Early land plant remains from the uppermost Ordovician–?lowermost Silurian Cedarberg Formation of South Africa

The Cape Supergroup forms a regionally extensive and extremely thick Ordovician to Carboniferous succession of sedimentary rocks in southwestern South Africa. It includes the LowerâMiddle Ordovicianâlowermost Devonian Table Mountain Group, which incorporates the uppermost Ordovician Soom Shale Lagerstätte (within the Cedarberg Formation). The Soom Shale Lagerstätte accumulated in an unusual cold-water setting, associated with the decaying South African ice sheet, towards the end of the Hirnantian glaciation. The deposits of this glacial marine environment, characterised by anoxic bottom waters, preserve a highly unusual marine biota. It includes specimens exhibiting exceptional preservation of their soft tissues in clay minerals. Overlying deposits of the Soom Shale are shales and thin sandstones ascribed to the Disa Member that accumulated in a shoreface-shelf setting. Associated with these deposits are relict Soom taxa, in addition to a handful of Clarkeia-type brachiopod faunas, suggesting a probable earliest Silurian age for the upper part of the Cedarberg Formation. Previous palynological investigations of the Soom Shale have yielded typical marine elements, including chitinozoans, scolecodonts and rare acritarchs, but also common terrestrial elements in the form of dispersed spore tetrads. The latter are historically important as they represent an early report, by Jane Gray and colleagues, of dispersed cryptospore tetrads and were the first evidence for early land plants from Africa south of the Sahara (Ordovician eastern Gondwana at 30Ë S). Herein we report on a palynological investigation of an exposure of the Cedarberg Formation from the northernmost outcrops of the Cape Supergroup at Matjiesgoedkloof, Western Cape Province. Recently the sedimentology and ichnology of the underlying ice-marginal shallow-marine deposits of the Pakhuis Formation were described. Although macrofossils have not been recovered from these strata, they yield a fascinating ichnofauna that is diverse and disparate, comprising trackways and burrows. These show colonisation of glacial deposits by makers of burrows and trackways that lived in brackish water conditions as ice sheets retreated. Our palynological investigation yielded assemblages of abundant and well-preserved palynomorphs. Although of moderateâhigh thermal maturity, they are much less coalified than palynomorphs from the more southerly exposures. Surprisingly, the assemblages are dominated by land plant spores with extremely rare, if any, marine palynomorphs. This may be a consequence of high freshwater influx from the decaying ice sheetâs glaciers excluding normal marine biota (although the ichnological evidence demonstrates the presence of at least some organisms). The dispersed spore assemblage is somewhat unusual in that it is dominated by tetrads to the exclusion of monads and dyads. Coeval assemblages from similar palaeolatitudes in Gondwana (e.g. from the Arabian Plate) are far more diverse. This possibly reflects the close proximity of the vegetation to the ice sheet

CpG Island microarray probe sequences derived from a physical library are representative of CpG Islands annotated on the human genome

An effective tool for the global analysis of both DNA methylation status and protein–chromatin interactions is a microarray constructed with sequences containing regulatory elements. One type of array suited for this purpose takes advantage of the strong association between CpG Islands (CGIs) and gene regulatory regions. We have obtained 20 736 clones from a CGI Library and used these to construct CGI arrays. The utility of this library requires proper annotation and assessment of the clones, including CpG content, genomic origin and proximity to neighboring genes. Alignment of clone sequences to the human genome (UCSC hg17) identified 9595 distinct genomic loci; 64% were defined by a single clone while the remaining 36% were represented by multiple, redundant clones. Approximately 68% of the loci were located near a transcription start site. The distribution of these loci covered all 23 chromosomes, with 63% overlapping a bioinformatically identified CGI. The high representation of genomic CGI in this rich collection of clones supports the utilization of microarrays produced with this library for the study of global epigenetic mechanisms and protein–chromatin interactions. A browsable database is available on-line to facilitate exploration of the CGIs in this library and their association with annotated genes or promoter elements

Social class origin and assortative mating in Britain, 1949-2010

This article examines trends in assortative mating in Britain over the last 60 years. Assortative mating is the tendency for like to form a conjugal partnership with like. Our focus is on the association between the social class origins of the partners. The propensity towards assortative mating is taken as an index of the openness of society which we regard as a macro level aspect of social inequality. There is some evidence that the propensity for partners to come from similar class backgrounds declined during the 1960s. Thereafter, there was a period of 40 years of remarkable stability during which the propensity towards assortative mating fluctuated trendlessly within quite narrow limits. This picture of stability over time in social openness parallels the well-established facts about intergenerational social class mobility in Britain

The Lost Library of Anne Conway

The philosopher Anne Conway (1631-1679) owned a large library, and her reading and book ownership shaped her intellectual life in distinctive ways. Until now, however, almost nothing has been known about the details of her reading or her book collection. Current scholarship assumes that her library, like that of her husband, the third Viscount Conway (c. 1623–1683), was lost or dispersed after her death. This article presents previously unrecognised evidence of Conway’s book ownership, and identifies, for the first time, the only books currently known to survive from her personal library. It traces their path to their current location in the Old Library of Jesus College, Cambridge, through the library of the soldier, book collector, and Cambridge Fellow Francis Sterling (c. 1652-1692). The article demonstrates that the newly identified books reveal previously unknown patterns of intellectual exchange amongst Conway’s family, and argues that they have significant implications for our understanding of her early intellectual development

Impact of Upadacitinib on laboratory parameters and related adverse events in patients with RA: Integrated data up to 6.5 years

Introduction: Upadacitinib (UPA) is a Janus kinase inhibitor that has demonstrated efficacy in moderate-to-severe rheumatoid arthritis (RA) with an acceptable safety profile. We investigated laboratory parameter changes in UPA RA clinical trials. Methods: Pooled data from six randomized trials in the SELECT phase 3 program were included. Key laboratory parameters and safety data were measured for UPA 15 and 30 mg once daily (QD), adalimumab (ADA) 40 mg every other week + methotrexate (MTX), and MTX monotherapy. Exposure-adjusted event rates (EAERs) of adverse events were calculated. Results: A total of 3209 patients receiving UPA 15 mg QD (10 782.7 patient-years [PY]), 1204 patients receiving UPA 30 mg QD (3162.5 PY), 579 patients receiving ADA + MTX (1573.2 PY), and 314 patients receiving MTX monotherapy (865.1 PY) were included, representing up to 6.5 years of total exposure. Decreases in mean levels of hemoglobin, neutrophils, and lymphocytes, and increases in mean levels of liver enzymes and creatinine phosphokinase were observed with UPA, with grade 3 or 4 changes observed in some patients. Mean low- and high-density lipoprotein cholesterol ratios remained stable for patients receiving UPA 15 mg QD. EAERs of anemia and neutropenia occurred at generally consistent rates between UPA and active comparators (3.1–4.3 and 1.7–5.0 events [E]/100 PY across treatment groups, respectively). Rates of hepatic disorder were higher with MTX monotherapy, UPA 15 mg and UPA 30 mg (10.8, 9.7, and 11.0 E/100 PY, respectively) versus ADA + MTX (6.4 E/100 PY). Rates of lymphopenia were highest with MTX monotherapy (3.2 E/100 PY). Treatment discontinuations due to laboratory-related events were rare, occurring in 1.1% and 2.2% of patients treated with UPA 15 and 30 mg QD, respectively. Conclusions: The results of this integrated long-term analysis of laboratory parameters continue to support an acceptable safety profile of UPA 15 mg QD for moderate-to-severe RA

The community-based prevention of diabetes (ComPoD) study: A randomised, waiting list controlled trial of a voluntary sector-led diabetes prevention programme

© 2019 The Author(s). Objective: This two-site randomised trial compared the effectiveness of a voluntary sector-led, community-based diabetes prevention programme to a waiting-list control group at 6 months, and included an observational follow-up of the intervention arm to 12 months. Methods: Adults aged 18-75 years at increased risk of developing type 2 diabetes due to elevated blood glucose and being overweight were recruited from primary care practices at two UK sites, with data collected in participants' homes or community venues. Participants were randomised using an online central allocation service. The intervention, comprising the prototype "Living Well, Taking Control" (LWTC) programme, involved four weekly two-hour group sessions held in local community venues to promote changes in diet and physical activity, plus planned follow-up contacts at two, three, six, nine and 12 months alongside 5 hours of additional activities/classes. Waiting list controls received usual care for 6 months before accessing the programme. The primary outcome was weight loss at 6 months. Secondary outcomes included glycated haemoglobin (HbA1c), blood pressure, physical activity, diet, health status and well-being. Only researchers conducting analyses were blinded. Results: The target sample of 314 participants (157 each arm) was largely representative of local populations, including 44% men, 26% from ethnic minorities and 33% living in deprived areas. Primary outcome data were available for 285 (91%) participants (141 intervention, 144 control). Between baseline and 6 months, intervention participants on average lost more weight than controls (- 1.7 kg, 95% CI - 2.59 to - 0.85). Higher attendance was associated with greater weight loss (- 3.0 kg, 95% CI - 4.5 to - 1.5). The prototype LWTC programme more than doubled the proportion of participants losing > 5% of their body weight (21% intervention vs. 8% control, OR 2.83, 95% CI 1.36 to 5.90) and improved self-reported dietary behaviour and health status. There were no impacts on HbA1c, blood pressure, physical activity and well-being at 6 months and, amongst intervention participants, few further changes from six to 12-months (e.g. average weight re-gain 0.36 kg, 95% CI - 0.20 to 0.91). There were no serious adverse events but four exercise-related injuries were reported in the intervention arm. Conclusions: This voluntary sector-led diabetes prevention programme reached a broad spectrum of the population and had modest effects on weight-related outcomes, but limited impacts on other diabetes risk factors. Trial registration: Trial registration number: ISRCTN70221670, 5 September 2014 Funder (National Institute for Health Research School for Public Health Research) project reference number: SPHR-EXE-PES-COM

Extensive microbial and functional diversity within the chicken cecal microbiome

Chickens are major source of food and protein worldwide. Feed conversion and the health of chickens relies on the largely unexplored complex microbial community that inhabits the chicken gut, including the ceca. We have carried out deep microbial community profiling of the microbiota in twenty cecal samples via 16S rRNA gene sequences and an in-depth metagenomics analysis of a single cecal microbiota. We recovered 699 phylotypes, over half of which appear to represent previously unknown species. We obtained 648,251 environmental gene tags (EGTs), the majority of which represent new species. These were binned into over two-dozen draft genomes, which included Campylobacter jejuni and Helicobacter pullorum. We found numerous polysaccharide- and oligosaccharide-degrading enzymes encoding within the metagenome, some of which appeared to be part of polysaccharide utilization systems with genetic evidence for the co-ordination of polysaccharide degradation with sugar transport and utilization. The cecal metagenome encodes several fermentation pathways leading to the production of short-chain fatty acids, including some with novel features. We found a dozen uptake hydrogenases encoded in the metagenome and speculate that these provide major hydrogen sinks within this microbial community and might explain the high abundance of several genera within this microbiome, including Campylobacter, Helicobacter and Megamonas

Developing and pre-testing a decision board to facilitate informed choice about delivery approach in uncomplicated pregnancy

<p>Abstract</p> <p>Background</p> <p>The rate of caesarean sections is increasing worldwide, yet medical literature informing women with uncomplicated pregnancies about relative risks and benefits of elective caesarean section (CS) compared with vaginal delivery (VD) remains scarce. A decision board may address this gap, providing systematic evidence-based information so that patients can more fully understand their treatment options. The objective of our study was to design and pre-test a decision board to guide clinical discussions and enhance informed decision-making related to delivery approach (CS or VD) in uncomplicated pregnancy.</p> <p>Methods</p> <p>Development of the decision board involved two preliminary studies to determine women's preferred mode of risk presentation and a systematic literature review for the most comprehensive presentation of medical risks at the time (VD and CS). Forty women were recruited to pre-test the tool. Eligible subjects were of childbearing age (18-40 years) but were not pregnant in order to avoid raising the expectation among pregnant women that CS was a universally available birth option. Women selected their preferred delivery approach and completed the Decisional Conflict Scale to measure decisional uncertainty before and after reviewing the decision board. They also answered open-ended questions reflecting what they had learned, whether or not the information had helped them to choose between birth methods, and additional information that should be included. Descriptive statistics were used to analyse sample characteristics and women's choice of delivery approach pre/post decision board. Change in decisional conflict was measured using Wilcoxon's sign rank test for each of the three subscales.</p> <p>Results</p> <p>The majority of women reported that they had learned something new (n = 37, 92%) and that the tool had helped them make a hypothetical choice between delivery approaches (n = 34, 85%). Women wanted more information about neonatal risks and personal experiences. Decisional uncertainty decreased (p < 0.001) and perceived effectiveness of decisions increased (p < 0.001) post-intervention.</p> <p>Conclusion</p> <p>Non-pregnant women of childbearing age were positive about the decision board and stated their hypothetical delivery choices were informed by risk presentation, but wanted additional information about benefits and experiences. This study represents a preliminary but integral step towards ensuring women considering delivery approaches in uncomplicated pregnancies are fully informed.</p

Supplement: "Localization and broadband follow-up of the gravitational-wave transient GW150914" (2016, ApJL, 826, L13)

This Supplement provides supporting material for Abbott et al. (2016a). We briefly summarize past electromagnetic (EM) follow-up efforts as well as the organization and policy of the current EM follow-up program. We compare the four probability sky maps produced for the gravitational-wave transient GW150914, and provide additional details of the EM follow-up observations that were performed in the different bands