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Peter Braude and Martin Johnson were young researchers, a doctor and a scientist, working with Robert Edwards at Cambridge. They both witnessed (from the inside) how the IVF programme and first birth changed the worlds of science and O&G over the next forty years. Johnson wrote Edward’s citation for the Nobel Prize. They are uniquely placed to act as a bridge from 1979 into speculating about the future and whether the course of science can even be predicted.
To determine the safety and feasibility of over-expansion of right ventricle to pulmonary artery conduits during transcatheter pulmonary valve placement.
Background:
Transcatheter pulmonary valve placement is an alternative to surgical pulmonary valve replacement. Traditionally, it was thought to be unsafe to expand a conduit to >110% of its original size.
Methods:
This retrospective cohort study from two centers includes patients with right ventricle to pulmonary artery conduits with attempted transcatheter pulmonary valve placement from 2010 to 2017. Demographic, procedural, echocardiographic and follow-up data, and complications were evaluated in control and overdilation (to >110% original conduit size) groups.
Results:
One hundred and seventy-two patients (51 overdilation and 121 control) had attempted transcatheter pulmonary valve placement (98% successful). The overdilation group was younger (11.2 versus 16.7 years, p < 0.001) with smaller conduits (15 versus 22 mm, p < 0.001); however, the final valve size was not significantly different (19.7 versus 20.2 mm, p = 0.2). Baseline peak echocardiographic gradient was no different (51.8 versus 55.6 mmHg, p = 0.3). Procedural complications were more frequent in overdilation (18%) than control (7%) groups (most successfully addressed during the procedure). One patient from each group required urgent surgical intervention, with no procedural mortality. Follow-up echocardiographic peak gradients were similar (24.1 versus 26 mmHg, p = 0.5).
Conclusions:
Over-expansion of right ventricle to pulmonary artery conduits during transcatheter pulmonary valve placement can be performed successfully. Procedural complications are more frequent with conduit overdilation, but there was no difference in the rate of life-threatening complications. There was no difference in valve function at most recent follow-up, and no difference in rate of reintervention. The long-term outcomes of transcatheter pulmonary valve placement with conduit over-expansion requires further study.
Anorexia nervosa (AN) is a psychiatric disorder with complex etiology, with a significant portion of disease risk imparted by genetics. Traditional genome-wide association studies (GWAS) produce principal evidence for the association of genetic variants with disease. Transcriptomic imputation (TI) allows for the translation of those variants into regulatory mechanisms, which can then be used to assess the functional outcome of genetically regulated gene expression (GReX) in a broader setting through the use of phenome-wide association studies (pheWASs) in large and diverse clinical biobank populations with electronic health record phenotypes.
Methods
Here, we applied TI using S-PrediXcan to translate the most recent PGC-ED AN GWAS findings into AN-GReX. For significant genes, we imputed AN-GReX in the Mount Sinai BioMe™ Biobank and performed pheWASs on over 2000 outcomes to test the clinical consequences of aberrant expression of these genes. We performed a secondary analysis to assess the impact of body mass index (BMI) and sex on AN-GReX clinical associations.
Results
Our S-PrediXcan analysis identified 53 genes associated with AN, including what is, to our knowledge, the first-genetic association of AN with the major histocompatibility complex. AN-GReX was associated with autoimmune, metabolic, and gastrointestinal diagnoses in our biobank cohort, as well as measures of cholesterol, medications, substance use, and pain. Additionally, our analyses showed moderation of AN-GReX associations with measures of cholesterol and substance use by BMI, and moderation of AN-GReX associations with celiac disease by sex.
Conclusions
Our BMI-stratified results provide potential avenues of functional mechanism for AN-genes to investigate further.
Rapid whole genome sequencing (rapid WGS) is a powerful diagnostic tool that is becoming increasingly practical for widespread clinical use. However, protocols for its use are challenging to implement. A significant obstacle to clinical adoption is that laboratory certification requires an initial research development phase, which is constrained by regulations from returning results. Regulations preventing return of results have ethical implications in cases which might impact patient outcomes. Here, we describe our experience with the development of a rapid WGS research protocol, that balanced the requirements for laboratory-validated test development with the ethical needs of clinically relevant return of results.
The limitations of self-report measures of dietary intake are well-known. Novel, technology-based measures of dietary intake may provide a more accurate, less burdensome alternative to existing tools. The first objective of this study was to compare participant burden for two technology-based measures of dietary intake among school-age children: the Automated-Self-Administered 24-hour Dietary Assessment Tool-2018 (ASA24-2018) and the Remote Food Photography Method (RFPM). The second objective was to compare reported energy intake for each method to the Estimated Energy Requirement for each child, as a benchmark for actual intake. Forty parent–child dyads participated in two, 3-d dietary assessments: a parent proxy-reported version of the ASA24 and the RFPM. A parent survey was subsequently administered to compare satisfaction, ease of use and burden with each method. A linear mixed model examined differences in total daily energy intake between assessments, and between each assessment method and the Estimated Energy Requirement (EER). Reported energy intake was 379 kcal higher with the ASA24 than the RFPM (P = 0·0002). Reported energy intake with the ASA24 was 231 kcal higher than the EER (P = 0·008). Reported energy intake with the RFPM did not differ significantly from the EER (difference in predicted means = −148 kcal, P = 0·09). Median satisfaction and ease of use scores were five out of six for both methods. A higher proportion of parents reported that the ASA24 was more time-consuming than the RFPM (74·4 % v. 25·6 %, P = 0·002). Utilisation of both methods is warranted given their high satisfaction among parents.
Twin studies function as natural experiments that reveal political ideology’s substantial genetic roots, but how does that comport with research showing a largely nonideological public? This study integrates two important literatures and tests whether political sophistication – itself heritable – provides an “enriched environment” for genetic predispositions to actualize in political attitudes. Estimates from the Minnesota Twin Study show that sociopolitical conservatism is extraordinarily heritable (74%) for the most informed fifth of the public – much more so than population-level results (57%) – but with much lower heritability (29%) for the public’s bottom half. This heterogeneity is clearest in the Wilson–Patterson (W-P) index, with similar patterns for individual index items, an ideological constraint measure, and ideological identification. The results resolve tensions between two key fields by showing that political knowledge facilitates the expression of genetic predispositions in mass politics.
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
Methods
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
Results
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
Conclusions
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
The rocky shores of the north-east Atlantic have been long studied. Our focus is from Gibraltar to Norway plus the Azores and Iceland. Phylogeographic processes shape biogeographic patterns of biodiversity. Long-term and broadscale studies have shown the responses of biota to past climate fluctuations and more recent anthropogenic climate change. Inter- and intra-specific species interactions along sharp local environmental gradients shape distributions and community structure and hence ecosystem functioning. Shifts in domination by fucoids in shelter to barnacles/mussels in exposure are mediated by grazing by patellid limpets. Further south fucoids become increasingly rare, with species disappearing or restricted to estuarine refuges, caused by greater desiccation and grazing pressure. Mesoscale processes influence bottom-up nutrient forcing and larval supply, hence affecting species abundance and distribution, and can be proximate factors setting range edges (e.g., the English Channel, the Iberian Peninsula). Impacts of invasive non-native species are reviewed. Knowledge gaps such as the work on rockpools and host–parasite dynamics are also outlined.
Centenarians have survived into very late life, but whether they reach very old age in good health remains unclear. The purpose of this study was to compare the cardiovascular health status and cognitive functioning of centenarians in the United States with centenarians in Japan.
Design, Setting, and Participants:
This cross-national design compared centenarians from the United States and Japan. The sample of U.S. centenarians was recruited from the Georgia Centenarian Study and included 287 centenarians. The sample of Japanese centenarians was recruited from the Tokyo Centenarian Study and included 304 centenarians.
Measurements:
Cognitive functioning was assessed with a mental status questionnaire, and cardiovascular disease by a health history assessment, blood pressure, and selected blood parameters.
Results:
The results suggest that Tokyo centenarians had lower disease experiences and BMI values, when compared to Georgia centenarians, but blood pressure was higher among Japanese centenarians. Lower levels of hemoglobin in Japanese centenarians and higher levels of C-reactive protein in Georgia were also found. The positive association of hypertension and albumin levels with cognitive functioning and the negative association of stroke occurrence with cognitive functioning were replicated in both countries. Differential effects were obtained for heart problems, BMI, and C-reactive protein (with positive effects for Tokyo centenarians, except for C-reactive protein).
Conclusion:
For extremely old individuals, some markers of cardiovascular disease are replicable across countries, whereas differential effects for cardiovascular health also need to be considered in cardiovascular health.
Regulating reproduction has involved far more than the law, but modern legal systems defined the bourgeois family and brought reproduction within an official framework, while disciplinary norms have operated in part through formal regulation. This chapter reviews some roles of law in reproduction since around 1800, mainly for the United Kingdom and the United States with their emphasis—influential through the British Empire—on common law rather than civil codes. With the focus on contraception, sterilization and abortion, on the one hand, and assisted conception, on the other, we review the expansion of the state and the medical profession into the market, especially through nineteenth-century anti-abortion and obscenity legislation, notably the Offences Against the Person Act 1861 and the Comstock laws; the reforms of the 1960s and 1970s, particularly those leading to the 1967 Abortion Act and Roe v. Wade (1973), that critiqued state control and medical authority, but also drew on agendas for change within the professions and sometimes strengthened medical power; and the rise of arms-length regulation of in vitro fertilization, donor insemination and other techniques of assisted conception, notably through the UK Human Fertilisation and Embryology Authority—in marked contrast to the largely unregulated US.
The goal of this study was to perform in situ electrochemical polymerization of poly(3,4-ethylenedioxythiophene) (PEDOT) in peripheral nerves to create a soft, precisely located injectable conductive polymer electrode for bi-directional communication. Intraneural PEDOT polymerization was performed to target both outer and inner fascicles via custom fabricated 3D printed cuff electrodes and monomer injection strategies using a combination electrode-cannula system. Electrochemistry, histology, and laser light sheet microscopy revealed the presence of PEDOT at specified locations inside of peripheral nerve. This work demonstrates the potential for using in situ PEDOT electrodeposition as an injectable electrode for recording and stimulation of peripheral nerves.
The ability to interface electronic materials with the peripheral nervous system is required for stimulation and monitoring of neural signals. Thus, the design and engineering of robust neural interfaces that maintain material-tissue contact in the presence of material or tissue micromotion offer the potential to conduct novel measurements and develop future therapies that require chronic interface with the peripheral nervous system. However, such remains an open challenge given the constraints of existing materials sets and manufacturing approaches for design and fabrication of neural interfaces. Here, we investigated the potential to leverage a rapid prototyping approach for the design and fabrication of nerve cuffs that contain supporting features to mechanically stabilize the interaction between cuff electrodes and peripheral nerve. A hybrid 3D printing and robotic-embedding (i.e., pick-and-place) system was used to design and fabricate silicone nerve cuffs (800 µm diameter) containing conforming platinum (Pt) electrodes. We demonstrate that the electrical impedance of the cuff electrodes can be reduced by deposition of the conducting polymer poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) on cuff electrodes via a post-processing electropolymerization technique. The computer-aided design and manufacturing approach was also used to design and integrate supporting features to the cuff that mechanically stabilize the interface between the cuff electrodes and the peripheral nerve. Both ‘self-locking’ and suture-assisted locking mechanisms are demonstrated based on the principle of making geometric alterations to the cuff opening via 3D printing. Ultimately, this work shows 3D printing offers considerable opportunity to integrate supporting features, and potentially even novel electronic materials, into nerve cuffs that can support the design and engineering of next generation neural interfaces.
Healthy adults (n 30) participated in a placebo-controlled, randomised, double-blinded, cross-over study consisting of two 28 d treatments (β2-1 fructan or maltodextrin; 3×5 g/d) separated by a 14-d washout. Subjects provided 1 d faecal collections at days 0 and 28 of each treatment. The ability of faecal bacteria to metabolise β2-1 fructan was common; eighty-seven species (thirty genera, and four phyla) were isolated using anaerobic medium containing β2-1 fructan as the sole carbohydrate source. β2-1 fructan altered the faecal community as determined through analysis of terminal restriction fragment length polymorphisms and 16S rRNA genes. Supplementation with β2-1 fructan reduced faecal community richness, and two patterns of community change were observed. In most subjects, β2-1 fructan reduced the content of phylotypes aligning within the Bacteroides, whereas increasing those aligning within bifidobacteria, Faecalibacterium and the family Lachnospiraceae. In the remaining subjects, supplementation increased the abundance of Bacteroidetes and to a lesser extent bifidobacteria, accompanied by decreases within the Faecalibacterium and family Lachnospiraceae. β2-1 Fructan had no impact on the metagenome or glycoside hydrolase profiles in faeces from four subjects. Few relationships were found between the faecal bacterial community and various host parameters; Bacteroidetes content correlated with faecal propionate, subjects whose faecal community contained higher Bacteroidetes produced more caproic acid independent of treatment, and subjects having lower faecal Bacteroidetes exhibited increased concentrations of serum lipopolysaccharide and lipopolysaccharide binding protein independent of treatment. We found no evidence to support a defined health benefit for the use of β2-1 fructans in healthy subjects.
Intensive field surveys were conducted in eastern Nebraska to determine the frequency distribution model and associated parameters of broadleaf and grass weed seedling populations. The negative binomial distribution consistently fit the data over time (1992 to 1993) and space (fields) for both the inter and intrarow broadleaf and grass weed seedling populations. The other distributions tested (Poisson with zeros, Neyman type A, logarithmic with zeros, and Poisson-binomial) did not fit the data as consistently as the negative binomial distribution. Associated with the negative binomial distribution is a k parameter. k is a nonspatial aggregation parameter related to the variance at a given mean value. The k parameter of the negative binomial distribution was consistent across weed density for individual weed species in a given field except for foxtail spp. populations. Stability of the k parameter across field sites was assessed using the likelihood ratio test There was no stable or common k value across field sites and years for all weed species populations. The lack of stability in k across field sites is of concern, because this parameter is used extensively in the development of parametric sequential sampling procedures. Because k is not stable across field sites, k must be estimated at the time of sampling. Understanding the variability in it is critical to the development of parametric sequential sampling strategies and understanding the dynamics of weed species in the field.
An intensive survey of two farmer-managed corn and soybean fields in eastern Nebraska was conducted to investigate parametric sequential sampling of weed seedling populations using a multistage procedure to estimate k, of the negative binomial distribution. k is a nonspatial aggregation parameter related to the variance at a given mean value. Mean weed seedling density ranged from 0.18 to 3.11 plants 0.38 m−2 (linear meter of crop row) based on 806 sampling locations. The average value of k, derived from 200 multistage estimation procedures, ranged from 0.17 to 0.32. A sequential sampling plan was developed with the goal of estimating the mean with a coefficient of variation (CV) of 10, 20, 30, and 40% of the sample mean. A sampling plan was also constructed to estimate the mean within a specified distance H of the true mean (H(x̄)= 0.10, 0.50 and 1.0 plants 0.38 m−2) with 80, 85, and 90% confidence. Estimating mean weed seedling density within a specified CV of the true mean CV(x̄) using parametric sequential sampling techniques was superior to estimating the mean within a specified distance (H(x̄)) of the true mean when considering the frequency of sampling and probability of error, especially at intermediate k values. At a k: value of 0.32 and 0.25, the difference between the actual CV(x̄) obtained from sampling and the CV(x̄) specified by the sampler was minimal. However, the accuracy of weed seedling density estimates was reduced with decreasing k values below 0.25, especially as the specified CV(x̄) increased.
Reports of unacceptable shattercane (Sorghum bicolor) control with acetolactate synthase (ALS)-inhibiting herbicides prompted the investigation of 29 fields in central and south-central Nebraska for ALS-resistant (ALSr) shattercane. These fields were located in three distinct geographical areas designated C, G, and P. Shattercane from 13 fields spanning all three areas was resistant to 80 g ai ha−1 (2 X field rate) primisulfuron. Accessions C and G were more resistant than accession P to primisulfuron and nicosulfuron. Accessions C and G were susceptible to imazethapyr, whereas accession P was resistant. The ALS resistance was associated with alterations in the ALS enzyme. Primisulfuron I50 values for ALS from ROX (forage sorghum), C, G, and P were 7, 8,510, 8,870, and 714 nM, respectively; nicosulfuron I50 values were 647, 4,110, 4,070, and 1,460 nM, respectively; and imazethapyr I50 values were 5,440, 13,100, 11,800, and 51,700 nM, respectively. Based on cross-resistance and enzyme sensitivities, at least two biotypes are represented in the three accessions of ALSr shattercane. Shattercane individuals from accessions C, G, and P were intercrossed to determine if the ALSr genes in each of the accessions were at independent loci. All the F2 populations were resistant to 80 g ai ha−1 primisulfuron, suggesting that the ALSr alleles in the three accessions are at the same locus or possibly linked loci. When the C, G, and P accessions were crossed with the wild type (WT), comparisons between the F1, susceptible, and resistant populations showed that primisulfuron resistance was expressed as a dominant, partially dominant, and additive trait for the C, G, and P accessions, respectively. The differences in ALSr allelic interactions indicate that primisulfuron resistance developed independently in each of the three accessions.
The ability to accurately estimate herbicide efficacy is critical for any decision-support system used in weed management. Recent efforts by weed scientists in the North Central United States to adopt WeedSOFT across a broad region have resulted in a number of regional research projects designed to assess and improve the predictive capability of WeedSOFT. Field studies were conducted from 2000 to 2002 in Nebraska, Missouri, and Illinois to evaluate herbicide-efficacy predictions made by WeedSOFT in two corn-row spacings. Following crop and weed emergence, input variables, such as weed densities and heights, were entered into WeedSOFT to generate a list of treatments ranked by predicted crop yields. The five treatments evaluated included those predicting highest crop-yield potential (recommended control treatment 1), a 10% yield reduction, a 20% yield reduction, a 10% yield reduction plus cultivation, and cultivation alone. These treatments were applied to corn grown in 38- and 76-cm rows. Generally, treatments applied in 38-cm rows had more accurate herbicide-efficacy predictions compared with 76-cm rows. WeedSOFT provided better control predictions for broadleaf than grass species. WeedSOFT provided excellent herbicide-efficacy predictions for the highest crop-yield potential, which indicates a good potential for practical use of this software for herbicide recommendations.