Evidence of assortative mating in autism spectrum disorder

Background Assortative mating is a non-random mating system in which individuals with similar genotypes and/or phenotypes mate with one another more frequently than would be expected in a random mating system. Assortative mating has been hypothesized to play a role in Autism Spectrum Disorder (ASD) in an attempt to explain some of the increase in the prevalence of ASD that has recently been observed. ASD is considered to be a heritable neurodevelopmental disorder but there is limited understanding of its causes. Assortative mating can be explored through both phenotypic and genotypic data, but up until now, has never been investigated through genotypic measures in ASD. Methods We investigated genotypically similar mating pairs using genome-wide Single Nucleotide Polymorphism (SNP) data on trio families (Autism Genome Project (AGP) data (1,590 parents) and Simons Simplex Collection (SSC) data (1962 parents)). To determine whether or not an excess in genetic similarity was present we employed kinship coefficients and examined spousal correlation between the principal components in both the AGP and SSC datasets. We also examined assortative mating using phenotype data on the parents to detect any correlation between ASD traits. Results We found significant evidence of genetic similarity between the parents of ASD offspring using both methods in the AGP dataset. In the SSC, there was also significant evidence of genetic similarity between the parents when explored through spousal correlation. Conclusions This gives further support to the hypothesis that positive assortative mating plays a role in ASD

Acute surgical wound-dressing procedure: Description of the steps involved in the development and validation of an observational metric

The aim of this study was to develop an observational metric that could be used to assess the performance of a practitioner in completing an acute surgical wound-dressing procedure using aseptic non-touch technique (ANTT). A team of clinicians, academics, and researchers came together to develop an observational metric using an iterative six-stage process, culminating in a Delphi panel meeting. A scoping review of the literature provided a background empirical perspective relating to wound-dressing procedure performance. Video recordings of acute surgical wound-dressing procedures performed by nurses in clinical (n = 11) and simulated (n = 3) settings were viewed repeatedly and were iteratively deconstructed by the metric development group. This facilitated the identification of the discrete component steps, potential errors, and sentinel (serious) errors, which characterise a wound dressing procedure and formed part of the observational metric. The ANTT wound-dressing observational metric was stress tested for clarity, the ability to be scored, and interrater reliability, calculated during a further phase of video analysis. The metric was then subjected to a process of cyclical evaluation by a Delphi panel (n = 21) to obtain face and content validity of the metric. The Delphi panel deliberation verified the face and content validity of the metric. The final metric has three phases, 31 individual steps, 18 errors, and 27 sentinel errors. The metric is a tool that identifies the standard to be attained in the performance of acute surgical wound dressings. It can be used as both an adjunct to an educational programme and as a tool to assess a practitioner's performance of a wound-dressing procedure in both simulated and clinical practice contexts

Older adult insights for age friendly environments, products and service Systems

The environments we grow old in present a challenge to be adaptive to our changing needs and limitations. Environments, in the context of this paper, are the spaces, products and product service systems that we engage with, alone or with others, within and outside the home. A design coalition (Manzini, 2015) was generated between a number of academic Institutions and ISAX (Ireland Smart Ageing Exchange) an ‘ageing think tank’ organisation in Ireland. The intention of this coalition was to generate awareness of needs requirements for age friendly environments and to provide an example of how participatory design research can inform innovation in business and policy development at a local and state level. A five-week study was conducted using design and ethnographic methods with twenty-two Older Adult participants (age range 69 – 80). The themes of study were identified as: Mobility, Public Spaces, Safety, Social Engagement, Services & Facilities. Cultural probes, semi-structured interviews and user observation, by both researchers and older adult participants, were used as methods to identify the unmet needs of participants within the sample group. A Co-Design Symposium (http://info.isax.ie/national-co-design-symposium) was held during June 2016 as an opportunity to demonstrate to a wider stakeholder audience the needs identified from this study. This Symposium was attended by over 100 people of various backgrounds (town planners, architects, transport experts, retailers, builders, health and other service providers). The older adult participants and designers (staff and researchers from the School of Design at the University of Limerick, IT Carlow, Limerick Institute of Technology and Limerick School of Art & Design) were placed within a team of ten. The research was presented using audio/visual presentation as well as artefacts from the fieldwork, completed diaries, scrapbooks, storyboards etc. Solutions were worked on, and delivered at end of day. This Symposium has impacted positively whereby policy makers in local government have invited ISAX to further discuss research outcomes and needs of older adults as a means to develop access areas in and around Limerick City. This paper outlines in further detail the design research methods used and the benefits through design education Student/ Researcher /Stakeholder collaboration by application ‘in the ‘field’ and displays the effectiveness of design coalitions in influencing and affecting change and insight into policy. It highlights how Co-Design collaborations can impact and generate design solutions that improve day to day experiences

Older adult insights for age friendly environments, products and service Systems.

  The environments we grow old in present a challenge to be adaptive to our changing needs and limitations. Environments, in the context of this paper, are the spaces, products and product service systems that we engage with, alone or with others, within and outside the home. A design coalition (Manzini, 2015) was generated between a number of academic Institutions and ISAX (Ireland Smart Ageing Exchange) an ‘ageing think tank’ organisation in Ireland. The intention of this coalition was to generate awareness of needs requirements for age friendly environments and to provide an example of how participatory design research can inform innovation in business and policy development at a local and state level. A five-week study was conducted using design and ethnographic methods with twenty-two Older Adult participants (age range 69 – 80).  The themes of study were identified as: Mobility, Public Spaces, Safety, Social Engagement, Services & Facilities. Cultural probes, semi-structured interviews and user observation, by both researchers and older adult participants, were used as methods to identify the unmet needs of participants within the sample group. A Co-Design Symposium (http://info.isax.ie/national-co-design-symposium )was held during June 2016 as an opportunity to demonstrate to a wider stakeholder audience the needs identified from this study. This Symposium was attended by over 100 people of various backgrounds (town planners, architects, transport experts, retailers, builders, health and other service providers). The older adult participants and designers (staff and researchers from the School of Design at the University of Limerick, IT Carlow, Limerick Institute of Technology and Limerick School of Art & Design) were placed within a team of ten. The research was presented using audio/visual presentation as well as artefacts from the fieldwork, completed diaries, scrapbooks, storyboards etc. Solutions were worked on, and delivered at end of day. This Symposium has impacted positively whereby policy makers in local government have invited ISAX to further discuss research outcomes and needs of older adults as a means to develop access areas in and around Limerick City. This paper outlines in further detail the design research methods used and the benefits through design education Student/ Researcher /Stakeholder collaboration by application ‘in the ‘field’ and displays the effectiveness of design coalitions in influencing and affecting change and insight into policy. It highlights how Co-Design collaborations can impact and generate design solutions that improve day to day experiences. Keywords: Older Adults, Co-Design, Needs Identification, Collaborative Coalitions, Product Service Systems

Designing and Developing Core Physiology Learning Outcomes for Pre-registration Nursing Education Curriculum

Physiology is a key element of ‘bioscience’ education within pre-registration nursing programmes, but there is a lack of clarity on what is included. Physiology and bioscience content and delivery is highly varied across both higher education institutions and the related programmes in the UK. Despite evidence highlighting concerns over nurses lack of bioscience knowledge and unsafe practice, there is no universally agreed curriculum with detailed outcomes of minimum levels of knowledge to support nurses in practice and patient care. This study aimed to inform the construction of discipline specific physiology learning outcomes to clarify relevant physiological topics required in pre-registration nursing. Initially, 360 learning outcomes were identified from various sources. Using a modified Delphi approach, an expert panel from the Bioscience in Nurse Education group reviewed and modified the list to 195 proposed outcomes. These were circulated to Universities in the UK who teach Nursing (n=65). Outcomes which had 80% consensus were automatically included to the next round with others recommended with modification (response rate 22%). The panel reviewed the modifications and 182 outcomes were circulated in the second questionnaire (response rate 23%) and further panel review resulting in 177 outcomes agreed. These learning outcomes do not suggest how they should be delivered but gives the basic level required for qualification as a nurse commensurate with the Nursing and Midwifery Council new standards for the 'future nurse'

Sudden cardiac death due to deficiency of the mitochondrial inorganic pyrophosphatase PPA2

We have used whole exome sequencing to identify biallelic missense mutations in the nuclearencoded mitochondrial inorganic pyrophosphatase (PPA2) in ten individuals from four unrelated pedigrees that are associated with mitochondrial disease. These individuals show a range of severity, indicating that PPA2 mutations may cause a spectrum of mitochondrial disease phenotypes. Severe symptoms include seizures, lactic acidosis and cardiac arrhythmia and death within days of birth. In the index family, presentation was milder and manifested as cardiac fibrosis and an exquisite sensitivity to alcohol, leading to sudden arrhythmic cardiac death in the second decade of life. Comparison of normal and mutated PPA2 containing mitochondria from fibroblasts showed the activity of inorganic pyrophosphatase significantly reduced in affected individuals. Recombinant PPA2 enzymes modeling hypomorphic missense mutations had decreased activity that correlated with disease severity. These findings confirm the pathogenicity of PPA2 mutations, and suggest that PPA2 is a new cardiomyopathy-associated protein, which has a greater physiological importance in mitochondrial function than previously recognized

Positive Affect Predicts Cerebral Glucose Metabolism in Late Middle-aged Adults.

Positive affect is associated with a number of health benefits; however, few studies have examined the relationship between positive affect and cerebral glucose metabolism, a key energy source for neuronal function and a possible index of brain health. We sought to determine if positive affect was associated with cerebral glucose metabolism in late middle-aged adults (n = 133). Participants completed the positive affect subscale of the Center for Epidemiological Studies Depression Scale at two time points over a two-year period and underwent 18F-fluorodeoxyglucose-positron emission tomography scanning. After controlling for age, sex, perceived health status, depressive symptoms, anti-depressant use, family history of Alzheimer’s disease, APOE ε4 status and interval between visits, positive affect was associated with greater cerebral glucose metabolism across para-/limbic, frontal, temporal and parietal regions. Our findings provide evidence that positive affect in late midlife is associated with greater brain health in regions involved in affective processing and also known to be susceptible to early neuropathological processes. The current findings may have implications for interventions aimed at increasing positive affect to attenuate early neuropathological changes in at-risk individuals

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570