The interplay between spatial and heliconical orientational order in twist-bend nematic materials.

The helical pitch formed by organic molecules, such as the α-helix of proteins, usually requires hydrogen bonding between chiral units and long-range positional order. It was recently found that certain liquid crystal oligomers can have a twist-bend nematic (NTB) phase with nanoscale heliconical structure without hydrogen bonding, molecular chirality or positional order. To understand the nature of this unique structure, here we present hard and resonant tender X-ray scattering studies of two novel sulfur containing dimer materials. We simultaneously measure the temperature dependences of the helical pitch and the correlation length of both the helical and positional order. In addition to an unexpected strong variation of the pitch with the length of the spacer connecting the monomer units, we find that at the transition to the NTB phase the positional correlation length drops. The helical structure was found not only in the NTB phase but observed even in the upper range of a smectic phase that forms just below the NTB state. The coexistence of smectic layering and the heliconical order indicates a layered (SmATB) phase wherein the rigid units of the dimers are tilted with respect to the smectic layer normal in order to accommodate the bent conformation of the dimers and the tilt direction rotates along the heliconical axis.

Decision-making for older patients undergoing emergency laparotomy: defining patient and clinician values and priorities.

AIM: There remains limited knowledge on what patients value and prioritize in their decision to undergo emergency laparotomy (ELap) and during their subsequent recovery. The aim of this study was to explore factors in decision-making and to reach a consensus amongst patients on the 10 most important priorities in decision-making in ELap. METHODS: Patients aged over 65 years who had required an ELap decision within the preceding 12 months (regardless of management) were identified and invited to attend a modified Delphi process focus group. RESULTS: A total of 20 participants attended: eight patients, four relatives and eight perioperative specialists. The perioperative specialists group defined 12 important factors for perioperative decision-making. The patient group agreed that only six (50%) of these factors were important: independence, postoperative complications, readmission to hospital, requirement for stoma formation, delirium (including long-term cognition) and presence of an advocate (such as a friend or family member). Open discussion refined multiple themes. Agreement was reached by patients and relatives about 10 factors that they valued as most important in their ELap patient journey: return to independence, realistic expectations, postoperative complications, what to expect postoperatively, readmission to hospital, nutrition, postoperative communication, stoma, follow-up and delirium. CONCLUSION: Patients and clinicians have different values and priorities when discussing the risks and implications of undergoing ELap. Patients value quality of life outcomes, in particular, the formation of a stoma, returning to their own home and remaining independent. This work is the first to combine both perspectives to guide future ELap research outcomes.

Soft modes of the dielectric response in the twist-bend nematic phase and identification of the transition to a nematic splay bend phase in the CBC7CB dimer.

The dielectric spectra of the twist-bend nematic phase (NTB) of (the bent-shaped) achiral liquid-crystal dimer 1''-,7''-bis(4-cyanobiphenyl-4'-yl)heptane (CB7CB) are studied for the determination of the different relaxation modes. Two molecular processes and one collective process were observed in the megahertz frequency range. Two molecular processes were assigned: one to the precessional rotation of the longitudinal components of the cyanobiphenyl groups and the second one to the spinning rotation of the transverse component of the CB7CB dimer. The peak, at a frequency of about 1 MHz, shows a peculiar temperature behavior at the NTB to N transition, reminiscent of the soft mode at the transition from the SmA to the SmC phase. This peak can be assigned to a collective fluctuation of the tilt angle of the coarse grained director N with respect to the pseudo-layer normal. This corresponds well with the electro-clinic effect observed as a response to an electric field in electro-optic experiments. The low frequency relaxation process, observed in the frequency range of 1 Hz-102 Hz can be identified as a Goldstone mode, related to long-scale fluctuation of the cone phase. The frequency drop of the mode on increasing the bias field is interpreted as unwinding of a helix and an indication of the formation of a field induced nematic splay bend phase (NSB). This finding is also confirmed by birefringence data in the presence of strong bias fields.

Describing nonequilibrium soft matter with mean field game theory.

We demonstrate that combining an emerging approach to game theory with self-consistent mean field theory provides realistic treatments of diblock copolymer phase evolution. We especially examine order-order phase transformations upon quenched temperature change involving hexagonal cylinders, lamellae, and the gyroid. Our findings demonstrate that (i) the game theoretical dynamics produce realistic trajectories for the evolution of the local compositions, (ii) the predicted small-angle scattering follows experimentally observed trends, (iii) nucleation and growth is active when the system is quenched far from the critical point, and (iv) epitaxial growth is manifest. To our knowledge, the methodology presented provides the first merger of mean field game theory and statistical mechanics for soft matter systems, giving a new inroad to studying polymer dynamics.

Dielectric response of electric-field distortions of the twist-bend nematic phase for LC dimers.

Wide band dielectric spectroscopy of bent-shaped achiral liquid-crystal dimers 1″-n″-bis(4-cyanobiphenyl-4'-yl) n-alkanes (CBnCB n = 7, 9, 11) has been investigated in a frequency range 0.1 Hz-100 MHz using planar-aligned cells of sample thicknesses ranging from 2 to 10 (µm) over a temperature range that covers both nematic and twist bend nematic phases. Two peaks in the dielectric spectrum in the higher frequency range are assigned to the molecular relaxation processes. The peak at the highest frequency, ∼40 to 80 MHz, is assigned to an internal precessional rotation of a single unit of the dimer around the director. The mode in the next lower frequency range of 2-10 MHz is assigned to the spinning rotation of the dimer around its long axis. This involves fluctuations of the dipole moment of the bent-shaped conformation that is directed along its arrow direction of the bow shape formed by the dimer. The peak in the frequency range 100 kHz-1 MHz can be assigned to the collective fluctuations of the local director with reference to the helical axis of the NTB structure. The dependence of its frequency on temperature is reminiscent of the soft mode observed at the SmA* to SmC* phase transition. This result clearly corresponds to the electro-clinic effect-the response of the director to the applied electric field in an electro-optic experiment. The lowest frequency mode, observed in the frequency range of 0.1 Hz-100 Hz, is identified with the Goldstone mode. This mode is concerned with the long range azimuthal angle fluctuations of the local director. This leads to an alternating compression and expansion of the periodic structure of the NTB phase.

Resource use and cost of annual health checks in primary care for people with intellectual disabilities.

BACKGROUND: The annual health check (AHC) programme, as part of a Directed Enhanced Service, offers an incentive to general practitioners in England to conduct health checks for people with intellectual disabilities (IDs). The aim of this analysis was to estimate the impact on health care costs of AHCs in primary care to the National Health Service in England by comparing adults with ID who did or did not have AHCs using data obtained from The Health Improvement Network. METHODS: Two hundred eight records of people with ID from The Health Improvement Network database were analysed. Baseline health care resource use was captured at the time the first AHC was recorded (i.e. index date), or the earliest date after 1 April 2008 for those without an AHC. We examined the volume of resource use and associated costs that occurred at the time AHCs were performed, as well as before and after the index date. We then estimated the impact of AHCs on health care costs. RESULTS: The average cost of AHC was estimated at £142.57 (95%CI £135.41 to £149.74). Primary, community and secondary health care costs increased significantly after the index date in the no AHC group owing to higher increase in resource utilisation. Regression analysis showed that the expected health care cost for those who have an AHC is 56% higher than for those who did not have an AHC. Age and gender were also associated with increase in expected health care cost. CONCLUSION: The level of resource utilisation increased in both (AHC and no AHC) groups after the index date. Although the level of resource use before index date was lower in the no AHC group, it increased after the index date up to almost reaching the level of resource utilisation in the AHC group. Further research is needed to explore if the AHCs are effective in reducing health inequalities.

TRPV6 compound heterozygous variants result in impaired placental calcium transport and severe undermineralization and dysplasia of the fetal skeleton.

Transient receptor potential vanilloid 6 (TRPV6) functions in tetramer form for calcium transport. Until now, TRPV6 has not been linked with skeletal development disorders. An infant with antenatal onset thoracic insufficiency required significant ventilatory support. Skeletal survey showed generalized marked undermineralization, hypoplastic fractured ribs, metaphyseal fractures, and extensive periosteal reaction along femoral, tibial, and humeral diaphyses. Parathyroid hormone (PTH) elevation (53.4-101 pmol/L) initially suggested PTH signaling disorders. Progressively, biochemical normalization with radiological mineralization suggested recovery from in utero pathophysiology. Genomic testing was undertaken and in silico protein modeling of variants. No abnormalities in antenatal CGH array or UPD14 testing. Postnatal molecular genetic analysis found no causative variants in CASR, GNA11, APS21, or a 336 gene skeletal dysplasia panel investigated by whole exome sequencing. Trio exome analysis identified compound heterozygous TRPV6 likely pathogenic variants: novel maternally inherited missense variant, c.1978G > C p.(Gly660Arg), and paternally inherited nonsense variant, c.1528C > T p.(Arg510Ter), confirming recessive inheritance. p.(Gly660Arg) generates a large side chain protruding from the C-terminal hook into the interface with the adjacent TRPV6 subunit. In silico protein modeling suggests steric clashes between interface residues, decreased C-terminal hook, and TRPV6 tetramer stability. The p.(Gly660Arg) variant is predicted to result in profound loss of TRPV6 activity. This first case of a novel dysplasia features severe but improving perinatal abnormalities. The TRPV6 compound heterozygous variants appear likely to interfere with fetoplacental calcium transfer crucial for in utero skeletal development. Astute clinical interpretation of evolving perinatal abnormalities remains valuable in complex calcium and bone pathophysiology and informs exome sequencing interpretation.

Jammed Limit of Bijel Structure Formation.

Over the past decade, methods to control microstructure in heterogeneous mixtures by arresting spinodal decomposition via the addition of colloidal particles have led to an entirely new class of bicontinuous materials known as bijels. Herein, we present a new model for the development of these materials that yields to both numerical and analytical evaluation. This model reveals that a single dimensionless parameter that captures both chemical and environmental variables dictates the dynamics and ultimate structure formed in bijels. We demonstrate that this parameter must fall within a fixed range in order for jamming to occur during spinodal decomposition, as well as show that known experimental trends for the characteristic domain sizes and time scales for formation are recovered by this model.

Molecular organization in the twist-bend nematic phase by resonant X-ray scattering at the Se K-edge and by SAXS, WAXS and GIXRD.

Using a magnetically aligned liquid crystal mixture containing a novel Se-labelled dimer and the difluoroterphenyl dimer DTC5C7, the twist-bend nematic phase (Ntb) was studied by the resonant scattering of hard X-rays and by conventional small and wide-angle X-ray scattering (SAXS, WAXS). Resonant diffraction spots indicated a helix with a 9-12 nm pitch in the Ntb phase and an unprecedentedly high helix orientation. This enabled deconvolution of global and local order parameters. These findings, combined with the simultaneously recorded resonant and non-resonant SAXS and WAXS data, allowed us to construct a locally layered molecular model of the Ntb phase, where the average twisted conformation of each molecule was idealised as a helical segment, matching the local heliconical director field. The dimers were found to be less bent in the Ntb phase than in their minimum energy conformation, and straightening further with increasing temperature. It is proposed that on further heating their low bend angle allows the transition to the normal nematic phase, where the molecules can freely move longitudinally, without the need to perform screw-like motion as in the Ntb phase. At the low-temperature end, the increasing molecular twist becomes unsustainable, leading to a transition to a smectic phase, where no twist is required.

Design and Validation of a Biosensor Implantation Capsule Robot.

We have proposed a long-term, noninvasive, nonrestrictive method of delivering and implanting a biosensor within the body via a swallowable implantation capsule robot (ICR). The design and preliminary validation of the ICR's primary subsystem-the sensor deployment system-is discussed and evidence is provided for major design choices. The purpose of the sensor deployment system is to adhere a small biosensor to the mucosa of the intestine long-term, and the modality was inspired by tapeworms and other organisms that employ a strategy of mechanical adhesion to soft tissue via the combined use of hooks or needles and suckers. Testing was performed to refine the design of the suction and needle attachment as well as the sensor ejection features of the ICR. An experiment was conducted in which needle sharpness, needle length, and vacuum volume were varied, and no statistically significant difference was observed. Finally, preliminary testing, coupled with prior work within a live porcine model, provided evidence that this is a promising approach for implanting a biosensor within the small intestine.

Anomalous Increase in Nematic-Isotropic Transition Temperature in Dimer Molecules Induced by a Magnetic Field.

We have determined the nematic-isotropic transition temperature as a function of an applied magnetic field in three different thermotropic liquid crystalline dimers. These molecules are comprised of two rigid calamitic moieties joined end to end by flexible spacers with odd numbers of methylene groups. They show an unprecedented magnetic field enhancement of nematic order in that the transition temperature is increased by up to 15 K when subjected to a 22 T magnetic field. The increase is conjectured to be caused by a magnetic-field-induced decrease of the average bend angle in the aliphatic spacers connecting the rigid mesogenic units of the dimers.

The stabilisation of the Nx phase in mixtures.

The phase behaviour of mixtures between two symmetric dimers, CBC9CB and the ether-linked analogue CBOC9OCB was investigated by Polarizing Optical Microscopy (POM), Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD) studies. The dimeric constituents are fully miscible and the construction of a temperature-composition phase diagram reveals a surprising amplification of the stability of the Nx phase in compositions of up to 37 wt% of CBOC9OCB in CBC9CB. The origin for this enhancement of stability is discussed and an explanation based on chiral recognition is developed.

Second harmonic light scattering induced by defects in the twist-bend nematic phase of liquid crystal dimers.

The nematic twist-bend (NTB) phase, exhibited by certain thermotropic liquid crystalline (LC) dimers, represents a new orientationally ordered mesophase - the first distinct nematic variant discovered in many years. The NTB phase is distinguished by a heliconical winding of the average molecular long axis (director) with a remarkably short (nanoscale) pitch and, in systems of achiral dimers, with an equal probability to form right- and left-handed domains. The NTB structure thus provides another fascinating example of spontaneous chiral symmetry breaking in nature. The order parameter driving the formation of the heliconical state has been theoretically conjectured to be a polarization field, deriving from the bent conformation of the dimers, that rotates helically with the same nanoscale pitch as the director field. It therefore presents a significant challenge for experimental detection. Here we report a second harmonic light scattering (SHLS) study on two achiral, NTB-forming LCs, which is sensitive to the polarization field due to micron-scale distortion of the helical structure associated with naturally-occurring textural defects. These defects are parabolic focal conics of smectic-like "pseudo-layers", defined by planes of equivalent phase in a coarse-grained description of the NTB state. Our SHLS data are explained by a coarse-grained free energy density that combines a Landau-deGennes expansion of the polarization field, the elastic energy of a nematic, and a linear coupling between the two.

Mesophase structure and behaviour in bulk and restricted geometry of a dimeric compound exhibiting a nematic-nematic transition.

We present structural studies of a dimeric compound composed of a central heptyl spacer linking two mesogens consisting of terphenyl units at which two adjacent fluoro groups are attached to each central ring. The terminal rings are linked to pentyl chains as terminal groups. The material exhibits a nematic-nematic transition and a low temperature modulated phase. The higher temperature nematic phase was found to exhibit an anomaly of the bend elastic constant similar to that of the dimers with N-Ntb phase sequence, and the physical properties of the low-temperature nematic phase are similar to those of the known Ntb materials. The structure of the low-temperature modulated smectic/columnar phase is described together with its ability to form freely suspended films and fibres. The relation of the modulated structure to the fibre formation and to the appearance of the labyrinthine instability in freely-suspended films is discussed.

Light scattering study of the "pseudo-layer" compression elastic constant in a twist-bend nematic liquid crystal.

The nematic twist-bend (TB) phase, exhibited by certain achiral thermotropic liquid crystalline (LC) dimers, features a nanometer-scale, heliconical rotation of the average molecular long axis (director) with equally probable left- and right-handed domains. On meso to macroscopic scales, the TB phase may be considered as a stack of equivalent slabs or "pseudo-layers", each one helical pitch in thickness. The long wavelength fluctuation modes should then be analogous to those of a smectic-A phase, and in particular the hydrodynamic mode combining "layer" compression and bending ought to be characterized by an effective layer compression elastic constant Beff and average director splay constant K. The magnitude of K is expected to be similar to the splay constant of an ordinary nematic LC, but due to the absence of a true mass density wave, Beff could differ substantially from the typical value of ∼106 Pa in a conventional smectic-A. Here we report the results of a dynamic light scattering study, which confirms the "pseudo-layer" structure of the TB phase with Beff in the range 103-104 Pa. We show additionally that the temperature dependence of Beff at the TB to nematic transition is accurately described by a coarse-grained free energy density, which is based on a Landau-deGennes expansion in terms of a heli-polar order parameter that characterizes the TB state and is linearly coupled to bend distortion of the director.

Fetal Sex and RHD Genotyping with Digital PCR Demonstrates Greater Sensitivity than Real-time PCR.

BACKGROUND: Noninvasive genotyping of fetal RHD (Rh blood group, D antigen) can prevent the unnecessary administration of prophylactic anti-D to women carrying RHD-negative fetuses. We evaluated laboratory methods for such genotyping. METHODS: Blood samples were collected in EDTA tubes and Streck® Cell-Free DNA™ blood collection tubes (Streck BCTs) from RHD-negative women (n = 46). Using Y-specific and RHD-specific targets, we investigated variation in the cell-free fetal DNA (cffDNA) fraction and determined the sensitivity achieved for optimal and suboptimal samples with a novel Droplet Digital™ PCR (ddPCR) platform compared with real-time quantitative PCR (qPCR). RESULTS: The cffDNA fraction was significantly larger for samples collected in Streck BCTs compared with samples collected in EDTA tubes (P < 0.001). In samples expressing optimal cffDNA fractions (≥4%), both qPCR and digital PCR (dPCR) showed 100% sensitivity for the TSPY1 (testis-specific protein, Y-linked 1) and RHD7 (RHD exon 7) assays. Although dPCR also had 100% sensitivity for RHD5 (RHD exon 5), qPCR had reduced sensitivity (83%) for this target. For samples expressing suboptimal cffDNA fractions (<2%), dPCR achieved 100% sensitivity for all assays, whereas qPCR achieved 100% sensitivity only for the TSPY1 (multicopy target) assay. CONCLUSIONS: qPCR was not found to be an effective tool for RHD genotyping in suboptimal samples (<2% cffDNA). However, when testing the same suboptimal samples on the same day by dPCR, 100% sensitivity was achieved for both fetal sex determination and RHD genotyping. Use of dPCR for identification of fetal specific markers can reduce the occurrence of false-negative and inconclusive results, particularly when samples express high levels of background maternal cell-free DNA.

Highly durable fuel cell electrodes based on ionomers dispersed in glycerol.

A major, unprecedented improvement in the durability of polymer electrolyte membrane fuel cells is obtained by tuning the properties of the interface between the catalyst and the ionomer by choosing the appropriate dispersing medium. While a fuel cell cathode prepared from aqueous dispersion showed 90 mV loss at 0.8 A cm(-2) after 30,000 potential cycles (0.6-1.0 V), a fuel cell cathode prepared from glycerol dispersion exhibited only 20 mV loss after 70,000 cycles. This minimum performance loss occurs even though there was an over 80% reduction of electrochemical surface area of the Pt catalyst. These findings indicate that a proper understanding and control of the catalyst-water-ionomer (three-phase) interfaces is even more important for maintaining fuel cell durability in typical electrodes than catalyst agglomeration, and this opens up a novel path for tailoring the functional properties of electrified interfaces.

30-day mortality in UK patients with bacteraemic community-acquired pneumonia.

OBJECTIVES: To determine 7 and 30-day mortality in consecutive patients with bacteraemic community-acquired pneumonia (CAP) and the association between predicted variables and likelihood of death. METHODS: From August 2007 to July 2011, demographic, clinical and microbiological data were prospectively collected on patients with bacteraemic CAP. Patients were followed until death, hospital discharge or recovery from infection. Univariate and multivariate analysis was performed to determine the association between predictor variables and 30-day mortality. RESULTS: 7-day mortality was 61/252 [24.4%, 95% confidence interval (CI) 19.1-30.0%] and by 30 days, this had risen to 77/252 (30.6%, 95% CI 24.9-36.6%). In univariate analysis, factors associated with 30-day mortality were age, speciality within 48 h of admission, blood culture isolate and Charlson co-morbidity index (CCI). In multivariate analysis, age and CCI remained significantly associated. There was also a trend towards significance for meticillin-sensitive Staphylococcus aureus (MSSA) and Pseudomonas aeruginosa blood culture isolates compared to Streptococcus pneumoniae. CONCLUSIONS: Overall, bacteraemic CAP was associated with high inpatient mortality. Because of their association with poor outcomes, patients with MSSA and P. aeruginosa bacteraemic CAP require further study.

Geographical Variation in Underlying Social Deprivation, Cardiovascular and Other Comorbidities in Patients with Potentially Curable Cancers in England: Results from a National Registry Dataset Analysis.

AIMS: To describe the prevalence of cardiovascular disease (CVD), multiple comorbidities and social deprivation in patients with a potentially curable cancer in 20 English Cancer Alliances. MATERIALS AND METHODS: This National Registry Dataset Analysis used national cancer registry data and CVD databases to describe rates of CVD, comorbidities and social deprivation in patients diagnosed with a potentially curable malignancy (stage I-III breast cancer, stage I-III colon cancer, stage I-III rectal cancer, stage I-III prostate cancer, stage I-IIIA non-small cell lung cancer, stage I-IV diffuse large B-cell lymphoma, stage I-IV Hodgkin lymphoma) between 2013 and 2018. Outcome measures included observation of CVD prevalence, other comorbidities (evaluated by the Charlson Comorbidity Index) and deprivation (using the Index of Multiple Deprivation) according to tumour site and allocation to Cancer Alliance. Patients were allocated to CVD prevalence tertiles (minimum: <33.3rd percentile; middle: 33.3rd to 66.6th percentile; maximum: >66.6th percentile). RESULTS: In total, 634 240 patients with a potentially curable malignancy were eligible. The total CVD prevalence for all cancer sites varied between 13.4% (CVD n = 2058; 95% confidence interval 12.8, 13.9) and 19.6% (CVD n = 7818; 95% confidence interval 19.2, 20.0) between Cancer Alliances. CVD prevalence showed regional variation both for male (16-26%) and female patients (8-16%) towards higher CVD prevalence in northern Cancer Alliances. Similar variation was observed for social deprivation, with the proportion of cancer patients being identified as most deprived varying between 3.3% and 32.2%, depending on Cancer Alliance. The variation between Cancer Alliance for total comorbidities was much smaller. CONCLUSION: Social deprivation, CVD and other comorbidities in patients with a potentially curable malignancy in England show significant regional variations, which may partly contribute to differences observed in treatments and outcomes.