Mesomorphic flexible chain polymers based on silicon

Poly(dialkylsiloxane)s and poly(dialkylsilane)s form a similar type of columnar mesophase. Although, the polysilanes are stiffer than polysiloxanes, both classes of polymers may be considered to be flexible due to the ability to form chain-folded crystals. Chain flexibility rather than the presence of chain stiffness determines whether the columnar mesophase is formed. A certain amphiphilic character does not appear to be required, as polysiloxanes with short side groups, e.g. polydiethylsiloxane display the same mesophase behaviour as polydialkylsilanes with long side chains and other nonpolar flexible chain molecules. The importance of the entropy gain upon conformational disordering is reflected in the increase in temperature stability with increasing alkyl side group length and the absence of mesophase behaviour in the case of the dimethyl substituted polymers

Field-cycling NMR realaxation spectroscopy of poly(di-n-alkylsiloxanes in solid, mesomorphic, and isotropic liquid phases

The frequency dependence of the proton spin-lattice relaxation times T1 and T1., in the laboratory and rotating frames, respectively, is reported for solid and liquid phases of poly(diethylsiloxane) (PDES) and in melts of poly(dimethylsiloxane) (PDMS). The total frequency range is 5 X 102 -3 X 108 Hz and is mainly covered by field-cycling NMR relaxation spectroscopy. The relaxation behavior of PDES in the liquid but ordered mesophase is compared to that of isotropic melts of PDES and PDMS and also to that of nematic main-chain liquid-crystal polymers. The frequency dependences of PDES and PDMS liquids can be represented at low and high frequencies by power laws, section by section. The relaxation behavior in the isotropic melts is entirely equivalent to that previously reported for other polymer species. In the PDES mesophase, the exponents of the power laws are significantly larger and the crossover frequency between the two regimes is reduced. The dynamics in this phase are discussed with respect to the influence of chain modes and order director fluctuations. The main conclusion is, on the whole, that data of the liquid phases are determined by chain modes rather than by local segment fluctuations. The chain dynamics in the PDES mesophase resemble the chain modes in isotropic melts modified for a microstructure with reduced randomness, whereas the influence of order director fluctuations can neither be confirmed nor ruled out

Patterns of joint involvement in juvenile idiopathic arthritis and prediction of disease course: A prospective study with multilayer non-negative matrix factorization.

BACKGROUND: Joint inflammation is the common feature underlying juvenile idiopathic arthritis (JIA). Clinicians recognize patterns of joint involvement currently not part of the International League of Associations for Rheumatology (ILAR) classification. Using unsupervised machine learning, we sought to uncover data-driven joint patterns that predict clinical phenotype and disease trajectories. METHODS AND FINDINGS: We analyzed prospectively collected clinical data, including joint involvement using a standard 71-joint homunculus, for 640 discovery patients with newly diagnosed JIA enrolled in a Canada-wide study who were followed serially for five years, treatment-naïve except for nonsteroidal anti-inflammatory drugs (NSAIDs) and diagnosed within one year of symptom onset. Twenty-one patients had systemic arthritis, 300 oligoarthritis, 125 rheumatoid factor (RF)-negative polyarthritis, 16 RF-positive polyarthritis, 37 psoriatic arthritis, 78 enthesitis-related arthritis (ERA), and 63 undifferentiated arthritis. At diagnosis, we observed global hierarchical groups of co-involved joints. To characterize these patterns, we developed sparse multilayer non-negative matrix factorization (NMF). Model selection by internal bi-cross-validation identified seven joint patterns at presentation, to which all 640 discovery patients were assigned: pelvic girdle (57 patients), fingers (25), wrists (114), toes (48), ankles (106), knees (283), and indistinct (7). Patterns were distinct from clinical subtypes (P \u3c 0.001 by χ2 test) and reproducible through external data set validation on a 119-patient, prospectively collected independent validation cohort (reconstruction accuracy Q2 = 0.55 for patterns; 0.35 for groups). Some patients matched multiple patterns. To determine whether their disease outcomes differed, we further subdivided the 640 discovery patients into three subgroups by degree of localization-the percentage of their active joints aligning with their assigned pattern: localized (≥90%; 359 patients), partially localized (60%-90%; 124), or extended ( CONCLUSIONS: Multilayer NMF identified patterns of joint involvement that predicted disease trajectory in children with arthritis. Our hierarchical unsupervised approach identified a new clinical feature, degree of localization, which predicted outcomes in both cohorts. Detailed assessment of every joint is already part of every musculoskeletal exam for children with arthritis. Our study supports both the continued collection of detailed joint involvement and the inclusion of patterns and degrees of localization to stratify patients and inform treatment decisions. This will advance pediatric rheumatology from counting joints to realizing the potential of using data available from uncovering patterns of joint involvement

Selective accumulation of differentiated CD8+ T cells specific for respiratory viruses in the human lung

The lungs are frequently challenged by viruses, and resident CD8+ T cells likely contribute to the surveillance of these pathogens. To obtain insight into local T cell immunity to respiratory viruses in humans, we determined the specificity, phenotype, and function of lung-residing CD8+ T cells and peripheral blood CD8+ T cells in a paired analysis. The lung contained markedly higher frequencies of influenza (FLU)-specific and respiratory syncytial virus (RSV)-specific CD8+ T cells when compared with the circulation. This contrasted with an equal distribution of cytomegalovirus- and Epstein-Bar virus–specific CD8+ T cells. Noticeably, a substantial fraction of the lung-residing FLU- and RSV-specific CD8+ T cells had progressed to a relatively late differentiation phenotype, reflected by low expression of CD28 and CD27. Lung-derived FLU-specific CD8+ T cells had low activation requirements, as expansion of these cells could be initiated by cognate peptide in the absence of helper cell–derived signals. Thus, the human lung contains high numbers of differentiated FLU- and RSV-specific memory CD8+ T cells that can readily expand upon reexposure to virus. Resident lung T cells may provide immediate immunological protection against pulmonary virus infections

The effect of TGFβRI inhibition on fibroblast heterogeneity in hypertrophic scar 2D in vitro models.

In burn patients, wound healing is often accompanied by hypertrophic scarring (HTS), resulting in both functional and aesthetic problems. HTSs are characterized by abundant presence of myofibroblasts (MFs) residing in the dermis. HTS development and MF persistence is primarily regulated by TGF-β signalling. A promising method to target the transforming growth factor receptor I (TGFβRI; also known as activin-like kinase 5 (ALK5)) is by making use of exon skipping through antisense oligonucleotides. In HTS the distinguishing border between the papillary dermis and the reticular dermis is completely abrogated, thus exhibiting a one layered dermis containing a heterogenous fibroblast population, consisting of papillary fibroblasts (PFs), reticular fibroblasts (RFs) and MFs. It has been proposed that PFs, as opposed to RFs, exhibit anti-fibrotic properties. Currently, it is still unclear which fibroblast subtype is most affected by exon skipping treatment. Therefore, the aim of this study was to investigate the effect of TGFβRI inhibition by exon skipping in PF, RF and HTS fibroblast monocultures. Morphological analyses revealed the presence of a PF-like population after exon skipping in the different fibroblast cultures. This observation was further confirmed by the expression of genes specific for PFs, demonstrated by qPCR analyses. Further investigations on mRNA and protein level revealed that indeed MFs and to a lesser extent RFs are targeted by exon skipping. Furthermore, collagen gel contraction analysis showed that ALK5 exon skipping reduced TGF-β- induced contraction together with decreased alpha-smooth muscle actin expression levels. In conclusion, we show for the first time that exon skipping primarily targets pro-fibrotic fibroblasts. This could be a promising step towards reduced HTS development of burn tissue

An integrated perspective linking physiological and psychological consequences of mild traumatic brain injury

Despite the often seemingly innocuous nature of a mild traumatic brain injury (mTBI), its consequences can be devastating, comprising debilitating symptoms that interfere with daily functioning. Currently, it is still difficult to pinpoint the exact cause of adverse outcome after mTBI. In fact, extensive research suggests that the underlying etiology is multifactorial. In the acute and early sub-acute stages, the pathophysiology of mTBI is likely to be dominated by complex physiological alterations including cellular injury, inflammation, and the acute stress response, which could lead to neural network dysfunction. In this stage, patients often report symptoms such as fatigue, headache, unstable mood and poor concentration. When time passes, psychological processes, such as coping styles, personality and emotion regulation, become increasingly influential. Disadvantageous, maladaptive, psychological mechanisms likely result in chronic stress which facilitates the development of long-lasting symptoms, possibly via persistent neural network dysfunction. So far, a systemic understanding of the coupling between these physiological and psychological factors that in concert define outcome after mTBI is lacking. The purpose of this narrative review article is to address how psychophysiological interactions may lead to poor outcome after mTBI. In addition, a framework is presented that may serve as a template for future studies on this subject

Cyber security fear appeals:unexpectedly complicated

Cyber security researchers are starting to experiment with fear appeals, with a wide variety of designs and reported efficaciousness. This makes it hard to derive recommendations for designing and deploying these interventions. We thus reviewed the wider fear appeal literature to arrive at a set of guidelines to assist cyber security researchers. Our review revealed a degree of dissent about whether or not fear appeals are indeed helpful and advisable. Our review also revealed a wide range of fear appeal experimental designs, in both cyber and other domains, which confirms the need for some standardized guidelines to inform practice in this respect. We propose a protocol for carrying out fear appeal experiments, and we review a sample of cyber security fear appeal studies, via this lens, to provide a snapshot of the current state of play. We hope the proposed experimental protocol will prove helpful to those who wish to engage in future cyber security fear appeal research

Pathways to professionalism? Quality improvement, care pathways, and the interplay of standardisation and clinical autonomy.

Care pathways are a prominent feature of efforts to improve healthcare quality, outcomes and accountability, but sociological studies of pathways often find professional resistance to standardisation. This qualitative study examined the adoption and adaptation of a novel pathway as part of a randomised controlled trial in an unusually complex, non-linear field - emergency general surgery - by teams of surgeons and physicians in six theoretically sampled sites in the UK. We find near-universal receptivity to the concept of a pathway as a means of improving peri-operative processes and outcomes, but concern about the impact on appropriate professional judgement. However, this concern translated not into resistance and implementation failure, but into a nuancing of the pathways-as-realised in each site, and their use as a means of enhancing professional decision-making and inter-professional collaboration. We discuss our findings in the context of recent literature on the interplay between managerialism and professionalism in healthcare, and highlight practical and theoretical implications