The significance of lifeworld and the case of hospice

Questions on what it means to live and die well are raised and discussed in the hospice movement. A phenomenological lifeworld perspective may help professionals to be aware of meaningful and important dimensions in the lives of persons close to death. Lifeworld is not an abstract philosophical term, but rather the opposite. Lifeworld is about everyday, common life in all its aspects. In the writings of Cicely Saunders, known as the founder of the modern hospice movement, facets of lifeworld are presented as important elements in caring for dying patients. Palliative care and palliative medicine today are, in many ways, replacing hospices. This represents not only a change in name, but also in the main focus. Hospice care was originally very much about providing support and comfort for, and interactions with the patients. Improved medical knowledge today means improved symptomatic palliation, but also time and resources spent in other ways than before. Observations from a Nordic hospice ward indicate that seriously ill and dying persons spend much time on their own. Different aspects of lifeworld and intersubjectivity in the dying persons’ room is presented and discussed

Recognition of and Response to Neonatal Intrapartum-related Complications in Home-birth Settings in Bangladesh

Intrapartum-related complications (previously called \u2018birth asphyxia\u2019) are a significant contributor to deaths of newborns in Bangladesh. This study describes some of the perceived signs, causes, and treatments for this condition as described by new mothers, female relatives, traditional birth attendants, and village doctors in three sites in Bangladesh. Informants were asked to name characteristics of a healthy newborn and a newborn with difficulty in breathing at birth and about the perceived causes, consequences, and treatments for breathing difficulties. Across all three sites \u2018no movement\u2019 and \u2018no cry\u2019 were identified as signs of breathing difficulties while \u2018prolonged labour\u2019 was the most commonly-mentioned cause. Informants described a variety of treatments for difficulty in breathing at birth, including biomedical and, less often, spiritual and traditional practices. This study identified the areas that need to be addressed through behaviour change interventions to improve recognition of and response to intrapartum-related complications in Bangladesh

Recognition of and Response to neonatal intrapartum-related complications in home-birth settings in Bangladesh.

Intrapartum-related complications (previously called 'birth asphyxia') are a significant contributor to deaths of newborns in Bangladesh. This study describes some of the perceived signs, causes, and treatments for this condition as described by new mothers, female relatives, traditional birth attendants, and village doctors in three sites in Bangladesh. Informants were asked to name characteristics of a healthy newborn and a newborn with difficulty in breathing at birth and about the perceived causes, consequences, and treatments for breathing difficulties. Across all three sites 'no movement' and 'no cry' were identified as signs of breathing difficulties while 'prolonged labour' was the most commonly-mentioned cause. Informants described a variety of treatments for difficulty in breathing at birth, including biomedical and, less often, spiritual and traditional practices. This study identified the areas that need to be addressed through behaviour change interventions to improve recognition of and response to intrapartum-related complications in Bangladesh

A population of proinflammatory T cells coexpresses αβ and γδ T cell receptors in mice and humans

T cells are classically recognized as distinct subsets that express αβ or γδ TCRs. We identify a novel population of T cells that coexpress αβ and γδ TCRs in mice and humans. These hybrid αβ-γδ T cells arose in the murine fetal thymus by day 16 of ontogeny, underwent αβ TCR–mediated positive selection into CD4+ or CD8+ thymocytes, and constituted up to 10% of TCRδ+ cells in lymphoid organs. They expressed high levels of IL-1R1 and IL-23R and secreted IFN-γ, IL-17, and GM-CSF in response to canonically restricted peptide antigens or stimulation with IL-1β and IL-23. Hybrid αβ-γδ T cells were transcriptomically distinct from conventional γδ T cells and displayed a hyperinflammatory phenotype enriched for chemokine receptors and homing molecules that facilitate migration to sites of inflammation. These proinflammatory T cells promoted bacterial clearance after infection with Staphylococcus aureus and, by licensing encephalitogenic Th17 cells, played a key role in the development of autoimmune disease in the central nervous system

Variation in Base-Substitution Mutation in Experimental and Natural Lineages of Caenorhabditis Nematodes

Variation among lineages in the mutation process has the potential to impact diverse biological processes ranging from susceptibilities to genetic disease to the mode and tempo of molecular evolution. The combination of high-throughput DNA sequencing (HTS) with mutation-accumulation (MA) experiments has provided a powerful approach to genome-wide mutation analysis, though insights into mutational variation have been limited by the vast evolutionary distances among the few species analyzed. We performed a HTS analysis of MA lines derived from four Caenorhabditis nematode natural genotypes: C. elegans N2 and PB306 and C. briggsae HK104 and PB800. Total mutation rates did not differ among the four sets of MA lines. A mutational bias toward G:C→A:T transitions and G:C→T:A transversions was observed in all four sets of MA lines. Chromosome-specific rates were mostly stable, though there was some evidence for a slightly elevated X chromosome mutation rate in PB306. Rates were homogeneous among functional coding sequence types and across autosomal cores, arms, and tips. Mutation spectra were similar among the four MA line sets but differed significantly when compared with patterns of natural base-substitution polymorphism for 13/14 comparisons performed. Our findings show that base-substitution mutation processes in these closely related animal lineages are mostly stable but differ from natural polymorphism patterns in these two species

JWST/NIRCam Transmission Spectroscopy of the Nearby Sub-Earth GJ 341b

We present a JWST/NIRCam transmission spectrum from $3.9-5.0$ $\mu$m of the recently-validated sub-Earth GJ 341b ($\mathrm{R_P} = 0.92$ $\mathrm{R_{\oplus}}$, $\mathrm{T_{eq}} = 540$ K) orbiting a nearby bright M1 star ($\mathrm{d} = 10.4$ pc, $\mathrm{K_{mag}}=5.6$). We use three independent pipelines to reduce the data from the three JWST visits and perform several tests to check for the significance of an atmosphere. Overall, our analysis does not uncover evidence of an atmosphere. Our null hypothesis tests find that none of our pipelines' transmission spectra can rule out a flat line, although there is weak evidence for a Gaussian feature in two spectra from different pipelines (at 2.3 and $2.9\sigma$). However, the candidate features are seen at different wavelengths (4.3 $\mu$m vs 4.7 $\mu$m), and our retrieval analysis finds that different gas species can explain these features in the two reductions (CO$_2$ at $3.1\sigma$ compared to O$_3$ at $2.9\sigma$), suggesting that they are not real astrophysical signals. Our forward model analysis rules out a low mean molecular weight atmosphere ($< 350\times$ solar metallicity) to at least $3\sigma$, and disfavors CH$_4$-dominated atmospheres at $1-3\sigma$, depending on the reduction. Instead, the forward models find our transmission spectra are consistent with no atmosphere, a hazy atmosphere, or an atmosphere containing a species that does not have prominent molecular bands across the NIRCam/F444W bandpass, such as a water-dominated atmosphere. Our results demonstrate the unequivocal need for two or more transit observations analyzed with multiple reduction pipelines, alongside rigorous statistical tests, to determine the robustness of molecular detections for small exoplanet atmospheres.Comment: 25 pages, 18 figures, 6 tables. Accepted for publication in A

Double Trouble: Two Transits of the Super-Earth GJ 1132 b Observed with JWST NIRSpec G395H

The search for rocky planet atmospheres with JWST has focused on planets transiting M dwarfs. Such planets have favorable planet-to-star size ratios, enhancing the amplitude of atmospheric features. Since the expected signal strength of atmospheric features is similar to the single-transit performance of JWST, multiple observations are required to confirm any detection. Here, we present two transit observations of the rocky planet GJ 1132 b with JWST NIRSpec G395H, covering 2.8-5.2 $\mu$m. Previous HST WFC3 observations of GJ 1132 b were inconclusive, with evidence reported for either an atmosphere or a featureless spectrum based on analyses of the same dataset. Our JWST data exhibit substantial differences between the two visits. One transit is consistent with either a H$_2$O-dominated atmosphere containing ~1% CH$_4$ and trace N$_2$O ($\chi^{2}_{\nu}$ = 1.13) or stellar contamination from unocculted starspots ($\chi^{2}_{\nu}$ = 1.36). However, the second transit is consistent with a featureless spectrum. Neither visit is consistent with a previous report of HCN. Atmospheric variability is unlikely to explain the scale of the observed differences between the visits. Similarly, our out-of-transit stellar spectra show no evidence of changing stellar inhomogeneity between the two visits - observed 8 days apart, only 6.5% of the stellar rotation rate. We further find no evidence of differing instrumental systematic effects between visits. The most plausible explanation is an unlucky random noise draw leading to two significantly discrepant transmission spectra. Our results highlight the importance of multi-visit repeatability with JWST prior to claiming atmospheric detections for these small, enigmatic planets.Comment: 22 pages, 10 figures, 2 tables. Accepted for publication in ApJ Letters. Co-First Authors. Bonus materials and spectral data: https://doi.org/10.5281/zenodo.1000208

Age at first birth in women is genetically associated with increased risk of schizophrenia

Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe

Gene expression imputation across multiple brain regions provides insights into schizophrenia risk

Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression

Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects

Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (OR=1.11, P=5.7×10−15), which persisted after excluding loci implicated in previous studies (OR=1.07, P=1.7 ×10−6). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 ×10−11) and neurobehavioral phenotypes in mouse (OR = 1.18, P= 7.3 ×10−5). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by non-allelic homologous recombination