Toward a limbic cortical inhibitory network: implications for hypothalamic-pituitary-adrenal responses following chronic stress

A network of interconnected cell groups in the limbic forebrain regulates hypothalamic-pituitary-adrenal (HPA) axis activation during emotionally stressful experiences, and disruption of these systems is broadly implicated in the onset of psychiatric illnesses. A significant challenge has been to unravel the circuitry and mechanisms providing for regulation of HPA output, as these limbic forebrain regions do not provide any direct innervation of HPA effector cell groups in the paraventricular hypothalamus (PVH). Recent evidence will be highlighted that endorses a discrete region within the bed nuclei of the stria terminalis serving as a neural hub for integrating and relaying HPA-inhibitory influences to the PVH during emotional stress, whereas the prevailing view has involved a more complex organization of mulitple cell groups arranged in parallel between the forebrain and PVH. A hypothesis will be advanced that accounts for the capacity of this network to constrain the magnitude and/or duration of HPA axis output in response to emotionally stressful experiences, and for how chronic stress-induced synaptic reorganization in key cell groups may lead to an attrition of these influences, resulting in HPA axis hyperactivity

Characterization, quantification, and replication of human sinus bone for surgery simulation phantoms

The requirement for artificial but realistic, tactile, anatomical models for surgical practice in medical simulation is increasingly evident and shows potential for greater efficiency and availability, and lower costs. Anatomically correct, detailed models with the physical surgical characteristics of real tissue, combined with the ability to reproduce one-off cases, would provide an invaluable tool in the development of surgery. This research work investigates the capture of geometrical and physical data from the human sinus to subsequently direct the production and optimization of such simulation phantoms. Micro-computed tomography analysis of the entire sinus was performed to characterize the sinus complex geometry. Following an extensive review, specialized mechanical testing apparatus and methods relevant to the surgical methods employed were designed and produced. This provided comparative analysis methods for both biological and artificial phantom materials and allowed the optimization of phantom materials with respect to the derived target values

Blue Water Trade-Offs With Vegetation in a CO2-Enriched Climate

Present and future freshwater availability and drought risks are physically tied to the responses of surface vegetation to increasing CO2. A single-model large ensemble identifies the occurrence of colocated warming- and CO2-induced leaf area index increases with summer soil moisture declines. This pattern of “greening” and “drying,” which occurs over 42% of global vegetated land area, is largely attributable to changes in the partitioning of precipitation at the land surface away from runoff and toward terrestrial vegetation ecosystems. Changes in runoff and ecosystem partitioning are inversely related, with changes in runoff partitioning being governed by changes in precipitation (mean and extremes) and ecosystem partitioning being governed by ecosystem water use and surface resistance to evapotranspiration (ET). Projections show that warming-influenced and CO2-enriched terrestrial vegetation ecosystems use water that historically would have been partitioned to runoff over 48% of global vegetated land areas, largely in Western North America, the Amazon, and Europe, many of the same regions with colocated greening and drying. These results have implications for how water available for people will change in response to anthropogenic warming and raise important questions about model representations of vegetation water responses to high CO2

Chemotherapy decision-making in advanced lung cancer: a prospective qualitative study

Objective To study how treatment decisions are made alongside the lung cancer clinical pathway. Methods A prospective, multicentre, multimethods, five-stage, qualitative study. Mediated discourse, thematic, framework and narrative analysis were used to analyse the transcripts. Results 51 health professionals, 15 patients with advanced lung cancer, 15 family members and 18 expert stakeholders were recruited from three UK NHS trusts. Multidisciplinary team (MDT) members constructed treatment recommendations around patient performance status, pathology, clinical information and imaging. Information around patients’ social context, needs and preferences were limited. The provisional nature of MDTs treatment recommendations was not always linked to future discussions with the patient along the pathway, that is, patients’ interpretation of their prognosis, treatment discussions occurring prior to seeing the oncologist. This together with the rapid disease trajectory placed additional stress on the oncologist, who had to introduce a different treatment option from that recommended by the MDT or patient’s expectations. Palliative treatment was not referred to explicitly as such, due to its potential for confusion. Patients were unaware of the purpose of each consultation and did not fully understand the non-curative intent of treatment pathways. Patients’ priorities were framed around social and family needs, such as being able to attend a family event. Conclusion Missed opportunities for information giving, affect both clinicians and patients; the pathway for patients with non-small cell lung cancer focuses on clinical management at the expense of patient-centred care. Treatment decisions are a complex process and patients draw conclusions from healthcare interactions prior to the oncology clinic, which prioritises aggressive treatment and influences decisions

The ME Bandwagon and other labels: Constructing the authentic case in talk about a controversial illness

This paper examines the discourse of morality surrounding ‘ME’ as a contested illness, looking at how GPs and ME group members differentiate between the category of ‘genuine ME sufferer’ and the ‘bandwagon’. ‘Jumping on the bandwagon’ is a metaphor commonly used to describe the activity of ‘following the crowd’ in order to gain an advantage. This discursive analysis shows how ‘bandwagon’ categories are constructed in contrast to the category of genuine sufferer. People who jump on the bandwagon are accused of matching their symptoms to media stereotypes, adopting trendy illnesses (‘fads’,) or using ‘tickets’ to avoid facing up to psychological illnesses. Both GPs and ME group members construct a differential moral ordering of physical and psychological illness categories, where the latter assumes a lesser status. The paper concludes that against a background of medical uncertainty and controversy, the ‘bandwagon’ and other derogatory labels function as contrast categories that work to establish the existence of ‘ME’ as a genuine illness

Incentives for smoking cessation

Background Financial incentives, monetary or vouchers, are widely used in an attempt to precipitate, reinforce and sustain behaviour change, including smoking cessation. They have been used in workplaces, in clinics and hospitals, and within community programmes. Objectives To determine the long‐term effect of incentives and contingency management programmes for smoking cessation. Search methods For this update, we searched the Cochrane Tobacco Addiction Group Specialised Register, clinicaltrials.gov, and the International Clinical Trials Registry Platform (ICTRP). The most recent searches were conducted in July 2018. Selection criteria We considered only randomised controlled trials, allocating individuals, workplaces, groups within workplaces, or communities to smoking cessation incentive schemes or control conditions. We included studies in a mixed‐population setting (e.g. community, work‐, clinic‐ or institution‐based), and also studies in pregnant smokers. Data collection and analysis We used standard Cochrane methods. The primary outcome measure in the mixed‐population studies was abstinence from smoking at longest follow‐up (at least six months from the start of the intervention). In the trials of pregnant women we used abstinence measured at the longest follow‐up, and at least to the end of the pregnancy. Where available, we pooled outcome data using a Mantel‐Haenzel random‐effects model, with results reported as risk ratios (RRs) and 95% confidence intervals (CIs), using adjusted estimates for cluster‐randomised trials. We analysed studies carried out in mixed populations separately from those carried out in pregnant populations. Main results Thirty‐three mixed‐population studies met our inclusion criteria, covering more than 21,600 participants; 16 of these are new to this version of the review. Studies were set in varying locations, including community settings, clinics or health centres, workplaces, and outpatient drug clinics. We judged eight studies to be at low risk of bias, and 10 to be at high risk of bias, with the rest at unclear risk. Twenty‐four of the trials were run in the USA, two in Thailand and one in the Phillipines. The rest were European. Incentives offered included cash payments or vouchers for goods and groceries, offered directly or collected and redeemable online. The pooled RR for quitting with incentives at longest follow‐up (six months or more) compared with controls was 1.49 (95% CI 1.28 to 1.73; 31 RCTs, adjusted N = 20,097; I2 = 33%). Results were not sensitive to the exclusion of six studies where an incentive for cessation was offered at long‐term follow up (result excluding those studies: RR 1.40, 95% CI 1.16 to 1.69; 25 RCTs; adjusted N = 17,058; I2 = 36%), suggesting the impact of incentives continues for at least some time after incentives cease. Although not always clearly reported, the total financial amount of incentives varied considerably between trials, from zero (self‐deposits), to a range of between USD 45 and USD 1185. There was no clear direction of effect between trials offering low or high total value of incentives, nor those encouraging redeemable self‐deposits. We included 10 studies of 2571 pregnant women. We judged two studies to be at low risk of bias, one at high risk of bias, and seven at unclear risk. When pooled, the nine trials with usable data (eight conducted in the USA and one in the UK), delivered an RR at longest follow‐up (up to 24 weeks post‐partum) of 2.38 (95% CI 1.54 to 3.69; N = 2273; I2 = 41%), in favour of incentives. Authors' conclusions Overall there is high‐certainty evidence that incentives improve smoking cessation rates at long‐term follow‐up in mixed population studies. The effectiveness of incentives appears to be sustained even when the last follow‐up occurs after the withdrawal of incentives. There is also moderate‐certainty evidence, limited by some concerns about risks of bias, that incentive schemes conducted among pregnant smokers improve smoking cessation rates, both at the end of pregnancy and post‐partum. Current and future research might explore more precisely differences between trials offering low or high cash incentives and self‐incentives (deposits), within a variety of smoking populations

Influence of internal variability on population exposure to hydroclimatic changes

Future freshwater supply, human water demand, and people's exposure to water stress are subject to multiple sources of uncertainty, including unknown future pathways of fossil fuel and water consumption, and 'irreducible' uncertainty arising from internal climate system variability. Such internal variability can conceal forced hydroclimatic changes on multi-decadal timescales and near-continental spatial-scales. Using three projections of population growth, a large ensemble from a single Earth system model, and assuming stationary per capita water consumption, we quantify the likelihoods of future population exposure to increased hydroclimatic deficits, which we define as the average duration and magnitude by which evapotranspiration exceeds precipitation in a basin. We calculate that by 2060, backsim31%–35% of the global population will be exposed to >50% probability of hydroclimatic deficit increases that exceed existing hydrological storage, with up to 9% of people exposed to >90% probability. However, internal variability, which is an irreducible uncertainty in climate model predictions that is under-sampled in water resource projections, creates substantial uncertainty in predicted exposure: backsim86%–91% of people will reside where irreducible uncertainty spans the potential for both increases and decreases in sub-annual water deficits. In one population scenario, changes in exposure to large hydroclimate deficits vary from −3% to +6% of global population, a range arising entirely from internal variability. The uncertainty in risk arising from irreducible uncertainty in the precise pattern of hydroclimatic change, which is typically conflated with other uncertainties in projections, is critical for climate risk management that seeks to optimize adaptations that are robust to the full set of potential real-world outcomes

Associative Pavlovian conditioning leads to an increase in spinophilin-immunoreactive dendritic spines in the lateral amygdala

Changes in dendritic spine number and shape are believed to reflect structural plasticity consequent to learning. Previous studies have strongly suggested that the dorsal subnucleus of the lateral amygdala is an important site of physiological plasticity in Pavlovian fear conditioning. In the present study, we examined the effect of auditory fear conditioning on dendritic spine numbers in the dorsal subnucleus of the lateral amygdala using an immunolabelling procedure to visualize the spine-associated protein spinophilin. Associatively conditioned rats that received paired tone and shock presentations had 35% more total spinophilin-immunoreactive spines than animals that had unpaired stimulation, consistent with the idea that changes in the number of dendritic spines occur during learning and account in part for memory