The Relationship Between Cumulative Adversity in Childhood and Adolescent Suicide and Accidental Death

On the whole research has concluded that most young people navigate adolescence with few difficulties, but a minority do find this stage of life challenging, and their ways of coping may have negative consequences for both themselves and others. For some the experience of adversity in earlier childhood, and the cumulative impact of multiple adversities has the potential to compromise a young person’s natural resilience. In some cases this may result in an adolescent feeling overwhelmed, and dying through suicide or other high risk behaviours. This article explores these issues with reference to eight young people who died by suicide in Northern Ireland. The article argues that young people exposed to multiple adversities in childhood require earlier, more sustained and better co-ordinated services from professionals if their psychological and emotional well-being is to be promoted.

CCAAT/enhancer binding protein α predicts poorer prognosis and prevents energy starvation-induced cell death in hepatocellular carcinoma

CCAAT enhancer binding protein α (C/EBPα) plays an essential role in cellular differentiation, growth, and energy metabolism. Here, we investigate the correlation between C/EBPα and hepatocellular carcinoma (HCC) patient outcomes and how C/EBPα protects cells against energy starvation. Expression of C/EBPα protein was increased in the majority of HCCs examined (191 pairs) compared with adjacent nontumor liver tissues in HCC tissue microarrays. Its upregulation was correlated significantly with poorer overall patient survival in both Kaplan-Meier survival (P = 0.017) and multivariate Cox regression (P = 0.028) analyses. Stable C/EBPα-silenced cells failed to establish xenograft tumors in nude mice due to extensive necrosis, consistent with increased necrosis in human C/EBPα-deficient HCC nodules. Expression of C/EBPα protected HCC cells in vitro from glucose and glutamine starvation-induced cell death through autophagy-involved lipid catabolism. Firstly, C/EBPα promoted lipid catabolism during starvation, while inhibition of fatty acid beta-oxidation significantly sensitized cell death. Secondly, autophagy was activated in C/EBPα-expressing cells, and the inhibition of autophagy by ATG7 knockdown or chloroquine treatment attenuated lipid catabolism and subsequently sensitized cell death. Finally, we identified TMEM166 as a key player in C/EBPα-mediated autophagy induction and protection against starvation.

CONCLUSION: The C/EBPα gene is important in that it links HCC carcinogenesis to autophagy-mediated lipid metabolism and resistance to energy starvation; its expression in HCC predicts poorer patient prognosis.

Squeezing of mechanical motion via qubit-assisted control

We propose a feedback control mechanism for the squeezing of the phononic mode of a mechanical oscillator. We show how, under appropriate working conditions, a simple adiabatic approach is able to induce mechanical squeezing. We then go beyond the limitations of such a working point and demonstrate the stationary squeezing induced by using repeated measurements and reinitialization of the state of a two-level system ancilla coupled to the oscillator. Our nonadaptive feedback loop offers interesting possibilities for quantum state engineering and steering in open-system scenarios.

Microwave-Assisted Preparation of Hydrogel-Forming Microneedle Arrays for Transdermal Drug Delivery Applications

A microwave (MW)-assisted crosslinking process to prepare hydrogel-forming microneedle (MN) arrays was evaluated. Conventionally, such MN arrays are prepared using processes that includes a thermal crosslinking step. Polymeric MN arrays were prepared using poly(methyl vinyl ether-alt-maleic acid) crosslinked by reaction with poly(ethylene glycol) over 24 h at 80 °C. Polymeric MN arrays were prepared to compare conventional process with the novel MW-assisted crosslinking method. Infrared spectroscopy was used to evaluate the crosslinking degree, evaluating the area of the carbonyl peaks (2000–1500 cm−1). It was shown that, by using the MW-assisted process, MN with a similar crosslinking degree to those prepared conventionally can be obtained in only 45 min. The effects of the crosslinking process on the properties of these materials were also evaluated. For this purpose swelling kinetics, mechanical characterisation, and insertion studies were performed. The results suggest that MN arrays prepared using the MW assisted process had equivalent properties to those prepared conventionally but can be produced 30 times faster. Finally, an in vitro caffeine permeation across excised porcine skin was performed using conventional and MW-prepared MN arrays. The release profiles obtained can be considered equivalent, delivering in both cases 3000–3500 μg of caffeine after 24 h.

"Republic of Instability":Artifice, Death and the Afterlife in Mark Doty's "Murano"

An article on a single poem by Mark Doty, published as part of the "Hospitable Forms: Post-Secular Thought in New-Century Poetics" feature.

The paternal genome and the health of the assisted reproductive technology child

As a number of children born by assisted reproductive technology (ART) are increasing each year across the developed world, the health of such offspring is a matter of public concern. Does the integrity of the paternal genome impact on offspring health? In societal terms, as birth rates fall, and the Western population become unsustainable, do the benefits outweigh the costs of creating and providing for this ART conceived sub population? There are little data to date to answer these questions. The long‑term health of such children has largely been ignored, and success measured only by early (pre-birth) outcomes such as embryo quality or pregnancy. However, there are powerful paradigms such as ageing and smoking that give vital clues as to the potential impact of unhealthy spermatozoa on disease risk, mental and physical health, fertility and mortality of these offspring.

Predictors of place of death for those in receipt of home-based palliative care services in Ontario, Canada

Many cancer patients die in institutional settings despite their preference to die at home. A longitudinal, prospective cohort study was conducted to comprehensively assess the determinants of home death for patients receiving home-based palliative care. Data collected from biweekly telephone interviews with caregivers (n=302) and program databases were entered into a multivariate logistic model. Patients with high nursing costs (odds ratio [OR]: 4.3; confidence interval [CI]: 1.8-10.2) and patients with high personal support worker costs (OR: 2.3; CI: 1.1-4.5) were more likely to die at home than those with low costs. Patients who lived alone were less likely to die at home than those who cohabitated (OR: 0.4; CI: 0.2-0.8), and those with a high propensity for a home-death preference were more likely to die at home than those with a low propensity (OR: 5.8; CI: 1.1-31.3). An understanding of the predictors of place of death may contribute to the development of effective interventions that support home death.

Evidence supporting a role for N-epsilon-(3-formyl-3,4-dehydropiperidino)lysine accumulation in Muller glia dysfunction and death in diabetic retinopathy

Purpose: Recent evidence suggests that neuroglial dysfunction and degeneration contributes to the etiology and progression of diabetic retinopathy. Advanced lipoxidation end products (ALEs) have been implicated in the pathology of various diseases, including diabetes and several neurodegenerative disorders. The purpose of the present study was to investigate the possible link between the accumulation of ALEs and neuroretinal changes in diabetic retinopathy.

Methods: Retinal sections obtained from diabetic rats and age-matched controls were processed for immunohistochemistry using antibodies against several well defined ALEs. In vitro experiments were also performed using a human Muller (Moorfields/Institute of Ophthalmology-Muller 1 [ MIO-M1]) glia cell line. Western blot analysis was used to measure the accumulation of the acrolein-derived ALE adduct N epsilon-(3-formyl-3,4-dehydropiperidino)lysine (FDP-lysine) in Muller cells preincubated with FDP-lysine-modified human serum albumin (FDP-lysine-HSA). Responses of Muller cells to FDP-lysine accumulation were investigated by analyzing changes in the protein expression of heme oxygenase-1 (HO-1), glial fibrillary acidic protein (GFAP), and the inwardly rectifying potassium channel Kir4.1. In addition, mRNA expression levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF alpha) were determined by reverse transcriptase PCR (RT-PCR). Apoptotic cell death was evaluated by fluorescence-activated cell sorting (FACS) analysis after staining with fluorescein isothiocyanate (FITC)-labeled annexin V and propidium iodide.

Results: No significant differences in the levels of malondialdehyde-, 4-hydroxy-2-nonenal-, and 4-hydroxyhexenal-derived ALEs were evident between control and diabetic retinas after 4 months of diabetes. By contrast, FDP-lysine immunoreactivity was markedly increased in the Muller glia of diabetic rats. Time-course studies revealed that FDP-lysine initially accumulated within Muller glial end feet after only a few months of diabetes and thereafter spread distally throughout their inner radial processes. Exposure of human Muller glia to FDP-lysine-HSA led to a concentration-dependent accumulation of FDP-lysine-modified proteins across a broad molecular mass range. FDP-lysine accumulation was associated with the induction of HO-1, no change in GFAP, a decrease in protein levels of the potassium channel subunit Kir4.1, and upregulation of transcripts for VEGF, IL-6, and TNF-alpha. Incubation of Muller glia with FDP-lysine-HSA also caused apoptosis at high concentrations.

Conclusions: Collectively, these data strongly suggest that FDP-lysine accumulation could be a major factor contributing to the Muller glial abnormalities occurring in the early stages of diabetic retinopathy.

'Talk to me': a mixed methods study on preferred physician behaviours during end-of-life communication from the patient perspective

Background
Despite the recognized importance of end-of-life (EOL) communication between patients and physicians, the extent and quality of such communication is lacking.

Objective
We sought to understand patient perspectives on physician behaviours during EOL communication.

Design
In this mixed methods study, we conducted quantitative and qualitative strands and then merged data sets during a mixed methods analysis phase. In the quantitative strand, we used the quality of communication tool (QOC) to measure physician behaviours that predict global rating of satisfaction in EOL communication skills, while in the qualitative strand we conducted semi-structured interviews. During the mixed methods analysis, we compared and contrasted qualitative and quantitative data.

Setting and Participants
Seriously ill inpatients at three tertiary care hospitals in Canada.

Results
We found convergence between qualitative and quantitative strands: patients desire candid information from their physician and a sense of familiarity. The quantitative results (n = 132) suggest a paucity of certain EOL communication behaviours in this seriously ill population with a limited prognosis. The qualitative findings (n = 16) suggest that at times, physicians did not engage in EOL communication despite patient readiness, while sometimes this may represent an appropriate deferral after assessment of a patient's lack of readiness.

Conclusions
Avoidance of certain EOL topics may not always be a failure if it is a result of an assessment of lack of patient readiness. This has implications for future tool development: a measure could be built in to assess whether physician behaviours align with patient readiness.