Developing an intervention to facilitate family communication about inherited genetic conditions, and training genetic counsellors in its delivery.

Many families experience difficulty in talking about an inherited genetic condition that affects one or more of them. There have now been a number of studies identifying the issues in detail, however few have developed interventions to assist families. The SPRinG collaborative have used the UK Medical Research Council's guidance on Developing and Evaluating Complex Interventions, to work with families and genetic counsellors (GCs) to co-design a psycho-educational intervention to facilitate family communication and promote better coping and adaptation to living with an inherited genetic condition for parents and their children (<18 years). The intervention is modelled on multi-family discussion groups (MFDGs) used in psychiatric settings. The MFDG was developed and tested over three phases. First focus groups with parents, young people, children and health professionals discussed whether MFDG was acceptable and proposed a suitable design. Using evidence and focus group data, the intervention and a training manual were developed and three GCs were trained in its delivery. Finally, a prototype MFDG was led by a family therapist and co-facilitated by the three GCs. Data analysis showed that families attending the focus groups and intervention thought MFDG highly beneficial, and the pilot sessions had a significant impact on their family' functioning. We also demonstrated that it is possible to train GCs to deliver the MFDG intervention. Further studies are now required to test the feasibility of undertaking a definitive randomised controlled trial to evaluate its effectiveness in improving family outcomes before implementing into genetic counselling practice.The National Institute of Health Research funded the study but any views expressed do not necessarily reflect those of the Authority. Funded by NIHR reference number: RP-DG-1211-10015

Endoluminal surface registration for CT colonography using Haustral Fold Matching

Computed Tomographic (CT) colonography is a technique used for the detection of bowel cancer or potentially precancerous polyps. The procedure is performed routinely with the patient both prone and supine to differentiate fixed colonic pathology from mobile faecal residue. Matching corresponding locations is difficult and time consuming for radiologists due to colonic deformations that occur during patient repositioning. We propose a novel method to establish correspondence between the two acquisitions automatically. The problem is first simplified by detecting haustral folds using a graph cut method applied to a curvature-based metric applied to a surface mesh generated from segmentation of the colonic lumen. A virtual camera is used to create a set of images that provide a metric for matching pairs of folds between the prone and supine acquisitions. Image patches are generated at the fold positions using depth map renderings of the endoluminal surface and optimised by performing a virtual camera registration over a restricted set of degrees of freedom. The intensity difference between image pairs, along with additional neighbourhood information to enforce geometric constraints over a 2D parameterisation of the 3D space, are used as unary and pair-wise costs respectively, and included in a Markov Random Field (MRF) model to estimate the maximum a-posteriori fold labelling assignment. The method achieved fold matching accuracy of 96.0% and 96.1% in patient cases with and without local colonic collapse. Moreover, it improved upon an existing surface-based registration algorithm by providing an initialisation. The set of landmark correspondences is used to non-rigidly transform a 2D source image derived from a conformal mapping process on the 3D endoluminal surface mesh. This achieves full surface correspondence between prone and supine views and can be further refined with an intensity based registration showing a statistically significant improvement (p<0.001p<0.001), and decreasing mean error from 11.9mm11.9mm to 6.0mm6.0mm measured at 1743 reference points from 17 CTC datasets

Alkali environments in tellurite glasses

Neutron diffraction measurements are reported for five binary alkali tellurite glasses, xM2O · (100 − x)TeO2 (containing 10 and 20 mol% K2O, 10 and 19 mol% Na2O, and 20 mol% 7Li2O), together with 23Na MAS NMR measurements for the sodium containing glasses. Differences between neutron correlation functions are used to extract information about the local environments of lithium and sodium. The Na–O bond length is 2.37(1) Å and the average Na–O coordination number, nNaO, decreases from 5.2(2) for x = 10 mol% Na2O to 4.6(1) for x = 19 mol% Na2O. The average Li–O coordination number, nLiO, is 3.9(1) for the glass with x = 20 mol% Li2O and the Li–O bond length is 2.078(2) Å. As x increases from 10 to 19 mol% Na2O, the 23Na MAS NMR peak moves downfield, confirming an earlier report of a correlation of peak position with sodium coordination number. The close agreement of the maximum in the Te–O bond distribution for sodium and potassium tellurite glasses of the same composition, coupled with the extraction of reasonable alkali coordination numbers using isostoichiometric differences, gives strong evidence that the tellurium environment in alkali tellurites is independent of the size of the modifier cation used

Gender Gap in Parental Leave Intentions: Evidence from 37 Countries

Despite global commitments and efforts, a gender-based division of paid and unpaid work persists. To identify how psychological factors, national policies, and the broader sociocultural context contribute to this inequality, we assessed parental-leave intentions in young adults (18–30 years old) planning to have children (N = 13,942; 8,880 identified as women; 5,062 identified as men) across 37 countries that varied in parental-leave policies and societal gender equality. In all countries, women intended to take longer leave than men. National parental-leave policies and women’s political representation partially explained cross-national variations in the gender gap. Gender gaps in leave intentions were paradoxically larger in countries with more gender-egalitarian parental-leave policies (i.e., longer leave available to both fathers and mothers). Interestingly, this cross-national variation in the gender gap was driven by cross-national variations in women’s (rather than men’s) leave intentions. Financially generous leave and gender-egalitarian policies (linked to men’s higher uptake in prior research) were not associated with leave intentions in men. Rather, men’s leave intentions were related to their individual gender attitudes. Leave intentions were inversely related to career ambitions. The potential for existing policies to foster gender equality in paid and unpaid work is discussed.Gender Gap in Parental Leave Intentions: Evidence from 37 CountriespublishedVersio

Gender Gap in Parental Leave Intentions: Evidence from 37 Countries

Despite global commitments and efforts, a gender-based division of paid and unpaid work persists. To identify how psychological factors, national policies, and the broader sociocultural context contribute to this inequality, we assessed parental-leave intentions in young adults (18–30 years old) planning to have children (N = 13,942; 8,880 identified as women; 5,062 identified as men) across 37 countries that varied in parental-leave policies and societal gender equality. In all countries, women intended to take longer leave than men. National parental-leave policies and women’s political representation partially explained cross-national variations in the gender gap. Gender gaps in leave intentions were paradoxically larger in countries with more gender-egalitarian parental-leave policies (i.e., longer leave available to both fathers and mothers). Interestingly, this cross-national variation in the gender gap was driven by cross-national variations in women’s (rather than men’s) leave intentions. Financially generous leave and gender-egalitarian policies (linked to men’s higher uptake in prior research) were not associated with leave intentions in men. Rather, men’s leave intentions were related to their individual gender attitudes. Leave intentions were inversely related to career ambitions. The potential for existing policies to foster gender equality in paid and unpaid work is discussed

Detection of very-high-energy gamma-ray emission from the vicinity of PSR B1706-44 with H.E.S.S

The energetic pulsar PSR B1706-44 and the adjacent supernova remnant (SNR) candidate G 343.1-2.3 were observed by H.E.S.S. during a dedicated observational campaign in 2007. A new source of very-high-energy (VHE; E > 100 GeV) gamma-ray emission, HESS J1708-443, was discovered with its centroid at RA(J2000) = 17h08m10s and Dec(J2000) = -44d21', with a statistical error of 3 arcmin on each axis. The VHE gamma-ray source is significantly more extended than the H.E.S.S. point-spread function, with an intrinsic Gaussian width of 0.29 +/- 0.04 deg. Its energy spectrum can be described by a power law with a photon index Gamma = 2.0 +/- 0.1 (stat) +/- 0.2 (sys). The integral flux measured between 1-10 TeV is ~17% of the Crab Nebula flux in the same energy range. The possible associations with PSR B1706-44 and SNR G343.1-2.3 are discussed

Influence of lone-pair cations on the germanate anomaly in glass

Neutron diffraction has been used to study the structure of a series of thallium germanate glasses, Tl(2)O-GeO(2), containing up to 40 mol % Tl(2)O, as a means of investigating the influence of lone-pair cations on the germanate anomaly. As observed previously in alkali germanate glasses, the average Ge-O coordination number, n(GeO), is found to rise above four as Tl(2)O is added to the glass. However, whereas for alkali germanates n(GeO) has its maximum value (similar to 4.36 +/- 0.03) at similar to 19 mol % R(2)O (e.g., R = Cs), for thallium germanates it continues to rise until 30 mol % Tl(2)O, with a higher maximum value of 4.44 +/- 0.02. For low Tl(2)O content, most thallium cations are on modifier sites with a high coordination number (6 or greater). As the Tl(2)O content increases, glass former [TlO(3)] sites become increasingly common, and it is predicted from an extrapolation of the results that a glass with a composition of 50 mol % Tl(2)O would be composed entirely of [TlO(3)] and [GeO(4)] units. It is shown that the presence of [TlO(3)] units allows higher coordinated Ge units to share an oxygen, and this is why n(GeO) continues to rise beyond the composition for which it is a maximum in alkali germanates. There is thus an interplay between the germanate anomaly and the environment of the lone-pair cation-an effect which does not occur in alkali germanates

ZBTB33 is mutated in clonal hematopoiesis and myelodysplastic syndromes and impacts RNA splicing

Clonal hematopoiesis results from somatic mutations in cancer driver genes in hematopoietic stem cells. We sought to identify novel drivers of clonal expansion using an unbiased analysis of sequencing data from 84,683 persons and identified common mutations in the 5-methylcytosine reader ZBTB33 as well as in YLPM1, SRCAP, and ZNF318. We also identified these mutations at low frequency in patients with myelodysplastic syndrome. Zbtb33-edited mouse hematopoietic stem and progenitor cells exhibited a competitive advantage in vivo and increased genome-wide intron retention. ZBTB33 mutations potentially link DNA methylation and RNA splicing, the two most commonly mutated pathways in clonal hematopoiesis and myelodysplastic syndromes.SIGNIFICANCE: Mutations in known driver genes can be found in only about half of individuals with clonal hematopoiesis. Here, we performed a somatic mutation discovery effort in nonmalignant blood samples, which identified novel candidate genes that may play biological roles in hematopoietic stem cell expansion and hematologic malignancies

High-resolution comparative analysis of great ape genomes

Genetic studies of human evolution require high-quality contiguous ape genome assemblies that are not guided by the human reference. We coupled long-read sequence assembly and full-length complementary DNA sequencing with a multiplatform scaffolding approach to produce ab initio chimpanzee and orangutan genome assemblies. By comparing these with two long-read de novo human genome assemblies and a gorilla genome assembly, we characterized lineage-specific and shared great ape genetic variation ranging from single- to mega-base pair-sized variants. We identified ∼17,000 fixed human-specific structural variants identifying genic and putative regulatory changes that have emerged in humans since divergence from nonhuman apes. Interestingly, these variants are enriched near genes that are down-regulated in human compared to chimpanzee cerebral organoids, particularly in cells analogous to radial glial neural progenitors