Costing the impact of interventions during pregnancy in the UK: a systematic review of economic evaluations.

OBJECTIVE: The aim of this review was to summarise the current evidence on the costing of resource use within UK maternity care, in order to facilitate the estimation of incremental resource and cost impacts potentially attributable to maternity care interventions. METHODS: A systematic review of economic evaluations was conducted by searching Medline, the Health Management Information Consortium, the National Health Service (NHS) Economic Evaluations Database, CINAHL and National Institute for Health and Care Excellence (NICE) guidelines for economic evaluations within UK maternity care, published between January 2010 and August 2019 in the English language. Unit costs for healthcare activities provided to women within the antenatal, intrapartum and postnatal period were inflated to 2018-2019 prices. Assessment of study quality was performed using the Quality of Health Economic Analyses checklist. RESULTS: Of 5084 titles or full texts screened, 37 papers were included in the final review (27 primary research articles, 7 review articles and 3 economic evaluations from NICE guidelines). Of the 27 primary research articles, 21 were scored as high quality, 3 as medium quality and 3 were low quality. Variation was noted in cost estimates for healthcare activities throughout the maternity care pathway: for midwife-led outpatient appointment, the range was £27.34-£146.25 (mean £81.78), emergency caesarean section, range was £1056.44-£4982.21 (mean £3508.93) and postnatal admission, range was £103.00-£870.10 per day (mean £469.55). CONCLUSIONS: Wide variation exists in costs applied to maternity healthcare activities, resulting in challenges in attributing cost to maternity activities. The level of variation in cost calculations is likely to reflect the uncertainty within the system and must be dealt with by conducting sensitivity analyses. Nationally agreed prices for granular unit costs are needed to standardise cost-effectiveness evaluations of new interventions within maternity care, to be used either for research purposes or decisions regarding national intervention uptake. PROSPERO REGISTRATION NUMBER: CRD42019145309

Mutation analysis of BRCA1 and BRCA2 genes in Iranian high risk breast cancer families

Background: Telomerase is a ribonucleoprotein enzyme that synthesises telomeres after cell division and maintains chromosomal stability leading to cellular immortalization. Telomerase has been associated with negative prognostic indicators in some studies. The present study aims to detect any association between telomerase sub-units: hTERT and hTR and the prognostic indicators including tumour's size and grade, nodal status and patient's age. Methods: Tumour samples from 46 patients with primary invasive breast cancer and 3 patients with benign tumours were collected. RT-PCR analysis was used for the detection of hTR, hTERT, and PGM1 (as a housekeeping) genes expression. Results: The expression of hTR and hTERT was found in 31(67.4%) and 38 (82.6%) samples respectively. We observed a significant association between hTR gene expression and younger age at diagnosis (p = 0.019) when comparing patients ≤ 40 years with those who are older than 40 years. None of the benign tumours expressed hTR gene. However, the expression of hTERT gene was revealed in 2 samples. No significant association between hTR and hTERT expression and tumour's grade, stage and nodal status was seen. Conclusion: The expression of hTR and hTERT seems to be independent of tumour's stage. hTR expression probably plays a greater role in mammary tumourogenesis in younger women (≤ 40 years) and this may have therapeutic implications in the context of hTR targeting strategies

Unsettling planning theory

Recent political developments in many parts of the world seem likely to exacerbate rather than ameliorate the planetary-scale challenges of social polarization, inequality and environmental change societies face. In this unconventional multi-authored essay, we therefore seek to explore some of the ways in which planning theory might respond to the deeply unsettling times we live in. Taking the multiple, suggestive possibilities of the theme of unsettlement as a starting point, we aim to create space for reflection and debate about the state of the discipline and practice of planning theory, questioning what it means to produce knowledge capable of acting on the world today. Drawing on exchanges at a workshop attended by a group of emerging scholars in Portland, Oregon in late 2016, the essay begins with an introduction section exploring the contemporary resonances of ‘unsettling’ in, of and for planning theory. This is followed by four, individually authored responses which each connect the idea of unsettlement to key challenges and possible future directions. We end by calling for a reflective practice of theorizing that accepts unsettlement but seeks to act knowingly and compassionately on the uneven terrain that it creates

Efficacy of a broad host range lytic bacteriophage against E. coli adhered to urothelium

Persistent urinary tract infections (UTI) are often caused by E. coli adhered to urothelium. This type of cells is generally recognized as very tolerant to antibiotics which renders difficult the treatment of chronic UTI. This work investigates the use of lytic bacteriophages as alternative antimicrobial agents, particularly the interaction of phages with E. coli adhered to urothelium and specifically determines their efficiency against this type of cells. The bacterial adhesion to urothelium was performed varying the bacterial cell concentrations and the period and conditions (static, shaken) of adhesion. Three collection bacteriophages (T1, T4 and phiX174 like phages) were tested against clinical E. coli isolates and only one was selected for further infection experiments. Based on the lytic spectrum against clinical isolates and its ability to infect the highest number of antibiotic resistant strains, the T1-like bacteriophage was selected. This bacteriophage caused nearly a 45 % reduction of the bacterial population after 2 h of treatment. This study provides evidence that bacteriophages are effective in controlling suspended and adhered cells and therefore can be a viable alternative to antibiotics to control urothelium adhered bacteria

Field of Attention for Instantaneous Object Recognition

BACKGROUND: Instantaneous object discrimination and categorization are fundamental cognitive capacities performed with the guidance of visual attention. Visual attention enables selection of a salient object within a limited area of the visual field; we referred to as "field of attention" (FA). Though there is some evidence concerning the spatial extent of object recognition, the following questions still remain unknown: (a) how large is the FA for rapid object categorization, (b) how accuracy of attention is distributed over the FA, and (c) how fast complex objects can be categorized when presented against backgrounds formed by natural scenes. METHODOLOGY/PRINCIPAL FINDINGS: To answer these questions, we used a visual perceptual task in which subjects were asked to focus their attention on a point while being required to categorize briefly flashed (20 ms) photographs of natural scenes by indicating whether or not these contained an animal. By measuring the accuracy of categorization at different eccentricities from the fixation point, we were able to determine the spatial extent and the distribution of accuracy over the FA, as well as the speed of categorizing objects using stimulus onset asynchrony (SOA). Our results revealed that subjects are able to rapidly categorize complex natural images within about 0.1 s without eye movement, and showed that the FA for instantaneous image categorization covers a visual field extending 20° × 24°, and accuracy was highest (>90%) at the center of FA and declined with increasing eccentricity. CONCLUSIONS/SIGNIFICANCE: In conclusion, human beings are able to categorize complex natural images at a glance over a large extent of the visual field without eye movement

Common Genetic Variants near the Brittle Cornea Syndrome Locus ZNF469 Influence the Blinding Disease Risk Factor Central Corneal Thickness

Central corneal thickness (CCT), one of the most highly heritable human traits (h2 typically>0.9), is important for the diagnosis of glaucoma and a potential risk factor for glaucoma susceptibility. We conducted genome-wide association studies in five cohorts from Australia and the United Kingdom (total N = 5058). Three cohorts were based on individually genotyped twin collections, with the remaining two cohorts genotyped on pooled samples from singletons with extreme trait values. The pooled sample findings were validated by individual genotyping the pooled samples together with additional samples also within extreme quantiles. We describe methods for efficient combined analysis of the results from these different study designs. We have identified and replicated quantitative trait loci on chromosomes 13 and 16 for association with CCT. The locus on chromosome 13 (nearest gene FOXO1) had an overall meta-analysis p-value for all the individually genotyped samples of 4.6×10−10. The locus on chromosome 16 was associated with CCT with p = 8.95×10−11. The nearest gene to the associated chromosome 16 SNPs was ZNF469, a locus recently implicated in Brittle Cornea Syndrome (BCS), a very rare disorder characterized by abnormal thin corneas. Our findings suggest that in addition to rare variants in ZNF469 underlying CCT variation in BCS patients, more common variants near this gene may contribute to CCT variation in the general population

Mutations of the BRCA1 and BRCA2 genes in patients with bilateral breast cancer

Mutations of the BRCA1 or BRCA2 genes have been shown to strongly predispose towards the development of contralateral breast cancer in patients from large multi-case families. In order to test the hypothesis that BRCA1 and BRCA2 mutations are more frequent in patients with bilateral breast cancer, we have investigated a hospital-based series of 75 consecutive patients with bilateral breast cancer and a comparison group of 75 patients with unilateral breast cancer, pairwise matched by age and family history, for mutations in the BRCA1 and BRCA2 genes. Five frameshift deletions (517delGT in BRCA1; 4772delA, 5946delCT, 6174delT and 8138del5 in BRCA2) were identified in patients with bilateral disease. No further mutations, apart from polymorphisms and 3 rare unclassified variants, were found after scanning the whole BRCA1 and BRCA2 coding sequence. Three pathogenic BRCA1 mutations (Cys61Gly, 3814del5, 5382insC) were identified in the group of patients with unilateral breast cancer. The frequencies of common BRCA1 and BRCA2 missense variants were not different between the 2 groups. In summary, we did not find a significantly increased prevalence of BRCA1 and BRCA2 mutations in a hospital-based cohort of German patients with bilateral breast cancer. We conclude that bilaterality of breast cancer on its own is not strongly associated with BRCA1 and BRCA2 mutations when adjusted for age and family history. The high frequency of bilateral disease in multi-case breast cancer families may be due to a familial aggregation of additional susceptibility factors modifying the penetrance of BRCA1 and BRCA2 mutations. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Cortisol coregulation in fish

Cortisol coregulation, which is the up- or down-regulation of partners’ physiological stress responses, has been described for individuals with strong attachment bonds, e.g. parents and their children, and romantic relationship partners. Research into moderating effects on cortisol coregulation suggests stronger covariation among distressed partners. Whether cortisol coregulation is unique to humans or can also be found in other species that share universal features of the vertebrate stress response remains unexplored. Using a repeated measures approach and non-invasive waterborne hormone analysis, we test the hypothesis that dyads of three-spined stickleback fish (Gasterosteus aculeatus) coregulate their cortisol levels in shared environments. Dyadic cortisol levels were unrelated when cohabiting (home tank), but significantly covaried when sharing a more stressful (as indicated by higher cortisol levels) environment (open field). Time-lag analysis further revealed that open field cortisol levels were predicted by partner’s cortisol levels prior to the shared experience. To our knowledge, this study provides the first evidence for coregulatory processes on cortisol responses in a non-human animal that lacks strong bonds and social attachment relationships, suggesting a shared evolutionary origin of cortisol coregulation in vertebrates. From an adaptive perspective, cortisol coregulation may serve to reduce risk in challenging, potentially threatening situations

The DESiGN trial (DEtection of Small for Gestational age Neonate), evaluating the effect of the Growth Assessment Protocol (GAP): study protocol for a randomised controlled trial.

BACKGROUND: Stillbirth rates in the United Kingdom (UK) are amongst the highest of all developed nations. The association between small-for-gestational-age (SGA) foetuses and stillbirth is well established, and observational studies suggest that improved antenatal detection of SGA babies may halve the stillbirth rate. The Growth Assessment Protocol (GAP) describes a complex intervention that includes risk assessment for SGA and screening using customised fundal-height growth charts. Increased detection of SGA from the use of GAP has been implicated in the reduction of stillbirth rates by 22%, in observational studies of UK regions where GAP uptake was high. This study will be the first randomised controlled trial examining the clinical efficacy, health economics and implementation of the GAP programme in the antenatal detection of SGA. METHODS/DESIGN: In this randomised controlled trial, clusters comprising a maternity unit (or National Health Service Trust) were randomised to either implementation of the GAP programme, or standard care. The primary outcome is the rate of antenatal ultrasound detection of SGA in infants found to be SGA at birth by both population and customised standards, as this is recognised as being the group with highest risk for perinatal morbidity and mortality. Secondary outcomes include antenatal detection of SGA by population centiles, antenatal detection of SGA by customised centiles, short-term maternal and neonatal outcomes, resource use and economic consequences, and a process evaluation of GAP implementation. Qualitative interviews will be performed to assess facilitators and barriers to implementation of GAP. DISCUSSION: This study will be the first to provide data and outcomes from a randomised controlled trial investigating the potential difference between the GAP programme compared to standard care for antenatal ultrasound detection of SGA infants. Accurate information on the performance and service provision requirements of the GAP protocol has the potential to inform national policy decisions on methods to reduce the rate of stillbirth. TRIAL REGISTRATION: Primary registry and trial identifying number: ISRCTN 67698474 . Registered on 2 November 2016