How often do we identify fetal abnormalities during routine third-trimester ultrasound? A systematic review and meta-analysis.

BACKGROUND: Routine third-trimester ultrasound is frequently offered to pregnant women to identify fetuses with abnormal growth. Infrequently, a congenital anomaly is incidentally detected. OBJECTIVE: To establish the prevalence and type of fetal anomalies detected during routine third-trimester scans using a systematic review and meta-analysis. SEARCH STRATEGY: Electronic databases (MEDLINE, Embase and the Cochrane library) from inception until August 2019. SELECTION CRITERIA: Population-based studies (randomised control trials, prospective and retrospective cohorts) reporting abnormalities detected at the routine third-trimester ultrasound performed in unselected populations with prior screening. Case reports, case series, case-control studies and reviews without original data were excluded. DATA COLLECTION AND ANALYSIS: Prevalence and type of anomalies detected in the third trimester. We calculated pooled prevalence as the number of anomalies per 1000 scans with 95% confidence intervals. Publication bias was assessed. MAIN RESULTS: The literature search identified 9594 citations: 13 studies were eligible representing 141 717 women; 643 were diagnosed with an unexpected abnormality. The pooled prevalence of a new abnormality diagnosed was 3.68 per 1000 women scanned (95% CI 2.72-4.78). The largest groups of abnormalities were urogenital (55%), central nervous system abnormalities (18%) and cardiac abnormalities (14%). CONCLUSION: Combining data from 13 studies and over 140 000 women, we show that during routine third-trimester ultrasound, an incidental fetal anomaly will be found in about 1 in 300 scanned women. This information should be taken into account when taking consent from women for third-trimester ultrasound and when designing and assessing cost of third-trimester ultrasound screening programmes. TWEETABLE ABSTRACT: One in 300 women attending a third-trimester scan will have a finding of a fetal abnormality.

Noise creates polarization artefacts.

The accuracy of calculations of both the degree and angle of polarization depend strongly on the noise in the measurements used. The noise in the measurements recorded by both camera based systems and spectrometers can lead to significant artefacts and incorrect conclusions about high degrees of polarization when in fact none exist. Three approaches are taken in this work: firstly, the absolute error introduced as a function of the signal to noise ratio for polarization measurements is quantified in detail. An important finding here is the reason for why several studies incorrectly suggest that black (low reflectivity) objects are highly polarized. The high degree of polarization is only an artefact of the noise in the calculation. Secondly, several simple steps to avoid such errors are suggested. Thirdly, if these points can not be followed, two methods are presented for mitigating the effects of noise: a maximum likelihood estimation method and a new denoising algorithm to best calculate the degree of polarization of natural polarization information.

The effects of surface structure mutations in Arabidopsis thaliana on the polarization of reflections from virus-infected leaves.

The way in which light is polarized when reflected from leaves can be affected by infection with plant viruses. This has the potential to influence viral transmission by insect vectors due to altered visual attractiveness of infected plants. The optical and topological properties of cuticular waxes and trichomes are important determinants of how light is polarized upon reflection. Changes in expression of genes involved in the formation of surface structures have also been reported following viral infection. This paper investigates the role of altered surface structures in virus-induced changes to polarization reflection from leaves. The percentage polarization of reflections from Arabidopsis thaliana cer5, cer6 and cer8 wax synthesis mutants, and the gl1 leaf hair mutant, was compared to those from wild-type (WT) leaves. The cer5 mutant leaves were less polarizing than WT on the adaxial and abaxial surfaces; gl1 leaves were more polarizing than WT on the adaxial surfaces. The cer6 and cer8 mutations did not significantly affect polarization reflection. The impacts of Turnip vein clearing virus (TVCV) infection on the polarization of reflected light were significantly affected by cer5 mutation, with the reflections from cer5 mutants being higher than those from WT leaves, suggesting that changes in CER5 expression following infection could influence the polarization of the reflections. There was, however, no significant effect of the gl1 mutation on polarization following TVCV infection. The cer5 and gl1 mutations did not affect the changes in polarization following Cucumber mosaic virus (CMV) infection. The accumulation of TVCV and CMV did not differ significantly between mutant and WT leaves, suggesting that altered expression of surface structure genes does not significantly affect viral titres, raising the possibility that if such regulatory changes have any adaptive value it may possibly be through impacts on viral transmission.

Systematic review of first-trimester ultrasound screening for detection of fetal structural anomalies and factors that affect screening performance.

OBJECTIVES: To determine the sensitivity and specificity of first-trimester ultrasound for the detection of fetal abnormalities and to establish which factors might impact on screening performance. METHODS: A systematic review and meta-analysis of all relevant publications was performed to assess the diagnostic accuracy of two-dimensional transabdominal and transvaginal ultrasound in the detection of congenital fetal anomalies prior to 14 weeks' gestation. The reference standard was detection of abnormalities at birth or postmortem. Factors that may impact on detection rates were evaluated, including population characteristics, gestational age, healthcare setting, ultrasound modality, use of an anatomical checklist for detection of first-trimester anomalies and type of malformation included in the study. In an effort to reduce the impact of study heterogeneity on the results of the meta-analysis, data from the studies were analyzed within subgroups of major anomalies vs all types of anomaly and low-risk/unselected populations vs high-risk populations. RESULTS: An electronic search (until 29 July 2015) identified 2225 relevant citations, from which a total of 30 studies, published between 1991 and 2014, were selected for inclusion. The pooled estimate for the detection of major abnormalities in low-risk or unselected populations (19 studies, 115 731 fetuses) was 46.10% (95% CI, 36.88-55.46%). The detection rate for all abnormalities in low-risk or unselected populations (14 studies, 97 976 fetuses) was 32.35% (95% CI, 22.45-43.12%), whereas in high-risk populations (six studies, 2841 fetuses) it was 61.18% (95% CI, 37.71-82.19%). Of the factors examined for their impact on detection rate, there was a statistically significant relationship (P < 0.0001) between the use of a standardized anatomical protocol during first-trimester anomaly screening and its sensitivity for the detection of fetal anomalies in all subgroups. CONCLUSIONS: Detection rates of first-trimester fetal anomalies ranged from 32% in low-risk groups to more than 60% in high-risk groups, demonstrating that first-trimester ultrasound has the potential to identify a large proportion of fetuses affected with structural anomalies. The use of a standardized anatomical protocol improves the sensitivity of first-trimester ultrasound screening for all anomalies and major anomalies in populations of varying risk. The development and introduction of international protocols with standard anatomical views should be undertaken in order to optimize first-trimester anomaly detection. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Disordered animal multilayer reflectors and the localization of light.

Multilayer optical reflectors constructed from 'stacks' of alternating layers of high and low refractive index dielectric materials are present in many animals. For example, stacks of guanine crystals with cytoplasm gaps occur within the skin and scales of fish, and stacks of protein platelets with cytoplasm gaps occur within the iridophores of cephalopods. Common to all these animal multilayer reflectors are different degrees of random variation in the thicknesses of the individual layers in the stack, ranging from highly periodic structures to strongly disordered systems. However, previous discussions of the optical effects of such thickness disorder have been made without quantitative reference to the propagation of light within the reflector. Here, we demonstrate that Anderson localization provides a general theoretical framework to explain the common coherent interference and optical properties of these biological reflectors. Firstly, we illustrate how the localization length enables the spectral properties of the reflections from more weakly disordered 'coloured' and more strongly disordered 'silvery' reflectors to be explained by the same physical process. Secondly, we show how the polarization properties of reflection can be controlled within guanine-cytoplasm reflectors, with an interplay of birefringence and thickness disorder explaining the origin of broadband polarization-insensitive reflectivity.

Non-polarizing broadband multilayer reflectors in fish.

Dielectric multilayer reflectors that are non-polarizing are an important class of optical device and have numerous applications within optical fibres [1], dielectric waveguides [2] and LEDs [3]. Here we report analyses of a biological non-polarizing optical mechanism found in the broadband guanine-cytoplasm "silver" multilayer reflectors of three species of fish. Present in the fish stratum argenteum are two populations of birefringent guanine crystal, each with their optic axes either parallel to the long axis of the crystal or perpendicular to the plane of the crystal. This arrangement neutralizes the polarization of reflection due the different interfacial Brewster's angles of each population. The fish reflective mechanism is distinct from existing non-polarizing mirror designs [4, 5, 6, 7] with the important feature that there is no refractive index contrast between the low index layers in the reflector and the external environment. It is a mechanism that could be readily manufactured and exploited in synthetic optical devices.

Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials.

AIMS/HYPOTHESIS: Observational studies suggest that metformin may reduce cancer risk by approximately one-third. We examined cancer outcomes and all-cause mortality in published randomised controlled trials (RCTs). METHODS: RCTs comparing metformin with active glucose-lowering therapy or placebo/usual care, with minimum 500 participants and 1-year follow-up, were identified by systematic review. Data on cancer incidence and all-cause mortality were obtained from publications or by contacting investigators. For two trials, cancer incidence data were not available; cancer mortality was used as a surrogate. Summary RRs, 95% CIs and I (2)statistics for heterogeneity were calculated by fixed effects meta-analysis. RESULTS: Of 4,039 abstracts identified, 94 publications described 14 eligible studies. RRs for cancer were available from 11 RCTs with 398 cancers during 51,681 person-years. RRs for all-cause mortality were available from 13 RCTs with 552 deaths during 66,447 person-years. Summary RRs for cancer outcomes in people randomised to metformin compared with any comparator were 1.02 (95% CI 0.82, 1.26) across all trials, 0.98 (95% CI 0.77, 1.23) in a subgroup analysis of active-comparator trials and 1.36 (95% CI 0.74, 2.49) in a subgroup analysis of placebo/usual care comparator trials. The summary RR for all-cause mortality was 0.94 (95% CI 0.79, 1.12) across all trials. CONCLUSIONS/INTERPRETATION: Meta-analysis of currently available RCT data does not support the hypothesis that metformin lowers cancer risk by one-third. Eligible trials also showed no significant effect of metformin on all-cause mortality. However, limitations include heterogeneous comparator types, absent cancer data from two trials, and short follow-up, especially for mortality.

Evidence for a dose effect of renin-angiotensin system inhibition on progression of microalbuminuria in Type 2 diabetes: a meta-analysis.

AIMS: Renin-angiotensin inhibitors in Type 2 diabetes and microalbuminuria reduce renal and cardiovascular risk, but evidence supporting use of maximal tolerated dose is unclear. We aimed to determine the extent of renin-angiotensin inhibitor dose-dependent effects from randomized trials carried out in a clinical setting. METHODS: In a meta-analysis of randomized clinical trials, alternate doses of angiotensin receptor blockers or angiotensin converting enzyme inhibitors in patients with Type 2 diabetes and microalbuminuria were compared. MEDLINE, EMBASE and the Cochrane Register of Controlled Trials were searched from January 2006 to August 2010. Trials prior to January 2006 were identified from a prior systematic review. Identified outcomes were albumin excretion rate, progression and regression of albuminuria and adverse events. RESULTS: Four trials including 1051 patients compared doses of angiotensin receptor blockers. No trials compared doses of angiotensin converting enzyme inhibitor. The percentage decline in albumin excretion rate from baseline was greater with higher doses (18% higher, 95% CI 8-28%), the regression to normoalbuminuria was greater (OR 1.66, 95% CI 1.22-2.27), with less progression to macroalbuminuria (OR 0.62, CI 0.38-1.02). Adverse events were fewer with lower-dose angiotensin receptor blockers (OR 1.32, 95% CI 0.90-1.92). CONCLUSIONS: Higher-dose compared with lower-dose angiotensin receptor blockers in Type 2 diabetes with microalbuminuria are associated with significantly reduced albumin excretion rate and increased regression to normoalbuminuria. Adverse events are more frequent, but not significantly so. There is potential for trials to determine clinical cardiovascular and renal outcomes at differing doses. Our findings support current recommendations to titrate renin-angiotensin inhibitors to maximum dose whilst considering risk of adverse side effects with higher doses.

A systematic review assessing the effectiveness of interventions to improve persistence with anti-resorptive therapy in women at high risk of clinical fracture.

BACKGROUND: despite availability of effective treatments for osteoporosis, impact on fracture rates may be suboptimal because of failure to adhere to recommended anti-resorptive therapy. OBJECTIVE: to identify randomized controlled trials (RCTs) evaluating interventions intended to improve persistence with anti-resorptive therapy for treating women with osteoporosis or osteopenia. The design of the study is a systematic review and meta-analysis of RCTs. METHODS: included trials were those reporting interventions to improve persistence with or adherence to anti-resorptive treatment compared to a control medication or usual care. A search of MEDLINE, EMBASE, CINAHL and the Cochrane Library was supplemented by review of cited literature. Reports were reviewed and data pooled where appropriate. The primary outcome was duration of persistence with medication. RESULTS: six trials met inclusion criteria, including four reporting persistence as an outcome measure indicating a relative reduction in non-persistence of 22% (pooled relative risk: 0.78, 95% confidence interval 0.65-0.95) for active compared to control interventions. Heterogeneity between the trial effects was present but not significant (I(2) = 47%, P = 0.11). Interventions were varied in design, and some measurements of adherence were subject to self-report bias. Two trials included the majority of participants (3386/3497), accounting for >90% of the weight in the pooled estimate. CONCLUSIONS: trials to date suggest potential for improving persistence with medication taking thus improving treatment outcomes and reducing fracture risk. More precise measurement of medication taking and promoting fidelity to a precisely defined intervention protocol may lead to better assessment of impact on clinically important outcomes.

Continuously rotating chiral liquid crystal droplets in a linearly polarized laser trap.

The transfer of optical angular momentum to birefringent particles via circularly polarized light is common. We report here on the unexpected, continuous rotation of chiral nematic liquid crystal droplets in a linearly polarized optical trap. The rotation is non-uniform, occurs over a timescale of seconds, and is observed only for very specific droplet sizes. Synchronized vertical motion of the droplet occurs during the rotation. The motion is the result of photo-induced molecular reorganization, providing a micron sized opto-mechanical transducer that twists and translates.

Deduction of the temperature-dependent structure of the four-layer intermediate smectic phase using resonant X-ray scattering.

A binary mixture of an antiferroelectric liquid-crystal material containing a selenium atom and a highly chiral dopant is investigated using resonant X-ray scattering. This mixture exhibits a remarkably wide four-layer intermediate smectic phase, the structure of which is investigated over a temperature range of 16K. Analysis of the resonant X-ray scattering data allows accurate measurement of both the helicoidal pitch and the distortion angle as a function of temperature. The former decreases rapidly as the SmC* phase is approached, whilst the latter remains constant over the temperature range studied at 8 degrees +/-3 degrees. We also observe that the senses of the helicoidal pitch and the unit cell of the repeating four-layer structure are opposite in this mixture and that there is no pitch inversion over the temperature range studied.

The optics of vertebrate photoreceptors: anisotropy and form birefringence.

The optics of vertebrate photoreceptors have been investigated with specific reference to the effect of form birefringence. The complex dielectric tensor of the lamellar-like outer segment structure has been derived, allowing the transverse spectral absorbance to be calculated for different incident polarizations. These results were used to calculate the changes in the cellular dichroic ratio as a function of both the volume occupied by the bilayers and the real and complex parts of the intrinsic birefringence of the bilayers. Physiologically realistic values of these parameters show the cellular dichroic ratio to be greater than the bilayer dichroic ratio by a factor of approximately 1.3. Furthermore, the calculations of spectral absorbance indicate that form birefringence may affect measurements of optical density in transversely orientated outer segments.

The absorption of polarized light by vertebrate photoreceptors.

A physiologically realistic model has been constructed for a theoretical study of the mechanisms by which the vertebrate visual system absorbs linearly polarized light. Using a 4 x 4 matrix technique, analytic solutions to Maxwell's equations have been deduced for rod and cone photoreceptors, allowing calculation of the absorbance as a function of wavelength for a variety of illumination geometries. With the use of experimentally measured optical parameters, the calculated absorbance spectra show excellent agreement in both magnitude and form with microspectrophotometric data. Moreover, failing to correct for the true nature of reflection or scattering in the sample, results in the elevated absorbance commonly seen at shorter wavelengths in experimental measurements. Finally, calculated dichroic ratios also accurately predict experimental results, mirroring the differences seen between rods and cones.

I-123 iofetamine SPECT scan in systemic lupus erythematosus patients with cognitive and other minor neuropsychiatric symptoms: a pilot study.

Accurate diagnosis of central nervous system (CNS) lupus remains difficult, especially when the manifestations are of subtle cognitive and affective changes. This pilot study reports on the use of I-123 iofetamine single photon emission computerized tomography (SPECT) scans in 18 such patients with documented systemic lupus erythematosus. Eight of the 18 scans were abnormal (44%), four in a diffuse bi-temporo-parietal pattern previously noted only in Alzheimer's disease, and four with large focal deficits. Neither the existence of the abnormal scan nor the particular pattern of abnormality correlated with the results of other diagnostic tests. These preliminary results raise the possibility that SPECT scans may offer an additional valuable diagnostic instrument in CNS lupus, although further studies are necessary to delineate their precise role.

A modification of the Health Assessment Questionnaire for the spondyloarthropathies.

A functional status measure was developed by adding 5 items to the Health Assessment Questionnaire (HAQ-S), and compared to anthropometric measures of spinal mobility. Forty-four patients with spondylitis were evaluated by the HAQ-S and measures of spine flexibility (finger-to-floor, Smythe test, neck rotation, and chest expansion). Modification of the HAQ raised the mean difficulty score by 29% from 0.38 (SD = 0.49) to 0.49 (SD = 0.51), indicating increased ability to capture functional limitations. Neck rotation correlated most strongly with the HAQ-S score (r = -0.57), which suggests an important role for this measure in clinical management and followup of spondylitis.