New reference ranges for interpreting forced expiratory manoeuvres in infants and implications for clinical interpretation: a multicentre collaboration

The raised volume rapid thoracoabdominal compression (RVRTC) technique is commonly used to obtain full forced expiratory manoeuvres from infants, but reference equations derived from 'in-house' equipment have been shown to be inappropriate for current commercially available devices

Antineoplastic activity of idazoxan hydrochloride

Idazoxan hydrochloride (IDA) is a 241 molecular weight imidazoline and adrenoreceptor ligand. It binds to mitochondrial membranes and promotes apoptosis of pancreatic beta cells. Since IDA has not been tested against tumor cells, the purpose of our study was to determine if IDA has antineoplastic activity. We used the conversion of a soluble tetrazolium salt to an insoluble formazan precipitate and differential staining cytotoxicity assays to determine if IDA was cytotoxic to cell lines of murine lung cancer and human prostate cancer, as well as to a variety of fresh human tumor samples. We used flow cytometry to analyze cell death and calreticulin expression. IDA is cytotoxic to both cell lines and against aliquots of specimens of breast, gastric, lung, ovarian and prostate cancers as well as non-Hodgkin’s lymphoma. It produces apoptotic cell death and promotes calreticulin expression, suggesting that IDA might be immunomodulatory in vivo. We anticipate that IDA will be clinically useful in cancer treatment

A nurse-led, preventive, psychological intervention to reduce PTSD symptom severity in critically ill patients: the POPPI feasibility study and cluster RCT

BACKGROUND: High numbers of patients experience severe acute stress in critical care units. Acute stress has been linked to post-critical care psychological morbidity, including post-traumatic stress disorder (PTSD). Previously, a preventive, complex psychological intervention [Psychological Outcomes following a nurse-led Preventative Psychological Intervention for critically ill patients (POPPI)] was developed by this research team, to be led by nurses, to reduce the development of PTSD symptom severity at 6 months. OBJECTIVES: The objectives were to (1) standardise and refine the POPPI intervention, and, if feasible, (2) evaluate it in a cluster randomised clinical trial (RCT). DESIGN: Two designs were used – (1) two feasibility studies to test the delivery and acceptability (to patients and staff) of the intervention, education package and support tools, and to test the trial procedures (i.e. recruitment and retention), and (2) a multicentre, parallel-group, cluster RCT with a baseline period and staggered roll-out of the intervention. SETTING: This study was set in NHS adult, general critical care units. PARTICIPANTS: The participants were adult patients who were > 48 hours in a critical care unit, receiving level 3 care and able to consent. INTERVENTIONS: The intervention comprised three elements – (1) creating a therapeutic environment in critical care, (2) three stress support sessions for patients identified as acutely stressed and (3) a relaxation and recovery programme for patients identified as acutely stressed. MAIN OUTCOMES MEASURES: Primary outcome – patient-reported symptom severity using the PTSD Symptom Scale – Self Report (PSS-SR) questionnaire (to measure clinical effectiveness) and incremental costs, quality-adjusted life-years (QALYs) and net monetary benefit at 6 months (to measure cost-effectiveness). Secondary outcomes – days alive and free from sedation to day 30; duration of critical care unit stay; PSS-SR score of > 18 points; depression, anxiety and health-related quality of life at 6 months; and lifetime cost-effectiveness. RESULTS: (1) A total of 127 participants were recruited to the intervention feasibility study from two sites and 86 were recruited to the RCT procedures feasibility study from another two sites. The education package, support tools and intervention were refined. (2) A total of 24 sites were randomised to the intervention or control arms. A total of 1458 participants were recruited. Twelve sites delivered the intervention during the intervention period: > 80% of patients received two or more stress support sessions and all 12 sites achieved the target of > 80% of clinical staff completing the POPPI online training. There was, however, variation in delivery across sites. There was little difference between baseline and intervention periods in the development of PTSD symptom severity (measured by mean PSS-SR score) at 6 months for surviving patients in either the intervention or the control group: treatment effect estimate −0.03, 95% confidence interval (CI) −2.58 to 2.52; p = 0.98. On average, the intervention decreased costs and slightly improved QALYs, leading to a positive incremental net benefit at 6 months (£835, 95% CI −£4322 to £5992), but with considerable statistical uncertainty surrounding these results. There were no significant differences between the groups in any of the secondary outcomes or in the prespecified subgroup analyses. LIMITATIONS: There was a risk of bias because different consent processes were used and as a result of the lack of blinding, which was mitigated as far as possible within the study design. The intervention started later than anticipated. Patients were not routinely monitored for delirium. CONCLUSIONS: Among level 3 patients who stayed > 48 hours in critical care, the delivery of a preventive, complex psychological intervention, led by nurses, did not reduce the development of PTSD symptom severity at 6 months, when compared with usual care. FUTURE WORK: Prior to development and evaluation of subsequent psychological interventions, there is much to learn from post hoc analyses of the cluster RCT rich quantitative and qualitative data. TRIAL REGISTRATION: This trial is registered as ISRCTN61088114 and ISRCTN53448131. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 23, No. 30. See the NIHR Journals Library website for further project information

Associations of Body Mass and Fat Indexes With Cardiometabolic Traits

Background Body mass index (BMI) is criticized for not distinguishing fat from lean mass and ignoring fat distribution, leaving its ability to detect health effects unclear. Objectives The aim of this study was to compare BMI with total and regional fat indexes from dual-energy x-ray absorptiometry in their associations with cardiometabolic traits. Duration of exposure to and change in each index across adolescence were examined in relation to detailed traits in young adulthood. Methods BMI was examined alongside total, trunk, arm, and leg fat indexes (each in kilograms per square meter) from dual-energy x-ray absorptiometry at ages 10 and 18 years in relation to 230 traits from targeted metabolomics at age 18 years in 2,840 offspring from the Avon Longitudinal Study of Parents and Children. Results Higher total fat mass index and BMI at age 10 years were similarly associated with cardiometabolic traits at age 18 years, including higher systolic and diastolic blood pressure, higher very low-density lipoprotein and low-density lipoprotein cholesterol, lower high-density lipoprotein cholesterol, higher triglycerides, and higher insulin and glycoprotein acetyls. Associations were stronger for both indexes measured at age 18 years and for gains in each index from age 10 to 18 years (e.g., 0.45 SDs [95% confidence interval: 0.38 to 0.53] in glycoprotein acetyls per SD unit gain in fat mass index vs. 0.38 SDs [95% confidence interval: 0.27 to 0.48] per SD unit gain in BMI). Associations resembled those for trunk fat index. Higher lean mass index was weakly associated with traits and was not protective against higher fat mass index. Conclusions The results of this study support abdominal fatness as a primary driver of cardiometabolic dysfunction and BMI as a useful tool for detecting its effects

Ancestral bias in the Hras1 gene and distal Chromosome 7 among inbred mice

Inbred strains of mice vary in their frequency of liver tumors initiated by a mutation in the Hras1 (H-ras) proto-oncogene. We sequenced 4.5 kb of the Hras1 gene on distal Chr 7 in a diverse set of 12 commonly used laboratory inbred strains of mice and detected no sequence variation to account for strain-specific differences in Hras1 mutation prevalence. Furthermore, the Hras1 sequence is essentially monoallelic for an ancestral gene derived from the M. m. domesticus species. To determine if the monoallelism and associated low rate of polymorphism are unique to Hras1 or representative of the general chromosomal locale, we extended the sequence analysis to 12 genes in the final 8 Mb of distal Chr 7. A region of at least 2.5 Mb that encompasses several genes, including Hras1 and the H19/Igf2 loci, demonstrates virtually no sequence variation. The 12 inbred strains share one dominant haplotype derived from the M. m. domesticus allele. Chromosomal regions flanking the monoallelic segment exhibit a significantly higher rate of variation and multiple haplotypes, a majority of which are attributed to M. m. domesticus or M. m. musculus ancestry

Building Babies - Chapter 16

In contrast to birds, male mammals rarely help to raise the offspring. Of all mammals, only among rodents, carnivores, and primates, males are sometimes intensively engaged in providing infant care (Kleiman and Malcolm 1981). Male caretaking of infants has long been recognized in nonhuman primates (Itani 1959). Given that infant care behavior can have a positive effect on the infant’s development, growth, well-being, or survival, why are male mammals not more frequently involved in “building babies”? We begin the chapter defining a few relevant terms and introducing the theory and hypotheses that have historically addressed the evolution of paternal care. We then review empirical findings on male care among primate taxa, before focusing, in the final section, on our own work on paternal care in South American owl monkeys (Aotus spp.). We conclude the chapter with some suggestions for future studies.Deutsche Forschungsgemeinschaft (HU 1746/2-1) Wenner-Gren Foundation, the L.S.B. Leakey Foundation, the National Geographic Society, the National Science Foundation (BCS-0621020), the University of Pennsylvania Research Foundation, the Zoological Society of San Dieg

Six years beyond pediatric trauma: child and parental ratings of children’s health-related quality of life in relation to parental mental health

Purpose: To examine the relationship between child self-report and parent proxy report of health-related quality of life (HRQL) and how parents’ mental health status relates to the HRQL ratings 6 years after minor to severe injury of the child. Materials and methods: This cross-sectional cohort study was performed at a regional pediatric trauma center in Stockholm, Sweden. The PedsQL 4.0 versions for ages 5–7, 8–12, and 13–18 years were completed by 177 child–parent dyads 6 years after injury to the child. The parents also rated their own mental health through the mental health domain (MH) in the SF-36 Health Survey. Results: The children’s median age was 13 years (IQR 10–16 years), 54 % were males, and the median ISS was 5 (IQR 2–9). Most of the parents were female (77 %), born in Sweden (79 %), and half had university degrees. There was no statistically significant difference between child self-report and parent proxy report in any of the PedsQL 4.0 scales or summary scales. The levels of agreement between child self-report and parent proxy reports were excellent (ICC ≥ 0.80) for all scales with the exception of emotional functioning (ICC 0.53) which also was the scale with the lowest internal consistency in child self-report (α 0.60). Multiple regression analyses showed that worse parental mental health status correlated with worse child self-report and parent proxy report of children’s HRQL. Conclusions: Children and their parents’ reports on child’s HRQL were in agreement. Decreased mental health in parents was associated with lower scores on parent proxy reports and child self-reports of HRQL after injury. The current investigation highlights the possible relationship between parent’s mental health status and children’s HRQL long after an injury, which should be considered in future investigations and in clinical care

Telepsychotherapy with children and families: Lessons gleaned from two decades of translational research

This is the author accepted manuscript. The final version is available from the American Psychological Association via the DOI in this recordThe novel coronavirus, COVID-19, has led to sweeping changes in psychological practice and the concomitant rapid uptake of telepsychotherapy. Although telepsychotherapy is new to many clinical psychologists, there is considerable research on telepsychotherapy treatments. Nearly two decades of clinical research on telepsychotherapy treatments with children with neurological conditions has the potential to inform emerging clinical practice in the age of COVID-19. Toward that end, we synthesized findings from 14 clinical trials of telepsychotherapy problemsolving and parent training interventions involving more than 800 children and families with diverse diagnoses including traumatic brain injury, epilepsy, brain tumors, congenital heart disease, and perinatal stroke. We summarize efficacy across studies and clinical populations and report feasibility and acceptability data from the perspectives of parents, children, and therapists. We describe adaptation for international contexts and strategies for troubleshooting technological challenges and working with families of varying socioeconomic strata. The extensive research literature reviewed and synthesized provides considerable support for the utility of telepsychotherapy with children with neurological conditions and their families and underscores its high level of acceptability with both diverse clinical populations and providers. During this period of heightened vulnerability and stress and reduced access to usual supports and services, telepsychotherapy approaches such as online family problem-solving treatment and online parenting skills training may allow psychologists to deliver traditional evidence-based treatments virtually while preserving fidelity and efficacyNational Institute for Health Research (NIHR

Animal cultures matter for conservation

This is the author accepted manuscript. The final version is available from AAAS via the DOI in this record.No abstrac