The impact of alkyl chain purity on lipid based nucleic acid delivery systems – is the utilization of lipid components with technical grade justified?

The physicochemical properties and transfection efficacies of two samples of a cationic lipid have been investigated and compared in 2D (monolayers at the air/liquid interface) and 3D (aqueous bulk dispersions) model systems using different techniques. The samples differ only in their chain composition due to the purity of the oleylamine (chain precursor). Lipid 8 (using the oleylamine of technical grade for cost-efficient synthesis) shows lateral phase separation in the Langmuir layers. However, the amount of attached DNA, determined by IRRAS, is for both samples the same. In 3D systems, lipid 8 p forms cubic phases, which disappear after addition of DNA. At physiological temperatures, both lipids (alone and in mixture with cholesterol) assemble to lamellar aggregates and exhibit comparable DNA delivery efficiency. This study demonstrates that non-lamellar structures are not compulsory for high transfection rates. The results legitimate the utilization of oleyl chains of technical grade in the synthesis of cationic transfection lipid

Posaconazole in the management of refractory invasive fungal infections

The rising incidence of invasive fungal infections due to the expanding population of immunocompromised hosts and the increasing prevalence of fungal resistance has led to the need for novel antifungal agents. Posaconazole, a new member of the triazole class has demonstrated in vitro activity against a broad spectrum of fungi and clinical activity against various fungal pathogens, including Aspergillus spp., Candida spp., zygomycetes, and Fusarium spp. To date, posaconazole has been approved for prophylaxis of invasive fungal infections in stem cell transplant recipients with acute graft versus host disease (GVHD) and neutropenic patients receiving intensive induction chemotherapy for acute myelogenous leukemia and myelodys-plastic syndrome. In addition, it has been licensed for use in oropharyngeal candidiasis and for salvage therapy in invasive aspergillosis, fusariosis, coccidioidomycosis, chromoblastomycosis, and mycetoma. Posaconazole is the only azole with activity against zygomycetes and other difficult-to-treat fungi, representing a potential treatment option for refractory invasive mycosis. This article reviews available preclinical and clinical data of posaconazole, focusing on its role in the teatment of refractory invasive fungal infections

The Physical Health of Caregivers of Children With Life-Limiting Conditions: A Systematic Review

CONTEXT: Parental caregiving for a child with a life-limiting condition (LLC) is complex physical and mental work. The impact of this caregiving on parents' physical health is unknown. OBJECTIVES: (1) To review existing evidence on the physical health of parents caring for a child with a LLC and (2) to determine how physical health of parents is measured. DATA SOURCES: Medline, Embase, PsycINFO, and Cumulative Index of Nursing and Allied Health Literature were searched. STUDY SELECTION: Peer-reviewed articles were included if they reported primary data on the physical health of a caregiver of a child with a LLC. Studies were excluded if they described only the caregiver's mental health or if the caregivers were bereaved at the time of data collection. DATA EXTRACTION: Of 69 335 unique citations, 81 studies were included in the review. RESULTS: Caregiver health was negatively impacted in 84% of studies. Pain and sleep disturbance were the most common problems. Ways of measuring the physical health of caregiver varied widely. We found an absence of in-depth explorations of the social and economic contexts, which could potentially mitigate the impact of caregiving. Furthermore, we find health interventions tailored to this group remain largely unexplored. LIMITATIONS: Studies were heterogenous in methodology, making comparisons of results across studies difficult. CONCLUSIONS: These findings support the need for improving access to interventions aimed at improving physical health in this population. The rate of health-seeking behaviors, preventive health care access and screening for health conditions is understudied and represent important directions for further research

Are You Tampering With My Data?

We propose a novel approach towards adversarial attacks on neural networks (NN), focusing on tampering the data used for training instead of generating attacks on trained models. Our network-agnostic method creates a backdoor during training which can be exploited at test time to force a neural network to exhibit abnormal behaviour. We demonstrate on two widely used datasets (CIFAR-10 and SVHN) that a universal modification of just one pixel per image for all the images of a class in the training set is enough to corrupt the training procedure of several state-of-the-art deep neural networks causing the networks to misclassify any images to which the modification is applied. Our aim is to bring to the attention of the machine learning community, the possibility that even learning-based methods that are personally trained on public datasets can be subject to attacks by a skillful adversary.Comment: 18 page

Stealthy Deception Attacks Against SCADA Systems

SCADA protocols for Industrial Control Systems (ICS) are vulnerable to network attacks such as session hijacking. Hence, research focuses on network anomaly detection based on meta--data (message sizes, timing, command sequence), or on the state values of the physical process. In this work we present a class of semantic network-based attacks against SCADA systems that are undetectable by the above mentioned anomaly detection. After hijacking the communication channels between the Human Machine Interface (HMI) and Programmable Logic Controllers (PLCs), our attacks cause the HMI to present a fake view of the industrial process, deceiving the human operator into taking manual actions. Our most advanced attack also manipulates the messages generated by the operator's actions, reversing their semantic meaning while causing the HMI to present a view that is consistent with the attempted human actions. The attacks are totaly stealthy because the message sizes and timing, the command sequences, and the data values of the ICS's state all remain legitimate. We implemented and tested several attack scenarios in the test lab of our local electric company, against a real HMI and real PLCs, separated by a commercial-grade firewall. We developed a real-time security assessment tool, that can simultaneously manipulate the communication to multiple PLCs and cause the HMI to display a coherent system--wide fake view. Our tool is configured with message-manipulating rules written in an ICS Attack Markup Language (IAML) we designed, which may be of independent interest. Our semantic attacks all successfully fooled the operator and brought the system to states of blackout and possible equipment damage