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1.
Clin Oncol (R Coll Radiol) ; 35(12): e708-e719, 2023 12.
Article in English | MEDLINE | ID: mdl-37741712

ABSTRACT

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.


Subject(s)
Breast Neoplasms , Carcinoma, Non-Small-Cell Lung , Cardiovascular Diseases , Colonic Neoplasms , Lung Neoplasms , Rectal Neoplasms , Humans , Male , Female , Carcinoma, Non-Small-Cell Lung/epidemiology , Lung Neoplasms/epidemiology , Comorbidity , England/epidemiology , Cardiovascular Diseases/epidemiology , Breast Neoplasms/epidemiology , Colonic Neoplasms/epidemiology , Social Deprivation , Registries
2.
Trials ; 24(1): 357, 2023 May 26.
Article in English | MEDLINE | ID: mdl-37237393

ABSTRACT

BACKGROUND: Venous leg ulcer(s) are common, recurring, open wounds on the lower leg, resulting from diseased or damaged leg veins impairing blood flow. Wound healing is the primary treatment aim for venous leg ulceration, alongside the management of pain, wound exudate and infection. Full (high) compression therapy delivering 40 mmHg of pressure at the ankle is the recommended first-line treatment for venous leg ulcers. There are several different forms of compression therapy available including wraps, two-layer hosiery, and two-layer or four-layer bandages. There is good evidence for the clinical and cost-effectiveness of four-layer bandage and two-layer hosiery but more limited evidence for other treatments (two-layer bandage and compression wraps). Robust evidence is required to compare clinical and cost-effectiveness of these and to investigate which is the best compression treatment for reducing time to healing of venous leg ulcers whilst offering value for money. VenUS 6 will therefore investigate the clinical and cost-effectiveness of evidence-based compression, two-layer bandage and compression wraps for time to healing of venous leg ulcers. METHODS: VenUS 6 is a pragmatic, multi-centre, three-arm, parallel-group, randomised controlled trial. Adult patients with a venous leg ulcer will be randomised to receive (1) compression wraps, (2) two-layer bandage or (3) evidence-based compression (two-layer hosiery or four-layer bandage). Participants will be followed up for between 4 and 12 months. The primary outcome will be time to healing (full epithelial cover in the absence of a scab) in days since randomisation. Secondary outcomes will include key clinical events (e.g. healing of the reference leg, ulcer recurrence, ulcer/skin deterioration, amputation, admission/discharge, surgery to close/remove incompetent superficial veins, infection or death), treatment changes, adherence and ease of use, ulcer related pain, health-related quality of life and resource use. DISCUSSION: VenUS 6 will provide robust evidence on the clinical and cost-effectiveness of the different forms of compression therapies for venous leg ulceration. VenUS 6 opened to recruitment in January 2021 and is currently recruiting across 30 participating centres. TRIAL REGISTRATION: ISRCTN67321719 . Prospectively registered on 14 September 2020.


Subject(s)
Varicose Ulcer , Adult , Humans , Compression Bandages , Cost-Benefit Analysis , Multicenter Studies as Topic , Pain , Quality of Life , Randomized Controlled Trials as Topic , Ulcer , Varicose Ulcer/diagnosis , Varicose Ulcer/therapy
3.
Nutrients ; 14(23)2022 Dec 02.
Article in English | MEDLINE | ID: mdl-36501164

ABSTRACT

Folate, vitamin D and iodine are key micronutrients in pregnancy, with deficiency associated with poor maternal and infant outcomes. For folate and vitamin D especially, deficiency is more common amongst women with obesity and recommended intakes and guidance on supplementation varies worldwide. The present study aims to investigate dietary and supplementary intakes of these micronutrients amongst a population of pregnant women with obesity in the United Kingdom, alongside key maternal demographic characteristics. Expectant women (n = 75) with a body mass index ≥ 30 kg/m2 at first antenatal appointment were recruited at 12 weeks gestation. Participants were asked about their supplement use preconception and during trimester one in a baseline questionnaire which also asked about demographic characteristics. Women also completed a four day diet diary from which dietary and supplemental intakes of micronutrients intakes were estimated. Folic acid was taken by 96% of women at any point in trimester 1, whilst only 26% of women took the higher 5 mg dose recommended for women with obesity in the UK. For vitamin D and iodine, 56% and 44% of women met the UK RNI, respectively. Maternal age was positively associated with taking supplements of any kind and the 5 mg folic acid supplement, whilst parity was inversely associated with both outcomes. This study strengthens the rationale for further work to be done raising awareness of the need for women with obesity to supplement both with a higher dose of folic acid and vitamin D and to be aware of the role of iodine during pregnancy.


Subject(s)
Folic Acid , Iodine , Female , Pregnancy , Humans , Vitamin D , Pregnancy Trimester, First , Vitamins , Dietary Supplements , Micronutrients , Eating , Obesity/epidemiology
4.
Phys Chem Chem Phys ; 23(7): 4055-4063, 2021 Feb 25.
Article in English | MEDLINE | ID: mdl-33587066

ABSTRACT

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.

5.
Early Hum Dev ; 154: 105307, 2021 03.
Article in English | MEDLINE | ID: mdl-33453458

ABSTRACT

BACKGROUND: It is widely acknowledged that maternal obesity and excessive gestational weight gain (GWG) are associated with increased risk of fetal macrosomia and recent studies have suggested a role for the timing and composition of GWG. AIMS: To examine the effect of the rate of change in GWG and maternal upper-body subcutaneous fat on neonatal anthropometric outcomes in a pilot observational study amongst women with obesity. STUDY DESIGN: Expectant women with a body mass index (BMI) > 30 kg/m2 at first antenatal appointment were recruited at 12 weeks gestation. Maternal height, weight and skinfold thickness (SFT) measurements were collected at baseline and repeated at 28 and 36 weeks gestation. Following delivery, World Health Organisation (WHO)-UK infant birthweight z-scores were calculated, and infant anthropometric measurements were obtained. RESULTS: The sum of upper body SFT measurements increased in mid-pregnancy (0.08 ± 0.71 mm/week) and decreased in late pregnancy (-0.04 ± 1.17 mm/week). After adjustment for maternal age, BMI and parity, mid- but not late- pregnancy GWG was positively associated with infant birthweight z-score (p<0.05), while mid- but not late-pregnancy changes in the sum of SFT were inversely associated with infant birthweight z-score (p<0.01). CONCLUSIONS: The present study suggests that mid- rather than late-pregnancy changes in weight and upper-body subcutaneous fat are associated with infant birthweight. Further research is required in larger, more diverse populations to explore whether pregnancy interventions aiming to improve maternal and offspring health can be personalised beyond BMI and GWG.


Subject(s)
Gestational Weight Gain , Birth Weight , Body Mass Index , Female , Humans , Obesity/epidemiology , Pregnancy , Subcutaneous Fat , Weight Gain
6.
Neurotoxicology ; 82: 146-157, 2021 01.
Article in English | MEDLINE | ID: mdl-33309840

ABSTRACT

Bisphenol A (BPA) is a ubiquitous environmental chemical that has been linked to behavioral differences in children and shown to impact critical neurodevelopmental processes in animal models. Though data is emerging, we still have an incomplete picture of how BPA disrupts neurodevelopment; in particular, how its impacts may vary across different genetic backgrounds. Given the genetic tractability of Drosophila melanogaster, they present a valuable model to address this question. Fruit flies are increasingly being used for assessment of neurotoxicants because of their relatively simple brain structure and variety of measurable behaviors. Here we investigated the neurodevelopmental impacts of BPA across two genetic strains of Drosophila-w1118 (control) and the Fragile X Syndrome (FXS) model-by examining both behavioral and neuronal phenotypes. We show that BPA induces hyperactivity in larvae, increases repetitive grooming behavior in adults, reduces courtship behavior, impairs axon guidance in the mushroom body, and disrupts neural stem cell development in the w1118 genetic strain. Remarkably, for every behavioral and neuronal phenotype examined, the impact of BPA in FXS flies was either insignificant or contrasted with the phenotypes observed in the w1118 strain. This data indicates that the neurodevelopmental impacts of BPA can vary widely depending on genetic background and suggests BPA may elicit a gene-environment interaction with Drosophila fragile X mental retardation 1 (dFmr1)-the ortholog of human FMR1, which causes Fragile X Syndrome and is associated with autism spectrum disorder.


Subject(s)
Benzhydryl Compounds/toxicity , Drosophila melanogaster/drug effects , Nervous System/drug effects , Phenols/toxicity , Animals , Courtship , Disease Models, Animal , Drosophila melanogaster/genetics , Drosophila melanogaster/growth & development , Female , Fragile X Syndrome/genetics , Fragile X Syndrome/veterinary , Grooming/drug effects , Larva/drug effects , Larva/physiology , Locomotion/drug effects , Male , Nervous System/growth & development
7.
Front Physiol ; 11: 822, 2020.
Article in English | MEDLINE | ID: mdl-32754053

ABSTRACT

Cell migration refers to the ability of cells to translocate across a substrate or through a matrix. To achieve net movement requires spatiotemporal regulation of the actin cytoskeleton. Computational approaches are necessary to identify and quantify the regulatory mechanisms that generate directed cell movement. To address this need, we developed computational tools, based on stochastic modeling, to analyze time series data for the position of randomly migrating cells. Our approach allows parameters that characterize cell movement to be efficiently estimated from cell track data. We applied our methods to analyze the random migration of Mouse Embryonic Fibroblasts (MEFS) and HeLa cells. Our analysis revealed that MEFs exist in two distinct states of migration characterized by differences in cell speed and persistence, whereas HeLa cells only exhibit a single state. Further analysis revealed that the Rho-family GTPase RhoG plays a role in determining the properties of the two migratory states of MEFs. An important feature of our computational approach is that it provides a method for predicting the current migration state of an individual cell from time series data. Finally, we applied our computational methods to HeLa cells expressing a Rac1 biosensor. The Rac1 biosensor is known to perturb movement when expressed at overly high concentrations; at these expression levels the HeLa cells showed two migratory states, which correlated with differences in the spatial distribution of active Rac1.

8.
Colorectal Dis ; 22(11): 1694-1703, 2020 11.
Article in English | MEDLINE | ID: mdl-32464712

ABSTRACT

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.


Subject(s)
Laparotomy , Quality of Life , Aged , Decision Making , Emergencies , Emergency Service, Hospital , Focus Groups , Humans
10.
Phys Chem Chem Phys ; 21(41): 22839-22848, 2019 Oct 24.
Article in English | MEDLINE | ID: mdl-31608911

ABSTRACT

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.

11.
J Chem Phys ; 151(11): 114908, 2019 Sep 21.
Article in English | MEDLINE | ID: mdl-31542029

ABSTRACT

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.

12.
J Hosp Infect ; 103(4): 441-446, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31494128

ABSTRACT

BACKGROUND: The Cepheid® GeneXpert® (GXP) can simultaneously test for norovirus (NV), Clostridium difficile (CD), influenza A/B (IFA/B) and respiratory syncytial virus (RSV). AIM: To compare centralized multiplex polymerase chain reaction (PCR) testing with localized GXP testing at a district general hospital. METHODS: From December 2017 to December 2018, samples received at Whipps Cross University Hospital (WCUH) were first tested at the local laboratory before transport centrally to the Royal London Hospital (RLH). At the RLH, a non-proprietary multiplex reverse transcriptase (RT) PCR assay was performed, which also tested for gastrointestinal or respiratory pathogens not tested for by the GXP. FINDINGS: A total of 1111 stool and respiratory samples were processed at both sites; 591 were respiratory and 520 were stool samples. Compared to centralized testing, the GXP gave sensitivity, specificity, and NPV all in excess of 97%, with the exception of RSV. The RSV assay had a sensitivity of 66.7% (95% confidence interval (CI) 24.1, 94.0) but an NPV of 99.7% (95% CI 98.6, 99.9). At the RLH, 65 (5.9%) additional respiratory or gastrointestinal viruses were detected, predominantly rhinovirus 35 (3.2%) and adenovirus 11 (1.0%). Compared to centralized testing, the median time saved for local respiratory and gastrointestinal sample testing was 19 h and 46 min and 17 h and 6 min, respectively. CONCLUSIONS: Local GXP testing compared to centralized multiplex PCR testing for IF, NV and CD, demonstrated sensitivities, specificities and NPV between 95% and 100%. Turnaround times were faster, enabling quicker infection prevention and control decision making. In our local setting (WCUH), the GXP demonstrated the potential to reduce NV and IFA/B outbreaks.


Subject(s)
Caliciviridae Infections/diagnosis , Clostridium Infections/diagnosis , Delivery of Health Care/organization & administration , Influenza, Human/diagnosis , Molecular Diagnostic Techniques/methods , Multiplex Polymerase Chain Reaction/methods , Respiratory Syncytial Virus Infections/diagnosis , Health Services Research , Hospitals, General , Humans , London , Sensitivity and Specificity , Time Factors
13.
Sci Rep ; 9(1): 8815, 2019 06 19.
Article in English | MEDLINE | ID: mdl-31217508

ABSTRACT

'Black silicon' (bSi) samples with surfaces covered in nanoneedles of length ~5 µm were fabricated using a plasma etching process and then coated with a conformal uniform layer of diamond using hot filament chemical vapour deposition to produce 'black diamond' (bD) nanostructures. The diamond needles were then chemically terminated with H, O, NH2 or F using plasma treatment, and the hydrophilicity of the resulting surfaces were assessed using water droplet contact-angle measurements, and scaled in the order O > H ≈NH2 >F, with the F-terminated surface being superhydrophobic. The effectiveness of these differently terminated bD needles in killing the Gram-negative bacterium E. coli was semi-quantified by Live/Dead staining and fluorescence microscopy, and visualised by environmental scanning electron microscopy. The total number of adhered bacteria was consistent for all the nanostructured bD surfaces at around 50% of the value for the flat diamond control. This, combined with a chemical bactericidal effect of 20-30%, shows that the nanostructured bD surfaces supported significantly fewer viable E. coli than flat surfaces. Moreover, the bD surfaces were particularly effective at preventing the establishment of bacterial aggregates - a precursor to biofilm formation. The percentage of dead bacteria also decreased as a function of hydrophilicity. These results are consistent with a predominantly mechanical mechanism for bacteria death based on the stretching and disruption of the cell membrane, combined with an additional effect from the chemical nature of the surface.


Subject(s)
Anti-Bacterial Agents/pharmacology , Diamond/pharmacology , Gram-Negative Bacteria/drug effects , Bacterial Adhesion/drug effects , Escherichia coli/drug effects , Escherichia coli/ultrastructure , Gram-Negative Bacteria/ultrastructure , Microbial Sensitivity Tests , Microbial Viability/drug effects , Silicon/pharmacology , Water
14.
J Chem Phys ; 150(17): 174905, 2019 May 07.
Article in English | MEDLINE | ID: mdl-31067911

ABSTRACT

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.

15.
Sleep Med ; 59: 110-113, 2019 07.
Article in English | MEDLINE | ID: mdl-30862439

ABSTRACT

BACKGROUND/OBJECTIVES: Short sleep duration has been linked to maternal hyperglycaemia following a 1-h 50 g oral glucose tolerance test (OGTT) in observational studies conducted primarily in the USA. Our objective was to examine the relationship between objectively measured sleep duration and plasma glucose values following the 2-h 75 g OGTT routinely used in the UK amongst women with obesity. METHODS: Sleep and OGTT data were available for 49 pregnant women who wore wrist actigraphs for at least two nights, and took a 2-h 75 g OGTT at the end of their second trimester. Multivariable regression was used to evaluate associations between sleep duration and OGTT results. RESULTS: Higher 2-h plasma glucose values were significantly associated with shorter sleep duration and higher maternal age and BMI, with no association observed between wake after sleep onset (WASO) and 2-h plasma glucose values. No associations were observed between fasting plasma glucose values and any sleep parameters. CONCLUSIONS: We found that shorter sleep duration, as measured using actigraphy, is associated with higher 2-h plasma glucose values following a 2-h 75 g OGTT in the UK. These findings are in keeping with those observed elsewhere in the world, employing alternative OGTT protocols. Future studies should investigate sleep extension as a potential candidate for inclusion in future RCTs aiming to improve glucose tolerance and prevent GDM amongst those at risk.


Subject(s)
Blood Glucose/metabolism , Gestational Weight Gain , Obesity/complications , Sleep/physiology , Actigraphy , Adult , Diabetes, Gestational/blood , Diabetes, Gestational/prevention & control , Female , Glucose Tolerance Test , Humans , Pregnancy
16.
J Intellect Disabil Res ; 63(3): 233-243, 2019 03.
Article in English | MEDLINE | ID: mdl-30461105

ABSTRACT

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.


Subject(s)
Facilities and Services Utilization/statistics & numerical data , General Practitioners/statistics & numerical data , Health Care Costs/statistics & numerical data , Intellectual Disability/therapy , Mass Screening/statistics & numerical data , Primary Health Care/statistics & numerical data , State Medicine/statistics & numerical data , Adult , England , Facilities and Services Utilization/economics , Female , General Practitioners/economics , Humans , Intellectual Disability/economics , Male , Mass Screening/economics , Middle Aged , State Medicine/economics
17.
Am J Med Genet A ; 176(9): 1950-1955, 2018 09.
Article in English | MEDLINE | ID: mdl-30144375

ABSTRACT

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.


Subject(s)
Bone Diseases, Developmental/diagnosis , Bone Diseases, Developmental/genetics , Calcium Channels/genetics , Genetic Association Studies , Genetic Predisposition to Disease , Genetic Variation , Heterozygote , TRPV Cation Channels/genetics , Alleles , Calcium Channels/chemistry , Comparative Genomic Hybridization , Exome , Female , Genetic Association Studies/methods , Humans , Models, Molecular , Placenta/metabolism , Pregnancy , Protein Conformation , Radiography , Severity of Illness Index , Structure-Activity Relationship , TRPV Cation Channels/chemistry , Exome Sequencing
18.
Biomater Sci ; 6(6): 1424-1432, 2018 May 29.
Article in English | MEDLINE | ID: mdl-29611852

ABSTRACT

'Black silicon' (bSi) samples with surfaces covered in nanoneedles of varying length, areal density and sharpness, have been fabricated using a plasma etching process. These nanostructures were then coated with a conformal uniform layer of diamond using hot filament chemical vapour deposition to produce 'black diamond' (bD) surfaces. The effectiveness of these bSi and bD surfaces in killing Gram-negative (E. coli) and Gram-positive (S. gordonii) bacteria was investigated by culturing the bacteria on the surfaces for a set time and then measuring the live-to-dead ratio. All the nanostructured surfaces killed E. coli at a significantly higher rate than the respective flat Si or diamond control samples. The length of the needles was found to be less important than their separation, i.e. areal density. This is consistent with a model for mechanical bacteria death based on the stretching and disruption of the cell membrane, enhanced by the cells motility on the surfaces. In contrast, S. gordonii were unaffected by the nanostructured surfaces, possibly due to their smaller size, thicker cell membrane and/or their lack of motility.


Subject(s)
Anti-Bacterial Agents/chemistry , Biocompatible Materials/chemistry , Diamond/chemistry , Nanostructures/chemistry , Silicon/chemistry , Anti-Bacterial Agents/pharmacology , Bacterial Infections/prevention & control , Biocompatible Materials/pharmacology , Boron Compounds/chemistry , Boron Compounds/pharmacology , Diamond/pharmacology , Escherichia coli/drug effects , Humans , Silicon/pharmacology , Streptococcus gordonii/drug effects , Surface Properties
19.
Langmuir ; 33(45): 13133-13138, 2017 11 14.
Article in English | MEDLINE | ID: mdl-29095625

ABSTRACT

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.

20.
Phys Chem Chem Phys ; 19(21): 13449-13454, 2017 May 31.
Article in English | MEDLINE | ID: mdl-28513674

ABSTRACT

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.

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