased mammary lipid biosynthesis. Gas chromatography analysis of the composition of milk fatty acids revealed a sharp rise in the total fatty acid content, mainly due to monounsaturated fatty acids. Liquid chromatography-mass spectrometry analysis of milk samples enabled identification and quantification of the main rabbit milk proteins and their main phosphorylated isoforms, and revealed important changes to individual casein and whey protein contents and to their most phosphorylated isoforms during early lactation. Taken together, these findings suggest that repeated daily exposure to diesel exhaust fumes during pregnancy at urban pollution levels can influence lipid metabolism in the mammary gland and the lipid and protein composition of milk. As milk may contribute to metabolic programming, such alterations affecting milk composition should be taken into account from a public health perspective

The Peak of the Fallback Rate from Tidal Disruption Events: Dependence on Stellar Type

A star completely destroyed in a tidal disruption event (TDE) ignites a luminous flare that is powered by the fallback of tidally stripped debris to a supermassive black hole (SMBH) of mass $M_{\bullet}$. We analyze two estimates for the peak fallback rate in a TDE, one being the "frozen-in" model, which predicts a strong dependence of the time to peak fallback rate, $t_{\rm peak}$, on both stellar mass and age, with $15\textrm{ days} \lesssim t_{\rm peak} \lesssim 10$ yr for main sequence stars with masses $0.2\le M_{\star}/M_{\odot} \le 5$ and $M_{\bullet} = 10^6M_{\odot}$. The second estimate, which postulates that the star is completely destroyed when tides dominate the maximum stellar self-gravity, predicts that $t_{\rm peak}$ is very weakly dependent on stellar type, with $t_{\rm peak} = \left(23.2\pm4.0\textrm{ days}\right)\left(M_{\bullet}/10^6M_{\odot}\right)^{1/2}$ for $0.2\le M_{\star}/M_{\odot} \le 5$, while $t_{\rm peak} = \left(29.8\pm3.6\textrm{ days}\right)\left(M_{\bullet}/10^6M_{\odot}\right)^{1/2}$ for a Kroupa initial mass function truncated at $1.5 M_{\odot}$. This second estimate also agrees closely with hydrodynamical simulations, while the frozen-in model is discrepant by orders of magnitude. We conclude that (1) the time to peak luminosity in complete TDEs is almost exclusively determined by SMBH mass, and (2) massive-star TDEs power the largest accretion luminosities. Consequently, (a) decades-long extra-galactic outbursts cannot be powered by complete TDEs, including massive-star disruptions, and (b) the most highly super-Eddington TDEs are powered by the complete disruption of massive stars, which -- if responsible for producing jetted TDEs -- would explain the rarity of jetted TDEs and their preference for young and star-forming host galaxies.Comment: 10 pages, 4 figures, ApJL accepte

Female psychopharmacology matters! Towards a sex-specific psychopharmacology

There is increasing recognition that women have a higher prevalence of certain psychiatric illnesses, and a differential treatment response and course of illness compared to men. Additionally, clinicians deal with a number of disorders like premenstrual syndrome, premenstrual dysphoric disorder, and postpartum depression, which affect women specifically and for which treatment and biological pathways are still unclear. In this article we highlight recent research which suggests that different biological mechanisms may underlie sex differences in responsiveness to stress. Sex differences are evident at the receptor level; where the corticotropin-releasing factor receptor shows differential coupling to adaptor proteins in males and females. The neuropeptide oxytocin also shows sex-specific effects in a range of social behaviors. It may act as a biomarker in post-traumatic stress disorder where sex differences are evident. Studies in women using hormonal contraception show that some of these oxytocin-mediated effects are likely influenced by sex hormones. In female rats rapid changes in circulating progesterone levels are associated with exaggerated behavioral responses to mild stress and blunted responses to benzodiazepines that could be prevented by acute treatment with low-dose fluoxetine. Perceived barriers in research on women have hindered progress. The development of a sex-specific psychopharmacology as a basis for translating this type of research into clinical practice is vital to improve treatment outcomes for women

Polyenylphosphatidylcholines as bioactive excipient in tablets for the treatment of liver fibrosis.

Liver fibrosis is a condition characterized by the accumulation of extracellular matrix (ECM) arising from the myofibroblastic transdifferentiation of hepatic stellate cells (HSCs) occurring as the natural response to liver damage. To date, no pharmacological treatments have been specifically approved for liver fibrosis. We recently reported a beneficial effect of polyenylphosphatidylcholines (PPCs)-rich formulations in reverting fibrogenic features of HSCs. However, unsaturated phospholipids' properties pose a constant challenge to the development of tablets as preferred patient-centric dosage form. Profiting from the advantageous physical properties of the PPCs-rich Soluthin® S 80 M, we developed a tablet formulation incorporating 70% w/w of this bioactive lipid. Tablets were characterized via X-ray powder diffraction, thermogravimetry, and Raman confocal imaging, and passed the major compendial requirements. To mimic physiological absorption after oral intake, phospholipids extracted from tablets were reconstituted as protein-free chylomicron (PFC)-like emulsions and tested on the fibrogenic human HSC line LX-2 and on primary cirrhotic rat hepatic stellate cells (PRHSC). Lipids extracted from tablets and reconstituted in buffer or as PFC-like emulsions exerted the same antifibrotic effect on both activated LX-2 and PRHSCs as observed with plain S 80 M liposomes, showing that the manufacturing process did not interfere with the bioactivity of PPCs

Invasive fungal diseases impact on outcome of childhood ALL - an analysis of the international trial AIEOP-BFM ALL 2009

In children with acute lymphoblastic leukemia (ALL), risk groups for invasive fungal disease (IFD) with need for antifungal prophylaxis are not well characterized, and with the advent of new antifungal compounds, current data on outcome are scarce. Prospectively captured serious adverse event reports of children enrolled in the international, multi-center clinical trial AIEOP-BFM ALL2009 were screened for proven/probable IFD, defined according to the updated EORTC/MSG consensus definitions. In a total of 6136 children (median age 5.2 years), 224 proven/probable IFDs (65 yeast and 159 mold) were reported. By logistic regression, the risk for proven/probable IFDs was significantly increased in children ≥12 years and those with a blast count ≥10% in the bone marrow on day 15 (P < 0.0001 each). Proven/probable IFDs had a 6-week and 12-week mortality of 10.7% and 11.2%, respectively. In the multivariate analysis, the hazard ratio for event-free and overall survival was significantly increased for proven/probable IFD, age ≥12 years, and insufficient response to therapy (P < 0.001, each). Our data define older children with ALL and those with insufficient treatment-response at high risk for IFD. As we show that IFD is an independent risk factor for event-free and overall survival, these patients may benefit from targeted antifungal prophylaxis

Phase I trial of viral vector based personalized vaccination elicits robust neoantigen specific antitumor T cell responses

Purpose: Personalized vaccines targeting multiple neoantigens (nAgs) are a promising strategy for eliciting a diversified antitumor T cell response to overcome tumor heterogeneity. NOUS-PEV is a vector based personalized vaccine, expressing 60 nAgs and consists of priming with a non-human Great Ape Adenoviral vector (GAd20) followed by boosts with Modified Vaccinia Ankara (MVA). Here, we report data of a phase Ib trial of NOUS-PEV in combination with pembrolizumab in treatment naïve metastatic melanoma patients (NCT04990479). Experimental Design: The feasibility of this approach was demonstrated by producing, releasing and administering to six patients 11 out of 12 vaccines within 8 weeks from biopsy collection to GAd20 administration. Results: The regimen was safe, with no treatment-related serious adverse events observed and mild vaccine-related reactions. Vaccine immunogenicity was demonstrated in all evaluable patients receiving the prime/boost regimen, with detection of robust neoantigen specific immune responses to multiple neoantigens comprising both CD4 and CD8 T cells. Expansion and diversification of vaccine-induced TCR clonotypes was observed in the post-treatment biopsies of patients with clinical response providing evidence of tumor infiltration by vaccine-induced neoantigen-specific T cell. Conclusions: These findings indicate the ability of NOUS-PEV to amplify and broaden the repertoire of tumor reactive T cells to empower a diverse, potent and durable antitumor immune response. Finally, a gene signature indicative for reduced presence of activated T cells together with very poor expression of the antigen processing machinery (APM) genes has been identified in pre-treatment biopsies as a potential biomarker of resistance to the treatment

Effect of two additional doses of intrathecal methotrexate during induction therapy on serious infectious toxicity in pediatric patients with acute lymphoblastic leukemia

Although initial central nervous system (CNS) involvement is rarely detected in childhood acute lymphoblastic leukemia (ALL), risk-adapted CNS-directed therapy is essential for all patients. Treatment intensity depends on the initial CNS status. In the AIEOP-BFM ALL 2009 trial, patients with cytomorphologic detection of leukemic blasts in initial cerebrospinal fluid were classified as CNS2 or CNS3 and received five intrathecal doses of methotrexate (MTX) in induction therapy compared to patients with CNS1 status (no blasts detected) who received three doses. The impact of additional intrathecal (IT) MTX on systemic toxicity in induction therapy is unknown. Between June 1st 2010 and February 28th 2017, a total of 6,136 ALL patients aged 1-17 years were enrolled onto the AIEOP-BFM ALL 2009 trial. The effect of three versus five doses of IT MTX during induction therapy on the incidence of severe infectious complications was analyzed. Among 4,706 patients treated with three IT MTX doses, 77 (1.6%) had a life-threatening infection during induction as compared to 59 of 1,350 (4.4%) patients treated with five doses (P<0.001; Odds Ratio 2.86 [95% Confidence Interval 1.99-4.13]). In a multivariate regression model, treatment with additional IT MTX proved to be the strongest risk factor for life-threatening infections (Odds Ratio 2.85 [1.96-4.14]). Fatal infections occurred in 16 (0.3%) and 38 (1.6%) patients treated with three or five IT MTX doses, respectively (P<0.001). As the relevance of additional intrathecal MTX in induction for relapse prevention in CNS2 patients is unclear, doses of intrathecal therapy have been reduced for these patients. (Clinicaltrials.gov identifiers: NCT01117441 and NCT00613457)

The role of parenting behaviors in childhood post-traumatic stress disorder: a meta-analytic review

Studies that have examined the association between parenting behaviors and childhood post-traumatic stress disorder (PTSD) have yielded mixed findings. To clarify the role of parenting in childhood PTSD we conducted a systematic review and meta-analysis of 14 studies that investigated the association between parenting and youth PTSD symptoms (total n = 4010). Negative parenting behaviors (e.g. overprotection, hostility) accounted for 5.3% of the variance in childhood PTSD symptoms. Positive parenting behaviors (e.g. warmth, support) account for 2.0% of variance. The negative and positive parenting and child PTSD symptom associations did not statistically differ in magnitude. Moderator analyses indicated that methodological factors and trauma variables may affect the association between parenting and child PTSD. Most studies relied upon questionnaire measures of general parenting style, and studies were predominantly cross-sectional with weaker evidence found in longitudinal studies. Given the small number of high quality studies available, only provisional recommendations about the role of parenting in childhood PTSD are made