On the Cause of Recent Variations in Lower Stratospheric Ozone

We use height‐resolved and total column satellite observations and 3‐D chemical transport model simulations to study stratospheric ozone variations during 1998–2017 as ozone‐depleting substances decline. In 2017 extrapolar lower stratospheric ozone displayed a strong positive anomaly following much lower values in 2016. This points to large interannual variability rather than an ongoing downward trend, as reported recently by Ball et al. (2018, https://doi.org/10.5194/acp‐18‐1379‐2018). The observed ozone variations are well captured by the chemical transport model throughout the stratosphere and are largely driven by meteorology. Model sensitivity experiments show that the contribution of past trends in short‐lived chlorine species to the ozone changes is small. Similarly, the potential impact of modest trends in natural brominated short‐lived species is small. These results confirm the important role that atmospheric dynamics plays in controlling ozone in the extrapolar lower stratosphere on multiannual time scales and the continued importance of monitoring ozone profiles as the stratosphere changes

Huntington disease: natural history, biomarkers and prospects for therapeutics

Huntington disease (HD) can be seen as a model neurodegenerative disorder, in that it is caused by a single genetic mutation and is amenable to predictive genetic testing, with estimation of years to predicted onset, enabling the entire range of disease natural history to be studied. Structural neuroimaging biomarkers show that progressive regional brain atrophy begins many years before the emergence of diagnosable signs and symptoms of HD, and continues steadily during the symptomatic or 'manifest' period. The continued development of functional, neurochemical and other biomarkers raises hopes that these biomarkers might be useful for future trials of disease-modifying therapeutics to delay the onset and slow the progression of HD. Such advances could herald a new era of personalized preventive therapeutics. We describe the natural history of HD, including the timing of emergence of motor, cognitive and emotional impairments, and the techniques that are used to assess these features. Building on this information, we review recent progress in the development of biomarkers for HD, and potential future roles of these biomarkers in clinical trials

Translational Cancer Research: Balancing Prevention and Treatment to Combat Cancer Globally

Cancer research is drawing on the human genome project to develop new molecular-targeted treatments. This is an exciting but insufficient response to the growing, global burden of cancer, particularly as the projected increase in new cases in the coming decades is increasingly falling on developing countries. The world is not able to treat its way out of the cancer problem. However, the mechanistic insights from basic science can be harnessed to better understand cancer causes and prevention, thus underpinning a complementary public health approach to cancer control. This manuscript focuses on how new knowledge about the molecular and cellular basis of cancer, and the associated high-throughput laboratory technologies for studying those pathways, can be applied to population-based epidemiological studies, particularly in the context of large prospective cohorts with associated biobanks to provide an evidence base for cancer prevention. This integrated approach should allow a more rapid and informed translation of the research into educational and policy interventions aimed at risk reduction across a population

The Anatomy of the bill Tip of Kiwi and Associated Somatosensory Regions of the Brain: Comparisons with Shorebirds

Three families of probe-foraging birds, Scolopacidae (sandpipers and snipes), Apterygidae (kiwi), and Threskiornithidae (ibises, including spoonbills) have independently evolved long, narrow bills containing clusters of vibration-sensitive mechanoreceptors (Herbst corpuscles) within pits in the bill-tip. These ‘bill-tip organs’ allow birds to detect buried or submerged prey via substrate-borne vibrations and/or interstitial pressure gradients. Shorebirds, kiwi and ibises are only distantly related, with the phylogenetic divide between kiwi and the other two taxa being particularly deep. We compared the bill-tip structure and associated somatosensory regions in the brains of kiwi and shorebirds to understand the degree of convergence of these systems between the two taxa. For comparison, we also included data from other taxa including waterfowl (Anatidae) and parrots (Psittaculidae and Cacatuidae), non-apterygid ratites, and other probe-foraging and non probe-foraging birds including non-scolopacid shorebirds (Charadriidae, Haematopodidae, Recurvirostridae and Sternidae). We show that the bill-tip organ structure was broadly similar between the Apterygidae and Scolopacidae, however some inter-specific variation was found in the number, shape and orientation of sensory pits between the two groups. Kiwi, scolopacid shorebirds, waterfowl and parrots all shared hypertrophy or near-hypertrophy of the principal sensory trigeminal nucleus. Hypertrophy of the nucleus basorostralis, however, occurred only in waterfowl, kiwi, three of the scolopacid species examined and a species of oystercatcher (Charadriiformes: Haematopodidae). Hypertrophy of the principal sensory trigeminal nucleus in kiwi, Scolopacidae, and other tactile specialists appears to have co-evolved alongside bill-tip specializations, whereas hypertrophy of nucleus basorostralis may be influenced to a greater extent by other sensory inputs. We suggest that similarities between kiwi and scolopacid bill-tip organs and associated somatosensory brain regions are likely a result of similar ecological selective pressures, with inter-specific variations reflecting finer-scale niche differentiation

Modelling chemistry in the nocturnal boundary layer above tropical rainforest and a generalised effective nocturnal ozone deposition velocity for sub-ppbv NOx conditions

Measurements of atmospheric composition have been made over a remote rainforest landscape. A box model has previously been demonstrated to model the observed daytime chemistry well. However the box model is unable to explain the nocturnal measurements of relatively high [NO] and [O3], but relatively low observed [NO2]. It is shown that a one-dimensional (1-D) column model with simple O3 -NOx chemistry and a simple representation of vertical transport is able to explain the observed nocturnal concentrations and predict the likely vertical profiles of these species in the nocturnal boundary layer (NBL). Concentrations of tracers carried over from the end of the night can affect the atmospheric chemistry of the following day. To ascertain the anomaly introduced by using the box model to represent the NBL, vertically-averaged NBL concentrations at the end of the night are compared between the 1-D model and the box model. It is found that, under low to medium [NOx] conditions (NOx <1 ppbv), a simple parametrisation can be used to modify the box model deposition velocity of ozone, in order to achieve good agreement between the box and 1-D models for these end-of-night concentrations of NOx and O3. This parametrisation would could also be used in global climate-chemistry models with limited vertical resolution near the surface. Box-model results for the following day differ significantly if this effective nocturnal deposition velocity for ozone is implemented; for instance, there is a 9% increase in the following day’s peak ozone concentration. However under medium to high [NOx] conditions (NOx > 1 ppbv), the effect on the chemistry due to the vertical distribution of the species means no box model can adequately represent chemistry in the NBL without modifying reaction rate constants

Is a Severe Clinical Profile an Effect Modifier in a Web-Based Depression Treatment for Adults With Type 1 or Type 2 Diabetes? Secondary Analyses From a Randomized Controlled Trial.

Background: Depression and diabetes are two highly prevalent and co-occurring health problems. Web-based, diabetes-specific cognitive behavioral therapy (CBT) depression treatment is effective in diabetes patients, and has the potential to be cost effective and to have large reach. A remaining question is whether the effectiveness differs between patients with seriously impaired mental health and patients with less severe mental health problems. Objective: To test whether the effectiveness of an eight-lesson Web-based, diabetes-specific CBT for depression, with minimal therapist support, differs in patients with or without diagnosed major depressive disorder (MDD), diagnosed anxiety disorder, or elevated diabetes-specific emotional distress (DM-distress). Methods: We used data of 255 patients with diabetes with elevated depression scores, who were recruited via an open access website for participation in a randomized controlled trial, conducted in 2008-2009, comparing a diabetes-specific, Web-based, therapist-supported CBT with a 12-week waiting-list control group. We performed secondary analyses on these data to study whether MDD or anxiety disorder (measured using a telephone-administered diagnostic interview) and elevated DM-distress (online self-reported) are effect modifiers in the treatment of depressive symptoms (online self-reported) with Web-based diabetes-specific CBT. Results: MDD, anxiety disorder, and elevated DM-distress were not significant effect modifiers in the treatment of self-assessed depressive symptoms with Web-based diabetes-specific CBT. Conclusions: This Web-based diabetes-specific CBT depression treatment is suitable for use in patients with severe mental health problems and those with a less severe clinical profile

Risk of acute kidney injury and survival in patients treated with Metformin:an observational cohort study

Background: Whether metformin precipitates lactic acidosis in patients with chronic kidney disease (CKD) remains under debate. We examined whether metformin use was associated with an increased risk of acute kidney injury (AKI) as a proxy for lactic acidosis and whether survival among those with AKI varied by metformin exposure. Methods: All individuals with type 2 diabetes and available prescribing data between 2004 and 2013 in Tayside, Scotland were included. The electronic health record for diabetes which includes issued prescriptions was linked to laboratory biochemistry, hospital admission, death register and Scottish Renal Registry data. AKI events were defined using the Kidney Disease Improving Global Outcomes criteria with a rise in serum creatinine of at least 26.5 μmol/l or a rise of greater than 150% from baseline for all hospital admissions. Cox Regression Analyses were used to examine whether person-time periods in which current metformin exposure occurred were associated with an increased rate of first AKI compared to unexposed periods. Cox regression was also used to compare 28 day survival rates following first AKI events in those exposed to metformin versus those not exposed. Results: Twenty-five thousand one-hundred fourty-eight patients were included with a total person-time of 126,904 person years. 4944 (19.7%) people had at least one episode of AKI during the study period. There were 32.4 cases of first AKI/1000pyrs in current metformin exposed person-time periods compared to 44.9 cases/1000pyrs in unexposed periods. After adjustment for age, sex, diabetes duration, calendar time, number of diabetes drugs and baseline renal function, current metformin use was not associated with AKI incidence, HR 0.94 (95% CI 0.87, 1.02, p = 0.15). Among those with incident AKI, being on metformin at admission was associated with a higher rate of survival at 28 days (HR 0.81, 95% CI 0.69, 0.94, p = 0.006) even after adjustment for age, sex, pre-admission eGFR, HbA1c and diabetes duration. Conclusions: Contrary to common perceptions, we found no evidence that metformin increases incidence of AKI and was associated with higher 28 day survival following incident AKI

Intragenic DNA methylation: implications of this epigenetic mechanism for cancer research

Epigenetics is the study of all mechanisms that regulate gene transcription and genome stability that are maintained throughout the cell division, but do not include the DNA sequence itself. The best-studied epigenetic mechanism to date is DNA methylation, where methyl groups are added to the cytosine base within cytosine–guanine dinucleotides (CpG sites). CpGs are frequently clustered in high density (CpG islands (CGIs)) at the promoter of over half of all genes. Current knowledge of transcriptional regulation by DNA methylation centres on its role at the promoter where unmethylated CGIs are present at most actively transcribed genes, whereas hypermethylation of the promoter results in gene repression. Over the last 5 years, research has gradually incorporated a broader understanding that methylation patterns across the gene (so-called intragenic or gene body methylation) may have a role in transcriptional regulation and efficiency. Numerous genome-wide DNA methylation profiling studies now support this notion, although whether DNA methylation patterns are a cause or consequence of other regulatory mechanisms is not yet clear. This review will examine the evidence for the function of intragenic methylation in gene transcription, and discuss the significance of this in carcinogenesis and for the future use of therapies targeted against DNA methylation

Evidence for a continuous decline in lower stratospheric ozone offsetting ozone layer recovery

Ozone forms in the Earth's atmosphere from the photodissociation of molecular oxygen, primarily in the tropical stratosphere. It is then transported to the extratropics by the Brewer–Dobson circulation (BDC), forming a protective "ozone layer" around the globe. Human emissions of halogen-containing ozone-depleting substances (hODSs) led to a decline in stratospheric ozone until they were banned by the Montreal Protocol, and since 1998 ozone in the upper stratosphere is rising again, likely the recovery from halogen-induced losses. Total column measurements of ozone between the Earth's surface and the top of the atmosphere indicate that the ozone layer has stopped declining across the globe, but no clear increase has been observed at latitudes between 60° S and 60° N outside the polar regions (60–90°). Here we report evidence from multiple satellite measurements that ozone in the lower stratosphere between 60° S and 60° N has indeed continued to decline since 1998. We find that, even though upper stratospheric ozone is recovering, the continuing downward trend in the lower stratosphere prevails, resulting in a downward trend in stratospheric column ozone between 60° S and 60° N. We find that total column ozone between 60° S and 60° N appears not to have decreased only because of increases in tropospheric column ozone that compensate for the stratospheric decreases. The reasons for the continued reduction of lower stratospheric ozone are not clear; models do not reproduce these trends, and thus the causes now urgently need to be established

A survey of the state-of-the-art techniques for cognitive impairment detection in the elderly

With a growing number of elderly people in the UK, more and more of them suffer from various kinds of cognitive impairment. Cognitive impairment can be divided into different stages such as mild cognitive impairment (MCI) and severe cognitive impairment like dementia. Its early detection can be of great importance. However, it is challenging to detect cognitive impairment in the early stage with high accuracy and low cost, when most of the symptoms may not be fully expressed. This survey paper mainly reviews the state of the art techniques for the early detection of cognitive impairment and compares their advantages and weaknesses. In order to build an effective and low-cost automatic system for detecting and monitoring the cognitive impairment for a wide range of elderly people, the applications of computer vision techniques for the early detection of cognitive impairment by monitoring facial expressions, body movements and eye movements are highlighted in this paper. In additional to technique review, the main research challenges for the early detection of cognitive impairment with high accuracy and low cost are analysed in depth. Through carefully comparing and contrasting the currently popular techniques for their advantages and weaknesses, some important research directions are particularly pointed out and highlighted from the viewpoints of the authors alone